Abstract
Nonoptimal gestational durations could be associated with neurodevelopmental disabilities, yet evidence regarding finer classification of gestational age and rates of multiple major neuropsychiatric disorders beyond childhood is limited. To comprehensively evaluate associations between 6 gestational age groups and rates of 9 major types and 8 subtypes of childhood and adult-onset neuropsychiatric disorders. This cohort study evaluated data from a nationwide register of singleton births in Denmark from January 1, 1978, to December 31, 2016. Data analyses were conducted from October 1, 2019, through November 15, 2020. Gestational age subgroups were classified according to data from the Danish Medical Birth Register: very preterm (20-31 completed weeks), moderately preterm (32-33 completed weeks), late preterm (34-36 completed weeks), early term (37-38 completed weeks), term (39-40 completed weeks, reference), and late or postterm (41-45 completed weeks). Neuropsychiatric diagnostic records (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes F00-F99) were ascertained from the Danish Psychiatric Central Register up to August 10, 2017. Poisson regression was used to estimate the incidence rate ratio (IRR) and 95% CI for neuropsychiatric disorders, adjusting for selected sociodemographic factors. Of all 2 327 639 singleton births studied (1 194 925 male newborns [51.3%]), 22 647 (1.0%) were born very preterm, 19 801 (0.9%) were born moderately preterm, 99 488 (4.3%) were born late preterm, 388 416 (16.7%) were born early term, 1 198 605 (51.5%) were born at term, and 598 682 (25.7%) were born late or postterm. A gradient of decreasing IRRs was found from very preterm to late preterm for having any or each of the 9 neuropsychiatric disorders (eg, very preterm: IRR, 1.49 [95% CI, 1.43-1.55]; moderately preterm: IRR, 1.23 [95% CI, 1.18-1.28]; late preterm: IRR, 1.17 [95% CI, 1.14-1.19] for any disorders) compared with term births. Individuals born early term had 7% higher rates (IRR, 1.07 [95% CI, 1.06-1.08]) for any neuropsychiatric diagnosis and a 31% higher rate for intellectual disability (IRR, 1.31 [95% CI, 1.25-1.37]) compared with those born at term. The late or postterm group had lower IRRs for most disorders, except pervasive developmental disorders, for which the rate was higher for postterm births compared with term births (IRR, 1.06 [95% CI, 1.03-1.09]). Higher incidences of all major neuropsychiatric disorders were observed across the spectrum of preterm births. Early term and late or postterm births might not share a homogeneous low risk with individuals born at term. These findings suggest that interventions that address perinatal factors associated with nonoptimal gestation might reduce long-term neuropsychiatric risks in the population.
Highlights
Gestation is a critical period for brain growth and development.[1,2] Nonoptimal gestational duration might have lifelong health consequences, including neurodevelopmental impairments and psychiatric morbidities.[1,3] Most epidemiological studies[4,5,6,7,8] that have found an association between gestational age and neuropsychiatric outcomes have quantified risks according to dichotomous classification of gestational measures using the 37-week cutoff as a marker of maturity
A gradient of decreasing incidence rate ratio (IRR) was found from very preterm to late preterm for having any or each of the 9 neuropsychiatric disorders compared with term births
Individuals born early term had 7% higher rates (IRR, 1.07 [95% CI, 1.06-1.08]) for any neuropsychiatric diagnosis and a 31% higher rate for intellectual disability (IRR, 1.31 [95% CI, 1.25-1.37]) compared with those born at term
Summary
Gestation is a critical period for brain growth and development.[1,2] Nonoptimal gestational duration might have lifelong health consequences, including neurodevelopmental impairments and psychiatric morbidities.[1,3] Most epidemiological studies[4,5,6,7,8] that have found an association between gestational age and neuropsychiatric outcomes have quantified risks according to dichotomous classification of gestational measures using the 37-week cutoff as a marker of maturity. The associations between the whole range of gestational age, considering the possible heterogeneity within gestational age groups before and after the cutoff, and multiple neuropsychiatric diseases in childhood and adulthood are less studied. Children born within 37 to 41 weeks of gestation have traditionally been considered as a homogeneous, low-risk group,[13] but emerging evidence has indicated that children born at early term (37-38 weeks) had poorer cognitive outcomes,[14] lower educational achievement,[15] and higher rates of mortality[16] compared with those born at 39 through 41 weeks of gestation. Some associations between postterm pregnancy (>42 weeks) and neurobehavioral[17] or mental health disorders[18] have been suggested, yet evidence remains inconclusive
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