Referral networks for pediatric patients with genetic conditions: The perspective of occupational therapists.

Families of children with developmental delays but no diagnosed genetic condition may benefit from connection to genetic systems of care. This work examines the role of occupational therapy as a space for families of pediatric patients to gain access to genetic services. Between September 2021 and February 2022, we interviewed 20 occupational therapists in New England who work primarily with pediatric patients. We transcribed the interviews and used a grounded theory approach to identify and code recurring themes. The data reveal several barriers to linking pediatric patients to genetic systems of care, including lack of insurance coverage, wait times for appointments and test results, hesitant primary care providers, and familial and cultural stigma of disability. We discuss the unique role of occupational therapists as professionals who spend substantial time with patients, often in their everyday environments, to bridge these barriers. We also address challenges associated with occupational therapists facilitating connections to genetics services, including their lack of specialized knowledge of genetics and barriers fully integrating with others on the medical team.

Assessment of a Simplified Cell-Free DNA Method for Prenatal Down Syndrome Screening.

BACKGROUND: Prenatal screening for common trisomies via cell-free (cfDNA) is usually implemented by technologies utilizing massively parallel sequencing, stringent environmental controls, complex bioinformatics, and molecular expertise. An alternative and less complex methodology utilizes rolling circle amplification (RCA). Further evaluation of its performance and related requirements are warranted. METHODS: At 16 sites, women at 10 to 20 weeks gestation provided informed consent, relevant information, and 2 to 3 blood samples. Samples shipped for testing were processed and stored. Women were enrolled at primary cfDNA screening, or following such screening at referral for diagnostic testing. RCA testing occurred post-enrollment, over 11 months. Diagnostic results and delivery notes determined clinical truth. Detection rates were based on confirmed trisomic pregnancies; false-positive rates were based on unaffected pregnancies from the general population. RESULTS: Detection rate for the common trisomies was 95.9% (117/122, 95% CI, 90.5%-98.5%); overall false-positive rate was 1.00% (22/2,205, 0.65%-1.51%). Test failure rate after repeat testing was 0.04%. When assay standard deviations were below pre-specified levels, the overall false-positive rate was much lower at 0.30% (P < 0.001). Fetal sex calls were correct for 99.7%. One technician analyzed 560 samples over 2 weeks, a rate of 14 000/year. CONCLUSIONS: Our assessment of this simplified cfDNA-based system for prenatal screening for common trisomies performed in a prenatal screening laboratory is encouraging. Improved detection, low failure rates and rapid reporting can be achieved by collecting 2 samples. Future priorities should include achieving higher run precision using a single collection tube. CLINICALTRIALS.GOV REGISTRATION NUMBER: NCT03087357.

Prenatal cell-free DNA screening test failures: a systematic review of failure rates, risks of Down syndrome, and impact of repeat testing.

PURPOSE: We systematically reviewed the published literature on test failure rates for the sequencing of cell-free DNA (cfDNA) in maternal plasma to identify Down syndrome. METHODS: We searched peer-reviewed English publications with diagnostic results on all pregnancies that provided test failure rates. Data on the odds of failure in Down syndrome and euploid pregnancies and the impact of repeat testing were extracted. Random-effects modeling was then used to identify moderators that could explain variability. RESULTS: Thirty articles satisfied the inclusion criteria for overall failure rates. Study location (Western and Asian with initial testing, and Western with repeat testing) were significant moderators with failure rates of 3.3, 0.6, and 1.2%, respectively (P = 0.001). The odds ratio for Down syndrome in successful versus failed tests was 0.98 (95% confidence interval: 0.62-1.55, I2 = 0%). Repeat testing from 14 large clinical cohort studies found that 83% (range: 52-100%) of failures were repeated, with 79% (range: 46-97%) being successful. CONCLUSION: Lower failure rates in Asian studies may be related to not routinely measuring the fetal fraction and to fewer obese women. Repeat cfDNA testing is effective in providing reliable results after initial failures. Protocols for primary cfDNA screening should focus on Down syndrome, with less common and more structurally abnormal trisomy 18 and 13 pregnancies treated as adjuncts.

The clinical utility of DNA-based screening for fetal aneuploidy by primary obstetrical care providers in the general pregnancy population.

