Prenatal Amino Acid Supplementation to Improve Fetal Growth: A Systematic Review and Meta-Analysis.

Fieke Terstappen,Jaap A Joles,Hendrik Gremmels,Kimberley E Wever,Angela J C Tol,Eline M Van Der Beek,Nina D Paauw,A Titia Lely

doi:10.3390/nu12092535

Abstract

Aberrant fetal growth remains a leading cause of perinatal morbidity and mortality and is associated with a risk of developing non-communicable diseases later in life. We performed a systematic review and meta-analysis combining human and animal studies to assess whether prenatal amino acid (AA) supplementation could be a promising approach to promote healthy fetal growth. PubMed, Embase, and Cochrane libraries were searched to identify studies orally supplementing the following AA groups during gestation: (1) arginine family, (2) branched chain (BCAA), and (3) methyl donors. The primary outcome was fetal/birth weight. Twenty-two human and 89 animal studies were included in the systematic review. The arginine family and, especially, arginine itself were studied the most. Our meta-analysis showed beneficial effects of arginine and (N-Carbamyl) glutamate (NCG) but not aspartic acid and citrulline on fetal/birth weight. However, no effects were reported when an isonitrogenous control diet was included. BCAA and methyl donor supplementation did not affect fetal/birth weight. Arginine family supplementation, in particular arginine and NCG, improves fetal growth in complicated pregnancies. BCAA and methyl donor supplementation do not seem to be as promising in targeting fetal growth. Well-controlled research in complicated pregnancies is needed before ruling out AA supplements or preferring arginine above other AAs.

Highlights

Divergence in fetal growth—both under- and overgrowth—remains a leading cause of perinatal mortality and morbidity [1,2]
Fetal overgrowth is observed in gestational diabetes mellitus (GDM) in which increased circulating amino acid (AA) levels interact with insulin sensitivity, and increased maternal glucose stimulates nutrient transport over the placenta [17,18,19,20]
The majority of exclusions during the full-text screen was based on no in vivo studies on pregnant animals or humans followed by no supplementation of the amino acids of interest and resulted in 501 studies for full-text screening, of which we included 111 studies in our systematic review (Figure A1)

Summary

Introduction

Divergence in fetal growth—both under- and overgrowth—remains a leading cause of perinatal mortality and morbidity [1,2]. Normal fetal growth requires adequate amino acid (AA) supply during all trimesters, which depends on the placental capacity to transfer AAs from the maternal to fetal side [9]. Several factors influence this transfer capacity, such as maternal plasma AA concentrations, utero-placental blood flow, and placental surface area [10]. Lower circulating levels of AAs of the arginine family and branched chain AAs (BCAA) and reduced expression or activity of placental AA transporters are observed in FGR pregnancies [11,12,13,14,15,16]. Fetal overgrowth is observed in gestational diabetes mellitus (GDM) in which increased circulating AA levels interact with insulin sensitivity, and increased maternal glucose stimulates nutrient transport over the placenta [17,18,19,20]

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