Circulating Cell-Free DNA to Determine the Fetal RHD Status in All Three Trimesters of Pregnancy.

OBJECTIVE: To estimate the accuracy of a new assay to determine the fetal RHD status using circulating cell-free DNA. METHODS: This was a prospective, observational study. Maternal blood samples were collected in each trimester of pregnancy in 520 nonalloimmunized RhD-negative patients. Plasma samples were analyzed for circulating cell-free DNA using the SensiGENE RHD test, which used primers for exons 4 and 7 as previously described and incorporated a new primer design for exon 5 of the RHD gene. Neonatal serology for RhD typing using cord blood at birth was undertaken and results were stored in a separate clinical database. After unblinding the data, results of the DNA analysis were compared with the neonatal serology. RESULTS: Inconclusive results secondary to the presence of the RHD pseudogene or an RHD variant were noted in 5.6%, 5.7%, and 6.1% of the first-, second-, and third-trimester samples, respectively. The incidence of false-positive rates for RhD (an RhD-negative fetus with an RHD-positive result) was 1.54% (95% confidence interval [CI] 0.42-5.44%), 1.53% (CI 0.42-5.40%), and 0.82% (CI 0.04-4.50%), respectively. There was only one false-negative diagnosis (an RhD-positive fetus with an RHD-negative result), which occurred in the first trimester (0.32%; 95% CI 0.08-1.78%). Genotyping for mismatches across repeated samples revealed that this error was related to mislabeling of samples from two patients collected on the same day at one of the collection sites. Overall test results were in agreement across all three trimesters (P>.99). CONCLUSION: Circulating cell-free DNA can accurately predict the fetal RhD status in all three trimesters of pregnancy.

Detection of microbial invasion of the amniotic cavity by analysis of cervicovaginal proteins in women with preterm labor and intact membranes.

OBJECTIVE: Microbial invasion of the amniotic cavity (MIAC) is common in early preterm labor and is associated with maternal and neonatal infectious morbidity. MIAC is usually occult and is reliably detected only with amniocentesis. We sought to develop a noninvasive test to predict MIAC based on protein biomarkers in cervicovaginal fluid (CVF) in a cohort of women with preterm labor (phase 1) and to validate the test in an independent cohort (phase 2). STUDY DESIGN: This was a prospective study of women with preterm labor who had amniocentesis to screen for MIAC. MIAC was defined by positive culture and/or 16S ribosomal DNA results. Nine candidate CVF proteins were analyzed by enzyme-linked immunosorbent assay. Logistic regression was used to identify combinations of up to 3 proteins that could accurately classify the phase 1 cohort (N = 108) into those with or without MIAC. The best models, selected by area under the curve (AUC) of the receiver operating characteristic curve in phase 1, included various combinations of interleukin (IL)-6, chemokine (C-X-C motif) ligand 1 (CXCL1), alpha fetoprotein, and insulin-like growth factor binding protein-1. Model performance was then tested in the phase 2 cohort (N = 306). RESULTS: MIAC was present in 15% of cases in phase 1 and 9% in phase 2. A 3-marker CVF model using IL-6 plus CXCL1 plus insulin-like growth factor binding protein-1 had AUC 0.87 in phase 1 and 0.78 in phase 2. Two-marker models using IL-6 plus CXCL1 or alpha fetoprotein plus CXCL1 performed similarly in phase 2 (AUC 0.78 and 0.75, respectively), but were not superior to CVF IL-6 alone (AUC 0.80). A cutoff value of CVF IL-6 ≥463 pg/mL (which had 81% sensitivity in phase 1) predicted MIAC in phase 2 with sensitivity 79%, specificity 78%, positive predictive value 38%, and negative predictive value 97%. CONCLUSION: High levels of IL-6 in CVF are strongly associated with MIAC. If developed into a bedside test or rapid laboratory assay, cervicovaginal IL-6 might be useful in selecting patients in whom the probability of MIAC is high enough to warrant amniocentesis or transfer to a higher level of care. Such a test might also guide selection of potential subjects for treatment trials.

Timing of and outcomes after selective termination of anomalous fetuses in dichorionic twin pregnancies.

