Impact of youth onset type 2 diabetes during pregnancy on microvascular and cardiac outcomes.

AIMS: To examine the impact of pregnancy on microvascular and cardiovascular measures in women with youth-onset T2D. METHODS: Microvascular and cardiovascular measures were compared in in a cohort of 116 women who experienced a pregnancy of ≥ 20 weeks gestation and 291 women who did not among women in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study. RESULTS: Cox regression models adjusted for participant characteristics at baseline including age, race/ethnicity, household income, diabetes duration, HbA1c (>6%), and BMI, demonstrated those who experienced pregnancy had 2.76 (1.38-5.49; p = 0.004) fold increased risk of hyperfiltration (eGFR ≥ 135 ml/min/1.73 m2), compared to those without a pregnancy. No differences were observed in rates of retinopathy (48.9% vs. 41.1%) or neuropathy (23.3% vs. 16.3%) in women who experienced pregnancy vs. women who did not, respectively. In fully adjusted models, pregnancy did not impact changes in echocardiographic or arterial stiffness compared to changes in women who were never pregnant. CONCLUSIONS: These results indicate that pregnancy increases the risk of hyperfiltration in women with youth-onset T2D, but not other micro or macrovascular complications. The rates of vascular complications are very high in youth-onset T2D potentially obscuring micro- and macrovascular changes attributable to pregnancy. CLINICAL TRIAL INFORMATION: ClinicalTrials.gov numbers,NCT01364350andNCT02310724.

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..

Prediction of Cerebral Palsy or Death among Preterm Infants Who Survive the Neonatal Period.

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..

Prenatal Nicotine or Cannabis Exposure and Offspring Neurobehavioral Outcomes.

OBJECTIVE: To study the association between nicotine or cannabis metabolite presence in maternal urine and child neurodevelopmental outcomes. METHODS: We conducted a secondary analysis of two parallel multicenter randomized controlled trials of treatment for hypothyroxinemia or subclinical hypothyroidism among pregnant individuals enrolled at 8-20 weeks of gestation. All maternal-child dyads with a maternal urine sample at enrollment and child neurodevelopmental testing were included (N=1,197). Exposure was urine samples positive for nicotine (cotinine) or cannabis 11-nor-9-carboxy-delta-9-tetrahydrocannabinol [THC-COOH]) or both metabolites. Primary outcome was child IQ at 60 months. Secondary outcomes included cognitive, motor and language, attention, behavioral and social competency, and differential skills assessments at 12, 24, 36, and 48 months. Quantile regression analysis was performed with confounder adjustment. RESULTS: Of 1,197 pregnant individuals, 99 (8.3%) had positive cotinine samples and 47 (3.9%) had positive THC-COOH samples; 33 (2.8%) were positive for both. Groups differed in self-reported race and ethnicity, education, marital status, insurance, and thyroid status. Median IQ was similar between cotinine-exposed and -unexposed children (90 vs 95, adjusted difference in medians -2.47, 95% CI -6.22 to 1.29) and THC-COOH-exposed and -unexposed children (89 vs 95, adjusted difference in medians -1.35, 95% CI -7.76 to 5.05). In secondary outcome analysis, children with THC-COOH exposure compared with those unexposed had higher attention scores at 48 months of age (57 vs 49, adjusted difference in medians 6.0, 95% CI 1.11-10.89). CONCLUSIONS: Neither prenatal nicotine nor cannabis exposure was associated with a difference in IQ. Cannabis exposure was associated with worse attention scores in early childhood. Longitudinal studies assessing associations between child neurodevelopmental outcomes and prenatal nicotine and cannabis exposure with a focus on timing and quantity of exposure are needed. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT00388297.

Hepatitis C Virus Antibody Screening in a Cohort of Pregnant Women: Identifying Seroprevalence and Risk Factors.

