History Of Congenital Diaphragmatic Hernia Research Articles

Effect of Chest Resistance and Expansion Exercises on Respiratory Muscle Strength, Lung Function, and Thoracic Excursion in Children with a Post-Operative Congenital Diaphragmatic Hernia.

Background. Congenital diaphragmatic hernia (CDH) is a life-threatening condition with long-term complications including respiratory tract infections, respiratory muscle weakness, and abnormal lung functions. This study was designed to ascertain the effects of chest resistance and chest expansion exercises on respiratory muscle strength, lung function, and chest mobility in children with post-operative CDH. Methods. This randomized controlled clinical study was conducted in the outpatient physiotherapy clinic at Prince Sattam bin Abdulaziz University. Thirty-two children with CDH aged 10–14 years between May 2020 and February 2021 were randomly allocated to the study group (n = 16) and the control group (n = 16). The control group underwent a usual chest physiotherapy program; however, the study group underwent a 12-week chest resistance exercise combined with chest expansion exercise in addition to usual chest physiotherapy, with three sessions per week. Respiratory muscle strength, lung function, and thoracic excursion were assessed pre- and post-treatment. Results. Using the 2 × 2 repeated ANOVA, significant time × group interactions were detected in favor of the study group, FVC (F = 4.82, 95% CI = −15.6 to −0.97, p = 0.005, and η2 = 0.16), FEV1 (F = 4.54, 95% CI = −11.99 to −2.8, p ˂ 0.001, and η2 = 0.14), PImax (F = 5.12, 95% CI = −15.71 to −5.3, p ˂ 0.001, and η2 = 0.15), and thoracic excursion (F = 4.41, 95% CI = −2.04 to −0.16, p = 0.036, and η2 = 0.17). Conclusions. Concurrent chest resistance and expansion exercises may improve respiratory muscle strength, lung function, and thoracic excursion in children with post-operative CDH. The study findings suggest that concurrent chest and chest expansion exercises be part of an appropriate pulmonary rehabilitation program in children with a history of CDH.

Comprehensive variant calling from whole-genome sequencing identifies a complex inversion that disrupts ZFPM2 in familial congenital diaphragmatic hernia.

BackgroundGenetic disorders contribute to significant morbidity and mortality in critically ill newborns. Despite advances in genome sequencing technologies, a majority of neonatal cases remain unsolved. Complex structural variants (SVs) often elude conventional genome sequencing variant calling pipelines and will explain a portion of these unsolved cases.MethodsAs part of the Utah NeoSeq project, we used a research‐based, rapid whole‐genome sequencing (WGS) protocol to investigate the genomic etiology for a newborn with a left‐sided congenital diaphragmatic hernia (CDH) and cardiac malformations, whose mother also had a history of CDH and atrial septal defect.ResultsUsing both a novel, alignment‐free and traditional alignment‐based variant callers, we identified a maternally inherited complex SV on chromosome 8, consisting of an inversion flanked by deletions. This complex inversion, further confirmed using orthogonal molecular techniques, disrupts the ZFPM2 gene, which is associated with both CDH and various congenital heart defects.ConclusionsOur results demonstrate that complex structural events, which often are unidentifiable or not reported by clinically validated testing procedures, can be discovered and accurately characterized with conventional, short‐read sequencing and underscore the utility of WGS as a first‐line diagnostic tool.

Impacts of Respiratory Muscle Training on Respiratory Functions, Maximal Exercise Capacity, Functional Performance, and Quality of Life in School-Aged Children with Postoperative Congenital Diaphragmatic Hernia.

