Pre- and perinatal risk factors for pyloric stenosis and their influence on the male predominance.

Pyloric stenosis occurs with a nearly 5-fold male predominance. To what extent this is due to environmental factors is unknown. In a cohort of all children born in Denmark, 1977-2008, the authors examined the association between pre- and perinatal exposures and pyloric stenosis and investigated whether these factors modified the male predominance. Information on pre- and perinatal factors and pyloric stenosis was obtained from national registers. Poisson regression models were used to estimate rate ratios. Among 1,925,313 children, 3,174 had surgery for pyloric stenosis. The authors found pyloric stenosis to be significantly associated with male sex, age between 2 and 7 weeks, early study period, being first born, maternal smoking during pregnancy, preterm delivery, small weight for gestational age, cesarean section, and congenital malformations. Among cases, 2,595 were males and 579 were females. Lower male predominance was associated with age at diagnosis outside the peak ages, early study period, no maternal smoking during pregnancy, preterm delivery, and congenital malformations. The authors have previously found a strong familial aggregation of pyloric stenosis indicating a genetic influence. This study shows that environmental factors during and shortly after pregnancy also play a role and that several of these modify the strong male predominance.

Early life events: infants with pyloric stenosis have a higher risk of developing chronic abdominal pain in childhood.

OBJECTIVE: We hypothesize that children who had pyloric stenosis are at greater risk for developing chronic abdominal pain because this cohort combines various risk factors: an early stressful event, gastric surgery, and perioperative nasogastric tube placement in most cases. STUDY DESIGN: This was a case control study of all children diagnosed with pyloric stenosis during infancy (cases) between January 1, 2000, and June 31, 2005, at Children's Memorial Hospital, Chicago. Because of their similar genetic and socioeconomic backgrounds, siblings aged 4 to 20 years without a history of pyloric stenosis were selected as controls. Parents of children with symptoms completed the parental form of the Pediatric GI Symptoms Rome III version questionnaire for both cases and controls. The primary outcome was the prevalence of chronic abdominal pain, and the secondary outcome was the presence of pain-associated functional gastrointestinal disorder (FGID), in accordance with Rome III criteria. RESULTS: Cases (n = 100; mean age, 7.49 ± 1.43 years; 29 girls) and controls (n = 91; mean age, 9.20 ± 4.19 years; 29 girls) participated in the study. Mean time to follow-up was 7.2 ± 1.6 years. Chronic abdominal pain was significantly more common in cases than in controls (20/80 [25%] vs 5/91 [5.8%]; OR, 4.3; 95% CI, 1.5-12; P = .0045). Seven out of 20 subjects (35%) met the Rome III criteria for diagnosis of a pain-associated FGID (3 with irritable bowel syndrome, 2 with functional dyspepsia, and 2 with functional abdominal pain), and 1 patient in the control group (with irritable bowel syndrome) met these criteria (OR, 6.8; 95% CI, 0.82-56; P = .043). CONCLUSION: We have described a new model to study early life events in infants. Our findings suggest that the presence of pyloric stenosis in infancy and factors involved in its perioperative care represent risk factors in the development of chronic abdominal pain in children at long-term follow-up. This study provides important data to sustain the multifactorial theoretical construct of pain-associated FGID and underscores the importance of early life events in the development of chronic abdominal pain in children.

Familial aggregation and heritability of pyloric stenosis.

CONTEXT: Pyloric stenosis is the most common condition requiring surgery in the first months of life. Case reports have suggested familial aggregation, but to what extent this is caused by common environment or inheritance is unknown. OBJECTIVES: To investigate familial aggregation of pyloric stenosis from monozygotic twins to fourth-generation relatives according to sex and maternal and paternal contributions and to estimate disease heritability. DESIGN, SETTING, AND PATIENTS: Population-based cohort study of 1,999,738 children born in Denmark between 1977 and 2008 and followed up for the first year of life, during which 3362 children had surgery for pyloric stenosis. MAIN OUTCOME MEASURE: Familial aggregation of pyloric stenosis, evaluated by rate ratios. RESULTS: The incidence rate (per 1000 person-years) of pyloric stenosis in the first year of life was 1.8 for singletons and 3.1 for twins. The rate ratios of pyloric stenosis were 182 (95% confidence interval [CI], 70.7-467) for monozygotic twins, 29.4 (95% CI, 9.45-91.5) for dizygotic twins, 18.5 (95% CI, 13.7-25.1) for siblings, 4.99 (95% CI, 2.59-9.65) for half-siblings, 3.06 (95% CI, 2.10-4.44) for cousins, and 1.60 (95% CI, 0.51-4.99) for half-cousins. We found no difference in rate ratios for maternal and paternal relatives of children with pyloric stenosis and no difference according to sex of cohort member or sex of relative. The heritability of pyloric stenosis was 87%. CONCLUSION: Pyloric stenosis in Danish children shows strong familial aggregation and heritability.

