Maternal Serum Heme-Oxygenase-1 (HO-1) Concentrations in Early Pregnancy and Subsequent Risk of Gestational Diabetes Mellitus

Background: Heme oxygenase-1 (HO-1) concentrations have been recently reported to be elevated in impaired glucose tolerance and type 2 diabetes mellitus (T2DM). However, no study has examined the association between HO-1 concentrations and gestational diabetes mellitus (GDM). Methods: In a case-control study, nested within a prospective cohort of pregnant women (186 GDM cases and 191 women who remained eu-glycemic through pregnancy), we assessed the association of maternal serum HO-1 concentrations, measured in samples collected at 16 weeks gestation, on average, with subsequent risk of GDM. Maternal serum HO-1 concentrations were determined using ELISA. We fitted multivariate logistic regression models to derive estimates of odds ratios (ORs) and 95% confidence intervals (CIs). Results: Median serum HO-1 concentrations in early pregnancy were lower in women who subsequently developed GDM compared with those who did not (1.60 vs. 1.80 ng/mL, p-value = 0.002). After adjusting for maternal age, race, family history of T2DM and pre-pregnancy body mass index, women with HO-1≥3.05 ng/mL (highest decile) experienced a 74% reduction of GDM risk (95% CI; 0.09–0.77) compared with women whose concentrations were<1.23 ng/mL (lowest quartile). Conclusion: Serum HO-1 concentrations were inversely associated with subsequent GDM risk. These findings underscore the role of oxidative stress in the pathogenesis of GDM. Additional studies are warranted to confirm the clinical utility of serum HO-1 in diagnosis of GDM, particularly in the early pregnancy

Sleep duration and plasma leptin concentrations in early pregnancy among lean and overweight/obese women: a cross sectional study

Background: Early-pregnancy short sleep duration is predictive of gestational diabetes and preeclampsia; mechanisms for these associations are unknown. Leptin, an adipocyte-derived peptide involved in regulating food intake and energy expenditure, may play a role in these observed associations. Given inconsistent reports linking short sleep duration with leptin, and absence of studies among pregnant women, we examined the association of maternal sleep duration with plasma leptin in early pregnancy. Methods: This cross-sectional study included 830 pregnant women. Plasma leptin was measured in samples collected around 13 weeks gestation. Sleep duration was categorized as: ≤5, 6, 7–8 (reference), and ≥9 hours. Differences in leptin concentrations across categories were estimated using linear regression. Analyses were completed for lean and overweight/obese women. Results: Overall, women with long sleep duration had elevated plasma leptin (p-value = 0.04). However, leptin concentrations were not statistically significantly elevated in women with a short sleep duration. There was no association of leptin with sleep duration among lean women. Among overweight/obese women, a U-shaped relation between leptin and sleep duration was observed: Mean leptin was elevated (β = 21.96 ng/ml, P < 0.001) among women reporting ≤5 hour of sleep compared with reference group; and women reporting ≥9 hours of sleep also had elevated leptin (β = 4.29 ng/ml, P = 0.09). Conclusions: Short sleep duration, and to a lesser extent long sleep duration, were associated with elevated leptin among overweight/obese women. These data add some evidence to help understand mechanistic relationships of sleep duration with pregnancy complications

Sex-specific associations of maternal birthweight with offspring birthweight in the Omega study.

PURPOSE: We investigated nonlinear and offspring sex-specific associations of maternal birthweight (BW) with offspring BW among participants of the Omega study, a pregnancy cohort. METHODS: Maternal BW was modeled as a continuous variable, linear spline and binary variable indicating low birthweight (LBW;≥2500 grams). Offspring BW was modeled as a continuous and binary variable in regression models. Nonlinearity was assessed using likelihood ratio tests (LRTs) in marginal linear spline models. RESULTS: For every 100-gram increase of maternal BW, offspring BW increased by 22.29 (95% CI: 17.57, 27.02) or 23.41 (95% CI: 6.87, 39.96) grams among mothers with normal BW or born macrosomic, respectively, but not among LBW mothers (β = -8.61 grams; 95% CI: -22.88, 5.65; LRT P-value = .0005). For every 100-gram increase in maternal BW, BW of male offspring increased 23.47 (95% CI: 16.75, 30.19) or 25.21 (95% CI: 4.35, 46.07) grams among mothers with normal BW or born macrosomic, respectively, whereas it decreased 31.39 grams (95% CI: -51.63, -11.15) among LBW mothers (LRT P-value \u3c .0001). Corresponding increases in BW of female offspring (16-22 grams) did not differ among mothers with LBW, normal BW or macrosomia (LRT P-value = .9163). CONCLUSIONS: Maternal and offspring BW associations are evident among normal BW and macrosomic mothers. These associations differ by offspring sex

Sleep duration, vital exhaustion, and odds of spontaneous preterm birth: a case–control study

