A Trial of Hyperimmune Globulin to Prevent Congenital Cytomegalovirus Infection.

BACKGROUND: Primary cytomegalovirus (CMV) infection during pregnancy carries a risk of congenital infection and possible severe sequelae. There is no established intervention for preventing congenital CMV infection. METHODS: In this multicenter, double-blind trial, pregnant women with primary CMV infection diagnosed before 24 weeks' gestation were randomly assigned to receive a monthly infusion of CMV hyperimmune globulin (at a dose of 100 mg per kilogram of body weight) or matching placebo until delivery. The primary outcome was a composite of congenital CMV infection or fetal or neonatal death if CMV testing of the fetus or neonate was not performed. RESULTS: From 2012 to 2018, a total of 206,082 pregnant women were screened for primary CMV infection before 23 weeks of gestation; of the 712 participants (0.35%) who tested positive, 399 (56%) underwent randomization. The trial was stopped early for futility. Data on the primary outcome were available for 394 participants; a primary outcome event occurred in the fetus or neonate of 46 of 203 women (22.7%) in the group that received hyperimmune globulin and of 37 of 191 women (19.4%) in the placebo group (relative risk, 1.17; 95% confidence interval [CI] 0.80 to 1.72; P = 0.42). Death occurred in 4.9% of fetuses or neonates in the hyperimmune globulin group and in 2.6% in the placebo group (relative risk, 1.88; 95% CI, 0.66 to 5.41), preterm birth occurred in 12.2% and 8.3%, respectively (relative risk, 1.47; 95% CI, 0.81 to 2.67), and birth weight below the 5th percentile occurred in 10.3% and 5.4% (relative risk, 1.92; 95% CI, 0.92 to 3.99). One participant in the hyperimmune globulin group had a severe allergic reaction to the first infusion. Participants who received hyperimmune globulin had a higher incidence of headaches and shaking chills while receiving infusions than participants who received placebo. CONCLUSIONS: Among pregnant women, administration of CMV hyperimmune globulin starting before 24 weeks' gestation did not result in a lower incidence of a composite of congenital CMV infection or perinatal death than placebo. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Center for Advancing Translational Sciences; ClinicalTrials.gov number, NCT01376778.).

Multiethnic growth standards for fetal body composition and organ volumes derived from 3D ultrasonography.

BACKGROUND: A major goal of contemporary obstetrical practice is to optimize fetal growth and development throughout pregnancy. To date, fetal growth during prenatal care is assessed by performing ultrasonographic measurement of 2-dimensional fetal biometry to calculate an estimated fetal weight. Our group previously established 2-dimensional fetal growth standards using sonographic data from a large cohort with multiple sonograms. A separate objective of that investigation involved the collection of fetal volumes from the same cohort. OBJECTIVE: The Fetal 3D Study was designed to establish standards for fetal soft tissue and organ volume measurements by 3-dimensional ultrasonography and compare growth trajectories with conventional 2-dimensional measures where applicable. STUDY DESIGN: The National Institute of Child Health and Human Development Fetal 3D Study included research-quality images of singletons collected in a prospective, racially and ethnically diverse, low-risk cohort of pregnant individuals at 12 U.S. sites, with up to 5 scans per fetus (N=1730 fetuses). Abdominal subcutaneous tissue thickness was measured from 2-dimensional images and fetal limb soft tissue parameters extracted from 3-dimensional multiplanar views. Cerebellar, lung, liver, and kidney volumes were measured using virtual organ computer aided analysis. Fractional arm and thigh total volumes, and fractional lean limb volumes were measured, with fractional limb fat volume calculated by subtracting lean from total. For each measure, weighted curves (fifth, 50th, 95th percentiles) were derived from 15 to 41 weeks' using linear mixed models for repeated measures with cubic splines. RESULTS: Subcutaneous thickness of the abdomen, arm, and thigh increased linearly, with slight acceleration around 27 to 29 weeks. Fractional volumes of the arm, thigh, and lean limb volumes increased along a quadratic curvature, with acceleration around 29 to 30 weeks. In contrast, growth patterns for 2-dimensional humerus and femur lengths demonstrated a logarithmic shape, with fastest growth in the second trimester. The mid-arm area curve was similar in shape to fractional arm volume, with an acceleration around 30 weeks, whereas the curve for the lean arm area was more gradual. The abdominal area curve was similar to the mid-arm area curve with an acceleration around 29 weeks. The mid-thigh and lean area curves differed from the arm areas by exhibiting a deceleration at 39 weeks. The growth curves for the mid-arm and thigh circumferences were more linear. Cerebellar 2-dimensional diameter increased linearly, whereas cerebellar 3-dimensional volume growth gradually accelerated until 32 weeks followed by a more linear growth. Lung, kidney, and liver volumes all demonstrated gradual early growth followed by a linear acceleration beginning at 25 weeks for lungs, 26 to 27 weeks for kidneys, and 29 weeks for liver. CONCLUSION: Growth patterns and timing of maximal growth for 3-dimensional lean and fat measures, limb and organ volumes differed from patterns revealed by traditional 2-dimensional growth measures, suggesting these parameters reflect unique facets of fetal growth. Growth in these three-dimensional measures may be altered by genetic, nutritional, metabolic, or environmental influences and pregnancy complications, in ways not identifiable using corresponding 2-dimensional measures. Further investigation into the relationships of these 3-dimensional standards to abnormal fetal growth, adverse perinatal outcomes, and health status in postnatal life is warranted.

