Parental risk factors for oesophageal atresia.

BACKGROUND: An Oesophageal atresia (OA) affects almost 1 in 3500 newborn and its aetiology for development between 4th to 6th pregnancy weeks had not yet been clarified. METHODS: This retrospective, observational control group-supported (n = 30) examination was performed with OA mothers (n = 20) who were interrogated via specialized questionnaires and interviews to evaluate data on medical pregnancy history including hormonal treatment, changing of life habits (nutrition, diet, medication), drug consumption (alcohol, smoking, illicit drugs) as well as exposure to nuclear waste or poisonous substance exposition. Aim was to assess risk factors during pregnancy and in particular in the first trimester. RESULTS: The body mass index (BMI) prior pregnancy of OA mothers was significant lower (p = 0.022) and the number of mothers with obesity (BMI>30) did not differ to control group mothers (p = 0.081). They had additionally more pre-existing illnesses (p = 0.009) and allergies (p = 0.001). Control group mothers changed dietary habits with higher meat (p = 0.032) and caffeine intake (p = 0.012) compared to OA mothers, which had higher rates of abnormalities during pregnancy (p < 0.001) and 38.7% of them suffered of ≥1 abortion in the past. The ethnical background of OA mothers was more often German (p < 0.033), while OA fathers had a lower socioeconomic status (p = 0.039). CONCLUSION: Maternal factors like previous abortions, obesity and immunological predispositions like existence of allergies combined with increased daily dairy consumption influenced obviously the occurrence of OA.

Guía de Práctica Clínica en atresia esofágica / Clinical practice guide on esophageal atresia

La atresia esofágica es una de las anomalías congénitas más frecuentes en la práctica quirúrgica neonatal. Se estima que tiene una incidencia de 1 por cada 3500 recién nacidos vivos a nivel mundial. La preparación de guías de actuación y protocolos asistenciales es tendencia en la práctica médica actual. Esta Guía de Práctica Clínica se elaboró respondiendo a la necesidad de protocolizar la atención médico-quirúrgica de la atresia esofágica. En el Centro Territorial de Cirugía Neonatal de Holguín, donde se regionaliza la atención a neonatos de las cinco provincias orientales del país con afecciones congénitas y quirúrgicas de alta complejidad, la atresia esofágica fue la afección quirúrgica más frecuente en los últimos diez años, con una supervivencia ascendente que alcanzó 94,4 por ciento en 2019. La guía que se presenta se aprobó en el Primer Consenso Nacional de Guías de Prácticas Clínicas en Cirugía Pediátrica, en Varadero, Matanzas en 2019. Incluye las principales pautas para el diagnóstico, tratamiento y seguimiento de los pacientes afectados y se considera una herramienta eficiente para mejorar los resultados en la asistencia médica y quirúrgica neonatal(AU)

Esophageal atresia is one of the most common congenital anomalies in neonatal surgical practice. It is estimated to have an incidence of 1 per 3500 live newborns globally. The preparation of action guides and care protocols is a trend in current medical practice. This Clinical Practice Guide was prepared in response to the need to protocolize the medical-surgical care of esophageal atresia. In the Territorial Center for Neonatal Surgery of Holguín, where the care of neonates from the five eastern provinces of the country with congenital and surgical conditions of high complexity is regionalized, esophageal atresia was the most frequent surgical condition in the last ten years, with an ascending survival that reached 94.4 percent in 2019. The guideline presented was approved in the First National Consensus of Clinical Practice Guidelines in Pediatric Surgery, in Varadero, Matanzas in 2019. It includes the main guidelines for the diagnosis, treatment and follow-up of affected patients and is considered an efficient tool to improve outcomes in neonatal medical and surgical care(AU)

Nutritional role of amniotic fluid: clues from infants with congenital obstruction of the digestive tract.

