Birth weight and McGoon Index predict mortality in newborn infants with congenital diaphragmatic hernia

Background

Despite improvements in clinical management, mortality of congenital diaphragmatic hernia (CDH) remains high. Early prediction of mortality risk helps in comparing strategies and/or performances of different centers. Birth weight (BW), Apgar Score at 5 minutes, and modified McGoon Index (MGI) calculated by the ratio between the diameters of pulmonary arteries and the descending aorta have been used to determine mortality of CDH.

Aim

The purpose of this study is to evaluate the relationship between early detectable variables and survival in newborns with CDH intubated at birth, managed with “gentle” ventilation and delayed surgery.

Methods

All medical records of patients affected by high-risk CDH and treated with a standardized protocol at Bambino Gesù Children's Hospital, Rome, Italy, between January 2002 and September 2004 were reviewed. Prenatal diagnosis, gestational age, BW, sex, side of hernia, and MGI were recorded on admission. The relationship with mortality of each variable was evaluated by univariate analysis. Subsequently, a predictive model of mortality was developed using a logistic regression: the explanatory variables, BW, and MGI were dichotomized in high (HBW and HMGI) and low (LBW and LMGI) according to the best cutoff found with receiver-operating characteristic curves.

Results

Thirty-four newborns with CDH, treated with a standardized protocol, were studied. The main characteristics of the 34 patients were BW, 2886 g (1500-3620 g); gestational age, 37.7 weeks (32-42 weeks); male/female, 22/12; right/left, 8/26; prenatal diagnosis, 29; MGI, 1.31 (0.9-1.85). Only BW and MGI were significantly (P < .05) associated with mortality at the univariate analysis. The best cutoff values were 2755 g for BW (sensitivity, 70%; specificity, 74%) and 1.25 for MGI (sensitivity, 73%; specificity, 78%). Using these limits, BW and MGI resulted independently associated with mortality in the multivariate analysis. Using the 4 possible combinations, the LBW associated with the LMGI presented the highest prediction of mortality (80%).

Conclusions

Birth weight and MGI, variously combined, were predictive of mortality. Because they are not influenced by subsequent modalities of care, they can be considered as valid early severity scores in CDH and used for comparing strategies and/or performances of different centers.     

33例新生儿先天性膈疝

目的 分析新生儿先天性膈疝的临床表现及诊治经验,以提高先天性膈疝病婴手术成功率及生存质量.方法 回顾性分析2004年1月至2009年9月新生儿重症监护室收治的33例先天性膈疝新生儿临床表现及治疗结果.结果 33例先天性膈疝中21例行手术治疗,术后生存17例,其中4例产前经超声检出者术后均生存.死亡4例,死因与肺发育不良有关.12例未行手术者全部死亡,其中1例生后即刻死亡.结论 新生儿先天性膈疝的病死率较高,应加强产前诊断及产科、新生儿科、小儿心胸外科的合作以提高先天性膈疝病婴的生存率.

Abstract：

Objective To review the clinical experience of diagnosis and treatment of the congenital diaphragmatic hernia in newborn infants. Methods Thirty-three neonates were diagnosed having congenital diaphragmatic hernia in our hospital from Jan. 1,2004 to Sept. 30, 2009. The clinical data was retrospectively reviewed. Results 21 cases were treated surgically and 17 survived, while 4 cases died. The main cause of death was congenital pulmonary dysplasia. Another 12 cases refused to accept surgical treatment and they all died, one died shortly after he was born. Four cases who had been diagnosed by prenatal ultrasonography were survived. Conclusion The mortality of congenital diaphragmatic hernia in neonates was still high. Prenatal diagnosis of the congenital diaphragmatic hernia is very important and the cooperation between the obstetrics, neonatology and cardiothoracic surgery will improve the survival rate of congenital diaphragmatic hernia in newborn infants.     

Ventral hernia with a skin-covered Silastic sheet for newborn infants with a diaphragmatic hernia.

The persistently high mortality rate for newborn infants with a congenital diaphragmatic hernia, which is symptomatic and treated in the first 24 hours of life, is due to multiple pulmonary and vascular factors. This demands the exclusion of any additional compromising elements. The effects of increased intra-abdominal pressure due to replacement of the intestine into the abdomen can be avoided by the formation of a ventral hernia. A large hernia can be produced best by suturing a sheet of Dacron reinforced Silastic to the fascia of a midline abdominal incision and covering it with skin flaps. This nonreactive prosthesis will remain in place for several months and later can be removed simply. This technique was used successfully in three infants and should improve the survival rate of precariously balanced newborn infants operated upon during the first few hours of life.     