Objectives Congenital diaphragmatic hernia (CDH) is a birth defect affecting the respiratory functions, functional performance, and quality of life (QOL) in school-aged children. Rarely have studies been conducted to evaluate the impacts of respiratory muscle training on school-aged children with postoperative CDH. The current study was designed to evaluate the impacts of respiratory muscle training on respiratory function, maximal exercise capacity, functional performance, and QOL in these children. Methods This study is a randomized control study. 40 children with CDH (age: 9-11 years) were assigned randomly into two groups. The first group conducted an incentive spirometer exercise combined with inspiratory muscle training (study group, n = 20), whereas the second group conducted only incentive spirometer exercise (control group, n = 20), thrice weekly for twelve consecutive weeks. Respiratory functions, maximal exercise capacity, functional performance, and pediatric quality of life inventory (PedsQL) were assessed before and after the treatment program. Results. Regarding the posttreatment analysis, the study group showed significant improvements in all outcome measures (FVC%, p < 0.001; FEV1%, p = 0.002; VO2max, p = 0.008; VE/VCO2 slope, p = 0.002; 6-MWT, p < 0.001; and PedsQL, p < 0.001), whereas the control group did not show significant changes (p > 0.05). Conclusion Respiratory muscle training may improve respiratory functions, maximal exercise capacities, functional performance, and QOL in children with postoperative CDH. Clinical commendations have to be considered to include respiratory muscle training in pulmonary rehabilitation programs in children with a history of CDH.

Asthma Medication Use in Congenital Diaphragmatic Hernia Survivors: A Retrospective Population Level Data Analysis.

The purpose of this study was to determine if congenital diaphragmatic hernia (CDH) survivors had worse long-term respiratory outcomes compared with age-matched controls, as measured by inhaled bronchodilator use, inhaled steroid use, and asthma-related physician visits. We performed a retrospective case-control study of infants with isolated CDH from 1991 to 2013. The primary outcome measures were inhaled bronchodilator prescriptions, inhaled steroid prescriptions, and asthma-related physician visits between 0 and 5 years of age and between 5 and 10 years of age. Subgroup analysis compared the same outcomes for CDH patients grouped by: birth weight, gestational age, side of defect, defect size, liver herniation, hernia sac, and pulmonary hypertension. Fifty-six patients with CDH and 753 age-matched controls met the inclusion criteria for the 0 to 5 years of age analysis. Between 0 and 5 years of age, more CDH survivors were prescribed an inhaled bronchodilator (odds ratio [OR] = 2.47[1.38-4.48], p = 0.001) and inhaled steroid (OR = 2.03[1.07-3.74], p = 0.03), and had an asthma-related physician visit (OR = 1.92[1.00-3.56], p = 0.04). Thirty-eight cases and 491 controls met the inclusion criteria for the 5 to 10 years of age analysis. Between 5 and 10 years of age, CDH survivors were not more likely to be prescribed inhaled bronchodilators, inhaled steroids, or have an asthma-related physician visit. Among the CDH patients, we did not find a clinical characteristic associated with increased inhaled bronchodilator or steroid prescriptions at any age. A history of CDH is associated with higher rates of inhaled bronchodilator prescriptions, inhaled steroid prescriptions, and asthma-related physician visits from 0 to 5 years of age compared with age-matched controls. However, this difference resolves by 5 to 10 years of age.

Exome sequencing identifies de novo pathogenic variants in FBN1 and TRPS1 in a patient with a complex connective tissue phenotype.

Here we describe a patient who presented with a history of congenital diaphragmatic hernia, inguinal hernia, and recurrent umbilical hernia. She also has joint laxity, hypotonia, and dysmorphic features. A unifying diagnosis was not identified based on her clinical phenotype. As part of her evaluation through the Undiagnosed Diseases Network, trio whole-exome sequencing was performed. Pathogenic variants in FBN1 and TRPS1 were identified as causing two distinct autosomal dominant conditions, each with de novo inheritance. Fibrillin 1 (FBN1) mutations are associated with Marfan syndrome and a spectrum of similar phenotypes. TRPS1 mutations are associated with trichorhinophalangeal syndrome types I and III. Features of both conditions are evident in the patient reported here. Discrepant features of the conditions (e.g., stature) and the young age of the patient may have made a clinical diagnosis more difficult in the absence of exome-wide genetic testing.

