Ultrasound for Pregnancy

Number: 0199

Policy
Applicable CPT / HCPCS / ICD-10 Codes
Background
References

Policy

Scope of Policy

This Clinical Policy Bulletin addresses ultrasound for pregnancy.

Medical Necessity

Aetna considers the following indications medically necessary unless otherwise stated:
1. Ultrasounds are considered not medically necessary if done solely to determine the fetal sex or to provide parents with a view and photograph of the fetus.
2. Fetal ultrasound with detailed anatomic examination for any of the following indications:
  1. To evaluate the fetus for amniotic band syndrome (also known as amniotic constriction band syndrome); or
  2. To evaluate fetuses with single umbilical artery (SUA); or
  3. To evaluate fetuses with soft sonographic markers of aneuploidy:
    1. Absent or hypoplastic nasal bone; or
    2. Choroid plexus cyst; or
    3. Echogenic bowel; or
    4. Echogenic intracardiac focus; or
    5. Fetal pyelectasis; or
    6. Increased nuchal translucency (fetal nuchal translucency measurement of 3.0 mm or greater in the first trimester); or
    7. Shortened long bones (femur or humerus); or
  4. When there are known or suspected fetal anatomic abnormalities, including:
    1. Abnormal serum markers screening for fetal aneuploidy (triple or quad screening) (see CPB 0464 - Serum and Urine Marker Screening for Fetal Aneuploidy); or
    2. Anatomic abnormalities due to genetic conditions (see attached ICD-10 coding); or
    3. Pregnancies resulting from in vitro fertilization (IVF); or
    4. Obesity (prepregnancy body mass index [BMI] of 30 kg/m2 or more) complicating pregnancy; or
    5. Known or suspected exposure to Zika virus; or
    6. Pregnancy in woman with untreated or inadequately treated syphilis; or
    7. Previous pregnancy with a fetus that had an omphalocele or other ultrasound detectable congenital anomaly associated with an elevated risk of recurrence in the current pregnancy; or
  5. To evaluate the fetus of a mother who has a bicornuate uterus or uterus didelphys; or
  6. To evaluate pregnant member with Arnold Chiari malformation type 1; or
  7. To evaluate pregnant member with maternal history of Klippel-Trenaunay syndrome; or
  8. To diagnose / evaluate uterus didelphys; or
  9. Use of detailed fetal US at 20 weeks based on previous pregnancy with a child with DiGeorge syndrome.
Experimental, Investigational, or Unproven

The following indications are considered experimental, investigational, or unproven because the effectiveness of these approaches has not been established:
1. More than 1 detailed ultrasound fetal anatomic examination per pregnancy per practice, as there is inadequate evidence of the clinical utility of multiple serial detailed fetal anatomic ultrasound examinations during pregnancy;
2. Detailed ultrasound fetal anatomic examination for all other indications including evaluation of pregnancy in which father of baby has a history of open spinal bifida; evaluation of hypo-coiled / hyper-coiled umbilical cord, McCune-Albright syndrome, placental cord insertion, (e.g., marginal cord insertion and velamentous insertion of umbilical cord), and septate or arcuate uterus, evaluation of members with 1st trimester exposure to amphetamine and dextroamphetamine (Adderall) or spironolactone (Aldactone); evaluation of members who are pregnant with a low fetal fraction; evaluation of pregnant members with a history of congenital atrophic kidney; members with HIV, routine evaluation of pregnant women who are on azathioprine (Imuran), pregnant women who are on bupropion (Wellbutrin) or levetiracetam (keppra), pregnant women with low pregnancy-associated plasma protein A, pregnant women with myasthenia gravis, and pregnant women who smoke or abuse cannabis. There is inadequate evidence of the clinical utility of detailed ultrasound fetal anatomic examination for indications other than evaluation of suspected fetal anatomic abnormalities. Detailed ultrasound fetal anatomic examination is not considered medically necessary for routine screening of normal pregnancy, or in the setting of maternal idiopathic pulmonary hemosiderosis;
3. Three-dimensional (3D) and four-dimensional (4D) fetal ultrasounds because of a lack of evidence that 3D and 4D ultrasounds alter management over standard two-dimensional (2D) ultrasounds such that clinical outcomes are improved.
Policy Limitations and Exclusions

Note: Pelvic ultrasound is considered to be clinically integral to the transvaginal examination and does not warrant separate reimbursement. A transvaginal ultrasound (TV-US) provides superior detail in images of pelvic structures. When TV-US is performed on a patient whose pelvic structures are within the bony pelvis, pelvic echography using an abdominal approach is duplicative of the TV-US.
Related Policies

For Aetna’s policy on first trimester ultrasonographic assessment of fetal nuchal skinfold thickness, see CPB 0282 - Noninvasive Down Syndrome Screening.

See also:

Table:
CPT Codes / HCPCS Codes / ICD-10 Codes
Code	Code Description
*Detailed fetal ultrasounds*:
CPT codes covered if selection criteria are met:
76811	Ultrasound, pregnant uterus, real time with image documentation, fetal and maternal evaluation plus detailed fetal anatomic examination, transabdominal approach; single or first gestation [second and/or third trimester]
+ 76812	each additional gestation (List separately in addition to code for primary procedure)
Other CPT codes related to the CPB:
76813	Ultrasound, pregnant uterus, real time with image documentation, first trimester fetal nuchal translucency measurement, transabdominal or transvaginal approach; single or first gestation
+76814	each additional gestation (List separately in addition to code for primary procedure)
Other specified HCPCS codes related to the CPB:
J1953	Injection, levetiracetam, 10 mg
ICD-10 codes covered (for detailed fetal ultrasounds) if selection criteria are met:
A92.5	Zika virus disease
A92.8	Other specified mosquito-borne viral fevers
B06.00 - B06.9	Rubella [German measles]
B50.0 - B54	Malaria
B97.6	Parvovirus as the cause of diseases classified elsewhere
E66.01	Morbid (severe) obesity due to excess calories [obesity with a BMI of 30 or>]
E66.09	Other obesity due to excess calories [obesity with a BMI of 30 or>]
G93.5	Compression of brain [Pregnant member with Arnold Chiari malformation type 1]
O09.511 - O09.519	Supervision of elderly primigravida
O09.521 - O09.529	Supervision of elderly multigravida
O09.811 - O09.819	Supervision of pregnancy resulting from assisted reproductive technology
O24.011 - O24.019, O24.111 - O24.119, O24.311 - O24.319, O24.410 -O24.419, O24.811 - O24.819, O24.911 - O24.919	Diabetes mellitus in pregnancy
O28.5	Abnormal chromosomal and genetic finding on antenatal screening of mother
O30.001 - O30.099	Twin pregnancy
O30.101 - O30.199	Triplet pregnancy
O30.201 - O30.299	Quadruplet pregnancy
O31.10X0 - O31.23X9	Continuing pregnancy after spontaneous abortion / intrauterine death of one fetus or more
O35.00X0 - 035.00X9	Maternal care for (suspected) central nervous system malformation in fetus
O35.10X0 – O35.10X9	Maternal care for (suspected) chromosomal abnormality in fetus
O35.2XX0 – O35.2XX9	Maternal care for (suspected) hereditary disease in fetus
O35.3XX0 – O35.3XX9	Maternal care for (suspected) damage to fetus from viral disease in mother
O35.4XX0 – O35.4XX9	Maternal care for (suspected) damage to fetus from alcohol
O35.5XX0 – 035.5XX9	Maternal care for (suspected) damage to fetus by drugs
O35.6XX0 – O35.6XX9	Maternal care for (suspected) damage to fetus by radiation
O35.8XX0 – 035.8XX9	Maternal care for other (suspected) fetal abnormality and damage
O35.9XX0 – 035.9XX9	Maternal care for (suspected) fetal abnormality and damage, unspecified
O35.AXX0 - O35.HXX9	Maternal care for other (suspected) fetal abnormality and damage
O36.0110 - O36.0999	Maternal care for rhesus isoimmunization
O36.1110 - O36.1999	Maternal care for other isoimmunization
O36.5110 - O36.5999	Maternal care for other known or suspected poor fetal growth
O40.1XX0 - O40.9XX9	Polyhydramnios
O41.00X0 - O41.03X9	Oligohydramnios
O69.81X0 - O69.89X9	Labor and delivery complicated by other cord complications
O71.9	Obstetric trauma, unspecified
O76	Abnormality in fetal heart rate and rhythm complicating labor and delivery
O98.311 - O98.319, O98.411 - O98.419, O98.511 - O98.519, O98.611 - O98.619, O98.711 - O98.719, O98.811 - O98.819	Other maternal infectious and parasitic diseases complicating pregnancy
O99.210 - O99.213	Obesity complicating pregnancy [obesity with a BMI of 30 or >]
O99.350 - O99.355	Diseases of the nervous system complicating pregnancy, childbirth, and the puerperium [Keppra] [Pregnant member with Arnold Chiari malformation type 1]
O99.411 - O99.419	Diseases of the circulatory system complicating pregnancy
P35.4	Congenital Zika virus disease
Q04.8	Other specified congenital malformations of brain [choroid plexus cyst]
Q27.0	Congenital absence and hypoplasia of umbilical artery
Q30.1	Agenesis and underdevelopment of nose [absent or hypoplastic nasal bone]
Q51.10 - Q51.11	Doubling of uterus with doubling of cervix and vagina [Uterus didelphys]
Q51.3	Bicornate uterus
Q62.0	Congenital hydronephrosis [fetal pyelectasis]
Q71.811 - Q71.819	Congenital shortening of upper limb [humerus]
Q72.811 - Q72.819	Congenital shortening of lower limb [femur]
Q92.0 - Q92.9	Other trisomies and partial trisomies of the autosomes, not elsewhere classified [fetuses with soft sonographic markers of aneuploidy]
R93.5	Abnormal findings on diagnostic imaging of other abdominal regions, including retroperitoneum
R93.8	Abnormal findings on diagnostic imaging of other specified body structures
Z03.73	Encounter for suspected fetal anomaly ruled out [pregnant women with known or suspected exposure to Zika virus]
Z20.821	Contact with and (suspected) exposure to Zika virus
Z20.828	Contact with and (suspected) exposure to other viral communicable diseases [pregnant women with known or suspected exposure to Zika virus]
Z68.30 - Z68.45	Body mass index (BMI) 30.0 - 70 or greater, adult
Z82.79	Family history of other congenital malformations, deformations and chromosomal abnormalities [not covered for maternal history of Klippel-Trenaunay syndrome] [paternal history of open spinal bifida]
ICD-10 codes not covered for indications listed in the CPB (not all-inclusive):
B20	Human immunodeficiency virus [HIV] disease
F12.10 - F12.19	Cannabis abuse
F12.23	Cannabis dependence with withdrawal
F12.93	Cannabis use, unspecified with withdrawal
F17.200 - F17.299	Nicotine dependence
G40.001 - G40.919	Epilepsy and recurrent seizures [Keppra]
G70.00 - G70.01	Myasthenia gravis
J84.03	Idiopathic pulmonary hemosiderosis
O36.8910 -O36.8999	Maternal care for other specified fetal problems [low fetal fraction]
O43.121 – O43.129	Velamentous insertion of umbilical cord
O43.191 – O43.199	Other malformation of placenta
O43.891 - O43.899	Other placental disorders [hypo-coiled / hyper-coiled umbilical cord]
O98.111 - O98.119	Syphilis complicating pregnancy
O99.320 - O99.323	Drug use complicating pregnancy
O99.330 - O99.335	Smoking (tobacco) complicating pregnancy, childbirth, and the puerperium
Q51.21 – Q51.28	Other doubling of uterus
Q51.810	Arcuate uterus
Q78.1	Polyostotic fibrous dysplasia
Z87.448	Personal history of other diseases of urinary system [history of congenital atrophic kidney]
*Three-dimensional (3D) and four-dimensional (4D) fetal ultrasounds*:
There are no specific codes for 3D and 4D fetal ultrasound
CPT codes not covered for indications listed in the CPB:
76376	3D rendering with interpretation and reporting of computed tomography, magnetic resonance imaging, ultrasound, or other tomographic modality with image postprocessing under concurrent supervision; not requiring image postprocessing on an independent workstation
76377	requiring image postprocessing on an independent workstation
Pelvic Ultrasound:
Other CPT codes related to the CPB:
76801	Ultrasound, pregnant uterus, real time with image documentation, fetal and maternal evaluation, first trimester (< 14 weeks 0 days), transabdominal approach; single or first gestation
76802	each additional gestation (List separately in addition to code for primary procedure)
76817	Ultrasound, pregnant uterus, real time with image documentation, transvaginal
76830	Ultrasound, transvaginal

Background

This policy is based in part on The American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin on Ultrasonography in Pregnancy and guidelines from the Society for Maternal-Fetal Medicine (SMFM).

Ultrasonography in pregnancy should be performed only when there is a valid medical indication. ACOG (2009) stated, "The use of either two-dimensional or three-dimensional ultrasonography only to view the fetus, obtain a picture of the fetus, or determine the fetal sex without a medical indication is inappropriate and contrary to responsible medical practice."

Indications for a first-trimester ultrasound (performed before 13 weeks and 6 days of gestation) include:

As adjunct to chorionic villus sampling, embryo transfer, or localization and removal of an intra-uterine device
To assess for certain fetal anomalies, such as anencephaly, in patients at high risk
To confirm cardiac activity
To confirm the presence of an intra-uterine pregnancy
To diagnosis or evaluate multiple gestations
To estimate gestational age
To evaluate a suspected ectopic pregnancy
To evaluate maternal pelvic or adnexal masses or uterine abnormalities
To evaluate pelvic pain
To evaluate suspected hydatidiform mole
To evaluate vaginal bleeding
To screen for fetal aneuploidy.

ACOG recommended that in the absence of specific indications, the optimal time for an obstetric ultrasound examination is between 18 to 20 weeks of gestation because anatomically complex organs, such as the fetal heart and brain, can be imaged with sufficient clarity to allow detection of many major malformations. This recommendation is based primarily on consensus and expert opinion (Level C). ACOG stated that it may be possible to document normal structures before 18 weeks of gestation but some structures can be difficult to visualize at that time because of fetal size, position, and movement; maternal abdominal scars; and increased maternal abdominal wall thickness. A second or third trimester ultrasound examination, however, may pose technical limitations for an anatomic evaluation due to suboptimal imaging, and when this occurs, ACOG recommended documentation of the technical limitation and that a follow-up examination may be helpful.

ACOG uses the terms "standard" (also called basic), "limited," and "specialized" (also called detailed) to describe various types of ultrasound examinations performed during the second or third trimesters.

Standard Examination

A standard ultrasound includes an evaluation of fetal presentation, amniotic fluid volume, cardiac activity, placental position, fetal biometry, and fetal number, plus an anatomic survey. A standard examination of fetal anatomy includes the following essential elements:

Abdomen (stomach, kidneys, bladder, umbilical cord insertion site into the fetal abdomen, umbilical cord vessel number)
Chest (heart)
Extremities (presence or absence of legs and arms)
Head, face and neck (cerebellum, choroid plexus, cisterna magna, lateral cerebral ventricles, midline falx, cavum septi pellucidi, upper lip)
Sex (medically indicated in low-risk pregnancies only for the evaluation of multiple gestations).
Spine (cervical, thoracic, lumbar, and sacral spine).

Limited Examination

A limited examination does not replace a standard examination and is performed when a specific question requires investigation (e.g., to confirm fetal heart activity in a patient experiencing vaginal bleeding or to establish fetal presentation during labor). A limited examination may be performed during the first trimester to evaluate interval growth, estimate amniotic fluid volume, evaluate the cervix, and assess the presence of cardiac activity.

Specialized Examination

A detailed or targeted anatomic examination is performed when an anomaly is suspected on the basis of history, laboratory abnormalities, or the results of either the limited or standard examination. Other specialized examinations might include fetal Doppler ultrasonography, biophysical profile, amniotic fluid assessment, fetal echocardiography, or additional biometric measurements. Specialized examinations are performed by an operator with experience and expertise in such ultrasonography who determines that components of the examination on a case-by-case basis.

Indications for a second and third trimester ultrasound include the following:

Adjunct to amniocentesis or other procedure
Adjunct to cervical cerclage placement
Adjunct to external cephalic version
Determination of fetal presentation
Estimation of gestational age
Evaluation for abnormal biochemical markers
Evaluation for fetal well-being
Evaluation for premature rupture of membranes of premature labor
Evaluation in those with a history of previous congenital anomaly
Evaluation of abdominal and pelvic pain
Evaluation of cervical insufficiency
Evaluation of fetal condition in late registrants for prenatal care
Evaluation of fetal growth
Evaluation of pelvic mass
Evaluation of suspected amniotic fluid abnormalities
Evaluation of suspected ectopic pregnancy
Evaluation of suspected fetal death
Evaluation of suspected multiple gestation
Evaluation of suspected placental abruption
Evaluation of suspected uterine abnormality (e.g., bicornuate uterus)
Evaluation of vaginal bleeding
Examination of suspected hydatidiform mole
Follow-up evaluation of a fetal anomaly
Follow-up evaluation of placental location for suspected placenta previa
Significant discrepancy between uterine size and clinical dates
To assess for findings that may increase the risk of aneuploidy
To screen for fetal anomalies.

The Society for Maternal-Fetal Medicine (SMFM) has stated that a fetal ultrasound with detailed anatomic examination (CPT 76811) is not necessary as a routine scan for all pregnancies (SMFM, 2004). Rather, this scan is necessary for a known or suspected fetal anatomic or genetic abnormality (i.e., previous anomalous fetus, abnormal scan this pregnancy, etc.), or increased risk for fetal abnormality (e.g. AMA, diabetic, fetus at risk due to teratogen or genetics, abnormal prenatal screen). Thus, the SMFM has stated that the performance of this scan is expected to be rare outside of referral practices with special expertise in the identification of, and counseling about, fetal abnormalities (SMFM, 2004; SMFM, 2012).

SMFM has also determined that no more than 1 fetal ultrasound with detailed anatomic examination is necessary per pregnancy, per practice, when medically necessary (SMFM, 2004; SMFM, 2012). Once this detailed fetal anatomical examination is done, a second one should not be performed unless there are extenuating circumstances with a new diagnosis. The SMFM has stated that it is appropriate to repeat the detailed fetal anatomical ultrasound examination when a patient is seen by another maternal-fetal medicine specialist practice, for example, for a second opinion on a fetal anomaly, or if the patient is referred to a tertiary center in anticipation of delivering an anomalous fetus at a hospital with specialized neonatal capabilities.

A focused ultrasound assessment is sufficient for follow-up to provide a re-examination of a specific organ or system known or suspected to be abnormal, or when doing a focused assessment of fetal size by measuring the bi-parietal diameter, abdominal circumference, femur length, or other appropriate measurements (SMFM, 2004).

An ultrasound without detailed anatomic examination is appropriate for a fetal maternal evaluation of the number of fetuses, amniotic/chorionic sacs, survey of intra-cranial, spinal and abdominal anatomy, evaluation of a 4-chamber heart view, assessment of the umbilical cord insertion site, assessment of amniotic fluid volume, and evaluation of maternal adenexa when visible and appropriate (SMFM, 2004).