OBJECTIVE: To describe the prevalence of hepatitis C virus (HCV) antibody, evaluate current risk factors associated with HCV antibody positivity, and identify novel composite risk factors for identification of groups most likely to demonstrate HCV antibody seropositivity in an obstetric population from 2012 to 2015. METHODS: The Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network initiated an observational study of mother-to-child transmission of HCV in 2012 that included offering HCV antibody screening to their entire obstetric population. Women presenting for prenatal care before 23 weeks of gestation without a known multifetal gestation were eligible. For each woman who was HCV antibody-positive, two women at similar gestational age who were HCV antibody-negative were identified and included for comparison. Risk factors were evaluated by patient interview and chart review. Women in the case group were identified to have a signal-to-cutoff value of at least 5 on the Abbott ARCHITECT platform. RNA status was evaluated for women in the case group. RESULTS: Of 106,842 women screened for the HCV antibody, 254 had positive results. The HCV antibody seroprevalence rate was 2.4 cases per 1,000 women (95% CI 2.1-2.7). One hundred thirty-one women in the case group and 251 women in the control group were included in the case-control analysis. Factors associated with HCV antibody positivity included injection drug use (adjusted odds ratio [aOR] 22.9, 95% CI 8.2-64.0), blood transfusion (aOR 3.7, 95% CI 1.3-10.4), having a partner with HCV (aOR 6.3, 95% CI 1.8-22.6), more than three lifetime sexual partners (aOR 5.3, 95% CI 1.4-19.8), and smoking (aOR 2.4, 95% CI 1.2-4.6). A composite of any of these potential risk factors provided the highest sensitivity for detecting HCV antibody (75/82 cases, 91%). CONCLUSION: In this cohort, the seroprevalence of HCV antibody was low, and the current risk factors for HCV screening were not identified. These findings may be useful in defining new strategies for identifying mothers with the HCV antibody and the neonates susceptible to maternal transmission of HCV. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT01959321.

Child Neurodevelopmental Outcomes by Prepregnancy Body Mass Index and Gestational Weight Gain.

OBJECTIVE: To study the association of prepregnancy body mass index (BMI) and gestational weight gain with child neurodevelopmental outcomes. METHODS: We performed a secondary analysis of data from two parallel, multicenter, randomized, double-blind, placebo-controlled thyroxine replacement trials in pregnant women with either hypothyroxinemia or subclinical hypothyroidism who delivered at term. Body mass index was categorized as normal (18.5-24.9), overweight (25.0-29.9), or obese (30 or greater). We also evaluated early (20 weeks of gestation or less), late (greater than 20 weeks of gestation), and total gestational weight gain and categorized gestational weight gain as inadequate, adequate, and excessive per 2009 Institute of Medicine guidelines. Neurodevelopmental outcomes included 5-year Wechsler Preschool and Primary Scale of Intelligence and 3-year Differential Ability Scales-II. Linear and logistic regression analyses were performed and adjusted for maternal age, race-ethnicity, education, insurance status, parity, smoking and alcohol use, thyroid status (subclinical hypothyroidism or hypothyroxinemia), treatment group, gestational age at delivery, and neonatal sex. RESULTS: Of the 948 women included, 380 (40%), 305 (32%), and 263 (28%) had normal, overweight, and obese prepregnancy BMI, respectively. A total of 106 (11%), 212 (22%), and 630 (66%) of women had inadequate, adequate, and excessive total rates of gestational weight gain, respectively. Maternal differences among the BMI categories included race-ethnicity, education, insurance type, parity, and thyroid status (all P<.01), whereas the gestational weight gain groups only differed by parity (P<.001). In unadjusted analysis, children of obese (93.2±12.8; 88.5±13.3) and overweight (94.1±15.6; 89.6±16.0) women had lower Wechsler Preschool and Primary Scale of Intelligence and Differential Ability Scales-II scores, respectively, than normal-weight women (97.4±15.4; 93.9±16.0; P<.001 for all comparisons); however, in adjusted analysis, there were no differences in neurodevelopmental outcomes by maternal BMI. The association was primarily accounted for by race-ethnicity and education. In unadjusted and adjusted analyses, there were no differences in neurodevelopmental outcomes by adequacy of early, late, or total gestational weight gain. CONCLUSION: In women with either subclinical hypothyroidism or hypothyroxinemia, neither prepregnancy BMI nor gestational weight gain was associated with neurodevelopmental outcomes among children born at term in adjusted analyses.

Association Between Gestational Weight Gain and Perinatal Outcomes.

