Atkinson Jessica A, Gordon Hannah G, Tong Stephen, Walker Susan P, Mehdipour Parinaz, Lindquist Anthea C, Hastie Roxanne M
Perinatal Epidemiology Group, Department of Obstetrics, Gynaecology, and Newborn Health, University of Melbourne, Melbourne, Victoria, Australia.
Mercy Perinatal, Mercy Hospital for Women, Heidelberg, Victoria, Australia.
PLoS Med. 2025 Sep 10;22(9):e1004558. doi: 10.1371/journal.pmed.1004558. eCollection 2025 Sep.
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.
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.
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.
妊娠高血压疾病可能会增加儿童出现不良神经发育结局的风险，不过目前尚无近期的全面荟萃分析。本研究的目的是进行一项系统评价和荟萃分析，以检验妊娠高血压疾病与儿童神经发育障碍、智力及教育结局之间的关联。
对MEDLINE、CINAHL、科学引文索引和心理学文摘数据库从建库至2024年9月18日进行检索。还对纳入论文的参考文献列表进行了筛选。纳入针对参照人群（未受影响的妊娠）报告妊娠高血压疾病后出生儿童的神经发育、认知或教育结局的观察性研究及随机试验的二次分析。两名审阅者独立筛选记录、提取数据，并使用系统评价和荟萃分析的首选报告项目评估研究质量。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。结局包括自闭症、注意力缺陷多动障碍、脑瘫、全面发育迟缓、智力残疾、智商和教育程度。结果以比值比（OR）或平均差（MD）及相应的95%置信区间（CI）报告。在筛选了13419条记录后，纳入了121项报告29649667名后代结局的研究。我们纳入了85项队列研究、30项病例对照研究、4项横断面研究和2项随机试验的二次分析。与未受影响的妊娠相比，妊娠高血压疾病与自闭症谱系障碍（OR 1.65（95%CI[1.49,1.83]）；p<0.001；n=26727500）、注意力缺陷多动障碍（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）的未调整发生可能性增加以及平均智力降低（MD -2.20 95%CI[-3.35,-1.06]）；p<0.001；n=1150664）相关。在调整胎龄和出生体重后，高血压与自闭症谱系障碍和全面发育迟缓之间的关联不再显著。在调整出生体重后，智商结果仍具有显著性，但调整胎龄后则不然。由于缺乏合适的研究，无法对注意力缺陷多动障碍和智力残疾进行调整分析。在敏感性分析中，排除存在高偏倚风险的论文后结果未变。本研究的局限性在于缺乏对混杂和中介因素进行调整的组成论文、纳入研究之间存在大量异质性以及某些结局可能存在发表偏倚。
妊娠高血压疾病可能与受影响后代的不良神经发育和认知结局相关。虽然导致这些关联的机制尚不清楚，但这些结果凸显了一组将受益于早期干预和支持以改善其神经发育结局的儿童。
