Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder among children born preterm, with the highest risk group being those born extremely preterm (birth before 28 weeks of gestation).1 In a large cohort of individuals born extremely preterm, ADHD was the most common psychiatric outcome at 15 years of age with a prevalence of 18%.2 As compared to individuals born at term, those born most extremely preterm (22–25 weeks of gestation) have a more than fourfold increase in odds of any ADHD diagnosis, with tenfold increase in odds of ADHD inattentive subtype.3 Identification of pre- , peri- , and postnatal risk factors for ADHD and a better understanding of the mechanisms linking preterm birth and ADHD later in life can inform the identification of ADHD to allow for early intervention, towards the goal of improving the life course of individuals born preterm. A better understanding of risk factors may also allow for interventions to modify or reduce the risk of ADHD among offspring of high-risk pregnancies.
Despite the potential value of such studies, very few research reports have described specific antecedents of ADHD among individuals born preterm. The study by Tso et al.1 begins to fill this knowledge gap by analyzing relationships between postnatal complications and ADHD in a large population-based sample of children born in Hong Kong. In this sample, early respiratory diseases, retinopathy of prematurity (ROP), and intraventricular hemorrhage mediated the relationship between preterm birth and ADHD, with the proportion mediated varying considerably as a function of prevalence. For example, ROP and intraventricular hemorrhage occurred very infrequently in infants born late preterm and thus were not mediators in this subgroup; in contrast, intraventricular hemorrhage and ROP mediated over 40% of the association among children born extremely preterm. Respiratory disease, which included all diagnosed respiratory infections in the first 2 years of life, mediated the highest proportion of the association. An unanswered question is whether there are unmeasured confounding prenatal risk factors that may be independently associated with preterm birth, postnatal complications, and ADHD outcomes. For example, modifiable prenatal risk factors of preterm birth and ADHD, such as maternal smoking during pregnancy, maternal obesity, and maternal diabetes, were not assessed. In addition to considering these potential confounders, more research is needed to identify mechanisms linking respiratory disease, ROP, and intraventricular hemorrhage to subsequent ADHD, towards the goal of interrupting these mechanisms.
Given the high frequency of ADHD among infants born preterm, prevention of preterm birth is a potential strategy for decreasing the prevalence of ADHD in children. Although the success of efforts to prevent preterm birth has been limited in high-income countries, the risk of recurrent preterm birth (among mothers with a history of prior preterm birth) can be decreased by treatment with 17-alpha-hydroxyprogesterone beginning in the 16th week of pregnancy.4 Each of the risk factors for ADHD that were identified by Tso et al. is potentially modifiable. Certain specific respiratory infections, including pertussis, diphtheria, and group B streptococcal pneumonia are preventable. The risk of ROP in infants born extremely preterm and very preterm can be reduced by targeting oxygen saturations,5 and the impact of ROP on visual function can be improved with surgical interventions. Evidence-based interventions to prevent intraventricular hemorrhage include antenatal treatment of mothers with corticosteroids and prophylactic indomethacin, although the latter has potential side effects that has limited its use. Equally important are rehabilitative therapies and educational support for children with early symptoms, and/or at high risk of ADHD. Future research is needed to determine if such interventions will modify the risk of ADHD, or if there are other modifiable prenatal risk factors that can moderate this increased risk.
DATA AVAILABILITY STATEMENT
No original data were used to develop this commentary
REFERENCES
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Data Availability Statement
No original data were used to develop this commentary