This is a literature review of recent journal articles published between the years 1994 and 2000. These researchers were on a mission to discover new ways to help identify children at risk for infantile hypertrophic pyloric stenosis (IHPS). The information assembled, combined with several case study reviews, reveals multiple new findings that can improve the detection of IHPS.
     IHPS is an occurrence in which the pyloric muscle, located between the pyloric par of the stomach and the duodenum, becomes hypertrophied (figure 1).¹ By and large it is a genetically influenced condition² that presents in infants usually between the ages of 3 and 6 weeks. However, it is rare to find an occurrence after 3 months. IHPS arises in males more often than

females (3-6:1). Reportedly, this condition appears in 3 of 1000 live births. 3      Symptoms that will present clinically will consist of   repeated non-bilious vomiting (sometimes described as projectile). Other conditions may be the primary reason for this. They include "chalasia, preampullary duodenal stenosis, or reversible pylorospasm."      In 1977, Teele and Smith documented the use of ultrasound to medically evaluate this condition. Although ultrasound has not yet been established or entirely accepted as the initiating modality of choice for detection of IHPS, it has been recognized in radiologic literature as such. 2      Recently, there have been multiple new findings

6 Figure 1- The pyloris muscle enlarges and creates a pyloric stenosis.

regarding IHPS. They involve: 1) the condition of the mandibular frenulum, 2) use of erythromycin during early infancy, 3) gallbladder location with regards to positive IHPS, and 4) accuracy of ultrasound in an infant with a non-palpable "olive".

In a recent study, clinical information was taken from 25 IHPS patients and 319 control infants without IHPS to ascertain if an infant would be more likely to have IHPS depending on the status of their mandibular frenulum (figure 2). The MF is the thin fold of membrane that connects the lower anterior gum-line to the inner portion of the lower lip. None of the study subjects had any "major congenital malformations, chromosomal any "major congenital malformations, chromosomal disorders, or

Figure 2 – A, a normal mandibular frenulum (arrow) with normal musocal attachment (arrowhead). B, a hypoplastic mandibular frenulum with secondary mucosal folds (arrowhead)3

recognizable syndromes."  Each of the infants were examined by two different clinicians, each unknowing of the other’s findings. The infants were then categorized into three groups: those who were found to have a normal MF, those who were found to have a hypoplastic MF, and those who were found to have an absent MF.      Twenty-three out of 25 of the infants with IHPS and 5 out of 319 control patients were found to have a hypoplastic or

absent MF. This result had a sensitivity of 92% and a specificity of 98.4%. It revealed that MF hypoplasia or agenesis is a common factor and clinically significant in the prediction of IHPS. It also was shown an indicator for infants who are high-risk candidates for IHPS.³

Another discovery has been made pertaining to the administration of erythromycin to young infants. The first reports of cases linking erythromycin and IHPS began in 1976. However, multiple factors prevented validation of the study. One important factor was the incomplete comparison between the current IHPS infants and previous infantile cases of IHPS. Without proper comparison studies, these studies could not be confirmed or denied. ⁵
     In March 1999 in Knoxville, Tennessee another incidence of erythromycin and IHPS was reported. ⁴ Earlier, in January and February 1999, an epidemic of pertusis among approximately 200 neonates broke out in a local community hospital, and erythromycin was prescribed. Among those given erythromycin, seven were diagnosed with IHPS. Among those not given the drug, no cases of IHPS were diagnosed.
     The seven IHPS cases had an age range of 2 to 17 days when they were first prescribed erythromycin for their pertusis. They continued to take the prescriptions for 10 to 18 days. "Compared with historical cases, index case-patients were younger at the time of admission for IHPS and were less likely to have a family history of IHPS."
     Previous studies of IHPS have not included erythromycin as a risk factor, probably because not many neonates included in these studies were actually administered the drug. Prior use of erythromycin in the treatment for infantile pertussis had been small, and thus a connection between erythromycin and IHPS had not been established. With these new findings, parents should be informed of an increased risk of IHPS if their newborns are prescribed erythromycin. ⁵

In most normal anatomy, the duodenum and gallbladder are contiguous, while the pylorus is located just posterior to the pancreas and anterior to the left lobe of the liver. In infants diagnosed with IHPS, it has been noted that the duodenum is displaced by the elongated pylorus. This causes the gallbladder to be located adjacent to and above the pylorus. This conclusion helps sonographers to locate the abnormal pylorus in an uncooperative patient.

