Mitchell, Allen A.
From the Boston University Slone Epidemiology Center, Boston, MA.
Address correspondence to: Allen A. Mitchell Boston University Slone Epidemiology Center, 1010 Commonwealth Ave., Boston, MA 02118. E-mail: firstname.lastname@example.org.
Pediatricians-in-training, if they are lucky, may palpate the “olive” (pyloric tumor) in a weeks-old infant who presents with projectile vomiting. Along with the right history, that physical finding is diagnostic, and after relatively simple surgery, the infant's parents can be reassured that all will be well. Although the diagnosis and treatment of this condition may be quite clear, its etiology remains a mystery. In his doctoral thesis published in 1952, Brian MacMahon focused attention on the epidemiology of pyloric stenosis; we are fortunate that, after a hiatus of 5 decades during which he became a leading and revered epidemiologist, he has revisited the topic, providing a comprehensive summary of the state of our knowledge and our ignorance about this serious but reparable condition.1
Although some might quibble with a point here and there (eg, I think there is good evidence supporting an etiologic role of erythromycin exposure in the first weeks of life), Dr. MacMahon's broad argument is critically important: accumulating data suggest that, at least in part, pyloric stenosis may be a disease of modern Western civilization, and, more particularly, our preference over past decades to place infants to sleep on their stomachs. This suggestion did not come from a prespecified biologically based hypothesis, but rather from observations made by Danish and Swedish researchers, who were struck by recent, unexpected, and very dramatic declines in the incidence of pyloric stenosis. These declines, they observed, coincided with recommendations in the early 1990s that were intended to reduce the rate of sudden infant death syndrome (SIDS) by changing infants’ sleep position from prone to supine.
The notion of reducing SIDS risk by the “back-to-sleep” intervention was not based on biologic understanding of SIDS etiology or even a biologic hypothesis. Instead, as was true for pyloric stenosis, it flowed from epidemiologic observations. Indeed, the apparent effectiveness of this intervention with respect to SIDS has prompted formulation of biologic theories to explain why prone sleep position may increase SIDS risk. So once again, an epidemiologic observation may guide us to biologic understanding.
However, for pyloric stenosis, how can the strong associations with family history, infant sex, and birth order be reconciled with sleep position as a risk factor? As Dr. MacMahon argues, family history can suggest genetic causes, but choice of sleep position also tracks in “families,” whether these families are nuclear or racial/ethnic. Male sex is of course genetic, raising the possibility of a gene–environment interaction. The birth-order effect is distinctly puzzling; if there is an environmental explanation for it, are we raising the possibility of an “environment–environment” interaction? For all these factors, one could argue that the disease occurs when one or more underlying risk factors (genetic or environmental) are “expressed” in the presence of the environmental trigger of prone sleep position.
We clearly should support Dr. MacMahon's call to explore whether the risks of pyloric stenosis and SIDS are both affected by sleep position. This research should consider, in addition, the possible etiologic role(s) of other behavioral and environmental factors that have also changed in recent years; in some countries, for example, secular changes in sleep position occurred at roughly the same time as increases in exposure to folic acid early in pregnancy. Further epidemiologic study will undoubtedly bear fruit that will help explain the olive's etiology. As a positive application of the “law of unintended consequences,” how welcome it would be if an intervention designed to reduce SIDS rates had the unexpected effect of reducing rates of pyloric stenosis at the same time!
ABOUT THE AUTHOR
ALLEN A. MITCHELL is Professor of Epidemiology and Pediatrics at Boston University Schools of Public Health and Medicine and Director of the Slone Epidemiology Center at Boston University. Since 1976, he has directed a case–control surveillance study of birth defects in relation to medication exposures; recently, he has also studied the safety of pediatric ibuprofen and evaluated risk management programs associated with isotretinoin and thalidomide.
1. MacMahon B. The continuing enigma of pyloric stenosis of infancy: a review. Epidemiology
© 2006 Lippincott Williams & Wilkins, Inc.