AIMS: To investigate the role played by amniotic fluid in late fetal nutrition by analysis of infants born with digestive tract atresia. METHODS: Birth weight (BW), gestational age and gender of infants born with oesophageal (OA), duodenal (DA), jejunal (JA) and ileal atresia (IA) were recorded and BW Z-scores compared. Infants with incomplete obstruction (stenosis), chromosomal or syndromic conditions and multiple congenital malformations were excluded. Term infants admitted with suspected postnatal intestinal obstruction in whom no congenital malformation was found were used as a control group. RESULTS: A total of 584 infants were identified comprising 148 OA, 60 DA, 26 JA and 57 IA with 293 in the control group. Infants with OA and DA had statistically significantly lower BW Z-score than controls. However, BW Z-score for infants with more distal atresia (JA and IA) was similar to controls. When compared with infants with OA, BW Z-score for infants with more distal atresia was higher than that for OA. BW Z-score in infants with OA was significantly lower in those born at term compared with those born preterm (mean±SD -0.92±1.0 vs -0.48±0.87; p=0.01) with a significant negative correlation between BW Z-score and increasing gestational age (R2=0.12; p<0.0001). This effect of gestational age was not seen in other atresias. CONCLUSION: These observations support the concept that reduced enteral absorption of amniotic fluid due to high digestive tract obstruction in utero reduces fetal growth. The effect is greater when the obstruction is more proximal and with advancing gestation.

Esophageal Atresia: Future Directions for Research on the Digestive Tract.

Esophageal atresia (EA) is a congenital malformation defined by the discontinuity of the esophagus occurring in 2.4 in 10,000 births. As survival rates are high, the significant medical morbidity became more relevant. Short-term and long-term morbidities involve the respiratory and gastrointestinal system in the majority of the patients. The impact of this morbidity seems large enough to inspire researchers to develop experimental animal models that may help understanding the pathogenesis and pathophysiology. These models can also be used to explore potential surgical therapies. We reviewed the clinical and experimental literature focusing on esophageal morbidity in EA. Although the consequences of esophageal motility disorders are very relevant in the clinical setting, research remains largely underexplored. Consequently, we suggest integrating motility function assessment in the existing research models.

Environmental factors in the etiology of isolated and nonisolated esophageal atresia in a Chinese population: A case-control study.

BACKGROUND: Esophageal atresia (EA) is a common birth defect that occurs with tracheoesophageal fistula (TEF), although etiological studies on EA/TEF have produced inconsistent results. METHODS: The aim of this study was to examine the association between environmental factors during pregnancy and the risk of EA/TEF in a Chinese population. Cases of isolated EA and nonisolated EA and unaffected controls were identified between July 2005 and November 2015, and face-to-face questionnaires concerning exposure to environmental factors were administered to the birth mothers of 130 cases and 400 controls. The adjusted odds ratio (OR) and 95% confidence interval (CI) were calculated to assess the association between environmental factors and the risk of EA/TEF. RESULTS: The results of this case-control study suggest that lower maternal education (p < 0.0001), maternal binge drinking (OR = 2.63; 95% CI, 1.05-6.6) and pickled food consumption (OR = 2.04; 95% CI, 1.31-3.71) during pregnancy increase the risk of EA in offspring, while maternal folic acid supplementation (OR = 0.45; 95% CI, 0.29-0.71) is significantly associated with a decreased risk of EA. CONCLUSION: These results suggest a role for environmental exposures in the etiology of EA/TEF; however, further studies are needed to replicate the observed associations. Birth Defects Research (Part A) 106:840-846, 2016. © 2016 Wiley Periodicals, Inc.

Hypertensive Emergencies in Pregnancy.

The prevalence of hypertensive disorders in pregnancy is increasing. The etiology and pathophysiology of hypertensive disorders in pregnancy remain poorly understood. Hypertensive disorders are a major cause of maternal and perinatal morbidity and mortality. Treatment of hypertension decreases the incidence of severe hypertension, but it does not impact rates of preeclampsia or other pregnancy complications. Several antihypertensive medications are commonly used in pregnancy, although there is a lack of randomized controlled trials. Severe hypertension should be treated immediately to prevent maternal end-organ damage. Appropriate antepartum, intrapartum, and postpartum management is important in caring for patients with hypertensive disorders.

Comparison of environmental risk factors for esophageal atresia, anorectal malformations, and the combined phenotype in 263 German families.

Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) and anorectal malformations (ARM) represent the severe ends of the fore- and hindgut malformation spectra. Previous research suggests that environmental factors are implicated in their etiology. These risk factors might indicate the influence of specific etiological mechanisms on distinct developmental processes (e.g. fore- vs. hindgut malformation). The present study compared environmental factors in patients with isolated EA/TEF, isolated ARM, and the combined phenotype during the periconceptional period and the first trimester of pregnancy in order to investigate the hypothesis that fore- and hindgut malformations involve differing environmental factors. Patients with isolated EA/TEF (n = 98), isolated ARM (n = 123), and the combined phenotype (n = 42) were included. Families were recruited within the context of two German multicenter studies of the genetic and environmental causes of EA/TEF (great consortium) and ARM (CURE-Net). Exposures of interest were ascertained using an epidemiological questionnaire. Chi-square, Fisher's exact, and Mann-Whitney U-tests were used to assess differences between the three phenotypes. Newborns with isolated EA/TEF and the combined phenotype had significantly lower birth weights than newborns with isolated ARM (P = 0.001 and P < 0.0001, respectively). Mothers of isolated EA/TEF consumed more alcohol periconceptional (80%) than mothers of isolated ARM or the combined phenotype (each 67%). Parental smoking (P = 0.003) and artificial reproductive techniques (P = 0.03) were associated with isolated ARM. Unexpectedly, maternal periconceptional multivitamin supplementation was most frequent among patients with the most severe form of disorder, i.e. the combined phenotype (19%). Significant differences in birth weight were apparent between the three phenotype groups. This might be attributable to the limited ability of EA/TEF fetuses to swallow amniotic fluid, thus depriving them of its nutritive properties. Furthermore, the present data suggest that fore- and hindgut malformations involve differing environmental factors. Maternal periconceptional multivitamin supplementation was highest among patients with the combined phenotype. This latter finding is contrary to expectation, and warrants further analysis in large prospective epidemiological studies.

Alveolar Capillary Dysplasia as a Cause of Persistent Pulmonary Hypertension.

BACKGROUND: Persistent pulmonary hypertension (PPHN) in a term or late preterm has varied etiology. CASE CHARACTERISTICS: A late preterm neonate operated for esophageal atresia with tracheo-esophageal fistula was complicated by severe pulmonary hypertension and unable to be weaned off from respiratory support. OUTCOME: The neonate expired by 15 weeks of life; diagnosis was made on postmortem lung biopsy. MESSAGE: Alveolarcapillary dysplasia should be considered in a neonate with idiopathic refractory PPHN, if associated with anomalies.

Anesthetic management for surgery of esophagus atresia in a newborn with Goldenhar's syndrome / Manejo anestésico para cirurgia de atresia de esôfago em um recém-nascido com síndrome de Goldenhar / Manejo anestésico para la cirugía de atresia de esófago en un neonato con síndrome de Goldenhar

Goldenhar's syndrome is a polymalformative condition consisting of a craniofacial dysostosis that determines difficult airway in up to 40% of cases. We described a case of a newborn with Goldenhar's syndrome with esophageal atresia and tracheoesophageal fistula who underwent repair surgery.

A síndrome de Goldenhar é um quadro de polimalformação que consiste em uma disostose craniofacial que determina uma via respiratória difícil em até 40% dos casos. Nós descrevemos um caso de um recém-nascido com síndrome de Goldenhar com atresia de esôfago e fístula traqueoesofágica para a qual foi feita cirurgia de reparo.

El síndrome de Goldenhar es un cuadro polimalformativo consistente en una disostosis craneofacial que condiciona una vía aérea difícil hasta en el 40% de los casos. Describimos un caso de un neonato con síndrome de Goldenhar con atresia de esófago y fístula traqueoesofágica al que se practicó cirugía de reparación de la misma.

Anesthetic management for surgery of esophagus atresia in a newborn with Goldenhar's syndrome.

BACKGROUND AND OBJECTIVES: Goldenhar's syndrome is a polymalformative condition consisting of a craniofacial dysostosis that determines difficult airway in up to 40% of cases. We described a case of a newborn with Goldenhar's syndrome with esophageal atresia and tracheoesophageal fistula who underwent repair surgery. CASE REPORT: We report the case of a 24-h-old newborn with Goldenhar's syndrome. He had esophageal atresia with distal tracheoesophageal fistula. It was decided that an emergency surgery would be performed for repairing it. It was carried out under sedation, intubation with fibrobronchoscope distal to the fistula, to limit the air flow into the esophagus, and possible abdominal distension. Following complete repair of the esophageal atresia and fistula ligation, the patient was transferred to the intensive care unit and intubated under sedation and analgesia. CONCLUSIONS: The finding of a patient with Goldenhar's syndrome and esophageal atresia assumes an exceptional situation and a challenge for anesthesiologists, since the anesthetic management depends on the patient comorbidity, the type of tracheoesophageal fistula, the usual hospital practice and the skills of the anesthesiologist in charge, with the main peculiarity being maintenance of adequate pulmonary ventilation in the presence of a communication between the airway and the esophagus. Intubation with fibrobronchoscope distal to the fistula deals with the management of a probably difficult airway and limits the passage of air to the esophagus through the fistula.