Figure 3- Pylorus in longitudinal view in a hypertrophic pyloric stenosis patient. The gallbladder is adjacent to the thickened and elongated pylorus muscle.7

A recent review of discharged patients from UCSF (Moffit Hospital) revealed 21 IHPS patients with ages ranging from 10 to 392 days. Of these 21 cases, 11 had undergone ultrasound examination. However, only 10 of the 11 films could be located. In each of these IHPS cases, the ultrasound images demonstrated the location of the gallbladder as adjacent to and above the pylorus.      An additional review was taken of 100 ulatrasound cases from Children’s Hospital, Boston. These were evaluated for the relative positions of the pylorus and the gallbladder. Thirteen cases were found to have the pylorus adjacent to and beneath the gallbladder. Twelve were positive for IHPS, and 1 were found to have a destended stomach.      In conclusion, there were a total of 22 positive cases and 1 false negative case that was found to have the pylorus

"located beneath the gallbladder but not immediately adjacent to it." This shows that "finding the pylorus subajacent to the gallbladder indicated, in the majority of cases, that the pylorus is enlarged." An overdestended stomach, however, can produce false negative results.⁷

Since it was first used to evaluate pyloric stenosis in 1977, ultrasound has been found to be highly accurate in the diagnosis of IHPS. Clinical diagnosis of IHPS is a positive identification of a palpable olive in the right upper quadrant of a nonbilious vomiting infant. Ultrasound is shown to be a valuable instrument in the examination of infants who present with nonbilious vomiting and a non-palpable olive.
     In a recent review, 152 infants without a plapable olive were referred for ultrasound examination. Sixty-six of the 152 infants were positively diagnosed with IHPS. These results were confirmed at surgery. None of the exams were proven to be false positives. Seventy-seven of the 152 infants were negative for IHPS. Forty-seven of these were referred for further testing to rule-out or confirm reflux, of which 39 were positive for reflux. In the remaining 7 infants, ultrasound detected an early, evolving pyloric stenosis. These infants continued under observation and pyloric stenosis did not develop.
     Although clinical palpation has been the diagnosing factor for IHPS for decades, ultrasound has been proven an accurate, non-invasive, cost-effective method of diagnosis when clinical methods are exhausted. (Infants without a palpable olive and infants that are crying and moving can be difficult to palpate clinically.) Even with the difficult patient, ultrasound is proven to be a valuable instrument in the diagnosis of IHPS.²

IHPS occurs in 3 of 1000 live birth, usually presenting in male infants ages 3 to 6 weeks. Previous known risk factors included familial history and occurrence in males more often than females (3-6:1). Recently, multipla new findings have improved the detection of this occurrence. One finding, the clinical discovery of a hypoplastic or absent mandibular fibululm, has been added as a common and significant factor for predicting possible IHPS cases. ³ Another important finding is an increased risk of IHPS with the use of erythromycin during early infancy (2 to 7 days) for a prolonged period of time (10 to 18 days). ¹ A third new finding is the location of the gallbladder in relation to the pylorus muscle. In an infant with IHPS, the gallbladder will be seen adjacent to and above the pylorus. However, an infant with an overdestended stomach can produce false negative results.⁷
     As we look into the future, others will most assuredly discover new risk factors to help detect IHPS. As for now, studies on the progress and circumstances surrounding previous IHPS cases have already begun to help us to identify and treat new cases.

1. Patterson, L MD, et al: Hypertrophic Pyloric Stenosis in Infants Following Pertussis Prophylaxis With Erythromycin – Knoxville, Tennessee, 1999. JAMA 283: 471-472, 2000.
2. Hernanz-Schulman, Marta MD, et al: Hypertrophic Pyloric Stenosis in the Infant without a Palpable Olive: Accuracy of Sonographic Diagnosis. Radiology 193: 771-776, 1994.
3. DeFelice, Claudio MD, et al: Hypoplastic or absent mandibular frenulum: A new predictive sign of infantile hypertrophic pyloric stenosis. J Pediatr 136: 408-409, 2000.
4. Hoey, John: Hypertrophic pyloric stenosis caused by erythromycin. CMAJ 162:1198, 2000.
5. Erickson, J.D.: Infantile hypertrophic pyloric stenosis after pertussis prophylaxis with erythromycin: a case review and cohort study. (Statistical Data Included). Lancet Dec 18, 1999: 9.
6. Illustration taken from www.adam.com
7. Levine, Deborah MD, et al : Pylorus Subajacent to the Gallbladder : An additional Finding in Hypertrophic Pyloric Stenosis. J Clin Ultrasound 23: 425-428, 1995.