OBJECTIVE: To evaluate the association between gestational weight gain and maternal and neonatal outcomes in a large, geographically diverse cohort. METHODS: Trained chart abstractors at 25 hospitals obtained maternal and neonatal data for all deliveries on randomly selected days over 3 years (2008-2011). Gestational weight gain was derived using weight at delivery minus prepregnancy or first-trimester weight and categorized as below, within, or above the Institute of Medicine (IOM) guidelines in this retrospective cohort study. Maternal (primary or repeat cesarean delivery, third- or fourth-degree lacerations, severe postpartum hemorrhage, hypertensive disease of pregnancy) and neonatal (preterm birth, shoulder dystocia, macrosomia, hypoglycemia) outcomes were compared among women in the gestational weight gain categories in unadjusted and adjusted analyses with odds ratios (ORs) and 95% CI reported. Covariates included age, race-ethnicity, tobacco use, insurance type, parity, prior cesarean delivery, pregestational diabetes, hypertension, and hospital type. RESULTS: Of the 29,861 women included, 51% and 21% had gestational weight gain above and below the guidelines, respectively. There was an association between gestational weight gain above the IOM guidelines and cesarean delivery in both nulliparous women (adjusted OR 1.44, 95% CI 1.31-1.59) and multiparous women (adjusted OR 1.26, 95% CI 1.13-1.41) and hypertensive diseases of pregnancy in nulliparous and multiparous women combined (adjusted OR 1.84, 95% CI 1.66-2.04). For the neonatal outcomes, gestational weight gain above the IOM guidelines was associated with shoulder dystocia (adjusted OR 1.74, 95% CI 1.41-2.14), macrosomia (adjusted OR 2.66, 95% CI 2.03-3.48), and neonatal hypoglycemia (adjusted OR 1.60, 95% CI 1.16-2.22). Gestational weight gain below the guidelines was associated with spontaneous (adjusted OR 1.50, 95% CI 1.31-1.73) and indicated (adjusted OR 1.34, 95% CI 1.12-1.60) preterm birth. CONCLUSION: In a large, diverse cohort with prospectively collected data, gestational weight gain below or above guidelines is associated with a variety of adverse pregnancy outcomes.

Depressive Symptoms, Antidepressant Medication Use, and Inflammatory Markers in the Diabetes Prevention Program.

OBJECTIVE: Antidepressant medication use (ADM) has been shown to predict diabetes. This article assessed the role of inflammatory markers in this relationship within the Diabetes Prevention Program (DPP). METHODS: DPP participants randomized to metformin (MET), life-style intervention (ILS), or placebo (PLB) were assessed for depression (Beck Depression Inventory [BDI]) annually, ADM use semiannually, serum inflammatory markers (C-reactive protein [CRP], interleukin 6 [IL-6]) at baseline and year 1, and diagnosis of type 2 diabetes mellitus (T2DM) semiannually (for 3.2 years). RESULTS: At baseline (N = 3187), M (SD) body mass index was 34 (6) kg/m and the median (interquartile range) BDI score was 3 (1-7). One hundred eighty-one (5.7%) reported ADM use and 328 (10%) had BDI scores of 11 or higher. CRP and IL-6 levels did not differ by treatment group. Baseline ADM, but not BDI score, was associated with higher levels of baseline CRP adjusted for demographic, anthropometric variables, and other medications (20% higher, p = .01). Year 1 CRP decreased for non-ADM users in the MET (-13.2%) and ILS (-34%) groups and ADM users in the ILS group (-29%). No associations were found with IL-6. CRP and continuous use of ADM predicted incident T2DM in the PLB group. In the ILS group, continuous and intermittent ADM, but not CRP, predicted T2DM. In the MET group, CRP predicted incident T2DM. CRP did not mediate the risk of T2DM with ADM use in any group. CONCLUSIONS: ADM was significantly associated with elevated CRP and incident T2DM. In the PLB group, ADM and CRP independently predicted onset of T2DM; however, CRP did not significantly mediate the effect of ADM.

Change in adiponectin explains most of the change in HDL particles induced by lifestyle intervention but not metformin treatment in the Diabetes Prevention Program.

OBJECTIVE: In addition to slowing diabetes development among participants in the Diabetes Prevention Program (DPP), intensive lifestyle change and metformin raised HDL-cholesterol (HDL-C) compared to placebo treatment. We investigated the lifestyle and metabolic determinants as well as effects of biomarkers of inflammation, endothelial dysfunction and coagulation and their changes resulting from lifestyle and metformin interventions on the increase in HDL-C in the DPP. METHODS: The effects of a 1year period of intensive lifestyle change aimed at achieving 7% weight loss or metformin 850mg twice daily versus placebo on HDL-C were assessed in 3070 participants with impaired glucose tolerance, and on HDL particle concentration (HDL-P) and size in a subgroup of 1645 individuals. Treatment-associated changes in lifestyle and metabolic factors as well as in novel biomarkers were investigated for their associations with change in HDL-C using multiple regression analysis. RESULTS: After adjusting for BMI, insulin resistance, glycemia, dietary saturated fat, alcohol intake, physical activity and nine different biomarkers, only adiponectin accounted for the effect of intensive lifestyle change on HDL-C via an increase in large HDL-P. By contrast baseline and change in BMI and tissue plasminogen activator levels attenuated the effect of metformin on HDL-C, with adiponectin having no specific effect. CONCLUSION: While both lifestyle and metformin interventions used to prevent diabetes increase HDL-C, the mechanisms involved differ between the two treatments and may have consequences for future risk of cardiovascular disease.