Nutritional Intake in Dichorionic Twin Pregnancies: A Descriptive Analysis of a Multisite United States Cohort.

INTRODUCTION: Twin gestations have greater nutritional demands than singleton gestations, yet dietary intakes of women with twin gestations have not been well described. METHODS: In a prospective, multi-site US study of 148 women with dichorionic twin gestations (2012-2013), we examined longitudinal changes in diet across pregnancy. Women completed a food frequency questionnaire during each trimester of pregnancy. We examined changes in means of total energy and energy-adjusted dietary components using linear mixed effects models. RESULTS: Mean energy intake (95% CI) across the three trimesters was 2010 kcal/day (1846, 2175), 2177 kcal/day (2005, 2349), 2253 kcal/day (2056, 2450), respectively (P = 0.01), whereas the Healthy Eating Index-2010 was 63.9 (62.1, 65.6), 64.5 (62.6, 66.3), 63.2 (61.1, 65.3), respectively (P = 0.53). DISCUSSION: Women with twin gestations moderately increased total energy as pregnancy progressed, though dietary composition and quality remained unchanged. These findings highlight aspects of nutritional intake that may need to be improved among women carrying twins.

Reducing decisional conflict in decisions about prenatal genetic testing: the impact of a dyadic intervention at the start of prenatal care.

OBJECTIVES: Decisional conflict and regret about prenatal genetic screening and diagnostic tests may have important consequences in the current pregnancy and for future reproductive decisions. Identifying mechanisms that reduce conflict associated with the decision to use or decline these options is necessary for optimal patient counseling. METHODS: We conducted a cluster-randomized controlled trial of a shared decision-making tool (NEST) at the beginning of prenatal care. Enrolled patients completed follow-up surveys at the time of testing (QTT) and in the second-third trimester (QFF), including the Decision Conflict Scale (DCS). Total DCS scores were analyzed using a multivariate linear mixed-effect model. RESULTS: Of the total number of participants (n=502) enrolled, 449 completed the QTT and QFF surveys. The mean age of participants was 31.6±3.8, with most parous at the time of study participation (n=321; 71.7 %). Both the NEST (the intervention) and control groups had lower median total DCS scores at QFF (NEST 13.3 [1.7, 25.0] vs. control 16.7 [1.7, 25.0]; p=0.24) compared to QTT (NEST 20.8 [5.0, 25.0] vs. control 18.3 [3.3, 26.7]; p=0.89). Participants exposed to NEST had lower decisional conflict at QFF compared to control (ß -3.889; [CI -7.341, -0.437]; p=0.027). CONCLUSIONS: Using a shared decision-making tool at the start of prenatal care decreased decisional conflict regarding prenatal genetic testing. Such interventions have the potential to provide an important form of decision-making support for patients facing the unique type of complex and preference-based choices about the use of prenatal genetic tests.

Oral Glucose Tolerance Test in Pregnancy and Subsequent Maternal Hypertension.

OBJECTIVE: The aim of the study is to evaluate whether values and the shape of the glucose curve during the oral glucose tolerance test (OGTT) in pregnancy identify women at risk of developing hypertension (HTN) later in life. STUDY DESIGN: This category includes the secondary analysis of a follow-up from a mild gestational diabetes mellitus (GDM) study that included a treatment trial for mild GDM (n = 458) and an observational cohort of participants with abnormal 1-hour glucose loading test only (normal OGTT, n = 430). Participants were assessed at a median of 7 (IQR 6-8) years after their index pregnancy, and trained staff measured their blood pressure (systolic blood pressure [SBP]; diastolic blood pressure [DBP]). The association between values and the shape of the glucose curve during OGTT in the index pregnancy and the primary outcome defined as elevated BP (SBP ≥120, DBP ≥80 mm Hg, or receiving anti-HTN medications), and secondary outcome defined as stage 1 or higher (SBP ≥130, DBP ≥80 mm Hg, or receiving anti-HTN medications) at follow-up were evaluated using multivariable regression, adjusting for maternal age, body mass index, and pregnancy-associated hypertension during the index pregnancy. RESULTS: There was no association between fasting, 1-hour OGTT, and the outcomes. However, the 2-hour OGTT value was positively associated (adjusted odds ratio [aRR] per 10-unit increase 1.04, 95% CI 1.01-1.08), and the 3-hour was inversely associated (aRR per 10-unit increase 0.96, 95% CI 0.93-0.99) with the primary outcome. When the shape of the OGTT curve was evaluated, a monophasic OGTT response (peak at 1 hour followed by a decline in glucose) was associated with increased risk of elevated BP (41.3vs. 23.5%, aRR 1.66, 95% CI 1.17-2.35) and stage 1 HTN or higher (28.5 vs. 14.7%, aRR 1.83, 95% CI 1.15-2.92), compared with a biphasic OGTT response. CONCLUSION: Among persons with mild GDM or lesser degrees of glucose intolerance, the shape of the OGTT curve during pregnancy may help identify women who are at risk of HTN later in life, with biphasic shape to be associated with lower risk. KEY POINTS: · The shape of the Oral Glucose Tolerance Test curve may help identify patients who are at risk of having elevated BP or HTN 5 to 10 years following pregnancy.. · The 2-hour Oral Glucose Tolerance Test values is positively associated with elevated BP 5 to 10 years following pregnancy.. · This supports the concept of pregnancy as a window to future health and represents a potential novel biomarker for maternal cardiovascular health screening..