Minimally invasive repair of pectus excavatum in a 17-year-old boy with a history of congenital diaphragmatic hernia and lack of pericardium

We reported a 17-year-old boy with very deep asymmetric pectus excavatum and with a history of congenital diaphragmatic hernia repair and hypoplastic left lung. We performed a minimally invasive repair of pectus excavatum as described by Nuss et al., in 1998. We performed a left-sided thoracoscopy, instead of the right-sided according our normal routine, to provide a safe route. We created a substernal tunnel to have a clear definition of the deviant anatomy after congenital diaphragmatic hernia repair. However, we noticed an absence of the pericardium, which, by itself, can increase the risk of cardiac injury in both bar insertion and removal. Instead of the usual right-sided thoracoscopy, we recommend providing a safe view by left-sided thoracoscopy in comparable cases (e.g. congenital diaphragmatic hernia, other cardiac or vascular malformations) to reduce the risk of rupture or perforation of cardiac structures.

Splenic torsion after congenital diaphragmatic hernia repair: Case report and review of the literature

Wandering spleen with torsion, a rare clinical diagnosis, was found to be the cause of chronic abdominal pain in an 11-year-old female with a history of congenital diaphragmatic hernia repaired at three days of age. Doppler ultrasound revealed patent vessels with splenomegaly, and computed tomography (CT) showed an absence of the spleen in the left subphrenic space with torsion at the splenic hilum. Due to the chronicity of pain and risk of ischemia from torsion, open splenopexy with Vicryl mesh was performed. This case report/review of the literature discusses the rarity of this condition, and the importance of timely diagnosis and intervention.

Physical activity, fitness, and dyspnea perception in children with congenital diaphragmatic hernia

We assessed whether physical activity could influence the performance and perception of dyspnea in children who were operated on for high risk congenital diaphragmatic hernia (CDH). We hypothesized that CDH children with normal activity would have better lung function and exercise performance level when compared to sedentary CDH subjects. We studied 18 children (11 males and 7 females, mean age 6.6 ± 2.6 years) who were surgically corrected. All children underwent physical examination, ECG at rest, and a maximal exercise stress test on a treadmill to measure the duration of exercise, maximal heart rate and blood pressure, maximal oxygen uptake (VO(2) max and VO(2) ml/kg/min). Lung function testing to measure forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV(1) ), and peak expiratory flow (PEF) was also performed. Following the stress test, the Dalhousie dyspnea and effort scale was shown to children as a pictorial panel with three groups of increasing (from 1 to 7) levels of effort perception, throat discomfort, and chest dyspnea. Children were divided into group A (sedentary) and group B (regular physical participation). There was no difference in CDH severity between the two groups. Group A had a statistically significant lower duration of exercise (P < 0.01), maximal oxygen consumption (VO(2) max P < 0.0001), VO(2) ml/kg/min (P < 0.001), higher throat closing feeling (P < 0.004), chest dyspnea (P < 0.001), and effort perception (P < 0.04) compared to group B. No differences were found in lung function tests. In conclusion, our data may suggest that children with a history of CDH who are active maintain a higher level of performance with less perception of dyspnea and effort.

Risk factors for elevation of ABR threshold in NICU-treated infants

Objective Several risk factors for hearing impairment among infants treated in the neonatal intensive care unit (NICU) have been reported, but there have been few studies that show the correlation strength between the risk factors in NICU-treated infants and hearing impairment in childhood. The aim of this study was to clarify the relationship between risk factors in NICU-treated infants and a deteriolation of auditory brainstem response (ABR) threshold in their childhood. Methods One hundred one NICU-treated infants with ABR threshold of 50 dBnHL or more underwent 2nd ABR test at 20 months after delivery. Multiple regression analysis was performed with ABR threshold change as an objective variable and risk factors as explanatory variables. Results Two ABR tests of the 101 infants resulted in that 7 showed an elevation of ABR threshold by 20 dB, 70 showed a drop of ABR threshold by 20 dB, and 24 showed no significant change. Multiple regression analysis revealed that the factors contributing to the elevation of ABR threshold were congenital diaphragmatic hernia, severe respiratory disease, and a high C-reactive protein (CRP) level. Conclusions In the infants treated in NICU, an incidence of ABR threshold of 50 dBnHL or more was 9.0%, and 6.9% of the infants with the ABR threshold abnormality showed a significant elevation of ABR threshold in their childhood. Factors significantly related to an elevation of ABR threshold were a history of congenital diaphragmatic hernia, severe respiratory disease, and elevation of CRP. In infants with such factors, periodical examination of hearing is required.

