Factors influencing visualization of the intracranial translucency during first-trimester screening for aneuploidy.

OBJECTIVE: Neural tube defects occur in 1/2000 live births. Imaging of the intracranial translucency (IT) during first-trimester screening has been proposed as an early screen for open neural tube defects (ONTD). This study evaluates visualization of the IT and factors influencing its visualization during first-trimester ultrasound screening for aneuploidy. METHODS: Ultrasound images for patients undergoing first-trimester screening for aneuploidy from January 1, 2009, through July 31, 2009, were reviewed for IT visualization, defined as an intracranial translucency parallel to the nuchal translucency. Second-trimester ultrasounds and delivery records were reviewed for the presence of fetal ONTD. RESULTS: The IT was visualized in 74.8% of 759 gestations studied at a mean gestational age of 12 weeks, 5 days. Among gestations where the IT was visualized, we found a larger crown-rump length, lower maternal weight, and more fetuses in the supine position (p < 0.0001). Predictive models for visualization of the IT were formulated based on these factors. CONCLUSION: The IT can be visualized in the majority of patients in the standard midsagittal plane used for measurement of the nuchal translucency. Visualization is significantly associated with crown-rump length, gestational age, maternal weight, and fetal position. Visualization of the IT is feasible.

Monochorionic diamniotic twin pregnancy: timing and duration of sonographic surveillance for detection of twin-twin transfusion syndrome.

OBJECTIVE: Twin-twin transfusion syndrome complicates up to 15% of monochorionic diamniotic gestations. Current recommendations for sonographic surveillance in monochorionic diamniotic pregnancies for detection of twin-twin transfusion syndrome vary. Our objective was to determine an appropriate frequency of sonographic surveillance to optimize detection of twin-twin transfusion syndrome in monochorionic diamniotic gestations. METHODS: A retrospective cohort analysis of all nonanomalous monochorionic diamniotic twins delivered at the University of North Carolina over a 9-year period was performed. The rate and gestational age of twin-twin transfusion syndrome onset were calculated. The time to the diagnosis of twin-twin transfusion syndrome was evaluated by a Kaplan-Meier survival curve; clinical factors at initial sonography were examined for their use in prediction of twin-twin transfusion syndrome. RESULTS: Of the 577 twin deliveries, 145 (25%) were monochorionic diamniotic and included for analysis. The rate of twin-twin transfusion syndrome was 17.93% (n = 26). The mean frequency of surveillance ± SD before diagnosis of twin-twin transfusion syndrome was 3.1 ± 2.1 weeks. The mean gestational age at diagnosis of twin-twin transfusion syndrome was 21.3 ± 3.4 weeks (range, 15-29 weeks). Both a discordant maximum vertical amniotic fluid pocket (>65% difference) and a discordant estimated fetal weight (>25% difference) at initial sonography showed a significantly shorter time to diagnosis of twin-twin transfusion syndrome (P < .0001). CONCLUSIONS: Evaluation for twin-twin transfusion syndrome should begin in the second trimester. Weekly surveillance for those pregnancies with estimated fetal weight or maximum vertical pocket discordance is recommended. For those with a concordant estimated fetal weight and maximum vertical pocket, sonographic evaluation every 2 weeks is warranted to 28 to 30 weeks. After that, development of twin-twin transfusion syndrome is less likely, and a different paradigm of antenatal testing may be reasonable.

Placenta previa in the second trimester: sonographic and clinical factors associated with its resolution.

We identify characteristics that predict resolution of placenta previa and develop a clinical model for likelihood of resolution. We conducted a retrospective study of 366 singleton pregnancies complicated by placenta previa diagnosed with resolution of the previa as the primary outcome. Regression analyses were performed to determine variables associated with resolution and optimal timing for repeat sonographic evaluation. A likelihood of resolution model was created using a parametric survival model with Weibull hazard function. Of the 366 cases, 84% of complete placentae previae and 98% of marginal placentae previae resolved at a mean gestational age of 28.6 ± 5.3 weeks. Only gestational age and distance from the internal cervical os at the time of diagnosis were significantly associated with resolution ( P < 0.01). Likelihood of resolution was not significantly associated with any other variables. Marginal previae diagnosed in the second trimester do not appear to warrant repeat ultrasound evaluation for resolution.

