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Objective To assess whether neonatal morbidities evident by the time of hospital discharge are associated with subsequent cerebral palsy (CP) or death. Study Design This is a secondary analysis of data from a multicenter placebo-controlled trial of magnesium sulfate for the prevention of CP. The association between prespecified intermediate neonatal outcomes (n = 11) and demographic and clinical factors (n = 10) evident by the time of discharge among surviving infants (n = 1889) and the primary outcome of death or moderate/severe CP at age 2 (n = 73) was estimated, and a prediction model was created. Results Gestational age in weeks at delivery (odds ratio [OR]: 0.74, 95% confidence interval [CI]: 0.67–0.83), grade III or IV intraventricular hemorrhage (IVH) (OR: 5.3, CI: 2.1–13.1), periventricular leukomalacia (PVL) (OR: 46.4, CI: 20.6–104.6), and male gender (OR: 2.5, CI: 1.4–4.5) were associated with death or moderate/severe CP by age 2. Outcomes not significantly associated with the primary outcome included respiratory distress syndrome, bronchopulmonary dysplasia, seizure, necrotizing enterocolitis, neonatal hypotension, 5-minute Apgar score, sepsis, and retinopathy of prematurity. Using all patients, the receiver operating characteristic curve for the final prediction model had an area under the curve of 0.84 (CI: 0.78–0.89). Using these data, the risk of death or developing CP by age 2 can be calculated for individual surviving infants. Conclusion IVH and PVL were the only neonatal complications evident at discharge that contributed to an individual infant's risk of the long-term outcomes of death or CP by age 2. A model that includes these morbidities, gestational age at delivery, and gender is predictive of subsequent neurologic sequelae. Key Points Factors known at hospital discharge are identified which are independently associated with death or CP by age 2. A model was created and validated using these findings to counsel parents. The risk of death or CP can be calculated at the time of hospital discharge. [ABSTRACT FROM AUTHOR]

Objective The fetal consequences of intrapartum fetal tachycardia with maternal fever or clinical chorioamnionitis are not well studied. We evaluated the association between perinatal morbidity and fetal tachycardia in the setting of intrapartum fever. Study Design Secondary analysis of a multicenter randomized control trial that enrolled 5,341 healthy laboring nulliparous women ≥36 weeks' gestation. Women with intrapartum fever ≥ 38.0°C (including those meeting criteria for clinical chorioamnionitis) after randomization were included in this analysis. Isolated fetal tachycardia was defined as fetal heart rate (FHR) ≥160 beats per minute for at least 10 minutes in the absence of other FHR abnormalities. FHR abnormalities other than tachycardia were excluded from the analysis. The primary outcome was a perinatal composite (5-minute Apgar's score ≤3, intubation, chest compressions, or mortality). Secondary outcomes included low arterial cord pH (pH < 7.20), base deficit ≥12, and cesarean delivery. Results A total of 986 (18.5%) of women in the trial developed intrapartum fever, and 728 (13.7%) met criteria to be analyzed; of these, 728 women 336 (46.2%) had maternal-fetal medicine (MFM) reviewer-defined fetal tachycardia, and 349 of the 550 (63.5%) women during the final hour of labor had validated software (PeriCALM) defined fetal tachycardia. After adjusting for confounders, isolated fetal tachycardia was not associated with a significant difference in the composite perinatal outcome (adjusted odds ratio [aOR] = 3.15 [0.82–12.03]) compared with absence of tachycardia. Fetal tachycardia was associated with higher odds of arterial cord pH <7.2, aOR = 1.48 (1.01–2.17) and of infants with a base deficit ≥ 12, aOR = 2.42 (1.02–5.77), but no significant difference in the odds of cesarean delivery, aOR = 1.33 (0.97–1.82). Conclusion Fetal tachycardia in the setting of intrapartum fever or chorioamnionitis is associated with significantly increased fetal acidemia defined as a pH <7.2 and base excess ≥12 but not with a composite perinatal morbidity. Key Points The perinatal outcomes associated with fetal tachycardia in the setting of maternal fever are undefined. Fetal tachycardia was not significantly associated with perinatal morbidity although the sample size was limited. Fetal tachycardia was associated with an arterial cord pH <7.2 and base deficit of 12 or greater. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective  We sought to determine if there is an association between fibroblast growth factor 21 (FGF21) levels and a history of gestational diabetes mellitus (GDM) in women with and without metabolic dysfunction, defined as a diagnosis of metabolic syndrome or type 2 diabetes (T2DM), 5 to 10 years following participation in a multiple cohort GDM study. Study Design  At 5 to 10 years after index pregnancy, women underwent a follow-up visit and were categorized as having no metabolic syndrome, metabolic syndrome, or T2DM. FGF21 levels were compared between women who did and did not have a history of GDM using multivariable linear regression. Results  Among 1,889 women, 950 underwent follow-up and 796 had plasma samples analyzed (413 GDM and 383 non-GDM). Total 30.7% of women had been diagnosed with T2DM or metabolic syndrome. Overall, there was no difference in median FGF21 levels in pg/mL between the prior GDM and non-GDM groups (p  = 0.12), and the lack of association was observed across all three metabolic categories at follow-up (p for interaction = 0.70). Conclusion  There was no association between FGF21 levels and prior history of mild GDM in women with and without metabolic dysfunction 5 to 10 years after the index pregnancy (ClinicalTrials.gov number, NCT00069576, original trial). [ABSTRACT FROM AUTHOR]