Maternal and Neonatal Outcomes in Nulliparous Participants Undergoing Labor Induction by Cervical Ripening Method.

OBJECTIVE: This study aimed to evaluate maternal and neonatal outcomes by method of cervical ripening for labor induction among low-risk nulliparous individuals. STUDY DESIGN: This is a secondary analysis of a multicenter randomized trial of labor induction at 39 weeks versus expectant management in low-risk nulliparous participants. Participants undergoing cervical ripening for labor induction in either group were included. Participants were excluded for preripening membrane rupture, abruption, chorioamnionitis, fetal demise, or cervical dilation ≥3.5 cm. Cervical ripening was defined by the initial method used: prostaglandin only (PGE; referent), Foley with concurrent prostaglandin (Foley-PGE), Foley only (Foley), and Foley with concurrent oxytocin (Foley-oxytocin). Coprimary outcomes were adverse maternal and neonatal composites. Secondary outcomes included cesarean delivery and length of labor and delivery (L&D) stay. Multivariable analysis was used to adjust for patient characteristics. RESULTS: Of 6,106 participants included in the trial, 2,376 (38.9%) met criteria for this analysis. Of these, 1,247 (52.4%) had cervical ripening with PGE, 290 (12.2%) had Foley-PGE, 385 (16.2%) had Foley, and 454 (19.1%) had Foley-oxytocin. The maternal composite outcome was similar among participants who received Foley-PGE (24.1%, adjusted relative risk [aRR] = 1.21, 95% confidence interval [CI]: 0.96-1.52), Foley (21.3%, aRR = 1.16, 95% CI: 0.92-1.45), or Foley-oxytocin (19.4%, aRR = 1.04, 95% CI: 0.83-1.29), compared with PGE (19.7%). The neonatal composite outcome was less frequent in participants who received the Foley-PGE (2.4%, aRR = 0.35, 95% CI: 0.16-0.75) or Foley (3.6%, aRR = 0.51, 95% CI: 0.29-0.89) but did not reach statistical significance for participants who received Foley-oxytocin (4.6%, aRR = 0.63, 95% CI: 0.40-1.01) compared with PGE only (6.8%). Participants who received Foley-PGE or Foley-oxytocin had a shorter L&D stay (adjusted mean difference = -1.97 hours, 95% CI: -3.45 to -0.49 and -5.92 hours, 95% CI: -7.07 to -4.77, respectively), compared with PGE. CONCLUSION: In term low-risk nulliparous participants, Foley alone or concurrent with PGE is associated with a lower risk of adverse neonatal outcomes than with PGE alone. Length of L&D stay was the shortest with concurrent Foley-oxytocin. KEY POINTS: · Adverse maternal outcomes are similar among different methods of cervical ripening in low-risk women.. · Adverse neonatal outcomes are less frequent with use of Foley alone or in combination with PGE.. · The use of Foley alone, or in combination with other agents, appears to be beneficial..

Long-Term Maternal Metabolic and Cardiovascular Phenotypes after a Pregnancy Complicated by Mild Gestational Diabetes Mellitus or Obesity.

OBJECTIVE: The aim of this study was to evaluate the association of mild gestational diabetes mellitus (GDM) and obesity with metabolic and cardiovascular markers 5 to 10 years after pregnancy. STUDY DESIGN: This was a secondary analysis of 5- to 10-year follow-up study of a mild GDM treatment trial and concurrent observational cohort of participants ineligible for the trial with abnormal 1-hour glucose challenge test only. Participants with 2-hour glucose tolerance test at follow-up were included. The primary exposures were mild GDM and obesity. The outcomes were insulinogenic index (IGI), 1/homeostatic model assessment of insulin resistance (HOMA-IR), and cardiovascular markers vascular endothelial growth factor, (VEGF), vascular cell adhesion molecule 1 (VCAM-1), cluster of differentiation 40 ligand (CD40L), growth differentiation factor 15 (GDF-15), and suppression of tumorgenesis 2 (ST-2). Multivariable linear regression estimated the association of GDM and obesity with biomarkers. RESULTS: Of 951 participants in the parent study, 642 (68%) were included. Lower 1/HOMA-IR were observed in treated and untreated GDM groups, compared with non-GDM (mean differences, -0.24 and -0.15; 95% confidence intervals [CIs], -0.36 to -0.12 and -0.28 to -0.03, respectively). Lower VCAM-1 (angiogenesis) was observed in treated GDM group (mean difference, -0.11; 95% CI, -0.19 to -0.03). GDM was not associated with IGI or other biomarkers. Obesity was associated with lower 1/HOMA-IR (mean difference, -0.42; 95% CI, -0.52 to -0.32), but not other biomarkers. CONCLUSION: Prior GDM and obesity are associated with more insulin resistance but not insulin secretion or consistent cardiovascular dysfunction 5 to 10 years after delivery. KEY POINTS: · Mild GDM increases the risk of insulin resistance 5 to 10 years postpartum but not pancreatic dysfunction.. · Obesity increases the risk of insulin resistance 5 to 10 years postpartum but not pancreatic dysfunction.. · Neither mild GDM nor obesity increased the risk of cardiovascular dysfunction 5 to 10 years postpartum..

