A double-blind randomized, placebo-controlled trial comparing the impact of 600 IU, 2000 IU, or 4000 IU of Vitamin D3 on third trimester 25(OH)D levels and change from baseline. The Vitamin D will be integrated in a standard prenatal vitamin, which will be taken from 12-16 weeks' gestation and continue throughout pregnancy. Umbilical cord 25(OH)D levels will also be determined. The investigators will generate preliminary data regarding Vitamin D intake and hypertensive disorders, blood pressure, and arterial function measured by tonography. The investigators will independently test blood pressure and proteinuria to identify preeclampsia cases.
Vitamin D deficiency (serum 25(OH)D levels \<20 ng/ml or 50 nmol/l) is widespread among Mongolians and is nearly universal during the winter months. The investigators have conducted a series of studies which have shown nearly universal Vitamin D deficiency in the winter months. Observational studies in the U.S. have linked low 25(OH)D levels in women to a higher risk of preeclampsia. Mongolians also report levels of preeclampsia that are 3 times higher than those in the U.S (official reports cite 15%, though this may include gestational hypertension). Given the widespread Vitamin D deficiency in Mongolian women, the high prevalence of hypertensive pregnancy in Mongolia, and the observational studies linking low 25(OH)D levels with preeclampsia risk, the investigators are conducting a pilot Vitamin D dosing trial to: * Determine what level of Vitamin D supplementation is needed to secure 25(OH)D levels of at least 20 ng/ml in pregnant Mongolian women * Generate preliminary data in support of a funding application for a larger trial of Vitamin D supplements to prevent preeclampsia in Mongolia A double-blind randomized, placebo-controlled trial comparing the impact of 600 IU, 2000 IU, or 4000 IU of Vitamin D3 on third trimester 25(OH)D levels and change from baseline. The Vitamin D will be integrated in a standard prenatal vitamin, which will be taken from 12-16 weeks' gestation and continue throughout pregnancy. Umbilical cord 25(OH)D levels will also be determined. The investigators will generate preliminary data regarding Vitamin D intake and hypertensive disorders, blood pressure, and arterial function measured by tonography. The investigators will independently test blood pressure and proteinuria to identify preeclampsia cases. The investigators will enroll 360 women who plan to receive their prenatal care and deliver at Zuun Kharaa Hospital in the Selenge province in northern Mongolia. Enrollment will be stratified by season. 120 women will be randomized to each of the three doses of vitamin D (600, 2000, 4000 IU) included in a standard prenatal vitamin. Calcemia will be monitored two months after randomization and weeks 36-40 of pregnancy. Adverse events of pregnancy will be reported to the Data Safety and Monitoring Board (DSMB) and Institutional Review Board (IRB) per protocol. Data will be gathered by a Mongolian study coordinator and local clinicians. A DSMB comprised of a U.S. and Mongolian clinicians and statisticians will monitor study data for safety.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
360
Women will receive 600 IU 25(OH)D in prenatal vitamin.
Women will receive 2000 IU 25(OH)D in prenatal vitamin.
Women will receive 4000 IU 25(OH)D in prenatal vitamin.
Zuun Kharaa Hospital
Selenge, Selenge Province, Mongolia
Total Serum 25(OH)D Concentration
Circulating vitamin D at the end of the study as measured by VIDAS® enzyme linked fluorescent assay (ELFA)
Time frame: 36 weeks gestation or delivery, if delivery occurred before 36 weeks
The Number of Participants With Preeclampsia
Preeclampsia as measured by new onset hypertension after 20 weeks gestation and proteinuria.
Time frame: After 20 weeks gestation
Average Monthly Blood Pressure
Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) were measured in mm Hg at each antenatal care visit by the Study Coordinator, using the Omron- Elite 7300 (Omron Healthcare, Bannockburn, Illinois, USA) automated blood pressure monitor. Three blood pressure readings were taken after at least five minutes seated rest. For the analysis of mean blood pressures at each antenatal visit, the three readings were averaged for each participant.
Time frame: During pregnancy
Arterial Tonometry
Investigators will assess Augmentation Index (AIx) and Pulse Wave Velocity (PWV) by study arm, as measured by AtCor Medical SphygmoCor device. THIS TONOMETER FAILED AND COULD NOT BE REPAIRED, SO WE ARE NOT PRESENTING THESE DATA AS OUTCOMES.
Time frame: 36 weeks gestation
Number of Patients With Preterm Delivery as Measured by Clinical Diagnosis
Gestational age was determined clinically by last menstrual period and by routine first trimester ultrasound which was universal; where these differed by more than 10 days, the ultrasound date was used. Gestational age at delivery was recorded by clinicians and rounded to the nearest week. Preterm delivery was defined as delivery before the 37th week of gestation.
Time frame: During pregnancy
Casarean Section as Measured by Medical Record Abstraction
Cesarean section was abstracted from the labor and delivery chart.
Time frame: Delivery
Assisted Vaginal Delivery as Measured by Medical Record Abstraction
Assisted vaginal delivery with forceps delivery was abstracted from the labor and delivery chart.
Time frame: Delivery
Number of Small for Gestational Age (SGA) Neonates as Measured by Medical Record Abstraction
SGA defined by the lowest 10th percentiles of sex-specific birthweight for gestational age charts of the INTERGROWTH-21st study
Time frame: Delivery
Number of Large for Gestational Age (LGA) Neonates as Measured by Medical Record Abstraction
LGA defined by the highest 10th percentiles of sex-specific birthweight for gestational age charts of the INTERGROWTH-21st study
Time frame: Delivery
Mean Calcemia as Measured by Serum Calcium Test (2mo)
Measured on a semi-automated photometer (Humalyzer 3500, Human Diagnostics, Magdeburg, Germany)
Time frame: 2 months after randomization
Number of Patients With Proteinuria as Measured by Urine Dipstick
Proteinuria at last antenatal visit (usually 36-40 weeks' gestation), measured by 1+ Standard Diagnostics UroColor 10 10 (Kyonggi-do, South Korea) reagent strips
Time frame: 36-40 weeks gestation/delivery
Number of Patients With Hypertensive Disorders of Pregnancy as Measured by Clinical Diagnosis
In Mongolia, clinician-diagnosed preeclampsia may include a blood pressure increases \>30 mm Hg above early pregnancy, with or without documented hypertension, proteinuria, or symptoms such as headache and edema
Time frame: During pregnancy
Number of Patients With Bacterial Vaginosis as Measured by Potassium Hydroxide (KOH) Wet Mount
Bacterial vaginosis was routinely screened by potassium hydroxide wet mount at the first antenatal visit, at 28 weeks' and 32 weeks' gestation. It was also diagnosed by whiff test. We included both wet mount and whiff test positive in the bacterial vaginosis endpoint
Time frame: During pregnancy
Mean Calcemia as Measured by Serum Calcium Test (36-40 Weeks)
Measured on a semi-automated photometer (Humalyzer 3500, Human Diagnostics, Magdeburg, Germany)
Time frame: 36-40 weeks of pregnancy/delivery
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