Quantitative lung index, contralateral lung area, or lung-to-head ratio to predict the neonatal outcome in isolated congenital diaphragmatic hernia?

OBJECTIVES: To estimate the accuracy of the quantitative lung index and contralateral lung area for prediction of the neonatal outcome in isolated congenital diaphragmatic hernia in comparison to other available prediction models. METHODS: Between January 2004 and December 2010, 108 fetuses with isolated (82 left-sided and 26 right-sided) congenital diaphragmatic hernia were prospectively evaluated. The quantitative lung index and observed-to-expected contralateral lung area were measured and compared to the neonatal survival rate and severe postnatal pulmonary arterial hypertension, along with the lung-to-head ratio, observed-to-expected lung-to-head ratio, and observed-to-expected total lung volume. RESULTS: Overall neonatal mortality was 64.8% (70 of 108). Severe pulmonary arterial hypertension was diagnosed in 68 (63.0%) of the cases, which was associated with neonatal death (P < .001). Both the quantitative lung index and observed-to-expected contralateral lung area were significantly associated with neonatal survival and pulmonary arterial hypertension (P < .001), with accuracy to predict survival of 70.9% and 70.0%, respectively, and accuracy to predict hypertension of 78.7% and 72.0%; however, they were both less accurate than the observed-to-expected total lung volume (83.3% and 86.1%; P < .01). The lung-to-head ratio (73.1% and 78.7%) and observed-to-expected lung-to-head ratio (75.9% and 72.2%; P > .05) had similar accuracy as the quantitative lung index and observed-to-expected contralateral lung area. CONCLUSIONS: The observed-to-expected total lung volume is the most accurate predictor of the neonatal outcome in cases of isolated congenital diaphragmatic hernia. Both the quantitative lung index and observed-to-expected contralateral lung area, albeit reasonably accurate, do not produce the same level of accuracy and render similar results as the lung-to-head ratio and observed-to-expected lung-to-head ratio.

Effect of nitrofen in the final stages of development of the diaphragm muscle in rats.

PURPOSE: To evaluate the expression of myosin in muscle fibers of the diaphragm in experimental congenital diaphragmatic hernia (CDH). METHODS: Fetuses of pregnant rats were divided into four groups: External Control (EC), composed of non-manipulated rats; Nitrofen, composed of pregnant rats that received 100 mg of nitrofen (2,4-dichloro-4'nitrodiphenyl ether) diluted in olive oil on gestational day (GD) 9.5, whose fetuses developed CDH (N+) or not (N-), and Olive Oil Placebo (OO), composed of pregnant rats that received the oil on the same GD. The fetuses were collected on GD 18.5, 19.5, 20.5 and 21.5 (term = 22 days). We obtained body weight (BW) and photographed the diaphragm area (DA), hernia area (HA) and subsequent calculated the HA/DA ratio in N+ group. Samples of Diaphragm muscle were processed for histological staining with H/E and immunohistochemistry (IHQ) for myosin. RESULTS: The fetuses of N- and N+ groups had decreased BW and DA compared to EC and OO groups (p < 0.001). HA was decreased on GD 18.5 compared to 21.5 (p < 0.001) and the HA/DA ratio showed no difference. IHQ showed decreased expression of myosin in nitrofen groups. CONCLUSION: CDH induced by nitrofen model contributes to the understanding of muscularization in the formation of the diaphragm where the myosin expression is decreased.

Effect of nitrofen in the final stages of development of the diaphragm muscle in rats / Efeito do nitrofen na fase final do desenvolvimento da musculatura do diafragma em ratos

