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

Ruo-Ting Xu, Qing-Xian Chang, Qi-Qiong Wang, Jian Zhang, Lai-Xin Xia, Nanbert Zhong, Yan-Hong Yu, Mei Zhong and Qi-Tao Huang _

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Oncotarget. 2018; 9:1291-1301. https://doi.org/10.18632/oncotarget.23030

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Ruo-Ting Xu1,2,*, Qing-Xian Chang3,*, Qi-Qiong Wang4, Jian Zhang5, Lai-Xin Xia6, Nanbert Zhong3,7,8, Yan-Hong Yu3, Mei Zhong3 and Qi-Tao Huang3

1Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, China

2First School of Clinical Medicine, Southern Medical University, Guangzhou, China

3Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, China

4Department of Neonatology, Nanfang Hospital, Southern Medical University, Guangzhou, China

5Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China

6Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China

7March of Dimes Global Network for Maternal and Infant Health, White Plains, NY, USA

8Department 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: [email protected]

Mei Zhong, email: [email protected]

Keywords: autism; childhood; pre-eclampsia; hypertensive disorders of pregnancy

Received: June 05, 2017     Accepted: September 21, 2017     Published: December 07, 2017


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.

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