Emollients for prevention of atopic dermatitis: 5-year findings from the BEEP randomized trial.

BACKGROUND: The effectiveness of emollients for preventing atopic dermatitis/eczema is controversial. The Barrier Enhancement for Eczema Prevention trial evaluated the effects of daily emollients during the first year of life on atopic dermatitis and atopic conditions to age 5 years. METHODS: 1394 term infants with a family history of atopic disease were randomized (1:1) to daily emollient plus standard skin-care advice (693 emollient group) or standard skin-care advice alone (701 controls). Long-term follow-up at ages 3, 4 and 5 years was via parental questionnaires. Main outcomes were parental report of a clinical diagnosis of atopic dermatitis and food allergy. RESULTS: Parents reported more frequent moisturizer application in the emollient group through to 5 years. A clinical diagnosis of atopic dermatitis between 12 and 60 months was reported for 188/608 (31%) in the emollient group and 178/631 (28%) in the control group (adjusted relative risk 1.10, 95% confidence interval 0.93 to 1.30). Although more parents in the emollient group reported food reactions in the previous year at 3 and 4 years, cumulative incidence of doctor-diagnosed food allergy by 5 years was similar between groups (92/609 [15%] emollients and 87/632 [14%] controls, adjusted relative risk 1.11, 95% confidence interval 0.84 to 1.45). Findings were similar for cumulative incidence of asthma and hay fever. CONCLUSIONS: Daily emollient application during the first year of life does not prevent atopic dermatitis, food allergy, asthma or hay fever.

Survival Trends and Syndromic Esophageal Atresia.

BACKGROUND AND OBJECTIVES: Presence of a syndrome (or association) is predictive of poor survival in esophageal atresia (EA). However, most reports rely on historical patient outcomes, limiting their usefulness when estimating risk for neonates born today. We hypothesized improved syndromic EA survival due to advances in neonatal care. METHODS: A retrospective single-center review of survival in 626 consecutive patients with EA from 1980 to 2017 was performed. Data were collected for recognized risk factors: preterm delivery; birth weight <1500 g; major cardiac disease; vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula, renal anomalies, and limb abnormalities (VACTERL); and non-VACTERL syndromes. Cox proportional hazards regression models were used to evaluate temporal trends in survival with respect to year of birth and syndromic EA. RESULTS: Overall, 87% of 626 patients with EA survived, ranging from 82% in the 1980s to 91% in the 2010s. After adjusting for confounders, syndromic EA survival did not improve during the study, with no association found between year of birth and survival (hazard ratio [HR] 0.98, 95% confidence interval [CI]: 0.95-1.01). Aside from lethal non-VACTERL syndromes, patients with nonlethal non-VACTERL syndromes (HR 6.85, 95% CI: 3.50-13.41) and VACTERL syndrome (HR 3.02, 95% CI: 1.66-5.49) had a higher risk of death than those with nonsyndromic EA. CONCLUSIONS: Survival of patients with syndromic EA has not improved, and patients with non-VACTERL syndromes have the highest risk of death. Importantly, this is independent of syndrome lethality, birth weight, and cardiac disease. This contemporary survival assessment will enable more accurate perinatal counseling of parents of patients with syndromic EA.

Selective approach to preoperative echocardiography in esophageal atresia.

PURPOSE: Preoperative echocardiography is used routinely in neonates with esophageal atresia to identify patients in whom congenital cardiac disease will impact upon anesthetic and surgical decision-making. We aimed to determine the suitability of selective preoperative echocardiography. METHODS: We performed a single-center retrospective review of neonates with esophageal atresia over 6 years (2010-2015) at our tertiary pediatric institution. Data included preoperative clinical examination, chest x-ray, and echocardiography. Endpoints were cardiovascular, respiratory, radiological, and echocardiography findings. Selective strategies were assessed using sensitivity, specificity, positive predictive value, and negative predictive value. RESULTS: We identified 115 neonates with esophageal atresia. All underwent preoperative echocardiography. Cardiac defects were identified in 49/115 (43%) (major 9/115, moderate 4/115). Sensitivity, specificity, positive predictive value, and negative predictive value of abnormal clinical and radiologic assessment for major and moderate cardiac defects were 92%, 25%, 13%, 96%; for clinical examination alone were 92%, 25%, 14%, 96%; for absence of murmur, cyanosis, and abnormal respiratory examination were 92%, 28%, 13%, 97%. Selective strategies reduce echocardiograms performed by 22%. CONCLUSION: Selective strategies allow for identification of neonates with esophageal atresia who may have deferral of echocardiogram unill after surgery. Selection may improve timeliness of care and resource utilization, without compromising patient safety.

