CAM 40114

Prenatal Screening for Fetal Aneuploidy

Category:Laboratory   Last Reviewed:July 2019
Department(s):Medical Affairs   Next Review:January 2020
Original Date:April 2003    

Description:
Ultrasound (US) markers can potentially increase the sensitivity of biochemical measures for first trimester detection of Down syndrome. Nuchal translucency (NT) refers to the US detection of subcutaneous edema in the fetal neck between weeks 10 and 13 of gestation. Fetal nasal bone examination involves US assessment at 11 to 14 weeks of gestation to identify the presence or absence of the nasal bone.

For individuals who are pregnant and in the first trimester who receive first-trimester Down syndrome screening of maternal serum markers and nuchal translucency, the evidence includes observational screening studies. Relevant outcomes are test accuracy and validity and resource utilization. There is sufficient evidence from 2 large multicenter prospective studies -- the Serum, Urine and Ultrasound Screening Study (SURUSS) the First and Second Trimester Evaluation of Risk (FASTER) trial -- as well as several smaller studies, that first-trimester screening for Down syndrome with measurement of fetal NT and maternal serum markers is at least as accurate as alternative tests and may allow earlier confirmation or exclusion of Down syndrome. The evidence is sufficient to determine qualitatively that the technology results in a meaningful improvement in the net health outcome. 

For individuals who are pregnant and in the first trimester who receive first-trimester Down syndrome screening of nuchal translucency alone, the evidence includes observational screening studies. Relevant outcomes are test accuracy and validity and resource utilization. The large multicenter prospective studies SURUSS and FASTER found, overall, that first-trimester screening with NT alone is inferior to first- or second-trimester combined screening. Additional testing may not be necessary in those few cases when NT is at least 4.0 mm due to the high likelihood of Down syndrome, but this would affect only a very small number of cases (0.09%-0.3%). The evidence is insufficient to determine the effects of the technology on health outcomes.

For individuals who are pregnant and in the first trimester who receive first-trimester Down syndrome screening of fetal nasal bone, the evidence includes several observational studies. Relevant outcomes are test accuracy and validity and resource utilization. The accuracy of testing in the published literature is variable, with some studies reporting relatively low sensitivity rates. The variability in accuracy reported may reflect the difficulty in performing and interpreting this test, and test results are likely prone to differences in operator characteristics. Limited evidence has suggested that there may be modest incremental benefit when the test is used in combination with NT measurement and serum markers, but the degree of benefit is unclear. The evidence is insufficient to determine the effects of the technology on health outcomes.

Background 
Definitive diagnosis of Down syndrome and other chromosomal abnormalities requires amniocentesis or chorionic villus sampling, both of which are invasive procedures that carry a risk of miscarriage estimated at 0.5% to 1%. Because of this risk, before biochemical screening existed, diagnosis was generally only offered to women aged 35 years or older, for whom the risk of the procedure approximated the risk of Down syndrome. However, most babies with Down syndrome are born to mothers younger than 35 years, even though the mothers are at lower individual risk. This situation created interest in developing less invasive screening programs based on assessment of serum markers that have shown associations with Down syndrome. In the late 1980s, biochemical screening at 16 weeks of gestation was developed and offered to all pregnant women. Biochemical screening consists of maternal serum measurements of α-fetoprotein, human chorionic gonadotropin (hCG) and unconjugated estriol (i.e., triple screen). More recently, a fourth marker has been used, inhibin-A (quadruple screen). The triple screen identifies approximately 69% of Down syndrome pregnancies and the quadruple screen 81%, both at a 5% false-positive rate.1 This false-positive rate refers to the proportion of all tests administered that are falsely positive at the cutoff point that produces that particular value of sensitivity. Among women who test positive, only about 2% actually have a fetus with Down syndrome.

There has been interest in ultrasound (US) markers to improve the accuracy of biochemical screening. One potential marker is fetal nuchal translucency (NT). This refers to the US detection of subcutaneous edema in the fetal neck, which is measured as the maximal thickness of the sonolucent zone between the inner aspect of the fetal skin and the outer aspect of the soft tissue overlying the cervical spine or the occipital bone. In the early 1990s, screening studies of pregnant women reported an association between increased NT in the first trimester of pregnancy (10-13 weeks of gestation) and chromosomal defects, most commonly Down syndrome (trisomy 21), but also trisomy 18 and 13. NT could be done alone as a first-trimester screen or in combination with maternal serum markers, free β subunit of hCG and pregnancy-associated plasma protein-A. These serum markers differ from those used in the second-trimester triple or quadruple screen.

Another potential US marker is fetal nasal bone examination. The technique for assessing the nasal bone is to view the fetal face longitudinally and exactly in the midline. The nasal bone synostosis resembles a thin echogenic line within the bridge of the nose. The nasal bones are considered to be present if this line is more echogenic than the overlying skin and absent if the echogenicity is the same or less than the skin, or if it is not visible. The absence of fetal nasal bone is considered to be a positive test result, indicating an increased risk of Down syndrome. In some cases, the sonographer will not be able to visualize the nasal area of the fetus’s face and, thus, cannot make a determination of the presence or absence of nasal bone. The inability to visualize the nasal bone is regarded as an unsuccessful examination, rather than a positive test result. Fetal nasal bone examination can be done from 11 weeks to just before 14 weeks of gestation. It is sometimes recommended that, if the nasal bone is absent on US done between 11 and 12 weeks of gestation, a second examination be done 2 weeks later. Fetal nasal bone assessment can be done along with NT, or in the second step of a 2-stage screen for cases that are borderline using other first-trimester markers.

Regulatory Status
Fetal US uses available instrumentation and, as a medical procedure, is not subject to regulation by the U.S. Food and Drug Administration.

