Trial Outcomes & Findings for Trial of Vitamin D Supplements to Raise Calcidiol Levels of Pregnant Women in Mongolia (NCT NCT02395081)

NCT ID: NCT02395081

Last Updated: 2021-03-23

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 360 participants
• Primary outcome timeframe: 36 weeks gestation or delivery, if delivery occurred before 36 weeks
• Results posted on: 2021-03-23

Participant Flow

Participant milestones

Measure	600 IU Women will receive prenatal vitamins containing 600 IU of Vitamin D. Dietary supplement: 600 IU Vitamin D3 in prenatal vitamin	2000 IU Women will receive prenatal vitamins containing 2000 IU of Vitamin D. Dietary supplement: 2000 IU Vitamin D in prenatal vitamin	4000 IU Women will receive prenatal vitamins containing 4000 IU of Vitamin D. Dietary supplement: 4000 IU Vitamin D3 in prenatal vitamin
Overall Study STARTED	119	121	120
Overall Study COMPLETED	112	116	116
Overall Study NOT COMPLETED	7	5	4

Reasons for withdrawal

Measure	600 IU Women will receive prenatal vitamins containing 600 IU of Vitamin D. Dietary supplement: 600 IU Vitamin D3 in prenatal vitamin	2000 IU Women will receive prenatal vitamins containing 2000 IU of Vitamin D. Dietary supplement: 2000 IU Vitamin D in prenatal vitamin	4000 IU Women will receive prenatal vitamins containing 4000 IU of Vitamin D. Dietary supplement: 4000 IU Vitamin D3 in prenatal vitamin
Overall Study Withdrawal by Subject	1	1	0
Overall Study Moved where blood couldn't be collected	4	1	3
Overall Study Fetal Loss	2	3	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	600 IU n=119 Participants Women will receive prenatal vitamins containing 600 IU of Vitamin D. Dietary supplement: 600 IU Vitamin D3 in prenatal vitamin	2000 IU n=121 Participants Women will receive prenatal vitamins containing 2000 IU of Vitamin D. Dietary supplement: 2000 IU Vitamin D in prenatal vitamin	4000 IU n=120 Participants Women will receive prenatal vitamins containing 4000 IU of Vitamin D. Dietary supplement: 4000 IU Vitamin D3 in prenatal vitamin	Total n=360 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	119 Participants n=5 Participants	121 Participants n=7 Participants	120 Participants n=5 Participants	360 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Sex: Female, Male Female	119 Participants n=5 Participants	121 Participants n=7 Participants	120 Participants n=5 Participants	360 Participants n=4 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: 36 weeks gestation or delivery, if delivery occurred before 36 weeks

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

Outcome measures

Measure	600 IU n=112 Participants Women will receive prenatal vitamins containing 600 IU of Vitamin D. Dietary supplement: 600 IU Vitamin D3 in prenatal vitamin	2000 IU n=116 Participants Women will receive prenatal vitamins containing 2000 IU of Vitamin D. Dietary supplement: 2000 IU Vitamin D in prenatal vitamin	4000 IU n=116 Participants Women will receive prenatal vitamins containing 4000 IU of Vitamin D. Dietary supplement: 4000 IU Vitamin D3 in prenatal vitamin
Total Serum 25(OH)D Concentration	46 nmol/l Standard Deviation 21	70 nmol/l Standard Deviation 23	81 nmol/l Standard Deviation 29

SECONDARY outcome

Timeframe: After 20 weeks gestation

Population: Women delivering after 20 weeks in study hospital

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

Outcome measures

Measure	600 IU n=112 Participants Women will receive prenatal vitamins containing 600 IU of Vitamin D. Dietary supplement: 600 IU Vitamin D3 in prenatal vitamin	2000 IU n=116 Participants Women will receive prenatal vitamins containing 2000 IU of Vitamin D. Dietary supplement: 2000 IU Vitamin D in prenatal vitamin	4000 IU n=117 Participants Women will receive prenatal vitamins containing 4000 IU of Vitamin D. Dietary supplement: 4000 IU Vitamin D3 in prenatal vitamin
The Number of Participants With Preeclampsia	1 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: During pregnancy

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.

