Maternal vitamin D concentrations during pregnancy, fetal growth patterns, and risks of adverse birth outcomes

Abstract

Background: Maternal vitamin D deficiency during pregnancy may affect fetal outcomes.

Objective: The objective of this study was to examine whether maternal 25-hydroxyvitamin D [25(OH)D] concentrations in pregnancy affect fetal growth patterns and birth outcomes.

Design: This was a population-based prospective cohort in Rotterdam, Netherlands in 7098 mothers and their offspring. We measured 25(OH)D concentrations at a median gestational age of 20.3 wk (range: 18.5-23.3 wk). Vitamin D concentrations were analyzed continuously and in quartiles. Fetal head circumference and body length and weight were estimated by repeated ultrasounds, and preterm birth (gestational age <37 wk) and small size for gestational age (less than the fifth percentile) were determined.

Results: Adjusted multivariate regression analyses showed that, compared with mothers with second-trimester 25(OH)D concentrations in the highest quartile, those with 25(OH)D concentrations in the lower quartiles had offspring with third-trimester fetal growth restriction, leading to a smaller head circumference, shorter body length, and lower body weight at birth (all P < 0.05). Mothers who had 25(OH)D concentrations in the lowest quartile had an increased risk of preterm delivery (OR: 1.72; 95% CI: 1.14, 2.60) and children who were small for gestational age (OR: 2.07; 95% CI: 1.33, 3.22). The estimated population attributable risk of 25(OH)D concentrations <50 nmol/L for preterm birth or small size for gestational age were 17.3% and 22.6%, respectively. The observed associations were not based on extreme 25(OH)D deficiency, but presented within the common ranges.

Conclusions: Low maternal 25(OH)D concentrations are associated with proportional fetal growth restriction and with an increased risk of preterm birth and small size for gestational age at birth. Further studies are needed to investigate the causality of these associations and the potential for public health interventions.

Keywords: 25(OH)D; birth weight; fetal growth; pediatrics; pregnancy; preterm birth; small-size for gestational age; vitamin D.

Figure 1. Associations of Maternal Second Trimester 25(OH)D Concentrations with Fetal Growth Patterns (N = 7098)

Values are estimates based on repeated linear regression models and reflect the standard deviation score for each growth characteristic in offspring of mothers whose 25(OH)D concentrations during pregnancy were in the first, second and third quartile compared to offspring from mothers who had 25(OH)D concentrations in the fourth quartile. Length at birth represents the full body length and weight at birth is the measured birth weight.

Figure 2. Associations of Maternal Second Trimester 25(OH)D Concentrations with the Risks of Adverse Birth Outcomes (N= 7098)

Values are logistic regression coefficients (95% confidence interval) and reflect the risk of adverse birth outcomes compared to the reference group. Continuous analyses reflect the risks of being preterm, having a low birth weight or being small-size for gestational age at birth per 1 SDS increase in maternal 25(OH)D. Multivariable model is adjusted for maternal characteristics (age, body mass index at intake, alcohol consumption, smoking during pregnancy, folic acid and vitamin supplements, energy, iron, zinc, and calcium dietary intake during pregnancy, education, ethnicity, gestational hypertensive disorders, gestational diabetes, parity, season when blood samples were drawn and the presence of anorexia).