COVID-19 in Pregnancy: Occupations With Higher Density of Population Exposure Associated With More Severe Disease.

OBJECTIVE: To define the symptomatology of SARS-CoV-2 infection in pregnancy and associations between occupation, sociodemographic factors, and comorbidities with the severity of COVID-19 disease in pregnancy in all trimesters, regardless of hospitalization. METHODS: We studied a retrospective cohort of a public health surveillance sample of persons with COVID-19 infection diagnosed during pregnancy. Data was collected March 2020 to August 2020 regarding symptoms, disease severity, comorbidities, obstetric history, and occupation. RESULTS: One hundred sixty-three individuals were identified. Constitutional (64%) and lower respiratory symptoms (61%) were most common. Seventeen individuals (13.6%) were hospitalized, and one person (0.7%) died due to COVID-19. Risk factors for severe disease were age and an occupation that had high intensity exposure to people. CONCLUSIONS: Occupational exposure is a risk factor for severe COVID-19 disease in pregnancy, justifying policy measures to ensure protection of this vulnerable population.

Ultrasound prediction of birthweight and growth restriction in fetal gastroschisis.

OBJECTIVE: Most ultrasound estimated fetal weight (EFW) formulas incorporate abdominal circumference, which may overstimate growth restriction in fetal gastroschisis. The aim of this study was to determine the optimal ultrasound formula for prediction of birthweight and fetal growth restriction (FGR) in gastroschisis. STUDY DESIGN: We conducted a retrospective cohort analysis of singleton fetuses with gastroschisis. Percentage of error between ultrasound EFW (performed within 2 weeks of delivery) and birthweight was calculated. Agreement between EFW by ultrasound formulas and birthweight was determined by Bland-Altman limits of agreement; concordance between ultrasound and birthweight diagnosis of FGR was evaluated with McNemar's test. RESULTS: Birthweight was best predicted by the formulas of Shepard et al and Siemer et al. Only these formulas demonstrated significant agreement with birthweight for prediction of FGR at the 5th and 10th percentiles. CONCLUSION: The formulas of Shepard et al and Siemer et al best estimate birthweight, and their use has the potential to reduce rates of overdiagnosis of FGR.

Influence of maternal BMI on genetic sonography in the FaSTER trial.

OBJECTIVE: We sought to evaluate the influence of maternal body mass index (BMI) on sonographic detection employing data from the FaSTER trial. METHOD: Unselected singleton pregnancies underwent detailed genetic sonogram to evaluate for structural fetal anomalies and soft markers for aneuploidy. BMI (kg/m(2)) were calculated from reported initial visit values. Sensitivity, specificity, false positive and false negative rates (FPR and FNR), likelihood ratio, detection rates, and a missed diagnosis rate (MDR: FNR + marker recorded as 'missing'/N) were calculated. RESULTS: Eight thousand five hundred and fifty-five patients with complete BMI information had detailed genetic sonography. A lower sensitivity with an elevated FNR and MDR was observed in obese women for multiple aneuploid markers (e.g. > or =2 markers 32% sensitivity with 68% FNR among BMI <25 vs 22% and 78% among BMI >30). Similarly, the detection rate for cardiac anomalies among women at BMI <25 was higher (21.6%) at a significantly lower FPR (78.4%; 95% CI 77.3-79.5%) in comparison to obese women (8.3% with FPR 91.7%; 95% CI 90.1-93.2%). In a logistic regression model, maternal obesity significantly decreased the likelihood of sonographic detection of common anomalies (adjusted OR 0.7; 95% CI 0.6-0.9; p = 0.001). CONCLUSION: The performance of second trimester genetic sonography is influenced by obesity, with a significantly higher MDR for multiple minor markers and lower likelihood for detecting common anomalies.

