Can a pregnant patient take melatonin?

Melatonin Use During Pregnancy

Melatonin appears to be safe for use during pregnancy based on available human evidence, though formal guidelines do not specifically address pregnancy use and data from randomized controlled trials remain limited.

Safety Profile in Pregnancy

The available human evidence suggests melatonin is probably safe during pregnancy, contrary to earlier concerns based on animal studies. 1

• Clinical trials using exogenous melatonin during pregnancy for various clinical conditions have not identified major safety concerns or adverse events 1
• Maternal melatonin levels naturally increase progressively throughout pregnancy, with highest levels in the third trimester, suggesting a physiological role 2
• The placenta itself is a major source of melatonin production during pregnancy, and maternal levels drop abruptly after delivery 2
• Melatonin receptors are expressed in the fetal brain, and maternal melatonin provides the first circadian signal to the developing fetus 3

Potential Benefits

Melatonin may offer neuroprotective effects for the developing fetus through its antioxidant, anti-inflammatory, and anti-apoptotic properties. 4, 5

• Animal studies support a fetal neuroprotective role when melatonin is administered to the mother during pregnancy 5
• Experimental supplementation has shown potential to reduce the frequency or severity of pregnancy complications including preeclampsia, fetal growth retardation, premature delivery, and stillbirth 4
• The fetal brain is highly susceptible to oxidative stress, and melatonin provides strong antioxidant protection both directly and through receptor activation 3

Current Evidence Limitations

The major limitation is the absence of randomized controlled trials specifically examining melatonin for sleep disorders or other indications during pregnancy. 5, 1

• A 2016 Cochrane review found no completed randomized trials assessing melatonin for fetal neuroprotection in pregnant women 5
• Insomnia was not the primary outcome measure in any of the human studies reviewed 1
• Most available data comes from case reports, cohort studies, and clinical trials examining other conditions 1

Perioperative Context

For surgical patients, melatonin can be continued perioperatively, including during pregnancy, as it demonstrates a good safety profile. 6

• A 2021 consensus statement from the Society for Perioperative Assessment and Quality Improvement recommends continuing melatonin perioperatively 6
• Available evidence demonstrates melatonin is safe in the perioperative period and may reduce anxiety as effectively as midazolam 6

Clinical Recommendation

Given the physiological increase in maternal melatonin during normal pregnancy, the lack of identified safety concerns in human studies, and potential neuroprotective benefits, melatonin can be used during pregnancy when clinically indicated. 1, 2

• The prevalence of melatonin use in pregnant populations is approximately 4% based on health administrative databases 1
• Evidence from clinical studies to date suggests melatonin use during pregnancy is probably safe in humans, contrary to animal study concerns 1
• Maternal melatonin plays an important role in brain formation and differentiation, and alteration in maternal melatonin levels has been associated with disrupted brain programming 3

Important Caveats

• High-quality randomized controlled trials are still needed to definitively establish safety and efficacy for specific indications during pregnancy 5
• The dose, timing, and duration of melatonin administration during pregnancy have not been systematically studied in humans 5
• While current evidence is reassuring, pregnant patients should be counseled about the limited nature of available data 1