Related Policies
40121 Sequencing-Based Tests to Determine Trisomy 21 from Maternal Plasma DNA

Policy:

  1. Screening test to detect Fetal Aneuploidy of chromosomes 13, 18, and 21 is considered MEDICALLY NECESSARY for women who are adequately counseled and desire information on the risk of having a child with Fetal Aneuploidy (e.g., Down syndrome) under the following conditions:
    • First-trimester (defined as 11-14 weeks) screening incorporating maternal serum markers (hCG, PAPP-A with NT).
    • Second-trimester (15-22 weeks) screening incorporating triple maternal serum markers (hCG, AFP, uE3 with NT) & Quad maternal serum markers (hCG, AFP, uE3, DIA with NT).
    • First (11-14 weeks) & second (15-22 weeks) trimester integrated screening incorporating maternal serum markers (PAPP-A with NT) & Quad maternal serum markers (hCG, AFP, uE3, DIA with NT).
    • First (11-14 weeks) & second (15-22 weeks) trimester sequential screening incorporating maternal serum markers (PAPP-A, hCG with NT) & Quad maternal serum markers (hCG, AFP, uE3, DIA with NT).
    • First (11-14 weeks) & second (15-22 weeks) trimester contingent screening incorporating maternal serum markers (PAPP-A, hCG with NT) if positive, Quad maternal serum markers (hCG, AFP, uE3, DIA with NT).
    • First & second trimester non-invasive prenatal screening (NIPS) for fetal aneuploidy (of at least 10 weeks gestation and singleton pregnancy) incorporating maternal serum cell-free fetal DNA.
  2. Sex chromosome testing incorporating maternal serum cell-free fetal DNA for detection of monosomy X (45, X or 45, XO) is considered MEDICALLY NECESSARY in suspected cases of Turner Syndrome.
  3. Confirmatory testing of equivocal and positive results from testing listed above via Chorionic Villa Sampling (CVS) or Amniocentesis should be offered, and is considered MEDICALLY NECESSARY for women wishing to pursue additional testing.+
  4. Screening for detection of Fetal Aneuploidies is considered NOT MEDICALLY NECESSARY under the following conditions:
    • Parallel or simultaneous testing with multiple screening methodologies for Fetal aneuploidy.
    • Screening of women with multiple gestation pregnancies with any testing other than nuchal translucency and/or subsequent diagnostic testing via Chorionic Villa Sampling (CVS) or Amniocentesis due to the risk of high false positive results.
    • repeat screening for women with negative screening results.
    • Egg donor pregnancies
    • For all uses other than the detection of fetal trisomy of 13, 18, and 21 and Turner syndrome (e.g., Microdeletion syndromes, unbalanced translocations, deletions, duplicaions).
    • For the determination of fetal sex.

Policy Guidelines
Since 2007, there are specific CPT codes for ultrasound measurement of nuchal translucency:

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.)

There is no specific CPT code for ultrasound assessment of fetal nasal bone translucency. It should be reported using CPT code 76815 - Ultrasound, pregnant uterus, real time with image documentation, limited (e.g., fetal heart beat, placental location, fetal position and/or qualitative amniotic fluid volume), one or more fetuses.

Protocols for the use of maternal serum markers in conjunction with fetal nuchal translucency may vary. However, the large U.S. BUN trial used a combination of free beta human chorionic gonadotropin (free beta hCG) and pregnancy-associated plasma protein A (PAPP-A). Other protocols have additionally used serum measurements of alpha-fetoprotein, unconjugated estriol and inhibin A. Regarding coding for the maternal serum factors, the CPT code for plasma protein (PAPP-A) is 84163. CPT code 84702 describes quantitative human chorionic gonadotropin. Effective in January 2008, CPT code 84704 describes free beta human chorionic gonadotropin. CPT code 82105 describes serum alpha-fetoprotein, code 82677 describes estriol and code 86336 describes inhibin A.

Effective in 2013, there are multianalyte assays with algorithmic analyses (MAAA) codes for some combinations of these maternal serum markers.

Prior to the creation of the specific MAAA codes for the triple, quad and penta screens, laboratories were reporting the codes for the component tests. Now that there are specific MAAA codes for these screens, the MAAA codes should be reported. If a component test (e.g., PAPP-A, hCG, AFP, etc.) is performed independently for a quantitative result without an algorithmic analysis or risk score, the CPT code for the individual test (84163, 84702, 82105, respectively) would be reported.

The 5 MAAA codes are:

81508 Fetal congenital abnormalities, biochemical assays of two proteins (PAPP-A, hCG [any form]), utilizing maternal serum, algorithm reported as a risk score

(Do not report 81508 in conjunction with 84163, 84702)

81509 Fetal congenital abnormalities, biochemical assays of three proteins (PAPP-A, hCG [any form], DIA), utilizing maternal serum, algorithm reported as a risk score

(Do not report 81509 in conjunction with 84163, 84702, 86336)

81510 Fetal congenital abnormalities, biochemical assays of three analytes (AFP, uE3, hCG [any form]) utilizing maternal serum, algorithm reported as a risk score (may include additional results from previous biochemical testing)

(Do not report 81510 in conjunction with 82105, 82677, 84702)

81511 Fetal congenital abnormalities, biochemical assays of four analytes (AFP, uE3, hCG [any form], DIA) utilizing maternal serum, algorithm reported as a risk score (may include additional results from previous biochemical testing)

(Do not report 81511 in conjunction with 82105, 82677, 84702, 86336)

81512 Fetal congenital abnormalities, biochemical assays of five analytes (AFP, uE3, total hCG, hyperglycosylated hCG, DIA) utilizing maternal serum, algorithm reported as a risk score

(Do not report 81512 in conjunction with 82105, 82677, 84702, 86336)

Note: It should be noted that appropriate training of ultrasonographers with ongoing quality assurance programs are considered critical to the accurate measurement of fetal nuchal translucency. In addition, in published studies of first-trimester screening, the laboratory and imaging components of screening (i.e., fetal nuchal translucency and measurement of maternal serum factors) are performed in a coordinated fashion.

Rationale
This evidence review was originally created in April 2003 and has been updated regularly with searches of the MEDLINE database. Most recently, the literature was reviewed through June 24, 2016. Following is a summary of the key literature.

In studies of first-trimester screening, the laboratory and imaging components of the screening are performed in a coordinated fashion. This process results in a set of predictions of Down syndrome, which can be summarized by receiver operator characteristic curve analysis or sensitivity and specificity estimates. Although multiple cutoff points are possible, a standard method of presenting results is to report the sensitivity at the cutoff that produces a 5% false-positive rate. In actual practice, however, patients are not just informed of a "positive" or "negative" result, but receive a numerical estimate ("1 of XX") of the probability of Down syndrome. These probability estimates may help aid further decision making by the patient.

Trial design issues include the population of patients studied (i.e., high-risk or average-risk) and the quality of follow-up to avoid verification bias. Verification bias refers to a problem in which the outcome status (Down syndrome or normal) is not assessed or is not available in certain patients. In the context of Down syndrome screening, spontaneous abortion is more likely in fetuses with chromosomal anomalies. Fetuses that miscarry may be more likely to have Down syndrome and may be missed among those who have negative screening tests. Therefore, unless karyotyping is performed in all cases of spontaneous abortion or stillbirth, it is likely that a certain percentage of Down syndrome fetuses will go undetected.2 Therefore, to avoid verification bias, it is important to have as complete a follow-up as possible of all pregnancy outcomes with karyotypic analysis on stillbirths and live births with dysmorphic features and phenotypic assessment of other live births.  