Declining incidence of pyloric stenosis in New Zealand.

BACKGROUND: Pyloric stenosis is a relatively common paediatric surgical condition, but a worldwide decline in its incidence has been observed in recent decades. The objective of this study was to identify if the incidence of pyloric stenosis in New Zealand has been declining. METHODS: A retrospective review of the four New Zealand paediatric surgical centres' theatre databases from 2007 to 2017. Demographic data were recorded for all infants who had a pyloromyotomy and annual incidences of pyloric stenosis calculated. RESULTS: A total of 393 infants underwent a pyloromyotomy for pyloric stenosis during the study period. Most infants (81%) were of European ethnicity. There was a significant decline (P = 0.0001) in the national incidence of pyloric stenosis from 0.73/1000 live births (LB) in 2007 to 0.39/1000 LB in 2017. From 2007 to 2017, the incidence of male infants with pyloric stenosis declined from 1.27/1000 LB to 0.62/1000 LB. The current annual incidence of pyloric stenosis in New Zealand is 0.39/1000 LB. CONCLUSIONS: The incidence of pyloric stenosis in New Zealand has significantly declined in the last decade and is currently the lowest reported incidence in the world involving a predominantly European cohort. A decline in male infants developing pyloric stenosis was also observed. Further study is required to investigate causes for this low incidence and declining trend.

Prevalence of infantile hypertrophic pyloric stenosis in Texas, 1999-2002.

BACKGROUND: The cause of infantile hypertrophic pyloric stenosis (IHPS) is poorly understood. This descriptive study of IHPS focuses on the effect of maternal nativity, maternal Hispanic ethnicity, subtypes of maternal Asian ethnicity, and the timing of the infant's surgery, that is, pyloromyotomy. METHODS: All cases of IHPS born in Texas from 1999 through 2002 were retrieved from the Texas Birth Defects Registry. Crude prevalence ratios and adjusted prevalence ratios (aPRs) were calculated using logistic regression. RESULTS: IHPS occurred predominantly in boys (aPR 4.21; 95% CI: 3.81, 4.65) compared with girls. Compared with Whites, there was a lower prevalence among Blacks (aPR 0.36; 95% CI: 0.30, 0.43), foreign-born Hispanics (aPR 0.61; 95% CI: 0.54, 0.69), Chinese (aPR 0.11; 95% CI: 0.01, 0.78), Vietnamese (aPR 0.17; 95% CI: 0.06, 0.46), Asian Indians (aPR 0.33; 95% CI: 0.15, 0.75), and Filipinos (aPR 0.22; 95% CI: 0.05, 0.91). In aggregate, foreign born Asians had a decreased risk of IHPS (aPR 0.20; 95% CI: 0.11, 0.37) compared to Whites. We observed no decrease in the risk of IHPS among US-born Asians (in aggregate) or US-born Hispanics. The strength of these risk factors did not vary according to the timing of the pyloromyotomy. CONCLUSIONS: This study confirmed previous findings that female infants and Black infants have a lower rate of IHPS. Large decreases in rates of IHPS were observed among foreign-born Hispanics and foreign-born Asians, but not among their US-born counterparts. These findings may be explained by differences in the frequency of behavioral risk factors for IHPS or differences in the frequency of ascertainment of mild cases of IHPS by ethnicity or nativity.

Changes in frequencies of select congenital anomalies since the onset of folic acid fortification in a Canadian birth defect registry.

