Response to Letter: Genetics and Vitamin D supplementation in pregnancy

We thank Dr Paschou and colleagues for their interest in our recent publication (1) and their thoughtfully considered clinical implications of our findings.

We agree that ethnic clustering of genotypes in DHCR7, which might have previously conferred an evolutionary advantage to protect against vitamin D toxicity, might now contribute to the paradoxically low 25-hydroxyvitamin D [25(OH)D] levels at latitudes close to the equator.

Antenatal vitamin D supplementation is a proven approach to increasing maternal 25(OH)D status in pregnancy (2) and reduces the incidence of symptomatic neonatal hypocalcaemia (3). We agree with Paschou et al that, based on our findings, genetic variation is likely to contribute to the poor response to supplementation in some women. However we have also previously demonstrated that lower 25(OH)D status before supplementation, poorer compliance with supplementation and greater weight gain during pregnancy are associated with a lower achieved 25(OH)D after supplementation (4). As such, in the absence of genetic screening incorporated into routine clinical practice, these clinical markers should be used to guide counselling regarding antenatal vitamin D supplementation. We have also previously identified a number of characteristics of women who are less likely to take prenatal vitamin D supplementation. These include: being of younger age, less well educated, a smoker, in second or subsequent pregnancy, and having a higher BMI (5). Women with these characteristics might therefore benefit from greater support to optimise antenatal health.

Any analysis of the economic and healthcare benefit of undertaking routine 25(OH)D screening in pregnancy will be country dependent; such an approach is not currently employed in the United Kingdom, but supplementation with 400 IU/day vitamin D throughout pregnancy is advised for all women (6). The 25(OH)D level which is considered to represent vitamin D repletion remains hotly debated, but, perhaps more importantly, confirmation of a seasonally dependent benefit of antenatal vitamin D supplementation for offspring bone mass demonstrated in the MAVIDOS trial (2), and elucidation of effects on other outcomes, is required through further rigorously conducted randomised controlled trials in pregnancy (7). Such as approach will be essential to demonstrate clear clinical benefits of supplementation, rather than selecting an optimal 25(OH)D level based on observational studies, which are subject to confounding and reverse causality (8).