First-Trimester Screening With Maternal Serum Markers and Nuchal Translucency
There are 3 large, prospective, multicenter studies on the sensitivity of first-trimester screening that include nuchal translucency (NT) measurements. The Serum, Urine and Ultrasound Screening Study (SURUSS) study enrolled over 47,000 women, 101 of whom had fetuses with Down syndrome.3 This study evaluated several tests in parallel, including first-trimester testing with NT and maternal markers, the triple test, second-semester quadruple test and a combined first- and second-trimester test (both with and without NT). There were very high rates of verification, and adjustments were applied to account for miscarriages. Calculation of risk for all tests was done with a similar analytic methodology. There was no abnormal cutoff threshold for any measurement of NT or maternal serum analyte, because all measurements were entered into the regression model as continuous variables. In a direct comparison of the first-trimester test to the triple test, at a threshold of 85% detection, the first-trimester test had a false-positive rate of 6.1% and the triple test had a false-positive rate of 9.3%. The lower false-positive rate at the same sensitivity means that the first-trimester test had superior discriminative capacity. Setting the false-positive rate at 5% resulted in a sensitivity of 83%, which was superior to what was historically expected of the triple test. The study also evaluated NT measurement alone. Its performance was considerably worse than either first-trimester testing or the triple test, with a false-positive rate of 20% at a diagnostic sensitivity of 85%.

The BUN (blood, urea, nitrogen) study was also published in 2003 and evaluated first-trimester screening using the NT and the same maternal markers (β subunit of human chorionic gonadotropin [β-hCG] and pregnancy-associated plasma protein-A [PAPP-A]) as the SURUSS study.4 Approximately 8,500 patients were enrolled, and 61 cases of Down syndrome were identified. Using a screening threshold of 1 in 270, 52 (85%) of 61 of Down syndrome cases were detected with a false-positive rate of 9.4%. If the threshold were changed to produce a false-positive rate of 5%, the detection rate was 78.7%. Taking into account possible biases due to miscarriages, the authors calculated that second-trimester screening would have to be 75% sensitive to be equivalent to the 78.7% sensitivity they found for first-trimester screening.

Another large, prospective, multicenter study similar in design to the SURUSS study was published in 2005.5 This was the First and Second Trimester Evaluation of Risk (FASTER) trial, conducted in the United States, and sponsored by the National Institutes of Health. The study enrolled 38,167 women, 117 of whom had a fetus with Down syndrome. All women underwent first-trimester testing with NT and maternal markers, and second-trimester quadruple screening. The study compared the results of each test, as well as stepwise sequential screening (results provided after each test analyzed), fully integrated screening (results only provided after all tests analyzed) and serum-integrated screening (similar to fully integrated but NT results not included). At a threshold of 5% false-positive rate, the rate of detection of Down syndrome was 87% for first-trimester combined screening performed at 11 weeks, 63% for NT alone at 11 weeks, 81% with second-trimester quadruple screening, 88% with serum-integrated screening and 96% for fully integrated screening (first-trimester screening at 11 weeks). The detection rate of first-trimester screening was somewhat lower if performed after 11 weeks: 85% at 12 weeks and 82% at 13 weeks. Results of the FASTER trial provided further evidence that first-trimester combined screening was effective, but not NT measurement alone, and that integrated first- and second-trimester screening provided higher detection rates.

Subsequent studies have confirmed combined first-trimester screening that includes NT measurement and maternal serum markers is superior to NT measurement alone.6-12 For example, in 2013, Peuhkurinen et al. in Finland reported on tests performed prospectively in 35,314 pregnant women.12 Ninety-five Down syndrome pregnancies were identified. The detection rate was 64.5% for NT alone and 72.4% for combined screening with NT and maternal serum markers. False-positive rates were 4.4% with NT alone and 4.0% with combined screening. Moreover, Ranta et al., in a retrospective review of data on 76,949 women in Finland, found that combined screening with maternal serum markers and NT is especially preferable in women aged 35 years and younger.10 

Studies continue to investigate the optimal approach to testing that balances the desires to maximize detection, minimize false-positive results, minimize unnecessary testing and provide information to women as early in their pregnancies as possible. As stated, the SURUSS and FASTER studies estimated the results of several approaches, including combination first-trimester testing only, stepwise sequential testing (results given after first-trimester testing, move on to second-trimester testing) and integrated screening (results given only after first- and second-trimester testing). A retrospective analysis of the prospectively collected FASTER data by Cuckle et al. introduced another screening approach — called "contingent screening."13 Initial risk was calculated from first trimester NT measurement or maternal serum markers and classified as positive (i.e., >1 in 20), borderline (i.e., 1 in 30-1,500) and negative (i.e., <1 in 1,500). Women with positive tests were offered immediate prenatal diagnosis, and those with borderline tests underwent second-trimester quadruple screening and risks were recalculated. A final risk of greater than 1 in 270 was considered positive. This approach differs from stepwise sequential testing in that only women with borderline results continued to second-trimester testing. First-trimester testing identified 52 (60%) of 86 affected fetuses with a 1.2% false-positive rate (401 false-positive results). The final detection rate with the contingent approach was 91% with a 4.5% false-positive rate. Detection rates were similar with the stepwise approach (92% with 5.1% false-positive results) but substantially more women received second-trimester testing, 31,868 with stepwise testing versus 7,360 with contingent testing.

Another retrospective analysis of prospectively collected screening data was published by Kagan et al. in 2010.14 Contingent screening resulted in better test performance than in other approaches. In this case, contingent screening involved first-stage screening using maternal age and NT thickness, with or without an additional ultrasound marker. Women with a risk of 1 in 50 or more were considered to test positive and those with a risk of less than 1 in 1,000 were considered to test negative. Patients with intermediate risk (i.e., 1 in 51 to 1 in 1,000) underwent second-stage screening with the biochemical markers free β-hCG and PAPP-A. An adjusted risk of at least 1 in 100 was then considered positive. The analysis used data from 21,141 singleton pregnancies, 122 of which had fetal trisomy 21.