OBJECTIVE: To assess the clinical utility of cell-free DNA (cfDNA)-based screening for aneuploidies offered through primary obstetrical care providers to a general pregnancy population. METHODS: Patient educational materials were developed and validated and providers were trained. Serum was collected for reflexive testing of cfDNA failures. Providers and patients were surveyed concerning knowledge, decision making, and satisfaction. Pregnancy outcome was determined by active or passive ascertainment. RESULTS: Between September 2014 and July 2015, 72 providers screened 2,691 women. The five largest participating practices increased uptake by 8 to 40%. Among 2,681 reports, 16 women (0.6%) were screen-positive for trisomy 21, 18, or 13; all saw genetic professionals. Twelve were confirmed (positive predictive value (PPV), 75%; 95% CI, 48-93%) and four were false-positives (0.15%). Of 150 failures (5.6%), 79% had a negative serum or subsequent cfDNA test; no aneuploidies were identified. Of 100 women surveyed, 99 understood that testing was optional, 96 had their questions answered, and 95 received sufficient information. Pretest information was provided by the physician/certified nurse midwife (55) or office nurse/educator (40); none was provided by genetic professionals. CONCLUSION: This first clinical utility study of cfDNA screening found higher uptake rates, patient understanding of basic concepts, and easy incorporation into routine obstetrical practices. There were no reported cases of aneuploidy among cfDNA test failures.Genet Med advance online publication 12 January 2017.

Evaluation of patient education materials: the example of circulating cell free DNA testing for aneuploidy.

Informed consent is the process by which the treating health care provider discloses appropriate information to a competent patient so that the patient may make a voluntary choice to accept or refuse treatment. When the analysis of circulating cell free DNA (ccfDNA) became commercially available in 2011 through the Prenatal Diagnostic Laboratory at Women & Infants Hospital of Providence, Rhode Island to "high-risk" women, it provided an opportunity to examine how commercial laboratories informed potential consumers. We identified, via an internet search, four laboratories offering such testing in the United States and one in Europe. We evaluated patient educational materials (PEMs) from each using the Flesch Reading Ease method and a modified version of the Suitability Assessment of Materials (SAM) criteria. Pamphlets were also reviewed for their inclusion of content recommendations from the International Society for Prenatal Diagnosis, the National Society of Genetic Counselors, the American College of Obstetricians and Gynecologists jointly with the Society of Maternal Fetal Medicine, and the American College of Genetics and Genomics. Reading levels were typically high (10th-12th grade). None of the pamphlets met all SAM criteria evaluated nor did any pamphlet include all recommended content items. To comply with readability and content recommendations more closely, Women & Infants Hospital created a new pamphlet to which it applied the same criteria, and also subjected it to focus group assessment. These types of analyses can serve as a model for future evaluations of similar patient educational materials.

Maternal plasma DNA testing for aneuploidy in pregnancies achieved by assisted reproductive technologies.

PURPOSE: We sought to compare measurements of circulating cell-free DNA as well as Down syndrome test results in women with naturally conceived pregnancies with those conceived using assisted reproductive technologies. METHODS: Data regarding assisted reproductive technologies were readily available from seven enrollment sites participating in an external clinical validation trial of nested case/control design. Measurements of circulating cell-free fetal and total DNA, fetal fraction (ratio of fetal to total DNA), chromosome-specific z-scores, and karyotype results were available for analysis. RESULTS: Analyses were restricted to 632 euploid (5.2% assisted reproductive technologies) and 73 Down syndrome (13.7% assisted reproductive technologies), including 16 twin pregnancies. No differences were found for fetal or total circulating cell-free DNA, or for the fetal fraction in euploid (P = 0.70) or Down syndrome (P = 0.58) pregnancies by method of conception. There appeared to be systematic z-score reductions for chromosomes 21, 18, and 13 in assisted reproductive technologies versus natural euploid pregnancies (P = 0.048, 0.0032, and 0.36, respectively). CONCLUSION: Assisted reproductive technologies and naturally conceived pregnancies contribute similar levels of circulating cell-free DNA into maternal circulation. Small differences in the z-scores of pregnancies achieved by assisted reproductive technologies were observed and do not appear to be test-related artifacts. However, the findings need confirmation before any consideration of changes to testing and reporting protocols.

The impact of maternal plasma DNA fetal fraction on next generation sequencing tests for common fetal aneuploidies.

