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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  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]

Objective: To determine the frequency of sepsis and other adverse neonatal outcomes in women with a clinical diagnosis of chorioamnionitis. Methods: We performed a secondary analysis of a multi-center placebo-controlled trial of vitamins C/E to prevent preeclampsia in low risk nulliparous women. Clinical chorioamnionitis was defined as either the "clinical diagnosis" of chorioamnionitis or antibiotic administration during labor because of an elevated temperature or uterine tenderness in the absence of another cause. Early-onset neonatal sepsis was categorized as "suspected" or "confirmed" based on a clinical diagnosis with negative or positive blood, urine or cerebral spinal fluid cultures, respectively, within 72 h of birth. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression. Results: Data from 9391 mother-infant pairs were analyzed. The frequency of chorioamnionitis was 10.3%. Overall, 6.6% of the neonates were diagnosed with confirmed (0.2%) or suspected (6.4%) early-onset sepsis. Only 0.7% of infants born in the setting of chorioamnionitis had culture-proven early-onset sepsis versus 0.1% if chorioamnionitis was not present. Clinical chorioamnionitis was associated with both suspected [OR 4.01 (3.16–5.08)] and confirmed [OR 4.93 (1.65–14.74)] early-onset neonatal sepsis, a need for resuscitation within the first 30 min after birth [OR 2.10 (1.70–2.61)], respiratory distress [OR 3.14 (2.16–4.56)], 1 min Apgar score of ≤3 [OR 2.69 (2.01–3.60)] and 4–7 [OR 1.71 (1.43–2.04)] and 5 min Apgar score of 4–7 [OR 1.67 (1.17–2.37)] (vs. 8–10). Conclusion: Clinical chorioamnionitis is common and is associated with neonatal morbidities. However, the vast majority of exposed infants (99.3%) do not have confirmed early-onset sepsis. [ABSTRACT FROM AUTHOR]

Objective To compare the risks of adverse maternal and neonatal outcomes associated with spontaneous (SPTB) versus indicated preterm births (IPTB). Methods A secondary analysis of a multicenter trial of vitamin C and E supplementation in healthy low-risk nulliparous women. Outcomes were compared between women with SPTB (due to spontaneous membrane rupture or labor) and those with IPTB (due to medical or obstetric complications). A primary maternal composite outcome included: death, pulmonary edema, blood transfusion, adult respiratory distress syndrome (RDS), cerebrovascular accident, acute tubular necrosis, disseminated intravascular coagulopathy, or liver rupture. A neonatal composite outcome included: neonatal death, RDS, grades III or IV intraventricular hemorrhage (IVH), sepsis, necrotizing enterocolitis (NEC), or retinopathy of prematurity. Results Of 9,867 women, 10.4% (N = 1,038) were PTBs; 32.7% (n = 340) IPTBs and 67.3% (n = 698) SPTBs. Compared with SPTB, the composite maternal outcome was more frequent in IPTB-4.4% versus 0.9% (adjusted odds ratio [aOR], 4.0; 95% confidence interval [CI], 1.4-11.8), as were blood transfusion and prolonged hospital stay (3.2 and 3.7 times, respectively). The frequency of composite neonatal outcome was higher in IPTBs (aOR, 1.8; 95% CI, 1.1-3.0), as were RDS (1.7 times), small for gestational age (SGA) < 5th percentile (7.9 times), and neonatal intensive care unit (NICU) admission (1.8 times). Conclusion Adverse maternal and neonatal outcomes were significantly more likely with IPTB than with SPTB. [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 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 The aim of the study was to evaluate associations between fetal growth and weight at 2 years in infants born preterm using a customized approach for birth weight. Study Design This is a secondary analysis of a multicenter trial that included a 2-year follow-up of children born prematurely. Customized birth weight percentiles were calculated using the Gardosi model for a U.S. population, and the relation between customized percentile and weight and height at 2 years (adjusted for gender using z-score) was determined using regression analysis and by comparing z-scores for children with birth weight <10th versus ≥10th percentile. Results Weight z-score at 2 years was significantly lower in the <10th than in the ≥10th percentile group (median [interguartile range, IQR]: -0.66 [-1.58, -0.01] vs. -0.23 [-1.05, 0.55]; p < 0.001 ), and remained after adjusting for maternal education (p < 0.001). A similar relationship was noted for height z-score between groups (median [IQR]: -0.56 [-1.29, 0.19] vs. -0.24 [-0.99, 0.37]; p < 0.001). Positive relationships between customized birth weight percentile and weight and height at 2 years were noted (p < 0.001 for both), but were not strong (R² = 0.04 and 0.02, respectively). Conclusion Customized birth weight percentile is a minor determinant of weight at 2 years among children born preterm. [ABSTRACT FROM AUTHOR]