Hypertensive Disorders of Pregnancy and Long-Term Maternal Cardiovascular and Metabolic Biomarkers.

OBJECTIVE: This study aimed to measure the association between hypertensive disorders of pregnancy (HDP) and long-term maternal metabolic and cardiovascular biomarkers. STUDY DESIGN: Follow-up study of patients who completed glucose tolerance testing 5 to 10 years after enrollment in a mild gestational diabetes mellitus (GDM) treatment trial or concurrent non-GDM cohort. Maternal serum insulin concentrations and cardiovascular markers VCAM-1, VEGF, CD40L, GDF-15, and ST-2 were measured, and insulinogenic index (IGI, pancreatic ß-cell function) and 1/ homeostatic model assessment (insulin resistance) were calculated. Biomarkers were compared by presence of HDP (gestational hypertension or preeclampsia) during pregnancy. Multivariable linear regression estimated the association of HDP with biomarkers, adjusting for GDM, baseline body mass index (BMI), and years since pregnancy. RESULTS: Of 642 patients, 66 (10%) had HDP: 42 with gestational hypertension and 24 with preeclampsia. Patients with HDP had higher baseline and follow-up BMI, higher baseline blood pressure, and more chronic hypertension at follow-up. HDP was not associated with metabolic or cardiovascular biomarkers at follow-up. However, when HDP type was evaluated, patients with preeclampsia had lower GDF-15 levels (oxidative stress/cardiac ischemia), compared with patients without HDP (adjusted mean difference: -0.24, 95% confidence interval: -0.44, -0.03). There were no differences between gestational hypertension and no HDP. CONCLUSION: In this cohort, metabolic and cardiovascular biomarkers 5 to 10 years after pregnancies did not differ by HDP. Patients with preeclampsia may have less oxidative stress/cardiac ischemia postpartum; however, this may have been observed due to chance alone given multiple comparisons. Longitudinal studies are needed to define the impact of HDP during pregnancy and interventions postpartum. KEY POINTS: · Hypertensive disorders of pregnancy were not associated with metabolic dysfunction.. · Cardiovascular dysfunction was not consistently seen after pregnancy hypertension.. · Longitudinal studies with postpartum interventions after preeclampsia are needed..

Evaluation of Hypoglycemia in Neonates of Women at Risk for Late Preterm Delivery: An Antenatal Late Preterm Steroids Trial Cohort Study.

OBJECTIVE: In the antenatal late preterm steroids (ALPS) trial betamethasone significantly decreased short-term neonatal respiratory morbidity but increased the risk of neonatal hypoglycemia, diagnosed only categorically (<40 mg/dL). We sought to better characterize the nature, duration, and treatment for hypoglycemia. STUDY DESIGN: Secondary analysis of infants from ALPS, a multicenter trial randomizing women at risk for late preterm delivery to betamethasone or placebo. This study was a reabstraction of all available charts from the parent trial, all of which were requested. Unreviewed charts included those lost to follow-up or from sites not participating in the reabstraction. Duration of hypoglycemia (<40 mg/dL), lowest value and treatment, if any, were assessed by group. Measures of association and regression models were used where appropriate. RESULTS: Of 2,831 randomized, 2,609 (92.2%) were included. There were 387 (29.3%) and 223 (17.3%) with hypoglycemia in the betamethasone and placebo groups, respectively (relative risk [RR]: 1.69, 95% confidence interval [CI]: 1.46-1.96). Hypoglycemia generally occurred in the first 24 hours in both groups: 374/385 (97.1%) in the betamethasone group and 214/222 (96.4%) in the placebo group (p = 0.63). Of 387 neonates with hypoglycemia in the betamethasone group, 132 (34.1%) received treatment, while 73/223 (32.7%) received treatment in placebo group (p = 0.73). The lowest recorded blood sugar was similar between groups. Most hypoglycemia resolved by 24 hours in both (93.0 vs. 89.3% in the betamethasone and placebo groups, respectively, p = 0.18). Among infants with hypoglycemia in the first 24 hours, the time to resolution was shorter in the betamethasone group (2.80 [interquartile range: 2.03-7.03) vs. 3.74 (interquartile range: 2.15-15.08) hours; p = 0.002]. Persistence for >72 hours was rare and similar in both groups, nine (2.4%, betamethasone) and four (1.9%, placebo, p = 0.18). CONCLUSION: In this cohort, hypoglycemia was transient and most received no treatment, with a quicker resolution in the betamethasone group. Prolonged hypoglycemia was uncommon irrespective of steroid exposure. KEY POINTS: · Hypoglycemia was transient and approximately two-thirds received no treatment.. · Neonates in the ALPS trial who received betamethasone had a shorter time to resolution than those with hypoglycemia in the placebo group.. · Prolonged hypoglycemia occurred in approximately 2 out of 100 late preterm newborns, irrespective of antenatal steroid exposure..

