Congenital malformations and perinatal morbidity associated with intestinal neuronal dysplasia

A close relation between different forms of dysganglionosis such as intestinal neuronal dysplasia (IND) type B and aganglionosis has been established. No systematic analysis of other malformations and diseases accompanying IND has been made as yet. Congenital malformations and perinatal morbidity were analyzed in 109 patients with IND seen at the Department of Pediatric Surgery in Mainz from 1977 to 1996. IND was associated with Hirschsprung's disease in 47 cases; 22 children with IND had other abdominal malformations, including anal atresia, rectal stenosis, sigmoidal stenosis, ileal atresia, pyloric stenosis, and esophageal atresia. A cystic bowel duplication, a choledochal cyst, and a persisting urachus were also found. Extra-abdominal malformations such as Down's syndrome, congenital diaphragmatic hernia, aortic stenosis, and malformations of vertebral bodies were seen. Twin siblings of children with IND were either healthy (n=3) or died in utero (n=1). Seventeen children with IND developed severe intra-abdominal complications during the perinatal period such as necrotizing enterocolitis (NEC), meconium ileus, or bowel perforations. NEC was frequently associated with preterm birth. Bowel perforations were seen in mature and preterm newborns with IND. Taken together, IND is found in a variety of obstructive bowel diseases. This may support the hypothesis that IND is a secondary phenomenon or that congenital atresias and stenoses of the digestive tract have a pathogenesis similar to that of intestinal innervation disturbances. IND may also be a part of complex malformation patterns since it occurs with a number of extraintestinal and non-obstructive intestinal malformations.     

Congenital cardiac malformations in neonates with apparently isolated gastrointestinal malformations

Background:  The association of congenital cardiac malformations (CCM) with malformations of the gastrointestinal tract/abdominal wall is known. Nevertheless, the data presently available are derived from patient populations that include some special conditions known to be associated with a high rate of CCM. The aim of the present study was therefore to determine the incidence of cardiac malformations among neonates with apparently isolated malformations of the gastrointestinal tract/abdominal wall.
Methods:  A total of 201 neonates with apparently isolated gastrointestinal malformations were screened on echocardiography.
Result:  Thirty-six (17.9%) of the neonates were diagnosed as having a CCM. When the four most frequent gastrointestinal malformations were evaluated, a CCM was diagnosed in 11/69 (15.9%) with anal atresia, in 9/38 (23.7%) with tracheoesophageal fistula/esophageal atresia, in 2/25 (8%) with diaphragmatic hernia and in 5/17 (29.4%) with intestinal atresia. In 11 of 36 patients (30.6%) with CCM, the cardiac problems were hemodynamically significant, requiring anti-congestive and/or surgical treatment.
Conclusion:  A significant number of neonates with apparently isolated gastrointestinal malformations had CCM. Because almost all patients with malformations of the gastrointestinal tract/abdominal wall require early surgical intervention, they should be evaluated on echocardiography to investigate CCM at the earliest opportunity.     

Congenitally Malformed Hearts from a Population of Children Undergoing Cardiac Transplantation: Comments on Sequential Segmental Analysis and Dissection

Our aim is to examine the types of cardiac malformations found in a population of children undergoing cardiac transplantation, and to discuss a method for examining cardiac explants based on intrinsic morphology. We describe in detail the congenital malformations found in 65 cardiac explants acquired from a population of children over a period of 15 years. The specimens were examined and diagnosed using the method of sequential segmental analysis. The most prevalent type of cardiac malformation was severe obstruction of the left heart (29.2%), followed by double-outlet right ventricle (15.4%), complete transposition (13.8%), hearts with left-hand ventricular topology (10.8%), ventricular septal defect(s) (9.2%), tricuspid valvar agenesis (4.6%), and tetralogy of Fallot (4.6%). These abnormalities accounted for 87.6% of the specimens studied. We also cataloged the extracardiac malformations found at autopsy in those patients who died despite the transplantation. Extracardiac malformations were identified in 10 of the 19 patients who came to autopsy. Three had heterotaxy syndrome with isomerism of the atrial appendages, one with right and two with left isomerism. Other anomalies included tracheoesophageal fistula, pulmonary sequestration, extrahepatic biliary atresia, duodenal atresia, choanal atresia, and vascular malformations. Our study shows that even the most complicated cardiac malformations can readily be diagnosed in an explanted heart using the segmental approach based on observed morphology. Received July 20, 1998; accepted July 15, 1999.     