PURPOSE: To evaluate the expression of myosin in muscle fibers of the diaphragm in experimental congenital diaphragmatic hernia (CDH). METHODS: Fetuses of pregnant rats were divided into four groups: External Control (EC), composed of non-manipulated rats; Nitrofen, composed of pregnant rats that received 100 mg of nitrofen (2,4-dichloro-4'nitrodiphenyl ether) diluted in olive oil on gestational day (GD) 9.5, whose fetuses developed CDH (N+) or not (N-), and Olive Oil Placebo (OO), composed of pregnant rats that received the oil on the same GD. The fetuses were collected on GD 18.5, 19.5, 20.5 and 21.5 (term = 22 days). We obtained body weight (BW) and photographed the diaphragm area (DA), hernia area (HA) and subsequent calculated the HA/DA ratio in N+ group. Samples of Diaphragm muscle were processed for histological staining with H/E and immunohistochemistry (IHQ) for myosin.} RESULTS: The fetuses of N- and N+ groups had decreased BW and DA compared to EC and OO groups (p <0.001). HA was decreased on GD 18.5 compared to 21.5 (p <0.001) and the HA/DA ratio showed no difference. IHQ showed decreased expression of myosin in nitrofen groups. CONCLUSION: CDH induced by nitrofen model contributes to the understanding of muscularization in the formation of the diaphragm where the myosin expression is decreased.

OBJETIVO: Avaliar a expressão da miosina na muscularização do diafragma na hérnia diafragmática congênita (CDH) experimental. MÉTODOS: Fetos de ratas foram divididos em quatro grupos: Controle Externo (EC), composto de ratas não manipuladas; Nitrofen, composto de ratas que receberam 100 mg de nitrofen (2,4-dicloro-4'nitrodifenil éter) diluído no azeite no dia de gestação (GD) 9.5, cujos fetos desenvolveram CDH (N+) ou não (N-) e Placebo óleo de oliva (OO), composto de ratas que ingeriram apenas óleo no mesmo GD. Os fetos foram coletados com 18,5, 19,5, 20,5 e 21,5 GD (termo = 22 dias). Foi obtido o peso corporal (BW) e tiradas fotografias da área do diafragma (DA), da hérnia (HA) e calculada a relação HA/DA no grupo N+. Amostras de diafragmas foram processadas histologicamente para coloração com H/E e imunohistoquímica. RESULTADOS: Os fetos dos grupos N- e N+ tiveram BW e DA diminuídos em relação aos grupos EC e OO (p<0.001). Só houve diferença na HA entre os GD 18.5 e 21.5 (p<0.001) e a relação HA/DA não mostrou diferença entre os grupos. A imunohistoquímica mostrou menor expressão de miosina nos grupos que receberam nitrofen. CONCLUSÃO: O modelo de CDH induzida por nitrofen contribui para entender a muscularização na formação do diafragma onde a expressão da miosina está diminuída.

A randomized controlled trial of fetal endoscopic tracheal occlusion versus postnatal management of severe isolated congenital diaphragmatic hernia.

OBJECTIVE: Severe pulmonary hypoplasia and pulmonary arterial hypertension are associated with reduced survival in congenital diaphragmatic hernia (CDH). We aimed to determine whether fetal endoscopic tracheal occlusion (FETO) improves survival in cases of severe isolated CDH. METHODS: Between May 2008 and July 2010, patients whose fetuses had severe isolated CDH (lung-to-head ratio < 1.0, liver herniation into the thoracic cavity and no other detectable anomalies) were assigned randomly to FETO or to no fetal intervention (controls). FETO was performed under maternal epidural anesthesia supplemented with fetal intramuscular anesthesia. Tracheal balloon placement was achieved with ultrasound guidance and fetoscopy between 26 and 30 weeks of gestation. All cases that underwent FETO were delivered by the EXIT procedure. Postnatal therapy was the same for both treated fetuses and controls. The primary outcome was survival to 6 months of age. Other maternal and neonatal outcomes were also evaluated. RESULTS: Twenty patients were enrolled randomly to FETO and 21 patients to standard postnatal management. The mean gestational age at randomization was similar in both groups (P = 0.83). Delivery occurred at 35.6 ± 2.4 weeks in the FETO group and at 37.4 ± 1.9 weeks in the controls (P < 0.01). In the intention-to-treat analysis, 10/20 (50.0%) infants in the FETO group survived, while 1/21 (4.8%) controls survived (relative risk (RR), 10.5 (95% CI, 1.5-74.7), P < 0.01). In the received-treatment analysis, 10/19 (52.6%) infants in the FETO group and 1/19 (5.3%) controls survived (RR, 10.0 (95% CI, 1.4-70.6) P < 0.01). CONCLUSION: FETO improves neonatal survival in cases with isolated severe CDH.

