Maternal vitamin D supplementation during pregnancy and lactation to promote infant growth in Dhaka, Bangladesh (MDIG trial): study protocol for a randomized controlled trial

doi:10.1186/s13063-015-0825-8

Randomized Controlled Trial

. 2015 Jul 14:16:300.

doi: 10.1186/s13063-015-0825-8.

Maternal vitamin D supplementation during pregnancy and lactation to promote infant growth in Dhaka, Bangladesh (MDIG trial): study protocol for a randomized controlled trial

Daniel E Roth^{1

2}, Alison D Gernand³, Shaun K Morris^{4

5}, Brendon Pezzack^{6

7}, M Munirul Islam⁸, Michelle C Dimitris^{9

10}, Shaila S Shanta¹¹, Stanley H Zlotkin^{12

13}, Andrew R Willan¹⁴, Tahmeed Ahmed¹⁵, Prakesh S Shah^{16

17}, Kellie E Murphy¹⁸, Rosanna Weksberg^{19

20}, Sanaa Choufani²¹, Rashed Shah²², Abdullah Al Mahmud²³

Affiliations

¹ Department of Paediatrics, University of Toronto and the Centre for Global Child Health, Hospital for Sick Children, 686 Bay Street, Toronto, ON, Canada. daniel.roth@sickkids.ca.
² Child Health Evaluative Sciences, SickKids Research Institute, Hospital for Sick Children, 686 Bay Street, Toronto, ON, Canada. daniel.roth@sickkids.ca.
³ Department of Nutritional Sciences, Penn State University, 110 Chandlee Laboratory, University Park, PA, USA. adg14@psu.edu.
⁴ Department of Paediatrics, University of Toronto and the Centre for Global Child Health, Hospital for Sick Children, 686 Bay Street, Toronto, ON, Canada. shaun.morris@sickkids.ca.
⁵ Child Health Evaluative Sciences, SickKids Research Institute, Hospital for Sick Children, 686 Bay Street, Toronto, ON, Canada. shaun.morris@sickkids.ca.
⁶ Department of Paediatrics, University of Toronto and the Centre for Global Child Health, Hospital for Sick Children, 686 Bay Street, Toronto, ON, Canada. bpezzack@gmail.com.
⁷ Child Health Evaluative Sciences, SickKids Research Institute, Hospital for Sick Children, 686 Bay Street, Toronto, ON, Canada. bpezzack@gmail.com.
⁸ Centre for Nutrition and Food Security, International Centre for Diarrhoeal Disease Research (ICDDR,B), 68 Shaheed Tajuddin Ahmed Sarani, Mohakhali, Dhaka, 1212, Bangladesh. mislam@icddrb.org.
⁹ Department of Paediatrics, University of Toronto and the Centre for Global Child Health, Hospital for Sick Children, 686 Bay Street, Toronto, ON, Canada. michelle.dimitris@sickkids.ca.
¹⁰ Child Health Evaluative Sciences, SickKids Research Institute, Hospital for Sick Children, 686 Bay Street, Toronto, ON, Canada. michelle.dimitris@sickkids.ca.
¹¹ Centre for Nutrition and Food Security, International Centre for Diarrhoeal Disease Research (ICDDR,B), 68 Shaheed Tajuddin Ahmed Sarani, Mohakhali, Dhaka, 1212, Bangladesh. shaila.sharmeen@icddrb.org.
¹² Department of Paediatrics, University of Toronto and the Centre for Global Child Health, Hospital for Sick Children, 686 Bay Street, Toronto, ON, Canada. stanley.zlotkin@sickkids.ca.
¹³ Child Health Evaluative Sciences, SickKids Research Institute, Hospital for Sick Children, 686 Bay Street, Toronto, ON, Canada. stanley.zlotkin@sickkids.ca.
¹⁴ Child Health Evaluative Sciences, SickKids Research Institute, Hospital for Sick Children, 686 Bay Street, Toronto, ON, Canada. andy@andywillan.com.
¹⁵ Centre for Nutrition and Food Security, International Centre for Diarrhoeal Disease Research (ICDDR,B), 68 Shaheed Tajuddin Ahmed Sarani, Mohakhali, Dhaka, 1212, Bangladesh. tahmeed@icddrb.org.
¹⁶ Department of Paediatrics, University of Toronto and the Centre for Global Child Health, Hospital for Sick Children, 686 Bay Street, Toronto, ON, Canada. pshah@mtsinai.on.ca.
¹⁷ Division of Neonatology, Mt. Sinai Hospital, 600 University Avenue, Toronto, ON, Canada. pshah@mtsinai.on.ca.
¹⁸ Department of Obstetrics and Gynecology, University of Toronto and Mt. Sinai Hospital, 600 University Avenue, Toronto, ON, Canada. kmurphy@mtsinai.on.ca.
¹⁹ Department of Paediatrics, University of Toronto and the Centre for Global Child Health, Hospital for Sick Children, 686 Bay Street, Toronto, ON, Canada. rweksb@sickkids.ca.
²⁰ Genetics and Genome Biology, SickKids Research Institute, Hospital for Sick Children, 686 Bay Street, Toronto, ON, Canada. rweksb@sickkids.ca.
²¹ Genetics and Genome Biology, SickKids Research Institute, Hospital for Sick Children, 686 Bay Street, Toronto, ON, Canada. sanaa.choufani@sickkids.ca.
²² Department of Health and Nutrition, Save the Children USA, 2000 L Street NW, Suite 500, Washington, DC, USA. mshah@savechildren.org.
²³ Centre for Child and Adolescent Health, International Centre for Diarrhoeal Disease Research (ICDDR,B), 68 Shaheed Tajuddin Ahmed Sarani, Mohakhali, Dhaka, 1212, Bangladesh. mahmud@icddrb.org.

