Gestational age at birth and risk of intellectual disability without a common genetic cause

Hein Heuvelman, Kathryn Abel, Susanne Wicks, Renee Gardner, Edward Johnstone, Brian Lee, Cecilia Magnusson, Christina Dalman, Dheeraj Rai

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

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. We therefore 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. 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 outcome-discordant siblings (n = 8034). Risk of intellectual disability was greatest among those born extremely early (adjusted OR 24 weeks  = 14.54 [95% CI 11.46–18.44]), lessening with advancing gestational age toward term (aOR 32 weeks  = 3.59 [3.22–4.01]; aOR 37 weeks  = 1.50 [1.38–1.63]); aOR 38 weeks  = 1.26 [1.16–1.37]; aOR 39 weeks = 1.10 [1.04–1.17]) and increasing with advancing gestational age post-term (aOR 42 weeks  = 1.16 [1.08–1.25]; aOR 43 weeks  = 1.41 [1.21–1.64]; aOR 44 weeks  = 1.71 [1.34–2.18]; aOR 45 weeks  = 2.07 [1.47–2.92]). Associations persisted in a cohort of matched siblings suggesting they were robust against confounding by shared familial traits. Risk of intellectual disability was greatest among children showing evidence of fetal growth restriction, especially when birth occurred before or after term. Birth at non-optimal gestational duration may be linked causally with greater risk of intellectual disability. The mechanisms underlying these associations need to be elucidated as they are relevant to clinical practice concerning elective delivery around term and mitigation of risk in post-term children.

Original languageEnglish
Pages (from-to)667-678
Number of pages12
JournalEuropean Journal of Epidemiology
Volume33
Issue number7
DOIs
StatePublished - 1 Jul 2018
Externally publishedYes

Keywords

  • Gestational age
  • Intellectual disability
  • Post-term birth
  • Regression splines
  • Siblings
  • Stockholm Youth Cohort

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