Pyloric stenosis affects males more commonly than females, with firstborn males affected about four times as often, and there is a genetic predisposition for the disease. It is commonly associated with people of Jewish ancestry. Pyloric stenosis is more common in whites than Hispanics, African Americans, or Asians. The incidence is 2.4 per 1000 live births in whites, 1.8 in Hispanics, 0.7 in African Americans, and 0.6 in Asians. It is also less common amongst children of mixed race parents. Caucasian babies with blood type B or O are more likely than other types to be affected.
Some scientists believe that babies with pyloric stenosis lack receptors in the pyloric muscle that detect nitric oxide, a chemical in the body that tells the pylorus muscle to relax. As a result, the muscle is in a state of contraction almost continually, which causes it to become larger and thicker over time. It may take some time for this thickening to occur, which is why pyloric stenosis usually appears in babies a few weeks after birth.