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The importance of multidisciplinary long-term follow-up for adults born with esophageal atresia (EA) is increasingly recognized. Hence, a valid, condition-specific instrument to measure health-related quality of life (HRQoL) becomes imperative. This study aimed to develop and validate such an instrument for adults with EA. The Specific Quality of life in Esophageal atresia Adults (SQEA) questionnaire was developed through focus group-based item generation, pilot testing, item reduction and a multicenter, nationwide field test to evaluate the feasibility, reliability (internal and retest) and validity (structural, construct, criterion and convergent), in compliance with the consensus-based standards for the selection of health measurement instruments guidelines. After pilot testing (n = 42), items were reduced from 144 to 36 questions. After field testing (n = 447), three items were discarded based on item-response theory results. The final SQEA questionnaire (33 items) forms a unidimensional scale generating an unweighted total score. Feasibility, internal reliability (Cronbach’s alpha 0.94) and test–retest agreement (intra-class coefficient 0.92) were good. Construct validity was discriminative for esophageal replacement (P

BACKGROUND: Adults with esophageal atresia (EA) require a multidisciplinary follow-up approach, taking into account gastroesophageal problems, respiratory problems and psychosocial wellbeing. Too little is known about the full scope of these individuals' healthcare needs. We aimed to map all medical and psychosocial needs of adults with EA and their family members, and to formulate healthcare recommendations for daily practice.METHODS: A qualitative study was performed, using data from recorded semi-structured interviews with two focus groups, one consisting of adult patients with EA (n = 15) and one of their family members (n = 13). After verbatim transcription and computerized thematic analysis, results were organized according to the International Classification of Functioning, Disability and Health. Ethical approval had been obtained.RESULTS: Healthcare needs were described through 74 codes, classified into 20 themes. Most important findings for patients included the impact of gastrointestinal and pulmonary problems on daily life, long-term emotional distress of patients and parents and the need of a standardized multidisciplinary follow-up program during both child- and adulthood.CONCLUSION: The focus groups revealed numerous physical and mental health problems, as well as social difficulties, that require attention from different healthcare providers. We have formulated several healthcare recommendations that physicians may use in long-term follow-up.

SUMMARY Background Endoscopic surveillance of adults with esophageal atresia is advocated, but the optimal surveillance strategy remains uncertain. This study aimed to provide recommendations on appropriate starting age and intervals of endoscopic surveillance in adults with esophageal atresia. Methods Participants underwent standardized upper endoscopies with biopsies. Surveillance intervals of 3–5 years were applied, depending on age and histopathological results. Patient’s age and time to development of (pre)malignant lesions were calculated. Results A total of 271 patients with esophageal atresia (55% male; median age at baseline endoscopy 26.7 (range 15.6–68.5) years; colon interposition n = 17) were included. Barrett’s esophagus was found in 19 (7%) patients (median age 32.3 (17.8–56.0) years at diagnosis). Youngest patient with a clinically relevant Barrett’s esophagus was 20.9 years. Follow-up endoscopies were performed in 108 patients (40%; median follow-up time 4.6 years). During surveillance, four patients developed Barrett’s esophagus but no dysplasia or cancer was found. One 45-year-old woman with a colon interposition developed an adenoma with high-grade dysplasia which was radically removed. Two new cases of esophageal carcinoma were diagnosed in patients (55 and 66 years old) who were not under surveillance. One of them had been curatively treated for esophageal carcinoma 13 years ago. Conclusions This study shows that endoscopic screening of patients with esophageal atresia, including those with a colon interposition, can be started at 20 years of age. Up to the age of 40 years a surveillance interval of 10 years appeared to be safe. Endoscopic surveillance may also be warranted for patients after curative esophageal cancer treatment.

