RT Journal Article
SR Electronic
T1 Gestational age at birth and risk of intellectual disability without a common genetic cause: findings from the Stockholm Youth Cohort
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 129049
DO 10.1101/129049
A1 Heuvelman, Hein
A1 Abel, Kathryn
A1 Wicks, Susanne
A1 Gardner, Renee
A1 Johnstone, Edward
A1 Lee, Brian
A1 Magnusson, Cecilia
A1 Dalman, Christina
A1 Rai, Dheeraj
YR 2017
UL http://biorxiv.org/content/early/2017/04/24/129049.abstract
AB 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 OR24 weeks=14.54 [95% CI 11.46–18.44]), lessening with advancing gestational age toward term (aOR32 weeks=3.59 [3.22–4.01]; aOR37 weeks=1.50 [1.38–1.63]); aOR38 weeks=1.26 [1.16-1.37]; aOR39 weeks=1.10 [1.04-1.17]) and increasing with advancing gestational age post-term (aOR42 weeks=1.16 [1.08–1.25]; aOR42 weeks=1.41 [1.21–1.64]; aOR44 weeks=1.71 [1.34–2.18]; aOR45 weeks=2.07 [1.47–2.92]). 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 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 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.