Delayed Diagnosis in Esophageal Atresia and Tracheoesophageal Fistula: Case Study.

BACKGROUND: Timely identification of esophageal atresia is challenging. Diagnosis may be suspected antenatally with a combination of polyhydramnios, associated with a small or absent stomach bubble or other anomalies. Esophageal atresia can be suspected postnatally in the presence of tachypnea, increased oral secretions, and an inability to advance an orogastric tube. Failure to recognize an esophageal atresia can have life-threatening implications. CLINICAL FINDINGS: A 5-day-old infant with a history of failure to thrive and respiratory distress presented in a community emergency department following a prolonged apnea associated with a breastfeed. PRIMARY DIAGNOSIS: Delayed postnatal diagnosis of esophageal atresia and tracheoesophageal fistula. INTERVENTIONS: During stabilization in the emergency department, a nasogastric tube was placed to decompress the stomach. A subsequent chest and abdominal radiograph identified the nasogastric tube curled in the upper esophagus, confirming an esophageal atresia. The abdominal radiograph demonstrated gaseous distension, suggesting the presence of a distal tracheoesophageal fistula. OUTCOMES: The neonate had a primary esophageal anastomosis and fistula ligation in a surgical neonatal unit. He was discharged home at 29 days of life. PRACTICE RECOMMENDATIONS: Understanding the challenges of an antenatal diagnosis and awareness of postnatal presentation with a view to improving postnatal recognition and better-quality outcomes for infants with an esophageal atresia and tracheoesophageal fistula.

H-type congenital tracheoesophageal fistula: Insights from 70 years of The Royal Children's Hospital experience.

BACKGROUND: The long-term outcomes of H-type tracheoesophageal fistula (TOF), an uncommon variant of esophageal atresia/tracheoesophageal fistula (OA/TOF), are rarely described in the literature. We reviewed our institutional experience of 70 years. METHODS: The Nate Myers Oesophageal Atresia Database was queried for patients with an H-type TOF (1948-2017). Data included presentation, diagnostic workup, surgical management, and outcomes. RESULTS: Of 1088 patients with OA/TOF, 56 (5.1%) had an H-type TOF. The most common presenting symptoms were cyanotic episodes (68%), choking with feeds (52%), and aspiration pneumonitis (46%). The majority (82%) were symptomatic in the first week of life. Coexisting congenital anomalies were present in 46%: cardiac (13/56, 23%), genitourinary (10/56, 18%), and vertebral/skeletal (9/56, 16%). Patients were consistently diagnosed with prone contrast tube esophagogram (77% sensitivity on the first study and 96% after a second study). The fistula was most commonly approached through a right cervical collar incision. Right vocal cord palsy occurred in 22%, with one case of bilateral palsies. Other complications included leak (5.6%), recurrence (9.3%), stricture (1.9%), and diverticulum (1.9%). Although there was a trend towards a lower recurrence rate when interposition material was used, this was not statistically significant (3.3% vs 16.7%, p = 0.16). Survival in operative cases was 98.2%, and when all diagnosed cases were considered was 89.3%. CONCLUSIONS: We have reported the largest single-center series of H-type TOF. Diagnosis is challenging, and surgical morbidity remains high. Despite this, long-term outcomes are favorable. LEVEL OF EVIDENCE: IV.

The burden of esophageal dilatations following repair of esophageal atresia.

AIM: To describe the burden of esophageal dilatations in patients following esophageal atresia (EA) repair. METHOD: A retrospective review was performed at The Royal Children's Hospital, Melbourne, of all neonates undergoing operative repair for EA over a 17-year period (1999-2015). Stricture was defined by radiological and/or intra-operative findings of narrowing at the esophageal anastomosis. Data recorded included EA type, perinatal details, operative approach, esophageal anastomosis outcome, dilatation requirement, and survival. Key endpoints were anastomotic leakage and tension, esophageal dilatation technique, dilatation frequency, fundoplication, and complications. RESULTS: During the study period, 287 newborn EA patients were admitted, of which 258 underwent operative repair and survived to primary discharge. Excluding 11 patients with isolated tracheoesophageal fistula, 247 patients were included in the final analysis. Intra-operative anastomotic tension was documented in 41/247 (16.6%), anastomotic leak occurred in 48/247 (19.4%), and fundoplication was performed in 37/247 (15.0%). Dilatations were performed in 149/247 (60.3%). Techniques included bougie-alone (92/149, 61.7%), combination of bougie and balloon (51/149, 34.2%), and balloon-alone (6/149, 4.0%). These patients underwent 1128 dilatations; median number of dilatations per patient was 4 (interquartile range 2-8). Long-gap EA and anastomotic tension were risk factors (p < 0.01) for multiple dilatations. Complications occurred in 13/1128 (1.2%) dilatation episodes: 11/13 esophageal perforation, 2/13 clinically significant aspiration. Perforations were rare events in both balloon (6/287, 2.1%) and bougie dilatations (4/841, 0.5%); one patient had a perforation from guidewire insertion. CONCLUSIONS: Esophageal dilatation occurred in a majority of EA patients. Long-gap EA was associated with an increased burden of esophageal dilatation. Perforations were rare events in balloon and bougie dilatations. TYPE OF STUDY: Original article - retrospective review. LEVEL OF EVIDENCE: II.

