Social disadvantage is associated with impaired increase in salivary diurnal melatonin amplitude throughout pregnancy

Abstract

Study objectives: Melatonin regulates daily rhythms and is important for maintaining a healthy pregnancy. Certain socioeconomic factors may affect melatonin release. This study evaluates whether the increase in melatonin with advancing gestation is associated with social disadvantage.

Methods: Data were prospectively collected from a socioeconomically diverse cohort of participants with singleton pregnancies (n = 921) at a Midwest academic center. Participants self-collected saliva every four hours over a 24-hour period once per trimester. Diurnal melatonin concentration was measured, and for each trimester, the maximum and mean diurnal melatonin concentration values were obtained. Cosinor-fitting was performed to obtain peak, mesor, and amplitude values, and melatonin profiles were also analyzed by calculating area under the curve. Participants were dichotomized by high and low social disadvantage score (SDS), and diurnal melatonin parameters were compared between participants with high and low SDS.

Results: Mean diurnal melatonin concentration increased at an average rate of 0.19 pg/mL/week, and amplitude increased by 0.04 pg/mL/week. Participants with high SDS had significantly lower diurnal melatonin concentration amplitudes, means, mesors, and peaks than those with low SDS. Participants with high SDS had a 2.19 [95%CI = 1.94, 2.47] adjusted relative risk for low diurnal amplitude melatonin and had a smaller increase in diurnal melatonin amplitude over weeks of pregnancy than those with low SDS (-0.04 vs. 0.11 pg/mL/week, p<.001).

Conclusions: Average salivary diurnal melatonin concentration increases across pregnancy, but the degree of increase varies among pregnant participants and is associated with social disadvantage.

Keywords: melatonin; pregnancy; social adversity; women’s health.

Figure 1

Schematic of the study design. Participants were asked to collect saliva at 4-hour intervals over a 24-hour period (up to 7 samples) outside the clinic once each trimester. An enzyme-linked immunosorbent assay was used to measure salivary diurnal melatonin concentration, and values were plotted against the times they were collected.

Figure 2

Raw and cosinor-fitted melatonin profiles. (A) Diurnal melatonin profiles from a representative pregnant woman collected over each trimester. (B) The corresponding Cosinor-fitted data, with the maximum, defined as the highest raw melatonin concentration, peak as the maximum of the Cosinor fit, Mesor as the mean of the Cosinor, and amplitude as the difference between the peak and the Mesor. Correlations between (C) peak and maximum values, and (D) mean and mesor values. PCC = Pearson’s correlation coefficient.

Figure 3

Participant enrollment flowchart.

Figure 4

Participants with high melatonin amplitude in early pregnancy show increased amplitude by the end of pregnancy. (A, B) Example raw diurnal melatonin profiles showing (A) a participant with strong melatonin rhythms and (B) a participant with weak melatonin rhythms in all three trimesters. (C) Diurnal melatonin amplitude for all participants over the course of pregnancy. Dashed lines represent the generalized linear model for amplitude over the course of pregnancy after dividing participants into quartiles according to their mean diurnal melatonin amplitude over all timepoints.

Figure 5

High SDS is associated with low diurnal melatonin maximum and amplitude. Daily melatonin (A) maximum, (B) mean, (C) amplitude, and (D) mesor plotted for all participants over the course of pregnancy. Dashed lines represent the generalized linear model for each statistic after dichotomizing individuals into high and low SDS groups.