Author-generated code for analyses.

BackgroundHypertensive 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 findingsA 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 n = 26,727,500), attention-deficit/hyperactivity disorder (OR 1.27 (95% CI [1.21,1.33]); p n = 12,987,737), intellectual disability (OR 1.77 (95% CI [1.31,2.38]); p n = 10,718,504), global developmental delay (OR 1.77 (95% CI [1.21,2.59]); p n = 2,961,195), and reduced mean intelligence (MD −2.20 95% CI [−3.35,-1.06]); p 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.ConclusionsHypertensive 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）可能会增加子代不良神经发育结局的发生风险，但目前尚无近期的全面荟萃分析（meta-analysis）相关报道。本研究旨在开展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（医学文献分析与检索系统）、CINAHL（护理与联合卫生文献累积索引）、Web of Science（科学网）及PsycINFO（心理学文摘数据库）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了人工筛查。本研究纳入以未受影响的妊娠人群为对照、报道妊娠高血压疾病患儿子代神经发育、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。两名研究人员独立完成文献筛查、数据提取及研究质量评价，评价过程遵循《系统综述与荟萃分析优先报告条目》（Preferred Reporting Items for Systematic Reviews and Meta-Analyses，PRISMA）。采用随机效应荟萃分析模型对结局指标相似的研究进行合并分析。本次研究的结局指标包括自闭症谱系障碍、注意缺陷多动障碍、脑性瘫痪、全面性发育迟缓、智力残疾、智商及教育成就。研究结果以比值比（odds ratio，OR）或均数差（mean difference，MD）及对应的95%置信区间（confidence interval，CI）进行报告。 经对13419条文献记录进行筛查后，最终纳入121项研究，涉及29649667例子代。其中包括85项队列研究、30项病例对照研究、4项横断面研究及2项随机对照试验的二次分析。 与未受影响的妊娠人群相比，妊娠高血压疾病患儿子代的未校正自闭症谱系障碍发生风险显著升高（OR=1.65，95%CI[1.49,1.83]；样本量n=26727500）、注意缺陷多动障碍发生风险升高（OR=1.27，95%CI[1.21,1.33]；样本量n=12987737）、智力残疾发生风险升高（OR=1.77，95%CI[1.31,2.38]；样本量n=10718504）、全面性发育迟缓发生风险升高（OR=1.77，95%CI[1.21,2.59]；样本量n=2961195），且平均智商水平显著降低（MD=-2.20，95%CI[-3.35,-1.06]；样本量n=1150664）。 在校正胎龄与出生体重后，妊娠高血压疾病与自闭症谱系障碍、全面性发育迟缓之间的关联不再具有统计学显著性。校正出生体重后，智商的关联仍具有统计学显著性，但校正胎龄后则无此显著性。由于缺乏合适的研究，无法开展注意缺陷多动障碍与智力残疾的校正分析。敏感性分析结果显示，排除高偏倚风险的文献后，研究结论未发生改变。本研究存在以下局限性：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，且部分结局指标可能存在发表偏倚。 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存在关联。尽管目前此类关联的潜在机制尚不明确，但本研究结果提示，该类儿童群体可从早期干预与支持中获益，以改善其神经发育结局。