Questioning Prophylactic Antibiotic Use for Pyloromyotomy: Analysis of the Pediatric Health Information System Database.

BACKGROUND: Pyloromyotomy has a low rate of wound complications, yet antibiotic prophylaxis is still given. The Pediatric Health Information System (PHIS) database was queried to determine whether prophylactic antibiotics decreased wound complications. METHODS: Records for infants with pyloric stenosis between 2016 and 2021 were extracted from the PHIS database and analyzed for demographics, comorbid conditions, and complications within 30 days of pyloromyotomy. Logistic regression was used to evaluate the effect of antibiotic prophylaxis on complications. RESULTS: Among 14,247 infants who underwent pyloromyotomy, 29.5% had antibiotic prophylaxis. These patients were more likely to have been admitted to the NICU and have chronic conditions and prematurity (p < 0.01). Antibiotic utilization varied among hospitals from 2.3 to 58.5%. Complication rates among those who received antibiotics was 1.64% versus 1.62% for those who did not. The odds for developing complications in those who received prophylaxis compared to those who did not was 1.10, (0.73, 1.41, 95%, p = 0.93) suggesting there is no effect of antibiotics on complication rates. CONCLUSIONS: There was a wide variation among hospitals in the usage of prophylactic antibiotics for pyloromyotomy. There was no difference in complication rates whether or not patients received antibiotics. These results suggest antibiotic prophylaxis is unnecessary for pyloromyotomy. LEVEL OF EVIDENCE: III.

Infantile hypertrophic pyloric stenosis: maternal diabetes and perinatal exposure to non-macrolide antibiotics.

OBJECTIVE: Infant exposure to macrolide antibiotics is a risk factor for infantile hypertrophic pyloric stenosis (IHPS). The aim of the study was to establish whether perinatal exposure to non-macrolide antibiotics was a risk factor for IHPS. STUDY DESIGN: A retrospective matched case-control study was performed using a database including all children born at Soroka University Medical Centre between 2006 and 2018. Cases and controls were compared using Student T-test and multiple logistic regression. RESULT: Of 189 461 children in the database, 63 infants were diagnosed with IHPS and underwent pyloromyotomy. There was no association between non-macrolide antibiotic exposure and IHPS. Maternal diabetes (DM) had an adjusted odds ratio for infants developing IHPS of 4.53 (p = 0.004). CONCLUSION: The lack of association between exposure to non-macrolide antibiotics and IHPS suggests a quality unique to macrolides. An association between DM and IHPS may suggest elevated levels of IGF-1 have a role.

Perinatal risk factors for infantile hypertrophic pyloric stenosis: A systematic review and meta-analysis.

BACKGROUND: Infantile hypertrophic pyloric stenosis (IHPS) is one of the most common diseases that require surgical intervention amongst the paediatric population. Although the treatment and the diagnosis of pyloric stenosis are well established, the perinatal risk factors associated with it still need further investigation. METHODS: We searched the following databases: Cochrane, Google Scholar, PubMed, and Scopus. Studies were included if they were case-control or cohort in design and studied the perinatal risk factors associated with IHPS. The quality of the included studies was assessed using the Newcastle-Ottawa scale (NOS). RESULTS: Twenty-one articles were included in this meta-analysis, including 18,104,753 participants. Our analysis showed a significant association between IHPS and male sex (RR=2.71, 95% CI:1.93-3.78), maternal smoking (RR=1.75, 95% CI: 1.54 - 2.00), bottle-feeding (RR=1.68, 95% CI: 1.42 - 1.98), being first born (RR=1.23, 95% CI:1.07-1.40), African ethnicity (RR=0.51, 95% CI: 0.35-0.75), and cesarean section (RR=1.57, 95% CI: 1.49-1.66). On the contrary, there was no significant association between IHPS and multiple gestations, preterm labour, being born in summer, and small for gestational age (SGA). CONCLUSION: In conclusion, our analysis showed that male sex, bottle feeding, maternal smoking and African ethnicity were significantly associated with the risk of IHPS. However, most of the included articles were retrospective in design which necessitates conducting future prospective well-designed studies to further investigate the risk factors of IHPS.

