Preterm birth before 37 weeks’ gestation has a global prevalence of 11 %, with rates of about 7–8 % in the US and Canada [1], [2]. Earlier birth -- a strong predictor of neonatal and infant mortality and morbidity -- may also adversely affect future brain development [1], [3]. Specifically, among those born preterm, reduced white and grey matter brain volumes in childhood have been observed, as well as clinical phenotypes of behavioural problems and impaired self-regulation by age 5 years [3], [4], [5], [6]. The neurocognitive effects of preterm birth can persist beyond early childhood. For example, birth before 34 weeks’ gestation is associated with substantial deficits in cognitive domains at 15–16 years of age and intelligence quotient (IQ) scores at 19 years of age [7]. Those who experience brain injury related to preterm birth particularly exhibit lower IQ scores when also exposed to a low socioeconomic environment and low parental education [8], [9], [10].

The structural and functional brain abnormalities following extreme preterm birth [3], [4], [5], [6] are similar to those seen in adolescents with injurious behaviours, and those among adolescents with substance use disorders [11], [12], [13], [14]. For example, functional MRI has shown altered cortical thickness in some non-suicidal self-harming youth and smaller cortical brain volume alongside functional changes at specific cortical regions in suicidal adults [3], [15]. Reduced activity and dysfunctional brain connectivity were revealed on functional MRI in persons with opioid dependence and other substance use disorders [16], [17]. In addition, the motor and cognitive disabilities following preterm birth, alongside the higher risk of developing attention deficit hyperactivity, can predispose to unintentional injury and premature mortality [18], [19].

Data from Sweden [20], [21], Norway [22], Finland [23], and recently, from Canada [24], has shown an association between preterm birth and adult mortality, including suicide. Among individuals aged 10–24 years, both suicide and unintentional overdose are increasingly becoming leading causes of mortality [25], [26], [27], [28], [29], [30], [31]. Given the potential behavioural consequences of preterm birth, and the somewhat similar structural brain changes seen in those with preterm birth, and separately, those with injurious behaviours, a logical question is whether preterm birth is associated with future risk of self-injury and unintentional (accidental”) injury during adolescence and early adulthood. Such knowledge could further guide neurodevelopmental interventions specific to infants and youth born extremely preterm, to improve their lives beyond childhood.

Ontario’s universal healthcare system enables the systematic linkage of data of all births to future deaths, emergency department (ED) visits, and hospitalizations related to injury, overdose, and death [27], [32]. This study evaluated the relation between preterm birth and self-injury, overdose and all-cause mortality.