Prediction and probability of neonatal outcome in isolated congenital diaphragmatic hernia using multiple ultrasound parameters.

OBJECTIVES: To evaluate the accuracy and probabilities of different fetal ultrasound parameters to predict neonatal outcome in isolated congenital diaphragmatic hernia (CDH). METHODS: Between January 2004 and December 2010, we evaluated prospectively 108 fetuses with isolated CDH (82 left-sided and 26 right-sided). The following parameters were evaluated: gestational age at diagnosis, side of the diaphragmatic defect, presence of polyhydramnios, presence of liver herniated into the fetal thorax (liver-up), lung-to-head ratio (LHR) and observed/expected LHR (o/e-LHR), observed/expected contralateral and total fetal lung volume (o/e-ContFLV and o/e-TotFLV) ratios, ultrasonographic fetal lung volume/fetal weight ratio (US-FLW), observed/expected contralateral and main pulmonary artery diameter (o/e-ContPA and o/e-MPA) ratios and the contralateral vascularization index (Cont-VI). The outcomes were neonatal death and severe postnatal pulmonary arterial hypertension (PAH). RESULTS: Neonatal mortality was 64.8% (70/108). Severe PAH was diagnosed in 68 (63.0%) cases, of which 63 died neonatally (92.6%) (P < 0.001). Gestational age at diagnosis, side of the defect and polyhydramnios were not associated with poor outcome (P > 0.05). LHR, o/e-LHR, liver-up, o/e-ContFLV, o/e-TotFLV, US-FLW, o/e-ContPA, o/e-MPA and Cont-VI were associated with both neonatal death and severe postnatal PAH (P < 0.001). Receiver-operating characteristics curves indicated that measuring total lung volumes (o/e-TotFLV and US-FLW) was more accurate than was considering only the contralateral lung sizes (LHR, o/e-LHR and o/e-ContFLV; P < 0.05), and Cont-VI was the most accurate ultrasound parameter to predict neonatal death and severe PAH (P < 0.001). CONCLUSIONS: Evaluating total lung volumes is more accurate than is measuring only the contralateral lung size. Evaluating pulmonary vascularization (Cont-VI) is the most accurate predictor of neonatal outcome. Estimating the probability of survival and severe PAH allows classification of cases according to prognosis.

Oclusão traqueal para fetos com hérnia diafragmática esquerda grave isolada: um estudo experimental controlado não randomizado / Tracheal occlusion for fetuses with severe isolated left-sided diaphragmatic hernia: a nonrandomized controlled experimental study

OBJETIVO: Comparar a sobrevida pós-natal de fetos com hérnia diafragmática congênita esquerda grave isolada, os quais foram submetidos à oclusão traqueal, com a de controles não randomizados contemporâneos. MÉTODOS: Estudo experimental não randomizado e controlado, conduzido de abril de 2007 a setembro de 2011. Fetos portadores de hérnia diafragmática congênita esquerda isolada com herniação hepática e relação pulmão/cabeça <1,0, que foram submetidos à oclusão traqueal (grupo de estudo) ou conduta expectante (controles não randomizados contemporâneos), foram comparados quanto à relação pulmão/cabeça e ao observado/esperado da relação pulmão/cabeça no diagnóstico, à idade gestacional por ocasião do parto e sobrevida neonatal com alta do berçário. A evolução da relação pulmão/cabeça e do observado/esperado da relação pulmão/cabeça depois da oclusão traqueal foi descrita. Testes de Fisher, Mann-Whitney e Wilcoxon foram usados na análise estatística. RESULTADOS: Não houve diferenças significativas entre o grupo de estudo (n=28) e o Controle (n=13) quanto à relação pulmão/cabeça (p=0,7) e ao observado/esperado da relação pulmão/cabeça (p=0,5), no momento do diagnóstico, nem à idade gestacional no parto (p=0,146). A sobrevida com alta do berçário foi maior (p=0,012) no grupo da oclusão traqueal (10/28=35,7 por cento) do que no Grupo Controle (0/13=0,0 por cento). Houve aumento da relação pulmão/cabeça (p<0,001) e do observado/esperado da relação pulmão/cabeça (p<0,001) entre o momento do diagnóstico da hérnia diafragmática congênita [relação pulmão/cabeça: 0,8 (0,4-0,9); observado/esperado da relação pulmão/cabeça: 27,0 (15,3-45,0)] e um dia antes da retirada do balão traqueal [relação pulmão/cabeça: 1,2 (0,5-1,8); observado/esperado da relação pulmão/cabeça: 40,0 (17,5-60,0)]. CONCLUSÕES: Houve melhora significativa na sobrevida pós-natal com alta do berçário de fetos com hérnia diafragmática congênita esquerda isolada grave, que foram submetidos à oclusão traqueal em relação a controles não randomizados contemporâneos.

