Project Summary/Abstract
Spontaneous labor in pregnant women is more often initiated at night when melatonin levels are normally
high. Melatonin administration in vitro increases uterine contractility, but whether exogenous melatonin can
increase uterine contractions in humans is unknown. Whether melatonin administration can increase uterine
contractions in the presence of light exposure at night, which suppresses melatonin levels, is also not known.
Light exposure at night is common both at home and in hospitalized settings, and the suppressed melatonin
levels may be associated with lower uterine contractions. Therefore, we propose to test the causal relationship
between circulating melatonin concentrations and uterine contractions during the day and during the evening.
This basic physiological information is needed before obstetric interventions using melatonin can be designed.
In our recent studies in 28 late-term pregnant women, we induced significant (40%) melatonin suppression
using monochromatic short-wavelength (blue/green) light exposure at night. In the control condition, the women
were exposed to long-wavelength (red) light, which did not suppress melatonin levels. The two light exposure
conditions created a range of circulating melatonin levels in which we found a significant positive relationship
between circulating melatonin concentration and the number of objectively measured uterine contractions.
Therefore, we propose to test 3 hypotheses in controlled inpatient hospital conditions by measuring uterine
contractions in full-term pregnant women after exogenous melatonin: (i) exogenous melatonin during the day
when endogenous melatonin levels are almost undetectable will increase uterine contractions, (ii) exogenous
melatonin administration at night during light exposure-induced suppression of normally high concentrations of
endogenous melatonin will increase uterine contractions; (iii) there is a positive correlation between circulating
melatonin levels and number of uterine contractions. The first experiment is a randomized double-blind trial in
which participants will receive a 0.0 mg (placebo), 0.5 mg (physiological), or a 3.0 mg (supraphysiological) dose
of melatonin in the morning (~4 h after wake). The second experiment is a randomized double-blind trial in which
participants will be exposed to monochromatic long-wavelength and a placebo pill during the evening on Night1
and then short-wavelength light with placebo or 0.5 mg dose of melatonin during the evening on Night2. In both
experiments, participants will be =40 weeks pregnant women and uterine contractions will be monitored
continuously using tocometry. Data from both experiments will be used for testing the correlation hypothesis.
Better understanding of the physiological role of melatonin in modulating uterine contractions is important for
designing interventions that can improve obstetric care. Ramifications of these physiological findings for the
practice of obstetrics could be dramatic, including the use of pharmaceutical-grade melatonin, its antagonists, or
light exposure that alters endogenous melatonin levels to modulate contractions. These low cost and low risk
interventions could also eventually be used in facilities with limited resources to improve labor and delivery.