Environmental exposure in the etiology of infantile hypertrophic pyloric stenosis: a systematic review and meta-analysis.

PURPOSE: To investigate the occupational and environmental factors in the etiology of infantile hypertrophic pyloric stenosis (IHPS). METHODS: Protocol was drafted according to the PRISMA guidelines and registered on PROSPERO (CRD42020152460). A search for a combination of terms related to IHPS, fetus and neonates, and environmental exposure was performed for studies published between 2000 and 2020 in the EMBASE, Pubmed, and MEDLINE databases. RESULTS: Overall, 2203 abstracts were identified and 829 were screened. The full text of the selected articles (N = 98) was assessed for eligibility. Fifteen studies were included in quantitative synthesis. IHPS risk was significantly lower in black and Hispanic mothers than in white mothers [OR 0.47 (95% CI 0.44-0.51, p < 0.001), OR 0.85 (95% CI 0.77-0.94, p = 0.002), respectively]. Lower maternal education level and maternal smoking were risk factor for IHPS. We further observed a non-significant association between maternal folic acid usage and IHPS risk. Data were insufficient to evaluate occupational exposure. CONCLUSION: This review provides an understanding of the role of environmental exposures in IHPS etiology. Lower maternal educational level, maternal smoking, and white ethnicity are associated with a significantly increased risk of IHPS, while folic acid use seems non-significantly associated with IHPS risk. LEVEL OF EVIDENCE: III.

Hypertrophic pyloric stenosis case series in twins and first cousins: genes, feeding patterns or both? (a case report).

We present two cases of dizygotic male twins and two cases of male first cousins with infantile hypertrophic pyloric stenosis (IHPS). All patients were treated with open pyloromyotomy. No complications were reported. The patients had the same risk factors for IHPS. First, all patients were first-born white males. Second, the twins were preterm (35 weeks). Third, the twins and the first cousins were exclusively bottle feeding. Thus, a combination of genetic and environmental factors may have contributed to the appearance of IHPS.

Protocol: A systematic review and meta-analysis of the role of fetal and infantile environmental exposure in etiopathogenesis of infantile hypertrophic pyloric stenosis.

Infantile hypertrophic pyloric stenosis (IHPS) is one of the hallmark pediatric surgical diseases. However, its etiology remains incompletely understood. By systematically reviewing the literature, we aim to clarify the effect of the effect of occupational and environmental factors and role of nitric oxide (NO) metabolism in the etiopathogenesis of IHPS. The systematic review is drafted with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement (PRISMA) and the Meta-analysis of Observational Studies in Epidemiology (MOOSE). Systematic literature search will be performed for the period 2000 (Jan) to 2020 (Dec) in the databases: MEDLINE, EMBASE, PubMed. The systematic search will cover the literature in English and Turkish language and will be limited to studies on human subjects. Four investigators will independently search the databases (MEDLINE, EMBASE, PubMed) according to the defined search strategy. The full-text of the selected articles will be screened independently by four reviewers, against the inclusion criteria. Descriptive data will be extracted from each study regarding: study details, methods, participants, outcomes and calculations of association for potential further statistical analysis. If meta-analysis could not be undertaken, systematic approach to analyzing the findings of included multiple studies will be described. Heterogeneity will be assessed by quantifying the inconsistency across studies using I2 statistic. Statistical analysis will be performed using Comprehensive Meta-Analysis Version 3.0 software. The p values lower than 0.05 will be considered statistically significant for all analyses.

Does Maternal Omega 3 Supplementation Protect Against Infantile Hypertrophic Pyloric Stenosis?