PMID: 26169781
PMCID: PMC4499946
DOI: 10.1186/s13063-015-0825-8

Randomized Controlled Trial

Maternal vitamin D supplementation during pregnancy and lactation to promote infant growth in Dhaka, Bangladesh (MDIG trial): study protocol for a randomized controlled trial

Daniel E Roth et al. Trials. 2015.

. 2015 Jul 14:16:300.

doi: 10.1186/s13063-015-0825-8.

Authors

Affiliations

¹ Department of Paediatrics, University of Toronto and the Centre for Global Child Health, Hospital for Sick Children, 686 Bay Street, Toronto, ON, Canada. daniel.roth@sickkids.ca.
² Child Health Evaluative Sciences, SickKids Research Institute, Hospital for Sick Children, 686 Bay Street, Toronto, ON, Canada. daniel.roth@sickkids.ca.
³ Department of Nutritional Sciences, Penn State University, 110 Chandlee Laboratory, University Park, PA, USA. adg14@psu.edu.
⁴ Department of Paediatrics, University of Toronto and the Centre for Global Child Health, Hospital for Sick Children, 686 Bay Street, Toronto, ON, Canada. shaun.morris@sickkids.ca.
⁵ Child Health Evaluative Sciences, SickKids Research Institute, Hospital for Sick Children, 686 Bay Street, Toronto, ON, Canada. shaun.morris@sickkids.ca.
⁶ Department of Paediatrics, University of Toronto and the Centre for Global Child Health, Hospital for Sick Children, 686 Bay Street, Toronto, ON, Canada. bpezzack@gmail.com.
⁷ Child Health Evaluative Sciences, SickKids Research Institute, Hospital for Sick Children, 686 Bay Street, Toronto, ON, Canada. bpezzack@gmail.com.
⁸ Centre for Nutrition and Food Security, International Centre for Diarrhoeal Disease Research (ICDDR,B), 68 Shaheed Tajuddin Ahmed Sarani, Mohakhali, Dhaka, 1212, Bangladesh. mislam@icddrb.org.
⁹ Department of Paediatrics, University of Toronto and the Centre for Global Child Health, Hospital for Sick Children, 686 Bay Street, Toronto, ON, Canada. michelle.dimitris@sickkids.ca.
¹⁰ Child Health Evaluative Sciences, SickKids Research Institute, Hospital for Sick Children, 686 Bay Street, Toronto, ON, Canada. michelle.dimitris@sickkids.ca.
¹¹ Centre for Nutrition and Food Security, International Centre for Diarrhoeal Disease Research (ICDDR,B), 68 Shaheed Tajuddin Ahmed Sarani, Mohakhali, Dhaka, 1212, Bangladesh. shaila.sharmeen@icddrb.org.
¹² Department of Paediatrics, University of Toronto and the Centre for Global Child Health, Hospital for Sick Children, 686 Bay Street, Toronto, ON, Canada. stanley.zlotkin@sickkids.ca.
¹³ Child Health Evaluative Sciences, SickKids Research Institute, Hospital for Sick Children, 686 Bay Street, Toronto, ON, Canada. stanley.zlotkin@sickkids.ca.
¹⁴ Child Health Evaluative Sciences, SickKids Research Institute, Hospital for Sick Children, 686 Bay Street, Toronto, ON, Canada. andy@andywillan.com.
¹⁵ Centre for Nutrition and Food Security, International Centre for Diarrhoeal Disease Research (ICDDR,B), 68 Shaheed Tajuddin Ahmed Sarani, Mohakhali, Dhaka, 1212, Bangladesh. tahmeed@icddrb.org.
¹⁶ Department of Paediatrics, University of Toronto and the Centre for Global Child Health, Hospital for Sick Children, 686 Bay Street, Toronto, ON, Canada. pshah@mtsinai.on.ca.
¹⁷ Division of Neonatology, Mt. Sinai Hospital, 600 University Avenue, Toronto, ON, Canada. pshah@mtsinai.on.ca.
¹⁸ Department of Obstetrics and Gynecology, University of Toronto and Mt. Sinai Hospital, 600 University Avenue, Toronto, ON, Canada. kmurphy@mtsinai.on.ca.
¹⁹ Department of Paediatrics, University of Toronto and the Centre for Global Child Health, Hospital for Sick Children, 686 Bay Street, Toronto, ON, Canada. rweksb@sickkids.ca.
²⁰ Genetics and Genome Biology, SickKids Research Institute, Hospital for Sick Children, 686 Bay Street, Toronto, ON, Canada. rweksb@sickkids.ca.
²¹ Genetics and Genome Biology, SickKids Research Institute, Hospital for Sick Children, 686 Bay Street, Toronto, ON, Canada. sanaa.choufani@sickkids.ca.
²² Department of Health and Nutrition, Save the Children USA, 2000 L Street NW, Suite 500, Washington, DC, USA. mshah@savechildren.org.
²³ Centre for Child and Adolescent Health, International Centre for Diarrhoeal Disease Research (ICDDR,B), 68 Shaheed Tajuddin Ahmed Sarani, Mohakhali, Dhaka, 1212, Bangladesh. mahmud@icddrb.org.