OBJECTIVE: The objective of this article is to determine if selective termination (ST) of an anomalous dichorionic twin at early gestational age (GA) is associated with a decreased risk of fetal loss and prematurity. METHOD: All patients who had ST for dichorionic twin pregnancies from 2004 through 2010 at Mount Sinai Medical Center were included. Data were collected via chart review and patient interview. Two case-control analyses were carried out: first, cases were nonviable deliveries, and controls were live births; and second, cases were live births <37 weeks' GA, and controls were live births ≥37 weeks' GA. Univariable and then multivariable analyses identified characteristics associated with pregnancy loss and prematurity. RESULTS: Among 80 participants, there were four (5%) fetal losses and 15 (19%) premature births. GA at ST was the only characteristic associated with pregnancy loss in multivariable exact logistic regression [OR = 1.43, 95% CI (1.03, 2.26), P = 0.03]. GA at ST was the only characteristic associated with premature delivery in multivariable exact logistic regression [OR = 1.18, 95% CI (1.02, 1.37), P = 0.03]. CONCLUSION: This study suggests that ST performed earlier in pregnancy is associated with decreased fetal loss and prematurity.

Diagnosis and management of neonatal alloimmune thrombocytopenia in pregnancy.

Neonatal alloimmune thrombocytopenia (NAIT) is the most common cause of severe thrombocytopenia in the healthy newborn, occurring in 1 in 1000 live births. NAIT is analogous to rhesus alloimmunization in pathophysiology; however, it often presents unexpectedly in first pregnancies. Presentation of NAIT varies from mild thrombocytopenia to life-threatening intracranial hemorrhage. It has been observed to be more severe in subsequent affected pregnancies. It is important that the diagnosis of NAIT be considered in the work-up of all cases of neonatal thrombocytopenia to determine the risk to future pregnancies and corresponding management plans. This article discusses the pathogenesis and incidence of NAIT and the antenatal and postnatal management of this condition.

8p23.1 duplication syndrome; common, confirmed, and novel features in six further patients.

The 8p23.1 duplication syndrome is a relatively rare genomic condition that has been confirmed with molecular cytogenetic methods in only 11 probands and five family members. Here, we describe another prenatal and five postnatal patients with de novo 8p23.1 duplications analyzed with oligonucleotide array comparative genomic hybridization (oaCGH). Of the common features, mild or moderate developmental delays and/or learning difficulties have been found in 11/12 postnatal probands, a variable degree of mild dysmorphism in 8/12 and congenital heart disease (CHD) in 4/5 prenatal and 3/12 postnatal probands. Behavioral problems, cleft lip and/or palate, macrocephaly, and seizures were confirmed as additional features among the new patients, and novel features included neonatal respiratory distress, attention deficit hyperactivity disorder (ADHD), ocular anomalies, balance problems, hypotonia, and hydrocele. The core duplication of 3.68 Mb contains 31 genes and microRNAs of which only GATA4, TNKS, SOX7, and XKR6 are likely to be dosage sensitive genes and MIR124-1 and MIR598 have been implicated in neurocognitive phenotypes. A combination of the duplication of GATA4, SOX7, and related genes may account for the variable penetrance of CHD. Two of the duplications were maternal and intrachromosomal in origin with maternal heterozygosity for the common inversion between the repeats in 8p23.1. These additional patients and the absence of the 8p23.1 duplications in published controls, indicate that the 8p23.1 duplication syndrome may now be considered a pathogenic copy number variation (pCNV) with an estimated population prevalence of 1 in 58,000.

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.

Noninvasive prenatal diagnosis: past, present, and future.

The presence of fetal cells in the maternal circulation was first noted by Georg Schmorl when he documented the presence of multinucleated syncytial giant cells of placental origin in the lung tissue of women who had died from complications of eclampsia. In the intervening century, advances in cellular and molecular biology further elucidated both the physiology and pathophysiology of communication within the fetomaternal unit. This concept is at the foundation of the rapidly expanding field of noninvasive prenatal diagnosis. However, the clinical utility of this phenomenon had been limited until the presence of cell-free fetal DNA circulating in the maternal plasma was reported in 1997 and fetal messenger RNA was demonstrated to circulate in the maternal plasma in 2000. These circulating nucleic acids are found free-floating in the maternal plasma, unencumbered by a surrounding fetal cell. The analysis of these 3 fetal markers (fetal cells, cell-free fetal DNA, and fetal messenger RNA) for diagnostic and screening purposes is now being developed. The scope of noninvasive prenatal diagnosis is not limited to only the diagnosis of fetal genetic traits and aneuploidies. Recently, researchers have focused their investigations on the role of cell-free fetal DNA and fetal messenger RNA in preeclampsia, intrauterine growth restriction, and preterm labor. These biomarkers, the result of inherent placental dysfunction or the byproducts of placental trophoblastic apoptosis, may allow for improvements in the diagnosis and management of high-risk pregnancies.

Role of second-trimester genetic sonography after Down syndrome screening.