Factors Associated With Sensorineural Hearing Loss Among Survivors of Extracorporeal Membrane Oxygenation Therapy

To endeavor to explain why some graduates of extracorporeal membrane oxygenation (ECMO) therapy develop sensorineural hearing loss (SNHL) whereas others do not, to study the variability seen in the degree of SNHL, to attempt to explain why some graduates with SNHL experience progressive worsening whereas others do not, and to describe the time course of the onset of SNHL on the basis of identified risk factors. A retrospective chart review with proportional-hazards regression analysis to identify specific risk factors for SNHL from a list of patient and treatment variables. Children's Hospital Boston, a pediatric tertiary-care facility and ECMO center. Neonatal ECMO graduates born in 1986-1994 who survived to discharge and underwent audiologic evaluations (n = 111) and a random sample of ECMO graduates who survived to discharge and did not undergo audiologic evaluations (n = 30). Audiologic data, including the presence or absence of SNHL, the severity of SNHL at the most recent evaluation, the stability or progressive worsening of hearing (with the first evaluation compared with the most recent evaluation), and the occurrence of delayed-onset SNHL. Twenty-nine (26%) of 111 ECMO graduates who underwent audiologic testing had SNHL at the last evaluation. Of these 29 subjects with SNHL, 21 (72%) had progressive SNHL, of whom 14 (48%) had delayed-onset SNHL. The age of identification of SNHL ranged from 4 months to 8 years 11 months. Factors identified with proportional-hazards regression analyses as being associated significantly with the time to onset of SNHL were a primary diagnosis of congenital diaphragmatic hernia (hazard ratio: 2.60), length of ECMO therapy (hazard ratio: 7.18), and number of days children received aminoglycoside antibiotics (hazard ratio: 5.56). Kaplan-Meier "time-to-event" curves were constructed to illustrate the time course of onset of SNHL, as affected by each of the variables identified as significant risk factors. These findings illustrate the need for early, routine, audiologic evaluations throughout childhood for all ECMO graduates. Children at even greater risk for developing SNHL because of a history of congenital diaphragmatic hernia, prolonged ECMO therapy, and/or a lengthy course of aminoglycoside antibiotic therapy should be monitored even more closely throughout childhood, depending on the child's individual risk indicators, as suggested here. On the basis of these risk indicators, efforts can be made to minimize the risk of hearing loss while a child is being treated with ECMO. In addition, these risk indicators can assist with counseling families of ECMO graduates regarding the child's specific risk of developing SNHL and how it can be managed should it occur.

Diaphragmatic rupture during labor

Diaphragmatic rupture during labor is uncommon and generally occurs in patients with a history of congenital diaphragmatic hernia or traumatic abdominal or chest injury. We present a case of a 41-year-old woman who presented with abdominal pain, vomiting and hypoventilation four days after a full-term home delivery. Chest radiography suggested the presence of a ruptured diaphragm, and laparotomy revealed a congenital left Bochdalek defect with herniation of the stomach, transverse colon and spleen into the left pleural cavity. Diaphragmatic hernia rupture during labor is a serious but rare complication that requires emergency surgery to prevent visceral perforation and cardio-respiratory failure.

Nitrofen-induced congenital diaphragmatic hernia in rat embryo: what model?