PURPOSE: To compare postnatal survival to hospital discharge of fetuses with severe isolated left-sided congenital diaphragmatic hernia, who underwent tracheal occlusion, with that of nonrandomized contemporaneous controls. METHODS: Experimental nonrandomized controlled study, performed from April 2007 to September 2011. Fetuses with severe isolated left-sided congenital diaphragmatic hernia with liver herniation into the chest and lung area-to-head circumference ratio <1.0, who underwent tracheal occlusion (study group) or expectant management (non-randomized contemporaneous controls), were compared in terms of lung area-to-head circumference ratio and observed/expected lung area-to-head circumference ratio (observed/expected lung area-to-head circumference ratio) at the time of diagnosis, gestational age at birth, and survival to hospital discharge. Modifications in lung area-to-head circumference ratio and o/e lung area-to-head circumference ratio after tracheal occlusion were also analyzed. Fisher's exact test, Mann-Whitney's or Wilcoxon's tests were used for the comparisons. RESULTS: There were no significant differences between the Study Group (TO=28) and Controls (n=13) in terms of the lung area-to-head circumference ratio (p=0.709) and the observed/expected lung area-to-head circumference ratio (p=0.5) at the time of diagnosis and gestational age at birth (p=0.146). The survival to hospital discharge was higher (p=0.012) in the tracheal occlusion group (10/28=35.7 percent) than in controls (0/13=0.0 percent). There was a significant increase in lung area-to-head circumference ratio (p<0.001) and observed/expected lung area-to-head circumference ratio (p<0.001) between the diagnosis of the congenital diaphragmatic hernia [lung area-to-head circumference ratio: 0.80 (0.40-0.94); observed/expected lung area-to-head circumference ratio: 27.0 (15.3-45.0)], and the day before retrieval of the balloon [lung area-to-head circumference ratio: 1.2 (0.50-1.80); observed/expected lung area-to-head circumference ratio: 40.0 (17.5-60.0)]. CONCLUSIONS: There was a significant improvement in the survival rate to hospital discharge of fetuses with severe isolated left-sided congenital diaphragmatic hernia, who underwent tracheal occlusion in comparison to nonrandomized contemporaneous controls.

[Tracheal occlusion for fetuses with severe isolated left-sided diaphragmatic hernia: a nonrandomized controlled experimental study]. / Oclusão traqueal para fetos com hérnia diafragmática esquerda grave isolada: um estudo experimental controlado não randomizado.

