The Association Between Maternal Blood Pressure And Child Neurodevelopment And The Mediating Effect Of Cord Glucocorticoid

Pregnancy is a special physiological period for women,and the circulatory system of pregnant women undergoes a series of adaptive changes to ensure adequate oxygen supply for mother and fetus.Blood pressure changes during pregnancy and is affected by many factors,such as cardiac output,circulating blood volume,peripheral vascular resistance,maternal age and weight.Studies have found that,a rise in maternal blood pressure may increase maternal mortality,affect fetal growth and development,as well as increase the risk of disease of offspring.However,no epidemiological study has been conducted to investigate the relationship between blood pressure during pregnancy and neurodevelopment in offspring.Therefore,based on a cohort study in China,our study aimed to explore the association of blood pressure during pregnancy with child neurodevelopment and the mediating effects of cord glucocorticoid wherein.Part 1: Association between maternal blood pressure and child neurodevelopmentObjective: We aimed to explore the association of maternal blood pressure with child neurodevelopment.Methods: From October 2013 to April 2016,1008 mother-child pairs were recruited from a prospective birth cohort in Wuhan.The basic sociodemographic data of pregnant women were collected by face-to-face questionnaires.The information of maternal blood pressure,mother’s health status,delivery mode,gestational age,birth weight and gender were obtained from the medical records of hospitals.At the age of 2,child neurodevelopment was assessed by the Chinese revision of Bayley scales of infant and toddler development(BSID-CR),with obtaining the Mental and Psychomotor Development Index(MDI and PDI).The score of BSID ≤ 79 was classified as low BSID score(MDI ≤ 79,low MDI score;PDI ≤ 79,low PDI score).Linear regression model was conducted to analyze the relationship between gestational blood pressure and neurodevelopment of offspring.Logistic regression model was used to estimate odds ratio(OR)between blood pressure level during pregnancy and low BSID score of offspring.Results: 1.Blood pressure fluctuated slightly during pregnancy and was low during the second trimester.1008 pregnant women involves 9135 blood pressure measurements in our study.The mean systolic and diastolic blood pressure was 112.3 ± 9.4 mmHg and 69.8 ± 8.6 mmHg during the first trimester;110.8 ± 17.3 mmHg and 68.3 ± 6.5 mmHg during the second trimester;112.5 ± 6.6 mmHg and 68.9 ± 5.7 mmHg during the third trimester.2.The mean scores of MDI and PDI were 102.8 ± 22.6 and 104.0 ± 19.2,respectively3.General linear regression analysis found that maternal blood pressure was negatively correlated with child neurodevelopmental.After adjusting for confounding covariates,linear regression analysis showed that,a 5 mmHg increase in the first-trimester diastolic blood pressure was associated with 1.04 scores decrease in PDI(95%CI:-1.79,-0.29);a similar increase in the second-trimester systolic blood pressure was associated with 1.20 scores decrease in MDI(95%CI:-2.21,-0.19).During the third trimester,systolic blood pressure was negatively correlated with neurodevelopment of offspring(for MDI: β =-1.54,95%CI:-2.60,-0.48;for PDI: β =-1.23,95%CI:-2.14,-0.31).In addition,diastolic blood pressure was significantly associated with child neurodevelopment(MDI: β =-1.32,95%CI:-2.53,-0.10;PDI: β =-1.37,95%CI:-2.42,-0.33).4.Logistic regression analysis revealed that a rise in the third-trimester systolic blood pressure increased the risk of low MDI scores in offspring.Each 5 mmHg increase in maternal third-trimester systolic blood pressure,an odds ratio of 1.38(95%CI: 1.01,1.91)was observed for low MDI in offspring.Conclusion: Our current research shows that increased maternal blood pressure was associated with decreased child neurodevelopment.Part 2: The mediation effect of cord glucocorticoid in the association between maternal blood pressure and child neurodevelopmentObjective: Glucocorticoid has been suggested to be related with child neurodevelopment.The aim of the study was to explore the possible role of cord glucocorticoid in the association between maternal blood pressure and child neurodevelopment.Methods: 1008 mother-child pairs recruited from a prospective birth cohort in Wuhan during October 2013 and April 2016,cord blood was collected after delivery and stored.The concentrations of cortisol and cortisone were determined by LC-MS/MS.Linear regression analysis was conducted to explore the relationship among blood pressure during pregnancy,cord glucocorticoid and child neurodevelopment,and mediating analysis was performed to estimate the mediating effect of cord glucocorticoid in the association between maternal blood pressure and child neurodevelopment.Results: 1.The detection rates of cord cortisol and cortisone were both 100%.The median for cord cortisol and cortisone were 43.5 ng/mL and 87.9 ng/mL,separately.2.General linear regression analysis showed that there was a positive correlation between cord glucocorticoid and BSID score of neurodevelopment,and a negative correlation between maternal blood pressure and cord glucocorticoid.Adjusting for potential covariates,we found significant associations between cord cortisol/cortisone ratio and PDI(adjusted β = 2.95;95%CI: 0.91,4.99),as well as between maternal third-trimester blood pressure and cord cortisol/cortisone ratio(adjusted β =-0.03;95%CI:-0.06,-0.01 for both systolic blood pressure and diastolic blood pressure).3.Mediation analysis founded that cord glucocorticoid might be a potential mediator in the relationship between maternal blood pressure and child neurodevelopment.Cord cortisol/cortisone ratio explained 6.29% of the association between systolic blood pressure and PDI,(Indirect effect,IE = 0.63,95%CI: 0.06,1.36)and 6.85% between diastolic blood pressure and PDI(IE = 0.63,95%CI: 0.06,1.36).Conclusion: We found cord glucocorticoid might play a mediating role in the association between maternal blood pressure and child neurodevelopment.