In utero exposure to maternal diabetes or hypertension and childhood hypothalamic gliosis.

Exposure to maternal diabetes (DM) or hypertension (HTN) during pregnancy impacts offspring metabolic health in childhood and beyond. Animal models suggest that induction of hypothalamic inflammation and gliosis in the offspring's hypothalamus is a possible mechanism mediating this effect. We tested, in children, whether in utero exposures to maternal DM or HTN were associated with mediobasal hypothalamic (MBH) gliosis as assessed by brain magnetic resonance imaging (MRI). The study included a subsample of 306 children aged 9-11 years enrolled in the ABCD Study®; 49 were DM-exposed, 53 were HTN-exposed, and 204 (2:1 ratio) were age- and sex-matched children unexposed to DM and/or HTN in utero. We found a significant overall effect of group for the primary outcome of MBH/amygdala (AMY) T2 signal ratio (F(2,300):3.51, p = 0.03). Compared to unexposed children, MBH/AMY T2 signal ratios were significantly higher in the DM-exposed (ß:0.05, p = 0.02), but not the HTN-exposed children (ß:0.03, p = 0.13), findings that were limited to the MBH and independent of adiposity. We concluded that children exposed to maternal DM in utero display evidence of hypothalamic gliosis, suggesting that gestational DM may have a distinct influence on offspring's brain development and, by extension, children's long-term metabolic health.

Cesarean delivery rates and indications in pregnancies complicated by diabetes.

OBJECTIVE: Rates of pregestational (PGDM) and gestational diabetes (GDM), and their associated pregnancy complications, are rising. Pregnancies complicated by diabetes have increased cesarean delivery (CD) rates; however, there are limited data regarding the current rates of, and contributing factors to, these deliveries. The Robson Ten Group Classification System (TGCS) is a clinically relevant, standardized framework that can be used to evaluate and analyze cesarean rates. The objective of this study was to evaluate rates of, and indications for, intrapartum, unplanned CD among pregnancies complicated by diabetes, compared to normoglycemic (NG) pregnancies, in a large United States birth cohort. METHODS: This retrospective cohort study used chart-abstracted data on births between 24 and 42 weeks' gestation at 17 hospitals that contributed to the Obstetrical Care Outcome Assessment Program database between 01/2016 and 03/2019. The CD rate for NG pregnancies, and pregnancies complicated by gestational and PGDM was calculated and compared using the Robson TGCS. The indications for intrapartum CD in patients with term, singleton, vertex gestations without a prior cesarean were then analyzed. Univariate and multivariate logistic regression models were used to compare the cesarean rate and indications for CD, between the diabetic groups and the NG group. Results were adjusted for maternal age, BMI, neonatal birth weight, and insurance status, as well as clustering by hospital. RESULTS: A total of 86,381 pregnant people were included in the study cohort. Of these 76,272 (88.3%) were NG, 8591 (9.9%) had GDM, and 1518 (1.8%) had PGDM. Compared to NG patients, overall cesarean rates were higher in patients with GDM (40.3% vs. 29.7%; aOR 1.25, 95%CI 1.18-1.31) and PGDM (60.0% vs. 29.7%; aOR 2.53, 95%CI 2.04-3.13). This finding remained true when the cohort was restricted to term, singleton, vertex laboring patients without a prior cesarean; compared to NG patients, the cesarean rate was higher in patients with GDM (17.4% vs. 12.2%, aOR 1.37, 95%CI 1.29-1.45) and PGDM (26.0% vs. 12.2%, aOR 2.55, 95%CI 2.00-3.25). The cesarean rate for fetal indications was similar in the GDM (5.7%) and NG (4.4%) groups, while those patients with PGDM had a significantly higher rate (10.4%; aOR 2.01, 95%CI 1.43-2.83). Similarly, the rate of cesarean for labor dystocia in patients with PGDM was significantly higher than in NG patients (16.9% vs. 7.0%, and aOR 2.28, 95%CI 1.66-3.13) while patients with GDM had an intermediate rate (10.6% vs. 7.0%, aOR 1.49, 95%CI 1.40-1.57). CONCLUSIONS: The CD rate is significantly higher in pregnancies complicated by diabetes, particularly pregestational, compared to NG pregnancies. Despite controlling for maternal factors and birth weight, pregnancies complicated by diabetes are more likely to undergo an unplanned intrapartum cesarean secondary to labor dystocia than their NG counterparts, but only pregnancies complicated by PGDM have an increased risk of cesarean for fetal indications. More research is needed to understand whether this higher cesarean rate is due to factors intrinsic to diabetes in laboring patients or is due to a difference in the way clinicians manage diabetics in labor.

Exposure to Gestational Diabetes Mellitus Prior to 26 Weeks Is Related to the Presence of Mediobasal Hypothalamic Gliosis in Children.

Intrauterine exposure to metabolic dysfunction leads to offspring metabolic dysfunction in human and rodent models, but underlying mechanisms are unclear. The mediobasal hypothalamus (MBH) is involved in energy homeostasis and weight regulation, and MBH gliosis is associated with obesity and insulin resistance. We tested the hypothesis that offspring exposed to gestational diabetes mellitus (GDM) in utero versus those unexposed would show evidence of MBH gliosis. Participants in the BrainChild Study (age 7-11 years with confirmed GDM exposure or no GDM exposure) underwent brain MRI to acquire T2-weighted images. By using the amygdala (AMY) and white matter (WM) as reference regions, MBH:AMY and MBH:WM T2 signal ratios were calculated as a radiologic measure of MBH gliosis. Linear regressions were used to examine associations between GDM exposure (GDM overall) and by timing of GDM exposure (≤26 weeks or >26 weeks) and MBH gliosis. Associations between prepregnancy BMI and child MBH gliosis were examined in secondary analyses. There were no differences in T2 signal ratios in children exposed versus not exposed to GDM overall, but children exposed to early GDM (≤26 weeks of gestation) had higher MBH:WM signal ratios than those not exposed (ß = 0.147; SE 0.06; P = 0.03), adjusting for child's age, sex, and BMI z score and maternal prepregnancy BMI, whereas no associations were seen for the control ratio (AMY:WM). Prepregnancy BMI was not associated with evidence of MBH gliosis. Early exposure to GDM was associated with radiologic evidence of MBH gliosis in children. These data provide mechanistic insight into brain pathways by which exposure to GDM may increase risk for metabolic dysfunction.