Studies examining total gestational weight gain (GWG) and outcomes associated with gestational age (GA) are potentially biased. The z-score has been proposed to mitigate this bias. We evaluated a regression-based adjustment for GA to remove the correlation between GWG and GA, and compared it to published weight-gain-for-gestational-age z-scores when applied to a study sample with different underlying population characteristics.Methods:
Using 65 643 singleton deliveries to normal weight women at 12 US clinical sites, we simulated a null association between GWG and neonatal mortality. Logistic regression was used to estimate approximate relative risks (RR) of neonatal mortality associated with GWG, unadjusted and adjusted for GA, and the z-score, overall and within study sites. Average RRs across 5000 replicates were calculated with 95% coverage probability to indicate model bias and precision, where 95% is nominal.Results:
Under a simulated null association, total GWG resulted in a biased mortality estimate (RR = 0.87; coverage = 0%); estimates adjusted for GA were unbiased (RR = 1.00; coverage = 94%). Quintile-specific RRs ranged from 0.97–1.03. Similar results were observed for site-specific analyses. The overall z-score RR was 0.97 (84% coverage) with quintile-specific RRs ranging from 0.64–0.90. Estimates were close to 1.0 at most sites, with coverage from 70–94%. Sites 1 and 6 were biased with RRs of 0.66 and 1.43, respectively, and coverage of 70% and 80%.Conclusions:
Adjusting for GA achieves unbiased estimates of the association between total GWG and neonatal mortality, providing an accessible alternative to the weight-gain-for-gestational-age z-scores without requiring assumptions concerning underlying population characteristics.