Prenatal vitamin D and cord blood insulin-like growth factors in Dhaka, Bangladesh

Abstract

Fetal growth restriction is linked to adverse health outcomes and is prevalent in low- and middle-income countries; however, determinants of fetal growth are still poorly understood. The objectives were to determine the effect of prenatal vitamin D supplementation on the insulin-like growth factor (IGF) axis at birth, to compare the concentrations of IGF-I in newborns in Bangladesh to a European reference population and to estimate the associations between IGF protein concentrations and birth size. In a randomized controlled trial in Dhaka, Bangladesh, pregnant women enrolled at 17-24 weeks of gestation were assigned to weekly oral vitamin D3 supplementation from enrolment to delivery at doses of 4200 IU/week, 16,800 IU/week, 28,000 IU/week or placebo. In this sub-study, 559 woman-infant pairs were included for analysis and cord blood IGF protein concentrations were quantified at birth. There were no significant effects of vitamin D supplementation on cord blood concentrations of IGF-I (P = 0.398), IGF-II (P = 0.525), binding proteins (BPs) IGFBP-1 (P = 0.170), IGFBP-3 (P = 0.203) or the molar ratio of IGF-I/IGFBP-3 (P = 0.941). In comparison to a European reference population, 6% of girls and 23% of boys had IGF-I concentrations below the 2.5th percentile of the reference population. IGF-I, IGF-II, IGFBP-3 and the IGF-I/IGFBP-3 ratio were positively associated with at least one anthropometric parameter, whereas IGFBP-1 was negatively associated with birth anthropometry. In conclusion, prenatal vitamin D supplementation does not alter or enhance fetal IGF pathways.

Keywords: IGF axis; fetal growth; pregnancy; vitamin D.

Figure 1

Cord blood IGF-I concentrations and newborn length-for-age z-scores (LAZ) for boys (A) and girls (B) in Dhaka, Bangladesh (n = 245 for boys; n = 247 for girls). Reference ranges for IGF-I and LAZ are shaded in gray, from the 2.5th to 97.5th percentiles of the reference population for IGF-I and −2 to +2 z-scores for LAZ. For IGF-I, the reference range was based on Bidlingmaier et al. (18), using 27–157 ng/mL for males and 17.9–125.6 ng/mL for females. LAZ was based on the INTERGROWTH-21st neonatal size standards; the range shown is from −2 to 2 z-score.