A Cohort Study Of Sleep Problems In Preschool Children With Combined Exposure To Bisphenol A And Anxiety During Pregnancy

Objectives To investigate the etiological association of maternal bisphenol A（BPA）exposure and pregnancy-related anxiety with sleep problems in preschool children during pregnancy.Method This study is based on the members of the Ma’anshan birth cohort,a sub-cohort of the China-Anhui Birth Cohort Study（C-ABCS）.The maternal general demographic information,environmental exposure during pregnancy,and psychological and behavioral status were collected using the Maternity Health Record Form and the Pregnancy-related Anxiety Questionnaire（PAQ）.Blood samples from pregnant women in the cohort were collected at the time of inclusion,and after centrifugation,serum was stored in a-80°C freezer.A total of 5084 pregnant women were included in this study,excluding spontaneous abortion（n = 92）,twins（n = 66）,induced labor and stillbirth（n = 55）,lost to follow-up（n = 202）,and the remaining 4669 singleton live births.From April 2014 to June 2015,a questionnaire follow-up survey was conducted among the cohort children in kindergartens in Ma’anshan City.The "Health Record Form for Preschool Children" was used to collect general demographic information and sleep problems of preschool children.From December 2012 to January 2014,the serum free BPA content of pregnant mothers was measured by solid phase extraction-isotopelabeling-high-performance liquid chromatography-tandem mass spectrometry（HPLC-MS/MS）.A total of 2452 pregnant women were tested for serum BPA,and the serum BPA values of 1783 pregnant women were obtained.The follow-up results of 38 cases without preschool children’s sleep problems and the data of 28 cases without pregnancy-related anxiety were excluded.Finally,a total of 1717 mother-child pairs were included in this study.SPSS 23.0 was used for analysis,and χ2 test and t test were used to analyze the demographic differences of BPA exposure during pregnancy;percentile regression model was used to determine the cutoff value of BPA exposure,and univariate and multivariate Logistic regression The effect of pregnancy-related anxiety on sleep problems in preschool children independently;according to the BPA exposure during pregnancy and pregnancy-related anxiety,the subgroups were classified.After controlling for other confounding factors,the combined exposure of the two in different pregnancy periods and different genders of children and preschool age were analyzed.Etiological associations of sleep problems in children.Results The results of the univariate exposure analysis showed that BPA exposure during pregnancy increased the risk of occasional sleep-related problems in preschool children（OR = 1.35,95% CI: 1.02-1.80）;The results showed that high maternal BPA exposure during pregnancy increased the risk of preschool sleep problems in girls,including occasional sleep problems and frequent insomnia.The OR（95%CI）values for problems were 1.66（1.10-2.50）and 1.97（1.22-3.17）,respectively;whereas the association between maternal BPA exposure during pregnancy and preschool sleep problems was not statistically significant in boys（P > 0.05）.Anxiety in early pregnancy increased the risk of sleep problems in preschoolers,with OR（95% CI）values of 1.41（1.07-1.87）and 1.71（126-2.35）for occasional and frequent sleep problems,respectively;stratifiedanalysis by gender showed that anxiety in early pregnancy increased preschool sleep problems in girls（OR = 1.59,95% CI: 1.07-2.37;OR = 1.86,95% CI: 1.19-2.92）and also increased the risk of frequent sleep problems（OR = 1.614,95% CI: 1.04-2.50）in boys.Pregnancy anxiety in mid-to late-pregnancy was not associated with sleep problems in preschool children,and after gender stratification,the analysis showed no statistical significance in either boys or girls（P > 0.05）.Combined exposure analysis revealed that combined exposure to high BPA during pregnancy and early pregnancy anxiety increased the risk of sleep problems in preschoolers（OR = 2.52,95% CI: 1.43-4.42;OR = 3.37,95% CI: 1.84-6.15）;after analysis stratified by gender,the results showed that combined exposure to high BPA during pregnancy and early pregnancy anxiety increased the risk of sleep problems in girls（OR = 4.52,95% CI: 1.80-11.34;OR = 7.98,95% CI: 3.05-20.89）;whereas in boys only the combined exposure to low BPA in pregnancy and early gestational anxiety was shown to be associated with frequent sleep problems in preschool boys（OR = 2.26,95% CI: 1.07-4.77）association and did not show the expected combined exposure effect.In the analysis of combined exposure to BPA in pregnancy and anxiety in mid-and late pregnancy,combined exposure to high BPA in pregnancy and anxiety in mid-and late pregnancy increased the risk of frequent sleep problems in preschool children（OR = 2.11,95% CI: 1.06-4.23）;after stratifying the analysis by gender,combined exposure to high BPA in pregnancy and anxiety in mid-and late pregnancy was associated with frequent sleep problems in girls at preschool age only in girls.Frequent sleep problems（OR = 3.44,95% CI: 1.30-9.13）were associated.Conclusion Both bisphenol A and anxiety exposure during pregnancy are risk factors for preschool children’s sleep problems,which are mainly manifested as the harm to girls’ preschool sleep problems;high bisphenol A during pregnancy and combined exposure to anxietyin early pregnancy and anxiety in the middle and late stages of pregnancy are both It will increase the risk of school-age sleep problems in girls,but it does not show joint exposure effects in boys.Also,the effect of early gestational anxiety on preschool-age sleep problems was higher than that of mid-and late-gestational anxiety.