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

ABSTRACT

Throughout the second half of the 20th century, clinicians noted that although African-American neonates were more likely than White neonates to weigh less than 2,500 g at birth (low birth weight), among low-birth-weight 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 focusing on perinatal epidemiology showed graphically, in an early use of directed acyclic graphs, that birth weight was a "collider" and that controlling for birth weight, whether by regression, stratification, or restriction, introduced confounding of the race-mortality association by all unmeasured common causes of birth weight 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 applicability to the "obesity paradox."