After first-stage screening using only maternal age and NT thickness, the risk was 1 in 50 or more in 1.4% of the euploid pregnancies and 75% of the trisomy 21 pregnancies. An intermediate risk was found in 28.3% of euploid pregnancies and 23% of the trisomy 21 pregnancies. After second-stage screening with serum markers, the overall detection rate for trisomy 21 was 89%, and the false-positive rate was 3.0%. The addition of fetal nasal bone evaluation in the first-stage screening resulted in a final detection rate of 90% with a false-positive rate of 2.6%. When first-stage screening consisted of maternal age and biochemical markers, and second-stage screening included fetal NT thickness and fetal nasal bone, the final detection rate was 92% with a false-positive rate of 5.2%. Other ultrasound (US) markers, not currently addressed herein, were evaluated in the Kagan study. With first-stage screening consisting of the marker ductus venosus flow added to maternal age and NT and second-stage screening for biochemical markers, there was a trisomy 21 pregnancy detection rate of 96% with a false-positive rate of 2.7%. When tricuspid flow was assessed instead of ductus venosus in the strategy previously described, there was a detection rate of 94% and a false-positive rate of 2.6%.

Several studies evaluating a particular screening approach in practice have been published. In 2015, Baer et al. reported on 452,901 women screened under the auspices of the California Prenatal Screening Program.15 Women received first-trimester screening with maternal serum markers and NT measurement when fetal crown rump length was 45 to 84 mm. About 91% of women also had second-trimester serum screening and, in these cases, findings of first- and second-trimester serum tests were integrated. Down syndrome was detected in 1,275 (0.28%) cases. A total of 1,184 of these had a positive screening test, with a Down syndrome detection rate of 92.9%. In 2009, Wald et al. in the U.K. reported on use of the integrated screening strategy.16 Records from 2 London hospitals were reviewed for 15,888 women who presented in the first trimester and were screened. Ninety-eight percent accepted integrated screening, and 94% of women completed both testing stages. The Down syndrome detection rate was 87%, consistent with an estimate of 89% predicted by SURUSS. The observed false-positive rate was 2.1%. A 2013 study by Torella et al. in Italy reported the performance of 2-stage first-trimester combined screening.17 Blood samples were taken at 8 weeks 0 days to 10 weeks 6 days, and NT measurement was performed at 12 weeks 0 days to 12 weeks 6 days. The combined screen was considered positive when the risk of Down syndrome was greater than 1 in 250. A total of 73 positive cases were identified among 713 women with singleton pregnancies who were screened. All 73 women underwent invasive testing and 5 cases of trisomy 21 were detected. There was also 1 false-negative case. Using this approach, the Down syndrome detection rate was 83% and the false-positive rate was 3.2%.

Section Summary: First-Trimester Screening With Maternal Serum Markers and Nuchal Translucency
Evidence from multiple large prospective studies establishes that the accuracy of US assessment of NT assessment combined with maternal serum markers for detection of Down syndrome is similar or higher to other available methods. This combination of tests offers advantages over alternatives in that it can be performed earlier in the pregnancy than other methods and may lead to an earlier confirmation or exclusion of Down syndrome. The accuracy of either component alone (i.e., serum markers or NT measurement) is less than that of the combined tests. The optimal timing of this test, and/or the optimal sequence or combination of this screening test with other tests, is not certain at this time.

First-Trimester Screening With Fetal Nuchal Translucency Alone
Several studies discussed in the section above evaluated NT measurement alone and combination maternal serum markers and NT measurement. In Peuhkurinen et al., a study with 35,314 pregnant women, the detection rate was 64.5% for NT measurement alone and 72.4% for combined screening with NT and maternal serum markers.12 The FASTER trial compared first-trimester testing with NT and maternal markers, and second-trimester quadruple screening in 38,167 women.5 At a threshold of 5% false-positive rate, the rate of detection of Down syndrome at 11 weeks was lower with NT measurement alone (63%) than with first-trimester combined screening (87%). A retrospective analysis of 36,120 patients in the prospective FASTER study, published in 2006, found no added benefit in waiting for serum screening results when NT was 4.0 mm or greater, and minimal benefit when NT was 3.0 mm or greater.18 However, there were only 32 (0.09%) fetuses with NT of at least 4.0 mm and 128 (0.3%) with NT at least 3.0 mm. Similarly, a retrospective study of 77,443 women in Quebec found that final combined first-trimester screening results were always positive in the 197 (0.3%) of cases where NT measurements were at least 4.0 mm.19

An ongoing issue with NT measurement is the possible variability of ultrasonographic interpretation. The Fetal Medicine Foundation in the U.K. has a training program that offers an internet-based certificate of competency in NT.20 Continuing medical education courses in the United States are also available through the Fetal Medicine Foundation’s U.S. affiliate.21 Training and certification, along with ongoing quality control, an appropriate reference database of patients and use of statistical methodology, are necessary to produce optimal diagnostic results. Two studies with large sample sizes22,23 have estimated the impact of measurement error on the results of first-trimester screening by taking actual screening results and artificially altering the NT values. Both studies found that even small deviations in measurement of NT affected the false-positive and false-negative rates. For example, in the Schmidt et al. study, which analyzed data from 10,116 pregnancies, underestimating the NT by 0.5 mm increased the number of false-negative results from 12 to 20 (an increase of 66.7%) and decreased the number of false-positive results from 479 to 281 (a decrease of 41.3%).23 On the other hand, overestimating the NT by 0.5 mm decreased the number of false-negative results from 12 to 11 (a decrease of 8.3%) and increased the number of false-positive results from 479 to 1,149 (an increase of 140%). Findings emphasized the importance of accurate measurement of NT and potential value of combining NT findings with maternal serum markers.

Section Summary: First-Trimester Screening With Nuchal Translucency Alone
Several studies on first-trimester screening for Down syndrome, including the large prospective FASTER trial, have found that the accuracy of NT measurement alone is lower than NT measurement and maternal serum markers. Moreover, there are potential measurement errors associated with interpreting NT values from US.

First-Trimester Screening for Fetal Nasal Bone
Performance of Fetal Nasal Bone Assessment Alone
A 2006 systematic review by Rosen et al. for the U.S.-based Maternal Fetal Medicine Foundation Nuchal Translucency Oversight Committee identified 10 studies on fetal nasal bone performance.24 A total of 35,312 women underwent first-trimester US assessment of fetal nasal bone. The fetal nasal bone was successfully imaged in 33,314 (94.3%) of cases; in 5.7% of cases, it could not be imaged. There were 479 Down syndrome fetuses, for a prevalence of 13.6 in 1,000. The authors note that this is 10 times the first-trimester incidence in the United States, suggesting a high-risk population had been screened. The fetal nasal bone was absent in 310 (65%) of 479 Down syndrome cases and in 274 (0.8%) of 34,048 chromosomally normal cases.