Short and long-term lifestyle coaching approaches used to address diverse participant barriers to weight loss and physical activity adherence.

BACKGROUND: Individual barriers to weight loss and physical activity goals in the Diabetes Prevention Program, a randomized trial with 3.2 years average treatment duration, have not been previously reported. Evaluating barriers and the lifestyle coaching approaches used to improve adherence in a large, diverse participant cohort can inform dissemination efforts. METHODS: Lifestyle coaches documented barriers and approaches after each session (mean session attendance = 50.3 ± 21.8). Subjects were 1076 intensive lifestyle participants (mean age = 50.6 years; mean BMI = 33.9 kg/m²; 68% female, 48% non-Caucasian). Barriers and approaches used to improve adherence were ranked by the percentage of the cohort for whom they applied. Barrier groupings were also analyzed in relation to baseline demographic characteristics. RESULTS: Top weight loss barriers reported were problems with self-monitoring (58%); social cues (58%); holidays (54%); low activity (48%); and internal cues (thought/mood) (44%). Top activity barriers were holidays (51%); time management (50%); internal cues (30%); illness (29%), and motivation (26%). The percentage of the cohort having any type of barrier increased over the long-term intervention period. A majority of the weight loss barriers were significantly associated with younger age, greater obesity, and non-Caucasian race/ethnicity (p-values vary). Physical activity barriers, particularly thought and mood cues, social cues and time management, physical injury or illness and access/weather, were most significantly associated with being female and obese (p < 0.001 for all). Lifestyle coaches used problem-solving with most participants (≥75% short-term; > 90% long term) and regularly reviewed self-monitoring skills. More costly approaches were used infrequently during the first 16 sessions (≤10%) but increased over 3.2 years. CONCLUSION: Behavioral problem solving approaches have short and long term dissemination potential for many kinds of participant barriers. Given minimal resources, increased attention to training lifestyle coaches in the consistent use of these approaches appears warranted.

Inadequate weight gain in overweight and obese pregnant women: what is the effect on fetal growth?

OBJECTIVE: We sought to evaluate inadequate gestational weight gain and fetal growth among overweight and obese women. STUDY DESIGN: We conducted an analysis of prospective singleton term pregnancies in which 1053 overweight and obese women gained >5 kg (14.4 ± 6.2 kg) or 188 who either lost or gained ≤5 kg (1.1 ± 4.4 kg). Birthweight, fat mass, and lean mass were assessed using anthropometry. Small for gestational age (SGA) was defined as ≤10th percentile of a standard US population. Univariable and multivariable analysis evaluated the association between weight change and neonatal morphometry. RESULTS: There was no significant difference in age, race, smoking, parity, or gestational age between groups. Weight loss or gain ≤5 kg was associated with SGA, 18/188 (9.6%) vs 51/1053 (4.9%); (adjusted odds ratio, 2.6; 95% confidence interval, 1.4-4.7; P = .003). Neonates of women who lost or gained ≤5 kg had lower birthweight (3258 ± 443 vs 3467 ± 492 g, P < .0001), fat mass (403 ± 175 vs 471 ± 193 g, P < .0001), and lean mass (2855 ± 321 vs 2995 ± 347 g, P < .0001), and smaller length, percent fat mass, and head circumference. Adjusting for diabetic status, prepregnancy body mass index, smoking, parity, study site, gestational age, and sex, neonates of women who gained ≤5 kg had significantly lower birthweight, lean body mass, fat mass, percent fat mass, head circumference, and length. There were no significant differences in neonatal outcomes between those who lost weight and those who gained ≤5 kg. CONCLUSION: In overweight and obese women weight loss or gain ≤5 kg is associated with increased risk of SGA and decreased neonatal fat mass, lean mass, and head circumference.

Umbilical cord serum interleukin-6, C-reactive protein, and myeloperoxidase concentrations at birth and association with neonatal morbidities and long-term neurodevelopmental outcomes.

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.

Perinatal outcomes in Hispanic and non-Hispanic white women with mild gestational diabetes.

