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Gestational Age At Birth And Risk Of Intellectual Disability Without A Common Genetic Cause: Findings From The Stockholm Youth Cohort
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Gestational Age At Birth And Risk Of Intellectual Disability Without A Common Genetic Cause: Findings From The Stockholm Youth Cohort

Hein Heuvelman, Kathryn Abel, Susanne Wicks, Renee Gardner, Edward Johnstone, Brian Lee, Cecilia Magnusson, Christina Dalman and Dheeraj Rai
bioRxiv
24 Apr 2017
DOI: https://doi.org/10.1101/129049
url
https://doi.org/10.1101/129049View
Published, Version of Record (VoR)CC BY V4.0,  Open

Abstract

Age Birth Children Fetuses Gestational age Intellectual disabilities Population studies Premature birth Siblings
Background: Preterm birth is linked to intellectual disability and there is evidence to suggest post-term birth may also incur risk. However, these associations have not yet been investigated in the absence of common genetic causes of intellectual disability (where risk associated with late delivery may be preventable) or with methods allowing stronger causal inference from non-experimental data. We aimed to examine risk of intellectual disability without a common genetic cause across the entire range of gestation, using a matched-sibling design to account for unmeasured confounding by shared familial factors. Methods and Findings: We conducted a population-based retrospective study using data from the Stockholm Youth Cohort (n=499,621) and examined associations in a nested cohort of matched siblings (n=8,034). Children born at non-optimal gestational duration (before/after 40 weeks 3 days) were at greater risk of intellectual disability. Risk was greatest among those born extremely early (adjusted OR 24 weeks=14.54 [95% CI 11.46 to 18.44]), lessening with advancing gestational age toward term (aOR 32 weeks=3.59 [3.22 to 4.01]; aOR 37 weeks=1.50 [1.38 to 1.63]); aOR 38 weeks=1.26 [1.16 to 1.37]; aOR 39 weeks=1.10 [1.04 to 1.17]) and increasing with advancing gestational age post-term (aOR 42 weeks=1.16 [1.08 to 1.25]; aOR 42 weeks=1.41 [1.21 to 1.64]; aOR 44 weeks=1.71 [1.34 to 2.18]; aOR 45 weeks=2.07 [1.47 to 2.92]). Associations persisted in a nested cohort of matched outcome-discordant siblings suggesting they were robust against confounding from shared genetic or environmental traits, although there may have been residual confounding by unobserved non-shared characteristics. Risk of intellectual disability was greatest among children showing evidence of fetal growth restriction, especially when birth occurred before or after term. Conclusions: Birth at nonoptimal gestational duration may be linked causally with greater risk of intellectual disability. The mechanisms underlying these associations need to be elucidated as they will be relevant to clinical practice concerning elective delivery within the term period and the mitigation of risk in children who are born post-term.

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