OBJECTIVES: Infantile hypertrophic pyloric stenosis (IHPS) is potentially life threatening. The etiology of IHPS remains unknown and many risk factors have been reported. We aimed to assess the prevalence of known risk factors and investigate maternal nutrition and habits as possible additional risk factors for IHPS. METHODS: This case-control study includes mothers of infants diagnosed with IHPS and control mothers of infants, age 2 to 11 months, hospitalized in the pediatric department due to other conditions. Cases of IHPS were identified by review of all infants diagnosed with IHPS and operated upon in 2010 to 2016 at 2 major hospitals in central Israel. Data regarding potential risk factors were collected via questionnaires in both study groups. RESULTS: Sixty-six cases and 67 controls were included in the study. Maternal omega 3 supplement consumption during pregnancy was significantly less common among cases of IHPS as compared with controls (P = 0.031). Consumption of omega 3 supplement was defined as consumption of at least 1 to 2 per week during the pregnancy period. Following adjustment for known risk factors, including male sex and maternal smoking, maternal omega 3 supplement consumption remained associated with a significantly lower risk of developing IHPS (odds ratio = 0.303, 95% confidence interval 0.111-0.828, P = 0.02). CONCLUSIONS: Maternal omega 3 supplement consumption during pregnancy was associated with a significantly reduced risk of IHPS. Further studies are needed to support these results and investigate possible mechanisms of the effect of omega 3.

The incidence of infantile hypertrophic pyloric stenosis and its association with folic acid supplementation during pregnancy: A nested case-control study.

BACKGROUND AND RATIONALE: Several studies have suggested that the incidence of infantile hypertrophic pyloric stenosis (IHPS) has decreased in recent decades. This decrement is controversial and not fully explained. Concurrently, there has been a major increase in folic acid consumption by pregnant women to prevent neural tube defects. We aimed to describe IHPS incidence in Israel in recent years and to assess its potential association with folic acid consumption. METHODS: Using the electronic medical database of a 2.1 million member health organization in Israel, we identified all cases (n = 1899) of IHPS occurring between 1999 and 2015. Cases were individually matched with up to 5 controls (n = 7350) by birth date, sex, and region. Odds ratios and 95% confidence intervals by tertiles of cumulative dose of supplemented folic acid between three months prior to pregnancy and up to birth of index child were calculated using conditional logistic regression. RESULTS: During the study period IHPS incidence declined from 4.3 in 1999 to 2.1 per 1000 live births in 2015(p < 0.0001). No significant (p = 0.81) association was observed between folic acid intake during pregnancy and risk of IHPS incidence. Preterm birth and infant's use of macrolides during first 3 postnatal months were significantly (p < 0.01) associated with increased risk of IHPS. CONCLUSIONS: Similar to other countries, IHPS incidence in Israel has decreased in recent years. The decrement cannot be explained by increased use of folic acid. TYPE OF STUDY: Case Control Study. LEVEL OF EVIDENCE: Level III. SUMMARY: Using linkage to a large electronic patient database, this study investigated the association between the decrease in infantile hypertrophic pyloric stenosis and maternal exposure to folic acid during pregnancy.

Hypertrophic pyloric stenosis following persistent pulmonary hypertension of the newborn: a case report and literature review.

BACKGROUND: Although persistent pulmonary hypertension of the newborn (PPHN) and infantile hypertrophic pyloric stenosis (HPS) are both well-known diseases that occur in early infancy, PPHN complicated by HPS is rare. As nitric oxide (NO) is an important mediator of biological functions, on both the vascular endothelium and smooth muscle cells, the decreased production of NO might play a role in the pathogenesis of both PPHN and HPS. We present the case of a neonate who developed HPS following PPHN, including a detailed review on research published to date, and we discuss the pathogenesis of PPHN and HPS. CASE PRESENTATION: A female neonate born at 38 weeks of gestation, weighing 3140 g, developed PPHN due to meconium aspiration syndrome. Intensive treatment with high frequency oscillations and inhaled NO were initiated, and sildenafil and bosentan were added. She gradually recovered. At 15 days of age, the patient developed recurrent vomiting after feeding and the diagnosis of HPS was made. Intravenous atropine therapy was started at 20 days of age, but the efficacy was clinically unsatisfactory. The coadministration with transdermal nitroglycerin improved the symptoms, and oral feeding was successfully re-introduced. CONCLUSIONS: Our patient recovered from both PPHN and HPS using NO-related medications. A decrease in NO synthesis is likely to be a common pathway for PPHN and HPS.

