Within-Family Analysis of Interpregnancy Interval and Adverse Birth Outcomes [1G]

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We examined the associations between interpregnancy interval, the duration from the preceding birth to the conception of the next-born index child, and adverse birth outcomes using designs that adjust for measured and unmeasured factors.


We used population-based Swedish registries to study a prospective cohort of children born 1973 to 2009 (n=1,418,820) to estimate the associations between interpregnancy interval and adverse birth outcomes. Analyses included cousin- and sibling-comparisons and postbirth intervals (i.e., the interval between second- and third-born offspring predicting second-born outcomes) to address unmeasured familial confounding.


Traditional cohort-wide analyses showed higher odds of preterm birth (PTB) [adjusted odds ratio (aOR) 1.51, 99% CI 1.39-1.63] and low birth weight (LBW; aOR 1.25, 99% CI 1.13-1.39) after short interpregnancy interval (0 to 5 months) compared to offspring born after an interpregnancy interval of 18 to 23 months. Except for PTB (aOR 1.72, 99% CI 1.26-2.35), associations were attenuated in cousin- and sibling-comparisons. For interpregnancy intervals of 60 months or more, odds of PTB (aOR 1.51, 99% CI 1.43-1.60), LBW (aOR 1.61, 99% CI 1.50-1.73), and SGA (aOR 1.54, 99% CI=1.42-1.66) were higher when compared with the reference interval. Associations between long interpregnancy interval and adverse birth outcomes, however, remained through cousin- and sibling-comparisons. Postbirth interval analyses showed familial confounding is present for short interpregnancy intervals, but supported independent associations for long interpregnancy intervals.


Familial confounding explains most of the association between short interpregnancy interval and adverse birth outcomes, while associations with long interpregnancy intervals were independent of measured and unmeasured factors.

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