Higher maternal leptin levels at second trimester are associated with subsequent greater gestational weight gain in late pregnancy

Abstract

Background: Excessive gestational weight gain (GWG) is associated with adverse pregnancy outcomes. In non-pregnant populations, low leptin levels stimulate positive energy balance. In pregnancy, both the placenta and adipose tissue contribute to circulating leptin levels. We tested whether maternal leptin levels are associated with subsequent GWG and whether this association varies depending on stage of pregnancy and on maternal body mass index (BMI). Methods: This prospective cohort study included 675 pregnant women followed from 1st trimester until delivery. We collected anthropometric measurements, blood samples at 1st and 2nd trimester, and clinical data until delivery. Maternal leptin was measured by ELISA (Luminex technology). We classified women by BMI measured at 1st trimester: BMI < 25 kg/m2 = normal weight; 25 ≤ BMI < 30 kg/m2 = overweight; and BMI ≥ 30 kg/m2 = obese. Results: Women gained a mean of 6.7 ± 3.0 kg between 1st and 2nd trimester (mid pregnancy GWG) and 5.6 ± 2.5 kg between 2nd and the end of 3rd trimester (late pregnancy GWG). Higher 1st trimester leptin levels were associated with lower mid pregnancy GWG, but the association was no longer significant after adjusting for % body fat (%BF; β = 0.38 kg per log-leptin; SE = 0.52; P = 0.46). Higher 2nd trimester leptin levels were associated with greater late pregnancy GWG and this association remained significant after adjustment for BMI (β = 2.35; SE = 0.41; P < 0.0001) or %BF (β = 2.01; SE = 0.42; P < 0.0001). In BMI stratified analyses, higher 2nd trimester leptin levels were associated with greater late pregnancy GWG in normal weight women (β = 1.33; SE = 0.42; P = 0.002), and this association was stronger in overweight women (β = 2.85; SE = 0.94; P = 0.003 - P for interaction = 0.05). Conclusions: Our results suggest that leptin may regulate weight gain differentially at 1st versus 2nd trimester of pregnancy: at 2nd trimester, higher leptin levels were associated with greater subsequent weight gain - the opposite of its physiologic regulation in non-pregnancy - and this association was stronger in overweight women. We suspect the existence of a feed-forward signal from leptin in second half of pregnancy, stimulating a positive energy balance and leading to greater weight gain.