Background Endoscopic dilatation is the first-line treatment of stricture formation after esophageal atresia (EA) repair. However, there is no consensus on how to perform these dilatation procedures which may lead to a large variation between centers, countries and doctor’s experience. This is the first cross-sectional study to provide an overview on differences in endoscopic dilatation treatment of pediatric anastomotic strictures worldwide. Methods An online questionnaire was sent to members of five pediatric medical networks, experienced in treating anastomotic strictures in children with EA. The main outcome was the difference in endoscopic dilatation procedures in various centers worldwide, including technical details, dilatation approach (routine or only in symptomatic patients), and adjuvant treatment options. Descriptive statistics were performed with SPSS. Results Responses from 115 centers from 32 countries worldwide were analyzed. The preferred approach was balloon dilatation (68%) with a guidewire (66%), performed by a pediatric gastroenterologist (n = 103) or pediatric surgeon (n = 48) in symptomatic patients (68%). In most centers, hydrostatic pressure was used for balloon dilatation. The insufflation duration was standardized in 59 centers with a median duration of 60 (range 5–300) seconds. The preferred first-line adjunctive treatments in case of recurrent strictures were intralesional steroids and topical mitomycin C, in respectively 47% and 31% of the centers. Conclusions We found a large variation in stricture management in children with EA, which confirms the current lack of consensus. International networks for rare diseases are required for harmonizing and comparing the procedures, for which we give several suggestions.

__Background:__ Patients born with esophageal atresia (EA) have a higher incidence of infantile hypertrophic pyloric stenosis (IHPS), suggestive of a relationship. A shared etiology makes sense from a developmental perspective as both affected structures are foregut derived. A genetic component has been described for both conditions as single entities and EA and IHPS are variable components in several monogenetic syndromes. We hypothesized that defects disturbing foregut morphogenesis are responsible for this combination of malformations. __Methods:__ We investigated the genetic variation of 15 patients with both EA and IHPS with unaffected parents using exome sequencing and SNP arraybased genotyping, and compared the results to mouse transcriptome data of the developing foregut. __Results:__ We did not identify putatively deleterious de novo mutations or recessive variants. However, we detected rare inherited variants in EA or IHPS disease genes or in genes important in foregut morphogenesis, expressed at the proper developmental time-points. Two pathways were significantly enriched (p < 1 × 10−5): proliferation and differentiation of smooth muscle cells and self-renewal of satellite cells. __Conclusions:__ None of our findings could fully explain the combination of abnormalities on its own, which makes complex inheritance the most plausible genetic explanation, most likely in combination with mechanical and/or environmental factors. As we did not find one defining monogenetic cause for the EA/IHPS phenotype, the impact of the corrective surgery could should be further investigated.

Background The most frequent complication after esophageal atresia repair remains anastomotic stricture formation. The initial treatment is endoscopic dilatation. Intralesional steroid injection (ISI) might be an effective adjuvant treatment in case of recurrent strictures. In this series we present our initial experience with this intervention. Methods Data on primary surgery, stricture treatment, postoperative complications, outcome and growth were retrospectively collected from electronic patient records. Findings were analyzed by descriptive statistics and mixed model analysis. Results Between 2014 and 2017, ISI was performed for severe recurrent anastomotic strictures in six patients (median age at injection 12.4 (2.1–34.7) months) after a median of 6 (2–20) dilatations. In five patients ISI was successful and the stenosis was cleared. No postoperative complications were reported, especially none related to acute adrenal suppression. Comparing the year before with the year after ISI, a significant positive change for weight (r = 0.70, p = 0.003) was calculated versus a negative change for height (r = − 0.87, p = 0.003). Conclusions We found ISI to be an effective adjuvant treatment to recurrent anastomotic stricture dilatation after esophageal atresia repair, without postoperative complications or symptoms of adrenal suppression. It remains important, however, to monitor growth effects. Further evaluation is required in a large prospective study. Type of study Treatment study, Level IV (case series).

