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Item Antenatal Fetal Adrenal Measurements at 22 to 30 Weeks' Gestation, Fetal Growth Restriction, and Perinatal Morbidity(Thieme, 2021) Blue, Nathan R.; Hoffman, Matthew; Allshouse, Amanda A.; Grobman, William A.; Simhan, Hyagriv N.; Turan, Ozhan M.; Parry, Samuel; Chung, Judith H.; Reddy, Uma; Haas, David M.; Myers, Stephen; Mercer, Brian; Saade, George R.; Silver, Robert M.; Obstetrics and Gynecology, School of MedicineObjective: Our objective was to test the association of fetal adrenal size with perinatal morbidity among fetuses with fetal growth restriction (FGR; estimated fetal weight [EFW] < 10th percentile). Study design: This was a secondary analysis of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be (nuMoM2b) adrenal study, which measured fetal adrenal gland size at 22 to 30 weeks' gestation. We analyzed the transverse adrenal area (TAA) and fetal zone area (absolute measurements and corrected for fetal size) and the ratio of the fetal zone area to the total transverse area using a composite perinatal outcome of stillbirth, neonatal intensive care unit admission, respiratory distress syndrome, necrotizing enterocolitis, retinopathy of prematurity, sepsis, mechanical ventilation, seizure, or death. Among fetuses with FGR, adrenal measurements were compared between those that did and did not experience the composite perinatal outcome. Results: There were 1,709 eligible neonates. Seven percent (n = 120) were diagnosed with FGR at the time of adrenal measurement, and 14.7% (n = 251) experienced perinatal morbidity. EFW-corrected and absolute adrenal measurements were similar among fetuses with and without FGR as well as among those who did and did not experience morbidity. The area under the curve for corrected TAA was 0.52 (95% confidence interval 0.38-0.67). Conclusion: In our cohort, adrenal size was not associated with risk of morbidity among fetuses with FGR.Item Customized versus Population Growth Standards for Morbidity and Mortality Risk Stratification Using Ultrasonographic Fetal Growth Assessment at 22 to 29 Weeks' Gestation(Thieme, 2021) Blue, Nathan R.; Grobman, William A.; Larkin, Jacob C.; Scifres, Christina M.; Simhan, Hyagriv N.; Chung, Judith H.; Saade, George R.; Haas, David M.; Wapner, Ronald; Reddy, Uma M.; Mercer, Brian; Parry, Samuel I.; Silver, Robert M.; Obstetrics and Gynecology, School of MedicineObjective: The aim of study is to compare the performance of ultrasonographic customized and population fetal growth standards for prediction adverse perinatal outcomes. Study design: This was a secondary analysis of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be, in which l data were collected at visits throughout pregnancy and after delivery. Percentiles were assigned to estimated fetal weights (EFWs) measured at 22 to 29 weeks using the Hadlock population standard and a customized standard (www.gestation.net). Areas under the curve were compared for the prediction of composite and severe composite perinatal morbidity using EFW percentile. Results: Among 8,701 eligible study participants, the population standard diagnosed more fetuses with fetal growth restriction (FGR) than the customized standard (5.5 vs. 3.5%, p < 0.001). Neither standard performed better than chance to predict composite perinatal morbidity. Although the customized performed better than the population standard to predict severe perinatal morbidity (areas under the curve: 0.56 vs. 0.54, p = 0.003), both were poor. Fetuses considered FGR by the population standard but normal by the customized standard had morbidity rates similar to fetuses considered normally grown by both standards.The population standard diagnosed FGR among black women and Hispanic women at nearly double the rate it did among white women (p < 0.001 for both comparisons), even though morbidity was not different across racial/ethnic groups. The customized standard diagnosed FGR at similar rates across groups. Using the population standard, 77% of FGR cases were diagnosed among female fetuses even though morbidity among females was lower (p < 0.001). The customized model diagnosed FGR at similar rates in male and female fetuses. Conclusion: At 22 to 29 weeks' gestation, EFW percentile alone poorly predicts perinatal morbidity whether using customized or population fetal growth standards. The population standard diagnoses FGR at increased rates in subgroups not at increased risk of morbidity and at lower rates in subgroups at increased risk of morbidity, whereas the customized standard does not.Item Developing a predictive model for perinatal morbidity among small for gestational age infants(Taylor & Francis, 2022) Blue, Nathan R.; Allhouse, Amanda A.; Grobman, William A.; Day, Robert C.; Haas, David M.; Simhan, Hyagriv N.; Parry, Samuel; Saade, George R.; Silver, Robert M.; Obstetrics and Gynecology, School of MedicineBackground: While neonates with birth weight <10th percentile are at increased risk of morbidity and mortality, most of these are constitutionally small and not at increased risk. There are no current strategies that reliably distinguish constitutionally small neonates from small neonates at the highest risk of morbidity, so additional tools for risk stratification are needed. Objective: Our objectives were to identify factors that are independently associated with perinatal morbidity