Perinatal mortality according to birth weight has an inverse J-pattern. Our aim was to estimate the influence of familial factors on this pattern, applying a cohort sibling design. We focused on excess mortality among macrosomic infants (>2 SD above the mean) and hypothesized that the birth weight-mortality association could be explained by confounding shared family factors. We also estimated how the participant's deviation from mean sibling birth weight influenced the association.
We included 1 925 929 singletons, born term or post-term to mothers with more than one delivery 1967-2011 registered in the Medical Birth Registry of Norway. We examined z-score birth weight and perinatal mortality in random-effects and sibling fixed-effects logistic regression models including measured confounders (e.g. maternal diabetes) as well as unmeasured shared family confounders (through fixed effects models). Birth weight-specific mortality showed an inverse J-pattern, being lowest (2.0 per 1000) at reference weight (z-score +1 to +2) and increasing for higher weights. Mortality in the highest weight category was 15-fold higher than reference. This pattern changed little in multivariable models. Deviance from mean sibling birth weight modified the mortality pattern across the birth weight spectrum: small and medium-sized infants had increased mortality when being smaller than their siblings, and large-sized infants had an increased risk when outweighing their siblings. Maternal diabetes and birth weight acted in a synergistic fashion with mortality among macrosomic infants in diabetic pregnancies in excess of what would be expected for additive effects.
The inverse J-pattern between birth weight and mortality is not explained by measured confounders or unmeasured shared family factors. Infants are at particularly high mortality risk when their birth weight deviates substantially from their siblings. Sensitivity analysis suggests that characteristics related to maternal diabetes could be important in explaining the increased mortality among macrosomic infants.
Notes
Cites: Stat Med. 2003 Aug 30;22(16):2591-60212898546
Cites: Epidemiology. 2003 Jul;14(4):490-212843776
Cites: Eur J Epidemiol. 2008;23(3):163-618224448
Cites: BMJ. 1997 May 10;314(7091):1376-809161309
Cites: Pediatrics. 2011 Jul;128(1):177-8121708807
Cites: Am J Epidemiol. 2006 Aug 15;164(4):312-4; discussion 315-616847041
Cites: Ann Hum Genet. 1969 Jul;33(1):71-95387613
Cites: N Engl J Med. 2005 Jun 16;352(24):2477-8615951574
Cites: BMC Pregnancy Childbirth. 2007 Nov 28;7:2818045458
Cites: N Engl J Med. 2009 Oct 1;361(14):1339-4819797280
Cites: BMC Pregnancy Childbirth. 2012 Mar 31;12:2322462760