D Mommy + D Baby — Vitamin D and Preeclampsia

Abstract & Commentary

By Russell H. Greenfield, MD. Dr. Greenfield is Clinical Assistant Professor, School of Medicine, University of North Carolina, Chapel Hill, and Visiting Professor, University of Arizona, College of Medicine, Tucson; he reports no financial relationships relevant to this field of study.

Source: Bodnar LM, et al: Maternal vitamin D deficiency increases the risk of preeclampsia. J Clin Endocrinol Metab. 2007;92:3517-3522.

This nested, case-control trial was designed to assess the independent effect of maternal 25-hydroxyvitamin D [25(OH)D] levels in early pregnancy on the risk of subsequent development of preeclampsia. Researchers were also interested in the newborns' vitamin D status.

Nulliparous pregnant women aged 14-44 years without preexisting medical conditions and with singleton pregnancies (n = 1198) were admitted into the trial and followed from < 16 weeks gestation to delivery at prenatal clinics and private practices. At enrollment, all subjects completed an interviewer-administered questionnaire regarding demographics, medical history, and health behaviors. Non-fasting blood samples were collected at typical clinically-indicated times, and medical record information was extracted to secure data on blood pressure and urinary protein measurements. Additional data and banked sera collected from women and newborns from 1997-2001 were used to complete the study, with 25(OH)D assays performed in 2006. Ideally, subjects' blood samples were available for evaluation from prior to 22 weeks gestation and pre-delivery, as well as a venous cord serum sample. The primary outcome measure was preeclampsia.

By trial's end, a total of 59 women had developed preeclampsia (4.9%). Adjusted serum 25(OH)D levels in early pregnancy were 15% lower in women who subsequently developed preeclampsia when compared with controls. After adjustment for potential confounders, a decrease in 25(OH)D level of 50 nmol/L doubled the risk of preeclampsia (OR = 2.4). As maternal 25(OH)D concentrations at < 22 weeks increased, the risk of preeclampsia decreased. Newborns of preeclamptic mothers were twice as likely as control newborns to have low 25(OH)D levels, with a significant correlation between pre-delivery maternal blood samples and cord samples. Findings were independent of confounders that included race/ethnicity and seasonality, and occurred in the context of widespread prenatal/multivitamin use among members of the cohort (93%). Bodnar and colleagues conclude that maternal vitamin D deficiency at < 22 weeks gestation is an independent risk factor for preeclampsia.

Commentary

Preeclampsia occurs in 3%-8% of pregnancies, and is especially common in primigravidas and African-American (AA) women. It is typically defined as new-onset gestational hypertension and proteinuria that develops after 20 weeks gestation, with return of all abnormalities to normal by 12 weeks postpartum. The illness places both mother and fetus at risk.

Optimal 25(OH)D levels have been suggested but not definitively agreed upon, yet maternal vitamin D deficiency has been called a neglected public health issue, with studies suggesting almost 30% of AA women affected. This latter point is important due to the intersection of increased risk for preeclampsia and high rates of vitamin D deficiency states among AA women, suggesting a significant role for vitamin D.

Beyond health benefits to the mother associated with presumed optimal 25(OH)D levels that include potential cancer chemoprevention, healthy bones and possible protection against multiple sclerosis, and now prevention of preeclampsia, there are important implications for the newborn. Fetal 25(OH)D levels are entirely dependent upon the mother's stores of vitamin D, and neonatal vitamin D deficiency has been associated with significant health issues that include skeletal problems, asthma, insulin-dependent diabetes, impaired growth, and schizophrenia.

Results from small trials have previously suggested a protective role for vitamin D against preeclampsia, but this is one of the first large, prospective investigations to explore the association between serum 25(OH)D levels and preeclampsia prior to symptom onset. The results are important, but weakened by the fact that calcium intake was not measured. It is known that low calcium states are a risk factor for vitamin D deficiency, and may also be a risk factor for preeclampsia.

Calls for further investigation into prenatal supplementation with vitamin D are appropriate, but many practitioners believe the time has come to institute this measure, especially for pregnant women with dark skin color for whom the risk of both preeclampsia and vitamin D deficiency is very high. It seems appropriate to supplement with additional vitamin D in early pregnancy beyond the amounts typically found in prenatal vitamins, especially over the winter months when less sun exposure can be expected. Broadly recommended intakes of vitamin D appear to be increasing monthly, but optimal levels for the pregnant woman have yet to be established. A daily dose of 1000 IU of vitamin D3 (cholecalciferol) seems a balanced general recommendation for expectant mothers in the absence of preexisting medical conditions or complicating factors.