Purpose The aim of this study was to investigate the natural history of congenital diaphragmatic hernia (CDH) in rat embryos with special attention to the pathomorphologic changes of diaphragm, liver, intestines, and lungs at various stages of embryonic development. Methods Pregnant Sprague-Dawley rats were given, via a gavage tube, 100 mg nitrofen (Wako Chemicals, Neuss, Germany) on day 10.5 of gestation. Fetuses were harvested by laparotomy on day 15.5, 16.5, 18, and 21. Anatomic study of the diaphragm, herniated viscera, and lungs was performed under stereoscope with special attention to the diaphragmatic defect. Results CDH occurred in 44 embryos on right, in 10 on the left, and in 34 bilateral. In the youngest embryos, the small defect was located in the dorsomedial portion of the diaphragm very close to the aortic hiatus. During pregnancy, the defect enlarged progressively to occupy more than half of the affected hemidiaphragm on day 21. In all animals, regardless of their age and side of the defect, the liver was found inside the chest. The intrathoracic mass was formed by ingrown hepatic tissue originating from the dorsal surface of the intraabdominal liver. It appeared as an accessory liver lobe. The amount of intrathoracic liver increased rapidly. From around day 18, the thoracic portion of liver, when examined in sagittal plane, was bent forward and assumed an uncinate shape. The stomach and small bowel loops were displaced into the chest in the oldest examined fetuses. The first sign of reduction of size of the lung was seen in 16, 5-day old embryos, and at further stages of embryonic development the lung growth impairment strictly paralleled the ingrowth of the liver. The natural history of the right and left CDH were very similar. In fetuses with bilateral CDH, asymmetry regarding size of the defect and volume of intrathoracic hepatic mass was noted with larger defects on the left side in more than 60% of animals. Conclusions Pathogenesis of nitrofen-induced diaphragmatic defect in the rat embryo and CDH in the human fetus seem to differ significantly. Nitrofen induces a complex malformation of the embryonic diaphragm and the liver. CDH in rat embryo bears more resemblance to a model of space-occupying lesion than to human CDH. The induction of localized hepatic proliferation may be a result of disturbance of as yet unknown regulatory interaction between hepatic and mesenchymal diaphragmatic cells.

The history of congenital diaphragmatic hernia from 1850s to the present.

Congenital diaphragmatic hernia (CDH) is believed to result from incomplete fusion of the pleuroperitoneal membrane, and passage of the abdominal contents into the chest. A historical review of the literature on this subject shows a wide divergence of opinion on the etiology of the various types of CDH, and on the recommended treatment. A variety of theories regarding its causes and the optimal way of approaching it have been published from the mid 19th century through the 20th century, and are reviewed in this article.

Congenital Diaphragmatic Hernia: In Utero Therapy and Ethical Considerations

Despite advances in neonatal medicine, the mortality rate for congenital diaphragmatic hernia remains high. The results of work in animal models suggest that this anomaly may be amenable to in utero surgical correction. In this article, the natural history of congenital diaphragmatic hernia in humans is reviewed, and the development of antenatal management strategies is traced. The ethical issues surrounding the management of fetuses with diaphragmatic hernias are also discussed. The ground-breaking nature of the development of strategies for management of congenital diaphragmatic hernia underscores the importance of establishing scientific and ethical guidelines for future endeavors with in utero therapy.

A population-based study of congenital diaphragmatic hernia in utah: 1988–1994

To define the natural history of congenital diaphragmatic hernia and to determine the potential impact of fetal therapy. This retrospective case series consisted of all fetuses and neonates with congenital diaphragmatic hernia born between 1988 and 1994 in the state of Utah that could be identified through genetic counseling referrals, delivery logs, and neonatal intensive care unit discharge diagnosis records. Maternal and neonatal hospital records were reviewed for antepartum, intrapartum, and postpartum variables. Based on existing recommendations, fetuses who might have benefited from fetal therapy were identified. Ninety-six cases were identified, for a frequency of one case in 2710 live births per year. Five pregnancies were terminated before 21 weeks' gestation. The overall survival rate excluding these five cases was 58.2%. Among the remaining 91 cases, survival was significantly better for infants diagnosed in the neonatal period than for those diagnosed prenatally (78% versus 35%; P < .001). The frequency of associated anomalies was similar for antepartum and postpartum cases. Sixty-two percent of nonsurvivors had some type of other anomaly, but no pattern was apparent. There were no accurate prenatal predictors for lethal pulmonary hypoplasia, but preterm birth and the presence of severe cardiac anomalies were predictors of neonatal death. Only two of 96 fetuses would have potentially benefited from fetal therapy. The outcome of infants with congenital diaphragmatic hernia is worse with preterm birth and if diagnosed prenatally. The survival rate we found was better than that reported in earlier studies, suggesting improved perinatal and neonatal management. Fetal therapy based on current eligibility criteria would have a minimal impact on survival of fetuses with congenital diaphragmatic hernia.

