Melatonin (Meloset) Safety in Pregnancy
Based on current human evidence, melatonin appears to be probably safe during pregnancy, though it should be used with caution given the lack of high-quality randomized controlled trials and theoretical concerns about fetal circadian programming. 1
Evidence Quality and Current Understanding
The evidence base for melatonin use in pregnancy consists primarily of observational studies, case reports, and clinical trials examining melatonin for conditions other than sleep disorders—no randomized controlled trials have specifically evaluated melatonin for insomnia during pregnancy. 1
Human Safety Data
Clinical trials using exogenous melatonin during pregnancy for various clinical conditions have not demonstrated major safety concerns or adverse events. 1
A scoping review of human studies found that approximately 4% of pregnant women use exogenous melatonin, suggesting relatively common real-world use. 1
Contrary to animal study concerns, evidence from clinical studies to date suggests melatonin use during pregnancy and breastfeeding is probably safe in humans. 1
Theoretical Concerns vs. Clinical Reality
Fetal Circadian Programming
Maternal melatonin naturally crosses the placenta and provides photoperiodic information to the fetus, influencing subsequent circadian and seasonal rhythms. 2, 3
The fetal suprachiasmatic nucleus (the biological clock) expresses melatonin receptors from early development, making it responsive to both endogenous and exogenous melatonin. 3
Melatonin receptors are widespread in the human fetus and occur in both central and peripheral tissues from early fetal development. 2
Neuroprotective Effects
Maternal melatonin levels increase progressively during normal pregnancy until term and play an important role in fetal brain formation and differentiation. 4
Melatonin has strong antioxidant and neuroprotective effects that may actually benefit fetal brain development, particularly in pregnancy disorders where maternal melatonin levels are decreased. 4
The fetal brain is highly susceptible to oxidative stress, and melatonin's protective effects have been studied as treatment for fetal brain injury. 4
Clinical Decision-Making Algorithm
When considering melatonin for a pregnant patient:
Assess the severity of sleep disturbance and whether non-pharmacologic interventions have been attempted (sleep hygiene, cognitive behavioral therapy for insomnia). 1
Recognize that while theoretical concerns exist based on animal studies, human clinical data have not demonstrated significant adverse outcomes. 1, 2
Consider that maternal melatonin naturally crosses the placenta as part of normal physiology, and exogenous supplementation may simply augment this natural process. 2, 3
Use the lowest effective dose if prescribing, given that melatonin receptors are more abundant during fetal development than in mature animals. 3
Avoid behaviors that disrupt the mother's endogenous melatonin rhythm (such as excessive light exposure at night), as this may be as concerning as exogenous supplementation. 3
Breastfeeding Considerations
Human studies examining melatonin during breastfeeding have not suggested major safety concerns. 1
The same scoping review that found probable safety during pregnancy also concluded probable safety during lactation based on available human evidence. 1
Important Caveats
The lack of randomized controlled trials specifically for sleep disorders in pregnancy represents a significant evidence gap. 1
Most safety data come from studies where melatonin was used for other clinical indications (such as neuroprotection), not specifically for insomnia. 1
Earlier recommendations to avoid melatonin during pregnancy were based primarily on animal studies and theoretical concerns about circadian programming, which have not materialized in human clinical experience. 2, 3
The widespread distribution of melatonin receptors during fetal development suggests potential for broader effects beyond circadian entrainment, though clinical significance remains unclear. 2