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.     

Prenatal pulmonary hypertension index: novel prenatal predictor of severe postnatal pulmonary artery hypertension in antenatally diagnosed congenital diaphragmatic hernia

Purpose

This study aim to assess the potential of prenatal predictors of postnatal severe pulmonary artery hypertension (PAH) in isolated left congenital diaphragmatic hernia (CDH) and to define a new prenatal pulmonary hypertension index (PPHI).

Methods

A retrospective chart review of CDH patients between May 2005 and October 2008 was conducted. Ten patients with systemic/suprasystemic and 9 patients with subsystemic pulmonary hypertension at 3 weeks of age were identified. Diameters of the right pulmonary artery, left pulmonary artery (LPA_d), aorta, and the length of vermis of the cerebellum were obtained from prenatal magnetic resonance imaging to calculate the PPHI [=(LPA_d/length of vermis of the cerebellum) × 10] and the modified McGoon index (MGI) [=(diameter of the right pulmonary artery + LPA_d)/diameter of aorta]. Prenatal pulmonary hypertension index and MGI were compared with lung-to-head ratio, percent predicted lung volume, and total lung volume for pulmonary hypertension and survival.

Results

The PPHI and MGI had a significant, negative correlation with pulmonary hypertension (r = −0.61, P = .005, and r = −0.72, P < .005, respectively). The PPHI and MGI are significantly lower in the systemic/suprasystemic PAH group compared with the subsystemic PAH group (1.11 ± 0.32 versus 1.63 ± 0.28, P = .004, and 0.71 ± 0.15 versus 1.05 ± 0.11, P < .001, respectively). There were no significant differences between the groups comparing the lung-to-head ratio, percent predicted lung volume, and total lung volume.

Conclusion

Both PPHI and MGI accurately predict the severity of postnatal PAH in isolated left CDH.     

Increase in fetal pulmonary artery diameters during late gestation is a predictor of outcome in congenital diaphragmatic hernia with liver herniation

Aim

Liver herniation (LH) in congenital diaphragmatic hernia (CDH) may not be a reliable prognostic indicator. We measured pulmonary artery (PA) diameters in CDH + LH as an alternative.

Methods

Of 41 consecutive cases of prenatally diagnosed left-sided CDH treated from 2002 to 2010, 19 had CDH + LH and 22 had CDH − LH. Ultrasonography and magnetic resonance imaging were used to assess LH and echocardiography to measure PA diameters during the third trimester (fetal; 32-34 weeks), at birth, and on day 2 of life.

Results

In CDH + LH survivors (9/19; 47%), fetal right PA (RPA) diameters were significantly larger than in nonsurvivors (2.58 ± 0.56 vs 1.82 ± 0.35 mm; P < .01), but left PA (LPA) diameters were not (1.73 ± 0.38 vs 1.59 ± 0.22). In survivors, fetal RPA was greater than 2 mm in all but one case, and both PA diameters increased significantly by birth (RPA, 2.58 ± 0.56 vs 3.52 ± 0.54; LPA, 1.73 ± 0.38 vs 2.60 ± 0.40; both P < .01). Final diameters at birth in survivors were at least 2.5 and 2.0 mm, respectively. In nonsurvivors, both PAs were significantly smaller (RPA, 3.52 ± 0.54 vs 2.04 ± 0.31; LPA, 2.60 ± 0.40 vs 1.68 ± 0.18; P < .01), with no observed increase by birth. Survival in CDH − LH was 82% (18/22).

Conclusion

PA diameter appears to be correlated with prognosis in infants with CDH + LH.     

Predicting perinatal outcome in isolated congenital diaphragmatic hernia using fetal pulmonary artery diameters

Objective

The aim of the study was to evaluate the potential of fetal pulmonary artery (PA) diameters to predict perinatal death and pulmonary arterial hypertension (PAH) in congenital diaphragmatic hernia (CDH).