Objective  The main purpose of this article is to evaluate whether identification and treatment of women with mild gestational diabetes mellitus (GDM) during pregnancy affects subsequent maternal body mass index (BMI), anthropometry, metabolic syndrome, and risk of diabetes. Study Design  This is a follow-up study of women who participated in a randomized controlled treatment trial for mild GDM. Women were enrolled between 5 and 10 years after their index pregnancy. Participants underwent blood pressure, height, weight, and anthropometric measurements by trained nursing personnel using a standardized approach. A nurse-assisted questionnaire regarding screening and treatment of diabetes or hypercholesterolemia, diet, and physical activity was completed. Laboratory evaluation included fasting serum glucose, fasting insulin, oral glucose tolerance test, and a lipid panel. Subsequent diabetes, metabolic syndrome, obesity, and adiposity in those diagnosed with mild GDM and randomized to nutritional counseling and medical therapy (treated) were compared with those who underwent routine pregnancy management (untreated). Multivariable analyses were performed adjusting for race/ethnicity and years between randomization and follow-up visit. Results  Four-hundred fifty-seven women with mild GDM during the index pregnancy were included in this analysis (243 treated; 214 untreated) and evaluated at a median 7 years after their index pregnancy. Baseline and follow-up characteristics were similar between treatment groups. Frequency of diabetes (9.2 vs. 8.5%, p =0.80), metabolic syndrome (32.2 vs. 34.3%, p =0.63), as well as adjusted mean values of homeostasis model assessment for insulin resistance (2.5 vs. 2.3, p =0.11) and BMI (29.4 vs. 29.1 kg/m 2 , p =0.67) were also not different. Conclusion  Identification and treatment of women with mild GDM during pregnancy had no discernible impact on subsequent diabetes, metabolic syndrome, or obesity 7 years after delivery. [ABSTRACT FROM AUTHOR]

Objective  This study aimed to evaluate the association between clinical and examination features at admission and late preterm birth. Study Design  The present study is a secondary analysis of a randomized trial of singleton pregnancies at 34 0/7 to 36 5/7 weeks' gestation. We included women in spontaneous preterm labor with intact membranes and compared them by gestational age at delivery (preterm vs. term). We calculated a statistical cut-point optimizing the sensitivity and specificity of initial cervical dilation and effacement at predicting preterm birth and used multivariable regression to identify factors associated with late preterm delivery. Results  A total of 431 out of 732 (59%) women delivered preterm. Cervical dilation ≥ 4 cm was 60% sensitive and 68% specific for late preterm birth. Cervical effacement ≥ 75% was 59% sensitive and 65% specific for late preterm birth. Earlier gestational age at randomization, nulliparity, and fetal malpresentation were associated with late preterm birth. The final regression model including clinical and examination features significantly improved late preterm birth prediction (81% sensitivity, 48% specificity, area under the curve = 0.72, 95% confidence interval [CI]: 0.68–0.75, and p -value < 0.01). Conclusion  Four in 10 women in late-preterm labor subsequently delivered at term. Combination of examination and clinical features (including parity and gestational age) improved late-preterm birth prediction. [ABSTRACT FROM AUTHOR]

Objective  To evaluate sex-specific genetic susceptibility to adverse neurodevelopmental outcome (ANO, defined as cerebral palsy [CP], mental, or psychomotor delay) at risk for early preterm birth (EPTB, < 32 weeks). Study Design  Secondary case–control analysis of a trial of magnesium sulfate (MgSO 4) before anticipated EPTB for CP prevention. Cases are infants who died by the age of 1 year or developed ANO. Controls, matched by maternal race and infant sex, were neurodevelopmentally normal survivors. Neonatal DNA was evaluated for 80 polymorphisms in inflammation, coagulation, vasoregulation, excitotoxicity, and oxidative stress pathways using Taqman assays. The primary outcome for this analysis was sex-specific ANO susceptibility. Conditional logistic regression estimated each polymorphism's odds ratio (OR) by sex stratum, adjusting for gestational age, maternal education, and MgSO 4 -corticosteroid exposures. Holm–Bonferroni corrections, adjusting for multiple comparisons (p  < 7.3 × 10 −4), accounted for linkage disequilibrium between markers. Results  Analysis included 211 cases (134 males; 77 females) and 213 controls (130 males; 83 females). An interleukin-6 (IL6) polymorphism (rs2069840) was associated with ANO in females (OR: 2.6, 95% confidence interval [CI]: 1.5–4.7; p  = 0.001), but not in males (OR: 0.8, 95% CI: 0.5–1.2; p  = 0.33). The sex-specific effect difference was significant (p  = 7.0 × 10 −4) and was unaffected by MgSO 4 exposure. No other gene–sex associations were significant. Conclusion  An IL6 gene locus may confer susceptibility to ANO in females, but not males, after EPTB. [ABSTRACT FROM AUTHOR]