Perinatal outcomes in isolated single umbilical artery.

We sought to determine the rate of adverse perinatal outcomes in pregnancies diagnosed with an isolated single umbilical artery (SUA). We performed a retrospective review comparing 68 pregnancies with an isolated SUA to 68 pregnancies with a three-vessel cord (3VC). Pregnancies with structural or karyotypic anomalies were excluded. Gestational age at delivery, birth weight, SGA rate, ponderal index, and rates of admission to the neonatal intensive care unit were compared between groups. Student T test and chi-square analysis were performed. Neonates with isolated SUA had a significantly smaller birth weight than those with a 3VC (3279 +/- 404 g versus 3423 +/- 374 g, P = 0.0168). There was no significant difference in rates of SGA (17.6% versus 8.8%, P = 0.06). Ponderal index was significantly less in those with SUA compared with 3VC (24.2 +/- 1.1 g/cm(3) versus 26.1 +/- 1.3 g/cm(3), P = 0.001). SUA neonates had a significantly longer length of neonatal intensive care unit stay than 3VC neonates (1.25 +/- 2.2 days versus 0.48 +/- 1.25 days, P < 0.023). Fetuses with a prenatal diagnosis of isolated umbilical artery have a significantly lower ponderal index compared with fetuses with a 3VC. Pregnancies with isolated SUA should undergo serial assessments for fetal growth.

Intrauterine growth patterns in fetal gastroschisis.

The objective of this study was to evaluate patterns of intrauterine growth in fetal gastroschisis. This was a retrospective review of prenatally diagnosed cases of fetal gastroschisis delivered at the University of North Carolina Hospital from January 2000 to January 2007. Fetal growth (biparietal diameter, head circumference, abdominal circumference, femur length, and estimated fetal weight) and amniotic fluid volume were evaluated by gestational age. Gastroschisis was diagnosed in 83 pregnancies; outcomes were available in 71 fetuses. The mean gestational age at diagnosis was 17 weeks and 1 day. The mean gestational age at delivery was 35 weeks and 4 days. Mean birth weight was 2306 g. As early as the second trimester, all morphometric measures demonstrated impaired in utero growth, with growth curves shifted to the right of the 50th percentile when compared with a standard population. Estimated fetal weight below the 10th percentile was suspected in 23% of pregnancies, and birth weight at less than the 10th percentile occurred in 47% of neonates. Amniotic fluid volumes remained stable throughout gestation. Fetuses with gastroschisis display impaired intrauterine growth, which is noted in the midsecond trimester of pregnancy and does not appear to progress throughout gestation.

Deletion of hepatocyte nuclear factor-1-beta in an infant with prune belly syndrome.

Prune belly syndrome is a rare congenital disorder characterized by deficiency of abdominal wall muscles, cryptorchidism, and urinary tract anomalies. We have had the opportunity to study a baby with prune belly syndrome associated with an apparently de novo 1.3-megabase interstitial 17q12 microdeletion that includes the hepatocyte nuclear factor-1-beta gene at 17q12. One previous patient, an adult, has been reported with prune belly syndrome and a hepatocyte nuclear factor-1-beta microdeletion. Hepatocyte nuclear factor-1-beta is a widely expressed transcription factor that regulates tissue-specific gene expression and is expressed in numerous tissues including mesonephric duct derivatives, the renal tubule of the metanephros, and the developing prostate of the mouse. Mutations in hepatocyte nuclear factor-1-beta cause the "renal cysts and diabetes syndrome," isolated renal cystic dysplasia, and a variety of other malformations. Based on its expression pattern and the observation of two affected cases, we propose that haploinsufficiency of hepatocyte nuclear factor-1-beta may be causally related to the production of the prune belly syndrome phenotype through a mechanism of prostatic and ureteral hypoplasia that results in severe obstructive uropathy with urinary tract and abdominal distension.

Preconceptional folate supplementation and the risk of spontaneous preterm birth: a cohort study.