Cervical Pessary for Prevention of Preterm Birth in Individuals With a Short Cervix: The TOPS Randomized Clinical Trial.

Importance: A short cervix as assessed by transvaginal ultrasound is an established risk factor for preterm birth. Study findings for a cervical pessary to prevent preterm delivery in singleton pregnancies with transvaginal ultrasound evidence of a short cervix have been conflicting. Objective: To determine if cervical pessary placement decreases the risk of preterm birth or fetal death prior to 37 weeks among individuals with a short cervix. Design, Setting, and Participants: We performed a multicenter, randomized, unmasked trial comparing a cervical pessary vs usual care from February 2017 through November 5, 2021, at 12 centers in the US. Study participants were nonlaboring individuals with a singleton pregnancy and a transvaginal ultrasound cervical length of 20 mm or less at gestations of 16 weeks 0 days through 23 weeks 6 days. Individuals with a prior spontaneous preterm birth were excluded. Interventions: Participants were randomized 1:1 to receive either a cervical pessary placed by a trained clinician (n = 280) or usual care (n = 264). Use of vaginal progesterone was at the discretion of treating clinicians. Main Outcome and Measures: The primary outcome was delivery or fetal death prior to 37 weeks. Results: A total of 544 participants (64%) of a planned sample size of 850 were enrolled in the study (mean age, 29.5 years [SD, 6 years]). Following the third interim analysis, study recruitment was stopped due to concern for fetal or neonatal/infant death as well as for futility. Baseline characteristics were balanced between participants randomized to pessary and those randomized to usual care; 98.9% received vaginal progesterone. In an as-randomized analysis, the primary outcome occurred in 127 participants (45.5%) randomized to pessary and 127 (45.6%) randomized to usual care (relative risk, 1.00; 95% CI, 0.83-1.20). Fetal or neonatal/infant death occurred in 13.3% of those randomized to receive a pessary and in 6.8% of those randomized to receive usual care (relative risk, 1.94; 95% CI, 1.13-3.32). Conclusions and Relevance: Cervical pessary in nonlaboring individuals with a singleton gestation and with a cervical length of 20 mm or less did not decrease the risk of preterm birth and was associated with a higher rate of fetal or neonatal/infant mortality. Trial Registration: ClinicalTrials.gov Identifier: NCT02901626.

Hypertension in pregnancy and adverse outcomes among low-risk nulliparous women expectantly managed at or after 39 weeks: a secondary analysis of a randomised controlled trial.

OBJECTIVE: To evaluate whether hypertensive disorders of pregnancy (HDP) among low-risk nulliparous women expectantly managed at or after 39 weeks of gestation are associated with adverse outcomes. DESIGN: Secondary analysis of a randomised trial. SETTING: Multicentre, USA. POPULATION: Individuals in the expectantly managed group who delivered on or after 39 weeks. METHODS: Multivariable analysis to estimate adjusted relative risks (aRR) for binomial outcomes, adjusted odds ratios (aOR) for multinomial outcomes and 95% CI. MAIN OUTCOME MEASURES: Composite adverse maternal outcome including placental abruption, pulmonary oedema, postpartum haemorrhage, postpartum infection, venous thromboembolism or intensive care unit admission. Secondary outcomes included a composite of perinatal death or severe neonatal complications, mode of delivery, small and large for gestational age and neonatal intermediate or intensive unit length of stay. RESULTS: Of the 3044 women randomised to expectant management in the original trial, 2718 (89.3%) were eligible for this analysis, of whom 373 (13.7%) developed HDP. Compared with participants who remained normotensive, those who developed HDP were more likely to experience the maternal composite (12% versus 6%, aRR 1.84, 95% CI 1.33-2.54) and caesarean delivery (29% versus 23%, aOR 1.32, 95% CI 1.01-1.71). Differences between the two groups were not significantly different for the adverse perinatal composite (7% versus 5%, aRR 1.38, 95% CI 0.92-2.07) or for other secondary outcomes. CONCLUSION: Almost 14% of low-risk nulliparous individuals expectantly managed at 39 weeks developed HDP, and were more likely to experience adverse maternal outcomes compared with those who did not develop HDP. TWEETABLE ABSTRACT: Almost 14% of low-risk nulliparous individuals expectantly managed at 39 weeks developed hypertensive disorders of pregnancy, and were more likely to experience adverse maternal outcomes compared with those who did not develop hypertensive disorders.

Fetal Growth Biometry as Predictors of Shoulder Dystocia in a Low-Risk Obstetrical Population.

