Analyzing retrospective data with time-varying exposure: a cautionary tale of H2 blockers in ELBW neonates

The objective of our study was to alert researchers to potential pitfalls involved in analysis of a potential association between risk factors and development of disease. We applied three different analytic methods -- retrospective cohort study analyzed using logistic regression, case-control analysis, and survival analysis with time-dependent exposure -- to retrospective data showing a correlation between histamine 2 (H(2)) blocker exposure and the occurrence of necrotizing enterocolitis in extremely low birthweight neonates. Using case-control and survival analysis methods, there was an apparent increase in necrotizing enterocolitis following exposure to H(2) blocker treatment. The retrospective cohort method led to the opposite conclusion because it failed to account appropriately for exposure. We concluded that the choice of the analytic methodology used in a retrospective study is critical and should take into account the timing and characteristics of the risk factors and condition under investigation. Erroneous conclusions may be reached if inappropriate statistical methods are used.