Maternal Multiple Micronutrient Supplementation Stabilizes Mitochondrial DNA Copy Number in Pregnant Women in Lombok, Indonesia

Lidwina Priliani; Elizabeth L Prado; Restuadi Restuadi; Diana E Waturangi; Anuraj H Shankar; Safarina G Malik

doi:10.1093/jn/nxz064

Maternal Multiple Micronutrient Supplementation Stabilizes Mitochondrial DNA Copy Number in Pregnant Women in Lombok, Indonesia

J Nutr. 2019 Aug 1;149(8):1309-1316. doi: 10.1093/jn/nxz064.

Authors

Lidwina Priliani^{1

2}, Elizabeth L Prado^{3

4}, Restuadi Restuadi^{1

5}, Diana E Waturangi², Anuraj H Shankar^{3

6}, Safarina G Malik¹

Affiliations

¹ Eijkman Institute for Molecular Biology, Ministry of Research, Technology and Higher Education and.
² Faculty of Biotechnology, Atma Jaya Catholic University of Indonesia, Jakarta, Indonesia.
³ Summit Institute of Development, Mataram, West Nusa Tenggara, Indonesia.
⁴ Department of Nutrition, University of California at Davis, Davis, CA.
⁵ Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.
⁶ Department of Nutrition, Harvard TH Chan School of Public Health, Boston, MA.

Abstract

Background: The Supplementation with Multiple Micronutrients Intervention Trial (SUMMIT) in Lombok, Indonesia showed that maternal multiple micronutrients (MMN), as compared with iron and folic acid (IFA), reduced fetal loss, early infant mortality, and low birth weight. Mitochondria play a key role during pregnancy by providing maternal metabolic energy for fetal development, but the effects of maternal supplementation during pregnancy on mitochondria are not fully understood.

Objective: The aim of this study was to assess the impact of MMN supplementation on maternal mitochondrial DNA copy number (mtDNA-CN).

Methods: We used archived venous blood specimens from pregnant women enrolled in the SUMMIT study. SUMMIT was a cluster-randomized double-blind controlled trial in which midwives were randomly assigned to distribute MMN or IFA to pregnant women. In this study, we selected 108 sets of paired baseline and postsupplementation samples (MMN = 54 and IFA = 54). Maternal mtDNA-CN was determined by real-time quantitative polymerase chain reaction in baseline and postsupplementation specimens. The association between supplementation type and change in mtDNA-CN was performed using rank-based estimation for linear models.

Results: In both groups, maternal mtDNA-CN at postsupplementation was significantly elevated compared with baseline (P < 0.001). The regression revealed that the MMN group had lower postsupplementation mtDNA-CN than the IFA group (β = -4.63, P = 0.003), especially for women with mtDNA-CN levels above the median at baseline (β = -7.49, P = 0.007). This effect was rapid, and observed within 33 d of initiation of supplementation (β = -7.39, P = 0.017).

Conclusion: Maternal MMN supplementation rapidly stabilized mtDNA-CN in pregnant women who participated in SUMMIT, indicating improved mitochondrial efficiency. The data provide a mechanistic basis for the beneficial effects of MMN on fetal growth and survival, and support the transition from routine IFA to MMN supplementation.This trial was registered at www.isrctn.com as ISRCTN34151616.

Keywords: iron and folic acid; mitochondrial DNA copy number; mtDNA-CN; multiple micronutrients; oxidative stress; pregnancy; supplementation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
DNA Copy Number Variations / drug effects*
DNA, Mitochondrial / genetics*
Dietary Supplements*
Female
Humans
Indonesia
Micronutrients / administration & dosage*
Micronutrients / pharmacology
Oxidative Stress / drug effects
Pregnancy
Randomized Controlled Trials as Topic
Young Adult

Substances

DNA, Mitochondrial
Micronutrients