PMID: 26169781
PMCID: PMC4499946
DOI: 10.1186/s13063-015-0825-8

Abstract

Background: Vitamin D regulates bone mineral metabolism and skeletal development. Some observational studies have suggested that prenatal vitamin D deficiency increases the risk of adverse pregnancy and/or birth outcomes; however, there is scant evidence from controlled trials, leading the World Health Organization to advise against routine vitamin D supplementation in pregnancy. Importantly, little is known about the effect of maternal vitamin D status on infant linear growth in communities in South Asia where stunting is highly prevalent and maternal-infant vitamin D status is commonly suboptimal.

Methods/design: The Maternal Vitamin D for Infant Growth study is a randomized, placebo-controlled, dose-ranging trial of maternal vitamin D supplementation during pregnancy and lactation in Dhaka, Bangladesh. The primary aims are to estimate (1) the effect of maternal prenatal oral vitamin D3 supplementation (4200 IU/wk, 16,800 IU/wk, or 28,000 IU/wk, administered as weekly doses) versus placebo on infant length at 1 year of age and (2) the effect of maternal postpartum oral vitamin D3 supplementation (28,000 IU/wk) versus placebo on length at 1 year of age among infants born to women who received vitamin D 28,000 IU/wk during pregnancy. Generally healthy pregnant women (n = 1300) in the second trimester (17-24 weeks of gestation) are randomized to one of five parallel arms: placebo 4200 IU/wk, 16,800 IU/wk, or 28,000 IU/wk in the prenatal period and placebo in the postpartum period or 28,000 IU/wk in the prenatal period and 28,000 IU/wk in the postpartum period. Household- and clinic-based follow-up of mother-infant pairs is conducted weekly by trained personnel until 26 weeks postpartum and every 3 months thereafter. The primary trial outcome measure is length for age z-score at 1 year of age. Anthropometric measurements, clinical information, and biological specimens collected at scheduled intervals will enable the assessment of a range of maternal, perinatal, and infant outcomes.

Discussion: The role of vitamin D in maternal and infant health remains unresolved. This trial is expected to contribute unique insights into the effects of improving maternal-infant vitamin D status in a low-income setting where stunting and adverse perinatal outcomes represent significant public health burdens.

Trial registration: ClinicalTrials.gov identifier: NCT01924013. Registered on 13 August 2013.

