Aagaard Kristina, Bach Cathrine Carlsen, Henriksen Tine Brink, Larsen René Tidemand, Matthiesen Niels Bjerregård
Perinatal Epidemiology Research Unit, Department of Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark.
Department of Pediatrics and Adolescent Medicine, Randers Regional Hospital, Randers, Denmark.
Paediatr Perinat Epidemiol. 2018 Sep;32(5):458-466. doi: 10.1111/ppe.12479. Epub 2018 Jun 8.
Early markers of Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) may improve the understanding and early recognition of these disorders. We aimed to estimate the association between head circumference at birth, a measure of cerebral size at birth, and the risk of ADHD and ASD.
We present a register-based cohort study of all Danish singletons born alive between 1997 and 2013. Cox proportional hazards regression was used for the statistical analyses. Sibling-matched analyses were performed to account for unmeasured confounding shared by siblings.
The analyses included 986 909 new-borns. Compared to normocephalic children, microcephaly was associated with an increased risk of ADHD (hazard ratio [HR] 1.22, 95% confidence interval [CI] 1.12, 1.32). Macrocephaly was associated with a decreased risk of ADHD (HR 0.90, 95% CI 0.82, 0.99). Neither microcephaly nor macrocephaly were associated with ASD (HR 1.06, 95% CI 0.94, 1.19 and 1.03, 95% CI 0.90, 1.19). The largest difference was found within the normocephalic children. A head circumference at the lower limit of normocephaly compared to a head circumference at the upper limit was associated with an increased risk of ADHD (HR 1.52, 95% CI 1.43, 1.63). The sibling analyses confirmed the increased risk of ADHD with decreasing head circumference in the normocephalic children. No other clear associations were present in the sibling analyses.
Within normocephalic children, smaller head circumference at birth was associated with a higher risk of ADHD. Restricted foetal brain growth may be a risk factor for the development of ADHD but not ASD.
注意缺陷多动障碍(ADHD)和自闭症谱系障碍(ASD)的早期标志物可能有助于增进对这些疾病的理解和早期识别。我们旨在评估出生时头围(一种出生时脑大小的测量指标)与ADHD及ASD风险之间的关联。
我们开展了一项基于登记册的队列研究,纳入了1997年至2013年间所有在丹麦存活出生的单胎婴儿。采用Cox比例风险回归进行统计分析。进行了同胞匹配分析以考虑同胞间共享的未测量混杂因素。
分析纳入了986909名新生儿。与头围正常的儿童相比,小头畸形与ADHD风险增加相关(风险比[HR]1.22,95%置信区间[CI]1.12,1.32)。巨头畸形与ADHD风险降低相关(HR 0.90,95%CI 0.82,0.99)。小头畸形和巨头畸形均与ASD无关(HR 1.06,95%CI 0.94,1.19和1.03,95%CI 0.90,1.19)。在头围正常的儿童中发现了最大差异。头围处于正常下限的儿童与头围处于正常上限的儿童相比,ADHD风险增加(HR 1.52,95%CI 1.43,1.63)。同胞分析证实了头围正常的儿童中,头围越小ADHD风险越高。同胞分析中未发现其他明显关联。
在头围正常的儿童中,出生时头围较小与ADHD风险较高相关。胎儿脑生长受限可能是ADHD而非ASD发生发展的一个风险因素。