RESUMO
Background: Congenital diaphragmatic hernia (CDH) is a severe embryological defect that causes pulmonary hypoplasia and hypertension. The prevalence and mortality rate of CDH varies around the world and little information is available about CDH in Latin America. Our aim was to estimate the general prevalence, mortality rate, prevalence of associated anomalies and features related to the outcomes of CDH in newborns from São Paulo state, Brazil. Methods: Population-based cross-sectional study based on data gathered from the Live Births Information System (SINASC) and the Mortality Information System (SIM) of children born in São Paulo state between January 1st, 2006, and December 31st, 2017. Findings: From 7,311,074 total survival discharges between 2006 and 2017, 1,155 were CDH-related, resulting in a prevalence rate of 1:6329 (95%CI = 1/6715 - 1/5984) and a mortality rate of 63·72% (95%CI = 60.95 - 66.50), 510 presented complex associated anomalies (44·15%). Maternal data showed higher prevalence among older mothers (older than 35 years old: 2·13 per 10,000) and, also, women with more years of schooling (higher than 12 years: 1·99 per 10,000). Presence of associated anomalies (95%CI = 5.69-11.10), 1-min Apgar (95%CI = 1.44-2.95), maternal schooling (95%CI = 1.06-2.43) and birth weight (95%CI = 1.04-2.26) were the most significant features associated with mortality. Interpretation: There was 1 CDH case for every 6329 newborns in São Paulo and the mortality rate among those cases was 63·72% - a high rate compared to other countries. Funding: This study didn't receive any specific grant from any funding agency in the public, commercial or not-for-profit sectors.
RESUMO
BACKGROUND/PURPOSE: Congenital diaphragmatic hernia (CDH) is a defect that presents high mortality because of pulmonary hypoplasia and hypertension. Mechanical ventilation changes signaling pathways, such as nitric oxide and VEGF in the pulmonary arterioles. We investigated the production of NOS2 and NOS3 and expression of VEGF and its receptors after ventilation in rat fetuses with CDH. METHODS: CDH was induced by Nitrofen. The fetuses were divided into 6 groups: 1) control (C); 2) control ventilated (CV); 3) exposed to nitrofen (N-); 4) exposed to nitrofen ventilated (N-V), 5) CDH and 6) CDH ventilated (CDHV). Fetuses were harvested and ventilated. We assessed body weight (BW), total lung weight (TLW), TLW/BW ratio, the median pulmonary arteriolar wall thickness (MWT). We analyzed the expression of NOS2, NOS3, VEGF and its receptors by immunohistochemistry and Western blotting. RESULTS: BW, TLW, and TLW/BW ratio were greater on C than on N- and CDH (p<0.05). The MWT was higher in CDH than in CDHV (p<0.001). CDHV showed increased expression of NOS3 (p<0.05) and VEGFR1 (p<0.05), but decreased expression of NOS2 (p<0.05) and VEGFR2 (p<0.001) compared to CDH. CONCLUSION: Ventilation caused pulmonary vasodilation and changed the expression of NOS and VEGF receptors.
Assuntos
Hérnia Diafragmática/metabolismo , Hérnias Diafragmáticas Congênitas/metabolismo , Óxido Nítrico Sintase/metabolismo , Respiração Artificial , Fator A de Crescimento do Endotélio Vascular/metabolismo , Vasodilatação/fisiologia , Animais , Animais Recém-Nascidos , Modelos Animais de Doenças , Feminino , Hérnia Diafragmática/induzido quimicamente , Hérnia Diafragmática/fisiopatologia , Ratos , Ratos Sprague-DawleyRESUMO
PURPOSE: To evaluate the intrauterine growth restriction (IUGR) by the expression of IR-ß, IRS-1, IRS-2, IGF-IRß and Ikappaß in experimental model of gastroschisis. METHODS: Pregnant rats at 18.5 days of gestation were submitted to surgery to create experimental fetal gastroschisis (term = 22 days) were divided in three groups: gastroschisis (G), control (C) and sham (S). Fetuses were evaluated for body weight (BW), intestinal (IW), liver (LW) and their relations IW/BW and LW/BW. IR-ß and IGF-IRß receptors, IRS-1 and IRS-2 substrates and Ikappaß protein were analyzed by western blotting. RESULTS: BW was lower in G, the IW and IW / BW were greater than C and S (p<0.05) groups. The liver showed no differences between groups. In fetuses with gastroschisis, compared with control fetuses, the expression of IGF-IRß (p<0.001) and Ikappaß (p<0.001) increased in the liver and intestine, as well as IR-ß (p<0.001) which decreased in both. In contrast to the intestine, IRS-1 (p<0.001) increased in the liver and IRS-2 decreased (p<0.01). CONCLUSION: The axis of the intestine liver has an important role in inflammation, with consequent changes in the metabolic pathway of glucose can contribute to the IUGR in fetuses with gastroschisis.