OBJECTIVE: This study aimed to evaluate fetal biometrics as predictors of shoulder dystocia (SD) in a low-risk obstetrical population. STUDY DESIGN: Participants were enrolled as part of a U.S.-based prospective cohort study of fetal growth in low-risk singleton gestations (n = 2,802). Eligible women had liveborn singletons ≥2,500 g delivered vaginally. Sociodemographic, anthropometric, and pregnancy outcome data were abstracted by research staff. The diagnosis of SD was based on the recorded clinical impression of the delivering physician. Simple logistic regression models were used to examine associations between fetal biometrics and SD. Fetal biometric cut points, selected by Youden's J and clinical determination, were identified to optimize predictive capability. A final model for SD prediction was constructed using backward selection. Our dataset was randomly divided into training (60%) and test (40%) datasets for model building and internal validation. RESULTS: A total of 1,691 women (98.7%) had an uncomplicated vaginal delivery, while 23 (1.3%) experienced SD. There were no differences in sociodemographic or maternal anthropometrics between groups. Epidural anesthesia use was significantly more common (100 vs. 82.4%; p = 0.03) among women who experienced SD compared with those who did not. Amniotic fluid maximal vertical pocket was also significantly greater among SD cases (5.8 ± 1.7 vs. 5.1 ± 1.5 cm; odds ratio = 1.32 [95% confidence interval: 1.03,1.69]). Several fetal biometric measures were significantly associated with SD when dichotomized based on clinically selected cut-off points. A final prediction model was internally valid with an area under the curve of 0.90 (95% confidence interval: 0.81, 0.99). At a model probability of 1%, sensitivity (71.4%), specificity (77.5%), positive (3.5%), and negative predictive values (99.6%) did not indicate the ability of the model to predict SD in a clinically meaningful way. CONCLUSION: Other than epidural anesthesia use, neither sociodemographic nor maternal anthropometrics were significantly associated with SD in this low-risk population. Both individually and in combination, fetal biometrics had limited ability to predict SD and lack clinical usefulness. KEY POINTS: · SD unpredictable in low-risk women.. · Fetal biometry does not reliably predict SD.. · Epidural use associated with increased SD risk.. · SD prediction models clinically inefficient..

Maternal Diabetes and Intrapartum Fetal Electrocardiogram.

OBJECTIVE: Fetal electrocardiogram (ECG) ST changes are associated with fetal cardiac hypoxia. Our objective was to evaluate ST changes by maternal diabetic status and stage of labor. METHODS: This was a secondary analysis of a multicentered randomized-controlled trial in which laboring patients with singleton gestations underwent fetal ECG scalp electrode placement and were randomly assigned to masked or unmasked ST-segment readings. Our primary outcome was the frequency of fetal ECG tracings with ST changes by the stage of labor. ECG tracings were categorized into mutually exclusive groups (ST depression, ST elevation without ST depression, or no ST changes). We compared participants with DM, gestational diabetes mellitus (GDM), and no DM. RESULTS: Of the 5,436 eligible individuals in the first stage of labor (95 with pregestational DM and 370 with GDM), 4,427 progressed to the second stage. ST depression occurred more frequently in the first stage of labor in participants with pregestational DM (15%, adjusted odds ratio [aOR] 2.20, 95% confidence interval [CI] 1.14-4.24) and with GDM (9.5%, aOR 1.51, 95% CI 1.02-2.25) as compared with participants without DM (5.7%). The frequency of ST elevation was similar in participants with pregestational DM (33%, aOR 0.79, 95% CI 0.48-1.30) and GDM (33.2%, aOR 0.91, 95% CI 0.71-1.17) as compared with those without DM (34.2%). In the second stage, ST depression did not occur in participants with pregestational DM (0%) and occurred more frequently in participants with GDM (3.5%, aOR 2.01, 95% CI 1.02-3.98) as compared with those without DM (2.0%). ST elevation occurred more frequently in participants with pregestational DM (30%, aOR 1.81, 95% CI 1.02-3.22) but not with GDM (19.0%, aOR 1.06, 95% CI 0.77-1.47) as compared with those without DM (17.8%). CONCLUSION: ST changes in fetal ECG occur more frequently in fetuses of diabetic mothers during labor. CLINICALTRIALS: gov number, NCT01131260. PRECIS: ST changes in fetal ECG, a marker of fetal cardiac hypoxia, occur more frequently in fetuses of diabetic parturients. KEY POINTS: · Fetal hypertrophic cardiomyopathy (HCM) and cardiac dysfunction occur frequently among fetuses of diabetic patients.. · Fetal ECG changes such as ST elevation and depression reflect cardiac hypoxia.. · Fetuses of diabetic patients demonstrate a higher prevalence of fetal ECG tracings with ST changes..

Racial/Ethnic Differences in Prenatal Supplement and Medication Use in Low-Risk Pregnant Women.

