A Randomized Control Trial of Vitamin D Prophylaxis in the Prevention of Hypertensive Disorders of Pregnancy

Optimizing Vitamin D status during pregnancy it thought to have maternal, fetal, and neonatal
benefit. Studies suggest that Vitamin D acts well beyond its most commonly thought of role in
establishing calcium homeostasis and maintaining maternal and neonatal skeletal integrity.
Vitamin D has also been found to modulate the maternal renal renin-angiotensin system,
maternal immune response, placental implantation and function, and angiogenesis. In light of
this, it is no surprise that the 2010 systematic review of vitamin D in pregnancy suggested
that Vitamin D deficiency may be associated with an increase risk in maternal and neonatal
morbidity. For example, vitamin D deficiency has correlated with an array of maternal
conditions, including gestational hypertension, preeclampsia, gestational diabetes, myopathy,
vaginal infection, and mental disease. Associated neonatal risks include preterm birth,
immunosuppression, infection, low birth weight, hypokalemia, neonatal seizures, asthma,
fractures and rickets.

Unfortunately, Vitamin D deficiency in pregnancy is an ongoing epidemic, affecting as many as
82% of pregnant women. While studies on Vitamin D supplementation in pregnancy have
consistently shown an associated increase in maternal and neonatal serum Vitamin D levels,
some studies have also suggested a concurrent decrease in adverse maternal and neonatal
outcomes. For example, Vitamin D supplementation in pregnancies with known deficiency has
been shown to decrease the incidence of preeclampsia as much as 32%. Other studies, on the
other hand, have suggested no benefit. The inconsistency in findings lie in the fact that
these studies were primarily observational in nature and plagued by small sample sizes,
recall bias, and inability to adjust for potential confounders. Given this, interpretation
regarding clinical significance is limited, preventing providers from making appropriate
recommendations to their patients. As such, the American Congress of Obstetricians and
Gynecologists (ACOG) has called for high quality studies to address whether the use of
Vitamin D supplementation beyond that found in prenatal vitamins is beneficial.

In an effort to elucidate the potential benefit of Vitamin D supplementation in an unscreened
population, the investigators propose conducting a randomized control trial in which Vitamin
D prophylaxis is provided to a cohort of pregnant women regardless of their Vitamin D status.
The aims of the study, therefore, are to:

Specific Aim 1: Determine if Vitamin D prophylaxis in pregnant women decreases the incidence
of hypertensive disorders of pregnancy.

Specific Aim 2: Compare neonatal outcomes in those who received Vitamin D prophylaxis to
those who did not receive Vitamin D prophylaxis.

Specific Aim 3: Compare placental histology and inflammatory markers in those who received
Vitamin D prophylaxis to those who did not receive Vitamin D prophylaxis.

Inclusion Criteria:

- 18 years of age and older

- With a confirmed intrauterine pregnancy, less than 16 weeks gestation

- Carrying a singleton gestation

Exclusion Criteria:

- Taking Vitamin D supplementation outside of prenatal vitamins

- Has a known disorder that will affect vitamin D levels (i.e, hyperparathyroidism,
mal-absorption disorder, history of gastric bypass surgery, immunocompromised state,
maternal use of immune-modulators etc.)

- Carrying a fetus with known aneuploidy or anomaly

- With fetal demise

- Women with chronic diuretic or cardiac medication therapy including calcium channel
blockers