Many women experience some degree of sleep disturbance during pregnancy. For a significant number of women, the sleep disruption may be so severe as to require some type of intervention.  Sleep disturbance is not only distressing but there is now evidence that sleep disturbance during pregnancy may predispose certain women to perinatal depression or anxiety.

Many women ask about the safety of using melatonin during pregnancy as a sleep aid.  

Melatonin is a hormone which is normally secreted by the pineal gland; it is involved in regulating normal sleep-wake cycles. It is also sold over the counter as a dietary supplement and is a popular natural remedy for sleep problems.  Because it is not classified as a drug or hormone, its production is not monitored by the Food and Drug Administration. 

When it comes to pregnancy, natural does not necessarily mean safer. Although melatonin is indeed “natural” and is normally produced by the body, the amount delivered by various over-the-counter preparations typically exceeds the quantities normally produced by the body. The dose used in most melatonin preparations is higher than what the body normally produces. A typical dose of melatonin (1 to 3 mg) elevates blood melatonin levels up to 20 times normal levels. 

As is the case with most supplements, we know very little about the impact high levels of melatonin may have on the developing fetus.  Animal studies have shown that exposure to very high levels of melatonin does not appear to exert any negative effects on the developing fetus; however, no studies have looked at the impact of high melatonin levels on human fetal development.  Thus, we typically advise women with sleep problems to use medications with a better characterized reproductive safety profile, such as doxylamine or benzodiazepines.  

Looking Ahead

While we don’t typically recommend using melatonin during pregnancy, there is some very interesting research going on with regard to the use of melatonin during pregnancy which may ultimately give us more information on the reproductive safety of melatonin.  

Most of this research comes from animal studies, where it has been shown that melatonin can reduce oxidative stress, acting as an antioxidant and scavenging free radicals.  Interestingly, the placenta produces melatonin and this source of melatonin is thought to be important to maintaining a normal, healthy pregnancy. In animal studies, it has been shown that supplementation with melatonin decreases the risk of pre-eclampsia, preterm birth and intrauterine growth retardation (IUGR). 

Studies of melatonin in humans with IUGR and pre-eclampsia are now in their earliest phases. Preliminary studies also suggest that melatonin supplementation may have a beneficial effect on fertilization rates and embryo quality, likely due to a reduction in oxidative damage.

Animal studies have also demonstrated the importance of melatonin in fetal development.  During pregnancy, night-time concentrations of melatonin increase steadily after 24 weeks of gestation.  Melatonin receptors are present throughout the developing fetus from the earliest stages. There is solid evidence that melatonin is neuroprotective and plays an important role in training circadian rhythms in the developing fetus; however, melatonin may have other important actions outside of the brain.

Hopefully these newer studies will soon yield more information on the reproductive safety of melatonin.

Ruta Nonacs, MD PhD

Alers NO, Jenkin G, Miller SL, Wallace EM.  Antenatal melatonin as an antioxidant in human pregnancies complicated by fetal growth restriction–a phase I pilot clinical trial: study protocol.  BMJ Open. 2013 Dec 23;3(12):e004141. 

Chaudhry SK, Susser LC.  Considerations in Treating Insomnia During Pregnancy: A Literature Review.  Psychosomatics. 2018 Jul – Aug; 59(4):341-348. 

Hobson SR, Lim R, Gardiner EE, Alers NO, Wallace EM.  Phase I pilot clinical trial of antenatal maternally administered melatonin to decrease the level of oxidative stress in human pregnancies affected by pre-eclampsia (PAMPR): study protocol.  BMJ Open. 2013 Sep 20;3(9):e003788. 

Hsu CN, Huang LT, Tain YL.  Perinatal Use of Melatonin for Offspring Health: Focus on Cardiovascular andNeurological Diseases.  Int J Mol Sci. 2019 Nov 13;20(22). Free Article

McCarthy R, Jungheim ES, Fay JC, Bates K, Herzog ED, England SK.

Riding the Rhythm of Melatonin Through Pregnancy to Deliver on Time.  Front Endocrinol (Lausanne). 2019 Sep 13;10:616. Free Article 

Seko LM, Moroni RM, Leitao VM, Teixeira DM, Nastri CO, Martins WP.  Melatonin supplementation during controlled ovarian stimulation for women undergoing assisted reproductive technology: systematic review and meta-analysis of randomized controlled trials.  Fertil Steril. 2014 Jan;101(1):154-161.

Voiculescu S, Zygouropoulos N, Zahiu C, Zagrean A.  Role of melatonin in embryo fetal development.  J Med Life. 2014 Oct-Dec;7(4):488-492. 

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