Outcome measures

Measure	600 IU n=119 Participants Women will receive prenatal vitamins containing 600 IU of Vitamin D. Dietary supplement: 600 IU Vitamin D3 in prenatal vitamin	2000 IU n=121 Participants Women will receive prenatal vitamins containing 2000 IU of Vitamin D. Dietary supplement: 2000 IU Vitamin D in prenatal vitamin	4000 IU n=120 Participants Women will receive prenatal vitamins containing 4000 IU of Vitamin D. Dietary supplement: 4000 IU Vitamin D3 in prenatal vitamin
Average Monthly Blood Pressure SBP wk 20-24	105.1 mmHg Standard Deviation 9.0	103.6 mmHg Standard Deviation 8.2	105.4 mmHg Standard Deviation 8.9
Average Monthly Blood Pressure DBP wk 16-20	63.8 mmHg Standard Deviation 8.7	63.7 mmHg Standard Deviation 8.7	65.2 mmHg Standard Deviation 9.0
Average Monthly Blood Pressure DBP wk 20-24	63.2 mmHg Standard Deviation 9.0	63.1 mmHg Standard Deviation 8.6	63.8 mmHg Standard Deviation 9.6
Average Monthly Blood Pressure SBP wk 16-20	104.5 mmHg Standard Deviation 9.2	104.5 mmHg Standard Deviation 8.7	105.5 mmHg Standard Deviation 9.7
Average Monthly Blood Pressure SBP wk 24-28	104.9 mmHg Standard Deviation 9.1	103.3 mmHg Standard Deviation 8.1	104.0 mmHg Standard Deviation 9.3
Average Monthly Blood Pressure SBP wk 28-32	104.5 mmHg Standard Deviation 8.7	103.9 mmHg Standard Deviation 9.7	105.4 mmHg Standard Deviation 9.3
Average Monthly Blood Pressure SBP wk 36-40	110.8 mmHg Standard Deviation 10.1	110.6 mmHg Standard Deviation 9.5	111.1 mmHg Standard Deviation 11.0
Average Monthly Blood Pressure DBP wk 24-28	64.2 mmHg Standard Deviation 9.8	62.6 mmHg Standard Deviation 9.4	63.5 mmHg Standard Deviation 9.6
Average Monthly Blood Pressure DBP wk 28-32	64.4 mmHg Standard Deviation 8.7	63.6 mmHg Standard Deviation 9.2	65.1 mmHg Standard Deviation 9.2
Average Monthly Blood Pressure DBP wk 32-36	67.2 mmHg Standard Deviation 8.8	66.5 mmHg Standard Deviation 9.4	67.1 mmHg Standard Deviation 9.5
Average Monthly Blood Pressure DBP wk 36-40	70.4 mmHg Standard Deviation 9.7	71.0 mmHg Standard Deviation 10.2	71.7 mmHg Standard Deviation 10.6

SECONDARY outcome

Timeframe: 36 weeks gestation

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 measures

Outcome data not reported

SECONDARY outcome

Timeframe: During pregnancy

Population: Women delivering after 20 weeks at study hospital

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.

Outcome measures

Measure	600 IU n=112 Participants Women will receive prenatal vitamins containing 600 IU of Vitamin D. Dietary supplement: 600 IU Vitamin D3 in prenatal vitamin	2000 IU n=116 Participants Women will receive prenatal vitamins containing 2000 IU of Vitamin D. Dietary supplement: 2000 IU Vitamin D in prenatal vitamin	4000 IU n=117 Participants Women will receive prenatal vitamins containing 4000 IU of Vitamin D. Dietary supplement: 4000 IU Vitamin D3 in prenatal vitamin
Number of Patients With Preterm Delivery as Measured by Clinical Diagnosis	9 Participants	8 Participants	5 Participants

SECONDARY outcome

Timeframe: Delivery

Population: Women who delivered after 20 weeks at study hospital

Cesarean section was abstracted from the labor and delivery chart.