Objective This study aims to evaluate whether magnesium sulfate administration for neuroprotection prolongs latency in women with preterm premature rupture of membranes (PPROM) between 24 and 316/7 weeks' gestation. Study Design This is a secondary analysis of a randomized controlled trial of magnesium sulfate for prevention of cerebral palsy. Gravid women with a singleton pregnancy between 24 and 316/7 weeks' gestation with PPROM without evidence of labor were randomized to receive magnesium sulfate, administered intravenously as a 6-g bolus followed by a constant infusion of 2 g per hour up to 12 hours, or placebo. Maternal outcomes for this analysiswere delivery in less than 48 hours and in less than 7 days from randomization. Neonatal outcomes included a composite of respiratory distress syndrome, interventricular hemorrhage grades 3 or 4, periventricular leukomalacia, sepsis, necrotizing enterocolitis, retinopathy of prematurity, or death. Results A total of 1,259 women were included. The rate of delivery < 48 hours was not different in the magnesium sulfate and the placebo groups (22.2 and 20.7%, p ј 0.51). Delivery < 7 days was similar between groups (55.4 and 51.4%, p ј 0.16). Median latency was also similar between groups (median [interquartile range], 6.0 days [range, 2.4-13.8 days] and 6.6 days [range, 2.4-15.1 days], p ј 0.29). Composite neonatal outcomes did not differ between groups. Conclusion Magnesium sulfate administration given for neuroprotection in women with a singleton gestation with PPROM and without labor before 32 weeks does not impact latency. [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 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 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 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]

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]

