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

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.