Pyloric stenosis: an enigma more than a century after the first successful treatment.

Despite hypertrophic pyloric stenosis (HPS) being one of the most frequently treated pediatric surgical conditions, its etiology remains incompletely understood. We review the diagnosis and treatment of this condition with an emphasis on the evolution of surgical techniques that led to laparoscopic pyloromyotomy, the most frequently performed technique for HPS today. In addition, we review key developments in the understanding of HPS etiology and treatment, including the postulated etiology of work-induced hypertrophy of the pylorus, its association with prokinetic macrolide antibiotics, and the emerging role of atropine sulfate as a medical treatment for HPS or a rescue treatment for incomplete myotomy.

Perinatal risk factors for infantile hypertrophic pyloric stenosis: A meta-analysis.

BACKGROUND: Infantile hypertrophic pyloric stenosis (IHPS) is the most common surgical cause of nonbilious vomiting in infancy. The etiology of IHPS is not completely understood. Hence, we performed a meta-analysis to investigate the association between perinatal factors and IHPS onset. METHODS: The MEDLINE, EMBASE, PubMed and Cochrane Library databases were searched for studies published in English before December 2016. The combined odd ratios (ORs) and 95% confidence intervals (CIs) were calculated using random-effects models. RESULTS: Fifteen studies were included. Several perinatal factors, including first-born (OR 1.19, 95% CI: 1.07-1.33), cesarean section delivery (OR 1.63, 95% CI: 1.53-1.73), preterm birth (OR 1.37, 95% CI: 1.12-1.67), and bottle-feed (OR 2.46, 95% CI: 1.76-3.43), were significantly associated with the IHPS onset. Among these, bottle-feed was the most significantly risk factor for IHPS onset. Although few studies have evaluated the relationship between perinatal factors and IHPS, they have major limitations including retrospective collection of data on perinatal events and testing of multiple hypotheses without appropriate statistical corrections. CONCLUSIONS: First-born, cesarean section delivery, preterm birth, and bottle-feed are associated with the development of IHPS. Well-designed future studies are needed to help understand the etiology of IHPS. TYPE OF STUDY: Systematic reviews and meta-analyses. LEVEL OF EVIDENCE: Level III.

Vomiting in an infant with congenital nephrotic syndrome: Questions.

BACKGROUND: Most patients with congenital nephrotic syndrome (CNS) exhibit a failure to thrive. A previous study reported that five of 41 (12 %) infants with CNS had hypertrophic pyloric stenosis (HPS) requiring surgery. The reason for this is undetermined, and there are few reports regarding the relationship between these conditions or their clinical course. CASE DIAGNOSIS/TREATMENT: We present the case of a 4-month-old girl with CNS. She did not show typical manifestations of HPS, but thickened mucosal and submucosal layers and hypertrophy of the pyloric muscle were detected by repeated ultrasound examinations prior to the diagnosis of HPS. Pyloroplasty was performed to improve her poor weight gain and led to ideal growth. CONCLUSIONS: Our case indicates that obstruction of the gastric outlet may be strongly associated with poor weight gain in patients with CNS. We should suspect involvement with HPS even if typical symptoms are lacking, and an aggressive intervention may improve poor growth. Thickened edematous mucosal and submucosal layers at the pyloric antrum have the potential to cause the high frequency of HPS in CNS.

Formula-feeding and hypertrophic pyloric stenosis: is there an association? A case-control study.