Maternal plasma contains circulating cell-free DNA fragments originating from both the mother and the placenta. The proportion derived from the placenta is known as the fetal fraction. When measured between 10 and 20 gestational weeks, the average fetal fraction in the maternal plasma is 10% to 15% but can range from under 3% to over 30%. Screening performance using next-generation sequencing of circulating cell-free DNA is better with increasing fetal fraction and, generally, samples whose values are less than 3% or 4% are unsuitable. Three examples of the clinical impact of fetal fraction are discussed. First, the distribution of test results for Down syndrome pregnancies improves as fetal fraction increases, and this can be exploited in reporting patient results. Second, the strongest factor associated with fetal fraction is maternal weight; the false negative rate and rate of low fetal fractions are highest for women with high maternal weights. Third, in a mosaic, the degree of mosaicism will impact the performance of the test because it will reduce the effective fetal fraction. By understanding these aspects of the role of fetal fraction in maternal plasma DNA testing for aneuploidy, we can better appreciate the power and the limitations of this impressive new methodology.

DNA sequencing of maternal plasma reliably identifies trisomy 18 and trisomy 13 as well as Down syndrome: an international collaborative study.

PURPOSE: To determine whether maternal plasma cell-free DNA sequencing can effectively identify trisomy 18 and 13. METHODS: Sixty-two pregnancies with trisomy 18 and 12 with trisomy 13 were selected from a cohort of 4,664 pregnancies along with matched euploid controls (including 212 additional Down syndrome and matched controls already reported), and their samples tested using a laboratory-developed, next-generation sequencing test. Interpretation of the results for chromosome 18 and 13 included adjustment for CG content bias. RESULTS: Among the 99.1% of samples interpreted (1,971/1,988), observed trisomy 18 and 13 detection rates were 100% (59/59) and 91.7% (11/12) at false-positive rates of 0.28% and 0.97%, respectively. Among the 17 samples without an interpretation, three were trisomy 18. If z-score cutoffs for trisomy 18 and 13 were raised slightly, the overall false-positive rates for the three aneuploidies could be as low as 0.1% (2/1,688) at an overall detection rate of 98.9% (280/283) for common aneuploidies. An independent academic laboratory confirmed performance in a subset. CONCLUSION: Among high-risk pregnancies, sequencing circulating cell-free DNA detects nearly all cases of Down syndrome, trisomy 18, and trisomy 13, at a low false-positive rate. This can potentially reduce invasive diagnostic procedures and related fetal losses by 95%. Evidence supports clinical testing for these aneuploidies.

DNA sequencing of maternal plasma to identify Down syndrome and other trisomies in multiple gestations.

OBJECTIVE: Studies on prenatal testing for Down syndrome (trisomy 21), trisomy 18, and trisomy 13 by massively parallel shotgun sequencing (MPSS) of circulating cell free DNA have been, for the most part, limited to singleton pregnancies. If MPSS testing is offered clinically, it is important to know if these trisomies will also be identified in multiple pregnancies. METHOD: Among a cohort of 4664 high-risk pregnancies, maternal plasma samples were tested from 25 twin pregnancies (17 euploid, five discordant and two concordant for Down syndrome; one discordant for trisomy 13) and two euploid triplet pregnancies [Correction made here after initial online publication.]. Results were corrected for GC content bias. For each target chromosome (21, 18, and 13), z-scores of 3 or higher were considered consistent with trisomy. RESULTS: Seven twin pregnancies with Down syndrome, one with trisomy 13, and all 17 twin euploid pregnancies were correctly classified [detection rate 100%, 95% confidence interval (CI) 59%-100%, false positive rate 0%, 95% CI 0%-19.5%], as were the two triplet euploid pregnancies. CONCLUSION: Although study size is limited, the underlying biology combined with the present data provide evidence that MPSS testing can be reliably used as a secondary screening test for Down syndrome in women with high-risk twin gestations.

DNA sequencing of maternal plasma to detect Down syndrome: an international clinical validation study.