Achieving maternal euglycemia in women with pregestational and gestational diabetes mellitus is critical to decreasing the risk of neonatal hypoglycemia, as maternal blood glucose levels around the time of delivery are directly related to the risk of hypoglycemia in the neonate. Many institutions use continuous insulin and glucose infusions during the intrapartum period, although practices are widely variable. At Northwestern Memorial Hospital, the "Management of the Perinatal Patient with Diabetes" policy and protocol was developed to improve consistency of management while also allowing individualization appropriate for the patient's specific diabetic needs. This protocol introduced standardized algorithms based on maternal insulin requirements to drive real-time maternal glucose control during labor as well as provided guidelines for postpartum glycemic control. This manuscript describes the development and implementation of this protocol to encourage other institutions to adopt a standardized protocol that allows highly individualized intrapartum care to women with diabetes. [ABSTRACT FROM AUTHOR]

Objective To evaluate the association of magnesium sulfate (MgSO4) exposure and candidate gene polymorphisms with adverse neurodevelopmental outcomes following preterm birth. Study Design We performed a nested case-control analysis of a randomized trial of maternal MgSO4 before anticipated preterm birth for the prevention of cerebral palsy (CP). Cases were children who died within 1 year of life or were survivors with abnormal neurodevelopment at age 2 years. Controls were race- and sex-matched survivors with normal neurodevelopment. We analyzed 45 candidate gene polymorphisms in inflammation, coagulation, and vascular regulation pathways and their association with (1) psychomotor delay, (2) mental delay, (3) CP, and (4) combined outcome of death/CP. Logistic regression analyses, conditional on maternal race and child sex, and adjusted for treatment group, gestational age at birth and maternal education, were performed. Results Four hundred and six subjects, 211 cases and 195 controls, were analyzed. The strongest association was for IL6R (rs 4601580) in which each additional copy of the minor allele was associated with an increased risk of psychomotor delay (adjusted odds ratio 3.3; 95% confidence interval, 1.7-6.5; p < 0.001). Conclusion Candidate gene polymorphisms are associated with death and adverse neurodevelopmental outcomes following preterm birth. MgSO4 may abrogate this genotype association for some loci. [ABSTRACT FROM AUTHOR]

Objective The objective was to estimate the optimal screen-positive 1-hour 50 g glucose challenge test (GCT) threshold for gestational diabetes (GDM) and predictive characteristics of increasing screen-positive GCT threshold values (135-199 mg/dL) for GDM. Study Design It is a secondary analysis of a multicenter mild GDM study. At 24 to 30 weeks' gestation, women with elevated GCT (135-199 mg/dL) completed a diagnostic 3-hour oral glucose tolerance test (OGTT). A novel change-point analysis method was used to compare the GDM rates for the adjacent GCT values, delineating categories of changing risk such that values within categories have equal risk for GDM. Positive (PPV) and negative (NPV) predictive values for GDM were computed for increasing GCT cut-offs. Results In 7,280 women with both GCT (135-199 mg/dL) and OGTT results, 4 GDM risk- equivalent GCT categories were identified with escalations at 144, 158, and 174 mg/dL (all p-values <0.05). The PPV for GDM increased from 33 to 64% as GCT increased from 135 to 199 mg/dL, while the NPV decreased from 80 to 67%. PPVs were only 20% and 61% for risk-equivalent categories of 135 to 143 mg/dL and 174 to 199 mg/dL, respectively. Conclusion Elevated GCT cut-off values between 135 and 143 mg/dL may carry equivalent GDM risk. No threshold GCTvalue <199 mg/dL alone sufficiently predicts GDM. [ABSTRACT FROM AUTHOR]

Objective To evaluate trends in the proportions and outcomes of dichorionic-triamniotic (DT) compared with trichorionic-triamniotic (TT) triplet gestations. Methods This is a retrospective cohort of all triplet gestations identified by first trimester ultrasound at an academic center between 2005 and 2016. Primary outcomes were the change in proportion of DT versus TT triplets overtime and the number of fetuses at delivery. Secondary outcomes included differences in mode of conception and maternal/perinatal outcomes by chorionicity. Results Of 258 identified triplet pregnancies, 65.5% (n = 169) were TT. The proportion of DT versus TT triplets increased from 2005 to 2016 (p < 0.001). Women with DT triplets were more likely to deliver a singleton (41.4 vs. 11.2%, p < 0.001). Mode of conception was known for 248 women, of whom 93.5% (n = 232) conceived through infertility treatment. Types of infertility treatment differed by chorionicity (p < 0.001 ), with DT triplets more likely to conceive through in vitro fertilization (88.3 vs. 60.7%). Women with DT delivered earlier than TT triplets (31.0 ± 5.0 vs. 33.1 ± 3.5 weeks; p = 0.03). Conclusion The proportion of DT triplet gestations increased significantly over time. Women with DT triplets delivered on average 2 weeks earlier than TT triplets. Women with DT triplets were more likely to reduce to a singleton gestation. [ABSTRACT FROM AUTHOR]