Study Design

In this prospective observational study, observed PA (main, right, and left) diameters were measured at the level of the 3 vessels in 21 fetuses with isolated CDH and in 85 controls at 22 to 36 weeks. The observed/expected (o/e) diameters of the main, contralateral, and ipsilateral PAs were calculated by comparing these measurements with reference values obtained in our previous study and correlated with perinatal death and postnatal PAH.

Results

The o/e PA diameters were significantly reduced in fetuses with CDH compared to controls (P < .001) and in fetuses with CDH who died (P < .050). However, there was no significant association between PA diameters and PAH (P ≥ .050).

Conclusions

The PA diameters might be useful to predict perinatal death in isolated CDH but not postnatal PAH, suggesting that PA diameters are probably related to the severity of pulmonary hypoplasia.     

“Acquired” congenital diaphragmatic hernia

“Acquired” congenital diaphragmatic hernia (ACDH), has been defined as delayed or late appearance of a congenital diaphragmatic hernia after a documented time period of postnatal life with no evidence of herniation. Three new cases are presented. This diagnosis has been characterized on the basis of a review of these cases and 14 additional patients from the literature. A classification based upon timing of herniation and state of pulmonary development is presented.     

The relationship of pulmonary artery pressure and survival in congenital diaphragmatic hernia

Background/purpose

Pulmonary hypertension is an integral part of the pathophysiology of the respiratory failure associated with congenital diaphragmatic hernia. Hypothesizing that the evolution of the pulmonary hypertension would determine clinical outcome, the authors examined pulmonary artery pressures in relation to survival in their CDH patients.

Methods

The authors performed a retrospective chart review of all neonates with the CDH from 1991 to 2002 at their institution eliminating infants with complex congenital heart disease, prematurity, or limited treatment. Cardiac ECHO data were used to estimate pulmonary artery pressures as a ratio to systemic pressure. Statistical analyses of estimated pulmonary pressure ratios stratified by survival status and time were performed using χ² and Fisher’s Exact Test methods.

Results

Forty-seven full-term CDH infants with 428 cardiac ECHO evaluations were studied. Long-term survival rate was 74%. Forty-nine percent of patients had normal pulmonary artery pressure estimates within the first 3 weeks of life. All patients survived. Seventeen percent had persistent systemic or suprasystemic pressure estimates unrelieved by treatment interventions resulting in 100% mortality rate. Thirty-four percent had intermediate reductions in pressure estimates over time with 75% survival rate. Systemic pulmonary artery pressures were associated with decreased survival at all time-points when compared with normal-pressure survivors: week 1, 60% (P < .003); week 3, 38% (P < .007); week 6, 0% (P < .02).

Conclusions

The evolution of pulmonary hypertension is a critical determinant of survival in CDH patients with current treatment strategies. Three groups can be modeled with markedly different clinical performance patterns. Using serial cardiac ECHO examinations, pulmonary artery pressure estimations can be used to predict clinical outcome.     

除草醚诱导的小鼠先天性膈疝肺发育不良模型的建立

目的 建立小鼠先天性膈疝(CDH)模型.方法 实验组10只妊娠第8天的BABL/C小鼠通过灌胃给于除草醚25 mg/只,正常对照组给予橄榄油,于妊娠第20天剖宫产取出子鼠,解剖显微镜下观察子鼠有无膈疝形成,测定子鼠体重及双肺重量,HE染色观测肺组织发育情况,逆转录-聚合酶链反应(RT-PCR)检测肺组织SP-B、SP-C和VEGF表达水平.结果 实验组69只子鼠中有膈疝形成者39只,成功率为56.5%,子鼠双肺重量较对照组显著降低(P＜0.01);实验组有膈疝形成和无膈疝形成者的肺组织均发育不良,处于假腺体期和原始肺小管期;与对照组比较,实验组胎肺组织中SP-B、SP-C和VEGF表达水平均显著下调(P＜0.01),且与膈疝形成与否无关.结论 采用除草醚能在小鼠成功建立CDH模型,具有简便、成功率高的优点,为深入研究CDH发病机制及其治疗提供了新的手段.     