OBJECTIVES: Fortification of grain products with folic acid has been shown to significantly reduce the occurrence of neural tube defects (NTDs) in Canada and elsewhere. However, the impact on non-NTD anomalies has not been well studied. METHODS: Using the Alberta Congenital Anomalies Surveillance System (ACASS), we examined changes in occurrence of select congenital anomalies where folic acid supplementation with multivitamins had previously been suggested to have an effect. Anomalies documented in the ACASS 1992-1996 (pre-fortification) were compared to 1999-2003 (post-fortification). RESULTS: A significant decrease in spina bifida (OR 0.51, 95% CI 0.36-0.73) and ostium secundum atrial septal defects (OR 0.80, 95% CI 0.69-0.93) was evident, but there was a significant increase in obstructive defects of the renal pelvisand ureter (OR 1.45, 95% CI 1.24-1.70), abdominal wall defects (OR 1.40, 95% CI 1.04-1.88) and pyloric stenosis (OR 1.49, 95% CI 1.18-1.89). CONCLUSIONS: Consistent with other studies, a 50% reduction in spina bifida was associated with the post-fortification time period. Supporting the possibility that folic acid fortification may play a role in preventing other birth defects, a 20% reduction in atrial septal defects was also associated. The increase in abdominal wall defects, most notably gastroschisis, is likely related to pre-existing increasing trends documented in several regions around the world. The increase in pyloric stenosis and obstructive urinary tract defects was not expected and any causal relationship with folic acid fortification remains unclear. Similar studies by other birth defects surveillance systems in Canada and elsewhere are needed to confirm these trends.

Prediction of three year outcomes using the Bayley-III for surgical, cardiac and healthy Australian infants at one year of age.

BACKGROUND: Previous predictive research has predominantly focussed on infants who are preterm, low birth weight, who have a specific condition or who have undergone a specific procedure. AIM: This study investigated the ability of outcomes at one year of age to predict outcomes at three years using the Bayley-III for infants who have undergone early major cardiac surgery (CS) or non-cardiac (NC) surgery and their healthy peers. STUDY DESIGN: Participants who were part of the Development After Infant Surgery (DAISy) study who had complete Bayley-III assessments at one and three years of age were included in the analyses. This included 103 infants who had undergone CS, 158 who had NC surgery and 160 controls. RESULTS: Bayley-III outcomes at one, although statistically significantly associated with three year outcomes in all domains were weak predictors of those outcomes for CS, NC surgical and healthy infants. Specificity for three year outcomes was good for cognitive, receptive language and fine motor domains for infants who had undergone CS and NC surgery. Sensitivity for <-1 SD at three years was poor for cognitive, expressive and receptive language, and fine motor outcomes for CS and NC surgical participants. CONCLUSION: It remains difficult to predict how performance at one year on the Bayley-IIII predicts performance at three on the Bayley-III for infants who have undergone early major CS or NC surgery and for healthy Australian infants.

[Infrared spectroscopy in assessment of the morpho-functional stomach changes at ulcerous pyloroduodenal stenosis].

In the present study authors have analyzed the suitability of the infrared (IR) spectroscopy for diagnosis of morphological and functional changes of the stomach in ulcer pyloroduodenal stenosis. Data obtained from 64 patients have shown that the IR spectroscopic features of the stomach were dependent on the stage of stenosis, secretory function of the stomach and the presence of the Helicobacter Pylori (HP) infection. IR spectroscopy can be a multi-purpose mean of assessment of the morphological and functional properties of the stomach in pyloroduodenal stenosis. IR spectroscopy provides the opportunity to assess the secretory state of the stomach at different stages of the disease. Using IR spectroscopy we were able to reveal the presence of HP in the stomach and the dynamics of its eradication during of conservative treatment and at any time after surgical intervention.

[Surgical tactics in the ulcer pyloroduodenal stenosis in decompensation stage].

In the ulcer pyloroduodenal stenosis the stages of complete and noncomplete decompensation are suggested. In 73% of observations, while performing an adequate preoperative preparation it was possible to convert pyloroduodenal stenosis from the stage of complete decompensation into the stage of noncomplete decompensation, in which the performance of organpreserving operation is possible. In the patients, suffering pyloroduodenal stenosis in the stage of noncomlete decompensation, resection of 2/3 of stomach is performed.

Intraoperative Endoscopic Botox Injection During Total Esophagectomy Prevents the Need for Pyloromyotomy or Dilatation.