Enhanced expression of vascular endothelial growth factor in lungs of newborn infants with congenital diaphragmatic hernia and pulmonary hypertension

BACKGROUND: Pulmonary hypoplasia accompanied by pulmonary hypertension resistant to treatment is an important feature of congenital diaphragmatic hernia (CDH). The pathogenesis of the pulmonary vascular abnormalities in CDH remains to be elucidated at the molecular level. Vascular endothelial growth factor (VEGF), an endothelial cell specific mitogen, is known to play a role in pulmonary angiogenesis and vascular remodelling but there are no data on VEGF expression in patients with CDH. METHODS: Necroscopic lung specimens from 21 patients with CDH with lung hypoplasia and from seven age matched control newborn infants without lung hypoplasia were processed for immunohistochemical analysis using affinity purified anti-human VEGF antibodies. All the cases of CDH had pulmonary hypoplasia, indicated by a lung/body weight index of 200 microm) and small (<200 microm) pulmonary arteries, the most intense staining being in the medial smooth muscle cells of the small pulmonary arteries. Endothelial cells were positive for VEGF staining in patients with CDH but not in controls. CONCLUSIONS: This is the first study of VEGF expression in newborn infants with CDH. Increased levels of VEGF, especially in the small, pressure regulating pulmonary arteries, point to a potential role in vascular remodelling. This may reflect an unsuccessful attempt by the developing fetus to increase the pulmonary vascular bed in the hypoplastic lungs to alleviate the associated pulmonary hypertension.     

胸、腹腔镜联合手术治疗小婴儿先天性膈疝

目的:探讨胸、腹腔镜联合手术治疗小婴儿先天性膈疝的可行性及治疗效果。方法:回顾分析2014年8月至2016年5月胸、腹腔镜联合手术治疗3例小婴儿先天性膈疝的临床资料,均为左后外侧疝,年龄分别为5个月、8个月、19个月。其中1例伴肠旋转不良,术中经腹腔镜处理。3例患儿先经腹腔镜疝内容物复位,再经胸腔镜行膈疝修补。结果:手术均顺利完成,手术时间分别为115 min、106 min、110 min。术中出血量3~5 ml,经腋前线第7肋间Trocar孔放置胸腔闭式引流。术后1周内复查胸片,心脏复位良好,肺膨胀良好。术后随访1~6个月无复发,患儿呼吸急促、呼吸困难症状消失,食欲好,体重增加明显。结论:胸、腹腔镜联合手术治疗小婴先天性膈疝操作方便,创伤较小,手术操作更加安全;同时能兼顾腹部,避免了因消化道畸形再次手术的可能。手术效果令人满意,也可作为备选的治疗方式。     

Bronchopulmonary innervation defects in infants and rats with congenital diaphragmatic hernia

Introduction

Pulmonary morbidity in survivors of congenital diaphragmatic hernia (CDH) is caused by hypoplasia, barotraumas, or other reasons. We have previously shown deficient tracheal innervation in rats with CDH. Now we examine whether bronchopulmonary innervation is also abnormal in both infants and rats with CDH.

Material and Methods

Sections of E15, E18, and E21 rat lungs were immunostained for Protein gene product 9.5 and S100 antibodies. Similar immunostaining was performed on tissue from infants dying from CDH (n = 6) and other causes (n = 6) with Neurofilament, S100, and Rearranged during transfection antibodies. Nerve trunks/bronchus were counted, and the proportion of glial and RET-positive cells/bronchial surface was calculated. Glial cell-line derived neurotrophic factor protein and mRNA were measured in rat lungs.

Results

Nerve trunks/bronchus were decreased in infants and rat fetuses with CDH. In contrast, glial and RET-positive cells/bronchial surface were increased in infants and rats with CDH. Both lungs were equally affected. GDNF protein was high, whereas GDNF mRNA was decreased in preterm animals with CDH.

Conclusions

The lungs of infants and rats with CDH have decreased neural components compensated by increased supporting glial cells and persistence high expression of RET and GDNF protein. Because bronchopulmonary innervation controls airway smooth muscle, vessels, and glandular secretions, it is tempting to hypothesize that these deficiencies might play a role in respiratory morbidity in CDH.     