Amniotic band sequence refers to a highly variable spectrum of congenital anomalies that occur in association with amniotic bands. Amniotic banding affects approximately 1 in 1,200 live births. It is also believed to be the cause of 178 in 10,000 miscarriages. Up to 50% of cases have other congenital anomalies including cleft lip, cleft palate, and clubfoot deformity. Hand and finger anomalies occur in up to 80%. The diagnosis is based upon the presence of characteristic structural findings on prenatal ultrasound or postnatal physical examination. The diagnosis should be suspected when limb amputations or atypical body wall or craniofacial defects are present, or when bands of amnion are seen crossing the gestational sac and adherent to the fetus.

In a practice bulletin on screening for fetal chromosomal anomalies, ACOG (2007) has stated that patients who have a fetal nuchal translucency measurement of 3.5 mm or greater in the first trimester, despite a negative result on an aneuploidy screen, normal fetal chromosomes, or both, should be offered a targeted ultrasound examination, fetal echocardiogram, or both, because such fetuses are at a significant risk for non-chromosomal anomalies, including congenital heart defects, abdominal wall defects, diaphragmatic hernias, and genetic syndromes.

An UpToDate review on “First-trimester combined test and integrated tests for screening for Down syndrome and trisomy 18” (Messerlian et al, 2021) states that “The best interpretation of nuchal translucency [NT] is by screening programs that combine its measurement with maternal age and first trimester serum markers to provide a patient specific risk of Down syndrome. One exception to this recommendation is for fetuses with a cystic hygroma or significantly enlarged NT. These pregnancies are at particularly high risk of aneuploidy. Many experts proceed directly to karyotype (some choose microarray) assessment in these cases, rather than checking maternal serum analyte levels. The optimum threshold for proceeding to chromosomal analysis without maternal serum screening is unclear. NT thresholds in the range of 3.0 to 4.0 mm have been suggested, given the relatively high risk of Down syndrome at this level”.

The ACOG practice bulletin on the use of psychiatric medications during pregnancy and lactation (2008) stated that atypical anti-depressants are non-tricyclic anti-depressants and non-selective serotonin reuptake inhibitors antidepressants that work by distinct pharmacodynamic mechanisms. The atypical anti-depressants include bupropion, duloxetine, mirtazapine, nefazodone, and venlafaxine. The limited data of fetal exposure to these anti-depressants do not suggest an increased risk of fetal anomalies or adverse pregnancy events. In the one published study of bupropion exposure in 136 patients, a significantly increased risk of spontaneous abortion, but not an increased risk of major malformations, was identified. In contrast, the bupropion registry maintained at GlaxoSmithKline has not identified any increased risk of spontaneous abortion, although these data have not undergone peer review.

In a Cochrane review, Stampalija and colleagues (2010) evaluated the effects on pregnancy outcome, and obstetric practice, of routine utero-placental Doppler ultrasound in first and second trimester of pregnancy in pregnant women at high- and low-risk of hypertensive complications. These investigators searched the Cochrane Pregnancy and Childbirth Group's Trials Register (June 2010) and the reference lists of identified studies. Randomized and quasi-randomized controlled trials of Doppler ultrasound for the investigation of utero-placental vessel waveforms in first and second trimesters compared with no Doppler ultrasound were included in this review. These researchers excluded studies where uterine vessels have been assessed together with fetal and umbilical vessels. Two authors independently assessed the studies for inclusion, assessed risk of bias and carried out data extraction. They found 2 studies involving 4,993 participants. The methodological quality of the trials was good. Both studies included women at low-risk for hypertensive disorders, with Doppler ultrasound of the uterine arteries performed in the second trimester of pregnancy. In both studies, pathological finding of uterine arteries was followed by low-dose aspirin administration. They identified no difference in short-term maternal and fetal clinical outcomes; identified no randomized studies assessing the utero-placental vessels in the first trimester or in women at high-risk for hypertensive disorders. The authors concluded that present evidence failed to show any benefit to either the baby or the mother when utero-placental Doppler ultrasound was used in the second trimester of pregnancy in women at low-risk for hypertensive disorders. However, this evidence can not be considered conclusive with only 2 studies included. There were no randomized studies in the first trimester, or in women at high-risk. They stated that more research is needed to examine if the use of utero-placental Doppler ultrasound may improve pregnancy outcome.

The American Institute for Ultrasound Medicine, the Society for Materanal Fetal Medicine, and other societies (Wax, et al., 2015) recommended a threshold BMI of greater than or equal to 30 kg/m² for performing a detailed fetal anatomic ultrasound for pregnancy complicated by obesity. A previous AIUM and SMFM report (Wax, et al., 2014) referred to and increased body mass index (BMI, ≥35 kg/m²) as the threshold for the detailed fetal anatomic ultrasound. However, the AIUM noted that "both of the cited publications [citing Rasmussen, et al., 2008; Stothard, et al., 2009] quote articles that use varied definitions of obesity based on prepregnancy or early pregnancy BMI but are closer to the more standard definition of BMI ≥30 kg/m², which should therefore be the definition of obesity for the purposes of indicating a 76811 examination."

Fetal ultrasound with detailed anatomic examination is recommended to further evaluate single umbilical artery found on initial imaging. Typically the umbilicord contains two arteries and one vein; however, a variation of umbilical cord anatomy may occur resulting in a single umbilical artery (SUA). SUA may be an isolated finding, or associated with aneuploidy or other congenital anomalies. Prevalence depends on the characteristics of the population studied. SUA is more common in pregnancies at "the extremes of maternal age and in Eastern Europeans", as well as, in twin pregnancies (3.9 to 8.8 percent). SUA is a finding that is found on an obstetrical ultrasound examination. The American Institute of Ultrasound in Medicine recommends imaging the umbilical cord as part of a standard prenatal ultrasound examination and evaluating the number of vessels in the cord, when possible, in the second and third trimesters. SUA can be detected in the first trimester; however, the sensitivity and specificity are higher in the second trimester. SUA occurs in approximately 0.5 percent of unselected pregnancies undergoing second-trimester ultrasound examination (Gimovsky et al., 2018).

The Society for Maternal-Fetal Medicine (SMFM, 2013) state that SUA can usually be detected on cross-section of the umbilical cord using 2-D imaging. SMFM recommends further SUA evaluation to include a detailed anatomic survey by an experienced provider, and include assessment of risk factors for aneuploidy, including maternal age, results of other screening or diagnostic tests, and family history.

Three-Dimensional and Four-Dimensional Ultrasound in Obstetrics

Three-dimensional (3D) ultrasound can furnish a 3D image of the fetus. To create a 3D image, a transducer takes a series of thin slices of the subject, and a computer translates these images and presents them in 3 dimensions.

Proponents of 3D ultrasound scanning have argued that volumetric measurements from 3D ultrasound scan are more accurate and that both clinicians and parents can better appreciate a certain abnormality with a 3D scan than a standard 2-dimensional (2D) scan. In addition, there is the possibility of increasing psychological bonding between the parents and the baby (Ji et al, 2005).

In the diagnosis of congenital anomalies, there is evidence to suggest that smaller defects such as spina bifida, cleft lip and palate, and polydactyly may be more lucidly demonstrated with 3D ultrasound (Gonçalves et al, 2005; Kurjak et al, 2007). Other more subtle features such as low-set ears, facial dysmorphia or clubbing of feet may be better assessed, which has the potential to lead to more effective diagnoses of chromosomal abnormalities.

In addition, the use of 3D technology can reduce scanning time while maintaining adequate visualization of the fetus in obstetrical ultrasound (Benacerraf et al, 2005; Benacerraf et al, 2006).

Jones et al (2010) examined the intra- and inter-observer reproducibility of 3D power Doppler (3DPD) data acquisition from women at 12 weeks gestation, which were then subsequently measured by a single observer. Women with an uncomplicated, viable singleton pregnancy were scanned between 12 + 0 and 13 + 6 weeks gestations with a Voluson 730 Expert. 3DPD data were acquired of the whole placenta by 2 observers: the first observer captured 2 data sets and the second a single dataset. Each data set was analysed using VOCAL in the A plane with 9 degree rotation steps. A total of 18 low-risk women were recruited with a total of 54 data sets analyzed. The intra-class correlation coefficient (ICC) was highest for the vascular indices vascularization index (VI) and vascularization-flow index (VFI), greater than 0.75. Intra-class correlation coefficient for flow index (FI) showed moderate correlation at 0.47 to 0.65. Bland Altman plots showed the most precise vascular index to be the FI (-15% to 10% for inter-observer agreement). There was no bias between datasets. Prospective studies are now required to identify if this analysis tool and method is sensitive enough to recognize patients with early-onset placental dysfunction.

More recently, 4-dimensional (4D) or dynamic 3D scanners have come on the market, with the attraction of being able to look at fetal movements. These have also been referred to as "reassurance scans" or "entertainment scans." Proponents argue that 4D scans may have an important catalytic effect for mothers to bond to their babies before birth. However, the impact of 4D scans on diagnosis and management of fetal abnormalities is unknown.

Three-dimensional ultrasound appears to have been useful in research on fetal embryology. However, there is no evidence that the results of 3D ultrasound alters clinical management over standard 2D ultrasound such that clinical outcomes are improved. Whether 3D ultrasound will provide unique, clinically relevant information remains to be seen.

Current guidelines on ultrasonography in pregnancy from ACOG (2009) state: "The technical advantages of 3-dimensional ultrasonography include its ability to acquire and manipulate an infinite number of planes and to display ultrasound planes traditionally inaccessible by 2-dimensional ultrasonography. Despite these technical advantages, proof of a clinical advantage of 3-dimensional ultrasonography in prenatal diagnosis in general is still lacking. Potential areas of promise include fetal facial anomalies, neural tube defects, and skeletal malformations where 3-dimensional ultrasonography may be helpful in diagnosis as an adjunct to, but not a replacement for, 2-dimensional ultrasonography. Until clinical evidence shows a clear advantage to conventional 2-dimensional ultrasonography, 3-dimensional ultrasonography is not considered a required modality at this time."

Yagel et al (2009) described the state of the science of 3D/4D ultrasound (3D/4D US) applications in fetal medicine. They noted that 3D/4D US applications are many and varied. Their use in fetal medicine varies with the nature of the tissue to be imaged and the challenges each organ system presents, versus the advantages of each ultrasound application. The investigators stated that 3D/4D US has been extensively applied to the study of the fetus. Fetal applications include all types of anatomical assessment, morphometry and volumetry, as well as functional assessment. The authors concluded that 3D/4D US provides many advantages in fetal imaging; however, its contribution to improving the accuracy of fetal scanning over rates achieved with 2D US, remains to be established.

In a prospective study, Chen et al (2009) examined the feasibility and reproducibility of measurements of nasal bone length using a 3D US in the first trimester. A total of 118 consecutive pregnant women attending for Down syndrome screening at 11- to 13(+6)-week were recruited. They had successful fetal nasal bone measurement by 2D US by 4 operators. Three-dimensional volumes were recorded in the mid-sagittal plane of fetal profile by the fifth operator and examined using multi-planar techniques. Another independent investigator randomly compared his measurements with 1 of the 4 operators. In the subsequent 3D examination, the nasal bone length could be examined in 94 cases (79.7%). The mean difference between the 2D and 3D measurements was 0.19 mm [95% confidence interval (CI): 0.08 to 0.31] (p < 0.05). Limits of agreement were -0.73 to 1.11. The mean differences between these 2 observers were 0.66 mm (95% CI: -0.47 to 0.86) (p < 0.05). The authors concluded that there was significant inter-method difference between the results obtained by 2D and 3D, as well as substantial inter-observer variation in 3D measurement of fetal nasal bone length in the first trimester. They stated that independent 3D measurement of nasal bone offers no additional advantages over 2D US.

Kurjak and colleagues (2010) stated that an evolving challenge for obstetricians is to better define normal and abnormal fetal neurological function in utero in order to better predict ante-natally which fetuses are at risk for adverse neurological outcome. In a multi-center study, these investigators examined the use of 4D US in the assessment of fetal neurobehavior in high-risk pregnancies. Pre-natal neurological assessment was carried out in high-risk fetuses using 4D US applying the recently developed Kurjak ante-natal neurodevelopmental test (KANET). Post-natal neurological assessment was performed using Amiel Tison's neurological assessment at term (ATNAT) for all live-borns and general movement (GM) assessment for those with borderline and abnormal ATNAT. Inclusion criteria were met by 288 pregnant women in 4 centers of whom 266 gave birth to a live-born baby. It was revealed that 234 fetuses were neurologically normal, 7 abnormal and 25 borderline. Out of 7 abnormal fetuses ATNAT was borderline in 5 and abnormal in 2, whereas GM assessment was abnormal in 5 and definitely abnormal in 2. Out of 25 KANET borderline fetuses, ATNAT was normal in 7, borderline in 17 and abnormal in 1, whereas the GM assessment was as follows: normal optimal in 4, normal suboptimal in 20, and abnormal in 1. In summary, out of 32 borderline and abnormal fetuses, ATNAT was normal in 7, borderline in 22 and abnormal in 3; GM assessment was normal optimal in 4, normal suboptimal in 20, abnormal in 6 and definitely abnormal in 2. The authors concluded that 4D US requires further studies before being recommended for wider clinical practice.

Hata et al (2011) presented 2 cases of amniotic band syndrome diagnosed using 2D ultrasound with 3D/4D ultrasound in early pregnancy. In case 1, at 13 weeks' gestation, multiple amniotic bands, acrania, the absence of fingers and amputation of the toes bilaterally were clearly shown using trans-vaginal 3D/4D ultrasound. In case 2, at 15 weeks' gestation, several amniotic bands, acrania and a cleft lip were depicted with trans-abdominal 3D/4D ultrasound. The spatial relationship between the amniotic bands and the fetus was clearly visualized and easily discernible by 3D/4D ultrasound. The parents and families could readily understand the fetal conditions and undergo counseling; they then choose the option of termination of pregnancy. The authors concluded that 3D/4D ultrasound has the potential to be a supplement to conventional 2D ultrasound in evaluating amniotic band syndrome.

In a pilot study, Antsaklis et al (2011) evaluated the use of 3D ultrasonography as an alternative for examining fetal anatomy and nuchal translucency (NT) in the first trimester of pregnancy. A total of 199 low-risk pregnant women undergoing first trimester ultrasound scan for fetal anomalies were included in this study. The NT and fetal anatomy were evaluated by 3D ultrasonography after the standard 2D examination. The gold standard in this study was the 2D ultrasonography. In some of the evaluated parameters, the 3D method approaches the conventional 2D results. These parameters are the crown-rump length (CRL), the skull-brain anatomy (93.5%), the spine (85.4%), the upper limbs (88.4%) and the lower limbs (87.9%) and the examination of the fetal abdomen (98.5%). Some of the anatomic parameters under evaluation revealed a statistically significant difference in favor of the 2D examination. During the 3D examination the nasal bone was identified in 62.1% of the cases, the stomach in 85.9%, and the urinary bladder in 57.3% of the cases. The NT was assessed accurately in 50% of the cases compared to 2D examination. The authors concluded that the 3D ultrasound is insufficient for the detailed fetal anatomy examination during the first trimester of pregnancy.

An UpToDate review on "Idiopathic pulmonary hemosiderosis" (Milman, 2012) does not mention the use of detailed ultrasound fetal anatomic examination.

According to the Product Insert of Keppra (Pregnancy Category C), there are no adequate and well-controlled studies in pregnant women. In animal studies, levetiracetam produced evidence of developmental toxicity, including teratogenic effects, at doses similar to or greater than human therapeutic doses. Keppra should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. As with other anti-epileptic drugs, physiological changes during pregnancy may affect levetiracetam concentration. There have been reports of decreased levetiracetam concentration during pregnancy. Discontinuation of anti-epileptic treatments may result in disease worsening, which can be harmful to the mother and the fetus.

In a Cochrane review, Grivell et al (2012) noted that policies and protocols for fetal surveillance in the pregnancy where impaired fetal growth is suspected vary widely, with numerous combinations of different surveillance methods. These researchers evaluated the effects of ante-natal fetal surveillance regimens on important peri-natal and maternal outcomes. These investigators searched the Cochrane Pregnancy and Childbirth Group's Trials Register (February 29, 2012). Randomized and quasi-randomized trials comparing the effects of described ante-natal fetal surveillance regimens were selected for analysis. Review authors independently assessed trial eligibility and quality and extracted data. They included 1 trial of 167 women and their babies. This trial was a pilot study recruiting alongside another study, therefore, a separate sample size was not calculated. The trial compared a twice-weekly surveillance regimen (biophysical profile, non-stress tests, umbilical artery and middle cerebral artery Doppler and uterine artery Doppler) with the same regimen applied fortnightly (both groups had growth assessed fortnightly). There were insufficient data to assess this review's primary infant outcome of composite peri-natal mortality and serious morbidity (although there were no peri-natal deaths) and no difference was seen in the primary maternal outcome of emergency caesarean section for fetal distress (risk ratio (RR) 0.96; 95% CI: 0.35 to 2.63). In keeping with the more frequent monitoring, mean gestational age at birth was 4 days less for the twice-weekly surveillance group compared with the fortnightly surveillance group (mean difference (MD) -4.00; 95% CI: -7.79 to -0.21). Women in the twice-weekly surveillance group were 25% more likely to have induction of labor than those in the fortnightly surveillance group (RR 1.25; 95% CI: 1.04 to 1.50). The authors concluded that there is limited evidence from randomized controlled trials to inform best practice for fetal surveillance regimens when caring for women with pregnancies affected by impaired fetal growth. They stated that more studies are needed to evaluate the effects of currently used fetal surveillance regimens in impaired fetal growth.

A choroid plexus cyst is a small fluid-filled structure within the choroid of the lateral ventricles of the fetal brain. Choroid plexus cysts are identified in approximately 1% to 2% of fetuses in the second trimester and they occur equally in male and female fetuses. According to the Society for Maternal-Fetal Medicine (SMFM, 2013), when a choroid plexus cyst is identified, the presence of structural malformations and other sonographic markers of aneuploidy should be assessed with a detailed fetal anatomic survey performed by an experienced provider. Detailed examination of the fetal heart (4-chamber view and outflow tracts view) and hands (for “clenching” or other abnormal positioning) should be included, as well as fetal biometry for assessment of intrauterine growth restriction. If no other sonographic abnormalities are present, the choroid plexus cyst is considered isolated.

Gindes et al (2013) evaluated the ability of 3D ultrasound for demonstrating the palate of fetuses at high-risk for cleft palate. A total of 57 fetuses at high-risk for cleft palate were referred to specialist for ultrasonography at 12 to 40 weeks' gestation. A detailed assessment of palate was made using both 2D and 3D ultrasounds on the axial plane. Antenatal diagnoses were compared with post-natal findings. Cleft palate was suspected in 13 (22.8%); a normal palate was demonstrated in 38 (67%), and in 6 (10.2%), the palate view could not be obtained. Mean gestational age at the first visit was 27 weeks 6 days (range of 12 to 40 weeks 3 days). Examination after delivery revealed that 1 of the 38 fetuses with presumed normal palate had a cleft hard palate, and 1 had a cleft soft palate (false negative = 5%). Among the 13 fetuses with suspected cleft palate, 3 had an intact palate (false-positive = 23%). Sensitivity, specificity, positive-predictive value, and negative-predictive value of detection of palatal clefts were 71.4%, 91.9%, 62.5%, and 94.4%, respectively. The authors concluded that using 3D ultrasounds, they diagnosed a cleft palate in 83% of high-risk cases, with 5% false negative. They stated that 3D technology might produce some technical artifacts resulting in a 23% false-positive rate.