BACKGROUND: The etiology of infantile hypertrophic pyloric stenosis (HPS) is not fully understood. The objective of this study was to determine whether formula-feeding is associated with increased incidence. METHODS: This case-control study included HPS cases and controls admitted between 1992 and 2012. Demographic data including feeding method were collected from patient charts and analyzed. RESULTS: We identified 882 HPS cases and 955 controls. The highest incidence of HPS presentation was in summer (P=0.0028). Infants with HPS were more likely to have been exclusively formula-fed, have a family history of HPS, and be male compared to infants in the control group (P<0.001); they were also more likely to live in rural areas, although not significantly so. After adjusting for family history, sex, place of residence, and season of presentation, exclusively formula-fed infants were 1.36 times more likely to develop HPS compared with exclusively breastfed infants (RR 1.36, 95% CI 1.18-1.57, P<0.005). CONCLUSIONS: Formula-feeding is associated with significantly increased risk of HPS. Further investigation may help to determine the components of formula that simulate hypertrophy of the pylorus muscle, or the components of breast milk that are protective, as well as other influencing factors. LEVEL OF EVIDENCE: 3b.

Maternal factors in the origin of infantile hypertrophic pyloric stenosis: A population-based case-control study.

In most patients affected by isolated infantile hypertrophic pyloric stenosis (IHPS) the etiology is largely unknown. Thus, the aim of this study was to estimate possible maternal risk factors in the origin of IHPS. The study samples included 241 cases with IHPS, 357 matched controls and 38,151 population controls without any defect in the population-based large dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996. Exposures that had been medically recorded in prenatal maternity logbooks during the critical period of IHPS were evaluated separately. The findings of this case-control study suggested that--beyond the well-known robust male excess (85.5%)--maternal hyperthyroidism (OR with 95% CI: 4.17, 1.53-11.38) and oral nalidixic acid treatment (OR with 95% CI: 6.53, 3.03-14.06) associated with a higher risk for IHPS in their children. In conclusion, our findings suggest that cases with IHPS had mothers with a higher proportion of hyperthyroidism and nalidixic acid treatment during pregnancy.

Association of prematurity with the development of infantile hypertrophic pyloric stenosis.

BACKGROUND: Infantile hypertrophic pyloric stenosis (IHPS) has several known risk factors. The association between prematurity and IHPS and the timeline of presentation are poorly defined. Our aim was to evaluate the associations between IHPS and prematurity. METHODS: We performed a retrospective cohort study of 1,074,236 children born between June 2001 and April 2012 in the US Military Health System. IHPS cases and gestational ages (GA) were identified using billing codes. Additional risk factors for IHPS were controlled for in a multivariable logistic regression model. RESULTS: The incidence of IHPS was 2.99 per 1,000 in preterm infants and 2.25 per 1,000 in full term (relative risk (RR) = 1.33, 95% confidence interval (CI) 1.16-1.54). The adjusted odds ratio for prematurity was 1.26 (95% CI 1.08-1.46). The median (interquartile range (IQR)) chronological age at presentation was 40 d (30-56) in preterm infants vs. 33 d (26-45) in full term (P < 0.001). Median postmenstrual age at presentation was 42 wk in preterm infants (40-42) vs. 45 wk (44-46) in full term (P < 0.001). CONCLUSION: Prematurity is associated with IHPS. Premature infants develop IHPS at a later chronological age, but earlier postmenstrual age, than term infants. Providers should have an increased concern for IHPS development in premature infants.

Investigation of the effects of enteral hormones on the pyloric muscle in newborn rats.

PURPOSE: To investigate the effects of enteral hormones on pyloric muscle in order to clarify the etiopathogenesis of hypertrophic pyloric stenosis (HPS). METHODS: Forty-two newborn Wistar-Albino rats were included. No intervention was done in the control group (CG, n=6). In the sham group (SG, n=6) 1ml saline (0.9% NaCl solution), in the Nw-nitro-l-arginine methyl ester hydrochloride (L-NAME) group (LNG, n=6) 100mg/kg/d L-NAME, in the somatostatin group (STG, n=6) 7mcg/kg/d ST, in the cholecystokinin group (CCKG, n=6) 3mcg/kg/d CCK, in the substance P group (SPG, n=6) 5ml/kg/d SP, and in the prostaglandin-E1 group (PGE1G, n=6) a cumulative dose of 360mcg/kg PGE1 was given intraperitoneally for 14days. On the 21st day, histopathological examination and muscle thickness measurements were done. Results were evaluated statistically. RESULTS: Total and circular pyloric muscle thicknesses were significantly increased in the LNG compared to the CG and SG (p<0.05). Circular pyloric muscle thickness was not increased in the STG, CCKG and SPG compared to the CG and SG (p>0.05). In the PGE1G, muscle thickness was significantly decreased in the pylorus and increased in the antrum compared to the CG and SG (p<0.05). CONCLUSION: Nitric oxide synthase (NOS) inhibition with L-NAME seems to be a causative factor in HPS by increasing pyloric muscle thickness. PGE predominantly affects antral gastric muscle and has no profound effect on pyloric muscle.

