Brand Judith S, Lawlor Deborah A, Larsson Henrik, Montgomery Scott
Clinical Epidemiology and Biostatistics, School of Medical Sciences, Örebro University, Örebro, Sweden.
Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.
JAMA Pediatr. 2021 Jun 1;175(6):577-585. doi: 10.1001/jamapediatrics.2020.6856.
Hypertensive disorders of pregnancy (HDP) have been associated with poorer neurodevelopmental outcomes in offspring, but the role of familial confounding in these associations is unclear.
To investigate associations of maternal HDP with risks in offspring of autism spectrum disorders (ASDs), attention-deficit/hyperactivity disorder (ADHD), and intellectual disability (ID), as well as variation in overall cognitive performance in offspring.
DESIGN, SETTING, AND PARTICIPANTS: This Swedish register-based study used data from a birth cohort divided into 1 085 024 individuals born between 1987 and 1996 and followed up until December 31, 2014, and 285 901 men born between 1982 and 1992 who attended assessments for military conscription, including a cognitive function test. Statistical analysis was performed from April 1, 2019, to June 1, 2020.
Diagnoses of HDP, which were provided by the Medical Birth Register.
Diagnoses of ASDs, ADHD, and ID were extracted from the National Patient Register. Cognitive function was assessed using written tests and summarized as a single 9-point score. Whole-cohort and within-sibship analyses were performed; the latter accounted for unmeasured familial confounding factors shared by siblings.
The study included 1 085 024 individuals (556 912 male participants [51.3%]) born between 1987 and 1996 and 285 901 men born between 1982 and 1992 who attended assessments for military conscription. The prevalence of maternal HDP was 4.0% in the 1987-1996 birth cohort (n = 42 980) and 5.1% in the military conscription cohort (n = 14 515). A total of 15 858 participants received a diagnosis of ASD, 36 852 received a diagnosis of ADHD, and 8454 received a diagnosis of ID. The mean (SD) cognitive score among the men in the conscription cohort was 5.1 (1.9). In whole-cohort analyses with multivariable adjustment, HDP were associated with offspring ASDs (hazard ratio [HR], 1.22; 95% CI, 1.13-1.31), ADHD (HR, 1.10; 95% CI, 1.05-1.16), and ID (HR, 1.39; 95% CI, 1.27-1.53). Analyses comparing siblings discordant for HDP were less statistically powered but indicated estimates of similar magnitude for ASDs (HR, 1.19; 95% CI, 1.00-1.42) and possibly ADHD (HR, 1.09; 95% CI, 0.95-1.24), but not for ID (HR, 1.04; 95% CI, 0.83-1.29). Hypertensive disorders of pregnancy were associated with somewhat lower cognitive scores in whole-cohort analysis (mean difference comparing offspring exposed with those unexposed, -0.10; 95% CI, -0.13 to -0.07), but in within-sibship analysis, the association was null (mean difference, 0.00; 95% CI, -0.09 to 0.08).
The study results suggest that HDP are associated with small increased risks of ASDs and possibly ADHD in offspring, whereas associations with ID and cognitive performance are likely confounded by shared familial (environmental or genetic) factors.
妊娠高血压疾病（HDP）与后代较差的神经发育结局相关，但家族性混杂因素在这些关联中的作用尚不清楚。
研究母亲患HDP与后代患自闭症谱系障碍（ASD）、注意力缺陷多动障碍（ADHD）和智力残疾（ID）的风险以及后代总体认知表现的差异之间的关联。
设计、设置和参与者：这项基于瑞典登记处的研究使用了一个出生队列的数据，该队列分为1987年至1996年出生的1085024人，并随访至2014年12月31日，以及1982年至1992年出生的285901名参加征兵评估（包括认知功能测试）的男性。统计分析于2019年4月1日至2020年6月1日进行。
医疗出生登记处提供的HDP诊断。
从国家患者登记处提取ASD、ADHD和ID的诊断。使用书面测试评估认知功能，并汇总为单一的9分评分。进行了全队列分析和同胞内分析；后者考虑了兄弟姐妹共有的未测量的家族性混杂因素。
该研究包括1987年至1996年出生的1085024人（556912名男性参与者[51.3%]）和1982年至1992年出生的285901名参加征兵评估的男性。1987 - 1996年出生队列中母亲患HDP的患病率为4.0%（n = 42980），征兵队列中为5.1%（n = 仅用于医学专业学术文献翻译14515）。共有15858名参与者被诊断为ASD，36852名被诊断为ADHD，8454名被诊断为ID。征兵队列中男性的平均（标准差）认知评分为5.1（1.9）。在进行多变量调整的全队列分析中，HDP与后代ASD（风险比[HR]，1.22；95%置信区间，1.13 - 1.31）、ADHD（HR，1.10；95%置信区间，1.05 - 1.16）和ID（HR，1.39；95%置信区间，1.27 - 1.53）相关。比较HDP不一致的兄弟姐妹的分析统计学效力较低，但显示ASD（HR，1.19；95%置信区间，1.00 - 1.42）和可能的ADHD（HR，1.09；95%置信区间，0.95 - 1.24）的估计值幅度相似，但ID不相关（HR，1.04；95%置信区间，0.83 - 1.29）。在全队列分析中，妊娠高血压疾病与认知评分略低相关（比较暴露后代与未暴露后代的平均差异，-0.10；95%置信区间，-0.