Kanenishi et al (2013) evaluated the frequency of fetal facial expressions at 25 to 27 weeks of gestation using 4D ultrasound. A total of 24 normal fetuses were examined using 4D ultrasound. The face of each fetus was recorded continuously for 15 mins. The frequencies of tongue expulsion, yawning, sucking, mouthing, blinking, scowling, and smiling were assessed and compared with those observed at 28 to 34 weeks of gestation in a previous study. Mouthing was the most common facial expression at 25 to 27 weeks of gestation; the frequency of mouthing was significantly higher than that of the other 6 facial expressions (p < 0.05). Yawning was significantly more frequent than the other facial expressions, apart from mouthing (p < 0.05). The frequencies of yawning, smiling, tongue expulsion, sucking, and blinking differed significantly between 25 to 27 and 28 to 34 weeks (p < 0.05). The authors concluded that the results indicated that facial expressions can be used as an indicator of normal fetal neurologic development from the second to the third trimester. They stated that 4D ultrasound may be a valuable tool for assessing fetal neurobehavioral development during gestation. These preliminary findings need to be validated by well-designed studies.

Votino et al (2013) evaluated prospectively the use of 4D spatio-temporal image correlation (STIC) in the evaluation of the fetal heart at 11 to 14 weeks' gestation. The study involved off-line analysis of 4D-STIC volumes of the fetal heart acquired at 11 to 14 weeks' gestation in a population at high-risk for congenital heart disease (CHD). Regression analysis was used to investigate the effect of gestational age, maternal body mass index, quality of the 4D-STIC volume, use of a trans-vaginal versus trans-abdominal probe and use of color Doppler ultrasonography on the ability to visualize separately different heart structures. The accuracy in diagnosing CHD based on early fetal echocardiography (EFE) using 4D-STIC versus conventional 2D ultrasound was also evaluated. A total of 139 fetuses with a total of 243 STIC volumes were included in this study. Regression analysis showed that the ability to visualize different heart structures was correlated with the quality of the acquired 4D-STIC volumes. Independently, the use of a trans-vaginal approach improved visualization of the 4-chamber view, and the use of Doppler improved visualization of the outflow tracts, aortic arch and inter-ventricular septum. Follow-up was available in 121 of the 139 fetuses, of which 27 had a confirmed CHD. A diagnosis based on EFE using 4D-STIC was possible in 130 (93.5%) of the 139 fetuses. Accuracy in diagnosing CHD using 4D-STIC was 88.7%, and the results of 45% of the cases were fully concordant with those of 2D ultrasound or the final follow-up diagnosis. Early fetal echocardiography using 2D ultrasound was possible in all fetuses, and accuracy in diagnosing CHD was 94.2%; 5 of the 7 false-positive or false-negative cases were minor CHD. The authors concluded that in fetuses at 11 to 14 weeks' gestation, the heart can be evaluated offline using 4D-STIC in a large number of cases, and this evaluation is more successful the higher the quality of the acquired volume. Moreover, they stated that 2D ultrasound remains superior to 4D-STIC at 11 to 14 weeks, unless volumes of good to high quality can be obtained.

Ahmed (2014) stated that CHD is the commonest congenital anomaly. It is much more common than chromosomal malformations and spinal defects. Its' estimated incidence is about 4 to 13 per 1,000 live births. Congenital heart disease is a significant cause of fetal mortality and morbidity. Antenatal diagnosis of CHD is extremely difficult and requires extensive training and expertise. The detection rate of CHD is very variable and it ranged from 35 to 86% in most studies. In the light of the above, the introduction of the new 3D/4D based STIC is highly welcomed to improve antenatal detection of CHD. Spatio-temporal image correlation is an automated device incorporated into the ultrasound probe and has the capacity to perform slow sweep to acquire a single 3D volume. This acquired volume is composed of a great number of 2D frames. This volume can be analyzed and re-analyzed as required to demonstrate all the required cardiac views. It also provides the examiner with the ability to review all images in a looped cine sequence. The author concluded that this technology has the ability to improve the ability to examine the fetal heart in the acquired volume and decrease examination time; it is a promising tool for the future.

Tonni et al (2014) described the application of a novel 3D ultrasound reconstructing technique (OMNIVIEW) that may facilitate the evaluation of cerebral midline structures at the second trimester anatomy scan. Fetal cerebral midline structures from 300 consecutive normal low-risk pregnant women were studied prospectively by 2D and 3D ultrasound between 19 to 23 weeks of gestation. All the newborn infants underwent pediatric follow-up and were considered normal up to 2 years of life. In addition, 5 confirmed pathologic cases were evaluated and the abnormal features using this technique were described in this clinical series. Off-line volume data sets displaying the corpus callosum and the cerebellar vermis anatomy were accurately reconstructed in 98.5% and 96% of cases from sagittal and axial planes, respectively. For pathological cases, an agreement rate of 0.96 and 0.91 for mid-sagittal and axial planes, respectively, was observed. The authors concluded that this study demonstrated the feasibility of including 3D ultrasound as an adjunct technique for the evaluation of cerebral midline structures in the second trimester fetus. Moreover, they stated that future prospective studies are needed to evaluate if the application of this novel 3D reconstructing technique as a step forward following 2D second trimester screening scan will improve the prenatal detection of cerebral midline anomalies in the low-risk pregnant population.

Sharp et al (2014) noted that fetal assessment following preterm premature rupture of membrane (PPROM) may result in earlier delivery due to earlier detection of fetal compromise. However, early delivery may not always be in the fetal or maternal interest, and the effectiveness of different fetal assessment methods in improving neonatal and maternal outcomes is uncertain. In a Cochrane review, these researchers examined the effectiveness of fetal assessment methods for improving neonatal and maternal outcomes in PPROM. Examples of fetal assessment methods that would be eligible for inclusion in this review include fetal cardiotocography, fetal movement counting and Doppler ultrasound. They searched the Cochrane Pregnancy and Childbirth Group's Trials Register (June 30, 2014) and reference lists of retrieved studies. Randomized controlled trials (RCTs) comparing any fetal assessment methods, or comparing one fetal assessment method to no assessment were selected for analysis. Two review authors independently assessed trials for inclusion into the review. The same 2 review authors independently assessed trial quality and independently extracted data. Data were checked for accuracy. These researchers included 3 studies involving 275 women (data reported for 271) with PPROM at up to 34 weeks' gestation. All 3 studies were conducted in the United States. Each study investigated different methods of fetal assessment. One study compared weekly endovaginal ultrasound scans with no assessment (n = 93), one compared amniocentesis with no assessment (n = 47), and one compared daily non-stress testing with daily modified biophysical profiling (n = 135). These investigators were unable to perform a meta-analysis, but were able to report data from individual studies. There was no convincing evidence of increased risk of neonatal death in the group receiving endovaginal ultrasound scans compared with the group receiving no assessment (risk ratio (RR) 7.30, 95% CI: 0.39 to 137.54; 1 study, 92 women), or in the group receiving amniocentesis compared with the group receiving no amniocentesis (RR 1.00, 95% CI: 0.07 to 15.00; 1 study, 44 women). For both these interventions, these researchers inferred that there were no fetal deaths in the intervention or control groups. The study comparing daily non-stress testing with daily modified biophysical profiling did not report fetal or neonatal death. Primary outcomes of maternal death and serious maternal morbidity were not reported in any study. Overall, there were few statistically significant differences in outcomes between the comparisons. The overall quality of evidence was poor, because participant blinding was not possible for any study. The authors concluded that there is insufficient evidence on the benefits and harms of fetal assessment methods for improving neonatal and maternal outcomes in women with PPROM to draw firm conclusions. The overall quality of evidence that does exist is poor. They stated that further high-quality RCTs are needed to guide clinical practice.

In a Cochrane review, Alfirevic et al (2015) examined the effects on obstetric practice and pregnancy outcome of routine fetal and umbilical Doppler ultrasound in unselected and low-risk pregnancies. These investigators searched the Cochrane Pregnancy and Childbirth Group Trials Register (February 28, 2015) and reference lists of retrieved studies. Randomized and quasi-randomized controlled trials of Doppler ultrasound for the investigation of umbilical and fetal vessels waveforms in unselected pregnancies compared with no Doppler ultrasound were selected for analysis. Studies where uterine vessels have been assessed together with fetal and umbilical vessels have been included. Two review authors independently assessed the studies for inclusion, assessed risk of bias and carried out data extraction. In addition to standard meta-analysis, the 2 primary outcomes and 5 of the secondary outcomes were assessed using GRADE software and methodology. These researchers included 5 trials that recruited 14,624 women, with data analyzed for 14,185 women. All trials had adequate allocation concealment, but none had adequate blinding of participants, staff or outcome assessors. Overall and apart from lack of blinding, the risk of bias for the included trials was considered to be low. Overall, routine fetal and umbilical Doppler ultrasound examination in low-risk or unselected populations did not result in increased antenatal, obstetric and neonatal interventions. There were no group differences noted for the review's primary outcomes of perinatal death and neonatal morbidity. Results for perinatal death were as follows: (average RR 0.80, 95% CI: 0.35 to 1.83; 4 studies, 11,183 participants). Only 1 included trial assessed serious neonatal morbidity and found no evidence of group differences (RR 0.99, 95% CI: 0.06 to 15.75; 1 study, 2,016 participants). For the comparison of a single Doppler assessment versus no Doppler, evidence for group differences in perinatal death was detected (RR 0.36, 95% CI: 0.13 to 0.99; 1 study, 3,891 participants). However, these results are based on a single trial, and these researchers would recommend caution when interpreting this finding. There was no evidence of group differences for the outcomes of caesarean section, neonatal intensive care admissions or preterm birth of less than 37 weeks. When the quality of the evidence for the main comparison of “All Doppler versus no Doppler” was assessed with GRADE software, the outcomes of perinatal death and serious neonatal morbidity data were graded as of low quality. Evidence for the outcome of stillbirth was graded according to regimen subgroups – with a moderate quality rating for stillbirth (fetal/umbilical vessels only) and a low quality rating for stillbirth (fetal/umbilical vessels + uterine artery vessels). Evidence for admission to neonatal intensive care unit was assessed as of moderate quality, and evidence for the outcomes of caesarean section and preterm birth of less than 37 weeks was graded as of high quality. There was no available evidence to assess the effect on substantive long-term outcomes such as childhood neurodevelopment and no data to assess maternal outcomes, particularly maternal satisfaction. The authors concluded that existing evidence does not provide conclusive evidence that the use of routine umbilical artery Doppler ultrasound, or combination of umbilical and uterine artery Doppler ultrasound in low-risk or unselected populations benefits either mother or baby. They stated that future studies should be designed to address small changes in perinatal outcome, and should focus on potentially preventable deaths.

In a Cochrane review, Bricker et al (2015) evaluated the effects on obstetric practice and pregnancy outcome of routine late pregnancy ultrasound, defined as greater than 24 weeks' gestation, in women with either unselected or low-risk pregnancies. These investigators searched the Cochrane Pregnancy and Childbirth Group's Trials Register (May 31, 2015) and reference lists of retrieved studies. All acceptably controlled trials of routine ultrasound in late pregnancy (defined as after 24 weeks) were selected for analysis. Three review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. A total of 13 trials recruiting 34,980 women were included in the systematic review. Risk of bias was low for allocation concealment and selective reporting, unclear for random sequence generation and incomplete outcome data and high for blinding of both outcome assessment and participants and personnel. There was no difference in ante-natal, obstetric and neonatal outcome or morbidity in screened versus control groups. Routine late pregnancy ultrasound was not associated with improvements in overall perinatal mortality. There is little information on long-term substantive outcomes such as neurodevelopment. There is a lack of data on maternal psychological effects. Overall, the evidence for the primary outcomes of perinatal mortality, pre-term birth of less than 37 weeks, induction of labor and caesarean section were assessed to be of moderate or high quality with GRADE software. There was no association between ultrasound in late pregnancy and perinatal mortality (RR 1.01, 95% CI: 0.67 to 1.54; participants = 30,675; studies = 8; I² = 29%), pre-term birth of less than 37 weeks (RR 0.96, 95% CI: 0.85 to 1.08; participants = 17,151; studies = 2; I² = 0%), induction of labor (RR 0.93, 95% CI: 0.81 to 1.07; participants = 22,663; studies = 6; I² = 78%), or caesarean section (RR 1.03, 95% CI: 0.92 to 1.15; participants = 27,461; studies = 6; I² = 54%). Three additional primary outcomes chosen for the “Summary of findings” table were pre-term birth of less than 34 weeks, maternal psychological effects and neurodevelopment at age 2. Because none of the included studies reported these outcomes, they were not assessed for quality with GRADE software. The authors concluded that based on existing evidence, routine late pregnancy ultrasound in low-risk or unselected populations did not confer benefit on mother or baby. There was no difference in the primary outcomes of perinatal mortality, pre-term birth of less than 37 weeks, caesarean section rates, and induction of labor rates if ultrasound in late pregnancy was performed routinely versus not performed routinely. Meanwhile, data were lacking for the other primary outcomes: pre-term birth of less than 34 weeks, maternal psychological effects, and neurodevelopment at age 2, reflecting a paucity of research covering these outcomes. The authors stated that these outcomes may warrant future research.

The Zika virus is a mosquito-borne virus that has been associated with congenital defects, primarily of the central nervous system (SMFM, 2016). According to the Centers for Disease Control and Prevention, the American College of Obstetricians and Gynecologists, and the Society for Maternal-Fetal Medicine, clinicians should screen pregnant women for possible Zika exposure, particularly if living or traveled to areas of active Zika transmission. Pregnant women exposed to Zika or who report clinical illness consistent with the virus should be tested for the virus based on national guidelines. Part of that testing involves fetal ultrasound to detect microcephaly or intracranial calcifications, and in certain cases, amniocentesis may be offered (SMFM, 2016).

Intra-Partum Ultrasound for Diagnosis of Mal-Positions and Cephalic Mal-Presentations

Bellussi and colleagues (2017) noted that fetal mal-positions and cephalic mal-presentations are well-recognized causes of failure to progress in labor. They frequently require operative delivery, and are associated with an increased probability of fetal and maternal complications. Traditional obstetrics emphasizes the role of digital examinations, but recent studies demonstrated that this approach is inaccurate and intra-partum US is far more precise. These investigators summarized the available evidence and provided recommendations to identify mal-positions and cephalic mal-presentations with US. These researchers proposed a systematic approach consisting of a combination of trans-abdominal and trans-perineal scans and described the findings that allow an accurate diagnosis of normal and abnormal position, flexion, and synclitism of the fetal head. The management of mal-positions and cephalic mal-presentation is currently a matter of debate, and individualized depending on the general clinical picture and expertise of the provider. The authors concluded that intra-partum US allows a precise diagnosis and thus offers the best opportunity to design prospective studies with the aim of establishing evidence-based treatment.

Ultrasound for Detection of Thrombosis in Pregnancy

Castro and associates (2017) determined the diagnostic accuracy of US to detect deep-vein thrombosis (DVT) in pregnant patients. These investigators searched PubMed, LILACS, Scopus, Google Scholar and System for Information on Grey Literature from inception to April 2016. The reference lists of the included studies were analyzed. Original articles from accuracy studies that analyzed US to diagnose DVT in pregnant women were included. Reference standard was the follow-up time. The QUADAS-2 score was used for quality assessment. Titles and summaries from 2,129 articles were identified; 4 studies that evaluated DVT in pregnant women were included; a total of 486 participants were enrolled. High risk of bias was seen in 3 out of 4 studies included regarding flow and timing domain of QUADAS-2. Negative predictive value was 99.39%. The authors concluded that accuracy of US to diagnose DVT in pregnant women was not determined due to the absence of data yielding positive results. They stated that further studies of low risk of bias are needed to determine the diagnostic accuracy of US in this clinical scenario.

Ultrasound for Detection of Bicornuate Uterus

A bicornuate uterus has a fundus that is indented 1 cm or more and the vagina and cervix are generally normal. It results from partial rather than complete fusion of the Müllerian ducts. Depending on the extent of fusion, separation of the uterine horns will be complete, partial, or minimal. The diagnosis is based on ultrasound findings of two usually moderately separated (ie, divergent) endometrial cavities and an indented fundal contour.

Czeizel et al (2011) studied the possible association between uterus uni- or bicornis in pregnant women and structural birth defects (ie, congenital abnormalities) in their offspring. There were 22,843 cases with congenital abnormality recorded in the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996. These subjects were matched to 38,151 controls without any defect. Prevalence of medically recorded uterus uni/bicornis in the prenatal maternity logbook in the mothers of subjects with different congenital abnormalities and of their matched controls without any defect were compared. Fifty-seven (0.25%) subjects and 67 (0.18%) controls had mothers with uterus uni/bicornis. There was a significant association of uterus uni/bicornis in pregnant women with a higher risk of total group of congenital abnormalities (adjusted odds ratio, 1.5; 95% confidence interval, 1.1-2.2) explained mainly by a significantly higher risk of clubfoot and particularly postural deformity association in their children (adjusted odds ratio, 4.7; 95% confidence interval, 2.4-9.1).The authors concluded that pregnant women with a uni/bicornis uterus have a significantly higher risk of clubfoot and postural deformity association.

Martinez-Frías et al (1998) stated most of the reports on mothers with bicornuate uterus analyze fertility, reproductive capacity, and pregnancy outcomes. Very few of them, however, mention the risk for congenital anomalies in their offspring. Further, to the authors’ knowledge, no epidemiologic studies estimating the risk for congenital defects and analyzing the type of anomalies observed in infants born to mothers with bicornuate uterus have been reported. Using a case-control study series, the authors estimated the risk of congenital anomalies in the offspring of women with a bicornuate uterus. To identify the specific defects associated with the presence of a bicornuate uterus in the mother, 26 945 consecutive malformed infants from the Spanish Collaborative Study of Congenital Malformations were assessed for the frequency of congenital anomalies in the offspring of mothers with a bicornuate uterus and in those born to mothers with a normal uterus. Then, the relative frequency, which is the quotient of the frequency of the individual defects in each group, was calculated. This figure expresses the times each congenital defect is more frequent in infants of mothers with a bicornuate uterus than in those born to mothers with a normal uterus. Offspring of mothers with a bicornuate uterus had a risk for congenital defects four times higher than infants born to women with a normal uterus. The risk was statistically significant for some specific defects such as nasal hypoplasia, omphalocele, limb deficiencies, teratomas, and acardia-anencephaly. The authors concluded that offspring of mothers with bicornuate uterus are not only at high risk for deformations and disruptions, but also for some type of malformations.

