Is melatonin safe for pregnant individuals?

Is Melatonin Safe During Pregnancy?

Current evidence from human studies suggests melatonin is probably safe during pregnancy, though formal guidelines do not specifically address its use and long-term safety data remain limited.

Current State of Evidence

The available evidence on melatonin safety in pregnancy comes primarily from research studies rather than formal clinical guidelines, as no major guideline explicitly addresses melatonin use during pregnancy. The most relevant data shows:

• Human clinical trials using exogenous melatonin during pregnancy for various clinical conditions have not suggested major safety concerns or adverse events 1
• A scoping review of human studies found that approximately 4% of pregnant populations use melatonin, and contrary to animal study concerns, evidence from clinical studies suggests melatonin use during pregnancy is probably safe in humans 1
• Melatonin naturally crosses the placenta and enters fetal circulation, providing photoperiodic information to the fetus and influencing circadian rhythm development 2, 3

Physiological Context

Understanding melatonin's natural role in pregnancy helps contextualize safety considerations:

• Maternal melatonin levels naturally increase incrementally toward the end of pregnancy, and this endogenous melatonin freely crosses the placenta without being altered 3
• Melatonin receptors are widespread in the human fetus and occur in both central and peripheral tissues from early in fetal development 2
• Melatonin functions as a circadian rhythm modulator, endocrine modulator, immunomodulator, and antioxidant during pregnancy, and appears essential for successful pregnancy 3

Potential Benefits vs. Theoretical Concerns

Emerging evidence suggests melatonin may actually protect against pregnancy complications:

• Experimental supplementation with melatonin has been shown to reduce the frequency or severity of stillbirth, recurrent fetal loss, preeclampsia, fetal growth retardation, premature delivery, and fetal teratology in conditions where elevated oxidative stress plays a role 4
• Melatonin protects the uteroplacental unit against oxidative stress and may improve pregnancy outcomes generally 4

However, older theoretical concerns exist:

• One 1998 review suggested melatonin ingestion by pregnant women may be inadvisable due to widespread fetal melatonin receptors and potential unknown effects on fetal development 2
• A 1997 safety review noted potential deleterious effects could include influence on the circadian status of the fetus and neonate when taken during pregnancy, though this was based on theoretical concerns rather than documented human harm 5

Critical Evidence Gap

The most significant limitation is the absence of randomized controlled trials specifically examining melatonin for sleep disorders during pregnancy:

• No studies included in the 2022 scoping review used insomnia as a primary outcome measure during pregnancy 1
• There are no published long-term safety data (beyond 6 months) for melatonin use during pregnancy 5
• Most human data comes from studies using melatonin for other clinical conditions (not sleep), which have shown reassuring safety profiles 1

Practical Clinical Approach

If considering melatonin during pregnancy, apply these principles:

• Start with the lowest effective dose (1-3 mg), as lower doses may be more effective than higher doses due to receptor saturation concerns 6
• Administer 1.5-2 hours before desired bedtime for optimal circadian effect 6
• Choose United States Pharmacopeial Convention Verified formulations for reliable dosing and purity, as melatonin is regulated as a dietary supplement with variable quality 6, 7
• Consider non-pharmacological sleep interventions first, particularly in early pregnancy when organogenesis occurs 7

Important Caveats

• Use caution in pregnant patients taking warfarin due to potential interactions 7
• Monitor for impaired glucose tolerance, as melatonin has been associated with this in healthy individuals after acute administration 7
• Avoid use if there is personal or family history of psychiatric disorder, as melatonin has been associated with increased depressive symptoms in some individuals 7
• The contrast between animal studies (which raised concerns) and human studies (which have been reassuring) highlights that animal data may not translate directly to human pregnancy 1

Comparison to Other Medications in Pregnancy

For context, guidelines do address other medications during pregnancy with varying levels of restriction:

• ACE inhibitors and ARBs are contraindicated during pregnancy due to documented fetal harm 8
• Statins should generally be avoided but can be considered in high-risk cases through shared decision-making 8
• ADHD stimulant medications show very low magnitude of documented risks, and consensus supports not stopping them if required for daily functioning 8

Melatonin's safety profile in available human studies appears more favorable than these medications, though the evidence base is less robust.