An unusual case of esophageal and laryngotracheal atresia

Esophageal atresia with or without tracheoesophageal fistula is a relatively common congenital anomaly. However, esophageal atresia with associated laryngotracheal atresia, double tracheoesophageal fistula and cardiac malformations is an extremely rare condition. In this article we report a newborn infant with severe respiratory distress at birth who had both esophageal and laryngotracheal atresia with congenital cardiac malformations, in an attempt to bring attention to the clinical presentation, and emergent diagnostic and therapeutic approaches.     

Congenital oesophageal stenosis distal to oesophageal atresia

Two cases with both oesophageal atresia and stenosis in the lower part of the oesophagus are reported. --The stenoses are congenital and most likely can be classified as malformations. --The stenoses had no clinical significance until the children began to eat solid food. Foreign bodies, which had been arrested in the oesophagus above the stenosis had to be removed several times. The importance is stressed of always including the distal oesophagus at the roentgenologic investigation of children with troubles after operation for oesophageal atresia.     

A population-based study on the incidence and possible pre- and perinatal etiologic risk factors of biliary atresia

OBJECTIVE: To study the incidence, etiologic risk factors, and outcome of biliary atresia. STUDY DESIGN: Register study using Swedish national health databases. The study population consisted of 1,204,791 children, corresponding to 99% of the entire cohort of Swedish children born between 1987 and 1997, with an end point of follow-up at 2 years of age. Cases with biliary atresia with and without major heart malformations were identified with indicators from various national health databases. RESULTS: Eighty-five cases with biliary atresia were identified, the incidence being 1 in 14,000. A major heart malformation was found in 13 (15%) cases. In a multivariate analysis, 4 independent risk factors were identified: high maternal age (odds ratio [OR] = 3.0), parity of at least 4 (OR = 2.2), prematurity (OR = 2.9), and low birth weight for gestational age (OR = 4.7). No significant differences were found in the distribution of birth months. The outcome did not differ between the two groups with and without major heart malformations, nor with respect to any of the risk factors. CONCLUSIONS: The Swedish incidence of biliary atresia is similar to that found in other European countries. The identified risk factors may suggest the existence of a maternal vulnerability and the importance of viral infections transmitted from mother to fetus/neonate.     

Oesophageal atresia,VACTERL association: Fanconi's anaemia related spectrum of anomalies

Oesophageal atresia usually occurs without any genetic background. Three cases associated with Fanconi''s anaemia are reported. One neonate had growth retardation and numerous malformations including oesophageal atresia and four other components of the VACTERL association. In the two others, oesophageal atresia was isolated. In patients with such malformations an early diagnosis of Fanconi''s anaemia may have important genetic and therapeutic implications.

     

Congenital Malformations: A Review of 672 Autopsies in Ibadan, Nigeria

The postmortem findings in 672 Nigerian children with lethal congenital malformations are reviewed. Eighty-six percent of the patients were less than 1 year of age and the male-to-female sex ratio was 1.3:1. The alimentary tract was the most common anatomic site involved (30%), intestinal and biliary atresia being the two lesions most frequently identified in this location. Twenty-six percent of the children had cardiovascular malformations, of which ventricular septal defect, patent ductus arteriosus, and tetralogy of Fallot were most important. There was an accentuated male predominance among cases with urogenital malformations due to the high frequency of posterior urethral valve. Hydrocephalus, spina bifida, and anencephaly were the most common lesions observed in the craniospinal axis. One-fifth of the children had complex malformations of multiple organ systems, 20% of which were associated with chromosomal anomalies, rubella, and other malformation syndromes.     

Hospitalizations due to respiratory syncytial virus in children with congenital malformations

Statewide respiratory syncytial virus (RSV) lower respiratory tract infection hospitalization data of Colorado children with congenital malformations was used to estimate the population-based risk and severity of disease of RSV hospitalizations. Spina bifida without anencephaly, cleft palate, lung agenesis or dysgenesis, and biliary atresia were associated with a higher risk of being hospitalized with RSV lower respiratory tract infection and an increased severity of disease when hospitalized.     

Liver transplantation for syndromic biliary atresia with a pedunculated accessory hepatic lobe

Faraj W, Dar F, Marangoni G, Alvarez FE, Howlader M, Mukherji D, Heaton N, Rela M. Liver transplantation for syndromic biliary atresia with a pedunculated accessory hepatic lobe.
Pediatr Transplantation 2010: 14: E1–E3. © 2009 John Wiley & Sons A/S.
Abstract:  Extrahepatic biliary atresia (EHBA) is the most common indication for liver transplantation in infants and children. Congenital malformations associated with EHBA are common and present in about 9%–37%. We describe a case of a child who received a left lobe liver transplant for syndromic EHBA.     