Simple Summary We investigated the increased prevalence of Barrett's esophagus in adults with esophageal atresia. A higher polygenic risk score and disturbances in inflammatory, stress response and oncological pathways upon acid exposure suggest a genetic susceptibility and increased induction of inflammatory processes. Although further research is required to explore this hypothesis, this could be a first-step into selecting patients that are more at risk to develop Barrett's esophagus and/or esophageal carcinoma. Currently, an endoscopic screening and surveillance program is in practice in our institution for patients born with esophageal atresia, to early detect (pre)malignant lesions. Since recurrent endoscopies can be a burden for the patient, selecting patients by for example genetic susceptibility would allow to only include those at risk in future practice. The prevalence of Barrett's esophagus (BE) in adults born with esophageal atresia (EA) is four times higher than in the general population and presents at a younger age (34 vs. 60 years). This is (partly) a consequence of chronic gastroesophageal reflux. Given the overlap between genes and pathways involved in foregut and BE development, we hypothesized that EA patients have an intrinsic predisposition to develop BE. Transcriptomes of Esophageal biopsies of EA patients with BE (n = 19, EA/BE); EA patients without BE (n = 44, EA-only) and BE patients without EA (n = 10, BE-only) were compared by RNA expression profiling. Subsequently, we simulated a reflux episode by exposing fibroblasts of 3 EA patients and 3 controls to acidic conditions. Transcriptome responses were compared to the differential expressed transcripts in the biopsies. Predisposing single nucleotide polymorphisms, associated with BE, were slightly increased in EA/BE versus BE-only patients. RNA expression profiling and pathway enrichment analysis revealed differences in retinoic acid metabolism and downstream signaling pathways and inflammatory, stress response and oncological processes. There was a similar effect on retinoic acid signaling and immune response in EA patients upon acid exposure. These results indicate that epithelial tissue homeostasis in EA patients is more prone to acidic disturbances.

OBJECTIVES: To longitudinally evaluate self-reported and proxy-reported health status (HS) and quality of life (QoL) of school-aged children born with esophageal atresia (EA). METHODS: We obtained Pediatric Quality of Life Inventory (HS) and DUX-25 (QoL) questionnaires from children born with EA between 1999 and 2011 at 8 and/or 12 years old. Children completed self-reports during neuropsychological assessments in a prospective longitudinal follow-up program. Parents filled out proxy-reports at home. Total and subscale scores were evaluated longitudinally and compared with sex-specific reference norms. RESULTS: In total, 110 participants (62% boys) were included. Self-reported HS improved significantly between 8 and 12 years for both boys (mean difference [md] 4.35, effect size [ES] 0.54, P = 0.009) and girls (md 3.26, ES 0.63, P = 0.004). Proxy-reported HS tended to improve over time, while self-reported and proxy-reported QoL tended to decline. Self-reported HS at 8 years was below normal for both boys (md -5.44, ES -0.35, P

Summary Background Although the survival rate of esophageal atresia (EA) has increased to over 90%, the risk of functional long-term neurodevelopmental deficits is uncertain. Studies on long-term outcomes of children with EA show conflicting results. Therefore, we provide an overview of the current knowledge on the long-term neurodevelopmental outcome of children with EA. Methods We performed a structured literature search in Embase, Medline Ovid, Web of Science, Cochrane CENTRAL, and Google scholar on November 8, 2020 with the keywords ‘esophageal atresia’, ‘long-term outcome’, ‘motor development’, ‘cognitive development’, and ‘neurodevelopment’. Results The initial search identified 945 studies, of which 15 were included. Five of these published outcomes of multiple tests or tested at multiple ages. Regarding infants, one of six studies found impaired neurodevelopment at 1 year of age. Regarding preschoolers, two of five studies found impaired neurodevelopment; the one study assessing cognitive development found normal cognitive outcome. Both studies on motor function reported impairment. Regarding school-agers, the one study on neurodevelopmental outcome reported impairment. Cognitive impairment was found in two out of four studies, and motor function was impaired in both studies studying motor function. Conclusions Long-term neurodevelopment of children born with EA has been assessed with various instruments, with contrasting results. Impairments were mostly found in motor function, but also in cognitive performance. Generally, the long-term outcome of these children is reason for concern. Structured, multidisciplinary long-term follow-up programs for children born with EA would allow to timely detect neurodevelopmental impairments and to intervene, if necessary.