BACKGROUND: Esophagectomy may lead to impairment in gastric emptying unless pyloric drainage is performed. Pyloric drainage may be technically challenging during minimally invasive esophagectomy and can add morbidity. We sought to determine the effectiveness of intraoperative endoscopic injection of botulinum toxin into the pylorus during robotic-assisted esophagectomy as an alternative to surgical pyloric drainage. MATERIALS AND METHODS: We performed a retrospective analysis of patients with adenocarcinoma and squamous cell carcinoma of the distal esophagus or gastroesophageal junction who underwent robotic-assisted transhiatal esophagectomy (RATE) without any surgical pyloric drainage. Patients with and without intraoperative endoscopic injection of 200 units of botulinum toxin in 10 cc of saline (BOTOX group) were compared to those that did not receive any pyloric drainage (noBOTOX group). Main outcome measure was the incidence of postoperative pyloric stenosis; secondary outcomes included operative and oncologic parameters, length of stay (LOS), morbidity, and mortality. RESULTS: From November 2006 to August 2014, 41 patients (6 females) with a mean age of 65 years underwent RATE without surgical drainage of the pylorus. There were 14 patients in the BOTOX group and 27 patients in the noBOTOX group. Mean operative time was not different between the comparison groups. There was one conversion to open surgery in the BOTOX group. No pyloric dysfunction occurred in the BOTOX group postoperatively, and eight stenoses in the noBOTOX group (30%) required endoscopic therapy (P < .05). There were no differences in incidence of anastomotic strictures or anastomotic leaks. One patient in group noBOTOX required pyloroplasty 3 months after esophagectomy. There was one death in the noBOTOX group postoperatively (30-day mortality 2.4%). Mean LOS was 9.6 days, and BOTOX patients were discharged earlier (7.4 versus 10.7, P < .05). CONCLUSION: Intraoperative endoscopic injection of botulinum toxin into the pylorus during RATE is feasible, safe, and effective and can prevent the need for pyloromyotomy.

Population demographic indicators associated with incidence of pyloric stenosis.

OBJECTIVES: To calculate incidence rates of pyloric stenosis (estimated by the rate of pyloromyotomy) among infants in Ontario and determine their association with population sociodemographic indicators. METHODS: Pyloromyotomy rates were calculated from hospital discharge data from 1993 through 2000. Four-year data (1993-1996 and 1997-2000) were combined to ensure the stability of the rates. Small-area variations in pyloromyotomy rates and correlations between sociodemographic indicators were studied. RESULTS: Approximately 84.0% of the patients were male infants (younger than 1 year). The sex-adjusted pyloromyotomy rates were 1.57 and 1.86 per 1000 with a 3.4-fold and 3.0-fold regional variation in 1993-1996 and 1997-2000, respectively. Urban areas consistently had the lowest pyloromyotomy rate (1.04 and 1.11 per 1000 in Metropolitan Toronto), but the highest rates were from more rural areas (3.30 and 3.38 per 1000 in Quinte, Kingston, Rideau). After adjusting for socioeconomic status and availability of surgeons in the region, living in a rural area remained a significant factor associated with a higher incidence of pyloromyotomy. The risk of pyloromyotomy for an infant who lives in a region with more than two thirds of its area classified as rural was 1.79 (95% confidence interval, 1.23-2.61; P<.005). CONCLUSIONS: The observed changes in incidence and a higher rate among male infants are consistent with results from previous comparative studies conducted in North America and Sweden. The rural/urban differences suggest that environmental influences related to living in these areas may have a role in the etiology of pyloric stenosis. Further research is needed to evaluate these differences.

Is erythromycin therapy teratogenic in humans?

The possible teratogenic effect of erythromycin therapy, noted previously, was studied. Women who had taken erythromycin or penicillin V in early pregnancy and their infants were studied, using the Swedish Medical Birth Register where information on drug use during pregnancy was recorded based on interviews in early pregnancy. The risk for any congenital malformation after erythromycin therapy (but not after penicillin V therapy) was increased (odds ratio 1.24, 95% confidence interval: 1.01-1.51) and this was due to an effect on cardiovascular malformations (odds ratio 1.92, 95% CI: 1.37-2.68). There was also an indicated increased risk for pyloric stenosis (risk ratio 3.0, 95% CI: 1.1-8.5 after exposure in early pregnancy). Various explanations to the finding are discussed, one of them linked to the fact that erythromycin inhibits a specific cardiac potassium channel (IKr) which seems to play a major role in cardiac rhythm regulation in the early embryo. Potent blocking drugs cause as a class effect cardiac defects in animal experiments.