Objective The objective of this study was to assess the relationship between first trimester cell-free total and fetal DNA in maternal plasma and the subsequent development of preeclampsia. Study Design Nested case-control study of patients enrolled in the Combined Antioxidant and Preeclampsia Prediction Studies prediction study of 175 women who did and 175 women who did not develop preeclampsia. The predictive values of cell-free total and fetal DNA and the subsequent development of preeclampsia were measured using receiver operating characteristic curves. Results Cell-free total DNA was higher in African American (median; 25-75%; 6.15; 0.14-28.73; p = 0.02) and Hispanic (4.95; 0.20-26.82; p = 0.037) compared with white women (2.33; 0.03-13.10). Levels of cell-free total DNA were also associated with maternal body mass index (BMI) (p = 0.02). Cell-free total DNA levels were similar between women who later developed preeclampsia (3.52; 0.11-25.3) and controls (3.74; 0.12-21.14, p = 0.96). Conclusion There is no significant difference in levels of cell-free total DNA in the first trimester in women who subsequently develop preeclampsia. Levels of cell-free total DNA in the first trimester are increased in African American and Hispanic compared with white women, and levels increase with increasing BMI. [ABSTRACT FROM AUTHOR]

Background The aim of this study was to determine whether racial/ethnic differences in psychosocial measures, independent of economic status, exist among a large population of pregnant nulliparas. Methods Between October 2010 and September 2013, nulliparous women at eight U.S. medical centers were followed longitudinally during pregnancy and completed validated instruments to quantify several psychosocial domains: Cohen Perceived Stress Scale, trait subscale of the Spielberger Anxiety Inventory, Connor-Davidson Resilience Scale, Multidimensional Scale of Perceived Social Support, Krieger Racism Scale, Edinburgh Postnatal Depression Scale, and the Pregnancy Experience Scale. Scores were stratified and compared by self-reported race, ethnicity, and income. Results Complete data were available for 8,128 of the 10,038 women enrolled in the study. For all measures, race and ethnicity were significantly associated (p < 0.001) with survey scores. Non-Hispanic black (NHB) women were most likely to score in the most unfavorable category for all measures, with the exception of the Pregnancy Experience Scale. The magnitude of these differences did not differ by income status (interaction, p > 0.05) except on the Krieger racism survey and the Edinburgh depression survey, which were exacerbated among NHB women with higher income (interaction, p < 0.001). Conclusion Significant racial/ethnic disparities, independent of income status, exist in psychosocial measures during pregnancy. [ABSTRACT FROM AUTHOR]

Objective The objective of this study was to examine whether there is an association between insulin resistance and subsequent development of puerperal infection by measuring insulin resistance in the mid-trimester using the homeostasis model assessment (HOMA:IR). Methods Secondary analysis of low-risk nulliparas enrolled in a multicenter pre-eclampsia prevention trial. HOMA:IR was measured on fasting plasma glucose and insulin concentrations among low-risk nulliparas between 22 and 26 weeks' gestation. Median HOMA:IR was compared between women who did and did not develop puerperal infection using Wilcoxon rank sum test. Logistic regression was used to control for potential confounders. Results Of 1,180 women with fasting glucose and insulin available, 121 (10.3%) had a puerperal infection. Median HOMA:IR was higher among those with subsequent puerperal infection (4.3 [interquartile, IQR: 2.2-20.5] vs. 2.6 [IQR: 1.5-6.7], p < 0.0001). After controlling for potentially confounding variables HOMA:IR was only marginally associated with an increased risk of development of puerperal infection, adjusted odds ratio: 1.01 (95% confidence interval: 1.00-1.02; p = 0.04) per unit increase. Elevated HOMA:IR performed poorly as a predictor of puerperal infection, with a positive predictive value of 15% and a negative predictive value of 92%. Conclusion Though associated with an increased risk of puerperal infection, insulin resistance, measured by HOMA:IR, is not a clinically useful predictor of puerperal infection. [ABSTRACT FROM AUTHOR]