Outcome measures

Measure	600 IU n=112 Participants Women will receive prenatal vitamins containing 600 IU of Vitamin D. Dietary supplement: 600 IU Vitamin D3 in prenatal vitamin	2000 IU n=116 Participants Women will receive prenatal vitamins containing 2000 IU of Vitamin D. Dietary supplement: 2000 IU Vitamin D in prenatal vitamin	4000 IU n=117 Participants Women will receive prenatal vitamins containing 4000 IU of Vitamin D. Dietary supplement: 4000 IU Vitamin D3 in prenatal vitamin
Casarean Section as Measured by Medical Record Abstraction	22 Participants	27 Participants	26 Participants

SECONDARY outcome

Timeframe: Delivery

Population: Women who delivered after 20 weeks at the study hospital

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

Outcome measures

Measure	600 IU n=112 Participants Women will receive prenatal vitamins containing 600 IU of Vitamin D. Dietary supplement: 600 IU Vitamin D3 in prenatal vitamin	2000 IU n=116 Participants Women will receive prenatal vitamins containing 2000 IU of Vitamin D. Dietary supplement: 2000 IU Vitamin D in prenatal vitamin	4000 IU n=117 Participants Women will receive prenatal vitamins containing 4000 IU of Vitamin D. Dietary supplement: 4000 IU Vitamin D3 in prenatal vitamin
Assisted Vaginal Delivery as Measured by Medical Record Abstraction	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Delivery

Population: Singleton deliveries at study hospital

SGA defined by the lowest 10th percentiles of sex-specific birthweight for gestational age charts of the INTERGROWTH-21st study

Outcome measures

Measure	600 IU n=109 Participants Women will receive prenatal vitamins containing 600 IU of Vitamin D. Dietary supplement: 600 IU Vitamin D3 in prenatal vitamin	2000 IU n=115 Participants Women will receive prenatal vitamins containing 2000 IU of Vitamin D. Dietary supplement: 2000 IU Vitamin D in prenatal vitamin	4000 IU n=114 Participants Women will receive prenatal vitamins containing 4000 IU of Vitamin D. Dietary supplement: 4000 IU Vitamin D3 in prenatal vitamin
Number of Small for Gestational Age (SGA) Neonates as Measured by Medical Record Abstraction	1 Participants	2 Participants	2 Participants

SECONDARY outcome

Timeframe: Delivery

Population: Singleton deliveries after 20 weeks at study hospital

LGA defined by the highest 10th percentiles of sex-specific birthweight for gestational age charts of the INTERGROWTH-21st study

Outcome measures

Measure	600 IU n=109 Participants Women will receive prenatal vitamins containing 600 IU of Vitamin D. Dietary supplement: 600 IU Vitamin D3 in prenatal vitamin	2000 IU n=115 Participants Women will receive prenatal vitamins containing 2000 IU of Vitamin D. Dietary supplement: 2000 IU Vitamin D in prenatal vitamin	4000 IU n=114 Participants Women will receive prenatal vitamins containing 4000 IU of Vitamin D. Dietary supplement: 4000 IU Vitamin D3 in prenatal vitamin
Number of Large for Gestational Age (LGA) Neonates as Measured by Medical Record Abstraction	25 Participants	26 Participants	33 Participants

SECONDARY outcome

Timeframe: 2 months after randomization

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

Outcome measures

Measure	600 IU n=116 Participants Women will receive prenatal vitamins containing 600 IU of Vitamin D. Dietary supplement: 600 IU Vitamin D3 in prenatal vitamin	2000 IU n=118 Participants Women will receive prenatal vitamins containing 2000 IU of Vitamin D. Dietary supplement: 2000 IU Vitamin D in prenatal vitamin	4000 IU n=119 Participants Women will receive prenatal vitamins containing 4000 IU of Vitamin D. Dietary supplement: 4000 IU Vitamin D3 in prenatal vitamin
Mean Calcemia as Measured by Serum Calcium Test (2mo)	2.2 mmol/L Standard Deviation 0.2	2.2 mmol/L Standard Deviation 0.2	2.2 mmol/L Standard Deviation 0.2

