Clinical trial NCT01924013: Maternal Vitamin D for Infant Growth (MDIG) Trial
Official title: Randomized Placebo-controlled Trial of Maternal Vitamin D Supplementation During Pregnancy and Lactation to Improve Infant Linear Growth in Dhaka, Bangladesh.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pregnancy
Keywords: Pregnancy
Infant Growth
Vitamin D
Bangladesh
Lead sponsor: The Hospital for Sick Children
Sponsor class: OTHER
Collaborators: name: International Centre for Diarrhoeal Disease Research, Bangladesh
name: Shimantik
name: Bill and Melinda Gates Foundation
First posted: 2013-08-16
Enrollment: 1300
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Infant Length-for-Age Z-Scores with Prenatal Supplementation
timeFrame: 1 year of age
measure: Infant Length-for-Age Z-Scores with Postpartum Supplementation
timeFrame: 1 year of age
Secondary outcomes:
measure: Serum calcium
timeFrame: 17 weeks gestation to birth (prenatal) and over 2 years postpartum
Other outcomes:
measure: Stunting (LAZ < -2 SD below the median) at 1 and 2 years of age.
timeFrame: 1-2 years
measure: Attained length and LAZ at 2 years of age.
timeFrame: 2 years postnatal
measure: Birth weight, low birth weight %, small-for-gestational age %
timeFrame: Birth
measure: Preterm birth %
timeFrame: Birth
measure: Stillbirth %
timeFrame: 17 weeks gestation to 39 weeks
measure: Maternal, perinatal, neonatal and infant severe morbidity and mortality
timeFrame: From 17 weeks gestation to 6 months postpartum
measure: Infant acute respiratory infections and diarrhea
timeFrame: 6 months postpartum
measure: 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).
timeFrame: 17 weeks gestation to 2 years postpartum
measure: Epigenetic patterns of genes involved in vitamin D metabolism.
timeFrame: Birth
Locations:
city: Dhaka
country: Bangladesh
facility: International Centre for Diarrhoeal Disease Research, Bangladesh
Study officials:
affiliation: The Hospital for Sick Children
name: Daniel Roth, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pell LG, Ohuma EO, Yonemitsu C, Loutet MG, Ahmed T, Mahmud AA, Azad MB, Bode L, Roth DE. The Human-Milk Oligosaccharide Profile of Lactating Women in Dhaka, Bangladesh. Curr Dev Nutr. 2021 Nov 13;5(12):nzab137. doi: 10.1093/cdn/nzab137. eCollection 2021 Dec.
citation: O'Callaghan KM, Shanta SS, Fariha F, Harrington J, Mahmud AA, Emdin AL, Gernand AD, Ahmed T, Abrams SA, Moore DR, Roth DE. Effect of maternal prenatal and postpartum vitamin D supplementation on offspring bone mass and muscle strength in early childhood: follow-up of a randomized controlled trial. Am J Clin Nutr. 2022 Mar 4;115(3):770-780. doi: 10.1093/ajcn/nqab396.
citation: Jukic AMZ, Zuchniak A, Qamar H, Ahmed T, Mahmud AA, Roth DE. Vitamin D Treatment during Pregnancy and Maternal and Neonatal Cord Blood Metal Concentrations at Delivery: Results of a Randomized Controlled Trial in Bangladesh. Environ Health Perspect. 2020 Nov;128(11):117007. doi: 10.1289/EHP7265. Epub 2020 Nov 23.
citation: Subramanian A, Korsiak J, Murphy KE, Al Mahmud A, Roth DE, Gernand AD. Effect of vitamin D supplementation during pregnancy on mid-to-late gestational blood pressure in a randomized controlled trial in Bangladesh. J Hypertens. 2021 Jan;39(1):135-142. doi: 10.1097/HJH.0000000000002609.
citation: Jeong JH, Korsiak J, Papp E, Shi J, Gernand AD, Al Mahmud A, Roth DE. Determinants of Vitamin D Status of Women of Reproductive Age in Dhaka, Bangladesh: Insights from Husband-Wife Comparisons. Curr Dev Nutr. 2019 Oct 7;3(11):nzz112. doi: 10.1093/cdn/nzz112. eCollection 2019 Nov.
citation: Roth DE, Morris SK, Zlotkin S, Gernand AD, Ahmed T, Shanta SS, Papp E, Korsiak J, Shi J, Islam MM, Jahan I, Keya FK, Willan AR, Weksberg R, Mohsin M, Rahman QS, Shah PS, Murphy KE, Stimec J, Pell LG, Qamar H, Al Mahmud A. Vitamin D Supplementation in Pregnancy and Lactation and Infant Growth. N Engl J Med. 2018 Aug 9;379(6):535-546. doi: 10.1056/NEJMoa1800927.
citation: Roth DE, Gernand AD, Morris SK, Pezzack B, Islam MM, Dimitris MC, Shanta SS, Zlotkin SH, Willan AR, Ahmed T, Shah PS, Murphy KE, Weksberg R, Choufani S, Shah R, Al Mahmud A. Maternal vitamin D supplementation during pregnancy and lactation to promote infant growth in Dhaka, Bangladesh (MDIG trial): study protocol for a randomized controlled trial. Trials. 2015 Jul 14;16:300. doi: 10.1186/s13063-015-0825-8.