Following the mother and child policy called the Revolusi KIA in East Nusa Tenggara Province, the registration for low birth weight (LBW) infants increased because mothers should deliver at health facilities. The South Central Timor (TTS) district was suffered with LBW and therefore raised a question why the problem occurred. A qualitative study in a sub district of TTS district was implemented. The area was approximately 60 Km away from the district capital and 160 Km from the provincial capital, Kupang. The target resource persons were a pregnant woman, mother with LBW baby, health cadres and health personnel from the primary health care. A house visit was done to explore the problem among pregnant women. We found no risk of smoking and drinking alcohol among them. Passive smoker might happen due to husband smoking at home. In the Puskesmas we observed risk of anemia, malaria and chronic under nutrition among the mothers as also the risk factors of LBW. However, we found no specific follow up afterwards. Education was made but not recorded. There was no complete record also, for each mother at delivery, which indicated a problem in the health care delivery. The Puskesmas’ task was to identify individual risk factors of pregnancy but not for the newborn in context of the community. Certainly, the Puskesmas was in needs for improvements of health care services, in this study, the maternal and child health care.

Increasing numbers of children and adults with chronic disease status highlight the need for a value-based healthcare system. Patient-reported outcome measures (PROMs) are essential to value-based healthcare, yet it remains unclear how they relate to clinical outcomes such as health and daily functioning. We aimed to assess the added value of self-reported PROMs for health status (HS) and quality of life (QoL) in the long-term follow-up of children with foregut anomalies. We evaluated data of PROMs for HS and/or QoL among eight-year-olds born with congenital diaphragmatic hernia (CDH), esophageal atresia (EA), or congenital lung malformations (CLM), collected within the infrastructure of a multidisciplinary, longitudinal follow-up program. Clinical outcomes were categorized into different outcome domains, and their relationships with self-reported HS and QoL were assessed through multivariable linear regression analyses. A total of 220 children completed HS and/or QoL self-reports. In children with CDH and EA, lower cognition was significantly associated with lower self-reported HS. Due to the low number of cases, multivariable linear regression analysis was not possible in children with CLM. HS, QoL, and clinical outcomes represent different aspects of a child’s wellbeing and should be measured simultaneously to facilitate a more holistic approach to clinical decision making.

Contains fulltext : 170587.pdf (Publisher’s version ) (Closed access) BACKGROUND: Open lung biopsy can help differentiate between reversible and irreversible lung disease and may guide therapy. To assess the risk-benefit ratio of this procedure in pediatric extracorporeal membrane oxygenation (ECMO) patients, we reviewed data of all patients who underwent an open lung biopsy during ECMO in one of the two pediatric ECMO centers in a nationwide study in the Netherlands. RESULTS: In nineteen neonatal and six pediatric patients (0-15.5years), twenty-five open lung biopsies were performed during the study period. In 13 patients (52%), a classifying diagnosis of underlying lung disease could be made. In another nine patients (36%), specific pathological abnormalities were described. In three patients (12%), only nonspecific abnormalities were described. The histological results led to withdrawal of ECMO treatment in 6 neonates with alveolar capillary dysplasia/misalignment of pulmonary veins (24%) and in another 6 patients, corticosteroids were started (24%). All patients survived the biopsy procedure. Hemorrhagic complications were rare. CONCLUSION: An open lung biopsy during an ECMO run in neonates and children is a safe procedure with a minimum risk for blood loss and biopsy-related death. It can be very useful in diagnosing the underlying pathology and can guide cessation of ECMO treatment and thereby avoid continuation of futile treatment, especially in neonatal patients. LEVEL OF EVIDENCE: III. TYPE OF STUDY: Diagnostic study.

