Maternal Vitamin D for Infant Growth (MDIG) Trial

Study Overview
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Brief Summary
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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.

Official Title
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Randomized Placebo-controlled Trial of Maternal Vitamin D Supplementation During Pregnancy and Lactation to Improve Infant Linear Growth in Dhaka, Bangladesh.

Conditions
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Pregnancy

Intervention / Treatment
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* Dietary Supplement: Vitamin D3 (cholecalciferol)
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Group A<br>Prenatal Period 0 IU; Postpartum Period 0 IU (placebo) Overall:The Prenatal Period will start at enrolment (17-24 weeks gestation) and last until delivery. The Postpartum Period will last from delivery until 6 months postpartum. | Dietary Supplement: Placebo<br>* This product will be identical in appearance, taste and texture to the experimental formulation but will not include any vitamin D3.<br>|
| Experimental: Group B<br>Prenatal Period 4,200 IU/week of vitamin D3 (=600 IU/d); Postpartum Period 0 IU/week (placebo) | Dietary Supplement: Vitamin D3 (cholecalciferol)<br>* 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.<br>Dietary Supplement: Placebo<br>* This product will be identical in appearance, taste and texture to the experimental formulation but will not include any vitamin D3.<br>|
| Experimental: Group C<br>Prenatal Period 16,800 IU/week of vitamin D3 (=2,400 IU/d); Postpartum Period 0 IU/week (placebo) | Dietary Supplement: Vitamin D3 (cholecalciferol)<br>* 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.<br>Dietary Supplement: Placebo<br>* This product will be identical in appearance, taste and texture to the experimental formulation but will not include any vitamin D3.<br>|
| Experimental: Group D<br>Prenatal Period 28,000 IU/week of vitamin D3 (=4,000 IU/d); Postpartum Period 0 IU/week (placebo) | Dietary Supplement: Vitamin D3 (cholecalciferol)<br>* 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.<br>Dietary Supplement: Placebo<br>* This product will be identical in appearance, taste and texture to the experimental formulation but will not include any vitamin D3.<br>|
| Experimental: Group E<br>Prenatal Period 28,000 IU/week of vitamin D3 (=4,000 IU/d); Postpartum Period 28,000 IU/week(=4,000 IU/d) | Dietary Supplement: Vitamin D3 (cholecalciferol)<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Infant Length-for-Age Z-Scores with Prenatal Supplementation |  | 1 year of age | 
| Infant Length-for-Age Z-Scores with Postpartum Supplementation | 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. | 1 year of age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum calcium | Maternal serum calcium will be measured during pregnancy as a primary biochemical safety parameter and post partum. | 17 weeks gestation to birth (prenatal) and over 2 years postpartum | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pregnancy, Infant Growth, Vitamin D, Bangladesh