Open Access Highly Accessed Study protocol

Preconception maternal nutrition: a multi-site randomized controlled trial

K Michael Hambidge1*, Nancy F Krebs1, Jamie E Westcott1, Ana Garces2, Shivaprasad S Goudar3, Balachandra S Kodkany3, Omrana Pasha4, Antoinette Tshefu5, Carl L Bose6, Lester Figueroa7, Robert L Goldenberg8, Richard J Derman9, Jacob E Friedman1, Daniel N Frank1, Elizabeth M McClure10, Kristen Stolka10, Abhik Das10, Marion Koso-Thomas11, Shelly Sundberg12 and the Preconception Trial Group

Author Affiliations

1 University of Colorado Denver, Aurora, CO, USA

2 Francisco Marroquin University, Guatemala City, Guatemala

3 KLE University’s Jawaharlal Nehru Medical College, Belgaum, Karnataka, India

4 Aga Khan University, Karachi, Pakistan

5 Kinshasa School of Public Health, Kinshasa, Democratic Republic of Congo (DRC

6 University of North Carolina, Chapel Hill, NC, USA

7 FANCAP, Guatemala City, Guatemala

8 Columbia University, New York, NY, USA

9 Christiana Care, Newark, DE, USA

10 RTI International, Research Triangle Park, NC, USA

11 Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville, MD, USA

12 Bill & Melinda Gates Foundation, Seattle, WA, USA

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BMC Pregnancy and Childbirth 2014, 14:111  doi:10.1186/1471-2393-14-111

Published: 20 March 2014

Abstract

Background

Research directed to optimizing maternal nutrition commencing prior to conception remains very limited, despite suggestive evidence of its importance in addition to ensuring an optimal nutrition environment in the periconceptional period and throughout the first trimester of pregnancy.

Methods/Study design

This is an individually randomized controlled trial of the impact on birth length (primary outcome) of the time at which a maternal nutrition intervention is commenced: Arm 1: ≥ 3 mo preconception vs. Arm 2: 12-14 wk gestation vs. Arm 3: none.

192 (derived from 480) randomized mothers and living offspring in each arm in each of four research sites (Guatemala, India, Pakistan, Democratic Republic of the Congo). The intervention is a daily 20 g lipid-based (118 kcal) multi-micronutient (MMN) supplement. Women randomized to receive this intervention with body mass index (BMI) <20 or whose gestational weight gain is low will receive an additional 300 kcal/d as a balanced energy-protein supplement. Researchers will visit homes biweekly to deliver intervention and monitor compliance, pregnancy status and morbidity; ensure prenatal and delivery care; and promote breast feeding. The primary outcome is birth length. Secondary outcomes include: fetal length at 12 and 34 wk; incidence of low birth weight (LBW); neonatal/infant anthropometry 0-6 mo of age; infectious disease morbidity; maternal, fetal, newborn, and infant epigenetics; maternal and infant nutritional status; maternal and infant microbiome; gut inflammatory biomarkers and bioactive and nutritive compounds in breast milk. The primary analysis will compare birth Length-for-Age Z-score (LAZ) among trial arms (independently for each site, estimated effect size: 0.35). Additional statistical analyses will examine the secondary outcomes and a pooled analysis of data from all sites.

Discussion

Positive results of this trial will support a paradigm shift in attention to nutrition of all females of child-bearing age.

Trial registration

ClinicalTrials.gov NCT01883193.

Keywords:
Preconception; Maternal; Nutrition; Birth length; Epigenetics; Microbiome