Clinical trial NCT02920593: A Randomized Control Trial of Vitamin D Prophylaxis in the Prevention of Hypertensive Disorders of Pregnancy
Official title: A Randomized Control Trial of Vitamin D Prophylaxis in the Prevention of Hypertensive Disorders of Pregnancy
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Gestational Hypertension
Toxemia
Superimposed Preeclampsia
Eclampsia
HELLP Syndrome
Keywords: Vitamin D; hypertensive disorders of pregnancy
Lead sponsor: Stony Brook University
Sponsor class: OTHER
First posted: 2016-09-30
Enrollment: 412
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The investigators aim to determine if Vitamin D prophylaxis in pregnancy reduces the incidence of hypertensive disorders of pregnancy.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Vitamin D prophylaxis in pregnant women and incidence of hypertensive disorders of pregnancy
timeFrame: 1.5 years
Secondary outcomes:
measure: Adverse neonatal outcome in those who received Vitamin D prophylaxis compared to those who did not receive Vitamin D prophylaxis
timeFrame: 2 years
measure: Placental pathology in those who received Vitamin D prophylaxis compared to those who did not receive Vitamin D prophylaxis
timeFrame: 2 years
measure: Placental TNF-alpha in those who received Vitamin D prophylaxis compared to those who did not receive Vitamin D prophylaxis
timeFrame: 2 years
measure: Placental inflammatory marker IL-6 in those who received Vitamin D prophylaxis compared to those who did not receive Vitamin D prophylaxis
timeFrame: 2 years
measure: Placental inflammatory marker IFN-gamma in those who received Vitamin D prophylaxis compared to those who did not receive Vitamin D prophylaxis
timeFrame: 2 years
measure: Placental inflammatory marker GMSCF-2 in those who received Vitamin D prophylaxis compared to those who did not receive Vitamin D prophylaxis
timeFrame: 2 years
measure: Placental inflammatory marker endometrial growth factor in those who received Vitamin D prophylaxis compared to those who did not receive Vitamin D prophylaxis
timeFrame: 2 years
measure: Maternal Vitamin D level in those who received Vitamin D prophylaxis compared to those who did not receive Vitamin D prophylaxis
timeFrame: 1.5 years
measure: Cord blood Vitamin D level in those who received Vitamin D prophylaxis compared to those who did not receive Vitamin D prophylaxis
timeFrame: 1.5 years
Other outcomes:
Locations:
city: Stony Brook
country: United States
facility: SUNY Stony Brook Hospital
state: New York
Study officials:
affiliation: SUNY Stony Brook Hospital
name: Diana J Garretto, MD
role: PRINCIPAL_INVESTIGATOR
References:
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