Maternal factors in the origin of isolated oesophageal atresia: A population-based case-control study.

BACKGROUND: In most patients affected by isolated oesophageal atresia (IOA) the etiology is largely unknown. Thus, the aim of this study was to analyze potential risk factors in mothers. METHODS: The study samples included 221 cases with IOA, 356 matched and 38,151 population controls without any defect in the population-based dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980 to 1996. Only those exposures were evaluated that were medically recorded in prenatal maternity logbooks during the critical period of IOA. RESULTS: The findings of this case-control study suggested that the mothers of cases with IOA had a higher proportion of first delivery and lower socioeconomic status. Acute respiratory diseases (odds ratio [OR] 95% confidence interval [CI], 3.8, 1.8-8.1) and essential hypertension treated with nifedipine (OR 95% CI, 3.8, 1.7-8.7) in the mothers of cases associated with a higher risk for IOA in their children. CONCLUSION: First delivery, lower socioeconomic status, acute respiratory diseases and essential hypertension treated with nifedipine in the mothers may associate with a higher risk for IOA in their children.

Oesophageal atresia and tracheo-oesophageal fistula.

Oesophageal atresia with tracheo-oesophageal fistula is a relatively common congenital anomaly occurring in around 1:2500 births. The aetiology and embryology of the condition remain unclear, whilst associations with other significant anomalies are common. Studies in rodent models are contributing to our understanding of the condition. Advances in surgical care and neonatal management have improved survival considerably to around 90%. Long-gap and isolated oesophageal atresia present significant management challenges. Post-operative and long-term complications including oesophageal stricture, gastro-oesophageal reflux and respiratory compromise however remain relatively common and continue to pose a challenge for the ongoing management of patients.

Clinical and etiological heterogeneity in patients with tracheo-esophageal malformations and associated anomalies.

Esophageal Atresia (EA) is a severe developmental defect of the foregut that presents with or without a Tracheo-Esophageal Fistula (TEF). The prevalence of EA/TEF over time and around the world has been relatively stable. EA/TEF is manifested in a broad spectrum of anomalies: in some patients it manifests as an isolated atresia or fistula, but in over half it affects several organ systems. While the associated malformations are often those of the VACTERL spectrum (Vertebral, Anorectal, Cardiac, Tracheo-Esophageal, Renal and Limb), many patients are affected by other malformations, such as microcephaly, micrognathia, pyloric stenosis, duodenal atresia, a single umbilical artery, and anomalies of the genitourinary, respiratory and gastrointestinal systems. Though EA/TEF is a genetically heterogeneous condition, recurrent genes and loci are sometimes affected. Tracheo-Esophageal (TE) defects are in fact a variable feature in several known single gene disorders and in patients with specific recurrent Copy Number Variations and structural chromosomal aberrations. At present, a causal genetic aberration can be identified in 11-12% of patients. In most, EA/TEF is a sporadic finding; the familial recurrence rate is low (1%). As this suggests that epigenetic and environmental factors also contribute to the disease, non-syndromic EA/TEF is generally believed to be a multifactorial condition. Several population-based studies and case reports describe a wide range of associated risks, including age, diabetes, drug use, herbicides, smoking and fetal alcohol exposure. The phenotypical and genetic heterogeneity seen in EA/TEF patients indicates not one underlying cause, but several. Unraveling the complex multifactorial and heterogeneous etiology of EA/TEF and associated features will require large cohorts of patients. Combined statistical analysis of component findings, genome sequencing, and genome wide association studies will elucidate new causal genetic defects and predisposing loci in the etiology within specific sub-populations. Improved knowledge of environmental risk factors, genetic predisposition and causal genetic syndromes may improve prediction and parental counseling, and prevent co-morbidity.

Upper gastrointestinal motility: prenatal development and problems in infancy.

