The Correlations Between Neonatal Serum Bilirubin Levels And Childhood Hypertension And Obesity

Objective:Previous studies confirmed that bilirubin was a powerful endogenous anti-inflammatory antioxidant.Negative correlations between serum bilirubin levels and chronic metabolic diseases,such as hypertension and obesity were observed in adults.At the same time,during neonatal period,elevated serum bilirubin level is a common clinical phenomenon,with the highest physiological bilirubin concentrations in the lifetime.But so far,there is no study on the associations between neonatal serum bilirubin levels and long-term chronic metabolic diseases,such as obesity and hypertension.Methods:The data was obtained from the Collaborative Perinatal Project,which was a large multi-center birth cohort study conducted from 1959 to 1965in the United States.The highest levels of neonatal TSB were used as the exposure variable,and the blood pressure and obesity at 7 years old were used as the outcome variables.According to the inclusion and exclusion criteria,a total of 32,175 infants(including 27,192 full term infants and 4,983 premature infants)were included in the study using blood pressure as the outcome,and 33,508infants(including 28,489 full term infants and 5,019 preterm infants)were included in,while by using obesity as the outcome.All the statistical analysis was performed in the SAS 9.2 software.First,the linear coefficients between neonatal serum TSB levels and blood pressure and BMI at 7 years old were calculated by the linear regression model.In the next step,the full term infants were categorized into 5 groups according to TSB<3 mg/dl,3 mg/dl?TSB<6 mg/dl,6 mg/dl?TSB<9 mg/dl,9 mg/dl?TSB<13 mg/dl and TSB?13 mg/dl,and the preterm infants were also categorized into 5 groups,according to TSB<3 mg/dl,3mg/dl?TSB<6 mg/dl,6 mg/dl?TSB<9 mg/dl,9 mg/dl?TSB<12 mg/dl and TSB?12 mg/dl.The Cochran-Mantel-Haenszel Chi-square test was used to compare the differences in maternal and infantile demographic characteristics between the five groups.Next,using the infants with TSB<3 mg/dl as the reference,a multivariable logistic regression model was used to calculate the ORs by controlling the potential confounding factors.A generalized estimation equation model was used to correct for the influences of the similar genetic factors and family environmental factors between the siblings.In addition,using CB and UCB as exposure variables,the same analyses were performed to explore the correlations between different types of serum bilirubin and hypertension/obesity at age of 7 years.Results:(1)The linear regression model demonstrated that there were no significant correlation between neonatal serum bilirubin levels and BMI/blood pressure at 7 years old in full term infants.The multivariate logistical regression model showed that,comparing with the full term infants with TSB<3 mg/dl,the full term infants with 3 mg/dl?TSB<6 mg/dl,6 mg/dl?TSB<9 mg/dl,9 mg/d?TSB<13 mg/dl had a lower risk of obesity at 7 years old,with the adjusted OR values of 0.91(95%CI:0.81,1.02),0.88(95%CI:0.78,0.99)and 0.83(95%CI:0.71,0.98),respectively.In addition,comparing with the full term infants with UCB<3 mg/dl,the risk of obesity at 7 years old was also lower in the full term infants with 3 mg/dl?UCB<6 mg/dl(adjusted OR 0.91;95%CI:0.81,1.02),6 mg/dl?UCB<9 mg/dl(adjusted OR 0.88;95%CI:0.78,0.99),9 mg/dl?UCB<13 mg/dl(adjusted OR0.83;95%CI:0.71,0.98),respectively.Furthermore,in full term infants with the serum bilirubin levels within 13 mg/dl,the risk of childhood obesity was decreased,and without the increased risk of neurodevelopment retardation.However,no significant associations were observed between neonatal serum bilirubin levels and hypertension at the age of 7 years in full term infants.(2)In premature infants,the linear regression model showed that,for increasing each 3 ml/dl in TSB and UCB,the systolic blood pressure at 7 years old elevated 0.50(95%CI:0.27,0.73)mmHg and 0.45(95%CI:0.13,0.77)mmHg,respectively.At the same time,it was also found that,for increasing each1 mg/dl in TSB,the BMI at the age of 7 years increased by 0.03(95%CI:0.02,0.04)kg/m~2.In the multivariate Logistical regression model,compared to the preterm infants with TSB<3 ml/dl,the preterm infants with 3 mg/dl?TSB<6 mg/dl,6mg/dl?TSB<9 mg/dl,9 mg/dl?TSB<12 mg/dl and TSB?12 mg/dl had an increased risk of hypertension and obesity in childhood:the adjusted ORs for hypertension at 7 years old were 1.44(95%CI:1.00,2.06),1.26(95%CI:0.88,1.79),1.68(95%CI:1.16,2.44)and 1.56(95%CI:1.07,2.26),and the adjusted ORs for obesity at 7 years old were 1.18(95%CI:0.87,1.59),1.25(95%CI:0.93,1.67),1.52(95%CI:1.11,2.09)and 1.67(95%CI:1.22,2.07),respectively.Moreover,there were similar positive correlations between UCB levels and hypertension/obesity at 7 years old.Compared with the preterm infants with UCB<3 mg/dl,the preterm infants had increased risks for hypertension in infants with3 mg/dl?UCB<6 mg/dl(adjusted OR 1.82;95%CI:1.06,3.15),6 mg/dl?UCB<9 mg/dl(adjusted OR 1.71;95%CI:1.04,2.80),9 mg/dl?UCB<12mg/dl(adjusted OR 1.61;95%CI:0.96,2.69)and UCB?12 mg/dl(adjusted OR1.79;95%CI:1.08,2.98),respectively.At the same time,the adjusted ORs for obesity at 7 years old were 1.07(95%CI:0.70,1.63),1.29(95%CI:0.86,1.93),1.54(95%CI:0.99,2.38)and 1.65(95%CI:1.08,2.51)in each group,respectively.Using the preterm infants with CB<1 mg/dl as the reference,the adjusted ORs for obesity at 7 years old in the preterm infants with 1 mg/dl?CB<2 mg/dl and CB?2 mg/dl were 1.22(95%CI:0.89,1.67)and 1.46(95%CI:0.88,1.41),respectively,while the adjusted ORs for hypertension at the age of 7years were 1.08(95%CI:0.76,1.55)and 0.99(95%CI:0.54,1.83),respectively.Conclusion:The correlations between neonatal serum bilirubin levels and childhood hypertension/obesity were different in full term infants and preterm infants.In full term infants,the negative correlations between neonatal TSB/UCB levels and childhood obesity were observed,while the positive correlations were existed between neonatal TSB/UCB levels and childhood obesity and hypertension in preterm infants.