One of the selected studies, a subanalysis of the FASTER study (previously discussed), involved a general population sample and had much lower rates of successful imaging than other studies.25 Assessment of fetal nasal bone was added to the FASTER protocol during the last 7 months but did not occur in all centers. A total of 6,324 women underwent a fetal nasal bone ultrasound and pregnancy outcome data were available for 6,228 (98.5%) of them. Sonographers failed to obtain an adequate view in 1,523 (24%) patients. Among the 4,801 cases with adequate images of the fetal profile, the nasal bones were described as being absent in 22 (0.5%) of them. There were 11 identified cases of Down syndrome. Fetal nasal bone assessment did not identify any of these cases as potentially high risk. In 9 (92%) of the 11 cases, the fetal nasal bones were judged to be present, and in 2 cases, it could not be determined. There were also 2 cases of trisomy 18; nasal bones were present in 1 and absent in the other. FASTER investigators concluded that first-trimester fetal nasal bone sonography did not seem to have a role in general population screening for Down syndrome. Other researchers have commented on the lower rate of successful fetal nasal bone assessment in the FASTER analysis. The Rosen review article noted that, although the sonographers were trained and experienced in NT measurement, they were new to fetal nasal bone assessment.24 Another review article by Sonek et al. stated that the likely explanation for the FASTER findings is that their techniques differed from those used by others.26 

One study identified directly compared the performance of fetal nasal bone assessment in unselected and selected populations.27 This prospective study included 7,672 pregnant women, 7,116 of whom were at average risk and 510 at increased risk (>1 in 300) of Down syndrome based on age, family history or previous pregnancy history. It was not possible to adequately assess the fetal nasal bones in 712 (10%) of 7,116 in a general population sample or in 42 (8.2%) of 510 in a high-risk sample. A total of 35 cases of Down syndrome were identified, 23 in the selected group and 12 in the unselected group. Two Down syndrome cases in the selected group were excluded because the US examination was not satisfactory. In the remaining cases, absent fetal nasal bones identified 10 (47.6%) of 21 Down syndrome cases in the selected population and 2 (16.7%) of 12 in the unselected group. An analysis including the 2 missing cases found that fetal nasal bone assessment was able to correctly identify 10 (43.5%) of 23 Down syndrome cases. In a logistic regression model including fetal nasal bone findings, as well as NT and demographic factors, absence of fetal nasal bone was found to be an independent predictor of trisomy 21 in the selected pregnancies group but not in the unselected pregnancies group.

A 2015 study by Chanprapaph et al. in Thailand assessed the presence or absence of fetal nasal bone in 190 fetuses.28 To be included in the study, pregnant women had to be at increased risk for fetal aneuploidy (e.g., advanced maternal age, previous pregnancy with abnormal chromosome, abnormal sonographic markers or serum tests). An absent nasal bone was identified in 5 (2.6%) of 190 of the fetuses and, as a stand-alone marker, had a sensitivity of 28.57% and specificity of 99.43% for detecting fetal aneuploidy. In this study, other sonographic markers were measured but no serum testing was conducted. The combination of a positive NT and fetal nasal bone test had a sensitivity of 71.43% and specificity of 95.45%.  

Performance of Fetal Nasal Bone Assessment as part of a Comprehensive Screening Program
Several studies identified evaluated the diagnostic accuracy of first-trimester screening programs that included fetal nasal bone measurements as part of a comprehensive screening program. None were conducted in the United States.

Cicero et al. conducted a single-center prospective screening study in the U.K.29 Down syndrome screening including fetal nasal bone assessment was conducted in 21,074 singleton pregnancies at 11 to 13 weeks of gestation. Data from 20,418 (97%) women were available for analysis. Chromosomal abnormalities were detected in 253 of the pregnancies; this included 140 cases of Down syndrome. An adequate view of the fetal profile could not be obtained in 243 (1.2%) of cases. Of the 20,175 cases with a fetal profile (i.e., "successful" examination), the nasal bone was recorded as absent in 238 (1.2%) of cases and present in 19,937 (97.6%). Combined screening with NT assessment and maternal serum markers achieved a detection rate of 90% at a fixed false-positive rate of 5%. With the detection rate fixed at 90%, the inclusion of nasal bone measurements using either screening strategy decreased the false-positive rate to 2.5%. In another analysis at a fixed false-positive rate of 5%, the inclusion of fetal nasal bone assessment of all women in the sample increased the detection rate to 93.6% at the 5% false-positive rate. The same increase in the detection rate, to 93.6%, was obtained when fetal nasal bone assessment was included only for women of intermediate risk (1 in 51 to 1 in 1,000).

A study by Sahota et al., conducted in Hong Kong retrospectively, analyzed 10,767 women who had been screened in a comprehensive first-trimester screening program.30 The analysis compared several approaches to screening. Among the 10,854 fetuses with a known outcome, 32 had Down syndrome. In a screening approach that combined NT assessment and maternal serum markers in this group, 27 (94%) of the pregnancies would have been classified as high risk, 4 as low risk and 1 as intermediate risk. The protocol included fetal nasal bone assessment of intermediate-risk pregnancies, with reclassification as high risk if the fetal nasal bone was absent. The 1 case classified as intermediate risk had an absent fetal nasal bone. In this study, too few cases were classified as intermediate risk to determine whether fetal nasal bone assessment in a contingent screening approach improves screening accuracy.

A 2014 prospective study conducted by Hsiao et al. in Taiwan included 20,586 women screened with maternal serum markers and various US markers.31 The combination of maternal serum markers and NT measurement had a 66.7% detection rate for trisomy 21. The addition of fetal nasal bone measurement increased the detection rate to 88.2%. Further inclusion of more US markers (i.e., tricuspid regurgitation) and the Doppler velocity waveform of the ductus venosus continued to increase the detection rate.

Techniques for evaluating fetal nasal bone images continue to be refined. A 2014 prospective study reported on the feasibility of assessing fetal nasal bone using the retronasal triangle view.32 A total of 1,977 women pregnant with singletons were scanned using this approach. The retronasal triangle view was successfully obtained for 1,970 (99.6%) fetuses. The prevalence of an absent or hypoplastic fetal nasal bone was 12 (0.7%) of 1,728 in euploid fetuses and 12 (70.6%) of 17 in fetuses with trisomy 21. The sensitivity and specificity of an absent or hypoplastic fetal nasal bone for detecting trisomy 21 were 70.6% and 99.3%, respectively. Another technique under investigation is 3-dimensional US to measure fetal nasal bone during the first trimester. Nanni et al. evaluated 161 women pregnant with singletons with both 2- and 3-dimensional US.33 There was high intraobserver and interobserver agreement using 3-dimensional US. The agreement between 2- and 3-dimensional US was moderate (correlation coefficient, 0.77).