Predictors of Mortality after Primary Discharge from Hospital in Patients with Esophageal Atresia.

OBJECTIVE: To describe esophageal atresia mortality rates and their associations in our cohort. STUDY DESIGN: Patients with esophageal atresia, managed at The Royal Children's Hospital, Melbourne (1980-2018), who subsequently died, were retrospectively identified from the prospective Nate Myers Oesophageal Atresia database. Data collected included patient and maternal demographics, vertebral anomalies, anorectal malformations, cardiovascular anomalies, tracheoesophageal fistula, renal anomalies, and limb defects (VACTERL) associations, mortality risk factors, and preoperative, operative, and postoperative findings. Mortality before discharge was defined as death during the initial admission. RESULTS: A total of 88 of the 650 patients (13.5%) died during the study period; mortality before discharge occurred in 66 of the 88 (75.0%); mortality after discharge occurred in 22 of the 88 (25.0%). Common causes of mortality before discharge were palliation for respiratory anomalies (15/66 [22.7%]), associated syndromes (11/66 [16.7%]), and neurologic anomalies (10/66 [15.2%]). The most common syndrome leading to palliation was trisomy 18 (7/66 [10.6%]). Causes of mortality after discharge had available documentation for 17 of 22 patients (77.3%). Common causes were respiratory compromise (6/17 [35.3%]), sudden unexplained deaths (6/17 [35.3%]), and Fanconi anemia (2/17 [11.8%]). Of the patients discharged from hospital, 22 of 584 (3.8%) subsequently died. There was no statistical difference in VACTERL association between mortality before discharge (31/61 [50.8%]) and mortality after discharge (11/20 [55.0%]), nor in incidence of twins between mortality before discharge (8/56 [14.3%]) and mortality after discharge (2/18 [11.1%]). CONCLUSIONS: We identified predictors of mortality in patients with esophageal atresia in a large prospective cohort. Parents of children with esophageal atresia must be counselled appropriately as to the likelihood of death after discharge from hospital.

Impact of Esophageal Atresia on the Success of Fundoplication for Gastroesophageal Reflux.

OBJECTIVES: Fundoplication is commonly performed in patients with a history of esophageal atresia (EA), however, the success of this surgery is reduced, as reflected by an increased rate of redo fundoplication. We aimed to determine whether EA impacts the prevalence of fundoplication, its timing, and performance of a redo operation. STUDY DESIGN: A single-center, retrospective review of all patients undergoing fundoplication over a 20-year period (1994-2013) was performed. Redo fundoplication was used as a surrogate for surgical failure. RESULTS: A total of 767 patients (patients with EA 85, those who did not have EA 682) underwent fundoplication during the study period. Median age (months) at primary fundoplication was lower in patients with EA (7.2 vs those who did not have EA 23.3; P < .001). Redo fundoplication rates between groups were not significantly different (EA 11/85 vs 53/682; P = .14). Median time (months) between primary and redo fundoplication was greater in patients with EA (36.2 vs 11.7; P = .03). CONCLUSIONS: Contrary to popular belief, the incidence of redo fundoplication was not significantly increased in patients with a history of EA. However, patients with EA underwent fundoplication at younger ages, which may be related to early life-threatening events in these patients. These results inform perioperative counseling, and highlight the importance of sustained surgical follow-up in patients with EA.

Baseline leptin and leptin reduction predict improvements in metabolic variables and long-term fat loss in obese children and adolescents: a prospective study of an inpatient weight-loss program.

