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BACKGROUND: Historically, prenatal screening has focused primarily on the detection of fetal aneuploidies. Cell-free DNA now enables noninvasive screening for subchromosomal copy number variants, including 22q11.2 deletion syndrome (or DiGeorge syndrome), which is the most common microdeletion and a leading cause of congenital heart defects and neurodevelopmental delay. Although smaller studies have demonstrated the feasibility of screening for 22q11.2 deletion syndrome, large cohort studies with confirmatory postnatal testing to assess test performance have not been reported. OBJECTIVE: This study aimed to assess the performance of single-nucleotide polymorphism-based, prenatal cell-free DNA screening for detection of 22q11.2 deletion syndrome. STUDY DESIGN: Patients who underwent single-nucleotide polymorphism-based prenatal cell-free DNA screening for 22q11.2 deletion syndrome were prospectively enrolled at 21 centers in 6 countries. Prenatal or newborn DNA samples were requested in all cases for genetic confirmation using chromosomal microarrays. The primary outcome was sensitivity, specificity, positive predictive value, and negative predictive value of cell-free DNA screening for the detection of all deletions, including the classical deletion and nested deletions that are ≥500 kb, in the 22q11.2 low-copy repeat A-D region. Secondary outcomes included the prevalence of 22q11.2 deletion syndrome and performance of an updated cell-free DNA algorithm that was evaluated with blinding to the pregnancy outcome. RESULTS: Of the 20,887 women enrolled, a genetic outcome was available for 18,289 (87.6%). A total of 12 22q11.2 deletion syndrome cases were confirmed in the cohort, including 5 (41.7%) nested deletions, yielding a prevalence of 1 in 1524. In the total cohort, cell-free DNA screening identified 17,976 (98.3%) cases as low risk for 22q11.2 deletion syndrome and 38 (0.2%) cases as high risk; 275 (1.5%) cases were nonreportable. Overall, 9 of 12 cases of 22q11.2 were detected, yielding a sensitivity of 75.0% (95% confidence interval, 42.8-94.5); specificity of 99.84% (95% confidence interval, 99.77-99.89); positive predictive value of 23.7% (95% confidence interval, 11.44-40.24), and negative predictive value of 99.98% (95% confidence interval, 99.95-100). None of the cases with a nonreportable result was diagnosed with 22q11.2 deletion syndrome. The updated algorithm detected 10 of 12 cases (83.3%; 95% confidence interval, 51.6-97.9) with a lower false positive rate (0.05% vs 0.16%; P

Background Preeclampsia and fetal growth restriction are major causes of perinatal death and handicap in survivors. Randomized clinical trials have reported that the risk of preeclampsia, severe preeclampsia, and fetal growth restriction can be reduced by the prophylactic use of aspirin in high-risk women, but the appropriate dose of the drug to achieve this objective is not certain. Objective We sought to estimate the impact of aspirin dosage on the prevention of preeclampsia, severe preeclampsia, and fetal growth restriction. Study Design We performed a systematic review and meta-analysis of randomized controlled trials comparing the effect of daily aspirin or placebo (or no treatment) during pregnancy. We searched MEDLINE, Embase, Web of Science, and Cochrane Central Register of Controlled Trials up to December 2015, and study bibliographies were reviewed. Authors were contacted to obtain additional data when needed. Relative risks for preeclampsia, severe preeclampsia, and fetal growth restriction were calculated with 95% confidence intervals using random-effect models. Dose-response effect was evaluated using meta-regression and reported as adjusted R 2 . Analyses were stratified according to gestational age at initiation of aspirin (≤16 and >16 weeks) and repeated after exclusion of studies at high risk of biases. Results In all, 45 randomized controlled trials included a total of 20,909 pregnant women randomized to between 50-150 mg of aspirin daily. When aspirin was initiated at ≤16 weeks, there was a significant reduction and a dose-response effect for the prevention of preeclampsia (relative risk, 0.57; 95% confidence interval, 0.43–0.75; P 2 , 44%; P = .036), severe preeclampsia (relative risk, 0.47; 95% confidence interval, 0.26–0.83; P = .009; R 2 , 100%; P = .008), and fetal growth restriction (relative risk, 0.56; 95% confidence interval, 0.44–0.70; P 2 , 100%; P = .044) with higher dosages of aspirin being associated with greater reduction of the 3 outcomes. Similar results were observed after the exclusion of studies at high risk of biases. When aspirin was initiated at >16 weeks, there was a smaller reduction of preeclampsia (relative risk, 0.81; 95% confidence interval, 0.66–0.99; P = .04) without relationship with aspirin dosage (R 2 , 0%; P = .941). Aspirin initiated at >16 weeks was not associated with a risk reduction or a dose-response effect for severe preeclampsia (relative risk, 0.85; 95% confidence interval, 0.64–1.14; P = .28; R 2 , 0%; P = .838) and fetal growth restriction (relative risk, 0.95; 95% confidence interval, 0.86–1.05; P = .34; R 2 , not available; P = .563). Conclusion Prevention of preeclampsia and fetal growth restriction using aspirin in early pregnancy is associated with a dose-response effect. Low-dose aspirin initiated at >16 weeks' gestation has a modest or no impact on the risk of preeclampsia, severe preeclampsia, and fetal growth restriction. Women at high risk for those outcomes should be identified in early pregnancy.