Background: Infants born <37 weeks' gestation are of public health concern since complications associated with preterm birth are the leading cause of mortality in children <5 years of age and a major cause of morbidity and lifelong disability. The administration of 17-alpha hydroxyprogesterone caproate reduces preterm birth by 33% in women with history of spontaneous preterm birth. We demonstrated previously that plasma concentrations of 17-alpha hydroxyprogesterone caproate vary widely among pregnant women and that women with 17-alpha hydroxyprogesterone caproate plasma concentrations in the lowest quartile had spontaneous preterm birth rates of 40% vs rates of 25% in those women with higher concentrations. Thus, plasma concentrations are an important factor in determining drug efficacy but the reason 17-alpha hydroxyprogesterone caproate plasma concentrations vary so much is unclear. Predominantly, 17-alpha hydroxyprogesterone caproate is metabolized by CYP3A4 and CYP3A5 enzymes.Objective: We sought to: (1) determine the relation between 17-alpha hydroxyprogesterone caproate plasma concentrations and single nucleotide polymorphisms in CYP3A4 and CYP3A5; (2) test the association between progesterone receptor single nucleotide polymorphisms and spontaneous preterm birth; and (3) test whether the association between plasma concentrations of 17-alpha hydroxyprogesterone caproate and spontaneous preterm birth varied by progesterone receptor single nucleotide polymorphisms.Study Design: In this secondary analysis, we evaluated genetic polymorphism in 268 pregnant women treated with 17-alpha hydroxyprogesterone caproate, who participated in a placebo-controlled trial to evaluate the benefit of omega-3 supplementation in women with history of spontaneous preterm birth. Trough plasma concentrations of 17-alpha hydroxyprogesterone caproate were measured between 25-28 weeks of gestation after a minimum of 5 injections of 17-alpha hydroxyprogesterone caproate. We extracted DNA from maternal blood samples and genotyped the samples using TaqMan (Applied Biosystems, Foster City, CA) single nucleotide polymorphism genotyping assays for the following single nucleotide polymorphisms: CYP3A4*1B, CYP3A4*1G, CYP3A4*22, and CYP3A5*3; and rs578029, rs471767, rs666553, rs503362, and rs500760 for progesteronereceptor. We adjusted for prepregnancy body mass index, race, and treatment group in a multivariable analysis. Differences in the plasma concentrations of 17-alpha hydroxyprogesterone caproate by genotype were evaluated for each CYP single nucleotide polymorphism using general linear models. The association between progesterone receptor single nucleotide polymorphisms and frequency of spontaneous preterm birth was tested using logistic regression. A logistic model also tested interaction between 17-alpha hydroxyprogesterone caproate concentrations with each progesterone receptor single nucleotide polymorphism for the outcome of spontaneous preterm birth.Results: The association between CYP single nucleotide polymorphisms *22, *1G, *1B, and *3 and trough plasma concentrations of 17-alpha hydroxyprogesterone caproate was not statistically significant (P = .68, .44, .08, and .44, respectively). In an adjusted logistic regression model, progesterone receptor single nucleotide polymorphisms rs578029, rs471767, rs666553, rs503362, and rs500760 were not associated with the frequency of spontaneous preterm birth (P = .29, .10, .76, .09, and .43, respectively). Low trough plasma concentrations of 17-alpha hydroxyprogesterone caproate were statistically associated with a higher frequency of spontaneous preterm birth (odds ratio, 0.78; 95% confidence ratio, 0.61-0.99; P = .04 for trend across quartiles), however no significant interaction with the progesterone receptor single nucleotide polymorphisms rs578029, rs471767, rs666553, rs503362, and rs500760 was observed (P = .13, .08, .10, .08, and .13, respectively).Conclusion: The frequency of recurrent spontaneous preterm birth appears to be associated with trough 17-alpha hydroxyprogesterone caproate plasma concentrations. However, the wide variation in trough 17-alpha hydroxyprogesterone caproate plasma concentrations is not attributable to polymorphisms in CYP3A4 and CYP3A5 genes. Progesterone receptor polymorphisms do not predict efficacy of 17-alpha hydroxyprogesterone caproate. The limitations of this secondary analysis include that we had a relative small sample size (n = 268) and race was self-reported by the patients. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to examine the association between gestational age (GA) at the time of treatment initiation for gestational diabetes mellitus (GDM) and maternal and perinatal outcomes.Study Design: We conducted a secondary analysis of a multicenter randomized treatment trial of mild GDM in which women with mild GDM were assigned randomly to treatment vs usual care. The primary outcome of the original trial, as well as this analysis, was a composite perinatal adverse outcome that included neonatal hypoglycemia, hyperbilirubinemia, hyperinsulinemia, and perinatal death. Other outcomes that were examined included the frequency of large for GA, birthweight, neonatal intensive care unit admission, gestational hypertension/preeclampsia, and cesarean delivery. The interaction between GA at treatment initiation (stratified as 24-26, 27, 28, 29, and ≥30 weeks of gestation) and treatment group (treated vs routine care), with the outcomes of interest, was used to determine whether GA at treatment initiation was associated with outcome differences.Results: Of 958 women whose cases were analyzed, those who initiated treatment at an earlier GA did not gain an additional treatment benefit compared with those who initiated treatment at a later GA (probability value for interaction with the primary outcome, .44). Similarly, there was no evidence that other outcomes were improved significantly by earlier initiation of GDM treatment (large for GA, P = .76; neonatal intensive care unit admission, P = .8; cesarean delivery, P = .82). The only outcome that had a significant interaction between GA and treatment was gestational hypertension/preeclampsia (P = .04), although there was not a clear cut GA trend where this outcome improved with treatment.Conclusion: Earlier initiation of treatment of mild GDM was not associated with stronger effect of treatment on perinatal outcomes. [ABSTRACT FROM AUTHOR]

Objective: To compare the rates of gestational diabetes among women who received serial doses of 17-alpha hydroxyprogesterone caproate vs placebo. Study Design: Secondary analysis of 2 double-blind randomized placebo-controlled trials of 17-alpha hydroxyprogesterone caproate given to women at risk for preterm delivery. The incidence of gestational diabetes was compared between women who received 17-alpha hydroxyprogesterone caproate or placebo. Results: We included 1094 women; 441 had singleton and 653 had twin gestations. Combining the 2 studies, 616 received 17-alpha hydroxyprogesterone caproate and 478 received placebo. Among singleton and twin pregnancies, rates of gestational diabetes were similar in women receiving 17-alpha hydroxyprogesterone caproate vs placebo (5.8% vs 4.7%; P = .64 and 7.4% vs 7.6%; P = .94, respectively). In the multivariable model, progesterone was not associated with gestational diabetes (adjusted odds ratio, 1.04; 95% confidence interval, 0.62–1.73). Conclusion: Weekly administration of 17-alpha hydroxyprogesterone caproate is not associated with higher rates of gestational diabetes in either singleton or twin pregnancies. [Copyright &y& Elsevier]