Combined Measurement of Placental Biomarkers Plus Ultrasound Assessment of Fetal Growth for the Identification of Placental Dysfunction

Heazell and colleagues (2019) noted that stillbirth affects 2.6 million pregnancies worldwide each year. While the majority of cases occur in low- and middle-income countries, stillbirth remains an important clinical issue for high-income countries (HICs) – with both the United Kingdom and the United States reporting rates above the mean for HICs. In HICs, the most frequently reported association with stillbirth is placental dysfunction. Placental dysfunction may be evident clinically as fetal growth restriction (FGR) and small-for-dates infants. It can be caused by placental abruption or hypertensive disorders of pregnancy and many other disorders and factors. Placental abnormalities are noted in 11% to 65% of stillbirths. Identification of FGA is difficult in-utero. Small-for-gestational age (SGA), as assessed following birth, is the most commonly used surrogate measure for this outcome. The degree of SGA is associated with the likelihood of FGR; 30% of infants with a birth-weight of less than 10th centile are thought to be FGR, while 70% of infants with a birth-weight less than third centile are thought to be FGR. Critically, SGA is the most significant antenatal risk factor for a stillborn infant. Correct identification of SGA infants is associated with a reduction in the perinatal mortality rate. However, currently used tests, such as measurement of symphysis-fundal height, have a low reported sensitivity and specificity for the identification of SGA infants. In a Cochrane review, these researchers compared the diagnostic accuracy of US assessment of fetal growth by estimated fetal weight (EFW) and placental biomarkers alone and in any combination used after 24 weeks of pregnancy in the identification of placental dysfunction as evidenced by either stillbirth, or birth of a SGA infant. Secondary objectives were to examine the effect of clinical and methodological factors on test performance. These investigators developed full search strategies with no language or date restrictions. The following sources were searched: Medline, Medline In Process and Embase via Ovid, Cochrane (Wiley) CENTRAL, Science Citation Index (Web of Science), CINAHL (EBSCO) with search strategies adapted for each database as required; ISRCTN Registry, UK Clinical Trials Gateway, WHO International Clinical Trials Portal and ClinicalTrials.gov for ongoing studies; specialist abstract and conference proceeding resources (British Library's ZETOC and Web of Science Conference Proceedings Citation Index). Search last conducted in October 2016. These investigators included studies of pregnant women of any age with a gestation of at least 24 weeks if relevant outcomes of pregnancy (livebirth/stillbirth; SGA infant) were assessed. Studies were included irrespective of whether pregnant women were deemed to be low or high risk for complications or were of mixed populations (low and high risk). Pregnancies complicated by fetal abnormalities and multi-fetal pregnancies were excluded as they have a higher risk of stillbirth from non-placental causes. With regard to biochemical tests, these researchers included assays performed using any technique and at any threshold used to determine test positivity. They extracted the numbers of true positive, false positive, false negative, and true negative test results from each study; and evaluated risk of bias and applicability using the QUADAS-2 tool. Meta-analyses were performed using the hierarchical summary ROC model to estimate and compare test accuracy.

These researchers included a total of 91 studies that evaluated 7 tests – blood tests for human placental lactogen (hPL), estriol, placental growth factor (PlGF) and uric acid, US-EFW and placental grading and urinary estriol – in a total of 175,426 pregnant women, in which 15,471 pregnancies ended in the birth of a small baby and 740 pregnancies which ended in stillbirth. The quality of included studies was variable with most domains at low risk of bias although 59% of studies were deemed to be of unclear risk of bias for the reference standard domain; 53% of studies were of high concern for applicability due to inclusion of only high- or low-risk women. Using all available data for SGA (86 studies; 159,490 pregnancies involving 15,471 SGA infants), there was evidence of a difference in accuracy (p < 0.0001) between the 7 tests for detecting pregnancies that were SGA at birth. US-EFW was the most accurate test for detecting SGA at birth with a diagnostic odds ratio (DOR) of 21.3 (95% CI: 13.1 to 34.6); hPL was the most accurate biochemical test with a DOR of 4.78 (95% CI: 3.21 to 7.13). In a hypothetical cohort of 1,000 pregnant women, at the median specificity of 0.88 and median prevalence of 19%, EFW, hPL, estriol, urinary estriol, uric acid, PlGF and placental grading will miss 50 (95% CI: 32 to 68), 116 (97 to 133), 124 (108 to 137), 127 (95 to 152), 139 (118 to 154), 144 (118 to 161), and 144 (122 to 161) SGA infants, respectively. For the detection of pregnancies ending in stillbirth (21 studies; 100,687 pregnancies involving 740 stillbirths), in an indirect comparison of the 4 biochemical tests, PlGF was the most accurate test with a DOR of 49.2 (95% CI: 12.7 to 191). In a hypothetical cohort of 1,000 pregnant women, at the median specificity of 0.78 and median prevalence of 1.7%, PlGF, hPL, urinary estriol and uric acid will miss 2 (95% CI: 0 to 4), 4 (2 to 8), 6 (6 to 7) and 8 (3 to 13) stillbirths, respectively. No studies examined the accuracy of US-EFW for detection of pregnancy ending in stillbirth. The authors concluded that biochemical markers of placental dysfunction used alone had insufficient accuracy to identify pregnancies ending in SGA or stillbirth. Studies combining US and placental biomarkers are needed to determine whether this approach improves diagnostic accuracy over the use of US estimation of fetal size or biochemical markers of placental dysfunction used alone. These researchers stated that many of the studies included in this review were performed between 1974 and 2016. Studies of placental substances were mostly carried out before 1991 and after 2013; earlier studies may not reflect developments in test technology. No studies were identified for this review that examined the accuracy of US and blood tests used together.

Routine Third Trimester Ultrasonography to Reduce Adverse Perinatal Outcomes in Low-Risk Pregnancy

In a randomized, multi-center, stepped-wedge cluster trial, Henrichs and colleagues (2019) examined the effectiveness of routine US in the third trimester in reducing adverse perinatal outcomes in low-risk pregnancies compared with usual care and the effect of this policy on maternal outcomes and obstetric interventions. A total of 60 midwifery practices in the Netherlands with 13,046 women aged 16 years or older with a low-risk singleton pregnancy were included in this study. These midwifery practices offered usual care (serial fundal height measurements with clinically indicated US). After 3, 7, and 10 months, 1/3 of the practices were randomized to the intervention strategy. As well as receiving usual care, women in the intervention strategy were offered 2 routine biometry scans at 28 to 30 and 34 to 36 weeks' gestation. The same multi-disciplinary protocol for detecting and managing fetal growth restriction was used in both strategies. The primary outcome measure was a composite of severe adverse perinatal outcomes: perinatal death, Apgar score of less than 4, impaired consciousness, asphyxia, seizures, assisted ventilation, septicemia, meningitis, broncho-pulmonary dysplasia (BPD), intra-ventricular hemorrhage, peri-ventricular leukomalacia, or necrotizing enterocolitis. Secondary outcomes were 2 composite measures of severe maternal morbidity, and spontaneous labor and birth. Between February 1, 2015 and February 29, 2016, 60 midwifery practices enrolled 13,520 women in mid-pregnancy (mean of 22.8 (standard deviation [SD] 2.4) weeks' gestation); 13,046 women (intervention n = 7,067, usual care n = 5,979) with data based on the national Dutch perinatal registry or hospital records were included in the analyses. Small for gestational age (SGA) at birth was significantly more often detected in the intervention group than in the usual care group (179 of 556 (32%) versus 78 of 407 (19%), p < 0.001). The incidence of severe adverse perinatal outcomes was 1.7% (n = 118) for the intervention strategy and 1.8% (n = 106) for usual care. After adjustment for confounders, the difference between the groups was not significant (odds ratio [OR] 0.88, 95% CI: 0.70 to 1.20). The intervention strategy showed a higher incidence of induction of labor (1.16, 1.04 to 1.30) and a lower incidence of augmentation of labor (0.78, 0.71 to 0.85). Maternal outcomes and other obstetric interventions did not differ between the strategies. The authors concluded that in low-risk pregnancies, routine US in the third trimester along with clinically indicated US was associated with higher antenatal detection of SGA fetuses but not with a reduced incidence of severe adverse perinatal outcomes compared with usual care alone. These researchers stated that these findings do not support routine US in the third trimester for low-risk pregnancies. They noted that challenges for future research are to identify the most appropriate fetal growth and birth-weight charts and to develop more sensitive and effective methods to detect fetal growth restriction. Such methods include other US markers of fetal compromise, maternal and placental biomarkers, and maternal awareness of fetal well-being.

The authors stated that this study had strengths and limitations. The cluster randomized design controlled for unknown confounders at the cluster level and limited contamination between the study strategies, which might occur in individual randomized trials. The stepped wedge design reduced confounding owing to differences between midwifery practices because each practice applied the control and intervention strategy for some of the time. Sonographers met pre-defined quality criteria, and a multi-disciplinary protocol was developed for detecting and managing fetal growth restriction to achieve the best quality care possible in a pragmatic nationwide study.

These investigators did not achieve their required sample size of 15,000 women. Owing to the stepped-wedge design, it was not possible to extend the data collection period because the midwifery practices had adopted the intervention strategy at the end of the study period; thus, they could not completely rule out that the study lacked the statistical power to determine if routine US had a beneficial or harmful effect on perinatal outcomes compared with usual care. Although these researchers found a difference of only 0.1% between the 2 strategies, it was unlikely that this difference would have met the pre-defined meaningful difference of 0.54% had the sample size been larger. Also, these researchers used registration data as an initial screening for potential severe adverse perinatal outcomes. Information was also obtained from many hospital records, but for most women only routine registration data for adverse outcomes were available. Because of the inherent limitations of these data, several outcomes might have been mis-classified as normal, resulting in an under-estimation of the primary outcome for both strategies. However, these investigators did not expect that this has biased the comparison between the 2 strategies as the incidence of adverse outcomes was similar to their estimations. Furthermore, because of the collinearity of time of inclusion period and study condition, these investigators were unable to adjust for time. The effect estimates of their main analyses might therefore be over-estimated. Also, this study was conducted in 1 country (the Netherlands) where primary antenatal care of uncomplicated pregnancies is provided by midwives who are educated, trained, and officially registered as independent health practitioners. When risk factors or complications occur, women are referred to obstetrician led care. For about 90% of women in the Netherlands, antenatal care is midwife led initially, and about 50% of women start labor in midwife led care. Also, most of the recommendations of the multi-disciplinary protocol for diagnosing and managing suspected fetal growth restriction in this study were similar to international guidelines in other countries (e.g., the Royal College of Obstetricians and Gynecologist), making these findings relevant to low-risk populations in other international care contexts.

Fetal Ultrasound with Detailed Anatomic Examination for Evaluation of the Fetus of a Mother who has Uterus Didelphys

Malini et al (1984) conducted a retrospective study of 68 female patients with sonographic diagnoses of genital tract anomalies. Corroboration by hysterosalpingography and/or surgery was available in 47 cases (69%) and by visualization of 2 cervices on physical examination in 3 cases (4%). Scan results were categorized as diagnostic, confirmatory, and incorrect; 50 patients were placed in the following proposed categories: segmental Mullerian agenesis (4 cases); "peculiar appearing" uterus (3 cases); uterus didelphys (19 cases); bicornuate and septate uterus (22 cases); obstructed lower with normal upper genital tract (2 cases).

Witters et al (2012) noted that hydrometrocolpos, occurring in approximately 1/6000 newborn girls, can be caused by a stenotic urogenital sinus, a severe cloacal malformation, but also by other conditions such as an imperforate hymen, a midline vaginal septum and vaginal atresia. The prenatal differential diagnosis of this wide spectrum of conditions is not easy and requires a multi-disciplinary approach with follow-up scans and MRI to access the severity of the condition. A non-consanguineous couple was referred in the 1st pregnancy at 30 weeks. The father, 30 years of age, of Caucasian origin, and the mother of Asian origin, 26 years of age. Ultrasound (US) at 30 weeks revealed ambiguous genitalia (with suspicion of clitoral hypertrophy), a septated structure located behind the bladder compatible with hydrometrocolpos with a uterine malformation (uterus didelphys), a single umbilical artery, mild ascites and growth on the 10th centile. The differential diagnosis included a vaginal atresia, a urogenital sinus and a more severe cloacal malformation. After serial scans, MRI and counselling by an experienced surgeon the preferential diagnosis of a cloacal malformation was made; and a late pregnancy termination was carried out. Pathological examination revealed: low vaginal atresia with uterus didelphys, anal atresia with rectovaginal fistula and a normal urinary tract. The differential diagnosis between hydrometrocolpos due to vaginal atresia or due to a more severe cloacal malformation is not straightforward. Care should be taken in decision-making and counselling patients with these complex prenatal malformations.

In a retrospective, cohort study, Crane et al (2012) examined if cervical length measured by transvaginal US (TVUS) in women with uterine anomalies predicts spontaneous preterm birth (SPTB). These researchers compared women with a uterine anomaly who were pregnant with singleton gestations and delivered August 2000 to April 2008 to a low-risk control group. Transvaginal ultrasonographic cervical lengths were measured 16 to 30 weeks gestation. Primary outcome was cervical length and SPTB less than 35 weeks and the primary exposure variable of interest was cervical length. Secondary outcomes were SPTB less than 37 weeks, less than 32 weeks, low birthweight, maternal and neonatal outcomes. Receiver operating characteristic curves (ROCs) were generated to identify the best cervical length cut-off. Women with a bicornuate uterus (n = 35) had shorter cervical length (3.46 cm) than the low-risk control group (n = 122, 4.32 cm, p < 0.0001). Women with a bicornuate or didelphys uterus, compared with low-risk women, had higher rates of SPTB less than 35 weeks (8.6% and 30.8% versus 0.8%, p = 0.0007), neonatal intensive care unit (NICU) admission more than 24 hours (26.5% and 41.7% versus 7.5%, p = 0.0021) and composite perinatal morbidity (32.4% and 69.2% versus 8.3%, p < 0.0001). Using a cut-off of 3.0 cm, TVUS cervical length in women with a bicornuate uterus predicted SPTB less than 35 weeks (positive predictive value [PPV] = 37.5% and negative predictive value [NPV] = 100%), birthweight less than 2,500 g (PPV = 50.0% and NPV = 96.3%) and respiratory distress syndrome (PPV = 37.5% and NPV = 100%). The authors concluded that women with a bicornuate uterus had shorter cervical lengths than low risk controls, and were at higher risk of SPTB less than 35 weeks; TVUS cervical length predicted SPTB less than 35 weeks, low birthweight and perinatal morbidity in these women.

Hughes et al (2020) noted that uterine anomalies occur in an estimated 5% of women and have been shown to confer a higher risk of SPTB. A sonographically short cervix (less than 25 mm) is a risk indicator for SPTB, although its predictive utility has been little studied in this specific high-risk population. In a historical cohort study, these researchers examined the pregnancy outcomes and predictive ability of short cervix in a cohort of women with uterine anomalies attending a high-risk antenatal clinic. They evaluated all pregnancies in women with congenital uterine anomalies referred to the Preterm labor Clinic at the Royal Women's Hospital, Melbourne, Australia, between 2004 and 2013. Logistic and linear regressions and ROCs were used to examine associations between cervical length and preterm birth. SPTB (less than 37 weeks' gestation) occurred in 23% of the 86 pregnancies (n = 20); rates by subgroup were: unicornuate uterus 60% (n = 3/5), uterus didelphys 40% (n = 6/15), bicornuate uterus 18% (n = 9/51), septate uterus 13% (n = 2/15). Preterm pre-labor rupture of membranes occurred in 55% of spontaneous preterm births and was not independently associated with the presence of cervical cerclage or ureaplasma urealyticum. Short cervical length was associated with SPTB in women with septate uterus. Short cervix at 24 weeks (not at 16 or 20 weeks) was moderately predictive of SPTB of less than 34 weeks. The authors concluded that women with uterine anomalies were at increased risk of spontaneous preterm birth, especially those with unicornuate uterus or uterus didelphys, but cervical surveillance did not identify these cases. Short cervix may be associated with SPTB in women with septate uterus. Preterm pre-labor rupture of membranes occurred in 55% of SPTB. Ultrasonography was one of the keywords listed in this study.

Furthermore, an UpToDate review on “Congenital uterine anomalies: Clinical manifestations and diagnosis” (Laufer and DeCherney, 2020) states that “Uterus didelphys, or double uterus, is a duplication of the reproductive structures. Generally, the duplication is limited to the uterus and cervix (uterine didelphys and bicollis [2 cervixes]), although duplication of the vulva, bladder, urethra, vagina, and anus may also occur. Fifteen to 20% of patients with didelphic uterus also have unilateral anomalies, such as an obstructed hemivagina and ipsilateral renal agenesis; the anomalies are on the right in 65% of cases. Uterine didelphys occurs when the 2 Mullerian ducts fail to fuse. Diagnosis is typically made by a combination of ultrasound showing 2 widely separated uterine horns with a deep fundal indentation and speculum examination showing 2 cervixes. MRI is rarely needed to make a definitive diagnosis”.

Obstetric Anatomic Ultrasound and Fetal Echocardiography in Detecting Congenital Heart Disease in High-Risk Pregnancies

Krishnan and colleagues (2021) examined the concordance between 2nd-trimester anatomic US and fetal echocardiography in detecting minor and critical CHD in pregnancies meeting American Heart Association (AHA) criteria. These investigators carried out a retrospective cohort study of pregnancies in which a 2nd-trimester fetal anatomic US examination (18 to 26 weeks) and fetal echocardiography were conducted between 2012 and 2018 at the authors’ institution based on AHA recommendations. Anatomic US studies were interpreted by maternal-fetal medicine specialists and fetal echocardiographic studies by pediatric cardiologists. The primary outcome was the proportion of critical CHD (CCHD) cases not detected by anatomic US but detected by fetal echocardiography. The secondary outcome was the proportion of total CHD cases missed by anatomic US but detected by fetal echocardiography. Neonatal medical records were reviewed for all pregnancies when obtained and available. A total of 722 studies met inclusion criteria. Anatomic US and fetal echocardiography were in agreement in detecting cardiac abnormalities in 681 (96.1%) studies (κ = 0.803; p < 0.001). The most common diagnosis not identified by anatomic US was a ventricular septal defect, accounting for 9 of 12 (75%) missed congenital heart defects. Of 664 studies with normal cardiac findings on the anatomic US examinations, no additional instances of CCHD were detected by fetal echocardiography. No unanticipated instances of CCHD were diagnosed postnatally. The authors concluded that with current AHA screening guidelines, automatic fetal echocardiography in the setting of normal detailed anatomic US findings provided limited benefit in detecting congenital heart defects that would warrant immediate post-natal interventions. These investigators stated that more selective use of automatic fetal echocardiography in at-risk pregnancies should be explored.