among neonates with birth weight <10th percentile (small for gestational age, SGA) and to create predictive models of perinatal morbidity among SGA neonates based on the timing of information availability. Study design: This secondary analysis of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be, was a nested case-control study. Participants were prospectively enrolled at eight U.S. centers, with data collection occurring at three standard time points during pregnancy and again after delivery. Our analysis included neonates with birth weights <10th percentile and excluded those with major congenital malformations or suspected or confirmed aneuploidy. The primary outcome was a composite of perinatal morbidity, defined as NICU admission >48 h, NEC, sepsis, RDS, mechanical ventilation, retinopathy of prematurity, seizures, grade 3 or 4 IVH, stillbirth, or death before discharge. Cases were SGA neonates that experienced the primary outcome, and controls were SGA neonates that did not. Maternal factors for potential inclusion in predictive modeling were drawn from a broad list of variables collected as part of the NuMoM2B study, including demographic, anthropometric, clinical, ultrasound, social/behavioral, dietary, and psychological variables. Characteristics that were different in bivariate analysis between cases and controls then underwent further evaluation and refinement. Continuous and multi-category variables were assessed using multiple approaches, including as continuous variables, using standard categories (such as for BMI) as well as empirically-derived cut-points identified by receiver-operating characteristics methodology. The approach for each variable that resulted in the best performance was selected for use in modeling. After variable optimization, multivariable analysis was used to derive prediction models using factors known at mid-pregnancy (Model 1) and delivery (Model 2). Results: Of the original cohort, 865 were eligible and analyzed, with 134 (15.5%) experiencing the primary outcome. After bivariable and multivariable analysis, these variables were included in Model 1: BMI, stress level, diastolic blood pressure, narcotic use (all in 1st trimester), and uterine artery pulsatility index at 16-21 weeks. Model 2 added the following variables to Model 1: preterm delivery, preeclampsia, and suspected fetal growth restriction. When models 1 and 2 were empirically tested and compared to predicted performance to demonstrate calibration, observed morbidity rates approximately followed expected rates within deciles. Models 1 and 2 had respective areas under the receiver-operating characteristic curve of 0.72 (95% CI 0.67-0.76) and 0.84 (0.80-0.88), to predict the composite morbidity. Conclusion: Using a deeply phenotyped cohort of nulliparous women, we created two models with the moderate-good prediction of perinatal morbidity among SGA neonates.Item Prospective Evaluation of Placental Abruption in Nulliparous Women(Taylor & Francis, 2022) Lueth, Amir; Blue, Nathan; Silver, Robert M.; Allshouse, Amanda; Hoffman, Matthew; Grobman, William A.; Simhan, Hyagriv N.; Reddy, Uma; Haas, David M.; Obstetrics and Gynecology, School of MedicineIntroduction: Because most data on placental abruption are derived from retrospective studies, multiple sources of bias may have affected the results. Thus, we aimed to characterize risk factors and outcomes for placental abruption in a large prospective cohort of nulliparous women. Methods: This was a secondary analysis of women enrolled in the Nulliparous Pregnancy Outcomes Study Monitoring-to-be (nuMom2b) study, a prospective observational cohort. Participants were recruited in their first trimester of pregnancy from 8 sites and had 4 study visits, including at delivery. Placental abruption was defined by confirmed clinical criteria. The primary analysis was restricted to abruption identified antepartum and intrapartum. As a secondary analysis, we examined antepartum and intrapartum abruptions separately. We compared risk factors (maternal demographic and clinical characteristics) and outcomes in women with and without placental abruption using univariable and multivariable analyses as appropriate. Results: 9450 women were included in the primary analysis. Abruption was identified in 0.66% (n = 62), of which 35 (56%) were antepartum and 27 (44%) intrapartum. For women with abruption, the mean gestational age at delivery was 35.6 ± 4.4 weeks and 38.8 ± 2.2 weeks for women without abruption. Gravidity was associated with abruption (OR 3.1, 95% CI: 1.6-6.0). In univariate analysis, abruption was associated with cesarean delivery (OR 3.7, 95% CI: 2.2-6.0), blood transfusion (OR 3.8, 95% CI: 1.4-10.7), PPROM (OR 9.0, 95% CI: 5.4-15.1), preterm birth (OR 8.5, 95% CI: 5.1-14.2), SGA (OR 4.0, 95% CI: 2.3-6.95), RDS (OR 5.5, 95% CI: 2.6-11.2), IVH 20.2 (OR 20.2, 95% CI: 5.9-68.8) and ROP (OR 12.2, 95% CI: 2.8-52.6). However, after adjustment for confounders including gestational age, abruption was only associated with increased odds of cesarean delivery and blood transfusion. Results were similar when restricted to antepartum and intrapartum abruptions. Conclusion: Abruption was identified in <1% of nulliparous women. However, few maternal risk factors were identified. Neonatal morbidities were associated with an abruption and were primarily driven by gestational age due to preterm birth.