As with NT measurement, there is possible variability in fetal nasal bone interpretation and a need for adequate training and quality control. The review article by Rosen et al. noted that mastering imaging of the nasal bone appears to be more difficult than mastering NT measurement.24 The Fetal Medicine Foundation in the U.K. has an internet-based certificate of competency in fetal nasal bone assessment; its website does not state how long this program has been available.20 

Generalizability of nasal bone assessment to general clinical practice is also a consideration. A committee of the Fetal Medicine Foundation recommended further evaluation of nasal bone assessment in low-risk populations and additional availability of adequately trained centers before nasal bone assessment is introduced into general practice. It also suggested considering a contingent screening strategy. This approach is similar to that used in the Sahota study30 (discussed earlier), in which fetal nasal bone assessment is used only in cases with a borderline risk determination by screening with NT and maternal serum markers. Were a contingency model used, patients could be referred to centers with developed expertise, although the authors noted that this may not be feasible or practical in all areas of the United States.

Section Summary: First-Trimester Screening for Fetal Nasal Bone
Assessment of fetal nasal bone by US is another method of screening for Down syndrome phenotype in utero. The accuracy of this test in the published literature varies, and some studies have reported a relatively low sensitivity. The variability in accuracy reported may reflect the difficulty in performing and interpreting this test, and the test results are likely prone to differences in operator characteristics. Limited evidence has suggested that there may be modest incremental benefit when used in combination with US NT and serum markers, but the degree of benefit is unclear.

Ongoing and Unpublished Clinical Trials
A search of ClinicalTrials.gov in July 2016 did not identify any ongoing or unpublished trials that would likely influence this review.

Summary of Evidence
For individuals who are pregnant and in the first trimester who receive first-trimester Down syndrome screening of maternal serum markers and nuchal translucency, the evidence includes observational screening studies. Relevant outcomes are test accuracy and validity and resource utilization. There is sufficient evidence from 2 large multicenter prospective studies -- the Serum, Urine and Ultrasound Screening Study (SURUSS) and the First and Second Trimester Evaluation of Risk (FASTER) trial -- as well as several smaller studies, that first-trimester screening for Down syndrome with measurement of fetal nuchal translucency (NT) and maternal serum markers is at least as accurate as alternative tests and may allow earlier confirmation or exclusion of Down syndrome. The evidence is sufficient to determine qualitatively that the technology results in a meaningful improvement in the net health outcome.

For individuals who are pregnant and in the first trimester who receive first-trimester Down syndrome screening of nuchal translucency alone, the evidence includes observational screening studies. Relevant outcomes are test accuracy and validity and resource utilization. The large multicenter prospective studies SURUSS and FASTER found, overall, that first-trimester screening with NT alone is inferior to first- or second-trimester combined screening. Additional testing may not be necessary in those few cases when NT is at least 4.0 mm due to the high likelihood of Down syndrome, but this would affect only a very small number of cases (0.09%-0.3%). The evidence is insufficient to determine the effects of the technology on health outcomes.

For individuals who are pregnant and in the first trimester who receive first-trimester Down syndrome screening of fetal nasal bone, the evidence includes several observational studies. Relevant outcomes are test accuracy and validity and resource utilization. The accuracy of testing in the published literature is variable, with some studies reporting relatively low sensitivity rates. The variability in accuracy reported may reflect the difficulty in performing and interpreting this test, and test results are likely prone to differences in operator characteristics. Limited evidence has suggested that there may be modest incremental benefit when the test is used in combination with NT measurement and serum markers, but the degree of benefit is unclear. The evidence is insufficient to determine the effects of the technology on health outcomes. 

Practice Guidelines and Position Statements
Society of Obstetricians and Gynaecologists of Canada
In 2011, consensus guidelines on maternal screening for fetal aneuploidy were published by the Society of Obstetricians and Gynaecologists of Canada.34 Recommendations relevant to this evidence review are as follows.

For singleton pregnancies:

  • "All pregnant women …, regardless of age, should be offered …the option of prenatal screening for the most common clinically significant fetal aneuploidies. In addition, they should be offered a second-trimester ultrasound for dating, assessment of fetal anatomy and detection of multiples. (I-A)"
  • First-trimester nuchal translucency should not be offered as a screen without biochemical markers. It should be measured by sonographers or sonologists trained and accredited for this service.

For twin pregnancies:

  • "Fetal nuchal translucency combined with maternal age is an acceptable first-trimester screening test for aneuploidies in twin pregnancies. (II-2)"
  • "First-trimester serum screening combined with nuchal translucency may be considered in twin pregnancies. It provides some improvement over the performance of screening by nuchal translucency and maternal age because the false-positive rate is lower. (II-3)" 

American College of Obstetricians and Gynecologists
In May 2016, the American College of Obstetricians and Gynecologists issued practice bulletin 16335 on screening for fetal aneuploidy, replacing practice bulletin 77.1 The following recommendations and conclusions in the bulletin are relevant to this evidence review:

Level A recommendations (based on good and consistent scientific evidence: 

"Women who have a negative screening test result should not be offered additional screening tests for aneuploidy because this will increase their potential for a false-positive test result." 

"If an enlarged nuchal translucency, an obvious anomaly or a cystic hygroma is identified on ultrasonography, the patient should be offered genetic counseling and diagnostic testing for aneuploidy, as well as follow-up ultrasonography for fetal structural abnormalities." 

"Patients with an enlarged nuchal translucency or cystic hygroma and normal fetal karyotype should be offered an anatomic evaluation in the second trimester, fetal cardiac ultrasonography and further counseling regarding the potential for genetic syndromes not detected by aneuploidy screening." 

"Women with a positive screening test result for fetal aneuploidy should be offered further detailed counseling and testing." 

Level C (based primarily on consensus and expert opinion): 

"Aneuploidy screening or diagnostic testing should be discussed and offered to all women early in pregnancy, ideally at the first prenatal visit." 

"All women should be offered the option of aneuploidy screening or diagnostic testing for fetal genetic disorders, regardless of maternal age." 

"If an isolated ultrasonographic marker for aneuploidy is detected, the patient should be offered aneuploidy screening if it was not offered previously." 

"Some women who receive a positive test result from traditional screening may prefer to have cell-free DNA screening rather than undergo definitive testing. This approach may delay definitive diagnosis and management and may fail to identify some fetuses with aneuploidy."