OBJECTIVE: Our purpose was to compare the biochemical composition of the fluid contained in pathologic and physiologic cavities in early pregnancy. STUDY DESIGN: The level of urea, creatinine, electrolytes, enzymes, total protein, and α-fetoprotein and the affinity of α-fetoprotein for concanavalin A Sepharose was measured in samples of vesicular fluid from complete ( n = 2) and partial ( n = 1) mole, nuchal fluid ( n = 4), and cystic hygroma fluid ( n = 4). For comparison samples of maternal serum ( n = 32), amniotic fluid ( n = 32), coelomic fluid ( n = 15), and fetal blood ( n = 13) were obtained from normal pregnancies at 10 to 16 weeks' gestation. RESULTS: Urea concentration was lower, whereas sodium, potassium, and total protein concentrations were higher in vesicular fluid than in amniotic and coelomic fluid. Urea, creatinine, sodium, potassium, chloride, and β2-microglobulin concentrations did not vary between nuchal or cystic hygroma fluid and amniotic fluid or fetal serum. The concentration of total protein in nuchal and hygroma fluid was significantly lower than in fetal serum and significantly higher than in amniotic fluid. The amniotic fluid contained extremely high τ-glutamyltransferase concentration compared with the other fluids and fetal serum. Alkaline phosphatase and amylase were not detectable in coelomic fluid, fetal serum, or nuchal and hygroma fluid. The nuchal and hygroma fluid composition was similar except for total protein and α-fetoprotein concentrations, which were significantly higher in nuchal than in hygroma fluid. The vesicular fluid from the partial mole, fetal serum, and nuchal and hygroma fluid contained extremely high α-fetoprotein concentrations, which were significantly higher that those found in amniotic fluid. In complete mole α-fetoprotein molecules were of the yolk sac type, whereas they were of the liver type in nuchal and hygroma fluid. CONCLUSIONS: The composition of vesicular fluid in complete mole reflects a possible origin from the maternal plasma, yolk sac, and trophoblast, whereas the composition of nuchal and cystic hygroma fluid suggests a leakage from the fetal circulation. (Am J Obstet Gynecol 1998;178:765-9.)

OBJECTIVE: Our purpose was to determine the incidence of cardiac septal defects in fetuses with trisomy 21 diagnosed by increased nuchal translucency thickness at 10 to 13 weeks' gestation. STUDY DESIGN: Pathologic examination of the fetal heart was performed in 36 fetuses with trisomy 21 after suction termination of pregnancy at 12 to 15 weeks' gestation. The diagnosis of trisomy 21 was made by chorion villus sampling because of increased (≥3 mm) fetal nuchal translucency thickness detected at routine first-trimester ultrasonographic examination. RESULTS: Perimembranous ventricular and atrioventricular septal defects were detected in 20 of 36 fetal hearts. A septal defect was observed in 1 of the 11 fetuses with nuchal translucency thickness of 3 mm and in 19 of the 25 with translucency ≥4 mm ( p CONCLUSION: The incidence of ventricular and atrioventricular septal defects is much higher in fetuses with trisomy 21 and increased nuchal translucency thickness at 10 t 13 weeks' gestation than in live-born infants with this chromosomal abnormality. The incidence of cardiac septal defects increases with nuchal translucency thickness.