Detailed Fetal US for Diagnosis / Evaluation of Uterus Didelphys

Hughes et al (2020) noted that uterine anomalies occur in an estimated 5 % of women and have been shown to confer a higher risk of SPTB. A sonographically short cervix (less than 25 mm) is a risk indicator for SPTB, although its predictive utility has been little studied in this specific high-risk population. In a historical cohort study, these researchers examined the pregnancy outcomes and predictive ability of short cervix in a cohort of women with uterine anomalies attending a high-risk antenatal clinic. They evaluated all pregnancies in women with congenital uterine anomalies referred to the Preterm labor Clinic at the Royal Women's Hospital, Melbourne, Australia, between 2004 and 2013. Logistic and linear regressions and ROCs were used to examine associations between cervical length and preterm birth. SPTB (less than 37 weeks' gestation) occurred in 23 % of the 86 pregnancies (n = 20); rates by subgroup were: unicornuate uterus 60 % (n = 3/5), uterus didelphys 40 % (n = 6/15), bicornuate uterus 18 % (n = 9/51), septate uterus 13 % (n = 2/15). Preterm pre-labor rupture of membranes occurred in 55 % of spontaneous preterm births and was not independently associated with the presence of cervical cerclage or ureaplasma urealyticum. Short cervical length was associated with SPTB in women with septate uterus. Short cervix at 24 weeks (not at 16 or 20 weeks) was moderately predictive of SPTB of less than 34 weeks. The authors concluded that women with uterine anomalies were at increased risk of spontaneous preterm birth, especially those with unicornuate uterus or uterus didelphys, but cervical surveillance did not identify these cases. Short cervix may be associated with SPTB in women with septate uterus. Preterm pre-labor rupture of membranes occurred in 55 % of SPTB. Ultrasonography was one of the keywords listed in this study.

Furthermore, an UpToDate review on “Congenital uterine anomalies: Clinical manifestations and diagnosis” (Laufer and DeCherney, 2021) states that “Uterus didelphys, or double uterus, is a duplication of the reproductive structures. Generally, the duplication is limited to the uterus and cervix (uterine didelphys and bicollis [2 cervixes]), although duplication of the vulva, bladder, urethra, vagina, and anus may also occur. Fifteen to 20 % of patients with didelphic uterus also have unilateral anomalies, such as an obstructed hemivagina and ipsilateral renal agenesis; the anomalies are on the right in 65 % of cases. Uterine didelphys occurs when the 2 Mullerian ducts fail to fuse. Diagnosis is typically made by a combination of ultrasound showing 2 widely separated uterine horns with a deep fundal indentation and speculum examination showing 2 cervixes. MRI is rarely needed to make a definitive diagnosis”.

Detailed Fetal US at 20 Weeks Based on Previous Pregnancy with a Child with DiGeorge Syndrome

The American Institute of Ultrasound in Medicine (AIUM)’s practice parameter on “Performance of detailed second- and third-trimester diagnostic obstetric ultrasound examinations” (AIUM, 2019) listed “previous fetus or child with a congenital, genetic, or chromosomal abnormality” as an indication for a detailed fetal anatomic examination.

GeneReviews’ webpage on “22q11.2 Deletion syndrome” (McDonald-McGinn et al, 2020) stated that fetus at high risk of having 22q11.2DS should undergo a level II US with fetal echocardiogram to evaluate for the following anomalies: congenital heart disease; airway, palate, swallowing, and gastro-intestinal (GI) differences possibly leading to polyhydramnios (congenital diaphragmatic hernia, tracheoesophageal fistula, subglottic stenosis, vascular ring, laryngeal web, cleft palate, and cleft and lip/palate); renal anomalies; skeletal differences such as club foot and craniosynostosis; and umbilical and inguinal hernia.

Furthermore, an UpToDate review on “Overview of ultrasound examination in obstetrics and gynecology” (Shipp, 2021) states that “Detailed examination -- A detailed (or specialized or comprehensive) fetal structural survey should only be undertaken by those with the necessary training and skills required for these advanced examinations. Indications for a detailed fetal examination include, but are not limited to, a previous pregnancy affected by a fetal anatomic or chromosomal abnormality; suspected, including those at increased risk for, or known fetal anatomic or chromosomal abnormality in the current pregnancy; known fetal growth disorder; and current pregnancy complications possibly affecting the fetus (e.g., congenital infection, abnormal amniotic fluid volume, alloimmunization, suspected placenta accreta spectrum). Fetal evaluation in these settings requires a more detailed examination of fetal and placental anatomy than a standard fetal survey and requires more advanced skills and knowledge”.

Detailed Fetal Ultrasound for Myasthenia Gravis During Pregnancy

Bansal and colleagues (2018) noted that the management of myasthenia gravis (MG) during pregnancy requires special skills as both diseases as well as its treatment can have deleterious effects on mother and fetus. MG often affects women in 2nd and 3rd decades of life during the child-bearing age. Exacerbations of MG are likely to occur during the 1st trimester and post-partum period. The treatment of MG during pregnancy needs to be individualized depending on the severity of MG as well as the effectiveness of various treatment modalities and their possible harmful effects on pregnancy. Furthermore, special attention has to be given to avoid drugs and other factors (such as urinary tract infections) that may worsen MG. The key to successful outcome during pregnancy in women with MG lies in multi-disciplinary care involving obstetricians, neurologists, anesthetist as well as neonatologist. The authors discussed various therapeutic options available for the management of MG during pregnancy and provided recommendations based on the current best evidence. Detailed fetal US is not mentioned as a management tool.

Furthermore, an UpToDate review on “Management of myasthenia gravis in pregnancy” (Bird et al, 2022) does not mention detailed / 3D fetal ultrasound as a management tool.

Detailed Fetal Ultrasound for Syphilis During Pregnancy

Junior et al (2012) noted that the numbers of syphilis cases have been increasing considerably, especially in Eastern Europe, thereby contributing towards greater chances of cases of congenital syphilis. Some of the complications of congenital syphilis can be detected on 2D ultrasonography (2DUS), and these are generally manifested in the 2nd trimester of pregnancy. The commonest ultrasonographic signs are hepato-splenomegaly, placentomegaly, and fetal growth restriction, while lower-frequency occurrences include intra-hepatic calcifications, ascites, fetal hydrops, and even fetal death. Three-dimensional ultrasonography (3DUS) is a relatively new imaging technique that is adjuvant to 2DUS and enables detailed assessment of the fetal surface anatomy. These researchers presented a case of a 21-year-old primigravida with a diagnosis of congenital syphilis, with obstetric 2DUS findings of hepato-splenomegaly, ascites, peri-cardial effusion and hyper-echogenicity of the cerebral parenchyma. 3DUS in rendering mode allowed clear assessment of the fetal limbs, especially the feet, which appeared twisted and lacked some toes. It allowed the parents to understand the pathological condition better and improved pre-natal management and neonatal follow-up. The authors concluded that 3DUS could be used routinely for assessing fetal malformations resulting from congenital infections.

Guidelines on sexually transmitted diseases from the Centers for Disease Control and Prevention (2021) state: "When syphilis is diagnosed during the second half of pregnancy, management should include a sonographic fetal evaluation for congenital syphilis. However, this evaluation should not delay therapy. Sonographic signs of fetal or placental syphilis (e.g., hepatomegaly, ascites, hydrops, fetal anemia, or a thickened placenta) indicate a greater risk for fetal treatment failure ; cases accompanied by these signs should be managed in consultation with obstetric specialists. A second dose of benzathine penicillin G 2.4 million units IM after the initial dose might be beneficial for fetal treatment in these situations."

An UpToDate review on “Syphilis in pregnancy” (Norwitz and Hicks, 2021) explains: "Fetal infection should be suspected if there are characteristic findings on ultrasound examination after 20 weeks of gestation in a woman with untreated or inadequately treated syphilis. Before 18 to 20 weeks, fetal abnormalities are not usually seen because of fetal immunologic immaturity.

Detailed Fetal Ultrasound for Pregnant Women with a Previous Pregnancy with a Fetus that had Omphalocele

The Consensus Report on “The detailed fetal anatomic ultrasound examination” (Wax et al, 2014) listed “Previous fetus or child with a congenital, genetic, or chromosomal abnormality” as an indication for a detailed fetal anatomic examination.

Detailed Fetal Ultrasound for Evaluation of Septate or Arcuate Uterus

In a prospective study, Kupesic and Kurjak (1998) compared the accuracy of TVUS, transvaginal color Doppler, hysterosonography, and 3D-US in the detection of septate uteri. These researchers also examined obstetrical prognosis of the septate uterus and examined the reproductive outcome following operative hysteroscopy. A total of 420 infertile patients undergoing hysteroscopy were examined during a 4-year period. TVUS and color Doppler were performed in all patients, whereas hysterosonography and 3D-US were used in 76 and 86 patients, respectively. The sensitivity of TVUS and transvaginal color Doppler in the identification of the septate uterus was 95.0 % and 99.3 %, respectively. Color and pulsed Doppler studies of the septal area revealed vascularity in 71.2 %. The sensitivity of hysterosonography and 3D-US in the detection of the septate uterus were 100 % and 93.6 %, respectively. However, the latter method predicted the existence of a congenital uterine defect in all the patients with septate uterus; but was inaccurate in differentiating it from other fusion anomalies. The pregnancy rate in 116 patients following the operative hysteroscopy for an intra-uterine septum in a prospective follow-up period of 24 months was 50.9 %: 44 patients (74.6 %) had term deliveries, 11 (18.6 %) had 1st trimester abortion, and 4 (6.8 %) had pre-term delivery (PTD). The authors concluded that transvaginal color Doppler and hysterosonography were highly accurate diagnostic tools for pre-operative evaluation of the uterine cavitary defects; 3D-US increased the accuracy of conventional 2D transvaginal scan, allowing precise reconstruction of the uterine cavity. Removing the intra-uterine septum in patients suffering from infertility and recurrent pregnancy wastage was beneficial.

In a prospective study, Heinonen (1999) analyzed 467 births among 255 women with uterine malformations and showed that 3 (0.64 %) newborns had limb reduction defects; 2 women had a subseptate uterus and 1 a complete septate uterus with a longitudinal vaginal septum. One newborn had a bilateral split hand and split foot, 1 had absence of left hand and wrist. One infant was born without left hand, wrist and 1 antebrachial bone associated with omphalocele, and diaphragmatic hernia died during the neonatal period. The author stated that an association between severe limb reduction defects and septate uterus was possible, although the mechanism was unclear. The author concluded that the findings of this analysis indicated a need to examine the uterine cavity if a newborn had this invalid defect, and a detailed US examination of fetal limbs was needed in a case of a pregnant septate uterus.

Woelfer et al (2001) examined reproductive outcomes in women with congenital uterine anomalies detected incidentally by 3D-US. These researchers studied 1,089 women with no history of infertility or recurrent miscarriage who were seen for a TVUS scan; they were screened for uterine abnormalities using 3D-US. These investigators determined prevalence of miscarriage and pre-term labor in women with normal and abnormal uterine morphology. They found that 983 women had a normally shaped uterine cavity, 72 an arcuate, 29 a subseptate, and 5 a bicornuate uterus. Women with a subseptate uterus had a significantly higher proportion of 1st-trimester loss (Zeta = 4.68, p < 0.01) compared with women with a normal uterus. Women with an arcuate uterus had a significantly greater proportion of 2nd-trimester loss (Zeta = 5.76, p < 0.01) and pre-term labor (Zeta = 4.1, p < 0.01). There were no other significant differences in pregnancy outcomes between women with normal and abnormal uterine morphology. The authors concluded that the findings of this study showed the potential value of 3D-US and confirmed that women with congenital uterine anomalies were more likely to have adverse pregnancy outcomes than women with a normal uterus.

Ghi et al (2012) stated that septate uterus appeared to be strongly associated with an adverse pregnancy outcome; however, the possible relationship between septate uterus and miscarriage has only been retrospectively studied. These investigators described the reproductive outcome in women with incidental diagnosis of malformed uterus at 1st trimester scan. Women at their 1st pregnancy attending the authors’ center for a routine viability scan with an incidental suspicion of uterine anomaly at standard US were submitted to TVUS. All the cases with a 3D diagnosis of septate uterus were prospectively recruited and followed-up. A total of 24 patients with a single intra-uterine pregnancy were included at a median gestational age of 8.2 weeks. The cumulative pregnancy progression rate, as quoted by Kaplan-Meier algorithm, was 33.3 % due to the occurrence of early (less than or equal to 13 weeks) or late miscarriages (14 to 22 weeks) in 13 and 3 cases, respectively. The authors concluded that the pregnancy outcome was poor if a septate uterus was incidentally diagnosed in the early stage of a viable intra-uterine pregnancy.

Ridout et al (2019) noted that congenital uterine anomalies are associated with late miscarriage and SPTB. In a retrospective, cohort study, these researchers determined the rate of SPTB in each type of congenital uterine anomaly; and examined the performance of quantitative fetal fibronectin (fFN) and cervical length (CL) measurement by TVUS in asymptomatic women with congenital uterine anomalies for the prediction of SPTB at less than 34 and less than 37 weeks of gestation. This trial included women with congenital uterine anomalies asymptomatic for SPTB, from 4 tertiary referral centers in the U.K. (2001 to 2016). Congenital uterine anomalies were categorized into fusion (unicornuate, didelphic, and bicornuate uteri) or resorption defects (septate, with or without resection, and arcuate uteri), based on pre-pregnancy diagnosis. All women underwent serial TVUS CL assessment in the 2nd trimester (16 to 24 weeks' gestation); a subgroup underwent quantitative fFN testing from 18 weeks' gestation. These investigators also examined the relationship between congenital uterine anomalies and predictive test performance for SPTB at less than 34 and less than 37 weeks' gestation. A total of 319 women were identified as having congenital uterine anomalies in this high-risk population. Of the women, 7 % (23/319) delivered spontaneously at less than 34 weeks' gestation and 18 % (56/319) at less than 37 weeks' gestation. Rates of SPTB by type were as follows: 26 % (7/27) for unicornuate, 21 % (7/34) for didelphic, 16 % (31/189) for bicornuate, 13 % (7/56) for septate, and 31 % (4/13) for arcuate. In all, 80 % (45/56) of women who had SPTB at less than 37 weeks did not develop a short CL (less than 25 mm) during the surveillance period (16 to 24 weeks). The diagnostic accuracy of short CL had a low sensitivity (20.3) for predicting SPTB at less than 34 weeks. Cervical length had an area under the ROC of 0.56 (95 % CI: 0.48 to 0.64) and 0.59 (95 % CI: 0.55 to 0.64) for prediction of SPTB at less than 34 and less than 37 weeks, respectively. The area under the curve for CL to predict SPTB at less than 34 weeks was 0.48 for fusion defects (95 % CI: 0.39 to 0.57) but 0.78 (95 % CI, 0.66 to 0.91) for women with resorption defects. Overall quantitative fFN had an area under the curve of 0.63 (95 % CI: 0.49 to 0.77) and 0.58 (95 % CI: 0.49 to 0.68) for prediction of SPTB birth at less than 34 and less than 37 weeks, respectively. The area under the curve for prediction of SPTB at less than 37 weeks with quantitative fFN for fusion defects was 0.52 (95 % CI: 0.41 to 0.63) but 0.79 (95 % CI 0.63 to 0.95) for women with resorption defects. Results were similar when women with intervention were excluded. The authors concluded that the commonly used markers of CL and quantitative fFN had utility in prediction of SPTB in resorption congenital uterine defects but not in fusion defects. This was contrary to findings in other high-risk populations. These researchers stated that these findings need to be accounted for when planning antenatal care; and had potential implications for predictive tests used in SPTB surveillance and intervention.

Hughes et al (2020) noted that uterine anomalies occur in an estimated 5 % of women and have been shown to confer a higher risk of SPTB. A sonographically short cervix (less than 25 mm) is a risk indicator for SPTB, although its predictive utility has been little studied in this specific high-risk population. In a historical cohort study, these researchers examined the pregnancy outcomes and predictive ability of short cervix in a cohort of women with uterine anomalies attending a high-risk antenatal clinic. This trial evaluated all pregnancies in women with congenital uterine anomalies referred to the Preterm Labor Clinic at the Royal Women's Hospital, Melbourne, Australia, between 2004 and 2013. Logistic and linear regressions and ROC were used to examine associations between CL and PTB. SPTB (less than 37 weeks' gestation) occurred in 23 % of the 86 pregnancies (n = 20); rates by subgroup were: unicornuate uterus 60 % (n = 3/5), uterus didelphys 40 % (n = 6/15), bicornuate uterus 18 % (n = 9/51), septate uterus 13 % (n = 2/15). PPROMs occurred in 55 % of SPTBs and was not independently associated with the presence of cervical cerclage or ureaplasma urealyticum. Short CL was associated with SPTB in women with septate uterus. Short cervix at 24 weeks (not at 16 or 20 weeks) was moderately predictive of SPTB at less than 34 weeks. The authors concluded that women with uterine anomalies were at increased risk of SPTB, especially those with unicornuate uterus or uterus didelphys; however, cervical surveillance did not identify these cases. Short cervix may be associated with SPTB in women with septate uterus; PPROMs occurred in 55 % of SPTB. The authors stated that more research is needed to examine the etiology of SPTB to help determine appropriate monitoring and treatment.

In a prospective, cohort study, Negm et al (2022) examined the reliability of 3D-US in the differentiation between subseptate and arcuate uteri due to the different associated pregnancy outcomes; refined the existing 3D-US parameters and assessed the concordance between 3D-US and MRI in diagnosing these anomalies. This trial enrolled 455 women suspected of having a Mullerian anomaly. The diagnosis of subseptate, bicornuate or arcuate uterus was made by 3D-US in 55 women. Two independent examiners manipulated the 3D-US volume datasets and recorded the internal inter-cornual distance, indentation length, indentation tip angle, and myometrial wall thickness in the coronal plane of the uterus. Subsequently, 48 women underwent MRI that was used as the reference test for diagnosis. These investigators calculated the degree of correlation between the 2 US assessors' 3D-US measurements using inter-class correlation coefficient and as well as a Bland-Altman plot. The mean values of the 4 parameters were used to create ROC for determining the best cut-off values for differentiation between subseptate and arcuate uteri. They used the Cohen's Kappa test to measure the level of agreement between 3D-US and MRI. There was good inter-observer agreement between the 2 3D-US assessors for all 4 parameters. There was a substantial level of agreement between 3D-US and MRI in differentiating between bicornuate, subseptate and arcuate uteri with a kappa value of 0.727 (95 % CI: 0.443 to 0.856). Distinction between subseptate and arcuate uterus was improved when using an indentation length of greater than or equal to 12.5 mm (AUC 0.99) and indentation tip angle of less than or equal to 89.25 degrees (AUC 0.97) as cut-offs for diagnosis but not the internal inter-cornual distance or myometrial wall thickness. The authors concluded that 3D-US evaluation of the coronal view of the uterus could be relied upon to make a non-invasive, accurate differentiation between subseptate and arcuate uteri. The fundal indentation length and indentation tip angle cut-offs of greater than or equal to 12.5 mm and less than or equal to 88 mm, respectively were found to be most accurate for distinction; therefore, allowing for individualizing pre-pregnancy management plans and patient-informed healthcare choices. There were no agreed upon criteria for differentiating arcuate from subseptate uteri. Such differentiation was critical for counseling and management due to the substantial difference in pregnancy outcome. These investigators aimed to propose cut-off values for US measurements standardized against MRI diagnostic criteria for accurate differentiation between arcuate and subseptate uteri. They demonstrated substantial agreement between 3D-US and MRI in differentiating between bicornuate, subseptate and arcuate uteri. The authors stated that 3D-US evaluation of the coronal view of the uterus was reliable to make an accurate differentiation between subseptate and arcuate uteri. Using the indentation length greater than or equal to 12.5 mm and indentation tip angle of less than or equal to 89.25 degrees as parameters to be measured on the coronal view by 3D-US increased its diagnostic accuracy for distinction between arcuate and subseptate uteri.

