Association of preterm birth and birth size status with neurodevelopmental and psychiatric disorders in spontaneous births

Abstract

Preterm birth (PTB) or small birth size are risk factors for certain neurodevelopmental disorders. The magnitude of these associations in spontaneous births, and of associations for combined PTB and birth size status on neurodevelopmental and psychiatric disorders is unexplored. We investigated whether PTB and small/large for gestational age (SGA/LGA), separately or combined, in spontaneous births, are associated with a wide spectrum of neurodevelopmental and psychiatric disorders. In this population-based registry cohort study, all singleton spontaneous births in Finland from 1996 to 2014 were followed until 2018 (n = 819 764). We show that PTB across gestational ages, and SGA, were associated with higher risks for anxiety disorders, intellectual disabilities, specific developmental disorders (SDD), autism spectrum disorders (ASD), attention-deficit/hyperactivity disorders (ADHD) and other emotional and behavioural disorders (F98). Most of these associations were not attributed to familial factors. Larger effect sizes were observed with lower gestational ages. Extremely PTB was associated at highest risks with intellectual disabilities (HR, 10.70 [95%CI, 8.69-13.17]) and SDD (HR, 8.91 [95%CI, 8.18-9.71]). Moreover, very preterm birth combined with SGA was associated with a higher risk for SDD (HR, 7.55 [95%CI, 6.61-8.62]) than that of very preterm or SGA birth alone. Conversely, LGA birth lowered the risk for SDD and other emotional and behavioural disorders among individuals born very preterm. In conclusion, PTB along with SGA is associated with higher risks for SDD than one exposure alone, whereas LGA lowers the risks for SDD and other emotional and behavioural disorders in individuals born spontaneously.

Keywords: ADHD; Birth size; Preterm birth; Psychiatric disorders; Specific developmental disorders; Spontaneous birth.

Fig. 1

Cumulative incidence of autism spectrum disorder (ASD), ADHD, specific developmental disorder (SDD), intellectual disability (ID) across age of the born children stratified by exposure to preterm birth categories, or born small for gestational age (SGA)

Fig. 2

Adjusted hazard ratios (HRs) for neurodevelopmental and psychiatric disorders in relation to gestational age and size for gestational age (All live spontaneous singleton pregnancies born between 1996 and 2014 in Finland followed until 2018). Hazard ratios are represented on the x-axis, while gestational age and/or size for gestational age are represented on the y-axis. To achieve a more appropriate alignment of hazard ratios concerning intellectual disabilities, SDD, and personality disorders, we have plotted them on a separate x-axis range. AGA appropriate for gestational age; SGA small for gestational age; LGA large for gestational age; SDD specific developmental disorders; ASD autism spectrum disorders; ADHD attention-deficit/hyperactivity disorders. Extremely preterm is defined as < 28 weeks; very preterm is defined as 28 to 31 completed weeks; moderate to late preterm is defined as 32–36 completed weeks; term is defined as 37–41 completed weeks; and post-term is defined as ≥ 42 weeks. p-values that survive multiple comparison correction (p < 0.001) are marked with an asterisk (*)

Fig. 3

Adjusted hazard ratios (HRs) for diagnosis in the second-born child after exposure to premature birth (< 37 weeks) or small for gestational age (SGA), as estimated by matched sibling pair analysis. Hazard ratios are represented on the x-axis. To better align hazard ratios related to intellectual disabilities, we have plotted them on a separate x-axis range. Abbreviations: both, both siblings in the pair were exposed to preterm birth or SGA; Second but not first sib exp, the second sibling but not the first sibling was exposed to preterm birth or SGA; First but not second sib exp, exposure to the first but not the second sibling; None, none of the siblings in the pair was exposed. The None group was used as a reference