SECONDARY outcome

Timeframe: 36-40 weeks gestation/delivery

Population: Women who attended a last clinical visit after 36 weeks and gave a urine sample

Proteinuria at last antenatal visit (usually 36-40 weeks' gestation), measured by 1+ Standard Diagnostics UroColor 10 10 (Kyonggi-do, South Korea) reagent strips

Outcome measures

Measure	600 IU n=92 Participants Women will receive prenatal vitamins containing 600 IU of Vitamin D. Dietary supplement: 600 IU Vitamin D3 in prenatal vitamin	2000 IU n=93 Participants Women will receive prenatal vitamins containing 2000 IU of Vitamin D. Dietary supplement: 2000 IU Vitamin D in prenatal vitamin	4000 IU n=87 Participants Women will receive prenatal vitamins containing 4000 IU of Vitamin D. Dietary supplement: 4000 IU Vitamin D3 in prenatal vitamin
Number of Patients With Proteinuria as Measured by Urine Dipstick	2 Participants	2 Participants	0 Participants

SECONDARY outcome

Timeframe: During pregnancy

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

Outcome measures

Measure	600 IU n=119 Participants Women will receive prenatal vitamins containing 600 IU of Vitamin D. Dietary supplement: 600 IU Vitamin D3 in prenatal vitamin	2000 IU n=121 Participants Women will receive prenatal vitamins containing 2000 IU of Vitamin D. Dietary supplement: 2000 IU Vitamin D in prenatal vitamin	4000 IU n=120 Participants Women will receive prenatal vitamins containing 4000 IU of Vitamin D. Dietary supplement: 4000 IU Vitamin D3 in prenatal vitamin
Number of Patients With Hypertensive Disorders of Pregnancy as Measured by Clinical Diagnosis	4 Participants	3 Participants	3 Participants

SECONDARY outcome

Timeframe: During pregnancy

Population: Women seen for antenatal care during the trial

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

Outcome measures

Measure	600 IU n=119 Participants Women will receive prenatal vitamins containing 600 IU of Vitamin D. Dietary supplement: 600 IU Vitamin D3 in prenatal vitamin	2000 IU n=121 Participants Women will receive prenatal vitamins containing 2000 IU of Vitamin D. Dietary supplement: 2000 IU Vitamin D in prenatal vitamin	4000 IU n=120 Participants Women will receive prenatal vitamins containing 4000 IU of Vitamin D. Dietary supplement: 4000 IU Vitamin D3 in prenatal vitamin
Number of Patients With Bacterial Vaginosis as Measured by Potassium Hydroxide (KOH) Wet Mount	17 Participants	19 Participants	18 Participants

SECONDARY outcome

Timeframe: 36-40 weeks of pregnancy/delivery

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

Outcome measures

Measure	600 IU n=112 Participants Women will receive prenatal vitamins containing 600 IU of Vitamin D. Dietary supplement: 600 IU Vitamin D3 in prenatal vitamin	2000 IU n=113 Participants Women will receive prenatal vitamins containing 2000 IU of Vitamin D. Dietary supplement: 2000 IU Vitamin D in prenatal vitamin	4000 IU n=113 Participants Women will receive prenatal vitamins containing 4000 IU of Vitamin D. Dietary supplement: 4000 IU Vitamin D3 in prenatal vitamin
Mean Calcemia as Measured by Serum Calcium Test (36-40 Weeks)	2.3 mmol/L Standard Deviation 0.2	2.3 mmol/L Standard Deviation 0.2	2.3 mmol/L Standard Deviation 0.2

Adverse Events

600 IU

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

2000 IU

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

4000 IU

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Janet Rich-Edwards

Brigham and Women's Hospital

Phone: 617-525-8264

Email: jr33@partners.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place