Hypertrophic pyloric stenosis in infants following pertussis prophylaxis with erythromycin--Knoxville, Tennessee, 1999.

In February 1999, pertussis was diagnosed in six neonates born at hospital A in Knoxville, Tennessee. Because a health-care worker at hospital A was most likely the source of exposure, the local health department recommended on February 25, 1999, that erythromycin be prescribed as postexposure prophylaxis for the approximately 200 infants born at hospital A during February 1-24, 1999. In March 1999, local pediatric surgeons noticed an increased number of cases of infantile hypertrophic pyloric stenosis (IHPS) in the area, with seven cases occurring during a 2-week period. All seven IHPS cases were in infants born in hospital A during February who were given erythromycin orally for prophylaxis following possible exposure to pertussis, although none had pertussis diagnosed. The Tennessee Department of Health and CDC investigated the cluster of IHPS cases and its possible association with use of erythromycin. This report summarizes the results of the investigation, which suggest a causal role of erythromycin in this cluster of IHPS cases.

A goodness-of-fit test for the polygenic threshold model: application to pyloric stenosis.

A new test of goodness of fit for the polygenic threshold model is proposed. This test, when applied to disorders showing different incidence rates in males and females, is designed to account for ascertainment in more detail than previously done by other investigators. This is accomplished by computing the expected distribution of nuclear families with more than one affected sib conditioned on several family-dependent variables, including whether each family was ascertained via only affected boys or via at least one affected girl. A direct measure of the probability of observing a data set is thereby derived. The test, when applied to data on pyloric stenosis, exposes the critical nature of the ascertainment procedures. Different levels of statistical significance are obtained when mode of ascertainment is taken into account than when the mode of ascertainment is ignored.

Some epidemiological aspects of pyloric stenosis in British Columbia.

The records of an ongoing Health Surveillance Registry that utilizing multiple sources of ascertainment were used to study the incidence rate of infantile hypertrophic pyloric stenosis (IHPS) in liveborn children in British Columbia during the period 1966--1977 inclusive. The incidence was 4.6 male/1,000 livebirths and 1.2 females/1,000 livebirths, giving a male to female ratio of 3.1 to 1. No significant overall incidence variations with time could be shown during the study period. There was suggestive evidence of independent sex-incidence variation in different geographical regions, which clearly warrants further investigation.

The epidemiology of infantile hypertrophic pyloric stenosis in a Danish population, 1950-84.

The epidemiology of Infantile Hypertrophic Pyloric stenosis (IHPS) was studied in a geographically well-delineated and demographically representative Danish region (The County of Funen), covering the period 1 January 1950 to 31 December 1984. Based upon 679 cases, the cumulative incidence from birth of IHPS was found to be virtually unchanged during the study period at a level of 4.8 per 1000 liveborn boys and 1.3 per 1000 liveborn girls. In an analysis of clinical and demographic variables, the development of IHPS was found to be associated with low parity status (regardless of maternal age). The preterm cases had a longer interval from birth to onset of symptoms, compared with those born at term. No statistically significant associations were found between IHPS and seasonal variations at onset of symptoms, ABO and Rhesus blood groups, and maternal age.

Very early exposure to erythromycin and infantile hypertrophic pyloric stenosis.

OBJECTIVE: To assess the link between very early erythromycin exposure and pyloric stenosis in young infants. DESIGN: Retrospective cohort study. PARTICIPANTS AND METHODS: Medicaid or TennCare (Tennessee's program for Medicaid enrollees and uninsured individuals) births in Tennessee from 1985 to 1997. Cases of infants with a hospital discharge diagnosis of pyloric stenosis and an associated surgical procedure code were used. Erythromycin exposure and other antibiotic exposure between 3 and 90 days of life were identified from prescription files. MAIN OUTCOME MEASURES: Hospital discharge diagnosis of pyloric stenosis, and an associated surgical procedure code. RESULTS: Of 933 239 births in Tennessee during the study period, 314 029 were enrolled in Medicaid. Among these infants, 804 (2.6/1000 infants) met the criteria for pyloric stenosis. Very early exposure to erythromycin (between 3 and 13 days of life) was associated with a nearly 8-fold increased risk of pyloric stenosis (adjusted incident rate ratio, 7.88; 95% confidence interval, 1.97-31.57). No increased risk of pyloric stenosis was seen in infants exposed to erythromycin after 13 days of life or in infants exposed to antibiotics other than erythromycin. CONCLUSIONS: The significant increase in pyloric stenosis in children with very early exposure to erythromycin is consistent with reports of other investigators. The risks and benefits of erythromycin should be weighed carefully prior to initiating such therapy in young infants.

