Infantile Pyloric Stenosis: Associated with Low Plasma Lipids

Bjarke Feenstra, Ph.D. Senior Research Scientist Statens Serum Institut Artillerivej 5, 2300 Copenhagen S Interview with:
Bjarke Feenstra, Ph.D.
Senior Research Scientist
Statens Serum Institut
Artillerivej 5, 2300 Copenhagen S
Denmark What are the main findings of the study?

Dr. Feenstra: We discovered a new genome-wide significant locus for infantile hypertrophic pyloric stenosis (IHPS) in a region on chromosome 11 harboring the apolipoprotein (APOA1/C3/A4/A5) gene cluster and also confirmed three previously reported loci. Characteristics of the new locus led us to propose the hypothesis that low levels of circulating lipids in infants are associated with increased risk of IHPS. We addressed this hypothesis by measuring plasma lipid levels in prospectively collected umbilical cord blood from a set of 46 IHPS cases and 189 matched controls. We found that levels were on average somewhat lower in the children who went on to develop the condition. Were any of the findings unexpected?

Dr. Feenstra: Yes, in the discovery phase of the study, we used a hypothesis-free approach to search the genome for variants associated with pyloric stenosis. Rather than focusing on specific candidate genes, we wanted to be able to discover unexpected connections. However, the association between low lipid levels and increased risk of the disease is consistent with a number of previous epidemiological findings.

•    Boys have four-fold higher risk of pyloric stenosis compared to girls, and their cholesterol levels are on average lower than levels in girls at birth.
•    Bottle-fed babies have higher risk of pyloric stenosis, and bottle-feeding is known to be associated with lower levels of circulating cholesterol.
•    Pyloric stenosis incidence dropped in several countries in the 1990s while breast feeding incidence (and thereby average lipid levels in infants) increased.
•    Pyloric stenosis is a prominent clinical feature in many reports of Smith-Lemli-Opitz syndrome, a rare inborn defect of cholesterol biosynthesis associated with low cholesterol levels in infants at birth. What should clinicians and patients take away from your report?

Dr. Feenstra: We must caution that further study is needed to determine whether our findings represent a causal link between cholesterol levels and risk of IHPS. If, however, that proves to be the case, it would be highly interesting to investigate whether dietary modifications to ensure normal lipid levels might protect newborns in families with a history of IHPS from developing the condition. What recommendations do you have for future research as a result of this study?

Dr. Feenstra: I think it would be really interesting to better understand the interplay between lipid metabolism and other genetic and environmental risk factors for IHPS. Which combination of risk factors is required for the condition to occur? Further study is clearly also needed to shed light on the biological mechanisms underlying our findings. One approach that might be revealing would focus on the essential role of cholesterol in nervous system development given the deficiencies in enteric innervation seen in pyloric sphincter muscle tissue from patients with IHPS.


Feenstra B, et al “Plasma lipids, genetic variants near APOA1, and the risk of infantile hypertrophic pyloric stenosis” JAMA 2013; 310(7): 714-721.