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.

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.

Reevaluation of discriminatory and threshold levels for serum ß-hCG in early pregnancy.

OBJECTIVES: To reevaluate both discriminatory and threshold levels associated with visualization of gestational sacs, yolk sacs, and fetal poles in patients presenting with vaginal bleeding, pain, or vaginal bleeding and pain in the first trimester of pregnancy using current ultrasonographic technology. METHODS: We reviewed the records of patients with first-trimester vaginal bleeding, pelvic pain, or both who were evaluated with a serum ß-hCG level and a transvaginal ultrasonogram within 6 hours of each other and had a known pregnancy outcome. Discriminatory and threshold ß-hCG levels for visualization of a gestational sac, yolk sac, and fetal pole were identified for all ultimately viable pregnancies. Logistic regression was used to model the predicted probability of visualizing these structures as a function of ß-hCG values using fractional polynomials. RESULTS: Six hundred fifty-one pregnancies met inclusion criteria; 366 were viable. Discriminatory ß-hCG levels at which structures would be predicted to be seen 99% of the time were 3,510 milli-international units/mL, 17,716 milli-international units/mL, and 47,685 milli-international units/mL for gestational sac, yolk sac, and fetal pole, respectively. In our population, threshold values for ß-hCG levels at which these structures could be seen were 390 milli-international units/mL, 1,094 milli-international units/mL, and 1,394 milli-international units/mL, respectively. CONCLUSIONS: Improvements in ultrasonographic technology have led to lower threshold ß-hCG values for ultrasonographic visualization of early intrauterine gestational structures. However, discriminatory levels for serum ß-hCG levels were higher than values currently used in practice. LEVEL OF EVIDENCE: II.

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.

Prenatal isolated mild ventriculomegaly is associated with persistent ventricle enlargement at ages 1 and 2.

BACKGROUND: Enlargement of the lateral ventricles is thought to originate from abnormal prenatal brain development and is associated with neurodevelopmental disorders. Fetal isolated mild ventriculomegaly (MVM) is associated with the enlargement of lateral ventricle volumes in the neonatal period and developmental delays in early childhood. However, little is known about postnatal brain development in these children. METHODS: Twenty-eight children with fetal isolated MVM and 56 matched controls were followed at ages 1 and 2 years with structural imaging on a 3T Siemens scanner and assessment of cognitive development with the Mullen Scales of Early Learning. Lateral ventricle, total gray and white matter volumes, and Mullen cognitive composite scores and subscale scores were compared between groups. RESULTS: Compared to controls, children with prenatal isolated MVM had significantly larger lateral ventricle volumes at ages 1 and 2 years. Lateral ventricle volume at 1 and 2 years of age was significantly correlated with prenatal ventricle size. Enlargement of the lateral ventricles was associated with increased intracranial volumes and increased gray and white matter volumes. Children with MVM had Mullen composite scores similar to controls, although there was evidence of delay in fine motor and expressive language skills. CONCLUSIONS: Children with prenatal MVM have persistent enlargement of the lateral ventricles through the age of 2 years; this enlargement is associated with increased gray and white matter volumes and some evidence of delay in fine motor and expressive language development. Further study is needed to determine if enlarged lateral ventricles are associated with increased risk for neurodevelopmental disorders.

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.

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.

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.

Prenatal and neonatal brain structure and white matter maturation in children at high risk for schizophrenia.

OBJECTIVE: Schizophrenia is a neurodevelopmental disorder associated with abnormalities of brain structure and white matter, although little is known about when these abnormalities arise. This study was conducted to identify structural brain abnormalities in the prenatal and neonatal periods associated with genetic risk for schizophrenia. METHOD: Prenatal ultrasound scans and neonatal structural magnetic resonance imaging (MRI) and diffusion tensor imaging were prospectively obtained in the offspring of mothers with schizophrenia or schizoaffective disorder (N=26) and matched comparison mothers without psychiatric illness (N=26). Comparisons were made for prenatal lateral ventricle width and head circumference, for neonatal intracranial, CSF, gray matter, white matter, and lateral ventricle volumes, and for neonatal diffusion properties of the genu and splenium of the corpus callosum and corticospinal tracts. RESULTS: Relative to the matched comparison subjects, the offspring of mothers with schizophrenia did not differ in prenatal lateral ventricle width or head circumference. Overall, the high-risk neonates had nonsignificantly larger intracranial, CSF, and lateral ventricle volumes. Subgroup analysis revealed that male high-risk infants had significantly larger intracranial, CSF, total gray matter, and lateral ventricle volumes; the female high-risk neonates were similar to the female comparison subjects. There were no group differences in white matter diffusion tensor properties. CONCLUSIONS: Male neonates at genetic risk for schizophrenia had several larger than normal brain volumes, while females did not. To the authors' knowledge, this study provides the first evidence, in the context of its limitations, that early neonatal brain development may be abnormal in males at genetic risk for schizophrenia.

