Association Between Early Life Adversity And Allostatic Load In Girls With Precocious Puberty

ObjectivesThe study aims to explore the relationship between early life adversity（ELA）and allostatic load（AL）in girls with precocious puberty,so as to provide theoretical basis for early identification of girls at risk of ELA-related disease and timely intervention to improve the lifelong health outcomes of girls with precocious puberty.MethodsBased on the field established in 2019 in the Department of Pediatric Endocrinology of the Second Affiliated Hospital of Anhui Medical University and the Department of Child Health Care of Anhui Provincial Children’s Hospital,a total of 213 girls with precocious puberty with an average age of（8.21±1.07）years were recruited in this study with informed consent.Pediatric endocrinologists used a combination of inspection and palpation to objectively assess the Tanner stage of breast and pubic hair development,measured blood pressure,height and weight at the same time.The demographic and multiple ELA experiences information was collected using self-administered parent questionnaires and child questionnaire interviews.This study assessed 8 types of ELA including parental fight,harsh physical punishment,peer bullying,neglect,low parental education,low family income,parental divorce and lack of parental warmth.Hair samples were collected to detect hair cortisol concentration（HCC）,and blood samples were collected to detect AL-related physiological indicators.We constructed an AL score based on thirteen biomarkers representing four regulatory systems:immune system（high sensitivity C-reactive protein）;cardiovascular system（systolic blood pressure,diastolic blood pressure and pulse）;metabolic system（BMI,Hb A1c,fasting plasma glucose,total cholesterol,triglycerides,high density lipoprotein and low density lipoprotein）and renal system（creatinine and blood urea nitrogen）.We used multivariate linear regression models to estimate associations between ELA and AL scores.HCC was divided into Q₁group（HCC<2.40 pg/mg）,Q₂group（HCC:2.40-5.61 pg/mg）,Q₃group（HCC:5.61-9.30 pg/mg）and Q4 group（HCC≥9.30 pg/mg）according to quartiles,with Q₁group as the reference,the association between HCC and AL total was analyzed by multiple linear regression.The AL total was dichotomized into a low group（AL total score<3）and a high group（AL total score≥3）,and the binary logistic regression model was used to analyze the association of HCC with high AL total.The dose-response relationship between HCC and AL was then analyzed using restricted cubic spline models.ResultsA total of 213 girls with precocious puberty were included in the study,the mean age was（8.21±1.07）years.The incidence of ELA ranged from 5.6%（neglect）to 25.4%（peer bullying）.64.8%of girls（138 girls）experienced at least one form of ELA and nearly one in third（70,32.90%）girls reported two or more ELA.The AL total ranged from 0 to 13 with a mean of（2.99±1.72）,and 52.2%of girls in the high group AL（AL total score≥3）.After controlling for covariates,multiple linear regression analysis showed that parental divorce was significantly positively associated with cardiovascular AL score（β=0.65,95%CI:0.13,1.17,P=0.014）.Compared with girls with highly educated parents,girls who reported low parental education had a significantly higher AL total（β=1.02,95%CI:0.21,1.83,P=0.014）.In contrast,peer bullying was significantly negatively associated with AL total（β=-0.89,95%CI:-1.64,-0.14,P=0.020）.For cumulative ELA,compared with no ELA exposure,the total AL and metabolic AL increased by 0.75 and0.67 in girls who experienced one ELA,respectively（β=0.75,95%CI:0.04,1.47,P=0.040;β=0.67,95%CI:0.16,1.18,P=0.011,respectively）.No significant differences were found in the AL scores between participants not exposed to ELA and those exposed to two or more ELA（all P values>0.05）.The results of multiple linear regression analysis of the associations between HCC variables and AL scores showed that there was no significant association between HCC and AL in all models（all P values>0.05）.Binary logistic regression analysis of the association between HCC and high AL total showed that after adequate adjustment for covariates,the girls in the Q₂（HCC:2.40～5.61 pg/mg）and Q₃（HCC:5.61～9.30 pg/mg）groups had a significantly lower risk of high AL total compared with girls in the Q₁（HCC<2.40 pg/mg）group（Q₂group:OR=0.22,95%CI:0.07,0.68,P=0.009;Q₃group:OR=0.24,95%CI:0.08,0.78,P=0.017,respectively）.Restricted cubic spline model indicated a linear dose-response relationship between HCC and the risk of high AL total after adjusting for covariates(χ~2_nonlinear=5.88,P _nonlinear=0.053).Compared with the group with HCC of 3.66-7.65 pg/mg,HCC<3.66pg/mg was associated with an increased risk of high AL total（OR=3.52,95%CI:1.36,9.15,P=0.010）.In the range of HCC<3.66 pg/mg,with the increase of HCC,the risk of high AL total decreased continuously,and after HCC exceeded 3.66 pg/mg,the risk of high AL total leveled off.The association between HCC and high AL total was not significant when HCC exceeded 7.65 pg/mg（OR=1.98,95%CI:0.77,5.08,P=0.155）.ConclusionIn girls with precocious puberty,early life adversity exposure was significantly associated with allostatic load,an indicator of physiological system attrition,and attention should be paid to girls who reported peer bullying,low parental education and parental divorce.There was a linear dose-response relationship between HCC,a biomarker of adversity exposure,and the AL total.Our study provide a new perspective for understanding the long-term physical and mental health risks of girls with precocious puberty,help to identify individuals at risk of ELA-related diseases,and timely intervention to reduce the risk of adverse health outcomes in later life in girls with precocious puberty.