OBJECTIVE: This study aimed to describe the overall quantity and type of supplements and medications used during pregnancy in a low-risk cohort and to examine any racial/ethnic differences in intake. STUDY DESIGN: We used data from 2,164 racially/ethnically diverse, nonobese, and low-risk pregnant women participating without pre-pregnancy chronic conditions in a prospective cohort study at 12 sites across the United States. Medication data were self-reported as free text in enrollment, follow-up visit questionnaires, and abstracted from medical records at delivery. Supplements and medications data were mapped to their active ingredients and categorized into corresponding classes using the Slone Drug Dictionary. The total number and classes of supplements and medications consumed during pregnancy were calculated. Modified Poisson regression models were used to estimate the racial/ethnic differences in supplements and medications intake. All models were adjusted for maternal sociodemographic factors and study site. RESULTS: 98% of women took at least one supplement during pregnancy, with prenatal vitamins/multivitamins being most common. While only 31% reported taking no medications during pregnancy, 23% took one, 18% took two, and 28% took three or more. The percentage of women taking at least one medication during pregnancy was highest among non-Hispanic white women and lowest among Asians (84 vs. 55%, p < 0.001). All racial/ethnic groups reported taking the same top four medication classes including central nervous system agents, gastrointestinal drugs, anti-infective agents, and antihistamines. Compared with non-Hispanic white women, Hispanic (adjusted relative risk [aRR]: 0.84, 95% confidence interval [CI]: 0.71-0.98), and Asian women (aRR: 0.83, 95% CI: 0.70-0.98) were less likely to take central nervous system agents, as well as gastrointestinal drugs (Hispanics aRR: 0.79, 95% CI: 0.66-0.94; Asians aRR = 0.75, 95% CI: 0.63-0.90), and antihistamines (Hispanics aRR: 0.65, 95% CI: 0.47-0.92). CONCLUSION: Supplement intake was nearly universal. Medication use was also common among this low-risk pregnancy cohort and differed by race/ethnicity. GOV IDENTIFIER: NCT00912132. KEY POINTS: · In women without chronic conditions, medication use is common.. · Racial/ethnic differences exist in prenatal medications use.. · Almost all women use supplements during pregnancy..

Neonatal Birthweight, Infant Feeding, and Childhood Metabolic Markers.

OBJECTIVE: Antenatal and early neonatal nutritional environment may influence later metabolic health. Infants of mothers with gestational diabetes mellitus (GDM) have higher risk for childhood obesity and metabolic syndrome (MetS). Leptin and adiponectin are known biomarkers for MetS and may guide interventions to reduce later obesity. We sought to examine the relationship between birthweight, early infancy feeding practices, and biomarkers for MetS in offspring of women with mild GDM. STUDY DESIGN: Secondary analysis of a prospective observational follow-up study on the offspring of women who participated in a multicenter randomized treatment trial on mild GDM. Children were evaluated by research coordinators and biospecimens collected at the age of 5 to 10. Plasma concentrations of leptin and adiponectin were compared between large for gestational age (LGA) and average birthweight (AGA) infants, and according to whether solid foods were introduced early (<6 months of age) or at the recommended age (≥6 months of age). Multivariable analysis adjusted for fetal sex, race/ethnicity, and maternal body mass index. RESULTS: Leptin and adiponectin were measured in 336 plasma samples. In bivariate analysis, compared with AGA children, LGA children had lower leptin (5.0 ng/mL [3.6-6.0] vs. 5.8 ng/mL [4.5 = 6.6], p = 0.01) and similar adiponectin (6.3 µg/mL [5.1-7.9] vs. 6.4 µg/mL [5.3-8.6], p = 0.49) concentrations. Maternal/child characteristics were similar between the early/delayed solid feeding groups. Leptin and adiponectin concentrations were similar in the early fed and delayed feeding groups (5.8 ng/mL [4.6-6.7] vs. 5.6 ng/mL [4.2-6.6], p = 0.50 and 6.4 µg/mL [5.4-8.1] vs. 6.4 µg/mL [5.1-8.8], p = 0.85, respectively). After controlling for covariates, children who were LGA and AGA at birth had similar leptin concentrations. CONCLUSION: Birthweight and early infancy feeding practice are not associated with alterations in leptin and adiponectin in children of women with mild GDM. KEY POINTS: · Adipocytokines are markers of metabolic status.. · Children of women with mild GDM may be at risk for MetS.. · Biomarkers similar in LGA and AGA groups.. · Biomarkers similar in early and delayed solid-fed groups.. · Nonhuman milk does not modify effect of feeding practice..

The Association between Prenatal Nicotine Exposure and Offspring's Hearing Impairment.

OBJECTIVE: The objective of this study is to evaluate whether there is an association between in-utero exposure to nicotine and subsequent hearing dysfunction. PATIENTS AND METHODS: Secondary analysis of a multicenter randomized trial to prevent congenital cytomegalovirus (CMV) infection among gravidas with primary CMV infection was conducted. Monthly intravenous immunoglobulin hyperimmune globulin therapy did not influence the rate of congenital CMV. Dyads with missing urine, fetal or neonatal demise, infants diagnosed with a major congenital anomaly, congenital CMV infection, or with evidence of middle ear dysfunction were excluded. The primary outcome was neonatal hearing impairment in one or more ears defined as abnormal distortion product otoacoustic emissions (DPOAEs; 1 to 8 kHz) that were measured within 42 days of birth. DPOAEs were interpreted using optimized frequency-specific level criteria. Cotinine was measured via enzyme-linked immunosorbent assay kits in maternal urine collected at enrollment and in the third trimester (mean gestational age 16.0 and 36.7 weeks, respectively). Blinded personnel ran samples in duplicates. Maternal urine cotinine >5 ng/mL at either time point was defined as in-utero exposure to nicotine. Multivariable logistic regression included variables associated with the primary outcome and with the exposure (p < 0.05) in univariate analysis. RESULTS: Of 399 enrolled patients in the original trial, 150 were included in this analysis, of whom 46 (31%) were exposed to nicotine. The primary outcome occurred in 18 (12%) newborns and was higher in nicotine-exposed infants compared with those nonexposed (15.2 vs. 10.6%, odds ratio [OR] 1.52, 95% confidence interval [CI] 0.55-4.20), but the difference was not significantly different (adjusted odds ratio [aOR] = 1.0, 95% CI 0.30-3.31). This association was similar when exposure was stratified as heavy (>100 ng/mL, aOR 0.72, 95% CI 0.15-3.51) or mild (5-100 ng/mL, aOR 1.28, 95% CI 0.33-4.95). There was no association between nicotine exposure and frequency-specific DPOAE amplitude. CONCLUSION: In a cohort of parturients with primary CMV infection, nicotine exposure was not associated with offspring hearing dysfunction assessed with DPOAEs. KEY POINTS: · Nicotine exposure was quantified from maternal urine.. · Nicotine exposure was identified in 30% of the cohort.. · Exposure was not associated with offspring hearing dysfunction..

