Association between hypertensive disorders of pregnancy and risk of autism in offspring: a systematic review and meta-analysis of observational studies

// Ruo-Ting Xu 1, 2, * , Qing-Xian Chang 3, * , Qi-Qiong Wang 4 , Jian Zhang 5 , Lai-Xin Xia 6 , Nanbert Zhong 3, 7, 8 , Yan-Hong Yu 3 , Mei Zhong 3 and Qi-Tao Huang 3 1 Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, China 2 First School of Clinical Medicine, Southern Medical University, Guangzhou, China 3 Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, China 4 Department of Neonatology, Nanfang Hospital, Southern Medical University, Guangzhou, China 5 Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China 6 Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China 7 March of Dimes Global Network for Maternal and Infant Health, White Plains, NY, USA 8 Department of Human Genetics, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA * These authors contributed equally to this work Correspondence to: Qi-Tao Huang, email: 15920454515@163.com Mei Zhong, email: zhongm1960@163.com Keywords: autism; childhood; pre-eclampsia; hypertensive disorders of pregnancy Received: June 05, 2017 Accepted: September 21, 2017 Published: December 07, 2017 ABSTRACT Background: Autism spectrum disorder (ASD) is a common severe pervasive neurodevelopmental disorder of undetermined etiology. Environmental exposures, especially pregnancy complications, have been increasingly recognized as a potential risk factor for ASD. Our aim was to (1) systematically evaluate the association between hypertensive disorders of pregnancy (HDP) and the risk of ASD in offspring, (2) specifically draw a subgroup analysis of disease severity in patients with HDP to achieve more sufficient evidence on this issue. Results: A total of 21 studies were identified with more than 6.5 million participants, including 31,027 ASD probands. A comparative meta-analysis established that offspring born premature to HDP were significantly associated with ASD than matched controls (OR = 1.42, 95% CI: 1.34–1.50). Subgroup analysis of clinical classification include: (1) gestational hypertension, (2) pre-eclampsia, (3) chronic hypertension complicating pregnancy (CHP). The offspring of mothers with pre-eclampsia and CHP have slightly higher risk (OR = 1.43; OR = 1.48, respectively) of ASD than those of mothers with gestational hypertension (OR = 1.37). In consistence with most previous researches, higher ASD prevalence was observed in male than female (OR = 1.38), indicating a potential role for gender in the pathophysiology of ASD. Materials and Methods: We conducted a systematic literature search on PubMed, EMBASE, Web of Science, PsycINFO database and China National Knowledge Infrastructure up to Jun. 2017. Statistical analysis was performed using Stata 10.0. Conclusions: This meta-analysis implies a possible link between HDP and the risk of ASD in offspring. However, further investigation should be conducted to confirm this conclusion, and intensive prenatal surveillance and early prediction for ASD is needed.