"Parallel or simultaneous testing with multiple screening methodologies for aneuploidy is not cost effective and should not be performed."

U.S. Preventive Services Task Force Recommendations
Not applicable.

References: 

  1. ACOG Committee on Practice Bulletins. ACOG Practice Bulletin No. 77: screening for fetal chromosomal abnormalities. Obstet Gynecol. Jan 2007;109(1):217-227. PMID 17197615
  2. Mol BW, Lijmer JG, van der Meulen J, et al. Effect of study design on the association between nuchal translucency measurement and Down syndrome. Obstet Gynecol. Nov 1999;94(5 Pt 2):864-869. PMID 10546775
  3. Wald NJ, Rodeck C, Hackshaw AK, et al. First and second trimester antenatal screening for Down's syndrome: the results of the Serum, Urine and Ultrasound Screening Study (SURUSS). J Med Screen. 2003;10(2):56-104. PMID 14746340
  4. Wapner R, Thom E, Simpson JL, et al. First-trimester screening for trisomies 21 and 18. N Engl J Med. Oct 9 2003;349(15):1405-1413. PMID 14534333
  5. Malone FD, Canick JA, Ball RH, et al. First-trimester or second-trimester screening, or both, for Down's syndrome. N Engl J Med. Nov 10 2005;353(19):2001-2011. PMID 16282175
  6. Leung TY, Chan LW, Leung TN, et al. First-trimester combined screening for trisomy 21 in a predominantly Chinese population. Ultrasound Obstet Gynecol. Jan 2007;29(1):14-17. PMID 17171632
  7. Schaelike M, Kossakiewicz M, Kossakiewicz A, et al. Examination of a first-trimester Down syndrome screening concept on a mix of 11,107 high- and low-risk patients at a private center for prenatal medicine in Germany. Eur J Obstet Gynecol Reprod Biol. Jun 2009;144(2):140-145. PMID 19362411
  8. Brameld KJ, Dickinson JE, O'Leary P, et al. First trimester predictors of adverse pregnancy outcomes. Aust N Z J Obstet Gynaecol. Dec 2008;48(6):529-535. PMID 19133038
  9. Kagan KO, Etchegaray A, Zhou Y, et al. Prospective validation of first-trimester combined screening for trisomy 21. Ultrasound Obstet Gynecol. Jul 2009;34(1):14-18. PMID 19526452
  10. Ranta JK, Marttala J, Laitinen P, et al. First trimester biochemistry at different maternal ages. Clin Chem Lab Med. Mar 2012;50(3):549-555. PMID 22112052
  11. Berktold L, C VK, Hillemanns P, et al. Analysis of the impact of PAPP-A, free beta-hCG and nuchal translucency thickness on the advanced first trimester screening. Arch Gynecol Obstet. Mar 2013;287(3):413-420. PMID 23080546
  12. Peuhkurinen S, Laitinen P, Honkasalo T, et al. Comparison of combined, biochemical and nuchal translucency screening for Down syndrome in first trimester in Northern Finland. Acta Obstet Gynecol Scand. Jul 2013;92(7):769-774. PMID 23369035
  13. Cuckle HS, Malone FD, Wright D, et al. Contingent screening for Down syndrome--results from the FaSTER trial. Prenat Diagn. Feb 2008;28(2):89-94. PMID 18236423
  14. Kagan KO, Staboulidou I, Cruz J, et al. Two-stage first-trimester screening for trisomy 21 by ultrasound assessment and biochemical testing. Ultrasound Obstet Gynecol. Nov 2010;36(5):542-547. PMID 20503223
  15. Baer RJ, Flessel MC, Jelliffe-Pawlowski LL, et al. Detection rates for aneuploidy by first-trimester and sequential screening. Obstet Gynecol. Oct 2015;126(4):753-759. PMID 26348180
  16. Wald NJ, Huttly WJ, Murphy KW, et al. Antenatal screening for Down's syndrome using the Integrated test at two London hospitals. J Med Screen. 2009;16(1):7-10. PMID 19349524
  17. Torella M, Tormettino B, Zurzolo V, et al. Screening for trisomy 21 by maternal age fetal nuchal translucency thickness and maternal serum sample. Minerva Ginecol. Dec 2013;65(6):653-659. PMID 23881389
  18. Comstock CH, Malone FD, Ball RH, et al. Is there a nuchal translucency millimeter measurement above which there is no added benefit from first trimester serum screening? Am J Obstet Gynecol. Sep 2006;195(3):843-847. PMID 16949423 
  19. Miron P, Cote YP, Lambert J. Nuchal translucency thresholds in prenatal screening for Down syndrome and trisomy 18. J Obstet Gynaecol Can. Mar 2009;31(3):227-235. PMID 19416569
  20. Fetal Medicine Foundation website. Certificate of Competence in the Measurement of Nuchal Translucency. . https://fetalmedicine.org/nuchal-translucency-scan. Accessed March 6, 2015.
  21. Fetal Medicine Foundation website. http://www.fetalmedicineusa.com/. Accessed July 22, 2016.
  22. Kagan KO, Wright D, Etchegaray A, et al. Effect of deviation of nuchal translucency measurements on the performance of screening for trisomy 21. Ultrasound Obstet Gynecol. Jun 2009;33(6):657-664. PMID 19408250
  23. Schmidt P, Staboulidou I, Elsasser M, et al. How imprecise may the measurement of fetal nuchal translucency be without worsening first-trimester screening? Fetal Diagn Ther. 2008;24(3):291-295. PMID 18818502
  24. Rosen T, D'Alton ME, Platt LD, et al. First-trimester ultrasound assessment of the nasal bone to screen for aneuploidy. Obstet Gynecol. Aug 2007;110(2 Pt 1):399-404. PMID 17666617
  25. Malone FD, Ball RH, Nyberg DA, et al. First-trimester nasal bone evaluation for aneuploidy in the general population. Obstet Gynecol. Dec 2004;104(6):1222-1228. PMID 15572480
  26. Sonek JD, Cicero S, Neiger R, et al. Nasal bone assessment in prenatal screening for trisomy 21. Am J Obstet Gynecol. Nov 2006;195(5):1219-1230. PMID 16615922
  27. Prefumo F, Sairam S, Bhide A, et al. First-trimester nuchal translucency, nasal bones, and trisomy 21 in selected and unselected populations. Am J Obstet Gynecol. Mar 2006;194(3):828-833. PMID 16522420
  28. Chanprapaph P, Dulyakasem C, Phattanchindakun B. Sensitivity of multiple first trimester sonomarkers in fetal aneuploidy detection. J Perinat Med. May 2015;43(3):359-365. PMID 25222592
  29. Cicero S, Avgidou K, Rembouskos G, et al. Nasal bone in first-trimester screening for trisomy 21. Am J Obstet Gynecol. Jul 2006;195(1):109-114. PMID 16813749
  30. Sahota DS, Leung TY, Chan LW, et al. Comparison of first-trimester contingent screening strategies for Down syndrome. Ultrasound Obstet Gynecol. Mar 2010;35(3):286-291. PMID 20052660
  31. Hsiao CH, Cheng PJ, Shaw SW, et al. Extended first-trimester screening using multiple sonographic markers and maternal serum biochemistry: a five-year prospective study. Fetal Diagn Ther. Feb 6 2014;35(4):296-301. PMID 24503519
  32. Adiego B, Martinez-Ten P, Illescas T, et al. First-trimester assessment of nasal bone using retronasal triangle view: a prospective study. Ultrasound Obstet Gynecol. 2014;43(3):272-276. PMID 23733531
  33. Nanni M, Maroni E, Bevini M, et al. The usefulness of volume NT software in measuring the fetal nasal bone at 11 to 13 + 6 weeks of gestation. Prenat Diagn. May 2014;34(5):500-504. PMID 24510896
  34. Audibert F, Gagnon A, Genetics Committee of the Society of Obstetricians and Gynaecologists of Canada, et al. Prenatal screening for and diagnosis of aneuploidy in twin pregnancies. J Obstet Gynaecol Can. Jul 2011;33(7):754-767. PMID 21749753
  35. ACOG Committee on Practice Bulletins. Screening for Fetal Aneuploidy (No. 163). www.acog.org. Accessed July, 2016.

