A Systematic Review and Meta-analysis of Prenatal, Birth, and Postnatal Factors Associated with Attention-Deficit/Hyperactivity Disorder in Children

Abstract

Previous studies have shown mixed results on the relationship between prenatal, birth, and postnatal ("pregnancy-related") risk factors and attention-deficit/hyperactivity disorder (ADHD). We conducted meta-analyses to identify potentially modifiable pregnancy-related factors associated with ADHD. A comprehensive search of PubMed, Web of Science, and EMBASE in 2014, followed by an updated search in January 2021, identified 69 articles published in English on pregnancy-related risk factors and ADHD for inclusion. Risk factors were included in the meta-analysis if at least three effect sizes with clear pregnancy-related risk factor exposure were identified. Pooled effect sizes were calculated for ADHD overall, ADHD diagnosis, inattention, and hyperactivity/impulsivity. Odds ratios (OR) were calculated for dichotomous measures and correlation coefficients (CC) for continuous measures. Prenatal factors (pre-pregnancy weight, preeclampsia, pregnancy complications, elevated testosterone exposure), and postnatal factors (Apgar score, neonatal illness, no breastfeeding) were positively associated with ADHD overall; the findings for ADHD diagnosis were similar with the exception that there were too few effect sizes available to examine pre-pregnancy weight and lack of breastfeeding. Prenatal testosterone was significantly associated with inattention and hyperactivity/impulsivity. Effect sizes were generally small (range 1.1-1.6 ORs, -0.16-0.11 CCs). Risk factors occurring at the time of birth (perinatal asphyxia, labor complications, mode of delivery) were not significantly associated with ADHD. A better understanding of factors that are consistently associated with ADHD may inform future prevention strategies. The findings reported here suggest that prenatal and postnatal factors may serve as potential targets for preventing or mitigating the symptoms of ADHD.

Fig-1

Flowchart of triage process for articles identified for meta-analyses of prenatal, birth, and postnatal risk factors associated with attention-deficit/hyperactivity disorder Note: Articles overlap across categories and therefore the n representing the sum of the individual risk factors is greater than the overall n for each box. Articles were identified through a comprehensive search of PubMed, Web of Science, and EMBASE and iterative reference mining in 2014, and an updated search of PubMed, Web of Science, and EMBASE in January 2021.