BACKGROUND: Low plasma folate concentrations in pregnancy are associated with preterm birth. Here we show an association between preconceptional folate supplementation and the risk of spontaneous preterm birth. METHODS AND FINDINGS: In a cohort of 34,480 low-risk singleton pregnancies enrolled in a study of aneuploidy risk, preconceptional folate supplementation was prospectively recorded in the first trimester of pregnancy. Duration of pregnancy was estimated based on first trimester ultrasound examination. Natural length of pregnancy was defined as gestational age at delivery in pregnancies with no medical or obstetrical complications that may have constituted an indication for delivery. Spontaneous preterm birth was defined as duration of pregnancy between 20 and 37 wk without those complications. The association between preconceptional folate supplementation and the risk of spontaneous preterm birth was evaluated using survival analysis. Comparing to no supplementation, preconceptional folate supplementation for 1 y or longer was associated with a 70% decrease in the risk of spontaneous preterm delivery between 20 and 28 wk (41 [0.27%] versus 4 [0.04%] spontaneous preterm births, respectively; HR 0.22, 95% confidence interval [CI] 0.08-0.61, p = 0.004) and a 50% decrease in the risk of spontaneous preterm delivery between 28 and 32 wk (58 [0.38%] versus 12 [0.18%] preterm birth, respectively; HR 0.45, 95% CI 0.24-0.83, p = 0.010). Adjustment for maternal characteristics age, race, body mass index, education, marital status, smoking, parity, and history of prior preterm birth did not have a material effect on the association between folate supplementation for 1 y or longer and spontaneous preterm birth between 20 and 28, and 28 to 32 wk (adjusted HR 0.31, 95% CI 0.11-0.90, p = 0.031 and 0.53, 0.28-0.99, p = 0.046, respectively). Preconceptional folate supplementation was not significantly associated with the risk of spontaneous preterm birth beyond 32 wk. The association between shorter duration (<1 y) of preconceptional folate supplementation and the risk of spontaneous preterm birth was not significant after adjustment for maternal characteristics. However, the risk of spontaneous preterm birth decreased with the duration of preconceptional folate supplementation (test for trend of survivor functions, p = 0.01) and was the lowest in women who used folate supplementation for 1 y or longer. There was also no significant association with other complications of pregnancy studied after adjustment for maternal characteristics. CONCLUSIONS: Preconceptional folate supplementation is associated with a 50%-70% reduction in the incidence of early spontaneous preterm birth. The risk of early spontaneous preterm birth is inversely proportional to the duration of preconceptional folate supplementation. Preconceptional folate supplementation was specifically related to early spontaneous preterm birth and not associated with other complications of pregnancy.

First-trimester or second-trimester screening, or both, for Down's syndrome.

BACKGROUND: It is uncertain how best to screen pregnant women for the presence of fetal Down's syndrome: to perform first-trimester screening, to perform second-trimester screening, or to use strategies incorporating measurements in both trimesters. METHODS: Women with singleton pregnancies underwent first-trimester combined screening (measurement of nuchal translucency, pregnancy-associated plasma protein A [PAPP-A], and the free beta subunit of human chorionic gonadotropin at 10 weeks 3 days through 13 weeks 6 days of gestation) and second-trimester quadruple screening (measurement of alpha-fetoprotein, total human chorionic gonadotropin, unconjugated estriol, and inhibin A at 15 through 18 weeks of gestation). We compared the results of stepwise sequential screening (risk results provided after each test), fully integrated screening (single risk result provided), and serum integrated screening (identical to fully integrated screening, but without nuchal translucency). RESULTS: First-trimester screening was performed in 38,167 patients; 117 had a fetus with Down's syndrome. At a 5 percent false positive rate, the rates of detection of Down's syndrome were as follows: with first-trimester combined screening, 87 percent, 85 percent, and 82 percent for measurements performed at 11, 12, and 13 weeks, respectively; with second-trimester quadruple screening, 81 percent; with stepwise sequential screening, 95 percent; with serum integrated screening, 88 percent; and with fully integrated screening with first-trimester measurements performed at 11 weeks, 96 percent. Paired comparisons found significant differences between the tests, except for the comparison between serum integrated screening and combined screening. CONCLUSIONS: First-trimester combined screening at 11 weeks of gestation is better than second-trimester quadruple screening but at 13 weeks has results similar to second-trimester quadruple screening. Both stepwise sequential screening and fully integrated screening have high rates of detection of Down's syndrome, with low false positive rates.

