Dataset Information

Children Exposed to Maternal Obesity or Gestational Diabetes Mellitus During Early Fetal Development Have Hypothalamic Alterations That Predict Future Weight Gain.

ABSTRACT:

Objective

Exposure in utero to maternal obesity or gestational diabetes mellitus (GDM) is linked to a high risk for obesity in offspring. Animal studies suggest that these exposures disrupt the development of the hypothalamus, a brain region that regulates body weight, predisposing offspring to develop obesity. This study tested the hypothesis in humans that in utero exposure to maternal obesity and/or GDM is associated with alterations in the hypothalamic response to glucose and the altered hypothalamic response would predict greater increases in child adiposity 1 year later.

Research design and methods

Participants were 91 children aged 7-11 years with and without in utero exposure to GDM. Maternal prepregnancy BMI and GDM exposures were determined from electronic medical records. Arterial spin labeling MRI was used to determine the child's hypothalamic blood flow response to oral glucose. Anthropometric measures were acquired in all children at their initial visit and again 1 year later in a subset of 44 children.

Results

Children exposed to GDM diagnosed at ≤26 weeks' gestation had increased hypothalamic blood flow (a marker of hypothalamic activation) in response to glucose when compared with unexposed children, and results remained after adjustments for child age, sex, BMI, and maternal prepregnancy BMI. Maternal prepregnancy BMI was positively associated with the child's hypothalamic response to glucose. Greater hypothalamic response to glucose predicted greater increases in child's BMI 1 year later.

Conclusions

Increased glucose-linked hypothalamic activation during childhood represents a possible mechanism by which exposure to maternal metabolic disorders during fetal development increases future risk for obesity.

SUBMITTER: Page KA

PROVIDER: S-EPMC6647040 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundClinical recommendations to limit gestational weight gain (GWG) imply high GWG is causally related to adverse outcomes in mother or offspring, but GWG is the sum of several inter-related complex phenotypes (maternal fat deposition and vascular expansion, placenta, amniotic fluid and fetal growth). Understanding the genetic contribution to GWG could help clarify the potential effect of its different components on maternal and offspring health. Here we explore the genetic contribution to total, early and late GWG.Participants and methodsA genome-wide association study was used to identify maternal and fetal variants contributing to GWG in up to 10 543 mothers and 16 317 offspring of European origin, with replication in 10 660 mothers and 7561 offspring. Additional analyses determined the proportion of variability in GWG from maternal and fetal common genetic variants and the overlap of established genome-wide significant variants for phenotypes relevant to GWG (for example, maternal body mass index (BMI) and glucose, birth weight).ResultsApproximately 20% of the variability in GWG was tagged by common maternal genetic variants, and the fetal genome made a surprisingly minor contribution to explain variation in GWG. Variants near the pregnancy-specific beta-1 glycoprotein 5 (PSG5) gene reached genome-wide significance (P=1.71 × 10-8) for total GWG in the offspring genome, but did not replicate. Some established variants associated with increased BMI, fasting glucose and type 2 diabetes were associated with lower early, and higher later GWG. Maternal variants related to higher systolic blood pressure were related to lower late GWG. Established maternal and fetal birth weight variants were largely unrelated to GWG.ConclusionsWe found a modest contribution of maternal common variants to GWG and some overlap of maternal BMI, glucose and type 2 diabetes variants with GWG. These findings suggest that associations between GWG and later offspring/maternal outcomes may be due to the relationship of maternal BMI and diabetes with GWG.