L-Arginine supplementation in pregnancy: a systematic review of maternal and fetal outcomes

Abstract

Background/aim of the study: L-Arginine (L-Arg)/Nitric Oxide (NO) system is involved in the pathophysiology of relevant Obstetric conditions. This review aims at summarizing the effects of L-Arg supplementation in pregnancy looking at safety and efficacy.

Methods: We conducted a systematic review of the literature utilizing PubMed for studies published from inception to September 2022. The search included human and animal studies where L-Arg was supplemented pre-conceptionally or during pregnancy, by either oral or intravenous route. The main perinatal outcomes were focused.

Results: Among 1028 publications, 51 studies were eligible for inclusion, 25 were performed in women, and the remnant in animals. Compared to controls/placebo, the supplementation with L-Arg reduced the development of pre-eclampsia (four studies), decreased blood pressure, and reduced the need for antihypertensive drugs in women with Hypertensive Disorders of Pregnancy (HDP, eight studies). In women carrying growth retarded fetuses, L-Arg improved fetoplacental circulation, birth weight and neonatal outcomes (five studies), while in the case of threatened preterm birth, L-Arg reduced uterine contractions (two studies). In several animal species, L-Arg supplementation in pregnancy improved reproductive performance by increasing the litter number and size. Moreover, in pre-eclamptic and metabolic syndrome experimental models, maternal hypertension and fetal growth were improved.

Conclusion: L-Arg displays biological activities in pregnancies complicated by HDP and growth restriction, both in women and animal models. L-Arg administration is safe and could be a candidate as an intervention beneficial to maternal and fetal outcomes, at least in moderate clinical disorders.

Keywords: L-Arginine; animal studies; human studies; perinatal outcomes; pregnancy.