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

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

doi:10.18632/oncotarget.23030

Abstract

BackgroundAutism 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.ResultsA 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 MethodsWe 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.ConclusionsThis 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.

Highlights

Autism spectrum disorders (ASD) is a neurodevelopmental syndrome characterized by various degrees of social impairment, deficits in language and communication, and repetitive patterns of behavior [1, 2], but the underlying mechanisms remain to be elucidated
Ratsep et al [13] reported that offspring of pre-eclamptic pregnancies exhibited altered brain structural and vascular anatomy as enlarged brain regional volumes of the cerebellum was detected by magnetic resonance imaging, which shared similarities with those seen in ASD
It is demonstrated that pregnancies affected by pre-eclampsia are correlated with an exaggerated immune responses, creating a chronic and uncontrolled state of inflammation [14, 15]

Summary

Introduction

Autism spectrum disorders (ASD) is a neurodevelopmental syndrome characterized by various degrees of social impairment, deficits in language and communication, and repetitive patterns of behavior [1, 2], but the underlying mechanisms remain to be elucidated. Hypertensive disorders of pregnancy (HDP) is a complex multisystem disorder, encompassing (1) gestational hypertension, (2) chronic hypertension complicating pregnancy (CHP), (3) pre-eclampsia and eclampsia [7], which can lead to severe maternal and fetal morbidity and even mortality [8]. Epidemiological studies suggest that maternal infections (such as parasitic, bacterial and viral infection) [16] and autoimmune disorders (such as rheumatoid arthritis, asthma, systemic lupus erythematosis) [17], all of which lead to elevated immune responses, have been confirmed as independent risk factors for ASD [18]. Our aim was to (1) systematically evaluate the association between hypertensive disorders of pregnancy (HDP) and the risk of ASD in offspring, (2) draw a subgroup analysis of disease severity in patients with HDP to achieve more sufficient evidence on this issue

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