Sleep disruption during pregnancy: How does it influence serum cytokines?

Abstract

Women report their sleep to be disrupted during pregnancy. Sleep deprivation has been linked to elevations in pro-inflammatory cytokine levels. No information currently addresses the sleep–immune relationship during pregnancy. This study explores the relationship between subjectively reported sleep variables and circulating serum cytokine levels.

Pregnant women (n = 35; mean age = 31.0 ± 3.7 years) seen once a trimester completed sleep questionnaires, gave blood and recorded their sleep on a sleep diary at home for 2 weeks. Nonpregnant women (n = 43; mean age = 28.2 ± 5.2 years) underwent the same protocol once. Subjective sleep variables were compared to serum cytokine levels for IL-4, -6, -10 and TNF-α as well as C-reactive protein (CRP) determined by ELISA. Nonparametric analyses and linear regression were performed to explore relationships between the sleep and immune variables.

Pregnant women subjectively reported their sleep to be worse than in the nonpregnant group. Serum cytokine levels differed between the two groups and varied by trimester. As anticipated, IL-10 was significantly higher in all trimesters; however CRP, an indicator of systemic inflammation, was higher in all trimesters compared to the nonpregnant sample. Subjectively reported sleep disruption was associated with increases in TNF-α in the pregnant sample and CRP in the nonpregnant sample.

These data confirm that disrupted sleep experienced during pregnancy, as well as during the nonpregnant state, is related to increases in inflammatory markers. Future exploration of these relationships should include functional assessments of immunity as well as polysomnographically recorded sleep.

Introduction

Current research documents the immunological consequences of illness, stress and psychopathology during gestation, but little is known regarding the effects of chronic sleep loss/disruption during pregnancy on maternal health, fetal health or pregnancy outcomes. Sleep changes throughout normal pregnancy (Lee et al., 2000) have been described, and a few studies have assessed the relationship between sleep abnormalities and pregnancy complications such as preeclampsia (Edwards et al., 2000, Ekholm et al., 1992) or labor duration and delivery type (Lee and Gay, 2004). To date, there are no studies of possible associations between sleep disturbance, immune alterations and pregnancy outcomes.

Studies of nonpregnant individuals (primarily men) suggest that elevations in pro-inflammatory cytokines, e.g. IL-6, and C-reactive protein (CRP) may be a consequence of insufficient sleep (Irwin, 2002, Meier-Ewert et al., 2004) and that sufficient sleep may be necessary to mount an effective response to an antigenic challenge (Lange et al., 2003, Spiegel et al., 2002, Born et al., 1997, Irwin et al., 2003). Studies of polysomnographically (PSG) recorded sleep or subjectively reported sleep in the home environment support these earlier findings (Cakirbay et al., 2004, Grossi et al., 2003, Savard et al., 1999).

Sleep is distinctly altered in the pregnant woman (Hedman et al., 2002, Shinkoda et al., 1999). Sleep quality and quantity changes by trimester, with the most sleep disruption occurring in the 3rd trimester (Hedman et al., 2002). The most common sleep-related complaints are multiple awakenings and the inability to fall back asleep in a reasonable time frame. Furthermore, several clinical studies have found that unrefreshing sleep and fatigue is increased in late pregnancy (Izci et al., 2005). No studies have evaluated how sleep may alter immune parameters during pregnancy.

Immunological changes take place during pregnancy (Piccinni et al., 2000, Saito et al., 1999). However, whether a dominance of anti-inflammatory cytokines (IL-4 and IL-10) and/or a reduction of pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) is required for a successful pregnancy remains debatable (Silver et al., 2004). Pro-inflammatory cytokines probably play a facilitating or positive role in early pregnancy events and at the onset of labor (Silver et al., 2004), but elevated pro-inflammatory cytokines as well as increased CRP levels and diminished anti-inflammatory cytokines have been associated with pregnancy complications such as spontaneous abortion (Clark et al., 1996), recurrent miscarriage (Raghupathy, 2001) and preeclampsia (Saito et al., 1999, Hennessy et al., 1999, Qiu et al., 2004). Higher levels of IL-4 and IL-10 are found in women with normal pregnancies compared to those with recurrent spontaneous abortion (RSA) (Raghupathy, 2001). Thus, from an immunological point of view, successful pregnancy is characterized by a synchronization of pro- and anti-inflammatory cytokines in a fashion consistent with at least partial immunosuppression and down-regulation of a cell-mediated immune response.

This study provides an initial exploration of the relationship between circulating levels of cytokines, including CRP, and subjective sleep parameters in healthy pregnant and nonpregnant women. Several exploratory hypotheses were considered. (1) Pregnant women would have more disturbed sleep than their nonpregnant counterparts, and their sleep would become more disrupted as pregnancy progressed. (2) Pregnant women would have higher levels of circulating anti-inflammatory cytokines than the nonpregnant women; no a priori hypotheses regarding pro-inflammatory cytokine or CRP differences between the groups were proposed. (3) More disturbed sleep would be associated with elevations in pro-inflammatory cytokines and CRP and/or decreases in anti-inflammatory cytokines.