The natural history of congenital diaphragmatic hernia and pulmonary hypoplasia in the embryo

Up to now, descriptions of the natural history of congenital diaphragmatic hernia (CDH) associated with pulmonary hypoplasia (PH) are based exclusively on observations made in the fetal period. However, nothing is known about the events that take place in an embryo with CDH. Recently, an animal model of CDH and PH has been established in rat embryos to study the embryology and natural history of this lesion. We exposed 36 pregnant Sprague-Dawley rats to a single dose of 100 mg nitrofen on day 11 of pregnancy. A total of 356 staged embryos and fetuses from day 13 to day 21 were studied by light and scanning electronmicroscopy. The litters of 9 untreated rats (124 normal age-matched embryos and fetuses) served as controls. The abnormal development of the diaphragmatic anlage was first seen in embryos aged 13 to 14 days. A defect appeared in the dorsal part of the diaphragm, normally on the right side. The liver grew through this defect early on. Gut was found in an intrathoracic position only in the very late stages (day 21 22 ) and newborns. Compared to controls, lungs of nitrofen-embryos with CDH were smaller, depending on the size of liver found in the thoracic cavity. Histologically, compression of lung was absent at these stages. Most authors speculate that CDH results because the pleuroperitoneal canals fail to close at the end of the embryonic period (ie, week 8 to 10 in human development) leading to a defect in the dorsolateral region of the diaphragm. However, contradictory to this assumption, our findings indicate that diaphragmatic defects develop in early embryonic life. They are easy to identify even in rat embryos as early as 14 days. The early ingrowth of liver into the thoracic cavity through these defects is the crucial step in the pathogenesis of PH in CDH, because it is the liver and not the gut that reduces the thoracic cavity in the embryo. Normal lung growth will be hampered in early embryonic stages according to the size of the liver mass inside the thoracic cavity. Recent reports suggest that the presence of liver in the fetal thoracic cavity affects the outcome of a fetus with CDH. This observation is in accordance with our findings, suggesting that the major events of pathogenesis take place in the embryo and not in the fetus, as often assumed.

Natural history of congenital diaphragmatic hernia: Implications for management: P. Puri and W.A. Gorman. Pediatr Surg Internat 2:327–330, (November), 1987

Natural history of congenital diaphragmatic hernia: Implications for management: P. Puri and W.A. Gorman. Pediatr Surg Internat 2:327–330, (November), 1987

Natural history of congenital diaphragmatic hernia: implications for management

Advances in ultrasonography have made it possible to accurately diagnose congenital diaphragmatic hernia (CDH) prenatally, and recently interest has been expressed in in-utero correction of CDH as a solution to the problem of high mortality. In an attempt to elucidate the natural history of CDH, we analysed the incidence and mortality of this disorder in a large maternity hospital with an autopsy rate of 100% for all stillbirths and neonatal deaths. Between 1973 and 1985, there were 47 cases of CDH among 99,062 births, an incidence of 1 in 2,107 birhts. There were 15 (32%) stillbirths and 32 (68%) live births. All 15 stillborns had lethal associated non-pulmonary anomalies. Of the 32 liveborn patients, 17 died prior to transfer to the referral centre and 11 of these had major associated anomalies. Prematurity was a feature in 65% of patients who died prior to transfer to the referral centre. Nine of the 15 patients who arrived at the referral centre survived. Our date suggest that the only patient who may benefit from prenatal correction of CDH is a fetus who has serious persistent pulmonary hypertension. However, in the absence of reliable criteria for the in-utero prediction of persistent pulmonary hypertension in association with CDH, surgical correction of CDH prenatally is not practicable at present even for this group of patients. Newer therapeutic approaches in the management of persistent pulmonary hypertension should be addressed as the most promising approach in the management of a CDH patient who develops respiratory failure in the first few hours of life.