Individualized norms of optimal fetal growth: fetal growth potential.

OBJECTIVE: To demonstrate that individualized optimal fetal growth norms, accounting for physiologic and pathologic determinants of fetal growth, better identify normal and abnormal outcomes of pregnancy than existing methods. METHODS: In a prospective cohort of 38,033 singleton pregnancies, we identified 9,818 women with a completely normal outcome of pregnancy and characterized the physiologic factors affecting birth weight using multivariable regression. We used those physiologic factors to individually predict optimal growth trajectory and its variation, growth potential, for each fetus in the entire cohort. By comparing actual birth weight with growth potential, population, ultrasound, and customized norms, we calculated for each fetus achieved percentiles, by each norm. We then compared proportions of pregnancies classified as normally grown, between 10th and 90th percentile, or aberrantly grown, outside this interval, by growth potential and traditional norms, in 14,229 complicated pregnancies, 1,518 pregnancies with diabetes or hypertensive disorders, and 1,347 pregnancies with neonatal complications. RESULTS: Nineteen physiologic factors, associated with maternal characteristics and early placental function, were identified. Growth potential norms correctly classified significantly more pregnancies than population, ultrasound, or customized norms in complicated pregnancies (26.4% compared with 18.3%, 18.7%, 22.8%, respectively, all P<.05), pregnancies with diabetes or hypertensive disorders (37.3% compared with 23.0%, 28.0%, 34.0%, respectively, all P<.05) and neonatal complications (33.3% compared with 19.7%, 24.9%, 29.8%, respectively, all P<.05). CONCLUSION: Growth potential norms based on the physiologic determinants of birth weight are a better discriminator of aberrations of fetal growth than traditional norms. LEVEL OF EVIDENCE: II.

Prediction of patient-specific risk for fetal loss using maternal characteristics and first- and second-trimester maternal serum Down syndrome markers.

OBJECTIVE: To develop and evaluate a method of estimating patient-specific risk for fetal loss by combining maternal characteristics with serum markers. STUDY DESIGN: Data were obtained on 36,014 women from the FaSTER trial. Separate likelihood ratios were estimated for significant maternal characteristics and serum markers. Patient-specific risk was calculated by multiplying the incidence of fetal loss by the likelihood ratios for each maternal characteristic and for different serum marker combinations. RESULTS: Three hundred eighteen women had fetal loss < 24 weeks (early) and 103 > 24 weeks (late). Clinical characteristics evaluated included maternal age, body mass index, race, parity, threatened abortion, previous preterm delivery, and previous early loss. Serum markers studied as possible predictors of early loss included first-trimester pregnancy-associated plasma protein A and second-trimester alpha-fetoprotein, and unconjugated estriol. A risk assessment for early loss based on all of these factors yielded a 46% detection rate, for a fixed 10% false-positive rate, 39% for 5% and 28% for 1%. The only significant marker for late loss was inhibin A. The detection rate was 27% for a fixed 10% false-positive rate and only increased slightly when clinical characteristics were added to the model. CONCLUSION: Patient-specific risk assessment for early fetal loss using serum markers, with or without maternal characteristics, has a moderately high detection. Patient-specific risk assessment for late fetal loss has low detection rates.

First- and second-trimester evaluation of risk for Down syndrome.