Background: Preterm birth is a leading cause of perinatal morbidity and mortality worldwide, resulting in a pressing need to identify risk factors leading to effective interventions. Limited evidence suggests potential relationships between maternal sleep or vital exhaustion and preterm birth, yet the literature is generally inconclusive. Methods: We examined the relationship between maternal sleep duration and vital exhaustion in the first six months of pregnancy and spontaneous (non-medically indicated) preterm birth among 479 Peruvian women who delivered a preterm singleton infant (<37 weeks gestation) and 480 term controls who delivered a singleton infant at term (≥37 weeks gestation). Maternal nightly sleep and reports of vital exhaustion were ascertained through in-person interviews. Spontaneous preterm birth cases were further categorized as those following either spontaneous preterm labor or preterm premature rupture of membranes. In addition, cases were categorized as very (<32 weeks), moderate (32–33 weeks), and late (34- <37 weeks) preterm birth for additional analyses. Logistic regression was used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). Results: After adjusting for confounders, we found that short sleep duration (≤6 hours) was significantly associated with preterm birth (aOR = 1.56; 95% CI 1.11-2.19) compared to 7–8 hours of sleep. Vital exhaustion was also associated with increased odds of preterm birth (aOR = 2.41; 95% CI 1.79-3.23) compared to no exhaustion (Ptrend <0.001). These associations remained significant for spontaneous preterm labor and preterm premature rupture of membranes. We also found evidence of joint effects of sleep duration and vital exhaustion on the odds of spontaneous preterm birth. Conclusions: The results of this case–control study suggest maternal sleep duration, particularly short sleep duration, and vital exhaustion may be risk factors for spontaneous preterm birth. These findings call for increased clinical attention to maternal sleep and the study of potential intervention strategies to improve sleep in early pregnancy with the aim of decreasing risk of preterm birth

Agreement of self-reported physician diagnosis of migraine with international classification of headache disorders-II migraine diagnostic criteria in a cross-sectional study of pregnant women

Background: Migraine, a common chronic-intermittent disorder among reproductive age women, has emerged as a novel risk factor for adverse perinatal outcomes. Diagnostic reliability of self-report of physician-diagnosed migraine has not been investigated in pregnancy cohort studies. We investigated agreement of self-report of physician-diagnosed migraine with the diagnostic criteria promoted by the International Classification of Headache Disorders, 2nd edition (ICHD-II). Methods: The cross-sectional study was conducted among 500 women who provided information on a detailed migraine questionnaire that allowed us to apply all ICHD-II diagnostic criteria. Results: Approximately 92% of women reporting a diagnosis of migraine had the diagnosis between the ages of 11 and 40 years (40 years 1.0%). We confirmed self-reported migraine in 81.6% of women when applying the ICHD-II criteria for definitive migraine (63.1%) and probable migraine (18.5%). Conclusion: There is good agreement between self-reported migraine and ICHD-II-based migraine classification in this pregnancy cohort. We demonstrate the feasibility of using questionnaire-based migraine assessment according to full ICHD-II criteria in epidemiological studies of pregnant women

Placental genetic variations in vitamin D metabolism and birthweight.

INTRODUCTION: Vitamin D has pleiotropic functions that regulate fetal growth and development. We investigated associations of common placental genetic variations in vitamin D metabolism with birthweight. METHODS: The study was conducted among participants (506 maternal-infant pairs) of a pregnancy cohort study. Data were collected using interviewer-administered questionnaires and post-delivery medical record abstraction. DNA, extracted from placental samples collected at delivery, was genotyped for eight single nucleotide polymorphisms (SNPs) in five vitamin D metabolism genes (CUBN, LRP2, VDR, GC, and CYP2R1). Linear and logistic regression models were used to evaluate associations of SNPs with birthweight and risk of low birthweight, respectively. Effect modification of associations by infant sex was examined using stratified analyses and interaction terms in regression models. RESULTS: Mean (standard-deviation) birthweight among all, male, and female infants was 3482.1 (549.9), 3544.6 (579.0) and 3419.2 (512.5) grams, respectively. Each copy of the minor allele of rs2282679 (GC) was associated with a 68.6 g (95%CI:3.1134.7 g) increase in birthweight overall. Sex-specific associations were observed for SNP rs4667591 (LRP2) (p-value for interaction \u3c 0.001). Each copy of the minor allele of rs4667591 was associated with a 124.7 g (95%CI:20.1229.0 g) increase in birthweight among female infants, and a suggested 81.6 g decrease in birthweight among male infants (95%CI:-183.7,20.5 g). DISCUSSION: Our study identified overall and sex-specific associations between placental genetic variations in vitamin D metabolism and birthweight. If confirmed by larger replication studies, observed associations may provide insight into mechanistic underpinnings of the relationships between placental vitamin D metabolism and birth size