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Figures

**Fig. 1**
Maternal Vitamin D for Infant Growth (MDIG) trial flow diagram. The allocated intervention in each group is shown as “prenatal intervention; postpartum intervention”

See this image and copyright information in PMC

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References

1. Liu L, Oza S, Hogan D, Perin J, Rudan I, Lawn JE, et al. Global, regional, and national causes of child mortality in 2000–13, with projections to inform post-2015 priorities: an updated systematic analysis. Lancet. 2015;385(9966):430–40. doi: 10.1016/S0140-6736(14)61698-6. - DOI - PubMed
1. Black RE, Allen LH, Bhutta ZA, Caulfield LE, de Onis M, Ezzati M, et al. Maternal and child undernutrition: global and regional exposures and health consequences. Lancet. 2008;371(9608):243–60. doi: 10.1016/S0140-6736(07)61690-0. - DOI - PubMed
1. Stevens GA, Finucane MM, Paciorek CJ, Flaxman SR, White RA, Donner AJ, et al. Trends in mild, moderate, and severe stunting and underweight, and progress towards MDG 1 in 141 developing countries: a systematic analysis of population representative data. Lancet. 2012;380(9844):824–34. doi: 10.1016/S0140-6736(12)60647-3. - DOI - PMC - PubMed
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[1] Liu L, Oza S, Hogan D, Perin J, Rudan I, Lawn JE, et al. Global, regional, and national causes of child mortality in 2000–13, with projections to inform post-2015 priorities: an updated systematic analysis. Lancet. 2015;385(9966):430–40. doi: 10.1016/S0140-6736(14)61698-6. - DOI - PubMed

[2] Liu L, Oza S, Hogan D, Perin J, Rudan I, Lawn JE, et al. Global, regional, and national causes of child mortality in 2000–13, with projections to inform post-2015 priorities: an updated systematic analysis. Lancet. 2015;385(9966):430–40. doi: 10.1016/S0140-6736(14)61698-6. - DOI - PubMed

[3] Black RE, Allen LH, Bhutta ZA, Caulfield LE, de Onis M, Ezzati M, et al. Maternal and child undernutrition: global and regional exposures and health consequences. Lancet. 2008;371(9608):243–60. doi: 10.1016/S0140-6736(07)61690-0. - DOI - PubMed

[4] Black RE, Allen LH, Bhutta ZA, Caulfield LE, de Onis M, Ezzati M, et al. Maternal and child undernutrition: global and regional exposures and health consequences. Lancet. 2008;371(9608):243–60. doi: 10.1016/S0140-6736(07)61690-0. - DOI - PubMed

[5] Stevens GA, Finucane MM, Paciorek CJ, Flaxman SR, White RA, Donner AJ, et al. Trends in mild, moderate, and severe stunting and underweight, and progress towards MDG 1 in 141 developing countries: a systematic analysis of population representative data. Lancet. 2012;380(9844):824–34. doi: 10.1016/S0140-6736(12)60647-3. - DOI - PMC - PubMed

[6] Stevens GA, Finucane MM, Paciorek CJ, Flaxman SR, White RA, Donner AJ, et al. Trends in mild, moderate, and severe stunting and underweight, and progress towards MDG 1 in 141 developing countries: a systematic analysis of population representative data. Lancet. 2012;380(9844):824–34. doi: 10.1016/S0140-6736(12)60647-3. - DOI - PMC - PubMed

[7] National Institute of Population Research and Training (NIPORT), Mitra and Associates, ICF International. Bangladesh demographic and health survey 2011. Dhaka, Bangladesh/Calverton, MD: NIPORT, Mitra and Associates, ICF International; January 2013. http://dhsprogram.com/pubs/pdf/FR265/FR265.pdf. Accessed 5 July 2015.

[8] National Institute of Population Research and Training (NIPORT), Mitra and Associates, ICF International. Bangladesh demographic and health survey 2011. Dhaka, Bangladesh/Calverton, MD: NIPORT, Mitra and Associates, ICF International; January 2013. http://dhsprogram.com/pubs/pdf/FR265/FR265.pdf. Accessed 5 July 2015.

[9] Victora CG, Adair L, Fall C, Hallal PC, Martorell R, Richter L, et al. Maternal and child undernutrition: consequences for adult health and human capital. Lancet. 2008;371(9609):340–57. doi: 10.1016/S0140-6736(07)61692-4. - DOI - PMC - PubMed

[10] Victora CG, Adair L, Fall C, Hallal PC, Martorell R, Richter L, et al. Maternal and child undernutrition: consequences for adult health and human capital. Lancet. 2008;371(9609):340–57. doi: 10.1016/S0140-6736(07)61692-4. - DOI - PMC - PubMed

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Maternal vitamin D supplementation during pregnancy and lactation to promote infant growth in Dhaka, Bangladesh (MDIG trial): study protocol for a randomized controlled trial

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Maternal vitamin D supplementation during pregnancy and lactation to promote infant growth in Dhaka, Bangladesh (MDIG trial): study protocol for a randomized controlled trial

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