Objective To determine the risk of gestational diabetes mellitus (GDM) and insulin resistance (IR) in obesity defined by body mass index (BMI), waist-to-hip ratio (WHR), or both combined. Methods Secondary analysis of a randomized multicenter trial of antioxidant supplementation versus placebo in nulliparous low-risk women to prevent pregnancy associated hypertension. Women between 9 and 16 weeks with data for WHR and BMI were analyzed for GDM (n = 2,300). Those with fasting glucose and insulin between 22 and 26 weeks (n = 717) were analyzed for IR by homeostatic model assessment of IR (normal, ≤ 75th percentile). WHR and BMI were categorized as normal (WHR, < 0.80; BMI, < 25 kg/m²); overweight (WHR, 0.8-0.84; BMI, 25-29.9 kg/m²); and obese (WHR, ≥ 0.85; BMI ≥ 30 kg/m²). Receiver operating characteristic curves and logistic regression models were used. Results Compared with normal, the risks of GDM or IR were higher in obese by BMI or WHR. The subgroup with obesity by WHR but not by BMI had no increased risk of GDM. [ABSTRACT FROM AUTHOR]

Objective This study aims to determine whether there is a threshold 3-hour oral glucose tolerance test (OGTT) value associated with accelerated risk of adverse pregnancy outcomes. Study Design In a secondary analysis of a cohort of women with untreated mild gestational glucose intolerance, we used generalized additive models with smoothing splines to explore nonlinear associations between each of the 3-hour OGTT values (fasting, 1-hour, 2-hour, and 3-hour) and adverse pregnancy outcomes, including the study's composite outcome (perinatal mortality, hypoglycemia, hyperbilirubinemia, neonatal hyperinsulinemia, and/or birth trauma), large for gestational age birth weight, small for gestational age birth weight, shoulder dystocia, neonatal hypoglycemia, gestational hypertension (gHTN), and preeclampsia. Results Among the 1,360 eligible women, each timed OGTT value was linearly associated with increased odds of composite adverse outcome. We found evidence of a departure from linearity only for the association between fasting glucose and gHTN/ preeclampsia, with a stronger association for values of 85 to 94 mg/dL (p ¼ 0.03). We found no evidence of departure from linearity for any other OGTT values and measured outcomes (all chi-square test p-values ≥ 0.05). Conclusion In a population of untreated women with mild gestational glucose intolerance and fasting OGTT < 95 mg/dL, we found an increasing risk of gHTN with a fasting glucose between 85 and 94 mg/dL. [ABSTRACT FROM AUTHOR]

Objective To test whether elevated umbilical cord serum inflammatory cytokine levels predicted subsequent cerebral palsy (CP) or neurodevelopmental delay (NDD). Study Design Nested case-control analysis within a clinical trial of antenatal magnesium sulfate (MgSO4) before anticipated preterm birth (PTB) for prevention of CP, with evaluation of surviving children at the age of 2. NDD was defined as a Bayley psychomotor developmental index (PDI) and/or mental developmental index (MDI) < 70. Controls, defined as surviving children without CP and with Bayley PDI and MDI ≥ 85, were matched by race and gestational age. Cord serum was analyzed for interleukin-8 (IL-8) interleukin-1 beta (IL-1β), and tumor necrosis factor-α (TNF-α) levels. Elevated cytokine levels were defined as ≥ 75th percentile in placebo-exposed controls. Analyses compared case/control cytokine levels, adjusting for MgSO4 exposure, gestational age, race/ethnicity, and sociodemographic differences. Results Logistic regression analysis with 339 cases and 276 controls showed that elevated IL-8 and IL-1β were more common in cord blood serum from infants with subsequent low MDI as compared with controls. After adjusting for additional confounders, the significant differences were no longer evident. Cytokine levels (IL-8, IL-1β, and TNF-α) were not elevated with CP or low PDI. Conclusion Cord serum IL-8, IL-1β, and TNF-α levels in preterm infants are not associated with subsequent CP or NDD. [ABSTRACT FROM AUTHOR]

Objective: The objective of the article is to describe latency for patients with preterm premature membrane rupture (PPROM) between 240/7 and 316/7 weeks' gestation. Study Design: Secondary analysis of data collected prospectively in a multicenter clinical trial of magnesium sulfate for cerebral palsy prevention. Women with PPROM and fewer than six contractions per hour at enrollment who were candidates for expectant management (n = 1,377) were included in this analysis. Length of latency was calculated in days by subtracting the time of delivery from the time of membrane rupture. Results: At each week of gestation, median latency between 24 and 28 weeks was similar at approximately 9 days, but it was significantly shorter with PPROM at 29, 30, and 31 weeks (p < 0.001). In addition, the percentage of patients remaining undelivered at 7 days and 14 days was similar for PPROM between 24 and 28 weeks, but it decreased significantly after that. For each gestational age, the proportion of patients remaining pregnant declined in a fashion similar to an exponential pattern. Conclusion: Median latency after PPROM is similar from 24 to 28 weeks' gestation, but it shortens with PPROM at and after 29 weeks. [ABSTRACT FROM AUTHOR]

