Pregnancy
Conditions
Keywords
Pregnancy, Infant Growth, Vitamin D, Bangladesh
Brief summary
The primary aims of this study are: 1) to determine whether maternal prenatal vitamin D3 supplementation (4200 IU/week, 16,800 IU/week, or 28,000 IU/week) versus placebo increases or decreases infant length at 1 year of age, and 2) to determine whether maternal postpartum vitamin D3 supplementation (28,000 IU/week) versus placebo increases or decreases length at 1 year of age among infants born to women who received vitamin D 28,000 U/week during pregnancy. Infants enrolled in the study will be followed for 2 years to document the persistence of any observed effects measured at 1 year of age. This study aims to enroll 1300 pregnant women in the 2nd trimester at a maternity hospital in Dhaka. Participants will be randomized to one of three doses of vitamin D3 (4200 IU/week, 16,800 IU/week, or 28,000 IU/week) or placebo throughout pregnancy. Women in the 28,000 IU/week group will be additionally randomized to either placebo or a continuation of 28,000 IU/week for 6 months postpartum. In addition to linear length, the trial will include analyses of inflammatory and hormonal determinants of infant growth, epigenetic phenomena that affect vitamin D metabolism, and diarrheal and respiratory morbidity in the infants.
Interventions
DIETARY_SUPPLEMENTVitamin D3 (cholecalciferol)
The intervention is an oral tablet containing vitamin D3 (cholecalciferol). This vitamin D supplement will be provided in the form of small tablets (approximately 10 mm diameter) and will be custom- manufactured by Toronto Institute for Pharmaceutical Technology (TIPT) in Toronto, Ontario, Canada. Each weekly dose will consist of a single tablet. Across trial groups, the tablets will only vary with respect to the vitamin D3 dose, as described above.
DIETARY_SUPPLEMENTPlacebo
This product will be identical in appearance, taste and texture to the experimental formulation but will not include any vitamin D3.
Sponsors
International Centre for Diarrhoeal Disease Research, Bangladesh
Shimantik
Bill and Melinda Gates Foundation
The Hospital for Sick Children
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 100 Years
Healthy volunteers
Yes
Inclusion criteria
* Women aged 18 years and above. * Gestational age of 17 to 24 completed weeks estimated based on recalled last menstrual period (LMP) and/or ultrasound. * Intends to permanently reside in the trial catchment area for at least 18 months.
Exclusion criteria
* History of medical conditions that may predispose the participant to vitamin D sensitivity, altered vitamin D metabolism and/or hypercalcemia, or history of renal calculi. * High-risk pregnancy based on one or more of the following findings by point-of-care testing: * Severe anemia: hemoglobin \<70 g/L assessed by Hemocue * Moderate-severe proteinuria: ≥ 300 mg/dl (3+ or 4+) based on urine dipstick * Hypertension: systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure ≥90 mm Hg * Multiple gestation, major congenital anomaly, or severe oligohydramnios based on maternal history and/or ultrasound. * Unwillingness to stop taking non-study vitamin D or calcium supplements or a multivitamin with calcium and/or vitamin D. * Currently prescribed vitamin D supplements as part of a physician's treatment plan for vitamin D deficiency. * Previous participation in the same study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Infant Length-for-Age Z-Scores with Prenatal Supplementation | 1 year of age | — |
| Infant Length-for-Age Z-Scores with Postpartum Supplementation | 1 year of age | A separate analysis will be performed to assess the effect of continuation of 28,000 IU/week postpartum supplementation versus placebo (postpartum) among participants randomized to 28,000 IU/week prenatal. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum calcium | 17 weeks gestation to birth (prenatal) and over 2 years postpartum | Maternal serum calcium will be measured during pregnancy as a primary biochemical safety parameter and post partum. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Preterm birth % | Birth | — |
| Stillbirth % | 17 weeks gestation to 39 weeks | Prenatal period |
| Maternal, perinatal, neonatal and infant severe morbidity and mortality | From 17 weeks gestation to 6 months postpartum | During intervention phase (prenatal and first 6 months postpartum) |
| Stunting (LAZ < -2 SD below the median) at 1 and 2 years of age. | 1-2 years | — |
| Biomarker concentrations (specific hormones, nutrients, environmental contaminants, and inflammatory markers potentially involved in the mediation or modification of the effect of vitamin D on infant stunting). | 17 weeks gestation to 2 years postpartum | Prenatal and first 2 years postnatal |
| Epigenetic patterns of genes involved in vitamin D metabolism. | Birth | — |
| Infant acute respiratory infections and diarrhea | 6 months postpartum | first 6 months postnatal |
| Attained length and LAZ at 2 years of age. | 2 years postnatal | — |
| Birth weight, low birth weight %, small-for-gestational age % | Birth | — |
Countries
Bangladesh
Outcome results
None listed