Prenatal treatment with retinoic acid promotes pulmonary alveologenesis in the nitrofen model of congenital diaphragmatic hernia

Background/Purpose

Severe pulmonary hypoplasia remains the main cause of the high mortality in newborn infants with congenital diaphragmatic hernia (CDH). Retinoids are a family of molecules derived from vitamin A, which play an important role in lung development. We hypothesized that retinoids promote alveologenesis at the end of gestation and therefore designed this study to investigate the effects of retinoid acid on nitrofen-induced hypoplastic lungs in CDH.

Methods

Pregnant rats were exposed to either olive oil or 100 mg nitrofen on day 9 of gestation. Retinoic acid 5 mg/kg was given intraperitoneally on days 18, 19, and 20 of gestation and fetuses were recovered on day 21. We had 4 study groups: control (n = 24), control + retinoic acid (n = 22), CDH (n = 24), and CDH + retinoic acid (n = 19). Lungs from the 4 study groups were fixed, and the following stereological measurements were performed on vertical random sections: total lung volume, volume density of airspaces, volume density of air walls, gas exchange surface area, alveolar volume, and total number of alveoli per lung. Total DNA content of each lung was measured using a spectrophotometer.

Results

Total lung volume increased in CDH lungs after the addition of retinoic acid but remained the same in the control group. Gas exchange surface area was larger in CDH lungs after the addition of retinoic acid but remained unchanged in the control group. The total number of alveoli per lung was higher after the addition of retinoic acid. Total DNA content as well as total DNA content-lung weight ratio of the left lung increased significantly in the CDH group after the addition of retinoic acid compared with CDH without retinoic acid.

Conclusions

Our results demonstrate that prenatal treatment with retinoic acid stimulates alveologenesis in hypoplastic lungs in CDH.     

Late-presenting congenital diaphragmatic hernia

Background

Late-presenting congenital diaphragmatic hernia (CDH) is a rare subset of CDH, most of the information derived from small series or case reports. The aim of this study was to document the clinical manifestations of late-presenting CDH using a large multicenter database.

Methods

Information about late-presenting CDH (diagnosed at later than 30 days of age) was identified from the database of the CDH Study Group (3098 cases collected during 1995-2004) and reviewed retrospectively.

Results

Seventy-nine cases (2.6%) from 30 centers met the inclusion criteria. Seven cases had a Morgagni hernia. There were 50 males (65%) and 27 females (35%). The mean age at diagnosis was 372 days (32 days to 15 years). Major associated anomalies (10 cardiac and 7 chromosomal abnormalities) were identified in 12 cases (15%). Presenting symptoms were respiratory in 20 (43%), gastrointestinal in 15 (33%), both in 6 (13%), and none (asymptomatic) in 5 (11%). The hernia was left-sided in 53 (69%), right-sided in 21 (27%), and central or bilateral in 3 (4%). Patients with gastrointestinal symptoms invariably had left-sided hernias (n = 19), whereas patients with respiratory symptoms (n = 24) seemed equally likely to have right- or left-sided lesions. A primary repair without patch was done in all cases with 100% survival.

Conclusions

Presenting symptoms of late-onset CDH can be respiratory or gastrointestinal, but presentation with gastrointestinal problems was more common in left-sided hernias, whereas respiratory symptoms predominated in right-sided lesions. The prognosis is excellent once the correct diagnosis is made.     