OBJECTIVE: To compare perinatal outcomes between self-identified Hispanic and non-Hispanic white women with mild gestational diabetes mellitus (GDM) or glucose intolerance. METHODS: In a secondary analysis of a mild GDM treatment trial, we compared perinatal outcomes by race and ethnicity for 767 women with glucose intolerance (abnormal 50-g 1-hour screen, normal 100-g 3-hour oral glucose tolerance test), 371 women with mild GDM assigned to usual prenatal care, and 397 women with mild GDM assigned to treatment. Outcomes included: composite adverse perinatal outcome (neonatal death, hypoglycemia, hyperbilirubinemia, hyperinsulinemia, stillbirth, birth trauma), gestational age at delivery, birth weight, and hypertensive disorders of pregnancy. Adjusted regression models included: 100-g 3-hour oral glucose tolerance test results, parity, gestational age, body mass index, maternal age at enrollment, and current tobacco use. RESULTS: The sample of 1,535 women was 68.3% Hispanic and 31.7% non-Hispanic white. Among women with glucose intolerance, Hispanic women had more frequent composite outcome (37% compared with 27%, adjusted odds ratio [OR] 1.62, 95% confidence interval [CI] 1.10-2.37) with more neonatal elevated C-cord peptide (19% compared with 13%, adjusted OR 1.79, 95% CI 1.04-3.08) and neonatal hypoglycemia (21% compared with 13%, adjusted OR 2.04, 95% CI 1.18-3.53). Among women with untreated mild GDM, outcomes were similar by race and ethnicity. Among Hispanic women with treated mild GDM, composite outcome was similar to non-Hispanic white women (35% compared with 25%, adjusted OR 1.62, 95% CI 0.92-2.86), but Hispanic neonates had more frequent hyperinsulinemia (21% compared with 10%, adjusted OR 2.96, 95% CI 1.33-6.60). CONCLUSION: Individual components of some neonatal outcomes were more frequent in Hispanic neonates, but most perinatal outcomes were similar between Hispanic and non-Hispanic ethnic groups. LEVEL OF EVIDENCE: II.

Repeated course antenatal steroids, inflammation gene polymorphisms, and neurodevelopmental outcomes at age 2.

OBJECTIVE: We sought to evaluate the interaction between repeated-course antenatal corticosteroids and inflammation gene polymorphisms with neurodevelopmental outcomes at age 2 years. STUDY DESIGN: We conducted nested case-control analysis of a randomized controlled trial of single- vs repeated-course antenatal corticosteroids. Cases had mental and/or psychomotor delay at age 2 years. Controls had normal neurodevelopment. Previous analyses of 125 cases and 147 controls identified 4 inflammation gene polymorphisms associated with neurodevelopmental delay at age 2 years. RESULTS: The interaction between repeated-course corticosteroids and the interleukin (IL)-6 -174 genotype with neurodevelopmental delay was significant (P = .046). The IL-6 -174 GG genotype was associated with neurodevelopmental delay at age 2 years in the single-course corticosteroid group (odds ratio, 6.47; 95% confidence interval, 1.86-22.50). Exposure to repeated-course antenatal corticosteroids abrogated this genotype effect (odds ratio, 1.30; 95% confidence interval, 0.48-3.54). Results were unchanged after controlling for potential confounders. CONCLUSION: Repeated-course antenatal steroids may reduce the increased risk of neurodevelopmental delay at age 2 years associated with IL-6 -174 GG genotype.

Maternal serum interleukin-6, C-reactive protein, and matrix metalloproteinase-9 concentrations as risk factors for preterm birth <32 weeks and adverse neonatal outcomes.

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.

Bone metabolism in pregnant women exposed to single compared with multiple courses of corticosteroids.

OBJECTIVE: To compare markers of maternal bone metabolism between women who received a single compared with multiple courses of antenatal corticosteroids. METHODS: This is an analysis of serum samples from a previously reported randomized, placebo-controlled, multicenter trial. Women at risk for preterm delivery after an initial course of corticosteroids were randomly assigned to weekly courses of betamethasone (active) or placebo. Serum levels of carboxy terminal propeptide of type I procollagen (PICP) and cross-linked carboxy terminal telopeptide of type I collagen (ICTP) were measured to assess the rate of bone formation and resorption, respectively, at three time points. The placebo group (n=93) was compared with the active group, receiving four or more courses of betamethasone (n=112). RESULTS: There were significant (P<.001) increases in PICP and ICTP between baseline and delivery in both groups. Cross-linked carboxy terminal telopeptide of type I collagen, but not PICP, was lower with corticosteroid exposure immediately before administration of the fourth study course (P<.001). No significant differences in PICP and ICTP were seen between groups at delivery. CONCLUSION: Increasing levels of PICP and ICTP with advancing gestation are consistent with physiologic changes in maternal bone metabolism. Multiple courses of corticosteroids for fetal maturation are not associated with persistent or cumulative effects on maternal bone metabolism as measured by PICP and ICTP. LEVEL OF EVIDENCE: II.