Association Of Maternal Exposures To Compound Hot Extremes During Pregnancy With Preterm Birth And The Potential Biological Mechanisms In Guangzhou

BackgroundPreterm birth(PTB)is the main cause of neonatal death,and the second leading cause of child death.Global warming may increase the frequency of compound hot extremes(CHEs).During pregnancy,the physiological changes of pregnant women increase the heat production and decrease the heat dissipation capacity of pregnant women,which may make them more susceptible to heat stress and easily lead to adverse pregnancy outcomes.However,there is still a lack of study assessing the associations between CHEs and PTB,and the underlying biological mechanisms remain unclear.In addition,with the improvement of human life quality,there are more and more pregnant women with gestational diabetes mellitus(GDM)and gain too much weight during pregnancy due to over-nutrition.And whether GDM and excessive weight gain during pregnancy can modify the relationship between prenatal CHEs exposure and PTB is still unclear.The biological mechanism of PTB caused by high-temperature exposure during pregnancy has not been fully understood.Recent studies suggest that inflammatory reaction,endothelial function changes,and oxidative stress may be the potential mechanisms of PTB caused by high temperature,but there is still no direct epidemiological evidence.ObjectiveThe prospective birth cohort study was used to evaluate the relationship between CHEs exposure during pregnancy and PTB,and the modification effects of GDM and weight gain during pregnancy on the relationship between prenatal CHEs exposure and PTB.The nested casecontrol study was used to explore the role of inflammatory reaction,oxidative stress,and endothelial function changes in the relationship between CHEs exposure and PTB.MethodsAll participants were selected from the Prenatal Environment and Offspring Health(PEOH)cohort conducted in Guangzhou.The participants were recruited in the largest hospital in Panyu district,Guangzhou from January 2016 to December 2017.In this study,2449 participants who gave birth from May to October were selected,among whom,311 premature pregnant women and control groups were collected blood samples at the time of delivery.Hot day/night was identified as a day in which the daily Tmax/Tmin was higher than its 90th centile in the warm seasons(2016-2017).CHE was defined as having both a hot night and a hot day.The meteorological station’s data were obtained from the China Meteorological Data Sharing Service System.The Anusplin National University Splines(Anusplin)was used to assess the maximum temperature(TMax),minimum temperature(TMin),and relative humidity(RH)of the participant residence.The enzyme-linked immunosorbent assay(ELISA)method was used to measure the C reactive protein(CRP),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),endothelin-1(ET1),and malondialdehyde(MDA)levels in maternal blood.A distributed lag nonlinear model(DLNM)was used to investigate the associations of exposure to hot day,hot night,and CHE during pregnancy with PTB and CRP,IL-6,ET-1,TNF-α,and MDA,and a logistic regression model was used to investigate the associations of CRP,IL-6,ET-1,TNF-α and MDA with PTB.ResultsThe incidence rate of PTB was 6.2%in all selected participants.Compared with the non-hot day,the RRs(95%CIs)of CHE in lag 3,7,and 14 days on PTB were 1.43(1.12-1.84),1.24(1.08-1.43),and 1.17(1.051.30),and the cumulative effects%difference(95%CI)of CHE in lag 14 days on maternal serum CRP,IL-6,TNF-α,ET-1,and MDA were 0.33%(-0.45%,1.12%),0.48%(-0.10%,1.07%),0.15%(-0.61%,0.90%),0.59%(0.11%,1.07%)and 0.57%(0.09%,1.05%)respectively.Compared with the Q1(lowest quartile)for CRP,IL-6,TNF-α,ET-1 and MDA,the RRs(95%CIs)of PTB in the Q4(highest quartile)were 1.27(95%CI:0.50,3.22),2.06(95%CI:0.70,6.08),1.29(95%CI:0.51,3.25),1.51(95%CI:0.61,-3.72),and 2.07(95%CI:0.81,-5.27),respectively.Compared with non-GDM and weight gain during pregnancy≤P75 kg pregnant women,the CHE exposure has a greater impact on pregnant women with GDM and weight gain during pregnancy>P75 kg pregnant women compared with non-hot days in lag 3 and 14day.ConclusionMaternal exposure to CHEs during pregnancy is associated with an increased risk of PTB in different lag days,and it will have a greater impact on GDM and pregnant women who gain more weight during pregnancy.Endothelial dysfunction,and oxidative stress in pregnant women may be an important biological mechanism of PTB caused by CHEs,but further research is needed to confirm it.