PURPOSE: Prenatal screening for Down syndrome has improved, but the number of resulting invasive diagnostic procedures remains problematic. Measurement of circulating cell-free DNA in maternal plasma might offer improvement. METHODS: A blinded, nested case-control study was designed within a cohort of 4664 pregnancies at high risk for Down syndrome. Fetal karyotyping was compared with an internally validated, laboratory-developed test based on next-generation sequencing in 212 Down syndrome and 1484 matched euploid pregnancies. None had been previously tested. Primary testing occurred at a CLIA-certified commercial laboratory, with cross validation by a CLIA-certified university laboratory. RESULTS: Down syndrome detection rate was 98.6% (209/212), the false-positive rate was 0.20% (3/1471), and the testing failed in 13 pregnancies (0.8%); all were euploid. Before unblinding, the primary testing laboratory also reported multiple alternative interpretations. Adjusting chromosome 21 counts for guanine cytosine base content had the largest impact on improving performance. CONCLUSION: When applied to high-risk pregnancies, measuring maternal plasma DNA detects nearly all cases of Down syndrome at a very low false-positive rate. This method can substantially reduce the need for invasive diagnostic procedures and attendant procedure-related fetal losses. Although implementation issues need to be addressed, the evidence supports introducing this testing on a clinical basis.

Maternal urine and serum steroid measurements to identify steroid sulfatase deficiency (STSD) in second trimester pregnancies.

OBJECTIVE: To document the performance of second trimester maternal urine and serum steroid measurements for detecting fetal steroid sulfatase deficiency (STSD). METHODS: We studied detection rate and false positive rate (DR, FPR) of analytes in maternal urine [combinations of 16alpha-OH-dehydroepiandrosterone sulfate (16alpha-OH-DHEAS), 11beta-hydroxyandrosterone, total estriol] and serum [combinations of 16alpha-OH-DHEAS, 11beta-hydroxyandrosterone, total estriol, unconjugated estriol (uE3)]. Samples were obtained from pregnancies which were screen positive for Smith-Lemli-Opitz syndrome (SLOS). RESULTS: Among 1 079 301 pregnancies, 3083 (0.29%) were screen positive for SLOS. Urine and/or serum samples were available from 917 viable pregnancies with known gender. We assigned likelihood ratios (LRs) to steroid measurements from male fetuses with known STSD and unaffected female fetuses. An LR > or = 100 was present in urine from 84 of 86 STSD pregnancies (98% DR, 95% CI 92-99), along with 0 of 198 pregnancies with normal female fetuses (0.0% FPR, CI 0-1.9). LRs were > or = 100 in 4 of 129 female fetuses with major abnormalities (3% FPR). In maternal serum, steroid measurements performed less effectively, achieving a 71% DR for STSD at a 1.6% FPR. CONCLUSION: Maternal urine steroid measurements are effective for detecting STSD, including those with point mutations and those with full deletions.

A genetic history questionnaire-based system in primary prenatal care to screen for selected fetal disorders.

DNA (and other) diagnostic tests are now available for a number of serious, but uncommon, fetal disorders. We designed and evaluated a screening system for this purpose in primary care, coupled with targeted information for practitioners and patients. We developed a 15-question family history form for completion by office staff or patients, addressing conditions for which definitive diagnosis was available, linked to secondary questionnaires to follow up on "yes" answers. Guidelines for assessing risk, follow-up recommendations, and information resources were also linked. Following pilot testing, this screening system was introduced throughout Maine. We enrolled 212 providers (85-90% of the state's pregnancies). In a subsequent survey, 85% of the practices were screening all new patients and 3% some; 12% did not use the system. Time for form completion averaged 7 min. Overall, provider satisfaction was 4.4 on a five-point scale. Patients responded favorably; a minority was anxious or overwhelmed. Total referral calls to Maine's genetic/perinatal centers did not increase, but calls about family history of genetic disorders or maternal conditions increased significantly. This screening system for guiding appropriate use of DNA (and other) testing in pregnancy can be used successfully in primary care.

Screening for thyroid disorders during pregnancy: results of a survey in Maine.

OBJECTIVE: Guidelines regarding prenatal screening for thyroid deficiency are conflicting, and current practice in primary care settings is unknown. Our survey sought to determine the: 1) extent of screening in Maine; 2) factors associated with screening; and 3) laboratory cut-off levels used. STUDY DESIGN: In 2004 we surveyed 61 prenatal care practices, representing 246 practitioners and 85% of Maine deliveries. RESULTS: Screening via thyroid-stimulating hormone (TSH) testing was routine in 48% of the practices. Obstetrician practices screened at a significantly higher rate than family practices (56% vs 8%; odds ratio [OR] 15.0, 95% CI 1.9-130.0). Nonsignificant higher rates were found for urban versus rural, and multipractitioner versus solo practices. The lower TSH cut-off levels ranged between 0.1 and 0.5 mU/L among practices; the upper cut-off levels ranged between 3.5 and 5.5 mU/L. CONCLUSION: Prenatal screening for thyroid deficiency varies among practices, reflecting conflicting guidelines. TSH cut-offs are also variable and might benefit from standardization.

