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

Sponsor

Stony Brook University (Other)

Overall Status

Unknown status

CT.gov ID

NCT02920593

Collaborator

(none)

412

Enrollment

Location

Arms

29.9

Duration (Months)

13.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Gestational Hypertension Toxemia Superimposed Preeclampsia Eclampsia HELLP Syndrome	Drug: Vitamin D3	Phase 4

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

412 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

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

Study Start Date :

Oct 1, 2016

Anticipated Primary Completion Date :

Jul 31, 2018

Anticipated Study Completion Date :

Mar 31, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Vitamin D Prophylaxis Participants will be provided Vitamin D 3000 IU daily or Vitamin D 4000 IU daily with and without concurrent use of prenatal vitamins, respectively.	Drug: Vitamin D3 Vitamin D prophylaxis Other Names: Vitamin D
No Intervention: No Vitamin D Prophylaxis Participants will not receive additional Vitamin D in the pregnancy.

Arm

Intervention/Treatment

Experimental: Vitamin D Prophylaxis

Participants will be provided Vitamin D 3000 IU daily or Vitamin D 4000 IU daily with and without concurrent use of prenatal vitamins, respectively.

Drug: Vitamin D3

Vitamin D prophylaxis

Other Names:

Vitamin D

No Intervention: No Vitamin D Prophylaxis

Participants will not receive additional Vitamin D in the pregnancy.

Outcome Measures

Primary Outcome Measures

Vitamin D prophylaxis in pregnant women and incidence of hypertensive disorders of pregnancy [1.5 years]
Number of participants diagnosed with a hypertensive disorder of pregnancy defined as: elevated blood pressure (systolic/diastolic > 140/90mmHg, 2 determinations, 4 hours apart) more than 20 weeks gestation +/- new onset proteinuria (300mg/24hour; protein/creatinine ratio > 3.0mg/dL; 1+ protein on dipstick) or abnormal labs (thrombocytopenia (platelet < 100,000 microliter), impaired liver function testing (AST/ALT twice higher than normal), renal insufficiency (creatinine >1.1mg/dL or doubling of creatinine in the absence of renal disease)) or pulmonary edema or seizure. The outcome will be dichotomized and coded as present or absent.

Secondary Outcome Measures

Adverse neonatal outcome in those who received Vitamin D prophylaxis compared to those who did not receive Vitamin D prophylaxis [2 years]
The number of participants with an adverse neonatal outcome will be determined by the presence of any of the following pregnancy characteristics: preterm birth <37 weeks; Apgar score <5 at 1 minute, <7 at 5 minutes; low birth weight <2500g; neonatal intensive care unit admission; fetal distress; respiratory distress syndrome; ventilation; neonatal infection; fracture; and neonatal death. The outcome will be dichotomized and coded as present or absent.
Placental pathology in those who received Vitamin D prophylaxis compared to those who did not receive Vitamin D prophylaxis [2 years]
The number of participants with abnormal placental evaluation will be based on the presence of any of the following: placental abruption, infarction, hypoxia, decidual vasculopathy, or thrombosis of fetal vessels. The outcome will be dichotomized and coded as present or absent.
Placental TNF-alpha in those who received Vitamin D prophylaxis compared to those who did not receive Vitamin D prophylaxis [2 years]
Number value of placental TNF-alpha level (ng/mL)
Placental inflammatory marker IL-6 in those who received Vitamin D prophylaxis compared to those who did not receive Vitamin D prophylaxis [2 years]
Number value of placental IL-6 (ng/mL)
Placental inflammatory marker IFN-gamma in those who received Vitamin D prophylaxis compared to those who did not receive Vitamin D prophylaxis [2 years]
Number value of IFN-gamma (ng/mL)
Placental inflammatory marker GMSCF-2 in those who received Vitamin D prophylaxis compared to those who did not receive Vitamin D prophylaxis [2 years]
Number value of GMSCF-2 (ng/mL)
Placental inflammatory marker endometrial growth factor in those who received Vitamin D prophylaxis compared to those who did not receive Vitamin D prophylaxis [2 years]
Number value of endometrial growth factor (ng/mL)
Maternal Vitamin D level in those who received Vitamin D prophylaxis compared to those who did not receive Vitamin D prophylaxis [1.5 years]
Number value of maternal serum levels of 25(OH)D (ng/mL)
Cord blood Vitamin D level in those who received Vitamin D prophylaxis compared to those who did not receive Vitamin D prophylaxis [1.5 years]
Number value of cord blood levels of 25(OH)D (ng/mL)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

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