Aims Preconception care (PCC) is care that aims to improve the health of offspring by addressing risk factors in the pre‐pregnancy period. Consultations are recognized as a method to promote perinatal health. However, prospective parents underutilize PCC services. Uptake can improve if delivery approaches satisfy consumer preferences. Aim of this study was to identify preferences of women (consumers) as a first step to social marketed individual PCC consultations. Methods In depth, semi‐structured interviews were performed to identify women's views regarding the four components of the social marketing model: product (individual PCC consultation), place (setting), promotion (how women are made aware of the product) and price (costs). Participants were recruited from general practices and a midwife's practice. Content analysis was performed by systematic coding with NVIVO software. Results The 39 participants reflected a multiethnic intermediately educated population. Product: Many participants had little knowledge of the need and the benefits of the product. Regarding the content of PCC, they wish to address fertility concerns and social aspects of parenthood. PCC was seen as an informing and coaching service with a predominant role for health‐care professionals. Place: the general practitioner and midwife setting was the most mentioned setting. Promotion: A professional led promotion approach was preferred. Price: Introduction of a fee for PCC consultations will make people reconsider their need for a consultation and could exclude vulnerable patients from utilization. Conclusion This study provides consumer orientated data to design a social marketed delivery approach for individual PCC consultations.

Patients born with esophageal atresia (EA) have a 30 times higher prevalence of infantile hypertrophic pyloric stenosis (IHPS). This makes sense from a developmental perspective as both the esophagus and the pyloric sphincter are foregut derived structures. EA and IHPS are variable features in several (monogenetic) syndromes. This, and twin and familial studies, indicates a genetic component for both conditions as single entities. We hypothesized that genetic defects, disturbing foregut morphogenesis, are responsible for this combination of malformations. Non-genetic factors could also contribute, as mice exposed to Adriamycin develop EA andin uterodiethylstilbestrol exposure is associated with EA.We investigated the copy number profiles and protein coding variants of 15 patients with both EA and IHPS. As all parents were unaffected, we first considered dominant(de novo)or recessive inheritance models but could not identify putatively deleterious mutations or recessive variants. We did identify inherited variants in genes either known to be involved in EA or IHPS or important in foregut morphogenesis in all patients. Unfortunately, variant burden analysis did not show a significant difference with unaffected controls. However, the IHPS associated risk SNP rs1933683 had a significantly higher incidence (OR 3.29, p=0.009).Although the genetic variation in likely candidate genes as well as the predisposing locus nearBARX1(rs1933683) suggest a genetic component, it does not fully explain the abnormalities seen in these patients. Therefore, we hypothesize that a combination of high impact genetic, mechanical and environmental factors together can shift the balance to abnormal development.Summary statementInstead of one affected gene, the higher incidence of IHPS in EA patients is more likely the result of multiple (epi)genetic and environmental factors together shifting the balance to disease development.

IntroductionAnastomotic stricture formation is the most common postoperative complication after oesophageal atresia (OA) repair. The standard of care is endoscopic dilatation. A possible adjuvant treatment is intralesional steroid injection, which is thought to inhibit scar tissue formation and thereby to prevent stricture recurrence. We hypothesise that this intervention could prevent refractory strictures and reduce the total number of dilatations needed in these children.Methods and analysisThis is an international multicentre randomised controlled trial. Children with OA type C (n=110) will be randomised into intralesional steroid injection followed by balloon dilatation or dilatation only. Randomisation and intervention will take place when a third dilatation is performed. The indication for dilatation will be confirmed with an oesophagram. One radiologist—blinded for randomisation—will review all oesophagrams. The primary outcome parameter is the total number of dilatations needed with 2 association test. Secondary outcome parameters include the level of dysphagia, the luminal oesophageal diameter and stricture length (measured on the oesophagrams), the influence of comedication on stricture formation, systemic effects of intralesional steroids (cortisol levels, length and weight) and the cost-effectiveness. Patients will undergo a second oesophagram; length and weight will be measured repeatedly; a scalp hair sample will be collected; and three questionnaires will be administered. The follow-up period will be 6 months, with evaluation at 2–3 weeks, 3 and 6 months after the intervention.Ethics and disseminationPatients will be included after written parental informed consent. The risks and burden associated with this trial are minimal. The institutional review board of the Erasmus Medical Centre approved this protocol (MEC-2018–1586/NL65364.078.18). The results of the trial will be published in a peer-reviewed scientific journal and will be presented at international conferences.Trial registration numbers2018-002863-24 and NTR7726/NL7484.

