High Birth Prevalence Rates for Congenital Anomalies in South American Regions

© 2015 Wolters Kluwer Health, Inc. All rights reserved. www.epidem.com | e53 exists between confounding bias reduction and increased bias and variance due to nonpositivity.4 to investigate this trade-off weights were progressively truncated for each method, and as levels of weight truncation increased, the marginal structural model effect estimates became more similar to the estimate from ordinary adjustment for timevarying covariates (table). the detailed analysis is presented in the eAppendix (http://links.lww.com/eDe/A939). to assess the relation between weight truncation and confounder imbalance, the inverse probability weights were used to fit a weighted exposure model with the R2 expected to be approximately zero.5 to find the level of truncation leading to a minimal confounder imbalance (lowest R2), this analysis was repeated for different levels of weight truncation. the normal exposure model (before weighting) had a R2 of 0.51, while refitting this exposure model with untruncated weights resulted in an increased R2 of 0.54. this indicates that untruncated weights from the normal model increased confounder imbalance. For the normal inverse probability weighted model, the minimum imbalance was observed at 4% truncation (R2 = 0.124). this indicates that there is still an association between confounders and exposure after weighting which may be due to exposure model misspecification. Noting the level of imbalance estimated by the weighted exposure model only quantifies imbalance with respect to that particular specification and distributional form of the exposure model, methods to assess balance with respect to separate confounders could be used.6 Despite large differences in weight distributions between methods for obtaining inverse probability weighting for continuous exposures, different methods yielded similar exposure–outcome effect estimates. However, these results should be interpreted cautiously since large untruncated weights, and remaining imbalance after truncation, suggest that nonpositivity (possibly with respect to a combination of confounders) may invalidate estimates. ACKNOWLEDGMENTS The authors thank P. M. C. Klein Klouwenberg, MD, PharmD, and W. Pasma, DVM, Department of Intensive Care Medicine, University Medical Centre Utrecht, Utrecht, The Netherlands, for their support and assistance in data acquisition and data management.