睡眠在怀孕早期高温暴露与早产风险关联中的中介效应

Mediating role of sleep in association between maternal heat exposure during early pregnancy and risk of preterm birth

[背景]早产相关并发症是导致新生儿及5岁以下儿童死亡的首要原因。既往研究发现高温暴露会影响孕妇的睡眠状况,也会增加早产的发生风险,但尚不清楚睡眠在高温暴露与早产风险中的作用。[目的]评估怀孕早期高温暴露与早产的关联,并探讨睡眠在高温与早产关联中的中介作用。[方法]本研究从2017年至今在广州市番禺区何贤纪念医院建立出生队列,孕妇于怀孕早期(8~13孕周)到医院进行产检时,签订知情同意书后被纳入本研究并进行初次问卷调查,然后进行随访直至分娩。本研究纳入分析的孕妇共有3268例。研究采用问卷收集孕妇的人口学特征、生活行为习惯和睡眠信息等。同时收集广州市气象监测站点气象数据并计算每位孕妇调查前4周的平均温度暴露水平,再分别以所有孕妇暴露平均温度的第75、80、85、90和95百分位数(P_(75)、P_(80)、P_(85)、P_(90)和P_(95))作为阈值定义高温暴露。采用logistic回归分别评估不同定义下的高温暴露对早产、睡眠状况(睡眠时长、入睡时间、觉醒时间)的影响,并进一步分析睡眠在高温暴露与早产关系中的中介效应。[结果]纳入的3268例研究对象中,早产例数为165,早产发生率为5.0%。调整协变量后,以P_(90)和P_(95)定义的高温暴露增加了早产风险,OR(95%CI)分别为1.66(1.04~2.57)和1.90(1.03~3.33)(P<0.05)。调整协变量后,存在高温暴露时:在P_(75)、P_(80)、P_(85)、P_(90)和P_(95)定义的高温暴露下,发生睡眠时长减少(<9 h vs.≥9 h,对照组:≥9 h)的OR(95%CI)分别为1.51(1.25~1.83)、1.44(1.17~1.77)、1.35(1.08~1.70)、1.43(1.09~1.87)和1.45(1.00~2.13);在P_(75)、P_(80)定义下,觉醒时间提前(<8:00 vs.≥8:00,对照组:<8:00)的OR(95%CI)分别为0.77(0.63~0.93)、0.76(0.61~0.93);未观察到高温暴露与入睡时间存在关联。中介效应分析发现:在P_(90)定义的高温暴露下,观察到睡眠时长具有统计学意义的中介效应,中介比例为6.07%(95%CI:0.17%~25.00%)(P<0.05);未观察到入睡时间、觉醒时间的中介效应。[结论]孕早期高温暴露可能会通过减少睡眠时长从而导致早产的风险。

[Background]Preterm birth-related complications are the leading cause of death in newborns and children under the age of 5 years.Maternal heat exposure has been associated with both sleep status during pregnancy and the increased risk of preterm birth.However,whether sleep status could mediate the association between heat exposure and preterm birth remains unclear.[Objective]To evaluate the association between maternal heat exposure in early pregnancy and preterm birth,and to further explore potential mediation effect of sleep status on the association between heat exposure and preterm birth.[Methods]A birth cohort was established in Guangzhou Panyu Maternal Child Health Hospital(Guangzhou Panyu District He Xian Memorial Hospital)from 2017 until now.Pregnant women(with gestational age between 8 and 13 weeks)were included in this study when they presented to the hospital for their first prenatal care visit and signed an informed consent.Then they were followed up until delivery.A total of 3268 pregnant women were included for the final analysis.Questionnaires were distributed to collect the demographic characteristics,lifestyles,and sleep status of pregnant women.Daily meteorological data during the study period were collected from meteorological monitoring stations in Guangzhou and the average ambient mean temperature of four weeks before the survey was calculated and assigned for each pregnancy.The 75th,80th,85th,90th,and 95th percentiles(P_(75),P_(80),P_(85),P_(90),and P_(95))of the average ambient temperature of all pregnant women were used as the thresholds to define heat exposure.Logistic regression was used to evaluate the effects of heat exposure in different definitions on preterm birth and sleep status(sleep duration,night sleep timing,and wake up timing).The mediation effects of sleep status on the relationship between heat exposure and preterm birth were also analyzed.[Results]Among all the included participants,165 newborns were preterm births with an incidence rate of 5.0%.Heat exposures with thresholds of P_(90)and P_(95)increased the risk of preterm birth,with ORs(95%CIs)of 1.66(1.04-2.57)and 1.90(1.03-3.33),respectively(P<0.05).Heat exposures with thresholds of P_(75),P_(80),P_(85),P_(90),and P_(95)decreased the sleep duration(<9 h vs.≥9 h,control group:≥9 h),and the ORs(95%CIs)were 1.51(1.25-1.83),1.44(1.17-1.77),1.35(1.08-1.70),1.43(1.09-1.87),and 1.45(1.00-2.13),respectively.Heat exposures with P_(75)and P_(80)thresholds resulted in earlier wake up timing(<8:00 vs.≥8:00,control group:<8:00),with ORs(95%CIs)of 0.77(0.63-0.93)and 0.76(0.61-0.93),respectively.No significant association was observed between heat exposure and night sleep timing.The mediation analyses showed that under heat exposure with P_(90)threshold,a statistically significant mediation effect was observed for sleep duration,and the proportion mediated was 6.07%(95%CI:0.17%-25.00%)(P<0.05).No significant mediation effect was observed for night sleep timing and wake up timing.[Conclusion]An elevated risk of preterm birth after heat exposure in early pregnancy may be partly mediated through reducing sleep duration.