Gestational diabetes and offspring birth size at elevated environmental pollutant exposures

Abstract

Background Gestational diabetes mellitus (GDM) is associated with increased availability of glucose and macronutrients in fetal circulation and macrosomia. Therefore, the role of GDM in the association between metabolism-disrupting chemicals and birth size deserves attention. Objective We examined whether GDM may mediate or modify the associations between maternal environmental pollutant exposures and offspring birth size measures. Methods We analysed 604 Faroese pregnant women and their offsprings born in 1997-2000. Maternal pregnancy serum concentrations of organochlorine compounds (OCs: polychlorinated biphenyl (PCB) congeners and dichlorodiphenyldichloroethylene (DDE)), and five perfluoroalkyl substances (PFASs), and hair and cord blood mercury concentrations were measured. We used regression (single-pollutants) and structural equation models (SEMs) (multiple-pollutant analyses using latent constructs of OCs, PFASs and mercury) to estimate the associations with GDM and birth size measures, accounting for mediation and/or effect modification by GDM. Results Serum-DDE and hair-mercury concentrations were associated with GDM (adjusted OR per concentration doubling: 1.29; 95% CI: 0.94, 1.77 for DDE, and 0.79; 95% CI: 0.62, 0.99 for mercury), but in multiple pollutant-adjusted SEMs only a positive association between OC exposure and GDM remained significant (change in GDM odds per OC doubling: 0.45; 95% CI: 0.05, 0.86). PCB and overall OC exposure were positively associated with head circumference (SEM; mean change per OC doubling: 0.13 cm; 95% CI, 0.01. 0.25). Overall PFAS exposure was inversely associated with birth weight (SEM; mean change per PFAS doubling: -169 g; 95% CI: -359, 21), and for many single-PFASs we found a pattern of inverse associations with birth weight and head circumference in boys, and positive or null associations in girls. None of the environmental pollutants was associated with offspring length. GDM neither modified nor mediated the associations with birth size measures. Conclusions We found associations with GDM and offspring birth size to be specific to the environmental pollutant or pollutant group. Associations with birth size measures appear to be independent of GDM occurrence.

Identification of sex-specific DNA methylation changes driven by specific chemicals in cord blood in a Faroese birth cohort

“…Our findings are in agreement with published studies, including a previous study in a Faroese birth cohort [69], showing inverse associations between cord blood PFOS, and head circumference, ponderal index [70,71], and/or birth weight [71,72]. In the Faroese study [69], inverse associations between PFOS exposure and birth size measures were more pronounced in boys, while mainly null or positive in girls, which is in line with the sex-specific DNA methylation changes noted for PFOS in the present study. In short, the persistent nature of these DNA methylation-associated chemicals raises concerns of their long-lasting health effects from birth to later-life.…”

Maternal Metabolic Health Parameters During Pregnancy in Relation to Early Childhood BMI Trajectories

“…Moreover, despite the known relationships of GDM with high birth size and increased obesity risk , we found no clear association between GDM and children's BMI trajectories. The prevalence of the clinical diagnosis of GDM in this cohort was relatively low (4.4%), which may be due to the fact that in Spain, as well as in other European regions , only women considered at high risk (based on their age and clinical history) undertake an OGCT. Misclassification of GDM cases is therefore likely and could have attenuated associations toward the null.…”

Perfluoroalkyl substances and glycemic status in pregnant Danish women: The Odense Child Cohort

“…Our mean concentration of PFNA was comparable to a Spanish cohort study of pregnant women with PFAS assessment at early pregnancy (13), PFHxS and PFOA concentrations were slightly lower and PFOS concentration was higher in our study. Our study findings 236 need to be considered in light of four previous studies (11)(12)(13) that investigated associations 237 between PFAS concentrations and diagnosis of IGT (12,13) and GDM (11)(12)(13)(14). In the first 238 study (11), researchers observed a positive trend between pre-pregnancy PFNA concentration 239 and self-reported GDM in U.S. women, and a higher PFOA concentration was associated 240…”

“…However, the authors (13) reported a positive trend between PFHxS or PFOS concentrations and GDM diagnosis. In contrast, a Faroese study (14) found no clear association between PFOS, PFOA, PFHxS, PFNA, or PFDA concentrations and risk of GDM diagnosis in pregnant women. In our study, glycemic status was thoroughly studied biochemically at fasting and during OGTT (N=318), whereas the self-reported GDM (11) Women diagnosed with early GDM might have received nutritional counseling or even insulin injections in order to regulate glucose metabolism.…”

“…The third trimester 78 represents a physiological window of opportunity to study possible effects of PFASs on gly-79 cemic status, as glucose homeostasis is already challenged. Four previous studies (11)(12)(13)(14) in 80 pregnant women looked at associations between PFAS concentrations and the diagnosis of 81 GDM alone or GDM including IGT based on self-reported data (11) or extracted from medi-82 cal records (12)(13)(14). However, glucose and insulin concentrations were not measured in any 83 of the studies, and only one report included measurements of fasting glucose (15).…”