Maternal Vitamin D for Infant Growth (MDIG) Trial

Phase 3CompletedNCT01924013

The Hospital for Sick Children1,300 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Enrollment

1,300

Conditions

Pregnancy

Interventions

Vitamin D3 (cholecalciferol)DIETARY_SUPPLEMENT

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.

PlaceboDIETARY_SUPPLEMENT

This product will be identical in appearance, taste and texture to the experimental formulation but will not include any vitamin D3.

Eligibility

Sex: FEMALEMin age: 18 YearsMax age: 100 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Infant Length-for-Age Z-Scores with Prenatal Supplementation

Time frame: 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.

Time frame: 1 year of age

Secondary Outcomes

Serum calcium

Maternal serum calcium will be measured during pregnancy as a primary biochemical safety parameter and post partum.

Time frame: 17 weeks gestation to birth (prenatal) and over 2 years postpartum