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Children born to mothers exposed to hypertensive disorders of pregnancy (HDP) were at increased risk of neurodevelopmental disorders including autism spectrum disorders (ASD) and attention deficit-hyperactivity disorder (ADHD), according to a systematic review.

A meta-analysis of 61 observational studies showed HDP was associated with a 35% increased risk of ASD and a 30% increase in ADHD risk, reported Gillian M. Maher MPH of Cork University Maternity Hospital in Ireland, and colleagues in .

The study also addressed links between HDP and other conditions including impaired cognitive function, developmental delay, behavioral disorders, and intellectual disability.

Of 61 studies included in the review 20 explored the association between HDP and ASD and 10 explored the link with ADHD. The association between hypertension and other neurological disorders was explored in the 31 remaining studies.

A pooled adjusted odds ratio of 1.35 (95% CI 1.11-1.64) was found in the 20 studies exploring the link between HDP and ADS. In the 10 studies exploring the association with ADHD, the pooled adjusted OR was 1.29 (95% CI 1.22-1.36). The researchers conducted a sub-analyses exploring the risk according to specific category of hypertension -- either preeclampsia or another type of hypertensive disorder. The sub-group differences were not statistically significant.

Of the 31 studies which explored the "other neurodevelopmental disorders" category, standalone sensitivity analysis was performed. The findings were largely inconsistent with only a few patterns of association observed. For example, a small number of studies suggested a potential association between HDP and intellectual disability.

Hypertension is a common complication of the prenatal period and a leading cause of maternal and fetal morbidity.

"Hypertensive disorders of pregnancy affect 5% to 15% of all pregnancies and therefore are among the most common prenatal complications. Hypertensive disorders of pregnancy create adverse in utero conditions that can alter fetal development and may increase the risk of long-term vascular, cognitive, and psychiatric sequelae in offspring," the authors wrote. This lends credence to the theory that ASD and ADHD, although containing a strong genetic component, may also be influenced by environmental factors, such as the mother's health."

"Given the increasing prevalence of HDP, partially owing to increasing levels of obesity, metabolic syndrome, and advanced maternal age, collating the existing evidence of the association of HDP with neurodevelopmental outcome is timely," they stated.

In an email to 番茄社区, study researcher Ali Khashan, PhD, of the School of Public Helath & INFANT Centre, Cork, Ireland, advised caution in over-interpretation of results, as, although statistically significant, "the absolute risk of ASD and ADHD is small even among children of women who had hypertensive disorders of pregnancy."

To be included in the review, studies were required to be original, peer reviewed cohort, case-control, or cross-sectional and in which a diagnosis of HDP was reported and neurodevelopmental disorders were the outcome of interest. A diagnosis of HDP was confirmed through medical records and/or physician diagnosed self-reporting.

"Although this study is suggestive of an association between HDP and neurodevelopmental disorders in offspring, it is difficult to rule out that antihypertensive medication used during pregnancy may be associated with adverse effects in offspring," the authors noted. Other explanatory mechanisms that may be at play are placental dysfunction, and maternal inflammation. Khashan noted that this was "an important research question and should be addressed in the future."

Study limitations included the fact that the review process only included English-language studies, difficulty in keyword research efforts on electronic databases, and the lack of sample size calculations that may limit the study's statistical power.

Most importantly was the presence of residual or unmeasured confounders. "Future research examining the association between HDP and neurodevelopmental outcomes needs to identify a comprehensive set of confounders to assess whether this association is attributable to residual or unmeasured confounding," they wrote.

They pointed out that if the association between in HDP and increased risk of ASD and ADHD is indeed found to be causal, this opens up the potential need for increased developmental screening to allow for early intervention and, in turn, improved neurodevelopmental outcomes.

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