Dataset used for unadjusted analyses.

Background
Hypertensive disorders of pregnancy may be associated with an increased risk of adverse neurodevelopmental outcomes for the child, though no recent comprehensive meta-analyses exist. The aim of this study was to conduct a systematic review and meta-analysis examining the association between hypertensive disorders of pregnancy and child neurodevelopmental disabilities, intelligence, and educational outcomes.
Methods and findings
A search was conducted of MEDLINE, CINAHL, Web of Science, and PsycINFO databases from inception until 18 September 2024. Reference lists of included papers were also screened. Observational studies and secondary analyses of randomized trials reporting neurodevelopmental, cognitive, or educational outcomes for children born following hypertensive disorders of pregnancy against a reference population (unaffected pregnancies) were included. Two reviewers independently screened records, extracted data, and assessed quality of studies using Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Studies reporting similar outcomes were pooled using a random-effects meta-analysis model. Outcomes included autism, attention-deficit/hyperactivity disorder, cerebral palsy, global developmental delay, intellectual disability, intelligence quotient, and educational attainment. Results were reported as odds ratios (OR) or mean difference (MD) with corresponding 95% confidence intervals (CI). After screening 13,419 records, 121 studies reporting outcomes of 29,649,667 offspring were included. We included 85 cohort studies, 30 case-control studies, four cross-sectional studies, and two secondary analyses of randomized trials. Compared with unaffected pregnancies, hypertensive disorders of pregnancy were associated with an increased unadjusted likelihood of autism spectrum disorder (OR 1.65 (95% CI [1.49,1.83]); p < 0.001; n = 26,727,500), attention-deficit/hyperactivity disorder (OR 1.27 (95% CI [1.21,1.33]); p < 0.001; n = 12,987,737), intellectual disability (OR 1.77 (95% CI [1.31,2.38]); p < 0.001; n = 10,718,504), global developmental delay (OR 1.77 (95% CI [1.21,2.59]); p < 0.001; n = 2,961,195), and reduced mean intelligence (MD −2.20 95% CI [−3.35,-1.06]); p < 0.001; n = 1,150,664). Associations between hypertension and autism spectrum disorder and global developmental delay were no longer significant after adjusting for gestational age and birthweight. Results for intelligence quotient remained significant when adjusting for birthweight, but not gestational age. Adjusted analyses for attention-deficit/hyperactivity disorder and intellectual disability could not be performed due to a lack of suitable studies. In sensitivity analyses, results were unchanged after exclusion of papers at high risk of bias. This study is limited by a lack of constituent papers which adjusted for confounding and mediating factors, a high amount of heterogeneity among included studies, and possible publication bias for some outcomes.
Conclusions
Hypertensive disorders of pregnancy are potentially associated with adverse neurodevelopmental and cognitive outcomes among affected offspring. While the mechanisms driving these associations are not clear, these results highlight a group of children that will benefit from early intervention and support to improve their neurodevelopmental outcomes.

### 背景
妊娠高血压疾病（Hypertensive disorders of pregnancy）可能与子代不良神经发育结局风险升高相关，但目前尚无最新的全面荟萃分析。本研究旨在开展一项系统综述与荟萃分析，探讨妊娠高血压疾病与儿童神经发育残疾、智力及教育结局之间的关联。

### 方法与结果
本研究检索了MEDLINE、CINAHL、Web of Science及PsycINFO数据库自建库至2024年9月18日的文献，并对纳入文献的参考文献列表进行人工筛查。纳入以未受影响妊娠人群为对照、报告妊娠高血压疾病患儿神经发育、认知或教育结局的观察性研究及随机对照试验的二次分析。由2名研究者独立完成文献筛选、数据提取及研究质量评估，评估工具采用系统综述与荟萃分析首选报告条目（Preferred Reporting Items for Systematic Reviews and Meta-Analyses, PRISMA）。对报告相似结局的研究采用随机效应荟萃分析模型进行合并分析。分析结局包括孤独症（autism）、注意缺陷多动障碍（attention-deficit/hyperactivity disorder）、脑瘫（cerebral palsy）、全面发育迟缓（global developmental delay）、智力残疾（intellectual disability）、智商（intelligence quotient）及教育成就（educational attainment）。结果以比值比（odds ratio, OR）或均数差（mean difference, MD）及对应95%置信区间（confidence interval, CI）报告。
经筛查13419条文献记录后，最终纳入121项研究，涉及29649667名子代。其中纳入队列研究85项、病例对照研究30项、横断面研究4项及随机对照试验二次分析2项。与未受影响妊娠人群相比，妊娠高血压疾病与未校正的孤独症谱系障碍（odds ratio [OR] 1.65, 95%置信区间[CI] [1.49, 1.83]; p < 0.001; n=26727500）、注意缺陷多动障碍（OR 1.27, 95%CI [1.21, 1.33]; p < 0.001; n=12987737）、智力残疾（OR 1.77, 95%CI [1.31, 2.38]; p < 0.001; n=10718504）、全面发育迟缓（OR 1.77, 95%CI [1.21, 2.59]; p < 0.001; n=2961195）及平均智商降低（均数差MD -2.20, 95%CI [-3.35, -1.06]; p < 0.001; n=1150664）的发生风险升高相关。在校正胎龄与出生体重后，妊娠高血压疾病与孤独症谱系障碍、全面发育迟缓的关联不再具有统计学意义；校正出生体重后，智商的关联仍具有统计学意义，但校正胎龄后则无此显著性。由于缺乏合适的研究，无法完成注意缺陷多动障碍与智力残疾的校正分析。敏感性分析显示，剔除高偏倚风险文献后，研究结果未发生改变。本研究存在一定局限性：缺乏针对混杂因素与中介因素进行校正的原始研究，纳入研究间异质性较高，且部分结局可能存在发表偏倚。

### 结论
妊娠高血压疾病可能与子代不良神经发育及认知结局相关。尽管介导此类关联的潜在机制尚未明确，但本研究结果提示，有一类儿童可通过早期干预与支持改善其神经发育结局。