Labor Induction versus Expectant Management in Low-Risk Nulliparous Women.

BACKGROUND: The perinatal and maternal consequences of induction of labor at 39 weeks among low-risk nulliparous women are uncertain. METHODS: In this multicenter trial, we randomly assigned low-risk nulliparous women who were at 38 weeks 0 days to 38 weeks 6 days of gestation to labor induction at 39 weeks 0 days to 39 weeks 4 days or to expectant management. The primary outcome was a composite of perinatal death or severe neonatal complications; the principal secondary outcome was cesarean delivery. RESULTS: A total of 3062 women were assigned to labor induction, and 3044 were assigned to expectant management. The primary outcome occurred in 4.3% of neonates in the induction group and in 5.4% in the expectant-management group (relative risk, 0.80; 95% confidence interval [CI], 0.64 to 1.00). The frequency of cesarean delivery was significantly lower in the induction group than in the expectant-management group (18.6% vs. 22.2%; relative risk, 0.84; 95% CI, 0.76 to 0.93). CONCLUSIONS: Induction of labor at 39 weeks in low-risk nulliparous women did not result in a significantly lower frequency of a composite adverse perinatal outcome, but it did result in a significantly lower frequency of cesarean delivery. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development; ARRIVE ClinicalTrials.gov number, NCT01990612 .).

The impact of the emergence of COVID-19 on women's prenatal genetic testing decisions.

OBJECTIVE: We conducted a study to examine the impact of COVID on patients' access and utilization of prenatal genetic screens and diagnostic tests at the onset of the COVID-19 pandemic in the United States. METHODS: We conducted telephone interviews with 40 patients to examine how the pandemic affected prenatal genetic screening and diagnostic testing decisions during the initial months of the pandemic in the United States. An interview guide queried experiences with the ability to access information about prenatal genetic testing options and to utilize the tests when desired. Audio recordings were transcribed and coded using NVivo 12. Analysis was conducted using Grounded Theory. RESULTS: The pandemic did not alter most participants' decisions to undergo prenatal genetic testing. Yet, it did impact how participants viewed the risks and benefits of testing and timing of testing. There was heightened anxiety among those who underwent testing, stemming from the risk of viral exposure and the fear of being alone if pregnancy loss or fetal abnormality was identified at the time of an ultrasound-based procedure. CONCLUSION: The pandemic may impact patients' access and utilization of prenatal genetic tests. More research is needed to determine how best to meet pregnant patients' decision-making needs during this time.

Decision-making for prenatal genetic screening: how will pregnant women navigate a growing number of aneuploidy and carrier screening options?

BACKGROUND: Prenatal genetic screens, including carrier screening (CS) and aneuploidy screening (AS), comprise an important component of reproductive healthcare delivery. Clinical practice guidelines emphasize the importance of informed decision-making and patient's preferences regarding the use of these screens. Yet, it is unclear how to achieve this ideal as prenatal genetic screening options rapidly become more complex and increasingly available to patients. With increased complexity and availability of reproductive testing options, decision-support strategies are critical to prepare patients to consider AS and/or CS. METHODS: A self-administered survey evaluated knowledge and decision-making preferences for expanded carrier (CS) and aneuploidy (AS) prenatal screening. The survey was administered to participants before their first prenatal visit to assess baseline decision-making needs and preference at the initiation of prenatal care. Analysis was approached as a descriptive process. RESULTS: Participants had similar familiarity with the concepts associated with AS compared to CS; mean knowledge scores for CS was 0.59 [possible range 0.00 to 1.00] and 0.55 for AS. Participants reported preferences to learn about a range of conditions, including those with severe or mild impact, childhood-onset, and adult-onset. Decision-making preference with respect to learning about the associated disease phenotypes for the contained on AS and CS panel shifted with the complexity of the panel, with a greater preference to learn about conditions post-test compared pre-test education as panels increased from 5 to 100 conditions. CONCLUSION: Patients' baseline knowledge of prenatal genetic screens coupled with evolving decision-making preferences presents challenges for the delivery of prenatal genetic screens. This calls for the development and implementation of innovative approaches to support pregnant patients' decision-making commensurate with advances in prenatal genomics.