Evidence that intrauterine and postnatal androgens affect the development of pyloric stenosis.

BACKGROUND: It is rather well established that the causal antecedents of pyloric stenosis (PS) contain both genetic and environmental factors. However, in spite of substantial quantities of epidemiological data, no widespread environmental causal agent has yet been established. There have been recent extensions of our knowledge of the endocrine consequences of fetal growth restriction and of the endocrine determinants of sex ratio. It seemed worth reviewing the epidemiological data on PS in the light of these new developments to see whether this would provide a basis for a plausible hypothesis on these suspected environmental causes of PS. METHODS AND RESULTS: The search terms "pyloric stenosis" and ("epidemiology" or "risk factors") were combined on the Ovid Medline data base for the years 1966 onwards. The data from the resulting papers were augmented by notes occasioned by almost daily reading at the Library of the Royal Society of Medicine (London) for the past 25 years. (Electronic data retrieval systems do not access incidentally recorded data such as sib sex ratios). CONCLUSIONS: It is hypothesized that high intrauterine and early postnatal androgen levels constitute an environmental cause of PS.

Fetal gastric size in normal and abnormal pregnancies.

OBJECTIVE: The aim of this observational study was to construct an ultrasound index of fetal gastric size for the prenatal detection of congenital digestive tract obstruction. SUBJECTS: A total of 386 fetal measurements were performed in routine ultrasonographic examinations of women with normal singleton pregnancies between 18 and 39 weeks of gestation. Gastric measurements were also performed in 13 fetuses with digestive tract obstruction. METHODS: The ultrasound plane which included the pylorus and which provided the largest stomach area was used for definition and measurement of gastric area and maximal longitudinal dimension. The transverse section at the center of the gastric corpus was used for transverse and anteroposterior dimensions. Gastric volumes were calculated as a prolate ellipsoid. The gastric area ratio was defined as the gastric area divided by the transverse abdominal area. Biparietal diameter (BPD) and abdominal transverse area were also measured. RESULTS: The fetal gastric area was significantly correlated with fetal gastric volume (r = 0.91) and gestational age (r = 0.74). However, the correlation coefficient for gastric area with gestational age was smaller than those of the BPD (r = 0.97) with gestational age and abdominal transverse area with gestational age (r = 0.97). Gastric area ratio decreased slightly towards term. The gastric area ratio was below the 95% confidence intervals for the predicted values in all five fetuses with esophageal atresia, and exceeded the 95% confidence intervals in seven of the eight fetuses with duodenal atresia or intestinal tract obstruction. CONCLUSION: Fetal gastric area correlates with ultrasound-determined gastric volume measurements and appears to be useful in the assessment of digestive tract anomalies.

Antenatal prediction of hypertrophic pyloric stenosis.

This is the first reported case where the diagnosis of hypertrophic pyloric stenosis (HPS) was entertained in the antenatal period and the neonate was followed up in the postnatal period on a prospective basis until the HPS became manifest.

The ontogeny of the peptide innervation of the human pylorus, with special reference to understanding the aetiology and pathogenesis of infantile hypertrophic pyloric stenosis.

Pyloric stenosis (PS) is a common condition in infancy, which is associated with smooth muscle hypertrophy that results in pyloric outlet obstruction. The author examines the ontogeny of the peptide innervation of the pylorus in fetal tissues and an experimental model in mice and evaluates the histochemical and morphological changes in the pylorus. The data suggest that PS is an intrauterine lesion that occurs by 12 weeks' gestation. This is associated with diminished nitric oxide in human tissues and reduced enzyme activity (resulting from a deficiency in an enzyme cofactor) in mice. Increased vasoactive intestinal polypeptide expression in pyloric myenteric ganglia may be an intrinsic mechanism for resolving this condition.

An immunochemical study with neuron-specific-enolase and substance P of human enteric innervation--the normal developmental pattern and abnormal deviations in Hirschsprung's disease and pyloric stenosis.

Human enteric innervation was studied immunochemically with neuron-specific-enolase (NSE), a specific neurone marker indicative of differentiation, and substance P, a potent member of the family of neuropeptides. By examining various levels of the gut in 28 normal human fetuses of gestational ages 9 to 21 weeks, we showed that enteric neurones as a whole, as well as peptidergic neurones in particular, followed a dual gradient of development proceeding from each end to the middle of the gut. This suggests the need for caution in accepting the hypothesis of the pathogenesis of Hirschsprung's disease based on the concept of a single craniocaudal gradient of enteric neuronal development. In studies of six infants with Hirschsprung's disease, NSE immunostaining was found to be potentially useful for diagnostic purposes. NSE activity suggested that the hypertrophied nerve bundles in aganglionic bowel were metabolically active and functionally mature. Substance P-immunoreactivity was decreased in both aganglionic and distal ganglionic bowel in Hirschsprung's disease, suggesting that substance P-nerves were more extensively affected developmentally than other enteric neurones. In 28 infants with pyloric stenosis (IHPS), the presence of intense NSE activity in the ganglia in the pylorus suggested that these neurones were neither immature nor severely degenerated. A decrease in substance P immunoreactivity in IHPS suggested possible involvement of peptidergic innervation in the pathogenesis of IHPS.