Objective The aim of the article is to determine whether maternal body mass index (BMI) influences the beneficial effects of diabetes treatment in women with gestational diabetes mellitus (GDM). Study Design Secondary analysis of a multicenter randomized treatment trial of women with GDM. Outcomes of interest were elevated umbilical cord c-peptide levels (> 90th percentile 1.77 ng/mL), large for gestational age (LGA) birth weight (> 90th percentile), and neonatal fat mass (g). Women were grouped into five BMI categories adapted from the World Health Organization International Classification of normal, overweight, and obese adults. Outcomes were analyzed according to treatment group assignment. Results A total of 958 women were enrolled (485 treated and 473 controls). Maternal BMI at enrollment was not related to umbilical cord c-peptide levels. However, treatment of women in the overweight, Class I, and Class II obese categories was associated with a reduction in both LGA birth weight and neonatal fat mass. Neither measure of excess fetal growth was reduced with treatment in normal weight (BMI < 25 kg/m(2)) or Class III (BMI ≥ 40 kg/m(2)) obese women. Conclusion There was a beneficial effect of treatment on fetal growth in women with mild GDM who were overweight or Class I and Class II obese. These effects were not apparent for normal weight and very obese women. [ABSTRACT FROM AUTHOR]

Objective The aim of the article is to determine whether prior spontaneous abortion (SAB) or induced abortion (IAB), or the interpregnancy interval are associated with subsequent adverse pregnancy outcomes in nulliparous women. Methods We performed a secondary analysis of data collected from nulliparous women enrolled in a completed trial of vitamins C and E or placebo for preeclampsia prevention. Adjusted odds ratios (ORs) for maternal and fetal outcomes were determined for nulliparous women with prior SABs and IABs as compared with primigravid participants. Results Compared with primigravidas, women with one prior SAB were at increased risk for perinatal death (adj. OR, 1.5; 95% CI, 1.1-2.3) in subsequent pregnancies. Two or more SABs were associated with an increased risk for spontaneous preterm birth (PTB) (adj. OR, 2.6, 95% CI, 1.7-4.0), preterm premature rupture of membranes (PROM) (adj. OR, 2.9; 95% CI, 1.6-5.3), and perinatal death (adj. OR, 2.8; 95% CI, 1.5-5.3). Women with one previous IAB had higher rates of spontaneous PTB (adj. OR, 1.4; 95% CI, 1.0-1.9) and preterm PROM (OR, 2.0; 95% CI, 1.4-3.0). An interpregnancy interval less than 6 months after SAB was not associated with adverse outcomes. Conclusion Nulliparous women with a history of SAB or IAB, especially multiple SABs, are at increased risk for adverse pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Objective The aim of the study is to determine if umbilical cord serum concentrations of interleukin-6 (IL-6), C-reactive protein (CRP), and myeloperoxidase (MPO), in pregnancies at risk for preterm birth (PTB), are associated with neonatal morbidities and/or altered neurodevelopmental outcomes in the children. Study Design Umbilical cord serum samples were collected at birth from 400 newborns delivered within a multicenter randomized controlled trial of repeated versus single course of antenatal corticosteroids (ACs), in women at increased risk for PTB. Newborns were followed through discharge and were evaluated between 36 and 42 months corrected age with neurological examination and Bayley Scales of Infant Development. Umbilical cord serum concentrations of IL-6, CRP, and MPO were determined using enzyme-linked immunoassays. Multivariate logistic regression analyses explored the relationship between umbilical cord serum IL-6, CRP, and MPO levels, adverse newborn outcomes, and PTB < 32 weeks of gestational age (GA). Results Univariate analysis revealed that umbilical cord IL-6 above the 75th percentile was associated with increased respiratory distress syndrome (RDS) and chronic lung disease (CLD), but not with necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), or neonatal sepsis; however, this association was not significant after adjusting for GA at delivery and treatment group. No significant associations between CRP or MPO and RDS, CLD, NEC, sepsis, or IVH were evident. Regression analysis revealed that CRP above the 75th percentile was associated with a decreased risk of CLD (odds ratio, 0.10; 95% confidence interval, 0.02-0.41). No associations between umbilical cord IL-6, CRP, or MPO and MDI < 70 or PDI < 70 were evident. Umbilical cord serum concentrations of IL-6, CRP, and MPO, above the 75th percentile, were associated with more frequent PTB < 32 weeks of GA. Conclusion Elevated umbilical cord serum concentration of CRP is associated with reduced risk for CLD even after adjusting for GA at delivery. Occurrence of levels > 75th percentile of IL-6, CRP, and MPO in umbilical cord serum was associated with PTB < 32 weeks of GA. Elevated umbilical cord serum concentrations of IL-6, CRP, and MPO at birth were not associated with poor neurodevelopmental outcomes. [ABSTRACT FROM AUTHOR]