OBJECTIVE: To estimate the effectiveness of second-trimester genetic sonography in modifying Down syndrome screening test results. METHODS: The First and Second Trimester Evaluation of Risk (FASTER) aneuploidy screening trial participants were studied from 13 centers where a 15- to 23-week genetic sonogram was performed in the same center. Midtrimester Down syndrome risks were estimated for five screening test policies: first-trimester combined, second-trimester quadruple, and testing sequentially by integrated, stepwise, or contingent protocols. The maternal age-specific risk and the screening test risk were modified using likelihood ratios derived from the ultrasound findings. Separate likelihood ratios were obtained for the presence or absence of at least one major fetal structural malformation and for each "soft" sonographic marker statistically significant at the P<.005 level. Detection and false-positive rate were calculated for the genetic sonogram alone and for each test before and after risk modification. RESULTS: A total of 7,842 pregnancies were studied, including 59 with Down syndrome. Major malformations and 8 of the 18 soft markers evaluated were highly significant. The detection rate for a 5% false-positive rate for the genetic sonogram alone was 69%; the detection rate increased from 81% to 90% with the combined test, from 81% to 90% with the quadruple test, from 93% to 98% with the integrated test, from 97% to 98% with the stepwise test, and from 95% to 97% with the contingent test. The stepwise and contingent use of the genetic sonogram after first-trimester screening both yielded a 90% detection rate. CONCLUSION: Genetic sonography can increase detection rates substantially for combined and quadruple tests and more modestly for sequential protocols. Substituting sonography for quadruple markers in sequential screening was not useful. LEVEL OF EVIDENCE: II.

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.

Contemporary outcomes with the latest 1000 cases of multifetal pregnancy reduction (MPR).

OBJECTIVE: This study was undertaken to report on the outcome of multifetal pregnancy reduction in the most up-to-date largest single center experience with this procedure, and compare the outcome to the first 1000 cases performed at the same institution. STUDY DESIGN: 1000 consecutive cases of multifetal pregnancy reduction performed at the Mount Sinai Medical Center between the years 1999-2006 were identified. Pregnancy outcomes were retrieved from a large database as well as chart review. Differences in means and proportions were evaluated by analysis of variance, chi-square, Cochran-Armitage test for trend or 2-tailed Fisher exact test as appropriate. RESULTS: Outcomes were available on 841 cases, for a follow-up rate of 84.1%; 95.2% of patients delivered after 24 weeks, for a complete loss rate of 4.7%. There was a significant trend toward decreasing loss rates with decreasing starting numbers. Mean gestational age at delivery was later, and birthweights greater, for reduction to singletons vs twins. CONCLUSION: Loss rates after multifetal pregnancy reduction have remained stable at 4.7%. The lowest loss rate occurred in the patients reducing from twins to a singleton (2.1%). Reduction to a singleton was also associated with higher birthweights and lower rates of preterm deliveries.

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.

Chorionic villus sampling and the risk of adverse outcome in patients undergoing multifetal pregnancy reduction.

OBJECTIVE: The objective of the study was to determine whether patients undergoing chorionic villus sampling (CVS) prior to MPR are at increased risk for adverse outcome compared to those who did not. STUDY DESIGN: We retrospectively identified multifetal pregnancy reduction (MPR) patients from an established database. Maternal demographic data were collected. Outcomes including complete pregnancy loss prior to 24 weeks' gestation, gestational age at delivery, and birthweight were analyzed. RESULTS: There was no significant difference in pregnancy loss between the 2 groups (CVS [4%] vs no CVS [7%], P = .098). When stratified by finishing number, there was a significantly lower loss rate in the singleton CVS group (2% vs 9%, P = .025) and no significant difference in reduced twins. There was no significant difference in the average gestational age of delivery or birthweight. CONCLUSION: CVS prior to MPR does not increase the risk of pregnancy loss. Our data suggest that CVS prior to singleton reduction may decrease the risk of adverse outcome.

Differences in fetal growth, discordancy, and placental pathology in reduced versus nonreduced twins.

This study evaluated the effect of multifetal pregnancy reduction on the incidence of small for gestational age (SGA) and discordance in reduced versus nonreduced twins and differences in placental pathology. A computerized ultrasound database was used to identify diamniotic-dichorionic twins who delivered at our institution. Reduced (n = 36) versus nonreduced twins (n = 243) were compared for differences in rates of SGA and discordancy (>or= 20%.) The groups were compared for differences in maternal and neonatal characteristics, as well as differences in placental pathology. Chi-square tests were used to compare differences in means. Stepwise logistic regression was used to adjust for potential confounders including placental pathology. The rate of SGA in either twin A or B remained nonsignificant after adjustment for the use of assisted reproductive technology and gestational age at delivery in the stepwise logistic model (odds ratio, 1.7 95%; confidence interval, 0.5, 5.2). The average discordance at delivery was 12.4% in reduced versus 11.4% in the nonreduced twins ( P = 0.54). We found no overall differences in placental pathology between the two groups. Reduced and nonreduced twins have no significant differences in SGA fetuses, growth discordancy, or placental pathology.

