Crossing Birthweight-Specific Mortality Curves: How a Puzzling Clinical Observation Led to an Important Advance in Epidemiologic Methods.

Abstract

Clinicians have long noted that although African-American neonates were more likely than white neonates to weigh <2500 grams at birth (low birthweight), among low birthweight infants African-Americans were more likely than whites to survive. However when born at normal weight, African-American infants were substantially less likely to survive. The observation generated much physiological speculation, and several clever mathematical manipulations were devised to "uncross the mortality curves." With the development and dissemination of Directed Acyclic Graphs in the early 2000s, methodologists focused on perinatal epidemiology showed graphically, in an early use of Directed Acyclic Graphs, that birthweight was a "collider", and that controlling for birthweight, whether by regression, stratification or restriction, introduced confounding of the race-mortality association by all unmeasured common causes of birthweight and mortality. These investigations showed that the crossing curves could be explained as an artifact of a conceptually flawed analysis. These results have applicability beyond perinatal epidemiology, including to the "obesity paradox."