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.

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.

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.

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.

Discordance of prenatal and neonatal brain development in twins.

BACKGROUND: Discordance of birth weight has been observed in twin pairs, though little is known about prenatal and early neonatal discordance of head and brain size, and the role that zygosity and chorionicity play in discordances of early brain development in twins. AIMS: To compare prenatal and neonatal discordances of head size in monozygotic-monochorionic (MZ-MC), monozygotic-dichorionic (MZ-DC), and same-sex dizygotic-dichorionic twin pairs (DZ). STUDY DESIGN: Subjects prospectively had ultrasounds at 22 and 32 weeks gestational age, and magnetic resonance imaging (MRI) of the brain MRI after birth. SUBJECTS: 88 twin pairs recruited from two university hospital prenatal diagnostic clinics; 22 MZ-MC, 17 MZ-DC, and 49 same-sex DZ pairs. OUTCOME MEASURES: Discordance of head circumference (HC) and weight at 22 weeks, 32 weeks and birth, as well as intracranial volume (ICV) on neonatal MRI. RESULTS: There were no group differences in discordance of head circumference and weight on the 22 or 32 week ultrasounds, or at birth. MZ-MC twins tended to have numerically greater discordances of HC and weight. There was a significant group difference in ICV on neonatal MRI (ANOVA, p=0.0143), with DZ twins having significantly greater discordance than MZ-MC (p=0.028) or MZ-DC (p=0.0131) twins. CONCLUSIONS: This study indicates that zygosity and chorionicity do not contribute to significant discordances of head size in late prenatal development. DZ twins do have significantly greater discordances of ICV on neonatal MRI, suggesting a relatively greater genetic influence on brain growth in the first weeks after birth.

Down syndrome serum screening also identifies an increased risk for multicystic dysplastic kidney, two-vessel cord, and hydrocele.

OBJECTIVE: The FASTER trial compared first and second trimester screening methods for aneuploidy. We examined relationships between maternal serum markers and common congenital anomalies in the pediatric outcome data set of 36 837 subjects. METHODS: We used nested case-control studies, with cases defined by the most common anomalies in our follow-up database, and up to four controls matched by enrollment site, maternal age and race, enrollment gestational age, and infant gender. Serum markers were dichotomized to > or = 2 or < 0.5 multiples of the median (MoM). Odds ratios (ORs) and 95% confidence intervals (CI) were estimated. RESULTS: Statistically significant (p < 0.05) associations were found between inhibin A > or = 2 MoM with fetal multicystic dysplastic kidney (MCDK) (OR = 27.5, 95% CI: 2.8-267.7) and two-vessel cord (OR = 4.22, 95% CI:1.6-10.9); hCG of > or = 2 MoM with MCDK (OR = 19.56, 95% CI: 1.9-196.2) and hydrocele (OR = 2.48, 95% CI: 1.3-4.6); and PAPP-A > or = 2.0 MoM with hydrocele (OR = 1.88, 95% CI:1.1-3.3). CONCLUSION: In this large prospective study, significant associations were found between several maternal serum markers and congenital anomalies. This suggests potential additional benefits to screening programs that are primarily designed to detect aneuploidy.

Prenatal mild ventriculomegaly predicts abnormal development of the neonatal brain.

BACKGROUND: Many psychiatric and neurodevelopmental disorders are associated with mild enlargement of the lateral ventricles thought to have origins in prenatal brain development. Little is known about development of the lateral ventricles and the relationship of prenatal lateral ventricle enlargement with postnatal brain development. METHODS: We performed neonatal magnetic resonance imaging on 34 children with isolated mild ventriculomegaly (MVM; width of the atrium of the lateral ventricle >/= 1.0 cm) on prenatal ultrasound and 34 age- and sex-matched control subjects with normal prenatal ventricle size. Lateral ventricle and cortical gray and white matter volumes were assessed. Fractional anisotropy (FA) and mean diffusivity (MD) in corpus callosum and corticospinal white matter tracts were determined obtained using quantitative tractography. RESULTS: Neonates with prenatal MVM had significantly larger lateral ventricle volumes than matched control subjects (286.4%; p < .0001). Neonates with MVM also had significantly larger intracranial volumes (ICV; 7.1%, p = .0063) and cortical gray matter volumes (10.9%, p = .0004) compared with control subjects. Diffusion tensor imaging tractography revealed a significantly greater MD in the corpus callosum and corticospinal tracts, whereas FA was significantly smaller in several white matter tract regions. CONCLUSIONS: Prenatal enlargement of the lateral ventricle is associated with enlargement of the lateral ventricles after birth, as well as greater gray matter volumes and delayed or abnormal maturation of white matter. It is suggested that prenatal ventricle volume is an early structural marker of altered development of the cerebral cortex and may be a marker of risk for neuropsychiatric disorders associated with ventricle enlargement.

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.