The epidemiology of infantile hypertrophic pyloric stenosis in New York State, 1983 to 1990.

OBJECTIVES: To investigate an apparent decline in the rate of infantile hypertrophic pyloric stenosis (IHPS) and to examine the characteristics of children with IHPS and any associated malformations. DESIGN: Cohort study in which children with IHPS were compared with the population of live births. Trends of IHPS were compared in two data sets: a population-based birth defects registry and hospital discharge data. PARTICIPANTS: Children with IHPS identified from a birth defects registry and the population of live-born infants born to residents of New York State from 1983 to 1990. MAIN OUTCOME MEASURE: Trends in the incidence of IHPS in the two data sets, and demographic characteristics and malformations associated with IHPS. RESULTS: The rate of IHPS declined from 2.4 per 1000 live births in 1984 to 1.7 in 1990. White race and male gender were associated with a higher occurrence of IHPS; high birth order, older maternal age, higher maternal education, and low birth weight were associated with lower occurrence. Seven percent of children with IHPS had a major malformation compared with 3.7% of the general population. Three major malformations occurred more frequently in children with IHPS: intestinal malrotation, obstructive defects of the urinary tract, and esophageal atresia. Fewer cases were found in the birth defects registry than in the hospital discharge data. CONCLUSIONS: Underreporting of IHPS to the birth defects registry accounts for some of the decline. Children with IHPS have more major malformations than the general population, although some of the excess could be attributed to increased detection. Further investigation is needed into the environmental factors, especially socioeconomic, associated with IHPS.

Prenatal prescription of macrolide antibiotics and infantile hypertrophic pyloric stenosis.

OBJECTIVE: To assess the association between prenatal antibiotics, including erythromycin, and infantile hypertrophic pyloric stenosis in a large cohort of infants. METHODS: This was a retrospective cohort study of births to women enrolled in Tennessee Medicaid/TennCare, 1985-1997. Prescriptions for erythromycin, nonerythromycin macrolides, and other antibiotics were identified from pharmacy files linked with birth certificate files. The primary study outcome was development of pyloric stenosis in the infant, identified from linked hospital discharge diagnosis and surgical procedure codes. RESULTS: The cohort included 260,799 mother/infant pairs. Among these women, 13,146 filled prescriptions for erythromycin (50.4 per 1000), and 621 filled prescriptions for nonerythromycin macrolides (2.4 per 1000). There was no association with prenatal erythromycin prescription and infantile hypertrophic pyloric stenosis either after 32 weeks' gestation (adjusted odds ratio 1.17, 95% confidence interval, 0.84, 1.64, P =.33) or at any time during pregnancy (adjusted odds ratio 1.15, 95% confidence interval 0.84, 1.56, P =.36). There was an association between maternal prescriptions for nonerythromycin macrolides and infantile hypertrophic pyloric stenosis (adjusted odds ratio 2.77, 95% confidence interval 1.22, 6.30, P =.01). CONCLUSION: The hypothesized association between erythromycin and infantile pyloric stenosis was not seen. Causal inference from the association between prenatal nonerythromycin macrolides and infantile hypertrophic pyloric stenosis is limited by the small number of affected children and the evidence of other differences between users of nonerythromycin macrolides and controls.

Infantile hypertrophic pyloric stenosis in Greater Manchester.

An "unprecedented" rise in the incidence of infantile hypertrophic pyloric stenosis (IHPS) was reported from the Central Region of Scotland in 1979. Examination of statistics from Greater Manchester showed a similar trend in some district health authorities but not others. Possible explanations are examined but future research is required. Hospital Activity Analysis can provide a useful tool for such research.