Does Higher Vitamin D Intake During Pregnancy Reduce the Risk of Multiple Sclerosis in Offspring?

Abstract & Commentary

By Jai S. Perumal, MD, Assistant Professor of Neurology, Weill Cornell Medical College. Dr Perumal is a consultant for Biogen Idec, and is on the speakers bureau for Teva and Biogen Idec.

Synopsis: Based on data from the Nurses' Health Study II, the authors report that higher maternal intake of vitamin D during pregnancy may be associated with a lower risk of multiple sclerosis in their children.

Source: Mirzaei F, et al. Gestational vitamin D and the risk of multiple sclerosis in offspring. Ann Neurol 2011;70:30-40.

There is growing evidence that vitamin d exposure is inversely associated with the risk of developing multiple sclerosis (MS) and the risk of relapses in patients with established disease. Both epidemiological studies and experimental data from animal models of MS support a protective role of vitamin D. Putative immune modulatory mechanisms for these effects have been proposed as well. The present study by Mirzaei et al takes this concept of "protection" further and examines the influence of gestational vitamin D on the subsequent risk of MS in the offspring.

The Nurses' Health Study II was a cohort of 116,430 female, registered nurses between the ages of 25-42 years, which began in 1989. At baseline and at subsequent biennial follow-up, the nurses provided information on demographics, lifestyle, health-related factors, and any newly diagnosed diseases including MS. The Nurses' Mothers Study began in 2001 when the Nurses' Health Study II participants free of cancer were requested for permission to send out questionnaires to their mothers. This was restricted to nurses with living biological mothers free of debilitating disease. The information collected from the mothers included diet during pregnancy, demographics, and lifestyle experiences; 35,794 nurses' mothers completed the questionnaire. The authors of this study assessed maternal exposure to different sources of vitamin D, including fortified milk intake and dietary vitamin D and predicted serum 25(OH)D. The mothers reported their milk intake by choosing one of seven categories ranging from never to four or more glasses/day. The total dietary vitamin D intake from food was calculated by summing up the vitamin D from each of the vitamin D containing food the mothers had reported to have taken. Direct serum 25(OH) measurements were not available. Predicted serum 25(OH)D was calculated using a prediction model factoring in several variables that influence vitamin D levels including race, vitamin D from food, vitamin D supplements, ultraviolet light-B flux, age, BMI, physical activity, alcohol intake, and hormonal use.

MS was diagnosed in 199 nurses, of which 147 were incident cases diagnosed after the start of the cohort in 1989 and 52 were prevalent cases diagnosed prior to recruitment. The association between maternal exposures to vitamin D and risk of developing MS in the offspring was investigated. Maternal milk intake was inversely associated with the daughters' risk of MS. The risk of MS among the nurse daughters was 38% lower if their mothers consumed 2-3 glasses of milk per day compared to mothers who consumed 3 or fewer glasses of milk per month. The pooled multivariate adjusted RR was 0.62 (95% confidence interval [CI], 0.40-0.95; P trend = 0.001). Mothers' vitamin D intake from food during pregnancy also was inversely associated with the risk of MS in their daughters, with a 40% lower risk when comparing the highest with the lowest quintile of vitamin D consumption. Similarly, predicted 25(OH)D levels in pregnant mothers was inversely associated with the risk of MS in their daughters. Using predicted 25(OH)D as a continuous variable, the pooled adjusted RR was 0.69 (95% CI, 0.56-0.86) for a 10 nmol/L increment.

Commentary

This large study with 35,794 nurse mothers and 199 MS cases among their daughters suggests an inverse association between maternal vitamin D exposure and risk of MS in their offspring. If these findings were indeed true, then ensuring a high intake of milk and increasing vitamin D intake and exposure during pregnancy would have a protective effect in lowering the risk of MS in offspring. As the authors acknowledge, there are several limitations to this study. The mothers provided information about their milk intake and diet from about 35-55 years prior to completing the questionnaire, the serum 25(OH)D levels were not actually measured but were predicted based on several variable factors, and the daughters also already were diagnosed with MS when their mothers were asked to provide the information, raising potential recall bias. The possibility that other ingredients in their diet or other environmental factors influenced the findings cannot be completely excluded as well. However, despite these limitations, the study does raise the possibility of a preventive intervention for a disease that is yet incurable. Further studies are warranted to confirm these findings and to determine the optimal levels of vitamin D exposure for conferring this protective effect. But in the meantime, at least in instances where the risk of MS in the offspring is high because of family history, and especially given the high prevalence of vitamin D deficiency, it might be worthwhile to check the maternal level of vitamin D during pregnancy and bring it up to the current established safe levels.