腹腔镜小儿先天性膈疝修补术

目的探讨腹腔镜小儿先天性膈疝修补术的疗效。方法2002年6月-2005年12月，我们对11例小儿先天性膈疝（3例新生儿年龄3—24h，余8例2—24个月）施行三孔或四孔腹腔镜手术。还纳疝内容物，丝线缝合膈肌修补缺损。结果10例手术修补成功。1例新生儿腹腔镜手术后3d膈疝复发，再次腹腔镜手术修补成功。手术时间55—180min，平均100min，术中出血量1—2ml。术后1—2d开始进食。11例随访9—24个月，平均16个月，X线检查膈肌位置正常。结论腹腔镜小儿先天性膈疝修补术安全可靠，创伤小，可清晰显露术野，术中还可探查有无腹部其他先天性畸形。     

Chylothorax after congenital diaphragmatic hernia repair

Purpose

Chylothorax after congenital diaphragmatic hernia (CDH) repair contributes significantly to morbidity. Our aim was to identify factors contributing to chylothorax and effective treatment strategies.

Methods

We reviewed 171 patients with CDH from 1997 to 2008 and analyzed hernia characteristics, extracorporeal membrane oxygenation (ECMO) use, operative details, and treatment approaches for chylothorax.

Results

Ten (7%) patients developed chylothorax; all were left sided. Using univariate analysis, prenatal diagnosis, ECMO use, and patch repair were associated with development of chylothorax. Logistic regression analysis showed that patch repair was the only variable predictive of chylothorax (P = .028; confidence interval, 0.032-0.823). Although survival was not affected, patients with chylothorax had a significant increase in ventilator days and length of stay (t = 3.57; P = .000; t = 2.74; P = .007). All received thoracostomy and total parenteral nutrition. Six patients received octreotide, 5 of whom required pleurectomy because of failed medical management; the remaining patient died of overwhelming sepsis.

Conclusions

The incidence of chylothorax at our institution was relatively low. Patch repair was associated with the formation of chylothorax. Morbidity was substantial, but survival was not significantly affected. Total parenteral nutrition and thoracostomy were appropriate initial treatments. Octreotide was not an effective adjunct. Refractory cases were successfully treated with pleurectomy.     

The presence of a hernia sac in isolated congenital diaphragmatic hernia is associated with less disease severity: A retrospective cohort study

IntroductionWe aimed to determine if the presence of a hernia sac in neonates with isolated congenital diaphragmatic hernia (CDH) was associated with better clinical outcomes.MethodsWe performed a retrospective cohort study of infants with isolated CDH from 1991 to 2015. Primary outcome measures were oxygen-dependence and mortality at 28 days. Secondary measures were: inhaled nitric oxide use, vasoactive medication use, ventilator support, and recurrence rates.ResultsSeventy-one patients met the inclusion criteria: 14 patients (19.7%) had a hernia sac, and 57 patients (80.3%) did not. Mortality did not differ between the 2 groups [0 of 14 versus 3 of 57 (5.3%) (p = 1.000)]. Hernia sac patients had similar oxygen-dependence after 28 days [1 of 14 (7.1%) versus 14 of 57 (24.6%) (p = 0.273)]. Hernia sac children required less iNO (0.64 ± 2.41 vs. 6.35 ± 12.2 days, p = 0.002), vasoactive medications (2.79 ± 3.07 vs. 5.36 ± 5.52, p = 0.027), and time on ventilation (7.62 ± 6.12 vs. 15.9 ± 19.2, p = 0.010). Hernia sac children had similar recurrence rates within 2 years [0 of 14 versus 7 of 57 (12.3%) (p = 0.331)].ConclusionThe presence of a hernia sac was not associated with lower rates of oxygen dependency or death at 28 days but was associated with decreased inhaled nitric oxide, vasoactive medication, and ventilator use.Level of evidenceIII     

先天性膈疝的诊治进展

先天性膈疝是新生儿外科危重症之一,目前病因及发病机制尚未明确。多数患儿可以产前发现,并能依据影像学检查结果对患儿的预后进行评估。外科手术是从根本上治疗先天性膈疝的主要手段。目前外科手术方式包括开放手术和腔镜手术两种。随着微创外科的日益发展,更多中心开始对新生JLN疝行腔镜下膈疝修补术治疗。     

Octreotide for chylous effusions in congenital diaphragmatic hernia

Background/Purpose

Chylothorax is a frequent complication in congenital diaphragmatic hernia (CDH) infants and is associated with significant morbidity. The optimal treatment strategy remains unclear. We hypothesize that octreotide decreases chylous effusions in infants with CDH.