Deglutition, or swallowing, refers to the process of propulsion of a food bolus from the mouth into the stomach and involves the highly coordinated interplay of swallowing and breathing. At 34 weeks gestational age most neonates are capable of successful oral feeding if born at this time; however, the maturation of respiration is still in progress at this stage. Infants can experience congenital and developmental pharyngeal and/or gastrointestinal motility disorders, which might manifest clinically as gastro-oesophageal reflux (GER) symptoms, feeding difficulties and/or refusal, choking episodes and airway changes secondary to micro or overt aspiration. These problems might lead to impaired nutritional intake and failure to thrive. These gastrointestinal motility disorders are mostly classified according to the phase of swallowing in which they occur, that is, the oral preparatory, oral, pharyngeal and oesophageal phases. GER is a common phenomenon in infancy and is referred to as GERD when it causes troublesome complications. GER is predominantly caused by transient relaxation of the lower oesophageal sphincter. In oesophageal atresia, oesophageal motility disorders develop in almost all patients after surgery; however, a congenital origin of disordered motility has also been proposed. This Review highlights the prenatal development of upper gastrointestinal motility and describes the most common motility disorders that occur in early infancy.

Maternal hyperthyroidism increases the prevalence of foregut atresias in fetal rats exposed to adriamycin.

PURPOSE: Gastrointestinal malformations such as esophageal atresia with tracheoesophageal fistula (EA/TEF) and duodenal atresia (DA) have been reported in infants born to hyperthyroid mothers or with congenital hypothyroidism. The present study aimed to test whether maternal thyroid status during embryonic foregut division has any influence on the prevalence of EA/TEF and DA in an accepted rat model of these malformations. METHODS: Pregnant rats received either vehicle or 1.75 mg/kg i.p. adriamycin on gestational days 7, 8 and 9. Transient maternal hyper or hypothyroidism was induced by oral administration of levothyroxine (LT4, 50 µg/kg/day) or propylthiouracil (PTU, 2 mg/kg/day), respectively, on days 7 to 12 of gestation. Plasma cholesterol, total T3, free T4 and TSH were measured at gestational days 7, 12, and 21. At the end of gestation, the mothers were sacrificed and embryo-fetal mortality was recorded. Fetuses were dissected to determine the prevalence of esophageal and intestinal atresias. RESULTS: At gestational day 12, mothers treated with LT4 or PTU had hyper or hypothyroid status, respectively; plasma cholesterol levels were similar. In the adriamycin-exposed fetuses from hyperthyroid mothers, the embryonal resorption rate and the prevalence of both EA/TEF and DA were significantly higher than in the other groups; maternal hypothyroidism during the same period did not have significant effect on the prevalence of atresias. CONCLUSIONS: Maternal hyperthyroidism during the embryonic window corresponding to foregut cleavage increased the prevalence of both EA/TEF and duodenal atresia in fetal rats exposed to adriamycin. This suggests that maternal thyroid hormone status might be involved in the pathogenesis of foregut atresias and invites further research on this likely clinically relevant issue in humans.

Surgical intervention for esophageal atresia in patients with trisomy 18.

Trisomy 18 is a common chromosomal aberration syndrome involving growth impairment, various malformations, poor prognosis, and severe developmental delay in survivors. Although esophageal atresia (EA) with tracheoesophageal fistula (TEF) is a potentially fatal complication that can only be rescued through surgical correction, no reports have addressed the efficacy of surgical intervention for EA in patients with trisomy 18. We reviewed detailed clinical information of 24 patients with trisomy 18 and EA who were admitted to two neonatal intensive care units in Japan and underwent intensive treatment including surgical interventions from 1982 to 2009. Nine patients underwent only palliative surgery, including six who underwent only gastrostomy or both gastrostomy and jejunostomy (Group 1) and three who underwent gastrostomy and TEF division (Group 2). The other 15 patients underwent radical surgery, including 10 who underwent single-stage esophago-esophagostomy with TEF division (Group 3) and five who underwent two-stage operation (gastrostomy followed by esophago-esophagostomy with TEF division) (Group 4). No intraoperative death or anesthetic complications were noted. Enteral feeding was accomplished in 17 patients, three of whom were fed orally. Three patients could be discharged home. The 1-year survival rate was 17%: 27% in those receiving radical surgery (Groups 3 and 4); 0% in those receiving palliative surgery (Groups 1 and 2). Most causes of death were related to cardiac complications. EA is not an absolute poor prognostic factor in patients with trisomy 18 undergoing radical surgery for EA and intensive cardiac management.