Objective To assess the relationship between a low 50-g 1-hour glucose loading test (GLT) and maternal and neonatal outcomes in women without diabetes. Study Design This was a secondary analysis of a multicenter observational cohort from a randomized trial of treatment for mild gestational diabetes. Maternal and neonatal outcomes were compared between women with GLT values < 90mg/dL and those with results 90 to 119 mg/dL. Results Of 436 enrolled women, 297 (68.1%) had a GLT result of 90 to 119 mg/dL and 139 (31.9%) had a result of < 90 mg/dL. There was a lower incidence of neonatal hypoglycemia in those with a GLT < 90 mg/dL (5.7% versus 16.5%, p ¼ 0.006). Other outcomes were not associated with test results. Conclusion A GLT result < 90 mg/dL compared with 90 to 119 mg/dL is associated with a lower risk of neonatal hypoglycemia, but no other significant findings. [ABSTRACT FROM AUTHOR]

Objective To compare the ability of customized versus normalized population fetal growth norms in identifying neonates at risk for adverse perinatal outcomes (APOs) associated with fetal overgrowth and gestational diabetes (GDM). Study Design Secondary analysis of a multicenter treatment trial of mild GDM. The primary outcome was a composite of neonatal outcomes associated with fetal overgrowth and GDM. Birth weight percentiles were calculated using ethnicity- and gender-specific population and customized norms (Gardosi). Results Two hundred three (9.8%) and 288 (13.8%) neonates were large for gestational age by population (LGApop) and customized (LGAcust) norms, respectively. Both LGApop and LGAcust were associated with the primary outcome and neonatal hyperinsulinemia, but neither was associated with hypoglycemia or hyperbilirubinemia. The ability of customized and population birth weight percentiles for predicting APOs were poor (area under the receiver operating characteristic curve < 0.6 for six of eight APOs). Conclusion Neither customized nor normalized population norms better identify neonates at risk of APOs related to fetal overgrowth and GDM. [ABSTRACT FROM AUTHOR]

Objective To compare population versus customized fetal growth norms in identifying neonates at risk for adverse outcomes (APO) associated with small for gestational age (SGA). Study Design Secondary analysis of an intrapartum fetal pulse oximetry trial in nulliparous women at term. Birth weight percentiles were calculated using ethnicity and gender-specific population norms and customized norms (Gardosi). Results Of the studied neonates, 508 (9.9%) and 584 (11.3%) were SGA by population (SGApop) and customized (SGAcust) norms, respectively. SGApop infants were significantly associated with a composite adverse neonatal outcome, neonatal intensive care admission, low fetal oxygen saturation, and reduced risk of cesarean delivery; both SGApop and SGAcust infants were associated with a 5-minute Apgar score < 4. The ability of customized and population birth weight percentiles in predicting APO was poor (12 of 14 APOs had area under the curve of <0.6). Conclusion In this intrapartum cohort, neither customized nor normalized population norms adequately identified neonates at risk of APO related to SGA. [ABSTRACT FROM AUTHOR]

We describe obstetric outcomes in a group of patients with prior cesarean delivery (CD) presenting with an intrauterine fetal demise (IUFD). A secondary analysis of an observational study of women with prior CD was performed. All antepartum singleton pregnancies with a prior CD and IUFD 20 weeks' gestation or 500 g were evaluated. Two hundred nine patients met inclusion criteria for analysis. The mean gestational age standard deviation at delivery was 31.36.5 weeks. The trial of labor rate was 75.6%(158/209), and the vaginal birth after cesarean (VBAC) success rate was 86.7%. Labor induction or augmentation occurred in 83.3% of attempted VBAC. Uterine rupture occurred in five women (2.4%), and in 3.4% of those being induced but none of these required hysterectomy. Women with a history of previous CD and an IUFD often undergo trial of labor with a high VBAC success rate. Uterine rupture complicates 2.4% of such cases. [ABSTRACT FROM AUTHOR]

We compared maternal and neonatal outcomes following repeat cesarean delivery (CD) of women with a prior classical CD with those with a prior low transverse CD. The Maternal Fetal Medicine Units Network Cesarean Delivery Registry was used to identify women with one previous CD who underwent an elective repeat CD prior to the onset of labor at >=36 weeks. Outcomes were compared between women with a previous classical CD and those with a prior low transverse CD. Of the 7936 women who met study criteria, 122 had a prior classical CD. Women with a prior classical CD had a higher rate of classical uterine incision at repeat CD (12.73% versus 0.59%; P < 0.001), had longer total operative time and hospital stay, and had higher intensive care unit admission. Uterine dehiscence was more frequent in women with a prior classical CD (2.46% versus 0.27%, odds ratio 9.35, 95% confidence interval 1.76 to 31.93). After adjusting for confounding factors, there were no statistical differences in major maternal or neonatal morbidities between groups. Uterine dehiscence was present at repeat CD in 2.46% of women with a prior classical CD. However, major maternal morbidities were similar to those with a prior low transverse CD. [ABSTRACT FROM AUTHOR]