BACKGROUND: It is unclear whether high plasma leptin in obese individuals represents leptin resistance or whether individuals with marked reductions in leptin concentrations in response to weight loss may be at greater risk of regaining weight. Moreover, whether changes in leptin predict metabolic improvements during weight loss is uncertain. OBJECTIVE: The objective was to prospectively examine associations between plasma leptin, body fat, and weight and metabolic risk factors in obese children during weight loss. DESIGN: In obese children and adolescents [n = 203; mean age: 14.1 y, >98th body mass index (BMI) percentile for age and sex] participating in a 2-mo inpatient weight-loss program, we measured changes in body composition (by dual-energy X-ray absorptiometry), plasma leptin, insulin, and lipids. After discharge, anthropometric measures and plasma leptin were remeasured at 6 (n = 139) and 12 (n = 100) mo. RESULTS: During the 2-mo program, mean (±SD) weight and fat loss were 13.9 ± 4.0 kg and 9.2 ± 2.5 kg, respectively; and mean plasma leptin decreased by 76%. Weight and fat loss were sustained, and no significant differences in BMI-SD score (SDS) or body composition were found between 12 and 2 mo. Baseline leptin was a negative predictor for percentage fat loss at 2, 6, and 12 mo (P < 0.05). The percentage change in leptin during the 2-mo intervention positively correlated with the relative change in fasting insulin, the relative change in LDL cholesterol at 2 mo, percentage fat loss, and change in BMI-SDS at 2 and 6 mo (P < 0.02). CONCLUSIONS: Even in obese children with strongly elevated baseline leptin, large leptin reductions that predict short- and long-term loss of body fat and improvements in lipids and insulin sensitivity can be achieved. Thus, increased plasma leptin in obese children may not necessarily reflect leptin resistance; many children appear to remain leptin sensitive at this age.

During rapid weight loss in obese children, reductions in TSH predict improvements in insulin sensitivity independent of changes in body weight or fat.

BACKGROUND: Although serum TSH is often elevated in obesity and may be linked to disorders of lipid and glucose metabolism, the clinical relevance of these relationships remains unclear. SUBJECTS: Subjects were obese children and adolescents (n=206; mean age 14 yr) undergoing rapid weight and fat loss in a standardized, multidisciplinary, 2-month, in-patient weight loss program. DESIGN: This was a prospective study that determined thyroid function, glucose and lipid parameters, leptin, anthropometric measures, and body composition measured by dual-energy x-ray absorption at baseline and at the end of the intervention. RESULTS: At baseline, 52% of children had TSH concentrations in the high normal range (>2.5 mU/liter), but TSH was not correlated with body weight, body mass index sd scores, lean body mass, or body fat percentage. At baseline, independent of adiposity, TSH significantly correlated with total cholesterol (P=0.008), low-density lipoprotein cholesterol (P=0.013), fasting insulin (P=0.010), homeostatic model assessment (HOMA) (P=0.004), and leptin (P=0.006). During the intervention, mean body fat, TSH, HOMA, and fasting insulin decreased by 21, 11, 53, and 54%, respectively. Change (Δ) in TSH did not correlate with Δbody weight or Δbody composition, but ΔTSH significantly correlated with, Δfasting insulin and ΔHOMA, independent of Δbody weight or Δbody composition (P<0.05). CONCLUSION: TSH concentrations are elevated in obese children but are not correlated with the amount of excess body weight or fat. During weight loss, independent of changes in body weight or composition, decreases in elevated serum TSH predict decreases in fasting insulin and HOMA. These findings suggest interventions that target high TSH concentrations during weight loss in obese subjects may improve insulin sensitivity.

Physical activity behaviours of adults in the Greater Green Triangle region of rural Australia.

OBJECTIVE: To assess physical activity (PA) behaviours of adults in rural Australia. DESIGN AND SETTING: Three cross-sectional surveys in the Greater Green Triangle area covering the south-east of South Australia (Limestone Coast), and south-west (Corangamite Shire) and north-west (Wimmera) of Victoria during 2004-2006. PARTICIPANTS: A total of 1546 persons, aged 25- 74 years, randomly selected from the electoral roll. MAIN OUTCOME MEASURES: Overall PA, leisure-time PA, occupational PA, active commuting and moderate-to-vigorous PA. RESULTS: Approximately 80% of participants, more women than men, engaged in 30 minutes or more of daily PA. Only 30% (95% CI 26.3, 33.0) of men and 21% (95% CI 18.3, 23.9) of women did moderate-to-vigorous PA for at least 20-30 minutes four or more times a week. In leisure time, most participants were moderately active; almost one-fifth were inactive and another fifth highly active. Two-thirds of men engaged in high-level occupational PA, compared with one-sixth of women. Only 30% of participants actively commuted to work. There was a tendency for a positive association between income level and leisure-time PA. CONCLUSIONS: One-fifth of adults in rural Australia were inactive. While there was a high prevalence of participants who engaged in daily PA, few did so at moderate-to-vigorous intensity to achieve health benefits. As occupational PA is difficult to change, improvements in levels of PA are more likely during leisure-time and for some people by engaging in commuting PA.