Patient and health professional acceptance of integrated serum screening for Down syndrome.

Integrated testing for Down syndrome combines first trimester maternal serum and nuchal translucency (NT) measurements with second trimester maternal serum measurements into a single second trimester Down syndrome risk. A variant of integrated testing, the integrated serum test, requires only the serum measurements and may be more suitable for widespread use in the general pregnancy population. Concern has been voiced that women will find the delay associated with waiting for screening results unacceptable for either fully integrated (including NT measurements) or integrated serum testing. To address this issue, we surveyed 60 women from a population of 8773 women enrolled in an integrated serum screening intervention trial in Maine. The women all had also undergone traditional second trimester screening 1 to 2 years earlier. All 60 women remembered having the integrated serum test, and 59 remembered having a prenatal test in their previous pregnancy. Three-quarters of women did not experience anxiety relating to the wait for final results in the second trimester, and 95% would consider being screened by the integrated serum test in a future pregnancy. Women receiving prenatal care at the primary care level are prepared to wait until the second trimester for more accurate Down syndrome risk estimates on which to base their decision-making.

Maternal plasma DNA testing: experience of women counseled at a prenatal diagnosis center.

AIMS: To evaluate the early introduction of circulating cell-free (ccf) DNA testing in a prenatal diagnosis center serving a statewide population. RESULTS: A retrospective chart review of patients at high aneuploidy risk counseled during the two 10-week periods that documents indication, risk, maternal age, insurance coverage, decisions, and reasoning behind that decision. Among the 299 included women, indication was advanced maternal age (17% with and 56% without an additional indication), positive serum screen (15%), and abnormal ultrasound (12%). Uptake increased from 10% to 17%, as did patient awareness of the test (4% to 14%). Women with lower copayments were more likely to complete testing (23% vs. 5%, p<0.001). Most women completing testing (75%) wanted to avoid an invasive procedure, while those declining cited testing would not change anything (47%), preferred diagnostic testing (16%), negative follow-up testing (20%), and cost/insurance issues (9%). One of 42 tests was positive (trisomy 21). CONCLUSIONS: Individual patient follow-up allows us to document ccfDNA-related patient decision-making. Nearly half of the women did not want further testing and one in seven preferred immediate diagnostic testing. Patient costs were a barrier to testing that, if avoided, could increase test uptake by 50% or more.

Feasibility of using plasma rather than serum in first and second trimester multiple marker Down's syndrome screening.

OBJECTIVE: To compare maternal plasma with serum for measuring markers currently used in first and second trimester screening for Down's syndrome. SETTING: A laboratory-based investigation of two sample types in assays used in prenatal screening for Down's syndrome. METHODS: A paired data-set included both plasma and serum from 101 pregnant women. A nested case/control data-set included only plasma samples from 34 first and 23 second trimester Down's syndrome pregnancies, each matched with six euploid controls. Analyte levels were measured and converted to multiples of the median (MoM). RESULTS: In the paired data-set, each of the five analytes (alphafetoprotein, unconjugated estriol, human chorionic gonadotropin, inhibin-A and pregnancy-associated plasma protein A) in serum and plasma was highly correlated (r > 0.970) and after conversion to MoM, the resulting distributions were equivalent (P > 0.7). In the matched data-set, plasma-based median MoM levels in cases were consistent with the published serum counterparts for all markers. CONCLUSIONS: This study provides strong evidence that current serum-based prenatal screening can be performed equally well using plasma samples. This may prove useful, especially if secondary screening using a DNA-based test requires maternal plasma.

Mid-gestational maternal free thyroxine concentration and offspring neurocognitive development at age two years.

