The Association of Cord Blood 25(OH)D Levels with Neonatal Body Size and Composition: The Healthy Start Study

Abstract

Micronutrient deficiencies during pregnancy are associated with an increased risk of chronic disease in offspring. There is some evidence that vitamin D deficiency in pregnancy is associated with increased offspring adiposity, but evidence from human studies is inconclusive. We examined associations of vitamin D (25‐hydroxyvitamin D [25(OH)D]) in cord blood with neonatal size and body composition in 600 mother‐infant dyads from the Healthy Start study, an ongoing, pre‐birth prospective cohort study in Denver, Colorado. Total 25(OH)D (nmol/L) was measured in cord blood serum collected at delivery (39.6±1.1 weeks gestation). Weight‐for‐gestational‐age z‐scores (WGAZ) were calculated from birth weight (g) and birth length (cm) measured at delivery. Neonatal fat mass (g) and fat‐free mass (g) were measured (median 1 day post‐birth) via air displacement plethysmography (PEA POD). We used multivariable linear regression to examine the association of cord blood 25(OH)D with neonatal outcomes, adjusting for maternal age, education, income, race/ethnicity, pre‐pregnant BMI, prenatal smoking, prenatal physical activity, gestational diabetes, gestational weight gain, offspring gestational age at birth, season of birth, and infant sex. We also evaluated effect modification by maternal race/ethnicity and pre‐pregnant BMI. We observed interactions of total 25(OH)D with race/ethnicity for the outcome of offspring birth weight and with maternal pre‐pregnant BMI for the outcomes of offspring birth weight and fat mass (p<0.05 for all interaction terms). The association between birth weight and 25(OH)D was modified by race (p=0.04). The largest effect was observed in Hispanic participants (β= −103.8 grams per 1 nmol/L increase in 25(OH)D, p=0.003) with smaller effects observed among non‐Hispanic white (β= −55.8g, p=0.03), non‐Hispanic black (β= −44.4g, p=0.21), and other (β= −44.4g, p= 0.28) offspring. Associations of total 25(OH)D with birth weight (p=0.02) and fat mass (p=0.04) also differed by maternal pre‐pregnant BMI. Each kg/m2 increase in pre‐pregnant BMI increased the magnitude of the association between 25(OH)D and birth weight by 0.24g per nmol/L 25(OH)D (p=0.02) and between 25(OH)D and fat mass by 0.08g per nmol/L 25(OH)D (p=0.04). Total 25(OH)D was not associated with offspring birth length (p=0.59), fat‐free mass (p=0.61), or WGAZ (p=0.79). In conclusion, we found that total cord blood 25(OH)D is associated with neonatal size and body composition, although the strength and direction of these associations differ according to maternal race/ethnicity and pre‐pregnant BMI. Further research is needed to understand the implications of these associations as infants grow.Support or Funding InformationSupported by the National Institutes of Health and the American Heart Association