With the resurgence of rickets in the 1990’s, the scientific community has focused increased attention on vitamin D.1
Vitamin D is a steroid hormone that is primarily derived from synthesis in the skin through exposure to ultraviolet B (UV-B) radiation. Vitamin D undergoes hydroxylation in the maternal liver to form 25-OH-vitamin D (25-OH-D) which is an inactive, supply form of this hormone. The active form of vitamin D (1,25-(OH)2
-vitamin D) results from the activity of 1-α-hydroxylase in the maternal kidney or placenta.2
Because the half life of 1,25-(OH)2
-vitamin D is only several minutes, the more accurate assessment of an individual’s vitamin D status is determined through measurement of 25-OH-D which has a half life of about three weeks.3
An adequate 25-OH-D level, has been determined to be 32 ng/mL or greater. Vitamin D insufficiency and deficiency are diagnosed at levels of less than 32 ng/mL and less than 20 ng/mL 25-OH-D, respectively.4
Using these criteria, vitamin D deficiency is very common in pregnancy with up to 50% of individuals classified as vitamin D deficient.5–8
Vitamin D deficiency has also been noted to have increased incidence among persons of African American race. This deficiency is likely secondary to increased melanin content preventing adequate exposure to UV-B radiation for conversion of 7-dehydrocholesterol within the skin to vitamin D.2, 7–8
With an increased incidence of vitamin D deficiency documented in these populations, there is heightened awareness of the potential impact on pregnancy outcome.
Vitamin D deficiency has been linked to adverse perinatal outcomes in recent epidemiologic data. Rickets, a hypomineralization of the skeletal structure, is a well described phenomenon of vitamin D deficiency.1
More recently, data supports associations of vitamin D deficiency and preterm birth, decreased birth weight, and hypertensive disease in pregnancy.9–14
Authors speculate that these conditions may result from the lack of action of vitamin D in immunosuppression or placental development among deficient patients.9, 15–17
Thus, vitamin D deficiency may be involved in the pathophysiology of preeclampsia.
Preeclampsia remains poorly characterized with regard to pathophysiology involved in the development of hypertensive disease in pregnancy. Preeclampsia has been described as a two stage disease in which stage I is heralded by poor placental invasion, development, and remodeling. Stage II develops later and involves the clinical recognition of preeclampsia in the form of maternal hypertension, proteinuria, and end-organ disease.18
Data suggesting an association between preeclampsia and vitamin D deficiency is now developing. In a recent investigation of 25-OH-D levels in pregnancy prior to the onset of preeclampsia, vitamin D levels assessed in early pregnancy were found to be lower among women who eventually developed preeclampsia. In fact, these investigators noted a two-fold increased risk for preeclampsia when serum vitamin D levels decreased by 20 ng/mL after adjusting for confounders.10
Another population based investigation in Norway among 23,423 nulliparious women found that vitamin D intake of 15–20 micrograms per day relative to less than 5 micrograms per day was associated with a 27% reduction in the risk for preeclampsia.13
Both of these investigations suggest an association between vitamin D deficiency and development of preeclampsia.
Early onset, severe preeclampsia (EOSPE) contributes 15% of the preterm births in the United States per annum and may also have ongoing increased risks for vascular disease in later life.19–20
These women and their fetuses are also recognized to be at the greatest risk for adverse outcomes in pregnancy with a 20-fold increased risk for maternal mortality and several-fold increased risk for neonatal morbidity or mortality dependent upon gestational age at delivery and presence of growth restriction in the fetus.21
Thus, this group may serve as a target population for improving outcomes of preeclampsia.
The purpose of this investigation was to examine the maternal plasma level of 25-OH-D in cases of EOSPE relative to controls that experience a normal pregnancy outcome. The hypothesis for this investigation was that women who were diagnosed with EOSPE would have decreased 25-OH-D levels relative to controls that experience a normal pregnancy outcome. This association would further support the significance of vitamin D deficiency in preeclampsia.