OBJECTIVE: To investigate the differences in costs and outcomes of Down syndrome screening using data from the First and Second Trimester Evaluation of Risk (FASTER) Trial. METHODS: Seven possible screening options for Down syndrome were compared: 1) Triple Screen-maternal serum alpha fetoprotein, estriol, and hCG; 2) Quad-maternal serum alpha fetoprotein, estriol, hCG, and Inhibin A; 3) Combined First-nuchal translucency, pregnancy-associated plasma protein A (PAPP-A), free beta-hCG; 4) Integrated-nuchal translucency, PAPP-A, plus Quad; 5) Serum Integrated-PAPP-A, plus Quad; 6) Stepwise Sequential-Combined First plus Quad with results given after each test; and 7) Contingent Sequential-Combined First and only those with risk between 1:30 and 1:1,500 have Quad screen. The detection rates for each option were used given a 5% false-positive rate except for Contingent Sequential with a 4.3% false-positive rate. Outcomes included societal costs of each screening regimen (screening tests, amniocentesis, management of complications, and cost of care of Down syndrome live births), Down syndrome fetuses identified and born, the associated quality-adjusted life years, and the incremental cost-utility ratio. RESULTS: Based on the screening results derived from the 38,033 women evaluated in the FASTER trial, the Contingent Sequential screen dominated (lower costs with better outcomes) all other screens. For example, the Contingent Sequential cost 32.3 million dollars whereas the other screens ranged from 32.8 to 37.5 million dollars. The Sequential strategy led to the identification of the most Down syndrome fetuses of all of the screens, but at a higher cost per Down syndrome case diagnosed ($719,675 compared with $690,427) as compared with the Contingent Sequential. Because of the lower overall false-positive rate leading to fewer procedure-related miscarriages, the Contingent Sequential resulted in the highest quality-adjusted life years as well. The Contingent Sequential remained the most cost-effective option throughout sensitivity analysis of inputs, including amniocentesis rate after positive screen, rate of therapeutic abortion after Down syndrome diagnosis, and rate of procedure-related miscarriages. CONCLUSION: Analysis of this actual data from the FASTER Trial demonstrates that the Contingent Sequential test is the most cost-effective. This information can help shape future policy regarding Down syndrome screening.

Nuchal translucency and the risk of congenital heart disease.

OBJECTIVE: To estimate whether nuchal translucency assessment is a useful screening tool for major congenital heart disease (CHD) in the absence of aneuploidy. METHODS: Unselected patients with singleton pregnancies at 10(3/7) to 13(6/7) weeks of gestation were recruited at 15 U.S. centers to undergo nuchal translucency sonography. Screening characteristics of nuchal translucency in the detection of major CHD were determined using different cutoffs (2.0 or more multiples of the median [MoM], 2.5 or more MoM, 3.0 or more MoM). RESULTS: A total of 34,266 euploid fetuses with cardiac outcome data were available for analysis. There were 224 cases of CHD (incidence 6.5 per 1,000), of which 52 (23.2%) were major (incidence 1.5 per 1,000). The incidence of major CHD increased with increasing nuchal translucency: 14.1 per 1,000, 33.5 per 1,000, and 49.5 per 1,000 at 2.0 or more MoM, 2.5 or more MoM, and 3.0 or more MoM cutoffs, respectively. Sensitivity, specificity, and positive predictive values were 15.4%, 98.4%, and 1.4% at 2.0 or more MoM; 13.5%, 99.4%, and 3.3% at 2.5 or more MoM; and 9.6%, 99.7%, and 5.0% at 3.0 or more MoM. Nuchal translucency of 2.5 or more MoM (99th percentile) had a likelihood ratio (95% confidence interval) of 22.5 (11.4-45.5) for major CHD. Based on our data, for every 100 patients referred for fetal echocardiography with a nuchal translucency of 99th percentile or more, three will have a major cardiac anomaly. CONCLUSION: Nuchal translucency sonography in the first trimester lacks the characteristics of a good screening tool for major CHD in a large unselected population. However, nuchal translucency of 2.5 or more MoM (99th percentile or more) should be considered an indication for fetal echocardiography. LEVEL OF EVIDENCE: II.