Evolving trends in 2000 cases of multifetal pregnancy reduction: a single-center experience.

OBJECTIVE: The purpose of this study was to examine changes in multifetal pregnancy reduction (MPR) procedures in 2000 cases and to evaluate evolving trends within the last 1000 MPRs. STUDY DESIGN: Two thousand patients who underwent MPR were identified. Data were collected from a computerized database. Comparisons were made between the first 1000 patients (group 1) and the second 1000 patients (group 2). In addition, changing trends within group 2 were also analyzed. Differences in proportions were evaluated by chi-square test and Fisher's exact test, as appropriate. RESULTS: There was a significant difference in the starting and finishing number of fetuses and a significant increase in the use of chorionic villus sampling before MPR in group 2 vs group 1 (43.7% vs 1.5%; P < .0001). The incidence of monochorionicity was significantly higher in group 2 (5.7%), compared with group 1 (2.1%; P < .001). CONCLUSION: Recent trends in MPR demonstrates significant increases in overall reductions to a singleton fetus, the use of chorionic villus sampling, and the presence of monochorionicity.

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.

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.

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.

Does sonographic determination of placental location predict fetal birth weight in diamniotic-dichorionic twins?

OBJECTIVE: The purpose of this study was to determine the association between placental location in diamniotic-dichorionic twins as determined at the time of anatomic survey and birth weight. METHODS: We retrospectively identified all diamniotic-dichorionic twins in our Maternal-Fetal Medicine sonography database between 2000 and 2005 who had an anatomic survey, went on to be delivered at our hospital, and had records available for review (n = 304). Placental location for each twin was determined at the time of anatomic survey and grouped into both anterior or both posterior versus separate anterior and posterior. Maternal and fetal characteristics were collected from chart review. Placental pathologic findings were available for 249 (83%) patients. Outcomes analyzed were percent discordance, small size for gestational age of twin A or B, and difference in birth weight as a continuous variable. Multivariable logistic regression using stepwise backward elimination was used to adjust for potential confounders. RESULTS: There was no difference in discordance of 20% or greater or incidence of small size for gestational age when both placentas were both anterior and both posterior compared with separate anterior and posterior: adjusted odds ratio (AdjOR), 1.38 (95% confidence interval [CI], 0.64-2.95); and AdjOR, 1.29 (95% CI, 0.57-2.89). The actual birth weight difference (A - B) was not affected by placental location (P = .36). Opposite sex fetuses and nulliparity were significantly associated with birth weight discordance: AdjOR, 2.68 (95% CI, 1.39-5.17); and AdjOR, 0.34 (95% CI, 0.28-0.94). CONCLUSIONS: We did not find a correlation between birth weight and placental location in our cohort analysis. The presence of sex-discordant twins was associated with birth weight discordance of 20% or greater, whereas nulliparity was protective.

Pregnancy loss rates after midtrimester amniocentesis.

OBJECTIVE: The purpose of this study was to quantify the contemporary procedure-related loss rate after midtrimester amniocentesis using a database generated from patients who were recruited to the First And Second Trimester Evaluation of Risk for Aneuploidy trial. METHODS: A total of 35,003 unselected patients from the general population with viable singleton pregnancies were enrolled in the First And Second Trimester Evaluation of Risk for Aneuploidy trial between 10 3/7 and 13 6/7 weeks gestation and followed up prospectively for complete pregnancy outcome information. Patients who either did (study group, n=3,096) or did not (control group, n=31,907) undergo midtrimester amniocentesis were identified from the database. The rate of fetal loss less than 24 weeks of gestation was compared between the two groups, and multiple logistic regression analysis was used to adjust for potential confounders. RESULTS: The spontaneous fetal loss rate less than 24 weeks of gestation in the study group was 1.0% and was not statistically different from the background 0.94% rate seen in the control group (P=.74, 95% confidence interval -0.26%, 0.49%). The procedure-related loss rate after amniocentesis was 0.06% (1.0% minus the background rate of 0.94%). Women undergoing amniocentesis were 1.1 times more likely to have a spontaneous loss (95% confidence interval 0.7-1.5). CONCLUSION: The procedure-related fetal loss rate after midtrimester amniocentesis performed on patients in a contemporary prospective clinical trial was 0.06%. There was no significant difference in loss rates between those undergoing amniocentesis and those not undergoing amniocentesis. LEVEL OF EVIDENCE: II-2.