Elevated concentrations of interleukin-6 (IL-6), C-reactive protein (CRP), and matrix metalloproteinase-9 (MMP-9) in fetal and neonatal compartments have been associated with an increased risk for preterm birth (PTB) and/or neonatal morbidity. The purpose of this study was to determine if the maternal serum concentration of IL-6, CRP, and MMP-9 in women at risk for PTB, who are not in labor and have intact membranes, are associated with an increased risk for PTB <32 weeks and/or neonatal morbidity. Maternal serum samples collected from 475 patients enrolled in a multicenter randomized controlled trial of single versus weekly corticosteroids for women at increased risk for preterm delivery were assayed. Serum was collected at randomization (24 to 32 weeks' gestation). Maternal serum concentrations of IL-6, CRP, and MMP-9 were subsequently determined using enzyme-linked immunoassays. Multivariate logistic regression analysis was performed to explore the relationship between maternal serum concentrations of IL-6, CRP, and MMP-9 and PTB <32 weeks, respiratory distress syndrome (RDS), chronic lung disease (CLD), intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), and any sepsis. Maternal serum concentrations of IL-6 and CRP, but not MMP-9, above the 90th percentile at the time of randomization were associated with PTB <32 weeks. In contrast, there was no significant relationship between RDS and NEC and the maternal serum concentration of IL-6, CRP, or MMP-9 (univariate analysis). The development of CLD was associated with a high (above 90th percentile) IL-6 and CRP in maternal serum, even after adjustment for gestational age (GA) at randomization and treatment group. However, when GA at delivery was added to the model, this finding was nonsignificant. Neonatal sepsis was more frequent in neonates born to mothers with a high maternal serum concentration of CRP (>90th percentile). However, there was no significant association after adjustment for GA at randomization and treatment group. Logistic regression analysis for each analyte indicated that high maternal serum concentrations of IL-6 and CRP, but not MMP-9, were associated with an increased risk of IVH (odds ratio [OR] 4.60, 95% confidence interval [CI] 1.86 to 10.68; OR 4.07, 95% CI 1.63 to 9.50) after adjusting for GA at randomization and treatment group. Most babies (25/30) had grade I IVH. When GA at delivery was included, elevated IL-6 remained significantly associated with IVH (OR 2.77, 95% CI 1.02 to 7.09). An elevated maternal serum concentration of IL-6 and CRP are risk factors for PTB <32 weeks and subsequent development of neonatal IVH. An elevated maternal serum IL-6 appears to confer additional risk for IVH even after adjusting for GA at delivery. [ABSTRACT FROM AUTHOR]

We compared neonatal outcomes in twin pregnancies following moderately preterm birth (MPTB), late preterm birth (LPTB), and term birth. A secondary analysis of a multicenter, randomized controlled trial of multiple gestations was conducted. MPTB was defined as delivery between 32 0/7 and 33 6/7 weeks and LPTB between 34 0/7 and 36 6/7 weeks. Primary outcome was a neonatal outcome composite consisting of one or more of the following: neonatal death, respiratory distress syndrome, early onset culture-proven sepsis, stage 2 or 3 necrotizing enterocolitis, bronchopulmonary dysplasia, grade 3 or 4 intraventricular hemorrhage, periventricular leukomalacia, pneumonia, or severe retinopathy of prematurity. Among 552 twin pregnancies, the MPTB rate was 14.5%, LPTB 49.8%, and term birth rate 35.7%. The rate of the primary outcome was different between groups: 30.0% for MPTB, 12.8% for LPTB, 0.5% for term birth (p<0.001). Compared with term neonates, the primary neonatal outcome composite was increased following MPTB (relative risk [RR] 58.5; 95% confidence interval [CI] 11.3 to 1693.0) and LPTB (RR 24.9; 95% CI 4.8 to 732.2). Twin pregnancies born moderately and late preterm encounter higher rates of neonatal morbidities compared with twins born at term. [ABSTRACT FROM AUTHOR]

We compared outcomes for neonates with forceps-assisted, vacuum-assisted, or cesarean delivery in the second stage of labor. This is a secondary analysis of a randomized trial in laboring, low-risk, nulliparous women at ≥36 weeks' gestation. Neonatal outcomes after use of forceps, vacuum, and cesarean were compared among women in the second stage of labor at station +1 or below (thirds scale) for failure of descent or nonreassuring fetal status. Nine hundred ninety women were included in this analysis: 549 (55%) with an indication for delivery of failure of descent and 441 (45%) for a nonreassuring fetal status. Umbilical cord gases were available for 87% of neonates. We found no differences in the base excess (p=0.35 and 0.78 for failure of descent and nonreassuring fetal status) or frequencies of pH below 7.0 (p=0.73 and 0.34 for failure of descent and nonreassuring fetal status) among the three delivery methods. Birth outcomes and umbilical cord blood gas values were similar for those neonates with a forceps-assisted, vacuum-assisted, or cesarean delivery in the second stage of labor. The occurrence of significant fetal acidemia was not different among the three delivery methods regardless of the indication. [ABSTRACT FROM AUTHOR]