Pulmonary hypertension (PH) is a life-threatening disease with a high mortality rate and a broad variety of underlying etiologies. The current golden standard for diagnosing PH and monitoring efficiency of treatment is right heart catheterization. As an alternative, serum biomarkers have been suggested. Cardiac troponin T (TnT), brain natriuretic peptide (BNP), and NT-proBNP seem the most potential. The aim of this systematic review was to evaluate the current literature on the prognostic value of these biomarkers in children with PH and their usefulness as a diagnostic tool. A systematic literature search yielded 14 studies on patients ≤18 years with proven PH with (NT-pro)BNP or TnT as primary outcome. TnT is suggested to be a promising biomarker, but its usefulness in clinical practice has not been proven. The levels of (NT-pro)BNP seemed to be reliable within one PH category, but differed significantly between categories. NT-proBNP showed a good correlation with mortality and might have a prognostic value.The lack of absolute levels makes (NT-pro)BNP unsuitable as a diagnostic marker, but in view of the relative changes, it could be used to monitor patients. Further investigation should explore differences in normal (NT-pro)BNP levels between the different categories of PH.• Pulmonary hypertension is a life-threatening disease. Diagnosis can be challenging in children; the current diagnostic options-right heart catheterization and echocardiography-are invasive and/or investigator-dependent procedures. • Biomarkers could be useful in this context because they are investigator independent and easy to obtain through blood samples. Brain natriuretic peptide (BNP) and its N-terminal cleavage product (NT-proBNP) seem to be the most promising. The value of these biomarkers in the diagnostic approach of PH has already been investigated in adults, with promising results. Pediatric studies are still scarce. What is new: • The levels of BNP and NT-proBNP in pediatric patients differ strongly between the different categories of PH. Within the same category, the levels are more or less equal. • The relative changes could render them a prognostic marker in the follow-up of a certain individual patient. At this moment there is not enough evidence to rely on BNP or NT-proBNP in clinical treatment of patients with PH.

Each year 9,900 equestrians present at Accident and Emergency Departments, 40% of them 10-19 year old females. The most common horse-riding injuries are to the head, brain, neck and face, torso and extremities. Because of the relatively larger head, children more often fall on their head. Wearing a helmet gives considerable protection. Despite the common use of a helmet by horseback riders, serious head injury still occurs regularly. Further research into improvement of the protective function of the helmet is indicated. The current safety vest (body protector) does not significantly reduce the risk of torso injury. Improvement of its protective function is necessary. Injury to the lower extremities is caused when they become trapped in the stirrup in a fall from or with the horse. Safety stirrups and sturdy footwear are possible preventive measures. Investment in the quality and promotion of preventive measures could reduce the frequency and severity of equestrian injuries.

Biomarkers may be helpful in prediction of outcomes of infants with congenital diaphragmatic hernia. The predictive value of high-sensitivity troponin T and N-terminal pro-brain natriuretic peptide was investigated in 128 infants with congenital diaphragmatic hernia. After correction for multiple testing, those biomarkers did not predict severe pulmonary hypertension, death, need of extracorporeal membrane oxygenation, or bronchopulmonary dysplasia. Trial registration Netherlands Trial Registry: 1310.