Perforation of a congenital umbilical hernia in a patient with Hurler's syndrome

Congenital umbilical hernias in Hurler’s syndrome (mucopolysaccharidosis I) are generally treated conservatively, because complications such as incarceration are, rare, and risks involved in surgical correction are high. This case report describes the surgical management of a ruptured umbilical hernia in a 3-year-old child with Hurler’s syndrome. Emergency repair of the hernia was performed with primary closure of the fascia; hernia recurrence 6 months later was treated laparoscopically using a PTFE mesh graft with no evidence of re-recurrence. In selected cases of Hurler’s syndrome (warning signs of rupture) elective surgical hernia repair may be indicated.     

Early perfluorodecalin lung distension in infants with congenital diaphragmatic hernia

Background/Purpose: Pulmonary hypoplasia contributes to mortality in infants with severe congenital diaphragmatic hernia (CDH). Accelerated postnatal lung growth with perfluorocarbon lung distension has been demonstrated in animals. The authors present a study measuring perfluorodecalin distension in neonates with severe CDH on extracorporeal membrane oxygenation (ECMO) support. Methods: Six consecutive neonates with CDH requiring ECMO support were recruited. The lungs were filled with perfluorodecalin, and continuous positive airway pressure was applied for 6 to 10 days (mean, 7.7 days [plusmn] 0.7). The perfluorodecalin was exchanged 4 times a day. Radiographic lung projections were measured, and from 2-dimensional measurements an estimated lung volume was calculated using the ECMO cannula as reference. Results: Perfluorodecalin instillation started soon after starting ECMO support (mean, 13.5 [plusmn] 5.3 hours). The volume required to fill the lungs increased significantly (P [lt ] .02). The radiographic dimension of the affected lung increased significantly (mean percentage increase, 272%; P [lt ] .02). The contralateral lung dimension also increased (mean percentage increase 51%; P [lt ] .02). CDH repair was undertaken on ECMO in all cases. All patients survived (follow-up, 3 to 42 months). Conclusions: This protocol of early perfluorodecalin lung distension in infants with severe CDH on ECMO support resulted in significant radiographic lung enlargement. Clinical outcomes are encouraging. Possible mechanisms include alveolar recruitment, alveolar dilatation, and accelerated postnatal lung growth. J Pediatr Surg 38:17-20.     

Presentation of congenital diaphragmatic hernia past the neonatal period

Congenital diaphragmatic hernias (CDHs) presenting beyond the neonatal period are a rare and unusual problem; they occurred in 11 of 83 children at our institution. Two discrete clinical groups were apparent: (1) younger children, with mainly respiratory symptoms; and (2) older children with gastrointestinal (GI) complaints. Chest roentgenograms suggested CDHs, but GI contrast studies were necessary for confirmation in eight patients. The diagnosis was made preoperatively in ten of 11 children. At operation, no peritoneal sacs were found, the hernial contents were viable in all patients, and malrotation was present in six of 11 patients. None had evidence of pulmonary hypoplasia. Congenital diaphragmatic hernias do present beyond the neonatal age group in a significant number of cases (13% in our series), and a diagnosis of CDH should be considered in any child with persistent GI or respiratory problems and abnormal chest x-ray film findings. The mortality rate in these patients is small, but morbidity may be significant.     

Pulmonary growth and remodeling in infants with high-risk congenital diaphragmatic hernia.

Infants born with congenital diaphragmatic hernia (CDH) have pulmonary hypoplasia, but the pattern of postnatal growth in these lungs has not been documented. The lungs of 21 children dying with CDH were analyzed to determine how the pulmonary morphology changed with age. The patients were stratified into three age groups for ANOVA analysis (less than 8 days, 8 to 21 days, greater than 21 days). Morphometric techniques previously described were used. Lung volume and weight as well as pulmonary artery length and diameter increased with age (P = .04), whereas the number of airway generations was similar for each group. Radial alveolar number also increased, particularly in the contralateral lung (P = .02). The percentage of intraacinar artery muscularization decreased with age (P = .02), while larger intraacinar arteries showed a nonmuscular structure, again particularly in the contralateral lung (P = .004). It is concluded that: (1) significant lung growth does occur postnatally at the alveolar level after CDH repair; and (2) there is postnatal vascular remodelling resulting in larger and less muscular arteries. These changes should contribute to a decrease in pulmonary arterial hypertension over time. However, the time period over which these changes occur exceeds the current limitations of invasive support measures such as extracorporeal membrane oxygenation. Elucidation of the factors responsible for this growth could result in new therapeutic strategies to enhance or accelerate postnatal pulmonary development in infants with CDH.