Official Title

Trial of Vitamin D Supplements to Raise Calcidiol Levels of Pregnant Women in Mongolia
  • Phase

    N/A
  • Study Type

    Interventional
  • Intervention/Treatment

    vitamin d3 ...
  • Study Participants

    360
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 Started
Feb 28
2015
Primary Completion
Dec 31
2016
Study Completion
Dec 31
2016
Results Posted
Mar 23
2021
Last Update
Mar 23
2021

Dietary Supplement 600 IU Vitamin D3 in prenatal vitamin

Women will receive 600 IU 25(OH)D in prenatal vitamin.

Dietary Supplement 2000 IU Vitamin D3 in prenatal vitamin

Women will receive 2000 IU 25(OH)D in prenatal vitamin.

Dietary Supplement 4000 IU Vitamin D3 in prenatal vitamin

Women will receive 4000 IU 25(OH)D in prenatal vitamin.

600 IU Placebo Comparator

Women will receive prenatal vitamins containing 600 IU of Vitamin D.

2000 IU Experimental

Women will receive prenatal vitamins containing 2000 IU of Vitamin D.

4000 IU Experimental

Women will receive prenatal vitamins containing 4000 IU of Vitamin D.

Criteria

Inclusion Criteria:

Age 18 or older
12-16 weeks pregnant
Receiving prenatal care at Zuun Kharaa Hospital and planning to deliver at Zuun Kharaa Hospital
Willing not to take any additional vitamin D supplements, other than the study dispensed pills

Exclusion Criteria:

Existing known seizure disorder, renal failure, parathyroid disease, thyroid disease, sarcoidosis, cancer, or tuberculosis. (Tuberculosis is routinely screened in pregnancy)
History of kidney stones
Known sensitivity to multivitamin preparations
Taking vitamin D supplements containing >600 IU/day.

Summary

600 IU

2000 IU

4000 IU

All Events

Event Type Organ System Event Term

Total Serum 25(OH)D Concentration

Circulating vitamin D at the end of the study as measured by VIDAS® enzyme linked fluorescent assay (ELFA)

600 IU

46.0
nmol/l (Mean)
Standard Deviation: 21

2000 IU

70.0
nmol/l (Mean)
Standard Deviation: 23

4000 IU

81.0
nmol/l (Mean)
Standard Deviation: 29

The Number of Participants With Preeclampsia

Preeclampsia as measured by new onset hypertension after 20 weeks gestation and proteinuria.

600 IU

2000 IU

4000 IU

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.

600 IU

DBP wk 16-20

63.8
mmHg (Mean)
Standard Deviation: 8.7

DBP wk 20-24

63.2
mmHg (Mean)
Standard Deviation: 9.0

DBP wk 24-28

64.2
mmHg (Mean)
Standard Deviation: 9.8

DBP wk 28-32

64.4
mmHg (Mean)
Standard Deviation: 8.7

DBP wk 32-36

67.2
mmHg (Mean)
Standard Deviation: 8.8

DBP wk 36-40

70.4
mmHg (Mean)
Standard Deviation: 9.7

SBP wk 16-20

104.5
mmHg (Mean)
Standard Deviation: 9.2

SBP wk 20-24

105.1
mmHg (Mean)
Standard Deviation: 9.0

SBP wk 24-28

104.9
mmHg (Mean)
Standard Deviation: 9.1

SBP wk 28-32

104.5
mmHg (Mean)
Standard Deviation: 8.7

SBP wk 36-40

110.8
mmHg (Mean)
Standard Deviation: 10.1

2000 IU

DBP wk 16-20

63.7
mmHg (Mean)
Standard Deviation: 8.7

DBP wk 20-24

63.1
mmHg (Mean)
Standard Deviation: 8.6

DBP wk 24-28

62.6
mmHg (Mean)
Standard Deviation: 9.4

DBP wk 28-32

63.6
mmHg (Mean)
Standard Deviation: 9.2

DBP wk 32-36

66.5
mmHg (Mean)
Standard Deviation: 9.4

DBP wk 36-40

71.0
mmHg (Mean)
Standard Deviation: 10.2

SBP wk 16-20

104.5
mmHg (Mean)
Standard Deviation: 8.7

SBP wk 20-24

103.6
mmHg (Mean)
Standard Deviation: 8.2

SBP wk 24-28

103.3
mmHg (Mean)
Standard Deviation: 8.1

SBP wk 28-32

103.9
mmHg (Mean)
Standard Deviation: 9.7

SBP wk 36-40

110.6
mmHg (Mean)
Standard Deviation: 9.5

4000 IU

DBP wk 16-20

65.2
mmHg (Mean)
Standard Deviation: 9.0

DBP wk 20-24

63.8
mmHg (Mean)
Standard Deviation: 9.6

DBP wk 24-28

63.5
mmHg (Mean)
Standard Deviation: 9.6

DBP wk 28-32

65.1
mmHg (Mean)
Standard Deviation: 9.2

DBP wk 32-36

67.1
mmHg (Mean)
Standard Deviation: 9.5

DBP wk 36-40

71.7
mmHg (Mean)
Standard Deviation: 10.6

SBP wk 16-20

105.5
mmHg (Mean)
Standard Deviation: 9.7

SBP wk 20-24

105.4
mmHg (Mean)
Standard Deviation: 8.9

SBP wk 24-28

104.0
mmHg (Mean)
Standard Deviation: 9.3

SBP wk 28-32

105.4
mmHg (Mean)
Standard Deviation: 9.3

SBP wk 36-40

111.1
mmHg (Mean)
Standard Deviation: 11.0

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.

Outcome Measure Data Not Reported

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.

600 IU

2000 IU

4000 IU

Casarean Section as Measured by Medical Record Abstraction

Cesarean section was abstracted from the labor and delivery chart.

600 IU

2000 IU

4000 IU

Assisted Vaginal Delivery as Measured by Medical Record Abstraction

Assisted vaginal delivery with forceps delivery was abstracted from the labor and delivery chart.

600 IU

2000 IU

4000 IU

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

600 IU

2000 IU

4000 IU

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

600 IU

2000 IU

4000 IU

Mean Calcemia as Measured by Serum Calcium Test (2mo)

Measured on a semi-automated photometer (Humalyzer 3500, Human Diagnostics, Magdeburg, Germany)

600 IU

2.2
mmol/L (Mean)
Standard Deviation: 0.2

2000 IU

2.2
mmol/L (Mean)
Standard Deviation: 0.2

4000 IU

2.2
mmol/L (Mean)
Standard Deviation: 0.2

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

600 IU

2000 IU

4000 IU

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

600 IU

2000 IU

4000 IU

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

600 IU

2000 IU

4000 IU

Mean Calcemia as Measured by Serum Calcium Test (36-40 Weeks)

Measured on a semi-automated photometer (Humalyzer 3500, Human Diagnostics, Magdeburg, Germany)

600 IU

2.3
mmol/L (Mean)
Standard Deviation: 0.2

2000 IU

2.3
mmol/L (Mean)
Standard Deviation: 0.2

4000 IU

2.3
mmol/L (Mean)
Standard Deviation: 0.2

Total

360
Participants

Age, Categorical

Sex: Female, Male

Overall Study

600 IU

2000 IU

4000 IU

Drop/Withdrawal Reasons

600 IU

2000 IU

4000 IU