CONTEXT: Lower neurocognitive development scores at age 2 yr have been reported in association with euthyroid hypothyroxinemia during early pregnancy. OBJECTIVE: The objective of this study was to further explore this association with euthyroid hypothyroxinemia during early pregnancy. DESIGN: This was an observational, nested case-control study. SETTING: The study was conducted at physician offices and prenatal clinics throughout Maine. STUDY SUBJECTS: Between May 2004 and March 2006, TSH was measured in 5734 women in conjunction with second-trimester Down syndrome screening. After completion of pregnancy, free T(4) was measured in stored second-trimester sera from euthyroid women (TSH 0.1-3.5 mIU/ml; n = 5560). Women with free T(4) at the third centile or less (n = 99) were matched with women whose free T(4) was at the 10th to the 90th centile (n = 99). INTERVENTIONS: There were no interventions. MAIN OUTCOME MEASURE: Bayley Scales of Infant Development (BSID III) were administered to the 198 offspring at age 2 yr. Scores for cognitive, language, and motor development were compared between matched pairs of offspring from the two groups before and after correcting for relevant variables. RESULTS: Unadjusted BSID-III scores (cognitive, language, and motor) were lower by about 3% at age 2 yr among offspring of 98 hypothyroxinemic women (cases), reaching borderline significance for cognitive and motor scores. After adjustment for gestational age, the child's age at testing, maternal weight, and education, all differences diminished and became nonsignificant. Scores less than 85 were more frequent among case children but did not reach statistical significance (P = 0.14). CONCLUSIONS: Isolated hypothyroxinemia during the second trimester is not associated with significantly lower BSID-III scores at age 2 yr, compared with scores for offspring of matched euthyroxinemic women.

Identifying Smith-Lemli-Opitz syndrome in conjunction with prenatal screening for Down syndrome.

BACKGROUND: Smith-Lemli-Opitz syndrome (SLOS) is a rare hereditary disorder of cholesterol metabolism. We examine the feasibility of identifying SLOS as a part of a routine prenatal screening and evaluate diagnostic testing in maternal urine (or serum), in addition to amniotic fluid. METHODS: Our SLOS risk algorithm utilized three Down syndrome screening markers (estimated 62% detection rate; 0.3% screen-positive rate). Fifteen North American prenatal screening programs implemented this algorithm. RESULTS: SLOS risk was assigned to 1 079 301 pregnancies; 3083 were screen-positive (0.29%). Explanations were found for 1174, including 914 existing fetal deaths. Among the remaining pregnancies, 739 were screen-positive only for SLOS; 1170 were also screen-positive for other fetal disorders. Five of six SLOS pregnancies (83%) were screen-positive. All six had sonographic findings, were biochemically confirmed, and were terminated. Maternal urine steroid measurements were confirmatory in four cases tested. Second-trimester prevalence among Caucasians was 1 in 101 000 (1 in 130 000 overall; no cases in other racial groups). Among 739 pregnancies screen-positive only for SLOS, two cases were identified; another 69 had major fetal abnormalities. CONCLUSIONS: Although SLOS occurred less often than previously reported, many other major abnormalities were detected. Implementing the algorithm as an adjunct to Down syndrome screening may be feasible.

Integrated serum screening for Down syndrome in primary obstetric practice.

OBJECTIVES: Integrated serum screening for Down syndrome is potentially more effective than current second-trimester screening. We report results of an intervention trial of integrated serum screening that involved 229 primary prenatal care practitioners throughout Maine. METHODS: Women provided a first-trimester serum (for PAPP-A) followed by a second-trimester serum (for AFP, uE3, hCG, and DIA). These five marker measurements were used to calculate a Down syndrome risk in the second trimester. Screen-positive women (risk > or = 1:100) were managed according to standard practice. RESULTS: During 24 months' enrollment, 11 159 women provided a first-trimester sample (61% of women receiving screening services). Nine thousand seven hundred twenty-three women also provided a second-trimester sample; 8773 women satisfied gestational age criteria for testing in both trimesters. Integrated serum screening detected 14 of 16 Down syndrome cases (87%) and 79% after adjustment for trimester-of-ascertainment bias. The initial false-positive rate was 3.2% and was 2.7% when restricted to ultrasound-dated pregnancies. Performance was better than any combination of second-trimester markers. Implementation challenges included initial samples being collected too early and sample matching. CONCLUSIONS: Integrated serum screening for Down syndrome was successfully implemented in primary care settings; screening performance was consistent with predictions. It provides an accessible and acceptable alternative to screening protocols that require nuchal translucency measurements.