Is melatonin safe to take during pregnancy?

Melatonin Safety During Pregnancy

Based on current human evidence, melatonin appears to be safe during pregnancy, with clinical trials showing no major safety concerns or adverse events, though formal guidelines do not yet address its use and high-quality randomized controlled trials are still lacking. 1

Current Evidence Base

Human Safety Data

• A 2022 scoping review of human studies found that clinical trials using exogenous melatonin during pregnancy have not suggested major safety concerns or adverse events 1
• Contrary to animal studies that raised concerns, evidence from clinical studies to date suggests melatonin use during pregnancy is probably safe in humans 1
• Large health administrative database surveys show approximately 4% of pregnant women use exogenous melatonin, indicating real-world usage is already occurring 1

Potential Benefits During Pregnancy

• Melatonin functions as a potent antioxidant that may protect against oxidative stress-related pregnancy complications including preeclampsia, intrauterine growth retardation (IUGR), recurrent fetal loss, and premature delivery 2, 3
• Short-term melatonin therapy has been shown to be highly effective and safe in reducing complications during pregnancy and the perinatal period 3
• Melatonin is considered a promising neuroprotective agent for the fetus, particularly in cases of perinatal asphyxia 3

Physiological Role in Pregnancy

• The fetus is dependent on maternal melatonin provided transplacentally since the fetal pineal gland develops completely only postpartum 4
• Maternal melatonin concentrations increase significantly after 24 weeks of gestation, with particularly high levels after 32 weeks 4
• Melatonin receptors are widespread in the embryo and fetus from early developmental stages 4

Critical Knowledge Gaps

Lack of Formal Guidelines

• No major obstetric or medical guidelines currently address melatonin use during pregnancy - the provided guidelines focus on ADHD medications, antihypertensives, antihistamines, and acetaminophen, but do not mention melatonin 5, 6, 7, 8
• There is a notable absence of randomized controlled trials examining melatonin's efficacy and safety specifically for sleep disorders during pregnancy 1

Research Limitations

• A 2016 Cochrane review found no completed randomized trials assessing melatonin for fetal neuroprotection in pregnant women, though one trial was ongoing at that time 9
• Most existing human studies used melatonin for clinical conditions other than insomnia, so data on its use specifically for sleep disorders in pregnancy remains limited 1

Clinical Recommendations

When to Consider Melatonin

• Melatonin can be considered for pregnant women with sleep disorders when the benefits of treating maternal insomnia outweigh theoretical risks 1
• It may be particularly valuable in pregnancies complicated by conditions involving oxidative stress (preeclampsia, IUGR, risk of preterm birth) 2, 3

Dosing Considerations

• Use the lowest effective dose for the shortest duration necessary, following the general principle applied to all medications during pregnancy 8
• While specific dosing guidelines for pregnancy are not established, clinical trials have used melatonin without major adverse events 1

Important Caveats

• The historical recommendation to avoid melatonin during pregnancy was based primarily on animal research rather than human data 2, 1
• Pregnant women should be informed that while human evidence is reassuring, large-scale randomized controlled trials are still needed 1, 9
• Melatonin appears safer than many alternatives: unlike NSAIDs (which should be avoided in first and third trimesters) or certain antihistamines (associated with cleft palate risk), melatonin has not been linked to major congenital malformations in human studies 7, 1