Methods

This is a retrospective study of all infants with CDH admitted to our institution from October 2006 to October 2011.

Results

Eleven (12%) infants developed a chylothorax. Five infants were managed conservatively with thoracostomy and total parenteral nutrition. Six infants were started on octreotide therapy. None of the infants required surgical intervention to stop the effusion. There was no significant difference in survival to discharge, length of stay, or average daily chest tube output between groups. There appeared to be a temporally associated drop in chest tube output upon initiation of octreotide in two infants; however, the overall rate of decline in chest tube drainage was unchanged. In addition, there were infants in the conservative group who demonstrated a similar drop in daily chest tube output despite the absence of octreotide.

Conclusions

Our data suggest that the majority of chylous effusions in CDH infants resolve with conservative therapy alone.     

In utero incarceration of congenital diaphragmatic hernia

In utero diagnosis of incarcerated congenital diaphragmatic hernia has never been reported. In our case, congenital diaphragmatic hernia presented at 34 weeks of gestation with dilated bowel loops, pleural effusion, and ascites on fetal ultrasound. Preterm delivery and emergency exploration revealed a tight posterolateral diaphragmatic defect with extensive bowel infarction.     

The decreasing incidence of pneumothorax and improving survival of infants with congenital diaphragmatic hernia

In the 6-year period between 1977 and 1982 inclusive, 75 newborn infants with congenital diaphragmatic hernia of Bochdelek underwent corrective surgery during the first 24 hours of life. A total of 40 infants (53%) survived. Beginning in January 1980, a standardized approach to care including early use of mechanical ventilation and paralysis with pancuronium as well as dopamine use prior to any Priscoline infusion, was instituted. To determine whether these approaches improved outcome, term infants without malformations from the years 1977 to 1979 were compared with a similar group treated after institution of standardized care between 1980 and 1982 inclusive. The infants were comparable in all respects, but survival improved from 45% to 82% between the two periods (P less than 0.03). There was an associated decrease in the incidence of pneumothorax (45% in first period; 14% in second period) paralleled by a concomitant increase in pancuronium use (18% and 85%, respectively). Although factors responsible for the improved survival are multifactorial these data indicate the detrimental effect of pneumothorax on outcome and the beneficial effect of a standardized approach to care using conventional intensive care techniques.     

Mortality prediction in congenital diaphragmatic hernia

Background

A validated risk stratification tool for congenital diaphragmatic hernia (CDH) is required for accurate outcomes analyses. Existing mortality-predictive models include those of the CDH Study Group (CDHSG) based on birth weight and 5-minute Apgar score, the Canadian Neonatal Network (CNN) based on gestational age and admission score in Score for Neonatal Acute Physiology version II, and the Wilford Hall/Santa Rosa clinical prediction formula (WHSR_PF) derived from blood gas measurements. The purpose of this study was to evaluate the calibration and discrimination of these predictive models using the Canadian Pediatric Surgical Network dataset.

Methods

Neonatal risk variables and birth hospital survivorship were collected prospectively in 11 perinatal centers, between May 2005 and October 2006. Actual vs predicted outcomes were analyzed for each equation to measure the calibration and discrimination of each model.

Results

Twenty (21.2%) of 94 infants with CDH died during birth hospitalization. The CDHSG model demonstrated superior discrimination (area under the receiver operator characteristic curve = 0.85; CNN = 0.79; WHSR_PF = 0.63). Model calibration reflected by the Hosmer-Lemeshow P value was poorest with the WHSR_PF = 0.37 and comparable between CDHSG and CNN (0.48 and 0.46, respectively).

Conclusion

Predictive outcome models are essential for risk-adjusted outcome analysis of CDH. The ideal predictive equation should prove robust across CDH datasets.