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Rates of Neuropsychiatric Disorders and Gestational Age at Birth in a Danish Population
Yuntian Xia1, Jingyuan Xiao1,2, Yongfu Yu3,4
1Yale Center for Perinatal, Pediatric, and Environmental Epidemiology, Yale School of Public Health, New Haven, Connecticut.
Insights
Preterm birth is linked to higher risks of neuropsychiatric disorders. Early term and postterm births may also carry increased risks, suggesting interventions for nonoptimal gestation could reduce long-term neurodevelopmental issues.
Area of Science:
- Neuroscience
- Psychiatry
- Public Health
Background:
- Nonoptimal gestational durations are suspected to increase neurodevelopmental disability risks.
- Limited evidence exists on the association between specific gestational age classifications and the rates of major neuropsychiatric disorders throughout life.
Purpose of the Study:
- To investigate the relationship between six distinct gestational age groups and the incidence of nine major neuropsychiatric disorders and eight subtypes.
- To analyze both childhood and adult-onset neuropsychiatric conditions in relation to gestational age.
Main Methods:
- A nationwide cohort study utilizing Danish singleton birth records from 1978 to 2016.
- Gestational age was categorized into: very preterm (20-31 weeks), moderately preterm (32-33 weeks), late preterm (34-36 weeks), early term (37-38 weeks), term (39-40 weeks), and late/postterm (41-45 weeks).
- Neuropsychiatric diagnoses were extracted from the Danish Psychiatric Central Register, with Poisson regression used to calculate incidence rate ratios (IRRs), adjusting for sociodemographic factors.
Main Results:
- A dose-response relationship was observed, with significantly higher IRRs for neuropsychiatric disorders in very preterm, moderately preterm, and late preterm infants compared to term infants.
- Early term births showed a 7% increased rate of any neuropsychiatric diagnosis and a 31% increase for intellectual disability.
- Late or postterm births had lower rates for most disorders, but a higher rate for pervasive developmental disorders.
Conclusions:
- Preterm birth is associated with increased incidence of major neuropsychiatric disorders across the spectrum.
- Early term and late/postterm births may not have the same low risk profile as term births.
- Interventions targeting perinatal factors related to nonoptimal gestation could potentially mitigate long-term neuropsychiatric risks.
Importance:
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.
Objective:
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.
Design, Setting, And Participants:
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.
Exposures:
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).
Main Outcomes And Measures:
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.
Results:
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]).
Conclusions And Relevance:
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.
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