Coding Section

Codes Number Description
CPT   See Policy Guidelines section
  81420  Fetal chromosomal aneuploidy (eg, trisomy 21, monosomy X) genomic sequence analysis panel, circulating cell-free fetal DNA in maternal blood, must include analysis of chromosomes 13, 18, and 21  
  81422  Fetal chromosomal microdeletion(s) genomic sequence analysis (eg, DiGeorge syndrome, Cri-du-chat syndrome), circulating cell-free fetal DNA in maternal blood 
  81479 Unlisted molecular pathology procedure 
  81507  Fetal aneuploidy (trisomy 21, 18, and 13) DNA sequence analysis of selected regions using maternal plasma, algorithm reported as a risk score for each trisomy
  81508  Fetal congenital abnormalities, biochemical assays of two proteins (PAPP-A, hCG), utilizing maternal serum, algorithm reported as risk score 
  81509  Fetal congenital abnormalities, biochemical assays of three proteins (PAPP-A, hCG, DIA), utilizing maternal serum, algorithm reported as risk score  
  81510  Fetal congenital abnormalities, biochemical assays of three analytes (AFP, uE3, hCG), utilizing maternal serum, algorithm reported as risk score 
  81511 Fetal congenital abnormatlities, biochemical assays of four analytes (AFP, uE3, hCG (any form), DIA), utiliizing maternal serum, algorithm reported as a risk score (may include additional results from previous biochemical testing) 
  81512  Fetal congenital abnormatlities, biochemical assays of four analytes (AFP, uE3, hCG (any form), DIA), utiliizing maternal serum, algorithm reported as a risk score (may include additional results from previous biochemical testing) 
  81599  Unlisted multianalyte assay with algorithmic analysis 
  82105  Alpha-fetoprotein; serum 
  82106 Alpha-fetoprotein; amniotic fluid 
  83516  Immunoassay for analyte other than infectious agent antibody or infectious agent antigen; qual or semiquant, multiple step method 
  83520  Immunoassay for analyte other than infectious agent antibody or infectious agent antigen; quantitative, not otherwise specified 
  83632  Lactogen, human placental human chorionic somatomammotropin 
  84703  Gonadotropin, chorionic (hcg); qualitative 
  84702  Gonadrotropin, chorionic; quantitative 
  84163  Pregnancy-associated plasma protein (PAPP-A) 
  86336  Inhibin A 
  88267  Chromosome analysis, amniotic fluid or chorionic villus, count 15 cells, 1 karyotype, with banding 
  88271  Molecular cytogenetics, DNA probe, each (e.g., FISH) 
  88280 

Chromosome analysis; additional karyotypes, each study 

  0009M  Fetal aneuploidy trisom risk 
  88235 Tissue culture for non-neoplastic disorders; amniotic fluid or chorionic villus cells 
  88267 Chromosome analysis, amniotic fluid or chorionic villus, count 15 cells, 1 karyotype, with banding 
  88280 Chromosome analysis; additional karyotypes, each study 
ICD-9 Diagnosis V23.81 Elderly primigravida
  V26.33 Genetic counseling and testing
  V28.3 Screening for malformation using ultrasonics
HCPCS    
ICD-10-CM (effective 10/01/12) O09.511 Supervision of elderly primigravide—First trimester
  Z31.430-Z31.438 Encounter for genetic testing - Female
  Z31.440-Z31.448 Encounter for genetic testing - Male
  Z36 Encounter for antenatal screening for mother
  Z36.82  Encounter for antenatal screening for nuchal translucency 
ICD-10-PCS (effective 10/01/15)   ICD-10-PCS codes are only for use on inpatient services. There is no specific ICD-10-PCS code for this testing.
Type of Service    
Place of Service    

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive. 

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, Blue Cross and Blue Shield Association technology assessment program (TEC) and other non-affiliated technology evaluation centers, reference to federal regulations, other plan medical policies and accredited national guidelines.

"Current Procedural Terminology© American Medical Association.  All Rights Reserved" 

History From 2014 Forward     

07/16/2019 

Interim review to add code Z36.82 to the coding section. 

01/24/2019 

Annual review, no change to policy intent. 

03/12/2018 

Updating policy verbiage

02/21/2018 

Annual review, updating policy, adding medical necessity criteria related to Turner Syndrome. Also updating title, reformatting policy verbiage for clarity and updating CPT and ICD coding. 

04/11/2017 

Annual review. Revision of policy verbiage to provide for much more specific testing based on weeks of gestation. Updating background, description, rationale, category, references and review date

03/08/2017 

Updating the coding section. 

04/06/2016 

Annual review, no change to policy intent. 

04/29/2015 

Annual review, no change to policy intent. Updated description, background, rationale and references. Added coding.

04/15/2014

Annual review. Updated references and guidelines. Added related policy. No change to policy intent.


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