Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
Department of Obstetrics and Gynaecology, BC Women's Hospital, Vancouver, Canada; School of Population and Public Health, The University of British Columbia, Vancouver, Canada.
Am J Obstet Gynecol. 2022 Aug;227(2):287.e1-287.e17. doi: 10.1016/j.ajog.2022.03.028. Epub 2022 Mar 16.
Evidence indicates that in utero exposure to chorioamnionitis might increase the risk of neurodevelopmental disorders in the offspring. However, findings on this topic have been inconsistent.
To examine the association between chorioamnionitis and neurodevelopmental disorders in offspring.
This was a retrospective population-based cohort study in Sweden. A total of 2,228,280 singleton live births and stillbirths between 1998 and 2019 were included in our study population. Data on maternal characteristics and neurodevelopmental disorders in offspring were obtained by individual record-linkages of nationwide Swedish registries. Chorioamnionitis was identified using the National Medical Birth Register. Inpatient and outpatient diagnoses were obtained for cerebral palsy, autism, attention deficit hyperactivity disorder, epilepsy, and intellectual disability. Multivariable Cox proportional hazards regression was used to estimate the association between chorioamnionitis and each neurodevelopmental disorder with adjusted hazard ratios and 95% confidence intervals. A causal mediation analysis of the relationship between chorioamnionitis and neurodevelopmental disorders with preterm delivery (<37 weeks) was performed.
A total of 5770 (0.26%) offspring were exposed to chorioamnionitis during pregnancy. During the study's follow-up time there were 4752 (0.21%) cases of cerebral palsy, 17,897 (0.80 %) cases of epilepsy, 50,570 (2.27 %) cases of autism, 114,087 (5.12%) cases of attention deficit hyperactivity disorder, and 14,574 (0.65%) cases of intellectual disability. After adjusting for potential confounders, exposure to chorioamnionitis increased the hazard ratios of cerebral palsy (adjusted hazard ratio, 7.43; 95% confidence interval, 5.90-9.37), autism (adjusted hazard ratio, 1.43; 95% confidence interval, 1.21-1.68), attention deficit hyperactivity disorder (adjusted hazard ratio, 1.17; 95% confidence interval, 1.03-1.33), and intellectual disability (adjusted hazard ratio, 1.99; 95% confidence interval, 1.53-2.58), whereas chorioamnionitis was not significantly associated with higher rates of epilepsy in offspring. Mediation analysis revealed that these associations were mainly explained through preterm delivery; however, increased risk was also observed among term infants.
Chorioamnionitis increases the risk of neurodevelopmental disorders, particularly cerebral palsy, autism, attention deficit hyperactivity disorder, and intellectual disability. These associations were mainly mediated through preterm delivery. Efforts for timely identification and appropriate interventions to treat infections during pregnancy will have sustained benefits in reducing the burden of neurologic complications in children at the population level.
有证据表明，胎儿期的绒毛膜羊膜炎可能会增加后代神经发育障碍的风险。然而，关于这个问题的研究结果并不一致。
探讨绒毛膜羊膜炎与后代神经发育障碍之间的关系。
这是一项在瑞典进行的回顾性基于人群的队列研究。我们的研究人群包括 1998 年至 2019 年间 2228280 例单胎活产和死产。通过全国性瑞典登记处的个体记录链接获取母婴特征和后代神经发育障碍的数据。绒毛膜羊膜炎通过国家医疗出生登记处确定。脑瘫、自闭症、注意缺陷多动障碍、癫痫和智力残疾的住院和门诊诊断。多变量 Cox 比例风险回归用于估计绒毛膜羊膜炎与每种神经发育障碍之间的关联，调整后的危害比和 95%置信区间。对绒毛膜羊膜炎与早产（<37 周）之间神经发育障碍的关系进行因果中介分析。
共有 5770 名（0.26%）后代在孕期接触到绒毛膜羊膜炎。在研究的随访期间，有 4752 例（0.21%）脑瘫、17897 例（0.80%）癫痫、50570 例（2.27%）自闭症、114087 例（5.12%）注意缺陷多动障碍和 14574 例（0.65%）智力残疾。在调整了潜在混杂因素后，暴露于绒毛膜羊膜炎增加了脑瘫（调整后的危害比，7.43；95%置信区间，5.90-9.37）、自闭症（调整后的危害比，1.43；95%置信区间，1.21-1.68）、注意缺陷多动障碍（调整后的危害比，1.17；95%置信区间，1.03-1.33）和智力残疾（调整后的危害比，1.99；95%置信区间，1.53-2.58）的风险比，而绒毛膜羊膜炎与后代癫痫发生率升高无显著相关性。中介分析显示，这些关联主要通过早产来解释；然而，在足月婴儿中也观察到了风险增加。
绒毛膜羊膜炎增加了神经发育障碍的风险，特别是脑瘫、自闭症、注意缺陷多动障碍和智力残疾。这些关联主要通过早产来解释。努力及时发现并适当干预妊娠期间的感染，将在人群层面上持续减少儿童神经并发症的负担。
