Association between maternal and fetal inflammatory biomarkers and offspring weight and BMI during the first year of life in pregnancies with GDM: MySweetheart study

Background: Gestational Diabetes Mellitus (GDM) is frequently associated with chronic, low-grade inflammation. Whether this environment affects offspring anthropometry during early childhood remains to be elucidated. The aim of this study was to investigate the associations between maternal and fetal (cord blood-umbilical artery) inflammatory biomarkers and offspring weight and BMI up to 1 year in pregnancies with GDM.

Methods: In this prospective secondary analysis of the MySweetheart study, we included 193 women with GDM and their offspring. Maternal and fetal (N=39) predictors included serum levels of inflammatory biomarkers including CRP, IL-6, and TNF-α at 24-32 weeks of gestational age (GA) and in the cord blood. Offspring outcomes were small and large for gestational age (SGA, LGA), sex- and age-adjusted weight, and BMI at birth and at 1 year. Univariate and multivariate regression models were performed. Associations were adjusted for maternal pre-pregnancy BMI, age, and ethnicity.

Results: Mean maternal age was 33.6 ± 4.8 years, and pre-pregnancy BMI 25.9 ± 5.6 kg/m2. Their mean gestational age at the 1st GDM visit was 29 ± 2.4 weeks. Gestational age at delivery was 39.7 ± 1.1 weeks, with a mean birthweight of 3.4 ± 0.46 kg; 11.8% of offspring were LGA and 10.8% were SGA. At 1 year of age, mean offspring weight was 9.8 ± 1.2 kg and BMI z-score 0.23 ± 1.1 kg/m2. In the models including only maternal predictors, TNF-α at 24-32 weeks of GA was positively associated with SGA and inversely with offspring weight and BMI at birth and at 1 year (p ≤0.034). In the models including only fetal predictors and the combined model, CRP was inversely associated with BMI at 1 year (p ≤0.020).

Conclusions: In women with GDM, maternal and fetal inflammatory biomarkers distinctively influenced offspring anthropometry during the first year of life, independent of maternal age, prepregnancy BMI and ethnicity. These results suggest that low-grade inflammation during pregnancy may affect the developing offspring by leading to a decrease in weight and BMI and may have implications for future personalized follow-up of women with GDM and their offspring.