Congenital Structural Abnormalities in Biliary Atresia: Evidence for Etiopathogenic Heterogeneity and Therapeutic Implications

ABSTRACT. The clinical, surgical, laboratory and histological data of 237 children with extrahepatic biliary atresia were reviewed. Forty-seven patients (20%) had associated congenital anomalies, and of these, 28 had cardiovascular, 22 digestive and 19 splenic malformations. Of the 19 patients with splenic malformations, 13 showed the polysplenia syndrome and two had asplenia. Chromosome studies were performed in eight children, six having associated anomalies, and two of them showed karyotype abnormalities (46,XX,del 18 p- and 49,XXXXY). These observations indicated that biliary atresia could be subdivided into four distinct etiopathogenic subgroups, three involving a congenital form that could arise through a malformation, a disruption or a chromosome abnormality, and the remaining to agents active in the perinatal period (the acquired form). The surgical outcome in 171 patients operated on by an experienced surgeon was not influenced by the presence of anomalies but by the timing of surgery. Seventy-one percent of 24 patients operated on by 8 weeks of age were jaundice-free as opposed to only 34% of those who had later surgery ( p <0.01)     

Congenital structural abnormalities in biliary atresia: evidence for etiopathogenic heterogeneity and therapeutic implications.

The clinical, surgical, laboratory and histological data of 237 children with extrahepatic biliary atresia were reviewed. Forty-seven patients (20%) had associated congenital anomalies, and of these, 28 had cardiovascular, 22 digestive and 19 splenic malformations. Of the 19 patients with splenic malformations, 13 showed the polysplenia syndrome and two had asplenia. Chromosome studies were performed in eight children, six having associated anomalies, and two of them showed karyotype abnormalities (46,XX,del 18 p- and 49,XXXXY). These observations indicated that biliary atresia could be subdivided into four distinct etiopathogenic subgroups, three involving a congenital form that could arise through a malformation, a disruption or a chromosome abnormality, and the remaining to agents active in the perinatal period (the acquired form). The surgical outcome in 171 patients operated on by an experienced surgeon was not influenced by the presence of anomalies but by the timing of surgery. Seventy-one percent of 24 patients operated on by 8 weeks of age were jaundice-free as opposed to only 34% of those who had later surgery (p less than 0.01).     

Clinical relevance of the tracheal bronchus

We report about 6 infants with serious respiratory disease who revealed a tracheal bronchus on bronchoscopic or bronchographic examination. In two of these children this finding seemed to be the main problem; it could be cured by surgical or conservative therapy. The course of the further 4 children's disease was determined by additional serious malformations (Oesophageal atresia, congenital heart disease, anomalies of the pulmonary arteries). In these cases, the tracheal bronchus did not influence the clinical course significantly.     

HLA in Egyptian children with biliary atresia

We studied the human leukocytes antigens in 18 Egyptian children with biliary atresia (BA) without extrahepatic congenital malformations. There was a significant increased frequency of both B8 and DR3 (83.3% and 94.4% in patients with BA compared with 6.5% and 14.9% in the general population, respectively). Ten patients had the B8/DR3 haplotype. Our results support the hypothesis that genetic factors may play a role in susceptibility to BA.     

The VATER association. Analysis of 46 patients

Evaluation of 46 patients with the VATER association indicates that in addition to the major defects seen in this association, numerous other abnormalities occur at lesser frequency. Four of the defects that are not usually associated with the VATER association, namely, inguinal hernias, small intestinal malformations, choanal atresia, and cleft lip and/or palate, were seen at a relatively high frequency in this patient population. Two children possessed defects found in both the VATER and CHARGE associations. The spectrum of defects in the 46 patients in this study also is compared with that in 186 cases derived from the literature.     

Does ”Cystic” Biliary Atresia Represent a Distinct Clinical and Etiological Subgroup? A Series of Three Cases

We describe a unique series of 3 cases of biliary atresia (BA) associated with a choledochal cyst. All 3 children presented with jaundice at birth and had no other abnormalities. Although these children had a fetal form of BA, their presentation and outcome differed from those of biliary atresia splenic malformation syndrome (BASM), the well-described form of early onset BA. Unlike those with BASM, these children had no other associated malformations, had a normal birth weight, and did not yet require a liver transplant. We believe that the present series of patients and their associated pathology may represent a distinct phenotype with a common, prenatally acquired etiology that is different from other fetal forms of BA, such as BASM, and from patients who present with the classic perinatal form of BA.     

Abnormalities associated with extrahepatic bile duct atresia]

In 19 cases of extrahepatic biliary atresia there were other malformations, 9 of which could be included in the polysplenia syndrome. The importance of these associated with malformations for the early diagnosis of extrahepatic biliary atresia and for eventual surgery for secondary portal hypertension is emphasized. The histological findings of the fibrous remnants of the biliary system are similar in those with and without associated malformations. Thus, these abnormalities do not contribute of the understanding of the pathophysiology of extrahepatic biliary atresia but they do suggest that the initial insult may occur early in pregnancy.     

Esophageal atresia (T-E fistula): an index for neonatal surgery.

During the period 1978-1990 (12.5 years), 929 neonatal general surgical emergencies were treated at the Seoul National University Children's Hospital. There were 308 anorectal malformations, 128 atresia/stenosis of the gut, 125 neonatal Hirschsprung's disease, 75 gastroschisis and 67 esophageal atresias. The highest operative mortality rate of 26.9% was experienced in esophageal atresia with or without tracheo-esophageal atresia. Problems in respiratory care and surgical technical failure were the main causes of failure. Esophageal atresia can be used as an index for the status of neonatal surgical care since analysis of mortality of other operations indicates a similar but less exaggerated pattern.     

先天性肛门直肠畸形相关排尿异常的尿动力学评估北大核心CSCD

先天性肛门直肠畸形(ARM)占小儿消化道畸形的首位,发病率在新生儿中为1/5000-1/1500。该病常表现为肛门狭窄或肛门闭锁,伴或不伴瘘管和泄殖腔畸形。其中泌尿生殖系统伴发畸形最多见,发生率为26%-55%。35%-50%的儿童出现脊髓束末梢畸形或神经源性下尿路功能障碍,这也是ARM合并排尿异常症状的常见原因。尿动力学检查(UDS)是评估ARM合并下尿路功能变化最好的方法,可以对膀胱尿道功能进行客观分类指导并制定精准治疗方案和随访治疗效果。现就ARM合并排尿异常的原因及相关UDS评估的进展进行综述,为临床提供参考。     

Adriamycin mouse model: a variable but reproducible model of tracheo-oesophageal malformations

A spectrum of tracheo-oesophageal malformations is seen in humans: oesophageal atresia, tracheal agenesis and laryngotracheo-oesophageal clefts. They are thought to share a common but unknown aetiology. These birth defects are frequently associated with other VACTERL anomalies. The adriamycin rat model (ARM) has proved to be a valuable model of the VACTERL anomalies, illustrating the dysmorphogenesis of oesophageal atresia and tracheal agenesis. As organogenesis relies on temporaspatially co-ordinated signalling systems, the next step would be to study the molecular pathogenesis of tracheo-oesophageal malformations. However, the mouse is the foremost mammal studied by developmental biologists, offering an expanding wealth of knowledge and scientific research techniques with which to investigate these anomalies. A limited dose response analysis of the teratogenicity of adriamycin in the mouse has identified a dose and timing of injections that produced tracheo-oesophageal malformations and other VACTERL anomalies. A clear account of the types and variability of the tracheo-oesophageal malformations produced by this dose is essential in order to be able to plan and interpret any future investigations of early gestation fetuses. CBA/Ca mice were accurately time-mated (n = 10). Nine dams received intraperitoneal injections of adriamycin (6 mg/kg) and one control dam received saline injections, on days 7 and 8. Fetuses were harvested on day 18, near term. Tracheo-oesophageal malformations were examined by dissecting microscope and serial transverse sections. Results are reported in the standard teratological manner as mean percentage per litter (±SEM). The resorption rate of the adriamycin treated fetuses was 50.4%. There were 29 adriamycin treated fetuses for inspection. Tracheo-oesophageal malformations were found in 29.2% (±10.3), affecting five out of nine litters. Oesophageal atresia occurred in 15.6% (±8.1), laryngotracheo-oesophageal cleft in 10.4% (±7) and tracheal agenesis in 3.1% (±3.1). All of these malformations occurred with a tracheo-oesophageal fistula. Unlike the ARM, the AMM can produce fetuses with complete laryngotracheo-oesophageal cleft as well as oesophageal atresia or tracheal agenesis. Their occurrence was found to be reproducible but variable. These are important considerations when planning and interpreting experiments using this model.