Infantile hypertrophic pyloric stenosis (IHPS): a study of its pathophysiology utilizing the newborn hph-1 mouse model of the disease.

Infantile hypertrophic pyloric stenosis (IHPS) is a common disease of unknown etiology. The tetrahydrobiopterin (BH4)-deficient hyperphenylalaninemia-1 (hph-1) newborn mouse has a similar phenotype to the human condition. For hph-1 and wild-type control animals, pyloric tissue agonist-induced contractile properties, reactive oxygen species (ROS) generation, cGMP, neuronal nitric oxide synthase (nNOS) content, and Rho-associated protein kinase 2 (ROCK-2) expression and activity were evaluated. Primary pyloric smooth muscle cells from wild-type newborn animals were utilized to evaluate the effect of BH4 deficiency. One-week-old hph-1 mice exhibited a fourfold increase (P < 0.01) in the pyloric sphincter muscle contraction magnitude but similar relaxation values when compared with wild-type animals. The pyloric tissue nNOS expression and cGMP content were decreased, whereas the rate of nNOS uncoupling increased (P < 0.01) in 1-wk-old hph-1 mice when compared with wild-type animals. These changes were associated with increased pyloric tissue ROS generation and elevated ROCK-2 expression/activity (P < 0.05). At 1-3 days of age and during adulthood, the gastric emptying rate of the hph-1 mice was not altered, and there were no genotype differences in pyloric tissue ROS generation, nNOS expression, or ROCK-2 activity. BH4 inhibition in pyloric smooth muscle cells resulted in increased ROS generation (P < 0.01) and ROCK-2 activity (P < 0.05). Oxidative stress upregulated ROCK-2 activity in pyloric tissue, but no changes were observed in newborn fundal tissue in vitro. We conclude that ROS-induced upregulation of ROCK-2 expression accounts for the increased pyloric sphincter tone and nNOS downregulation in the newborn hph-1 mice. The role of ROCK-2 activation in the pathogenesis of IHPS warrants further study.

Maternal and pregnancy characteristics and risk of infantile hypertrophic pyloric stenosis.

BACKGROUND/PURPOSE: The incidence of infantile hypertrophic pyloric stenosis (IHPS) in Sweden decreased dramatically during the 1990s. The aim of the study was to examine IHPS risk factors and the possible change in them as the incidence declined. METHODS: This is a case-control study including 3608 surgically treated IHPS cases and 17588 matched controls during 1973-2008. Cases were identified in the Swedish National Patient Register and data on possible risk factors were collected from the Swedish Medical Birth Register. The association between study variables and IHPS was analyzed using conditional logistic regression for the whole study period and separately for periods with high and low IHPS incidences. RESULTS: Prematurity (OR, 2.54; 95% CI, 2.06-3.14), caesarean delivery (OR, 1.67; 95% CI, 1.51-1.86), maternal smoking (OR, 1.82; 95% CI, 1.53-2.16), and young maternal age (< 20yrs) (OR, 1.42; 95% CI, 1.17-1.73) were associated with an increased IHPS risk. Birth order 2 (OR, 0.78; 95% CI, 0.71-0.85) or more was associated with a lower IHPS risk. ORs for smoking increased at low incidence rate. CONCLUSION: We report caesarean section, prematurity, primiparity, young maternal age, and smoking as significant IHPS risk factors. The impact of smoking was higher during periods with a low incidence.