The contribution of birth defects to preterm birth and low birth weight.

OBJECTIVE: To assess the impact of birth defects on preterm birth and low birth weight. METHODS: Data from a large, prospective multi-center trial, the First and Second Trimester Evaluation of Risk (FASTER) Trial, were examined. All live births at more than 24 weeks of gestation with data on outcome and confounders were divided into two comparison groups: 1) those with a chromosomal or structural abnormality (birth defect) and 2) those with no abnormality detected in chromosomes or anatomy. Propensity scores were used to balance the groups, account for confounding, and reduce the bias of a large number of potential confounding factors in the assessment of the impact of a birth defect on outcome. Multiple logistic regression analysis was applied. RESULTS: A singleton liveborn infant with a birth defect was 2.7 times more likely to be delivered preterm before 37 weeks of gestation (95% confidence interval [CI] 2.3-3.2), 7.0 times more likely to be delivered preterm before 34 weeks (95% CI 5.5-8.9), and 11.5 times more likely to be delivered very preterm before 32 weeks (95% CI 8.7-15.2). A singleton liveborn with a birth defect was 3.6 times more likely to have low birth weight at less than 2,500 g (95% CI 3.0-4.3) and 11.3 times more likely to be very low birth weight at less than 1,500 g (95% CI 8.5-15.1). CONCLUSION: Birth defects are associated with preterm birth and low birth weight after controlling for multiple confounding factors, including shared risk factors and pregnancy complications, using propensity scoring adjustment in multivariable regression analysis. The independent effects of risk factors on perinatal outcomes such as preterm birth and low birth weight, usually complicated by numerous confounding factors, may benefit from the application of this methodology, which can be used to minimize bias and account for confounding. Furthermore, this suggests that clinical and public health interventions aimed at preventing birth defects may have added benefits in preventing preterm birth and low birth weight. LEVEL OF EVIDENCE: II.

First- and second-trimester screening: detection of aneuploidies other than Down syndrome.

OBJECTIVE: To evaluate the performance of first- and second-trimester screening methods for the detection of aneuploidies other than Down syndrome. METHODS: Patients with singleton pregnancies at 10 weeks 3 days through 13 weeks 6 days of gestation were recruited at 15 U.S. centers. All patients had a first-trimester nuchal translucency scan, and those without cystic hygroma had a combined test (nuchal translucency, pregnancy-associated plasma protein A, and free beta-hCG) and returned at 15-18 weeks for a second-trimester quadruple screen (serum alpha-fetoprotein, total hCG, unconjugated estriol, and inhibin-A). Risk cutoff levels of 1:300 for Down syndrome and 1:100 for trisomy 18 were selected. RESULTS: Thirty-six thousand one hundred seventy-one patients completed first-trimester screening, and 35,236 completed second-trimester screening. There were 77 cases of non-Down syndrome aneuploidies identified in this population; 41 were positive for a cystic hygroma in the first trimester, and a further 36 had a combined test, of whom 29 proceeded to quadruple screening. First-trimester screening, by cystic hygroma determination or combined screening had a 78% detection rate for all non-Down syndrome aneuploidies, with an overall false-positive rate of 6.0%. Sixty-nine percent of non-Down syndrome aneuploidies were identified as screen-positive by the second-trimester quadruple screen, at a false-positive rate of 8.9%. In the combined test, the use of trisomy 18 risks did not detect any additional non-Down syndrome aneuploidies compared with the Down syndrome risk alone. In second-trimester quadruple screening, a trisomy 18-specific algorithm detected an additional 41% non-Down syndrome aneuploidies not detected using the Down syndrome algorithm. CONCLUSION: First-trimester Down syndrome screening protocols can detect the majority of cases of non-Down aneuploidies. Addition of a trisomy 18-specific risk algorithm in the second trimester achieves high detection rates for aneuploidies other than Down syndrome. LEVEL OF EVIDENCE: II.

The effect of low body mass index on the development of gestational hypertension and preeclampsia.