An UpToDate review on “Congenital uterine anomalies: Clinical manifestations and diagnosis” (Laufer and DeCherney, 2022) states that “In a literature review of studies including infertile and fertile patients with CUAs, the frequencies of specific anomalies were: septate (35 %), bicornuate (26 %), arcuate (18 %), unicornuate (10 %), didelphys (8 %), and agenesis (3 %). However, these frequencies can vary substantially depending upon the specific population studied and the methodology used to identify the abnormalities. In the well-designed study of patients with normal reproductive outcomes described above, the frequencies were: septate (90 %), bicornuate (5 %), and didelphic (5 %) … Most patients undergo 2D-US examination as the initial imaging modality. It also provides information about relevant nonuterine structures (e.g., ovaries, kidneys). 3D-US is helpful to assess the outer contour of the fundus (i.e., differentiate between a septate and a bicornuate uterus). Hysterosalpingography provides information about fallopian tube patency and size and configuration of the uterine cavity or cavities. Saline infusion sonohysterography and hysterosalpingography both delineate the uterine cavity well”.

Furthermore, the Consensus Report on “The detailed fetal anatomic ultrasound examination” (Wax et al, 2014) did not list “septate or arcuate uterus” as indications for a detailed fetal anatomic examination.

Detailed Fetal Ultrasound for Hypo-Coiled / Hyper-Coiled Umbilical Cord

In a prospective study, Verkleij et al (2013) examined if there was an association between US-assessed hyper- or hypo-coiling of the umbilical cord and the presence of trisomy 21, to provide reference values for the antenatal umbilical coiling index (aUCI) at a gestational age of 16 to 21 weeks and to examine if these measurements were reliable and reproducible. This study included 737 pregnancies in which the aUCI was measured between 16 and 21 weeks of gestation by US at the time of amniocentesis. The aUCI was calculated as the reciprocal value of the mean length (in cm) of 1 complete coil. These investigators created reference curves and studied the relationship with trisomy 21 and other chromosomal defects. In 30 pregnancies, these researchers examined the intra- and inter-observer variation in measurements using Bland-Altman plots with associated 95 % CI and intra-class correlation coefficients. aUCI was found to be non-linearly related to gestational age at 16 to 21 weeks and reference curves were created for the mean aUCI and the 2.3rd , 10th , 90th and 97.7th percentiles. There was no significant difference in aUCI values between the reference group (n = 714) and cases with trisomy 21 (n = 16) or other aneuploidies (n = 7) (1-way ANOVA, p = 0.716). There was good intra- and inter-observer agreement in aUCI measurements. The authors concluded that the aUCI could be measured reliably and varied according to gestational age at 16 to 21 weeks. The aUCI was not significantly associated with trisomy 21 or other chromosomal defects.

In a systematic review, Jessop et al (2014) determined the frequency of pre-defined clinical outcomes in relation to umbilical cord coiling indices greater than 90th percentile and less than 10th percentile in an unselected population of more than 1,000 women with a singleton pregnancy resulting in livebirth delivering at or near-term. Placentas of consecutive deliveries from an unselected low-risk population with greater than 15 cm attached umbilical cords were included in the study. Clinical outcomes included interventional delivery, birthweight of less than 10th percentile, Apgar score of less than 7 at 1 min, neonatal acidosis (pH of less than 7.2) and admission to neonatal special care. Standard MOOSE (Meta-analysis of Observational Studies in Epidemiology) guidelines were observed for the systematic review. UCI was determined for 1,082 placentas. Mean maternal age was 30.7 years (SD = 5.7) and 519 women (48 %) were primiparous. Mean cord length was 43 cm (SD = 13) and mean cord coiling index 0.20 (SD = 0.09). A total of 866 cords were normally coiled, and 108 cases were hyper-coiled (greater than 90th centile) and 108 cases were under-coiled (less than 10th percentile). There were no differences between cases of over-coiled, normally coiled or under-coiled cords for any clinical outcome studied. The systematic review yielded a small number of clinical studies that were too statistically and clinically heterogenous to allow meta-analysis. The authors concluded that there was insufficient evidence either from this unselected cohort study or from a systematic review to support the previous suggestion that UCI of greater than 90th centile or less than 10th centile was associated with adverse clinical outcome in an unselected population. Previous studies that draw a link between abnormal cord coiling and clinical outcome were generally too small and/or selective to allow meaningful conclusions or applicability to low-risk populations.

In a cross-sectional study, Sharma et al (2018) examined the relationship between aUCI measured at 18 to 20 weeks along with level-II US and adverse perinatal outcomes. This trial was carried out on 408 antenatal women, enrolled at the time of fetal anatomic survey, and their aUCI was measured, and its association with perinatal outcomes was observed. UCI was classified as hypo-coiled if UCI was less than 10th percentile, hyper-coiled if UCI was greater than 90th percentile, normo-coiled if UCI was between 10th and 90th percentile. A total of 408 antenatal women were enrolled for this trial. Mean aUCI was 0.43 ± 0.30 (normo-coiled group), 0.18 ± 0.4 (hypo-coiled), and 0.53 ± 0.05 (hyper-coiled group). The average gestational age at delivery in hypo-coiled group was 36.8 ± 2.34 weeks, and it was shorter than 38.3 ± 1.82 weeks of the normo-coiled group and 38.9 ± 1.72 weeks of the hyper-coiled group. Mean birthweight observed was 2,055 ± 744 (hypo-coiled group), 3,049 ± 564 (hyper-coiled), and 3,102 ± 564 (normo-coiled); p < 0.001. PTBs 52 (59 %) and low birthweight 76 (69 %) were significantly associated with hypo-coiling. The authors concluded that abnormal UCI, detected at the fetal US anatomic survey in the 2nd trimester (18 to 20 weeks), could be used potentially as a screening or as a predictive tool for adverse antenatal or perinatal events.

Krzyzanowski et al (2019) noted that umbilical cord anatomy should be examined in the US examination in the 1st trimester. It is of vital importance to confirm the correct number of umbilical vessels and their intra-abdominal course, as well as carefully evaluating the abdominal and placental insertion sites. In the latter half of pregnancy, the use of the Doppler imaging enables evaluation of the function of the fetal-placental vessels; thus, providing valuable information regarding the condition of the fetus. Moreover, these investigators stated that the detection in pre-natal examinations of a single umbilical artery (SUA) should therefore lead to a detailed US assessment of all organs and systems.

In a meta-analysis and sequential analysis, Pergialiotis et al (2020) examined the potential association of abnormal cord coiling with adverse pregnancy outcomes. These investigators used the Medline (1966 to 2018), Scopus (2004 to 2018), Clinicaltrials.gov (2008 to 2018), Embase (1980 to 2018), Cochrane Central Register of Controlled Trials CENTRAL (1999 to 2018), and Google Scholar (2004 to 2018) databases. The date of last search was set on May 31, 2018. Language, country, or date restrictions were not employed during the literature research to prevent bias. All observational (both prospective and retrospective) studies that reported maternal and neonatal antenatal and perinatal outcomes based on the UCI status were considered as eligible for inclusion. Meta-analysis of the RR and MD among hypo-coiled/hyper-coiled and normo-coiled cases was carried out with RevMan 5.3 software. Univariate meta-regression and leave-one-out meta-analysis was carried out with Open Meta-Analyst statistical software. Trial sequential analysis was carried out with the trial sequential analysis (TSA) software. A total of 24 studies were included, entailing 9,553 pregnant women. Umbilical cord coiling was examined with the use of the UCI. Values of the UCI below the 10th percentile were deemed hypo-coiled and above the 90th percentile as hyper-coiled. Hypo-coiled cords were significantly associated with increased prevalence of preterm birth (PTB) of less than 37 weeks, need for interventional delivery due to fetal distress, meconium-stained liquor, Apgar scores of less than 7 at 5 mins, SGA neonates, fetal anomalies, need for admission in the NICU, fetal heart rate (HR) abnormalities, and fetal death. Hyper-coiled cords were significantly associated with increased prevalence of PTB of less than 37 weeks, need for interventional delivery due to fetal distress, meconium-stained liquor, Apgar scores of less than 7 at 5 mins, SGA neonates, fetal anomalies, fetal growth restriction, fetal HR abnormalities, fetal acidosis, and fetal death. The authors concluded that the findings of this meta-analysis underlined the correlation of UCI abnormalities with antenatal and perinatal pathology. Moreover, these researchers stated that more studies are needed to examine if antenatal assessment of the UCI could be used as routine in clinical practice as well as its value in uncomplicated pregnancies.

Hayes et al (2020) stated that current data on the role of the umbilical cord in pregnancy complications are conflicting; estimates of the proportion of stillbirths due to cord problems ranged from 3.4 % to 26.7 %. In a systematic review and meta-analysis, these investigators determined which umbilical cord abnormalities are associated with stillbirth and related adverse pregnancy outcomes. Medline, Embase, CINAHL and Google Scholar were searched from 1960 to present day. Reference lists of included studies and grey literature were also searched. Cohort, cross-sectional, or case-control studies of singleton pregnancies after 20 weeks' gestation that reported the frequency of umbilical cord characteristics or cord abnormalities and their relationship to stillbirth or other adverse outcomes were included. Quality of included studies was assessed using NIH quality assessment tools; analyses were performed in STATA. This review included 145 studies. Nuchal cords were present in 22 % of births (95 % CI: 19 to 25); multiple loops of cord were present in 4 % (95 % C: 3 to 5) and true knots of the cord in 1 % (95 % CI: 0 to 1) of births. There was no evidence for an association between stillbirth and any nuchal cord (OR 1.11, 95 % CI: 0.62 to 1.98). Comparing multiple loops of nuchal cord to single loops or no loop gave an OR of 2.36 (95 % CI: 0.99 to 5.62). These researchers were unable to examine the effect of tight or loose nuchal loops. The likelihood of stillbirth was significantly higher with a true cord knot (OR 4.65, 95 % CI: 2.09 to 10.37). The authors concluded that this systematic review and meta-analysis demonstrated links between umbilical cord abnormalities (UCA) and several adverse pregnancy outcomes, although not all analyses were adequately powered; and some comparisons were restricted by the methodologies of the original studies. These researchers stated that further studies are needed to allow robust clinical recommendations on the management of UCA to be made. These should make use of the information presented regarding normal cord characteristics to inform thresholds for abnormalities and examine multiple UCA and a range of adverse perinatal outcomes. Ideally, UCA should also be recorded antenatally in blinded studies so that prognostic accuracy could be calculated. Until such data are available, clinicians should be cautious about assigning causality of an adverse outcome based on an isolated observation of UCA.

Furthermore, the Consensus Report on “The detailed fetal anatomic ultrasound examination” (Wax et al, 2014) did not list “hypo-coiled / hyper-coiled umbilical cord” as indications for a detailed fetal anatomic examination.

Detailed Fetal Ultrasound for McCune-Albright syndrome

Gaspari et al (2012) noted that beyond the classic triad of peripheral precocious puberty, café-au-lait skin pigmentation and polyostotic fibrous dysplasia, partial presentation McCune-Albright syndrome (MAS) has been reported, including the association of isolated recurrent ovarian cysts in early infancy. These researchers examined if isolated voluminous fetal unilateral ovarian cysts (diameter of greater than 4 cm) may be associated with a Gsα activating mutation, suggestive of MAS. They followed 5 female fetuses presenting with voluminous unilateral ovarian cysts by ultrasonography (US) until delivery. At birth, all patients underwent percutaneous cyst aspiration; and 2 patients later underwent ovariectomy. A sensitive polymerase chain reaction (PCR)-based method was used to analyze the Gsα activating mutation in DNA obtained from ovarian cystic fluids or tissue. Among the 5 cases, 1 Gsα mutation (R201C) was identified in the ovarian tissue. The authors demonstrated for the 1st time that voluminous fetal unilateral ovarian cysts may be suggestive of MAS. Systematic search for the Gsα mutation should be carried out in all newborns with voluminous fetal unilateral ovarian cysts requiring percutaneous cyst aspiration, because early diagnosis of MAS prevents unnecessary oophorectomy to eliminate questions of malignancy and imposes long-term clinical, biological, and imaging follow-up to detect other early manifestations of MAS. Detailed fetal US was not mentioned as a management tool.

Furthermore, an UpToDate review on “Definition, etiology, and evaluation of precocious puberty” (Harrington and Palmert, 2022) does not mention detailed fetal US as a management option.

Detailed Fetal Ultrasound for Placental Cord Insertion

In a retrospective, case-control study, Sinkin et al (2018) examined perinatal outcomes in singleton and twin pregnancies with pathologically confirmed velamentous cord insertion (VCI) without vasa previa (VP). This study included all non-anomalous singleton and twin pregnancies with pathologically confirmed VCI delivered in a single center between January 1, 2005, and July 1, 2015, and having an US examination by maternal-fetal medicine. For each case, the next 2 consecutive deliveries matched for gestational age at delivery ± 1 week and, in twins, amnionicity and chorionicity served as controls. Primary outcomes included surgical delivery for a non-reassuring intra-partum fetal heart rate (HR) tracing, umbilical arterial cord pH of less than 7.2, 5-min Apgar score of less than 7, birthweight below the 10th percentile, neonatal intensive care unit (ICU) admission, fetal or neonatal death, and cord avulsion necessitating manual placental extraction. Outcomes were available for 53 singletons with 103 matched controls and 33 twin pregnancies with 65 matched controls. In singletons, velamentous cord insertion was associated with cord pH of less than 7.2 (OR 3.5; 95 % CI: 1.1 to 11.2; p = 0.039), 5-min Apgar score of less than 7 (OR, 5.3; 95 % CI: 0.99 to 28.1; p = 0.045), and cord avulsion requiring manual placental extraction (7.5 % versus 0 %; p = 0.012). Associations were suggested with increased surgical delivery for a non-reassuring intra-partum fetal HR tracing (OR, 2.4; 95 % CI: 0.9 to 6.9; p = 0.14), birthweight below the 10th percentile (OR, 2.1; 95 % CI: 0.8 to 5.9; p = 0.21), and fetal or neonatal death (3.8 % versus 0 %; p = 0.11). VCIs were also associated with placental abruption in singletons (7.5 % versus 0 %; p = 0.013). Among twins, VCI was associated with fetal or neonatal death (9.1 % versus 0 %; p = 0.036). The authors concluded that isolated confirmed VCI was associated with adverse perinatal outcomes in singleton and twin gestations.

However, these researchers stated that this study could not address the question of whether ante-partum fetal surveillance or modifying ante-partum and intra-partum care could reduce the frequency of VCI-associated adverse outcomes. Moreover, given the association of VCI and adverse perinatal outcomes, research specifically addressing these questions is needed. About 1/4 to 1/3 of VCIs are prenatally diagnosed by US. Although a lower maternal BMI and anterior placentas may be associated with improved detection, diagnosis may be hampered when the placenta is located posteriorly in twins. These investigators stated that further research is needed to develop uniform, accurate, and reproducible US criteria for diagnosing VCI and imaging protocols permitting consistent, accurate, and reliable characterization of the placental cord insertion, as well as to determine how best to care for pregnancies when VCI is identified.

Buchanan-Hughes et al (2020) stated that VCI is an umbilical cord attachment to the membranes surrounding the placenta instead of the central mass. VCI is strongly associated with VP, where umbilical vessels lie in close proximity to the internal cervical os. VP leaves the vessels vulnerable to rupture, which could result in fatal fetal exsanguination. Screening for VP using 2nd-trimester trans-abdominal sonography (TAS) to detect VCI has been proposed. These investigators carried out a rapid review examining the quality, quantity and direction of evidence available on the epidemiology, screening test accuracy and post-screening management pathways for VCI. Medline, Embase and the Cochrane Library were searched on July 5, 2016 and again on October 11, 2019, using general search terms for VP and VCI. Only peer-reviewed studies reporting on the epidemiology of VCI, the accuracy of the screening test and/or down-stream management pathways for VCI pregnancies were included. Quality and risk of bias of each included study were examined using pre-specified tools. A total of 41 relevant publications were identified; all but 1 were based on non-U.K. pregnancy cohorts, and most included relatively few VCI cases. The estimated incidence of VCI was 0.4 % to 11 % in singleton pregnancies, with higher incidence in twin pregnancies (1.6 % to 40 %). VCI incidence was also increased among pregnancies with 1 or more other risk factors, including IVF pregnancies or nulliparity. VCI incidence among women without any known risk factors was unclear. VCI was associated with adverse perinatal outcomes, most notably pre-term birth (PTB) and emergency caesarean section in singleton pregnancies, and perinatal mortality in twins; however, associations varied across studies and the increased risk was typically low or moderate compared with pregnancies without VCI. In studies on limited numbers of cases, screening for VCI using TAS had good overall accuracy, driven by high specificity. No studies on post-screening management of VCI were identified. The authors concluded that the evidence on VCI epidemiology and outcomes is limited and low-quality. The accuracy of 2nd-trimester TAS and the benefits and harms of screening could not be determined without prospective studies in large cohorts.

These researchers stated that the accuracy of the test for VCI has not been well established, and no management pathway is available for women with VCI detected by screening, nor for those with marginal cord insertion (MCI) who would also be detected if screening was to be implemented. These factors limited the strength of the evidence needed to inform a U.K. National Screening Committee (NSC) recommendation in this area. Further meta-analyses on a wider range of outcomes in subgroups of the pregnant population may help examine the level of risk from VCI more thoroughly. However, well-designed prospective studies in larger cohorts of women are needed to produce more robust estimates of VCI incidence and risks, test accuracy and the practicality of 2nd-trimester testing for VCI. Furthermore, modelling studies may be the 1st step towards understanding whether such studies would be achievable and of value.

In a retrospective study, Liu et al (2022) examined the feasibility and accuracy of trans-abdominal color Doppler US (TA-CDUS) and trans-vaginal color Doppler US (TV-CDUS) as screening methods for pregnant women with VP and VCI. This trial was carried out on 5,434 pregnant women from 2018 to 2021, who underwent both TA-CDUS and TV-CDUS. Diagnostic performance of TA-CDUS and TV-CDUS was determined using specificity, PPV, NPV, accuracy, and positive and negative likelihood ratios (LR+ and LR-), using the delivery information (gross examination) as the "gold-standard". Patient records were reviewed for demographics and diagnosis. The combination of VP and VCI was diagnosed in 37/5,434 (0.68%) women at delivery. The sensitivity, specificity, PPV, NPV, and overall test accuracy of TA-CDUS were 72.97 %, 99.85 %, 77.14 %, 99.81 %, and 99.67 %, respectively, for diagnosing VP with VCI. The corresponding values for TV-CDUS were 89.19 %, 99.87 %, 82.50 %, 99.93 %, and 99.80 %, respectively. Moreover, the sensitivity of combination of TA-CDUS and TA-CDUS in determining VP with VCI was 97.30 %, specificity 99.98 %, PPV 97.30 %, NPV 99.98 %, and accuracy 99.96 %. No significant difference in the misdiagnosis and missed diagnosis was found between the examination by TA-CDUS and TV-CDUS. The authors concluded that both TA-CDUS and TV-CDUS could be acceptable diagnostic tools for assessment of pregnant women with VP and VCI, with a better application of TV-CDUS with higher accuracy. Moreover, the combination of TA-CDUS and TV-CDUS could provide an objective imaging basis for choosing clinical treatment strategies and predicting prognosis. However, detailed US fetal anatomic examination was not mentioned as a management option.

