Maternal Body Mass Index, Early-Pregnancy Metabolite Profile, and Birthweight

Abstract

Context: Maternal prepregnancy body mass index (BMI) has a strong influence on gestational metabolism, but detailed metabolic alterations are unknown.

Objective: First, to examine the associations of maternal prepregnancy BMI with maternal early-pregnancy metabolite alterations. Second, to identify an early-pregnancy metabolite profile associated with birthweight in women with a higher prepregnancy BMI that improved prediction of birthweight compared to glucose and lipid concentrations.

Design, setting, and participants: Prepregnancy BMI was obtained in a subgroup of 682 Dutch pregnant women from the Generation R prospective cohort study.

Main outcome measures: Maternal nonfasting targeted amino acids, nonesterified fatty acid, phospholipid, and carnitine concentrations measured in blood serum at mean gestational age of 12.8 weeks. Birthweight was obtained from medical records.

Results: A higher prepregnancy BMI was associated with 72 altered amino acids, nonesterified fatty acid, phospholipid and carnitine concentrations, and 6 metabolite ratios reflecting Krebs cycle, inflammatory, oxidative stress, and lipid metabolic processes (P-values < 0.05). Using penalized regression models, a metabolite profile was selected including 15 metabolites and 4 metabolite ratios based on its association with birthweight in addition to prepregnancy BMI. The adjusted R2 of birthweight was 6.1% for prepregnancy BMI alone, 6.2% after addition of glucose and lipid concentrations, and 12.9% after addition of the metabolite profile.

Conclusions: A higher maternal prepregnancy BMI was associated with altered maternal early-pregnancy amino acids, nonesterified fatty acids, phospholipids, and carnitines. Using these metabolites, we identified a maternal metabolite profile that improved prediction of birthweight in women with a higher prepregnancy BMI compared to glucose and lipid concentrations.

Keywords: birth complications; metabolomics; obesity; pregnancy.

Figure 1.

Significant associations of maternal prepregnancy BMI with maternal early-pregnancy metabolites.

Figure 2.

Significant associations of maternal prepregnancy overweight or obesity with maternal early-pregnancy metabolites. Regression coefficients were obtained from linear regression models that reflect the difference in maternal early-pregnancy metabolite concentrations in SD score (SDS) per kg/m² increase in maternal prepregnancy body mass index (Fig. 1) and difference in maternal early-pregnancy metabolite concentrations in SDS for overweight or obese women as compared to normal weight women (Fig. 2) of associations with false discovery rate corrected P-values < 0.05. Models were adjusted for gestational age at blood sampling, age, educational level, parity, smoking, alcohol consumption, folic acid supplementation, daily total energy intake, systolic blood pressure, and fetal sex. Abbreviations: AA, amino acid; NEFA, nonesterified fatty acid; PC.aa diacyl-phosphatidylcholines, PC.ae, acyl-alkyl-phosphatidylcholines; Lyso.PC.a, acyl-lysophosphatidylcholines; SM, sphingomyelines Carn.a, acylcarnitines.