Is melatonin safe for use during pregnancy?

Melatonin Safety in Pregnancy

Melatonin can be safely continued during pregnancy based on available evidence from clinical trials and perioperative guidelines, which demonstrate no major safety concerns or adverse events in humans. 1

Evidence-Based Safety Profile

Guideline Support for Safety

• The Society for Perioperative Assessment and Quality Improvement (SPAQI) explicitly recommends continuing melatonin perioperatively, concluding that available evidence demonstrates melatonin is safe in the perioperative period, including for pregnant patients. 1
• A Cochrane review found that preoperative melatonin reduces anxiety compared with placebo and may be as effective as midazolam, with a good safety profile. 1

Human Clinical Evidence

• Clinical trials using exogenous melatonin during pregnancy for various conditions have not suggested major safety concerns or adverse events. 2
• Contrary to animal studies that raised theoretical concerns, evidence from clinical studies to date suggests that melatonin use during pregnancy is probably safe in humans. 2
• Large health administrative database surveys show that approximately 4% of pregnant populations use exogenous melatonin, indicating widespread real-world use. 2

Physiological Rationale for Safety

Natural Pregnancy Changes

• Maternal melatonin levels increase progressively throughout normal pregnancy until term, and melatonin is highly transferred to the fetus with an important role in brain formation and differentiation. 3
• Maternal melatonin provides the first circadian signal to the fetus and crosses the placenta freely without being altered. 4
• Melatonin appears to be essential for successful pregnancy, working as a circadian rhythm modulator, endocrine modulator, immunomodulator, and antioxidant. 4

Neuroprotective Properties

• Melatonin has strong antioxidant protective effects and may protect against fetal brain injury through its neuroprotective effects. 3
• The fetal brain is highly susceptible to oxidative stress, and melatonin's antioxidant properties may be beneficial rather than harmful. 3

Important Caveats

Limitations in Current Evidence

• There is a lack of randomized controlled trials specifically examining melatonin for insomnia treatment during pregnancy, though this does not indicate harm. 2
• Most safety data comes from clinical trials using melatonin for other conditions (not sleep disorders), case reports, and cohort studies rather than large-scale RCTs. 2
• A Cochrane review found no completed trials specifically for fetal neuroprotection, though one trial is ongoing. 5

Theoretical Concerns from Animal Studies

• Animal studies have raised concerns about potential effects on reproductive function, timing of puberty, and fetal circadian development, but these have not been substantiated in human studies. 6
• The disconnect between animal and human data emphasizes the importance of relying on human clinical evidence. 2

Clinical Application

For pregnant patients requiring melatonin for sleep disorders or anxiety:

• Continue melatonin use based on the SPAQI consensus statement and available human safety data. 1
• Use typical doses (5 mg or less oral fast-release formulation), as this has been the most studied dosing in clinical contexts. 6
• Reassure patients that human clinical evidence supports safety, despite theoretical concerns from animal research. 2