Bohilțea et al (2022) stated that umbilical cord abnormalities are not rare, and are often associated with structural or chromosomal abnormalities, fetal intra-uterine growth restriction (IUGR), and poor pregnancy outcomes; the latter could be a result of prematurity, placentation deficiency or, implicitly, an increased index of cesarean delivery due to the presence of fetal distress, higher admission to NICU, and increased prenatal mortality rates. Even if the incidence of velamentous insertion, VP and umbilical knots is low, these pathologies increase the fetal morbidity and mortality prenatally and intrapartum. Moreover, these investigators noted that there is a vast heterogeneity among societies' guidelines regarding the umbilical cord examination. They considered the mandatory introduction of placental cord insertion examination in the 1st and 2nd trimester to practice guidelines for fetal US scans. In addition, during the mid-trimester scan, these researchers recommended a TVUS and color Doppler assessment of the internal cervical os for low-lying placentas, marginal or velamentous cord insertion, and the evaluation of umbilical cord entanglement between the insertion sites whenever it is incidentally found. The authors recommended detailed fetal anatomical survey for SUA/umbilical artery hypoplasia, and umbilical cord cyst/tumors.

Detailed Ultrasound Fetal Anatomic Examination for Patients with New Diagnosis of HIV

Brogly et al (2010) stated that several studies have detected associations between in-utero anti-retroviral therapy (ARV) exposure and birth defects; however, evidence is inconclusive. In this study, a total of 2,202 HIV-exposed children enrolled in the Pediatric AIDS Clinical Trials Group 219 and 219C protocols before 1year of age were included. Birth defects were classified using the Metropolitan Atlanta Congenital Defects Program (MACDP) coding. Logistic regression models were used to examine associations between 1st trimester in-utero ARV exposure and birth defects. A total of 117 live-born children had birth defects for a prevalence of 5.3 % (95 % CI: 4.4 to 6.3). Prevalence did not differ by HIV infection status or overall ARV exposure; rates were 4.8 % (95 % CI: 3.7 to 6.1) and 5.8 % (95 % CI: 4.2 to 7.8) in children without and with 1st trimester ARV exposure, respectively. The defect rate was higher among children with 1st trimester efavirenz exposure (5/32, 15.6 %) versus children without 1st trimester efavirenz exposure [adjusted odds ratio (aOR) = 4.31 (95 % CI: 1.56 to 11.86)]. Protective effects of 1st trimester zidovudine exposure on musculoskeletal defects were detected [aOR = 0.24 (95 % CI: 0.08 to 0.69)], while a higher risk of heart defects was found [aOR = 2.04 (95 % CI: 1.03 to 4.05)]. The authors concluded that the prevalence of birth defects was higher in this cohort of HIV-exposed children than in other pediatric cohorts. There was no association with overall ARV exposure; however, there were some associations with specific agents including efavirenz. These researchers stated that additional studies are needed to rule out confounding and to examine newer ARV agents.

Williams et al (2015) noted that most studies examining the association of pre-natal ARV exposures with congenital anomalies (CAs) in children born to HIV-infected women have been reassuring; however, some studies suggested increased risk with specific ARV. In a prospective, cohort, multi-center study (the Pediatric HIV/AIDS Cohort Study (PHACS) Surveillance Monitoring of ART Toxicities (SMARTT) Trial), these investigators examined associations of in-utero ARV exposures with CAs in HIV-exposed uninfected children. A total of 2,580 HIV-exposed, uninfected children were enrolled in the SMARTT Trial (22 U.S. medical centers) between 2007 and 2012; they experienced 1st trimester exposure to any ARV and to specific anti-retroviral medications. The primary endpoint was a CA, based on clinician review of infant physical examinations according to the Antiretroviral Pregnancy Registry modification of the Metropolitan Atlanta Congenital Defects Program. Rates of CAs were estimated overall and by birth year. Logistic regression models were used to examine associations of CAs with 1st trimester ARV exposures, adjusting for demographic and maternal characteristics. CAs occurred in 175 of 2,580 children, yielding a prevalence of 6.78 % (95 % CI: 5.85 % to 7.82 %); there were 242 confirmed major CAs (72 musculoskeletal, 55 cardiovascular). The prevalence of CAs increased significantly in successive birth cohorts (3.8 % for children born before 2002 up to 8.3 % for children born 2008 to 2010). In adjusted models, there was no association of 1st trimester exposures to any ARV, to combination ARV regimens, or to any drug class with CAs. No individual anti-retroviral in the reverse transcriptase inhibitor drug classes was associated with increased risk of CAs. Among protease inhibitors, higher odds of CAs were observed for atazanavir (aOR = 1.93, 95 % CI: 1.23 to 3.03) and for ritonavir used as a booster (aOR = 1.52, 95 % CI: 1.08 to 2.14). With 1st trimester atazanavir, risks were highest for skin and musculoskeletal CAs (aORs = 5.24 and 2.55, respectively). The authors concluded that few individual ARV and no drug classes were associated with increased risk of CAs following adjustment for calendar year and maternal characteristics. While the overall risk remained low, there was a relative increase in successive years and with atazanavir exposure. Given the low absolute CA risk, the benefits of recommended ARV use during pregnancy still outweigh such risks, although further studies are needed.

Furthermore, the Centers for Disease Control and Prevention (CDC)’s webpage on “Risk for Neural Tube Defects among Pregnancies of Women with HIV” (CDC, last reviewed: January 9, 2020) states that “Linking data from birth defects and HIV/AIDS programs, scientists found that the risk for neural tube defects among pregnancies of women diagnosed with HIV is similar to that of the general U.S. population. About 1 in every 1,250 babies is born with a neural tube defect each year in the United States”.

Tukei et al (2021) stated that without treatment, HIV infection in pregnant women is associated with adverse pregnancy outcomes. These researchers compared adverse pregnancy outcomes among HIV-positive women on ARV and HIV-negative women who enrolled for antenatal care in selected health facilities in Maseru district, Lesotho. They enrolled a cohort of HIV-positive and HIV-negative women at their 1st antenatal visit and followed them through delivery. Study data on miscarriage, still-birth, preterm birth (PTB), low birthweight and birth defects were collected through participant interviews and medical record abstraction. These researchers used the Rao-Scott χ2 test and the t-test to examine differences in characteristics and outcomes between HIV-positive and HIV-negative women and generalized estimating equations for multi-variable analysis. A total of 614 HIV-positive and 390 HIV-negative pregnant women were enrolled in the study with delivery information on 571 (93.1 %) and 352 (90.3 %) respectively. In the delivery cohort, the median age at enrolment was 28 years for HIV-positive women and 23 years for HIV-negative women with median gestational ages of 20 and 21 weeks, respectively. A total of 149 singleton pregnancies had documented adverse pregnancy outcomes -- 33 (9.6 %) HIV-negative pregnancies and 116 (20.6%) HIV-positive pregnancies. Compared with their HIV-negative counterparts, HIV-positive women were more likely to experience an adverse pregnancy outcome (aOR = 2.6; 95 % CI: 1.71 to 3.97); an intra-uterine death (miscarriage or stillbirth), aOR = 2.64; 95 % CI: 1.25 to 5.49); or a low birthweight delivery, aOR = 1.89; 95 % CI: 1.16 to 3.09). The authors concluded that adverse pregnancy outcomes remained 2 to 3 times higher among HIV-positive women compared with HIV-negative women despite universal ARV. Moreover, these investigators stated that the lack of association of maternal ARV with birth defects observed in this trial was consistent with findings from other studies, as well as the Antiretroviral Pregnancy Registry, that confirm the safety of efavirenz-based ARV regimens as used in this cohort of women. The lack of association between this regimen and birth defects is reassuring; however, as countries move away from efavirenz to dolutegravir-based regimens, there is a need for continued pharmaco-vigilance of pregnant women receiving the newer ARV regimens for adverse outcomes.

Klippel-Trenaunay Syndrome

Harnarayan and Harnanan (2022) noted that the Klippel-Trenaunay syndrome (KTS) is an unusual syndrome of vascular and dermatologic manifestation in which patients exhibit hemi-hypertrophy of the soft tissue and bones of one limb, cutaneous hemangiomas and varicosities in anatomically abnormal positions. Described in 1900 by 2 French physicians, the etiology remained unclear until recently, when evidence emerged that there was a genetic basis for this sporadic disorder. Genes that encoded pathological angiogenic factors and caused vascular dysmorphogenesis, explaining the molecular bases of this syndrome, were identified. Several angiogenic genes were identified but 1 gene, the AGGF1 (formerly VG5Q) gene, was observed in mutations involving patients diagnosed with KTS. In addition, KTS was also noted to have overlapping clinical features linked with the “overgrowth syndromes”, in which genetic mutations along somatic lines were identified. These involved the PI3K enzyme that forms part of the phosphoinositide 3-kinase pathway which is encoded by the PIK3CA-gene. This enzyme mediates embryonic cellular growth in-utero; and diseases involved in this pathway are classified as members of the PIK3CA-related overgrowth syndrome. These investigators examined the status of what is now known regarding the molecular genetics of this unusual, but clinically challenging disorder and its differentiation from similar diseases, linked with the PIK3CA-gene and the related overgrowth syndromes.

Appendix

According to the Society for Maternal Fetal Medicine (SMFM, 2012), a detailed fetal anatomic ultrasound (CPT code 76811) includes all of the components of the routine fetal ultrasound (CPT code 76805), plus a detailed fetal anatomical survey. The SMFM (2012) has stated that the following are fetal and maternal anatomical components for the detailed fetal anatomic ultrasound (CPT code 76811). Not all components will be required. Components considered integral to the code are marked with an asterisk: Footnote2*Component considered integral to the CPT code 76811.

Evaluation of Intracranial, Facial, and Spinal Anatomy

Lateral ventriclesFootnote2*, third and fourth ventricles
CerebellumFootnote2*, integrity of lobesFootnote2*, vermisFootnote2*
Cavum septum pellucidum
Cisterna magna measurementFootnote2*
Nuchal thickness measurement (15-20 weeks)Footnote2*
Integrity of cranial vault
Examination of brain parenchyma, (e.g. for calcifications)
Ear position, size
Face
Upper lip integrityFootnote2*
PalateFootnote2*
Facial profileFootnote2*
Evaluation of the neck (e.g. for masses)

Evaluation of the Chest

Presence of massesFootnote2*
Pleural effusionFootnote2*
Integrity of both sides of the diaphragmFootnote2*
Appearance of ribs

Evaluation of the Heart

Cardiac location and axisFootnote2*
Outflow tractsFootnote2*

Evaluation of the Abdomen

BowelFootnote2*
Adrenal glands
Gallbladder
Liver
Spleen
AscitesFootnote2*
Masses

Evaluation of Genitalia

Gender (whether or not parents wish to know sex of child)

Evaluation of Limbs

Number, size, and architectureFootnote2*
Anatomy and position of handsFootnote2*
Anatomy and position of feetFootnote2*

Evaluation of the Placenta and Cord

Placental cord insertion siteFootnote2*
Placental massesFootnote2*
Umbilical-cord (number of arteries)

Evaluation of Amniotic Fluid

Amniotic Fluid IndexFootnote2*
Evaluation of the cervix (Not required)
Evaluation of the maternal adnexa when feasibleFootnote2*

Note: If any of the required fetal or maternal components are non-visualized due to fetal position, late gestational age, maternal habitus, etc., it must be clearly noted in the ultrasound report in order to meet the requirements to bill for the service (SMFM, 2012).

Follow-up ultrasound performed after a detailed anatomic ultrasound (CPT code 76811), should be reported as CPT 76816 (Ultrasound, pregnant uterus, real time with image documentation, follow-up) (SMFM, 2012). This includes performing a focused assessment of fetal size by measuring the BPD, abdominal circumference, femur length, or other appropriate measurements, or a detailed re-examination of a specific organ or system known or suspected to be abnormal.

CPT code 76805 (Ultrasound, pregnant uterus, real time with image documentation, fetal and maternal evaluation, after first trimester (greater than or equal to 14 weeks 0 days), would be reported to determine the number of fetuses, amniotic/chorionic sacs, survey of intracranial, spinal, and abdominal anatomy, evaluation of a 4-chamber heart view, assessment of the umbilical cord insertion site, assessment of amniotic fluid volume, and evaluation of maternal adnexa when visible when appropriate (SMFM, 2012).

CPT code 76805 and ICD-10 code Z36 are reported when performing a routine screening ultrasound (no maternal or fetal indications or abnormal findings) (SMFM, 2012).

References

The above policy is based on the following references:

ACOG Committee on Practice Bulletins -- Obstetrics. ACOG Practice Bulletin: Clinical management guidelines for obstetrician-gynecologists number 92, April 2008 (replaces practice bulletin number 87, November 2007). Use of psychiatric medications during pregnancy and lactation. Obstet Gynecol. 2008;111(4):1001-1020.
ACOG Committee on Practice Bulletins. ACOG Practice Bulletin No. 77: Screening for fetal chromosomal abnormalities. Obstet Gynecol. 2007;109(1):217-227.
Ahmed BI. The new 3D/4D based spatio-temporal imaging correlation (STIC) in fetal echocardiography: A promising tool for the future. J Matern Fetal Neonatal Med. 2014;27(11):1163-1168.
Alfirevic Z, Stampalija T, Dowswell T. Fetal and umbilical Doppler ultrasound in high-risk pregnancies. Cochrane Database Syst Rev. 2017;6:CD007529.
Alfirevic Z, Stampalija T, Gyte GM. Fetal and umbilical Doppler ultrasound in normal pregnancy. Cochrane Database Syst Rev. 2010;(8):CD001450.
Alfirevic Z, Stampalija T, Gyte GM. Fetal and umbilical Doppler ultrasound in high-risk pregnancies. Cochrane Database Syst Rev. 2010;(1):CD007529.
Alfirevic Z, Stampalija T, Medley N. Fetal and umbilical Doppler ultrasound in normal pregnancy. Cochrane Database Syst Rev. 2015;4:CD001450.
American Academy of Pediatrics (AAP) and American College of Obstetricians and Gynecologists (ACOG). Guidelines for Perinatal Care. 4th ed. Elk Grove Village, IL: AAP; August 1997.
American College of Obstetricians and Gynecologists (ACOG Committee on Ethics. ACOG Committee Opinion. Number 297, August 2004. Nonmedical use of obstetric ultrasonography. Obstet Gynecol. 2004;104(2):423-424.
American College of Obstetricians and Gynecologists (ACOG) Committee on Health Care for Underdeserved Women; ACOG Committee on Obstetric Practice. ACOG committee opinion. Number 316, October 2005. Smoking cessation during pregnancy. Obstet Gynecol. 2005;106(4):883-888.
American College of Obstetricians and Gynecologists (ACOG), Committee on Obstetric Practice. Guidelines for diagnostic imaging during pregnancy. ACOG Committee Opinion No. 158. Washington, DC: ACOG; September 1995.
American College of Obstetricians and Gynecologists (ACOG), Committee on Practice Bulletins -- Obstetrics. ACOG Practice Bulletin. Clinical Management Guidelines for Obstetrician-Gynecologists. Prenatal diagnosis of fetal chromosomal abnormalities. Obstet Gynecol. 2001;97(5 Pt 1):suppl 1-12.
American College of Obstetricians and Gynecologists (ACOG), Committee on Practice Bulletins -- Obstetrics. Ultrasonography in pregnancy. ACOG Practice Bulletin No. 58. Washington, DC: ACOG; December 2004.
American College of Obstetricians and Gynecologists (ACOG), Committee on Practice Bulletins -- Obstetrics. Ultrasonography in pregnancy. ACOG Practice Bulletin No. 98. Washington, DC: ACOG; October 2008.
American College of Obstetricians and Gynecologists (ACOG), Committee on Practice Bulletins -- Obstetrics. Ultrasonography in pregnancy. ACOG Practice Bulletin No. 101. Washington, DC: ACOG; February 2009.
American College of Obstetricians and Gynecologists (ACOG). Multiple gestation. ACOG Technical Bulletin No.131. Washington, DC: ACOG; August 1989.
American College of Obstetricians and Gynecologists. ACOG Committee Opinion #296: First-trimester screening for fetal aneuploidy. Obstet Gynecol. 2004;104(1):215-217.
Antsaklis A, Daskalakis G, Theodora M, et al. Assessment of nuchal translucency thickness and the fetal anatomy in the first trimester of pregnancy by two- and three-dimensional ultrasonography: A pilot study. J Perinat Med. 2011;39(2):185-193.
Bansal R, Goyal MK, Modi M. Management of myasthenia gravis during pregnancy. Indian J Pharmacol. 2018;50(6):302-308.
Barnett SB, Maulik D; International Perinatal Doppler Society. Guidelines and recommendations for safe use of Doppler ultrasound in perinatal applications. J Matern Fetal Med. 2001;10(2):75-84.
Bellussi F, Ghi T, Youssef A, et al. The use of intrapartum ultrasound to diagnose malpositions and cephalic malpresentations. Am J Obstet Gynecol. 2017;217(6):633-641.
Benacerraf BR, Shipp TD, Bromley B. Improving the efficiency of gynecologic sonography with 3-dimensional volumes: A pilot study. J Ultrasound Med. 2006;25(2):165-171.
Benacerraf BR, Shipp TD, Bromley B. Three-dimensional US of the fetus: Volume imaging. Radiology. 2006;238(3):988-996.
Benacerraf BR, Shipp TD, Bromley B. How sonographic tomography will change the face of obstetric sonography: A pilot study. J Ultrasound Med. 2005;24(3):371-378.
Benacerraf CR. Sonographic findings associated with fetal aneuploidy. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed February 2015.
Bird SJ, Stafford IP, Dildy GA, III. Management of myasthenia gravis in pregnancy. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed December 2021.
Bofill JA, Sharp GH. Obstetric sonography. Who to scan, when to scan, and by whom. Obstet Gynecol Clin North Am. 1998;25(3):465-478.
Bohilțea RE, Dima V, Ducu I, et al. Clinically relevant prenatal ultrasound diagnosis of umbilical cord pathology. Diagnostics (Basel). 2022;12(2):236.
Bricker L, Garcia J, Henderson J, et al. Ultrasound screening in pregnancy: A systematic review of the clinical effectiveness, cost-effectiveness and women's views. Health Technol Assess. 2000;4(16):i-vi, 1-193.
Bricker L, Medley N, Pratt JJ. Routine ultrasound in late pregnancy (after 24 weeks' gestation). Cochrane Database Syst Rev. 2015;6:CD001451.
Brogly SB, Abzug MJ, Watts DH, et al. Birth defects among children born to HIV-infected women: Pediatric AIDS Clinical Trials Protocols 219 and 219C. Pediatr Infect Dis J. 2010;29(8):721-727.
Buchanan-Hughes A, Bobrowska A, Visintin C, et al. Velamentous cord insertion: Results from a rapid review of incidence, risk factors, adverse outcomes and screening. Syst Rev. 2020;9(1):147.
Buonsenso D, Raffaelli F, Tamburrini E, et al. Clinical role of lung ultrasound for diagnosis and monitoring of COVID-19 pneumonia in pregnant women. Ultrasound Obstet Gynecol. 2020;56(1):106-109.
Castro AA, Lima FJC, Sousa-Rodrigues CF, Barbosa FT. Accuracy of ultrasound to detect thrombosis in pregnancy: A systematic review. Rev Assoc Med Bras (1992). 2017;63(3):278-283.
Centers for Disease Control and Prevention (CDC). Sexually Transmitted Infections Treatment Guidelines, 2021. Atlanta, GA: CDC; 2021.
Chen M, Lee CP, Lam YH, et al. Comparison of nuchal and detailed morphology ultrasound examinations in early pregnancy for fetal structural abnormality screening: A randomized controlled trial. Ultrasound Obstet Gynecol. 2008;31(2):136-146; discussion 146.
Chen M, Wang HF, Leung TY, et al. First trimester measurements of nasal bone length using three-dimensional ultrasound. Prenat Diagn. 2009;29(8):766-770.
Clinical Practice Obstetrics Committee; Maternal Fetal Medicine Committee, Delaney M, Roggensack A, Leduc DC, et al. Guidelines for the management of pregnancy at 41+0 to 42+0 weeks. J Obstet Gynaecol Can. 2008;30(9):800-823.
Crane J, Scott H, Stewart A, et al. Transvaginal ultrasonography to predict preterm birth in women with bicornuate or didelphus uterus. J Matern Fetal Neonatal Med. 2012;25(10):1960-1964.
Czeizel AE, Puhó EH, Dakhlaoiu A, et al. Association between uterus uni/bicornis in pregnant women and postural deformities in their offspring. Am J Obstet Gynecol. 2011;205(6):560.e1-6.
Davies G, Wilson RD, Desilets V, et al. Amniocentesis and women with hepatitis B, hepatitis C, or human immunodeficiency virus. J Obstet Gynaecol Can. 2003;25(2):145-148, 149-152.
Demianczuk NN, Van Den Hof MC, Farquharson D, et al. The use of first trimester ultrasound. Obstet Gynaecol Can. 2003;25(10):864-875.
Dubbins PA. Screening for chromosomal abnormality. Semin Ultrasound CT MR. 1998;19(4):310-317.
Evans MI, Chervenak FA, Eden RD. Report of the Council on Scientific Affairs of the American Medical Association: Ultrasound evaluation of the fetus. Fetal Diagnosis Therapy. 1991;6(3-4):132-147.
Fuchs KM, Society for Maternal-Fetal Medicine (SMFM). Isolated fetal choroid plexus cysts. Their implications and outcome. Contemp Obstet Gynecol. April 1, 2013.
Garmel SH, D'Alton ME. Diagnostic ultrasound in pregnancy: An overview. Semin Perinatol. 1994;18(3):117-132.
Gaspari L, Paris F, Nicolino M, et al. Fetal ovarian cysts: An early manifestation of McCune-Albright syndrome? Prenat Diagn. 2012;32(9):859-63.
Gebauer C, Lowe N. The biophysical profile: Antepartal assessment of fetal well-being. J Obstet Gynecol Neonatal Nursing. 1993;22(2):115-123.
Ghi T, De Musso F, Maroni E, et al. The pregnancy outcome in women with incidental diagnosis of septate uterus at first trimester scan. Hum Reprod. 2012;27(9):2671-2675.
Gimovsky ML, Tejero Rosa E, Sepulveda W. Single umbilical artery. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed January 2018.
Gindes L, Weissmann-Brenner A, Zajicek M, et al. Three-dimensional ultrasound demonstration of the fetal palate in high-risk patients: The accuracy of prenatal visualization. Prenat Diagn. 2013;33(5):436-441.
Gomez KJ, Copel JA. Ultrasound screening for fetal structural anomalies. Curr Opin Obstet Gynecol. 1993;5(2):204-210.
Goncalves LF, Lee W, Espinoza J, Romero R. Three- and 4-dimensional ultrasound in obstetric practice: Does it help? J Ultrasound Med. 2005;24(12):1599-1624.
Grivell RM, Wong L, Bhatia V. Regimens of fetal surveillance for impaired fetal growth. Cochrane Database Syst Rev. 2012;6:CD007113.
Hata T, Kanenishi K, Inubashiri E, et al. Three-dimensional sonographic features of placental abnormalities. Gynecol Obstet Invest. 2004;57(2):61-65.
Hata T, Tanaka H, Noguchi J. 3D/4D sonographic evaluation of amniotic band syndrome in early pregnancy: A supplement to 2D ultrasound. J Obstet Gynaecol Res. 2011;37(6):656-660.
Harnarayan P, Harnanan D. The Klippel-Trenaunay syndrome in 2022: Unravelling its genetic and molecular profile and its link to the limb overgrowth syndromes. Vasc Health Risk Manag. 2022;18:201-209.
Harrington J, Palmert MR. Definition, etiology, and evaluation of precocious puberty. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed December 2022.
Hayes DJL, Warland J, Parast MM, et al. Umbilical cord characteristics and their association with adverse pregnancy outcomes: A systematic review and meta-analysis. PLoS One. 2020;15(9):e0239630.
Heazell AE, Hayes DJ, Whitworth M, et al. Biochemical tests of placental function versus ultrasound assessment of fetal size for stillbirth and small-for-gestational-age infants. Cochrane Database Syst Rev. 2019;5:CD012245
Heinonen PK. Limb anomalies among offspring of women with a septate uterus: A report of three cases. Early Hum Dev. 1999;56(2-3):179-184.
Henrichs J, Verfaille V, Jellema P, et al. Effectiveness of routine third trimester ultrasonography to reduce adverse perinatal outcomes in low risk pregnancy (the IRIS study): Nationwide, pragmatic, multicentre, stepped wedge cluster randomised trial. BMJ. 2019;367:l5517.
Hughes KM, Kane SC, Haines TP, Sheehan PM. Cervical length surveillance for predicting spontaneous preterm birth in women with uterine anomalies: A cohort study. Acta Obstet Gynecol Scand. 2020;99(11):1519-1526.
Institute for Clinical Systems Improvement (ICSI). Prenatal ultrasound as a screening test. ICSI Technology Assessment Report No. 16. Bloomington, MN: ICSI; updated October 2002.
Jessop FA, Lees CC, Pathak S, et al. Umbilical cord coiling: Clinical outcomes in an unselected population and systematic review. Virchows Arch. 2014;464(1):105-112.
Ji EK, Pretorius DH, Newton R, et al. Effects of ultrasound on maternal-fetal bonding: A comparison of two- and three-dimensional imaging. Ultrasound Obstet Gynecol. 2005;25(5):473-477.
Jones NW, Raine-Fenning N, Mousa H, et al. Evaluation of the intraobserver and interobserver reliability of data acquisition for three-dimensional power Doppler angiography of the whole placenta at 12 weeks gestation. Ultrasound Med Biol. 2010;36(9):1405-1411.
Junior EA, Santana EFM, Rolo LC, et al. Prenatal diagnosis of congenital syphilis using two- and three-dimensional ultrasonography: Case report. Case Rep Infect Dis. 2012;2012:478436.
Jurkovic D. Three-dimensional ultrasound in gynecology: A critical evaluation. Ultrasound Obstet Gynecol. 2002;19(2):109-117.
Kanenishi K, Hanaoka U, Noguchi J, et al. 4D ultrasound evaluation of fetal facial expressions during the latter stages of the second trimester. Int J Gynaecol Obstet. 2013;121(3):257-260.
Krishnan R, Deal L, Chisholm C, et al. Concordance between obstetric anatomic ultrasound and fetal echocardiography in detecting congenital heart disease in high-risk pregnancies. J Ultrasound Med. 2021;40(10):2105-2112.
Krzyzanowski A, Kwiatek M, Geca T, et al. Modern ultrasonography of the umbilical cord: Prenatal diagnosis of umbilical cord abnormalities and assessment of fetal wellbeing. Med Sci Monit. 2019;25:3170-3180.
Kupesic S, Kurjak A. Diagnosis and treatment outcome of the septate uterus. Croat Med J. 1998;39(2):185-190.
Kupesic S, Kurjak A, Hajder E. Ultrasonic assessment of the postmenopausal uterus. Maturitas. 2002;41(4):255-267.
Kurjak A, Abo-Yaqoub S, Stanojevic M, et al. The potential of 4D sonography in the assessment of fetal neurobehavior -- multicentric study in high-risk pregnancies. J Perinat Med. 2010;38(1):77-82.
Kurjak A, Kupesic S, Simunic V. Ultrasonic assessment of the peri- and postmenopausal ovary. Maturitas. 2002;41(4):245-254.
Kurjak A, Miskovic B, Andonotopo W, et al. How useful is 3D and 4D ultrasound in perinatal medicine? J Perinat Med. 2007;35(1):10-27.
Lakhani K, Seifalian AM, Atiomo WU, Hardiman P. Polycystic ovaries. Br J Radiol. 2002;75(889):9-16.
Laufer MR, DeCherney AH. Congenital uterine anomalies: Clinical manifestations and diagnosis. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed August 2018; December 2020; December 2021; December 2022.
Liu Q, Zhang Q, Liu P. The diagnostic accuracy of transabdominal and transvaginal color Doppler ultrasound for pregnant women with vasa previa and velamentous cord insertion. J Environ Public Health. 2022;2022:1685783.
Malini S, Valdes C, Malinak LR. Sonographic diagnosis and classification of anomalies of the female genital tract. J Ultrasound Med. 1984;3(9):397-404.
Martinez-Frías ML, Bermejo E, Rodríguez-Pinilla E, et al. Congenital anomalies in the offspring of mothers with a bicornuate uterus. Pediatrics. 1998;101(4):E10.
McDonald-McGinn DM, Hain HS, Emanuel BS, Zackai EH. 22q11.2 Deletion syndrome. GeneReviews [internet]. Last updated: February 27, 2020. Available at: https://www.ncbi.nlm.nih.gov/books/NBK1523/. Accessed July 22, 2022.
Messerlian GM, Farina A, Palomaki GE. First-trimester combined test and integrated tests for screening for Down syndrome and trisomy 18. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed January 2021.
Milman N. Idiopathic pulmonary hemosiderosis. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed October 2012.
Morin L, Van den Hof MC; Society of Obstetricians and Gynaecologists of Canada. SOGC clinical practice guidelines. Ultrasound evaluation of first trimester pregnancy complications. Number 161, June 2005. Int J Gynaecol Obstet. 2006;93(1):77-81.
Negm SM, Kamel RA, El-Zayat HA, et al. The value of three-dimensional ultrasound in identifying Mullerian anomalies at risk of adverse pregnancy outcomes. J Matern Fetal Neonatal Med. 2022;35(16):3201-3208.
No authors listed. AIUM practice parameter for the performance of detailed second- and third-trimester diagnostic obstetric ultrasound examinations. J Ultrasound Med. 2019;38(12):3093-3100.
No authors listed. Committee Opinion No. 723 Summary: Guidelines for diagnostic imaging during pregnancy and lactation. Obstet Gynecol. 2017;130(4):933-934.
Norwitz ER, Hicks CB. Syphilis in pregnancy. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed December 2021.
Pergialiotis V, Kotrogianni P, Koutaki D, et al. Umbilical cord coiling index for the prediction of adverse pregnancy outcomes: A meta-analysis and sequential analysis. J Matern Fetal Neonatal Med. 2020;33(23):4022-4029.
Rasmussen SA, Chu SY, Kim SY, et al. Maternal obesity and risk of neural tube defects: A metaanalysis. Am J Obstet Gynecol. 2008; 198:611–619.
Richardson A, Gallos I, Dobson S, et al. Accuracy of first-trimester ultrasound in diagnosis of tubal ectopic pregnancy in the absence of an obvious extrauterine embryo: Systematic review and meta-analysis. Ultrasound Obstet Gynecol. 2016;47(1):28-37.
Ridout AE, Ibeto LA, Ross GN, et al. Cervical length and quantitative fetal fibronectin in the prediction of spontaneous preterm birth in asymptomatic women with congenital uterine anomaly. Am J Obstet Gynecol. 2019;221(4):341.e1-341.e9.
Rodney WM, Deutchman ME, Hartman, KJ, et al. Obstetric ultrasound by family physicians. J Family Practice. 1992;34(2):186-200.
Salvesen K. Routine ultrasound scanning in pregnancy. BMJ. 1993;307(6911):1064.
Seeds JW. The routine or screening obstetrical ultrasound examination. Clin Obstet Gynecol. 1996;39(4):814-830.
Sharma R, Radhakrishnan G, Manchanda S, Singh S. Umbilical coiling index assessment during routine fetal anatomic survey: A screening tool for fetuses at risk. J Obstet Gynaecol India. 2018;68(5):369-375.
Sharp GC, Stock SJ, Norman JE. Fetal assessment methods for improving neonatal and maternal outcomes in preterm prelabour rupture of membranes. Cochrane Database Syst Rev. 2014;10:CD010209.
Shipp TD. Overview of ultrasound examination in obstetrics and gynecology. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed December 2021.
Sinkin JA, Craig WY, Jones M, et al. Perinatal outcomes associated with isolated velamentous cord insertion in singleton and twin pregnancies. J Ultrasound Med. 2018;37(2):471-478.
Soceity for Maternal-Fetal Medicine (SMFM). Single umbilical artery: What you need to know. Publications & Guidelines. Washington, DC: SMFM; February 1, 2013. Available at: https://www.smfm.org/publications/104-single-umbilical-artery-what-you-need-to-know. Accessed March 7, 2019.
Society for Maternal Fetal Medicine (SMFM), Coding Committee. White paper on ultrasound code 76811. Announcements. Washington, DC: SMFM; revised May 26, 2012.
Society for Maternal-Fetal Medicine (SMFM), Coding Committee. Coding for Zika virus. Washington, DC: SMFM; updated August 22, 2016.
Society for Maternal-Fetal Medicine (SMFM), Coding Committee. White paper on ultrasound code 76811. Announcements. Washington, DC: SMFM; May 24, 2004.
Stampalija T, Gyte GM, Alfirevic Z. Utero-placental Doppler ultrasound for improving pregnancy outcome. Cochrane Database Syst Rev. 2010;(9):CD008363.
Stothard KJ, Tennant PW, Bell R, Rankin J. Maternal overweight and obesity and the risk of congenital anomalies: A systematic review and metaanalysis. JAMA. 2009; 301:636–650.
Tao H, Wang R, Liu W, et al. The value of intrapartum ultrasound in the prediction of persistent occiput posterior position: Systematic review and meta-analysis. Eur J Obstet Gynecol Reprod Biol. 2019;238:25-32.
Timor-Tritsch IE, Platt LD. Three-dimensional ultrasound experience in obstetrics. Curr Opin Obstet Gynecol. 2002;14(6):569-575.
Tonni G, Grisolia G, Sepulveda W. Second trimester fetal neurosonography: Reconstructing cerebral midline anatomy and anomalies using a novel three-dimensional ultrasound technique. Prenat Diagn. 2014;34(1):75-83.
Tukei VJ, Hoffman HJ, Greenberg L, et al. Adverse pregnancy outcomes among HIV-positive women in the era of universal antiretroviral therapy remain elevated compared with HIV-negative women. Pediatr Infect Dis J. 2021;40(9):821-826.
Verkleij CPM, van Oppen ACC, Mulder EJH, et al. Evaluation of antenatal umbilical coiling index at 16-21 weeks of gestation as a predictor of trisomy 21 and other chromosomal defects. Ultrasound Obstet Gynecol. 2013;42(5):545-552.
Votino C, Cos T, Abu-Rustum R, et al. Use of spatiotemporal image correlation at 11-14 weeks' gestation. Ultrasound Obstet Gynecol. 2013;42(6):669-678.
Wagner RK, Calhoun BC. The routine obstetric ultrasound examination. Obstet Gynecol Clin North Am. 1998;25(3):451-463.
Wax J, Minkoff H, Johnson A. Consensus report on the detailed fetal anatomic ultrasound examination: Indications, components, and qualifications. J Ultrasound Med. 2014; 33:189-195.
Wax JR, Benacerraf BR, Copel J, et al. Consensus Report on the 76811 Scan: Modification. J Ultrasound Med. 2015t;34(10):1915.
Whitworth M, Bricker L, Neilson JP, Dowswell T. Ultrasound for fetal assessment in early pregnancy. Cochrane Database Syst Rev. 2010;(4):CD007058.
Williams PL, Crain M, Yildirim C, et al; or the Pediatric HIV/AIDS Cohort Study. Congenital anomalies and in utero antiretroviral exposure in HIV-exposed uninfected infants. JAMA Pediatr. 2015;169(1):48-55.
Witters I, Meylaerts L, Peeters H, et al. Fetal hydrometrocolpos, uterus didelphys with low vaginal and anal atresia: Difficulties in differentiation from a complex cloacal malformation: A case report. Genet Couns. 2012;23(4):513-517.
Woelfer B, Salim R, Banerjee S, et al. Reproductive outcomes in women with congenital uterine anomalies detected by three-dimensional ultrasound screening. Obstet Gynecol. 2001;98(6):1099-103.
Yagel S, Cohen SM, Messing B, Valsky DV. Three-dimensional and four-dimensional ultrasound applications in fetal medicine. Curr Opin Obstet Gynecol. 2009;21(2):167-174.
Youssef A, Cavalera M, Azzarone C, et al. The use of lung ultrasound during the COVID-19 pandemic: A narrative review with specific focus on its role in pregnancy. J Popul Ther Clin Pharmacol. 2020;27(S Pt 1):e64-e75.

Last Review 11/05/2024

Effective: 02/05/1998

Next Review: 02/13/2025
Review History
Definitions

Ultrasound for Pregnancy

Table Of Contents

Policy

Scope of Policy

Medical Necessity

Experimental, Investigational, or Unproven

Policy Limitations and Exclusions

Related Policies

CPT Codes / HCPCS Codes / ICD-10 Codes

Detailed fetal ultrasounds:

CPT codes covered if selection criteria are met:

Other CPT codes related to the CPB:

Other specified HCPCS codes related to the CPB:

ICD-10 codes covered (for detailed fetal ultrasounds) if selection criteria are met:

ICD-10 codes not covered for indications listed in the CPB (not all-inclusive):

Three-dimensional (3D) and four-dimensional (4D) fetal ultrasounds:

CPT codes not covered for indications listed in the CPB:

Pelvic Ultrasound: