Life-threatening Congenital Anomalies Research Articles

Non-VACTERL Association of Pure Esophageal Atresia with Lumbar Meningocele and White Forelock of Hair: A Case Report

Abstract Background: After the introduction of term VATER for the association of anomalies of vertebra, anorectum, tracheoesophageal, and renal systems by Quan and Smith in 1973, cardiac and limb defects were added by Nora and Nora in 1975, and the acronym was extended to VACTERL. However, other defects such as genitourinary, neural tube defects, and cleft lip or palate are even more common than the VACTERL association. A white forelock of hair is often associated with Hirschsprung’s disease and is considered a part of neurocristopathies but rarely seen with the esophageal atresia (EA) and meningocele. We are reporting such a rare case of EA associated with meningocele and white forelock. Case Report: A one-day-old male baby presented to the emergency room with complaints of respiratory distress, frothing of saliva, and swelling at the back with a white forelock. The baby was diagnosed as pure EA with meningocele, and a surgical repair of both anomalies was done at the same sitting. The baby could not survive due to prematurity, low-birth weight, and multiple congenital anomalies. Conclusion: Presence of white forelock along with this kind of associations should raise the suspicion of severe life-threatening congenital anomalies, and the baby should be kept under neonatal intensive care.

An aborted case suspected to CHARGE Syndrome; A rare case with cardiac, intestinal and kidney abnormalities

BackgroundCHARGE syndrome is a life-threatening congenital anomaly. The syndrome associations consist of coloboma, heart disease, atresia of the choanae, retarded growth and development, genital hypoplasia/genitourinary anomalies, and ear anomalies and or hearing loss. The aim of this paper is to describe and discuss a rare case of CHARGE syndrome.Case presentationDuring the routine dissection, atrial septal defect, overriding aorta from both ventricles, patent ductus arteriosus, duodenal anomaly, absent pancreas, right side descending and sigmoid, intestinal herniation in lesser sac, and left kidney anomaly were observed.ConclusionsThis rare case is of importance in re-considering the criteria of CHARGE and understanding the importance of the orchestrated morphologic driving forces of embryonic development.

Genetic and Cellular Interaction During Cardiovascular Development Implicated in Congenital Heart Diseases.

Congenital heart disease (CHD) is the most common life-threatening congenital anomaly. CHD occurs due to defects in cardiovascular development, and the majority of CHDs are caused by a multifactorial inheritance mechanism, which refers to the interaction between genetic and environmental factors. During embryogenesis, the cardiovascular system is derived from at least four distinct cell lineages: the first heart field, second heart field, cardiac neural crest, and proepicardial organ. Understanding the genes involved in each lineage is essential to uncover the genomic architecture of CHD. Therefore, we provide an overview of recent research progress using animal models and mutation analyses to better understand the molecular mechanisms and pathways linking cardiovascular development and CHD. For example, we highlight our recent work on genes encoding three isoforms of inositol 1,4,5-trisphosphate receptors (IP3R1, 2, and 3) that regulate various vital and developmental processes, which have genetic redundancy during cardiovascular development. Specifically, IP3R1 and 2 have redundant roles in the atrioventricular cushion derived from the first heart field lineage, whereas IP3R1 and 3 exhibit redundancy in the right ventricle and the outflow tract derived from the second heart field lineage, respectively. Moreover, 22q11.2 deletion syndrome (22q11DS) is highly associated with CHD involving the outflow tract, characterized by defects of the cardiac neural crest lineage. However, our studies have shown that TBX1, a major genetic determinant of 22q11DS, was not expressed in the cardiac neural crest but rather in the second heart field, suggesting the importance of the cellular interaction between the cardiac neural crest and the second heart field. Comprehensive genetic analysis using the Japanese genome bank of CHD and mouse models revealed that a molecular regulatory network involving GATA6, FOXC1/2, TBX1, SEMA3C, and FGF8 was essential for reciprocal signaling between the cardiac neural crest and the second heart field during cardiovascular development. Elucidation of the genomic architecture of CHD using induced pluripotent stem cells and next-generation sequencing technology, in addition to genetically modified animal models and human mutation analyses, would facilitate the development of regenerative medicine and/or preventive medicine for CHD in the near future.

Glycerin suppositories used prophylactically in premature infants (supp): A pilot randomized controlled trial

Glycerin suppositories are often used to facilitate meconium evacuation in premature infants. The evidence for this practice is inconclusive. The purpose of this study was to assess the feasibility of a multicenter randomized controlled trial on the effectiveness of this treatment strategy. We conducted an external pilot study for a multicenter randomized controlled trial of premature infants randomized to glycerin suppositories or placebo procedure. Participants were included if they were gestational age of 24 weeks 0 days to 31 weeks 6 days and/or birthweight of 500 to 1500 grams. We excluded infants with life-threatening congenital anomalies, contraindications to receiving suppositories, or signs of clinical instability. Outcomes included cost, recruitment, and treatment-related adverse events. A total of 109 were screened, 79 were initially eligible, and 34 consented to participate. Four of these infants were excluded prior to randomization due to thrombocytopenia, 30 were randomized, and 26 reached full enteral feeds. Three infants (10%) experienced rectal bleeding 5 to 43 days after completing study treatments. An anal fissure was noted in two of these patients. There were no cases of rectal perforation but one infant assigned to active treatment developed necrotizing enterocolitis. Conducting a multicenter randomized controlled trial on the use of glycerin suppositories in premature infants is feasible. Minor modifications to the study protocol are needed to increase participant recruitment and simplify the administration of study treatments.

Disturbances in the Acute Cardiorespiratory Adaptation of Full-Term Neonates

Summary We studied the incidence and causes of transition disturbances in the first 30 minutes of life in full-term newborns. This one-year study was retrospective and included 1147 full- term live-born neonates without life-threatening congenital anomalies and surgical complications. They were divided into four groups: 0 (with normal transition), 1 (resuscitated without endotracheal intubation), and 2 (intubated); A (without underlying maternal, obstetric or fetal/neonatal problem, with adequate for GA eight and from single birth) and B (with one or more of following: underlying maternal, obstetric or fetal/neonatal problem, SGA or LGA, from multiple pregnancies). Of the newborns, 9.1% of required resuscitation and 1.6% - extensive resuscitation with intubation. The groups significantly differed in the incidence of underlying maternal, obstetric, or fetal/neonatal problems. Resuscitated babies were born via Caesarean section (CS), in abnormal presentation (PaN) and by vacuum extraction or forceps (V/F) predominantly. The highest incidence of the small for gestational age (GA) babies – SGA, was detected in Group 2. Twins and large for GA (LGA) had prevalence in Group 1. Resuscitation was necessary for 18.1% of CS-delivered babies. V/F and PaN lead to the highest need for intubation. According to our data, every 10th of the full-term neonates required assistance in the fetal-to-neonatal transition. The causes could be diseases of the mother or fetus/newborn, multiple births, SGA, or LGA. A compromised medical decision about the time and way of delivery may result in iatrogenic transition disturbances.

Surgical management of critical congenital malformations in the delivery room

Newborn emergencies that occur in the delivery room are frequently the result of life-threatening congenital anomalies that can result in death or severe disability if not treated in the immediate postnatal period. Prompt recognition and treatment of such disorders are paramount to ensuring the wellbeing of the infant. As congenital anomalies are frequently being diagnosed earlier due to improved prenatal detection, the coordination of planned interventions for life-threatening malformations is also becoming more common. This article serves as a guide for the presentation and initial management of the most common non-cardiac, newborn surgical emergencies.

Metabolic disturbances of the vitamin A pathway in human diaphragmatic hernia.

Congenital diaphragmatic hernia (CDH) is a common life-threatening congenital anomaly resulting in high rates of perinatal death and neonatal respiratory distress. Some of the nonisolated forms are related to single-gene mutations or genomic rearrangements, but the genetics of the isolated forms (60% of cases) still remains a challenging issue. Retinoid signaling (RA) is critical for both diaphragm and lung development, and it has been hypothesized that subtle disruptions of this pathway could contribute to isolated CDH etiology. Here we used time series of normal and CDH lungs in humans, in nitrofen-exposed rats, and in surgically induced hernia in rabbits to perform a systematic transcriptional analysis of the RA pathway key components. The results point to CRPBP2, CY26B1, and ALDH1A2 as deregulated RA signaling genes in human CDH. Furthermore, the expression profile comparisons suggest that ALDH1A2 overexpression is not a primary event, but rather a consequence of the CDH-induced lung injury. Taken together, these data show that RA signaling disruption is part of CDH pathogenesis, and also that dysregulation of this pathway should be considered organ specifically.

A Novel Approach: Trans-ascending Aorta Balloon Aortic Valvuloplasty via Sternotomy for Treating Severe Valvular Aortic Stenosis in a Low-Weight Infant

Severe congenital aortic stenosis in infants is a life-threatening congenital heart anomaly that is typically treated using percutaneous balloon aortic valvuloplasty. The usual route is the femoral artery under radiographic guidance. However, this procedure may be limited by the small size of the femoral artery in low-weight infants. An infant weighing only 7 kg with severe aortic stenosis (peak gradient was 103 mmHg) was successfully treated with a novel approach, that is trans-ascending aorta balloon aortic valvuloplasty guided by transesophageal echocardiography. The patient tolerated the procedure well, and no major complications developed. After the intervention, transesophageal echocardiography indicated a significant reduction of the aortic valvular peak gradient from 103 mmHg to 22 mmHg, no aortic regurgitation was found. Eighteen months after the intervention, echocardiography revealed that the aortic valvular peak gradient had increased to 38 mmHg and that still no aortic regurgitation had occurred. In our limited experience, trans-ascending aorta balloon aortic valvuloplasty for severe aortic stenosis under transesophageal echocardiography guidance effectively reduces the aortic peak gradient. As this is a new procedure, long-term follow up and management will need to be established. It may be an alternative technique to treat congenital aortic stenosis in low-weight patients.

Trends in the treatment and outcome of congenital diaphragmatic hernia over the last decade

Congenital diaphragmatic hernia (CDH) remains a challenging and life-threatening congenital anomaly. The aim was to evaluate whether treatment and survival has changed during the last decade. We retrospectively analysed all consecutive infants with CDH referred to two European tertiary paediatric surgical centres over 11 years (January 1999 to December 2009). Minimum follow-up was 1 year. χ(2) test for trend was used to evaluate significance. There were 234 infants. There was no significant variation over time in the proportion of infants receiving high frequency oscillatory ventilation (HFOV) (p = 0.89), inhaled nitric oxide (iNO) (p = 0.90) or extracorporeal membrane oxygenation (ECMO) (p = 0.22). 205 infants (88 %) were stabilised and underwent surgical repair; of these, 186 (79 %) survived after surgery. Over time there was a significant increase in the proportion of infants undergoing surgical repair (p = 0.018) without a concomitant significant improvement in survival (p = 0.099). This multicentre analysis indicates that the survival rate of infants with CDH referred to two European paediatric surgical centres is high (79 %). The use of HFOV, iNO and ECMO has not changed in recent years. We observed a significant increase in the proportion of infants who undergo surgery but this has not resulted in a significant increase in the overall survival rate.

A mobile Meckel!

A technetium-99m pertechnetate Meckel scan is the standard diagnostic test to diagnose Meckel diverticulum. Although a negative scan does not exclude Meckel diverticulum, it should be kept in mind that the diagnosis can be missed on the basis of a single negative scan. Another important point is the typical position of this anatomical abnormality in the scan. We report a peculiar anatomical variation of Meckel diverticulum as seen in the technetium-99m pertechnetate scan. Recognizing this variant of Meckel diverticulum is important to avoid missing such a potentially life-threatening congenital anomaly.

A plea for conservative treatment of large, unruptured omphaloceles.

Forty-six babies with an unruptured omphalocele were admitted over a 10-year period. The conservative treatment consisted of the application of mercurochrome or an antibiotic powder, while the primary surgical treatment consisted of either full-layer closure or silastic sac insertion. Liver containing omphaloceles were considered large. Of the 25 babies without associated life-threatening congenital anomalies, all 9 with a small omphalocele survived, irrespective of the method of treatment. Sixteen babies had a large omphalocele of which all 8 conservatively treated babies survived against only 4 of the 7 who underwent surgery. The remaining baby, weighting 960 g, died prior to treatment, due to respiratory distress. Eighteen of the 21 babies with associated life-threatening congenital anomalies died, irrespective the extent of the defect. Although the conservative treatment of the large defects did not result in an improved survival rate, therapy-related complications did not occur. From this study it appears that large unruptured omphaloceles should be treated conservatively. Babies not doing well with a small omphalocele or a large one treated conservatively, will have one or more major associated anomalies, necessitating urgent diagnosis and treatment.

Familial Syndromic Esophageal Atresia Maps to 2p23-p24

Esophageal atresia (EA) is a common life-threatening congenital anomaly that occurs in 1/3,000 newborns. Little is known of the genetic factors that underlie EA. Oculodigitoesophageoduodenal (ODED) syndrome (also known as "Feingold syndrome") is a rare autosomal dominant disorder with digital abnormalities, microcephaly, short palpebral fissures, mild learning disability, and esophageal/duodenal atresia. We studied four pedigrees, including a three-generation Dutch family with 11 affected members. Linkage analysis was initially aimed at chromosomal regions harboring candidate genes for this disorder. Twelve different genomic regions covering 15 candidate genes (approximately 15% of the genome) were excluded from involvement in the ODED syndrome. A subsequent nondirective mapping approach revealed evidence for linkage between the syndrome and marker D2S390 (maximum LOD score 4.51 at recombination fraction 0). A submicroscopic deletion in a fourth family with ODED provided independent confirmation of this genetic localization and narrowed the critical region to 7.3 cM in the 2p23-p24 region. These results show that haploinsufficiency for a gene or genes in 2p23-p24 is associated with syndromic EA.

Antenatal diagnosis of isolated congenital diaphragmatic hernia is not an indicator of outcome

It has been reported previously that infants diagnosed with congenital diaphragmatic hernia (CDH) antenatally have a much poorer prognosis than those diagnosed postnatally. The authors identified 173 high-risk (symptomatic within the first 6 hours of life) infants with CDH treated in the past decade. Seventy-seven cases were diagnosed antenatally and 96 were diagnosed postnatally. The survival rate was slightly worse for the antenatal group (34% v 48% for the postnatal group; P = .04). However, 59 of the 173 patients (34%) had other life-threatening congenital anomalies. Among the 114 patients with isolated CDH, the survival rate increased to 59% in the antenatal group and 63% in the postnatal group—a difference that was not significant. The timing of antenatal diagnosis (> or <25 weeks) had no impact on the statistics ( P = .08). The only parameter consistently different between all groups and subgroups was the Apgar score at 5 minutes, which was always better in the antenatal group ( P < .02), possibly reflecting more efficient resuscitation. Of the 59 patients with other life-threatening anomalies (42 cardiac), there was one survivor among the 34 in the antenatal group and only two among the 25 in the postnatal group, despite the fact that 39 patients had undergone resuscitation, which included ECMO in 25. From these data the authors conclude that (1) antenatal diagnosis of an isolated CDH, regardless of its timing (< or > 25 weeks), is of no value in predicting outcome; (2) survival for patients with antenatally diagnosed isolated CDH is much higher than previously reported, a fact that should be considered when antenatal manipulations such as in utero CDH repair or termination of pregnancy are contemplated; (3) awareness of CDH by antenatal diagnosis leads to more effective resuscitation after birth; and (4) CDH associated with another significant anomaly, especially cardiac, currently has a dismal prognosis, irrespective of timing of diagnosis.

Withholding and withdrawal of life support from surgical neonates with life-threatening congenital anomalies

We evaluated why and how life support was withheld or withdrawn in surgical neonates. During the study period, January 1988 through December 1991, 529 neonates were admitted, 52 of whom died (10%). Twenty-eight deaths were due to the underlying disease. The other 24 patients died because treatment was withheld or withdrawn. In 15 of 24 (group A, mean stay 9.2 ± 9.1 days) treatment was initially started but later withdrawn ( 13 15 ) because of the severity of congenital anomalies alone ( 7 12 ) or congenital anomalies associated with chromosomal anomalies ( 5 12 ). In 9 of 24 (group B, mean stay 20.3 ± 17.3 days) treatment was withdrawn because of serious complications. In all cases often lengthy discussions have led the doctors and nurses together with the parents to chose unanimously for withdrawal of treatment. Mechanical ventilation was the intervention most frequently withdrawn ( 10 15 group A, 9 9 group B). Vasoactive and other drugs were withheld in 5 patients of group A. Sedatives and analgetics were administrated as supportive care permitting the child to die in a humane way, 17 in the lap of a parent and 7 in the lap of a nurse. We conclude that life-sustaining care is withheld or withdrawn relatively frequently from patients at our ICU. Such decisions are ethical ones, taken in the light of professional and technical expertise. Evaluation of withholding or withdrawal of treatment is difficult but necessary to evolve appropriate decision-making procedures and to formulate humane standards of intensive care. Discussions about decision-making with regard to forgoing life-support should form an important part of the continuing education of doctors and nurses who are involved with treatment of newborn infants with congenital anomalies.

Surgical Management of Tracheal Stenosis in an Infant with Multiple Congenital Anomalies: When is Baby Inoperable?

Congenital tracheal stenosis is a rare disorder that carries a significant morbidity and mortality. It is an even greater challenge when present in combination with other life-threatening congenital anomalies. We present an infant with multiple congenital anomalies, including trisomy 21, who was diagnosed with congenital tracheal stenosis at 3 months of age. At age 5 months, the infant underwent tracheoplasty with costal cartilage graft and pulmonary artery banding. Bronchoscopy 3 weeks later revealed a patent airway. However, the patient died 2 months postoperatively of cardiac complications. At autopsy, whole organ and histologic specimens revealed excellent incorporation of the graft with no evidence of re-stenosis. Our documentation of graft incorporation in this patient is evidence that long segments of stenotic trachea can be successfully treated by tracheoplasty utilizing rib cartilage grafts.

Esophageal atresia. Prognostic factors and contribution of preoperative telescopic endoscopy.

In recent years, the surgical correction of esophageal atresia with distal tracheoesophageal fistula (TEF) has become increasingly successful. However, there remains a group of high-risk patients with specific anatomical abnormalities in whom the mortality remains appreciable. These associated disorders include cardiac, renal, and chromosomal anomalies as well as severe respiratory distress syndrome. These factors, rather than low birth weight or early gestational age, are primarily responsible for surgical mortality. Preoperative telescopic bronchoscopy has been a useful adjuvant confirming the diagnosis, identifying unusual variants, and permitting the proper anatomic placement of the endotracheal tube. A Fogarty balloon catheter can be passed bronchoscopically into the distal TEF in patients with severe respiratory distress syndrome to occlude the fistula and facilitate effective positive pressure ventilation. Thirty-two patients were treated for esophageal atresia among whom 28 had esophageal atresia with distal TEF, three had esophageal atresia alone, and one had esophageal atresia with proximal TEF. The higher-risk group comprised those with severe respiratory insufficiency as evidenced by a room air paO2 of less than 60 mmHg; this group accounted for nine of the ten deaths in the total series. There was one late death following surgical correction. In summary, in the absence of severe respiratory insufficiency or associated life-threatening congenital anomalies, the results of surgical correction for esophageal atresia are remarkably good and survival in this group approximates 100%.

Surgical repair of total cleft sternum

There are two objectives in the surgical repair of congenital total cleft sternum:(1) to afford normal bony protection to the mediastinal structures and (2) to provide stability of the anterior thorax so that respiratory function and circulation can be maintained physiologically within normal pressure relationships. A case is presented, and a new method for repair of this life-threatening congenital anomaly is described.

Choanal Atresia and/or Cardiac Disease

There are few catastrophies in the neonatal period which present so dramatically and uniquely, yet are remedied so quickly and simply, as congenital atresia of the posterior choanae. The lesion, once thought to be rare, is being detected more frequently and probably accounts for 0.5% per thousand major congenital anomalies. Unfortunately, even with early accurate diagnosis, many of these infants do not survive associated organic defets.1-4 Over 50% of the patients with bilateral choanal atresia studied at the Children's Hospital of Philadelphia between January 1960 and January 1967 had associated life-threatening congenital anomalies, especially cardiac disorders. One might speculate that maldevelopment in both organ systems occurs during the sixth to eighth week of fetal development, although no chromosomal aberration, chemical agent, or physical agent has been correlated.

The management of infants with tracheo-oesophageal fistula.

Our technique of dealing with the problelms associated with repair of tracheooesophageal fistula has been described as we have developed it over the years, This method employs basic principles of paediatric anaesthesia and takes cognizance of the many additional factors which present themselves in this condirtion. These are due primarily to involvement of the respiratory tree in the disease, and the frequent coexistence of prematurity and other life-threatening congenital anomalies. With an incidence variously reported as 1:1,300 to 1:4,500 of live births, it is obvious that the condition is relatively infrequently encountered in the average general hospital. In an operation beset with so many problems and pitfalls, in which meticulous attention to even the most minor detail is essential and which is seen at most six times a year in any but the largest general hospitals or in children’s hospitals, it is essential that for best results the management should be limited to one team, so that avoidable mistakes are not repeated by combinations of different individuals. When one thinks in terms of a team, this must, in addition to surgeon and anaesthetist, include the nurses in the intensive treatment area upon whose skill and acute appraisal of abnormal situations the survival of these infants depends to a large measure in the postoperative period. The paediatricians contribute by their advice on fluid replacement therapy and other non-surgical problems and they regulate the oral feeding regimen until such time as the infants are returned to their primary care during convalescence. Until then, all treatment orders are written by one person only (usually by the surgeon or by his resident under his direct orders), after due consultation with other members of the team. This avoids the confusion arising out of contradictory orders or the omission of others, and ensures that at least one person is completely in the picture at all times of every phase of treatment.

Safe transportation of newborn infants for emergency surgery.

The transfer of a newborn infant from one hospital to another for the correction of a life-threatening congenital anomaly should be supervised by one person, and this person should be one who appreciates the need for dispatch. A competent attendant, preferably a nurse trained in the care of newborn infants, must accompany the patient. Air travel is not dangerous to the infant if traveling incubators and adequate nursing are available. It is desirable for the father to travel with the infant and nurse and to confer with the surgeon. The nurse must be provided with means for aspirating mucus in cases of esophageal atresia and for preventing intestinal distention in cases of omphalocele, diaphragmatic hernia, intestinal obstruction, and imperforate anus. The difficulties of transferring an infant from one hospital to another are outweighed by the advantages if the latter institution has a staff or provides equipment better adapted to the requirements of the case.