Writing in the Journal of Clinical Endocrinology and Metabolism, researchers from the University of Pittsburgh Schools of the Health Sciences have linked low vitamin D levels in mothers to a five-fold increased risk of preeclampsia, a serious complication in pregnancy which can lead to fetal death (Badnar et al. 2007).

Preeclampsia is the leading cause of premature delivery and maternal and fetal illness and death worldwide, thought to contribute to 76,000 deaths each year. Affecting up to seven per cent of first pregnancies, preeclampsia, also known as toxemia, costs an estimated $7 billion a year in the United States alone, according to the Preeclampsia Foundation. Clinical symptoms are soaring blood pressure, swelling of the hands and feet, and proteinuria (spilling of protein into the urine).

Badnar et al. analyzed data for 1,198 women enrolled in the Pregnancy Exposures and Preeclampsia Prevention Study (with data and banked blood samples taken from women and newborns between 1997 and 2001 at Magee-Women’s Hospital of the University of Pittsburgh Medical Center (UPMC) and affiliated private obstetrician practices), a prospective survey designed to examine factors that may predispose women to preeclampsia. 55 cases of preeclampsia and 220 controls were selected for further study from this group. Maternal blood samples were taken prior to 22 weeks pregnancy and again just before delivery. Newborn umbilical cord blood samples also were tested for 25 hydroxyvitamin D, an indicator of vitamin D status.

According to Bodnar et al. “low vitamin D early in pregnancy was associated with a five-fold increase in the odds of preeclampsia. Data showed this increase risk persisted even after adjusting for other known risk factors such as race, ethnicity and pre-pregnancy body weight.

Also troubling was the fact that many of the women reported taking prenatal vitamins, which typically contain 200 to 400 International Units of vitamin D.” (Badnar et al. 2007). They further noted that “even a small decline in vitamin D concentration more than doubles the risk of preeclampsia. Women who developed preeclampsia had vitamin D concentrations that were significantly lower early in pregnancy compared to women whose pregnancies were normal. And even though vitamin D deficiency was common in both groups, the deficiency was more prevalent among those who went on to develop preeclampsia.” (Badnar et al. 2007).

Their results show that maternal vitamin D deficiency early in pregnancy is a strong, independent risk factor for preeclampsia and vitamin D supplementation in early pregnancy should be explored for preventing preeclampsia and promoting neonatal well-being.

The pathogenesis of preeclampsia involve biological processes which vitamin D is involved in either directly or indirectly such as: immune dysfunction, excessive inflammation, hypertension, abnormal angiogenesis, and placental implantation (Cardus et al. 2006, Evans et al. 2004,Hewison 1992, Li YC et al. 2002). While vitamin D has direct influence on molecular pathways proposed to be important in the pathogenesis of preeclampsia, the Badnar study is the first where the vitamin D-preeclampsia relation has been evaluated (Badnar et al. 2007).

The active form of vitamin D (1, 25-dihydroxyvitamin D₃) has been shown to regulate the transcription and function of genes associated with placental invasion, normal implantation, and angiogenesis via vascular endothelial growth factor (Evans et al. 2004, Daftary et al. 2006). These are mechanism by which maternal vitamin D status could alter risk of preeclampsia.

Preeclampsia is hypothesized to be a two stage disorder (Roberts et al. 2005): one which involves reduced placental perfusion secondary to abnormal implantation and the other being the pathophysiological changes that result from the materials produced by a poorly perfused placental environment. Abnormal implantation is believed in part to be mediated by an abnormal immune response and the immunomodulatory properties of the active form of vitamin D may play a role here (Hewison 1992, Muller et al. 1991).

Vitamin D deficiency may predispose to an increase in inflammatory response (Hewison 1992) and when coupled with abnormal endothelial function changes (from poor placental perfusion seen in abnormal implantation) could result in vascular structure and function changes. In fact, vascular compliance, elasticity, and intima media thickness are more favorable among vitamin D supplemented women (Braam et al. 2004). Active vitamin D has been shown to regulate angiogenic processes (forming of new blood capillaries) through direct effects on vascular endothelial growth factor (VEGF) gene transcription (Cardus et al. 2006). In vitamin D deficiency, angiogenesis is blocked due to decreased VEGF. Lack of renal VEGF is thought to mediate the proteinuria of preeclampsia. Vitamin D deficiency has also been reported to elevate blood pressure (Li YC et al. 2002). Taken together these findings may account for the main symptoms of preeclampsia.

This study adds to an ever-growing weight of the importance of vitamin D, which has been linked to a host of health benefits, including improving diabetes, hypertension, heart health, breast and colon cancer. Additionally, vitamin D deficiency in pregnancy has been associated with a number of health problems in offspring including asthma, impaired growth, skeletal problems, type 1 diabetes and schizophrenia (Holick 2006).

Sources:

Bodnar et al. Maternal vitamin D deficiency increases the risk of preeclampsia. J Clin Endocrinol & Metab 2007;92(9):3517-22.
Braam et al. Thromb Haemost 2004;91:373-80.
Cardus et al. Kidney Int 2006;69:1377-84.
Daftary et al. Endocrine Rev 2006;27:331-55.
Evans et al.J Soc Gynecol Investig 2004;11:263-71.
Hewison. J Endocrinol 1992;132:173-5.
Holick. J Clin Invest 2006;116:2062-72.
Li YC et al. J Clin Invest 2002;110:229-38.
Muller et al. Immunol Lett 1991;28:115-20.
Roberts et al. Hypertension 2005;46:1243-49.