Ultrasound for Pregnancy

Number: 0199

Policy

1. Aetna considers ultrasounds not medically necessary if done solely to determine the fetal sex or to provide parents with a view and photograph of the fetus

2. Aetna considers a fetal ultrasound with detailed anatomic examination medically necessary for 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. If there are known or suspected fetal anatomic abnormalities, including:

      1. Abnormal serum markers screening for fetal aneuploidy (triple or quad screening) (see CPB 464 - 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 advanced reproductive technology (ART) Footnote1*; 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. Previous pregnancy with a fetus that had an 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.

3. More than 1 detailed ultrasound fetal anatomic examination per pregnancy per practice is considered experimental and investigational, as there is inadequate evidence of the clinical utility of multiple serial detailed fetal anatomic ultrasound examinations during pregnancy.

4. Aetna considers detailed ultrasound fetal anatomic examination experimental and investigational for all other indications including routine evaluation of pregnant women who are on bupropion (Wellbutrin) or levetiracetam (Keppra), pregnant women with low pregnancy-associated plasma protein A, 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.

5. Aetna considers three-dimensional (3D) and four-dimensional (4D) fetal ultrasounds experimental and investigational 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.

Footnote1*Assisted Reproductive Technology (ART) is a form of complex infertility treatment where the egg and sperm are fertilized outside the body and the resulting embryo is transferred back into the uterus. The most well-recognized forms of ART include in-vitro fertilization (IVF), frozen embryo transfers (FET), and intra-cytoplasmic sperm injection (ICSI).

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

See also: CPB 0106 - Fetal Echocardiography and Magnetocardiography.

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) refered 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 pregancies 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 clubbling 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 recognise 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 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 (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 (2020) 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.

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).

Table: CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Information in the [brackets] below has been added for clarification purposes.   Codes requiring a 7th character are represented by "+":
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 specified 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>]
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, O24.811 - 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
O31.10x+ - O31.23x+	Continuing pregnancy after spontaneous abortion / intrauterine death of one fetus or more
O33.6xx+	Maternal care for disproportion due to hydrocephalic fetus
O33.7xx+	Maternal care for disproportion due to other fetal deformities
O35.0xx+	Maternal care for (suspected) central nervous system malformation in fetus
O35.1xx+	Maternal care for (suspected) chromosomal abnormality in fetus
O35.2xx+	Maternal care for (suspected) hereditary disease in fetus
O35.3xx+	Maternal care for (suspected) damage to fetus from viral disease in mother
O35.4xx+	Maternal care for (suspected) damage to fetus from alcohol
O35.5xx+	Maternal care for (suspected) damage to fetus by drugs
O35.6xx+	Maternal care for (suspected) damage to fetus by radiation
O35.8xx+	Maternal care for other (suspected) fetal abnormality and damage
O35.9xx+	Maternal care for (suspected) fetal abnormality and damage, unspecified
O36.011+ - O36.099+	Maternal care for rhesus isoimmunization
O36.111+ - O36.199+	Maternal care for other isoimmunization
O36.511+ - O36.599+	Maternal care for other known or suspected poor fetal growth
O40.1xx+ - O40.9xx+	Polyhydramnios
O41.00x+ - O41.03x+	Oligohydramnios
O69.81x+ - O69.89x+	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 >]
O99.320 - O99.323	Drug use complicating pregnancy
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
ICD-10 codes not covered for indications listed in the CPB (not all-inclusive):
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]
J84.03	Idiopathic pulmonary hemosiderosis
O99.330 - O99.335	Smoking (tobacco) complicating pregnancy, childbirth, and the puerperium
O99.350 - O99.355	Diseases of the nervous system complicating pregnancy, childbirth, and the puerperium [Keppra]
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

The above policy is based on the following references: