Melatonin in Preeclampsia: a Systematic Review of its Role in Pathogenesis and Therapeutic Potential.

Preeclampsia (PE) is a hypertensive disorder of pregnancy that contributes substantially to maternal and fetal morbidity and mortality. Because current therapeutic options remain limited, melatonin (ML), with its antioxidant and anti-inflammatory properties has been proposed as a potential adjunct therapy. This review systematically evaluates and meta-analyses the available human and animal evidence on the effects of ML in PE. A systematic search of PubMed, Scopus, Web of Science, and Google Scholar was conducted up to the end of 2024. Eligible studies included clinical trials evaluating the effect of exogenous ML in PE models. Data extraction and quality assessment were performed independently by two reviewers. A random-effects model was used for meta-analysis. Nine studies were included: one human trial and eight animal studies. The human trial showed that ML (30 mg/day) extended the interval from diagnosis to delivery by 6 days without adverse effects, though proteinuria increased. Animal studies consistently showed that ML reduced oxidative stress and inflammation, while enhancing antioxidant defenses. Meta-analysis of six animal studies showed significant reductions in systolic blood pressure (-17.94 mmHg; 95% CI: -28.35 to -7.52) and proteinuria. ML had no significant effect on fetal weight (mean difference: 0.23 gr; 95% CI: -0.03 to 0.50) but slightly increased placental weight (0.01 gr; 95% CI: 0.00 to 0.03) among preeclamptic animal models. ML may offer limited benefit for maternal PE symptoms, but current evidence for fetal safety and fetal benefit is weak, conflicting, and insufficient for clinical recommendation. Larger human trials are needed to clarify its risk–benefit profile.