OBJECTIVES: To evaluate the relationship between low maternal body mass index (BMI) as calculated in the first trimester and the risk of preeclampsia and gestational hypertension. METHODS: Patients enrolled in the First And Second Trimester Evaluation of Risk for aneuploidy (FASTER) trial were grouped into three weight categories: low BMI (BMI <19.8 kg/m2), normal BMI (BMI 19.8 - 26 kg/m2), and overweight BMI (26.1 - 29 kg/m2). The incidences of gestational hypertension and preeclampsia were ascertained for each group. Tests for differences in crude incidence proportions were performed using Chi-square tests. Multiple logistic regression was used to adjust for maternal age, race, parity, obesity, use of assisted reproductive technology (ART), in vitro fertilization (IVF), gestational diabetes, pre-gestational diabetes, cocaine use, and smoking. RESULTS: The proportion of patients having gestational hypertension in the low BMI group was 2.0% compared to 3.2% for normal BMI and 6.0% for overweight BMI (p < 0.0001). Women with low BMI were also less likely to develop preeclampsia, 1.1% vs. 1.9% for normal BMI and 2.8% for overweight BMI (p < 0.0001). CONCLUSIONS: We found that women with low BMI in the first trimester were significantly less likely to develop gestational hypertension or preeclampsia than women with a normal BMI.

Relationship between crown-rump length and early detection of cardiac activity.

OBJECTIVE: To investigate whether improvements in sonographic technology would allow detection of embryonic demise at a crown-rump length (CRL) < 5 mm. STUDY DESIGN: A prospectively collected, computerized ultrasound database was queried for singleton gestations with CRL < or = 5 mm from January 2000 to February 2003. Embryonic viability was determined by repeat ultrasound examination after 6 weeks'gestation confirming cardiac activity or by documentation of an ongoing pregnancy. Viability rates in the presence or absence of cardiac activity were calculated for CRL of 2.0-2.9, 3.0-3.4, 3.5-3.9, 4.0-4.4, 4.5-4.9 and 5.0 mm. Sensitivity, specificity, positive predictive value and negative predictive value for embryonic demise were calculated, with a subanalysis based on the presence of vaginal bleeding. RESULTS: Outcome was available for 179 of 195 gestations meeting inclusion criteria. The absence of cardiac activity at CRL > or = 3.5 mm had 100% positive predictive value and specificity. The presence of vaginal bleeding did not affect this cutoff. CONCLUSION: Improved sonographic technology permits diagnosis of embryonic demise at a CRL > or = 3.5 mm under ideal conditions. Vaginal bleeding increases the likelihood of demise, but does not alter test performance. Further investigation is warranted, as our data suggest a limit closer to 3 mm.

The fetal dandy walker complex: associated anomalies, perinatal outcome and postnatal imaging.

OBJECTIVE: This study compares the diagnostic accuracy of prenatal ultrasound with postnatal imaging and evaluates for associated fetal anomalies and their impact on immediate neonatal outcome in fetal Dandy Walker complex (DWC). METHODS: Cases of fetal DWC diagnosed in a single ultrasound unit from January 2000 through July 2004 were reviewed for associated fetal anomalies, fetal karyotype, immediate neonatal outcome and postnatal head imaging. RESULTS: A total of 55 fetuses with DWC were identified. Of liveborn cases, postnatal imaging confirmed prenatal intracranial findings in 50% of Dandy Walker variant (DWV) and 100% of Dandy Walker malformation (DWM), with additional central nervous system findings noted in 21% of all cases. Additional fetal anomalies were seen in 26/40 (65%) cases of DWV and 15/15 (100%) cases of DWM. Immediate neonatal survival was predicted by karyotype and associated fetal anomalies. CONCLUSION: The sonographic diagnosis of fetal DWM is accurate. Significant discrepancies exist in prenatal and postnatal diagnosis of DWV. Comprehensive fetal ultrasound and karyotype should be offered for all fetuses with DWC. Postnatal imaging should be performed on all fetal DWC.