PURPOSE: To compare postnatal survival to hospital discharge of fetuses with severe isolated left-sided congenital diaphragmatic hernia, who underwent tracheal occlusion, with that of nonrandomized contemporaneous controls. METHODS: Experimental nonrandomized controlled study, performed from April 2007 to September 2011. Fetuses with severe isolated left-sided congenital diaphragmatic hernia with liver herniation into the chest and lung area-to-head circumference ratio <1.0, who underwent tracheal occlusion (study group) or expectant management (non-randomized contemporaneous controls), were compared in terms of lung area-to-head circumference ratio and observed/expected lung area-to-head circumference ratio (observed/expected lung area-to-head circumference ratio) at the time of diagnosis, gestational age at birth, and survival to hospital discharge. Modifications in lung area-to-head circumference ratio and o/e lung area-to-head circumference ratio after tracheal occlusion were also analyzed. Fisher's exact test, Mann-Whitney's or Wilcoxon's tests were used for the comparisons. RESULTS: There were no significant differences between the Study Group (TO=28) and Controls (n=13) in terms of the lung area-to-head circumference ratio (p=0.709) and the observed/expected lung area-to-head circumference ratio (p=0.5) at the time of diagnosis and gestational age at birth (p=0.146). The survival to hospital discharge was higher (p=0.012) in the tracheal occlusion group (10/28=35.7%) than in controls (0/13=0.0%). There was a significant increase in lung area-to-head circumference ratio (p<0.001) and observed/expected lung area-to-head circumference ratio (p<0.001) between the diagnosis of the congenital diaphragmatic hernia [lung area-to-head circumference ratio: 0.80 (0.40-0.94); observed/expected lung area-to-head circumference ratio: 27.0 (15.3-45.0)], and the day before retrieval of the balloon [lung area-to-head circumference ratio: 1.2 (0.50-1.80); observed/expected lung area-to-head circumference ratio: 40.0 (17.5-60.0)]. CONCLUSIONS: There was a significant improvement in the survival rate to hospital discharge of fetuses with severe isolated left-sided congenital diaphragmatic hernia, who underwent tracheal occlusion in comparison to nonrandomized contemporaneous controls.

Antenatal steroid and tracheal occlusion restore vascular endothelial growth factor receptors in congenital diaphragmatic hernia rat model.

OBJECTIVE: Investigate the effects of antenatal steroids and tracheal occlusion on pulmonary expression of vascular endothelial growth factor receptors in rats with nitrofen-induced congenital diaphragmatic hernia. STUDY DESIGN: Fetuses were exposed to nitrofen at embryonic day 9.5. Subgroups received dexamethasone or were operated on for tracheal occlusion, or received combined treatment. Morphologic variables were recorded. To analyze vascular endothelial growth factor receptor 1 and vascular endothelial growth factor receptor 2 expression, we performed Western blotting and immunohistochemistry. Morphologic variables were analyzed by analysis of variance and immunohistochemistry by Kruskal-Wallis test. RESULTS: Congenital diaphragmatic hernia decreased body weight, total lung weight, and lung-to-body weight ratio. Tracheal occlusion increased total lung weight and lung-to-body weight ratio (P < .05). Fetuses with congenital diaphragmatic hernia had reduced vascular endothelial growth factor receptor 1 and vascular endothelial growth factor receptor 2 expression, whereas steroids and tracheal occlusion increased their expression. Combined treatment increased expression of receptors, but had no additive effect. CONCLUSION: Vascular endothelial growth factor signaling disruption may be associated with pulmonary hypertension in congenital diaphragmatic hernia. Tracheal occlusion and steroids provide a pathway for restoring expression of vascular endothelial growth factor receptors.

Hérnia diafragmática congênita: revisão da literatura e relato de casos / Congenital diaphragmatic hernia: a literature review and case reports

A hérnia diafragmática congênita, tipicamente se apresenta na infância, no período neonatal imediato ou mais tardiamente em lactentes ou pré escolares, mas pode ser raramente detectada em adultos...Atualmente, com o advento de imagens digitais o diagnóstico precoce, até mesmo pré-natal, da hérnia diafragmática congênita tem contribuído para melhorar a morbidade e reduzir a mortalidade. O objetivo deste trabalho monográfico é fazer uma breve revisão bibliográfica sobre o tema em questão, revisando livros e artigos sobre o tema e descrevendo o mesmo de forma sucinta para então correlacioná-lo com os casos clínicos acompanhados no ambulatório de pediatria e pneumologia pediátrica do Hospital Universitário Antônio Pedro (HUAP).