Assuntos
Retardo do Crescimento Fetal/etiologia , Trato Gastrointestinal/metabolismo , Gastrosquise/complicações , Fígado/fisiopatologia , Receptor de Insulina/metabolismo , Animais , Modelos Animais de Doenças , Feminino , Proteínas I-kappa B/metabolismo , Fígado/metabolismo , Gravidez , Ratos , Ratos Sprague-DawleyRESUMO
PURPOSE: To evaluate the effect of corticosteroids on intestinal and liver interleukin profile in an experimental model of gastroschisis in fetal rats. METHODS: Sprague-Dawley rats at 19.5 days of gestation had its fetuses operated for the creation of gastroschisis. Two groups of fetuses were studied with and without maternal administration of dexamethasone. Each group was composed of fetuses who underwent gastroschisis (G), control fetuses without manipulation (C) and sham fetuses (S). A dosage of the following interleukins was carried out in fetal intestinal and liver tissues: IL-1, IL-6, IL-10, tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ). The differences between the groups and subgroups were tested by ANOVA with Tukey post-test, with significant values of p<0.05. RESULTS: Dexamethasone led to an increase in intestinal and liver IL-6 (p<0.05) and a decrease in intestinal TNF-α (p<0.001) in fetuses with gastroschisis. CONCLUSION: Corticosteroids had an effect on the intestinal interleukin profile and a small effect on the liver interleukin profile due to immunological immaturity of the fetus, and also of fetuses with gastroschisis. The steroid action may not be exclusively anti-inflammatory, but also pro-inflammatory, varying with time of pregnancy.
Assuntos
Citocinas/análise , Dexametasona/farmacologia , Gastrosquise/tratamento farmacológico , Glucocorticoides/farmacologia , Intestinos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Gastrosquise/embriologia , Gastrosquise/metabolismo , Interferon gama/análise , Interferon gama/metabolismo , Interleucinas/análise , Interleucinas/metabolismo , Mucosa Intestinal/metabolismo , Fígado/metabolismo , Gravidez , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/metabolismoRESUMO
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.
Assuntos
Hérnias Diafragmáticas Congênitas , Miosinas/metabolismo , Praguicidas/toxicidade , Éteres Fenílicos/toxicidade , Animais , Modelos Animais de Doenças , Feminino , Hérnia Diafragmática/induzido quimicamente , Hérnia Diafragmática/embriologia , Hérnia Diafragmática/patologia , Imuno-Histoquímica , Gravidez , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVES: To evaluate the histological changes of tracheal cartilage and epithelium caused by tracheal occlusion at different gestational ages in a fetal rat model. METHODS: Rat fetuses were divided into two groups: a) External control, composed of non-operated rats, and b) Interventional group, composed of rats operated upon on gestational day 18.5 (term = 22 days), divided into triads: 1) Tracheal occlusion, 2) Internal control and 3) Sham (manipulated but not operated). Morphological data for body weight, total lung weight and total lung weight/body weight ratio were collected and measured on gestational days 19.5, 20.5 and 21.5. Tracheal samples were histologically processed, and epithelial, chondral and total tracheal thicknesses were measured on each gestational day. RESULTS: The tracheal occlusion group exhibited an increase in total lung weight/body weight ratio (p<0.001). Histologically, this group had a thicker epithelial thickness (p<0.05) and thinner chondral (p<0.05) and total tracheal thicknesses (p<0.001). These differences were more prominent on gestational days 20.5 and 21.5. CONCLUSION: Tracheal occlusion changed tracheal morphology, increased epithelial thickness and considerably decreased total tracheal thickness. These changes in the tracheal wall could explain the development of tracheomegaly, recently reported in some human fetuses subjected to tracheal occlusion.
Assuntos
Feto/cirurgia , Idade Gestacional , Modelos Animais , Oclusão Terapêutica/métodos , Traqueia/cirurgia , Fatores Etários , Animais , Peso Corporal , Feto/anatomia & histologia , Feto/embriologia , Pulmão/anatomia & histologia , Pulmão/embriologia , Tamanho do Órgão , Ratos , Reprodutibilidade dos Testes , Oclusão Terapêutica/efeitos adversos , Fatores de Tempo , Traqueia/anatomia & histologia , Traqueia/embriologiaRESUMO
OBJECTIVES: To evaluate the histological changes of tracheal cartilage and epithelium caused by tracheal occlusion at different gestational ages in a fetal rat model. METHODS: Rat fetuses were divided into two groups: a) External control, composed of non-operated rats, and b) Interventional group, composed of rats operated upon on gestational day 18.5 (term = 22 days), divided into triads: 1) Tracheal occlusion, 2) Internal control and 3) Sham (manipulated but not operated). Morphological data for body weight, total lung weight and total lung weight/body weight ratio were collected and measured on gestational days 19.5, 20.5 and 21.5. Tracheal samples were histologically processed, and epithelial, chondral and total tracheal thicknesses were measured on each gestational day. RESULTS: The tracheal occlusion group exhibited an increase in total lung weight/body weight ratio (p<0.001). Histologically, this group had a thicker epithelial thickness (p<0.05) and thinner chondral (p<0.05) and total tracheal thicknesses (p<0.001). These differences were more prominent on gestational days 20.5 and 21.5. CONCLUSION: Tracheal occlusion changed tracheal morphology, increased epithelial thickness and considerably decreased total tracheal thickness. These changes in the tracheal wall could explain the development of tracheomegaly, recently reported in some human fetuses subjected to tracheal occlusion.
Assuntos
Animais , Ratos , Feto/cirurgia , Idade Gestacional , Modelos Animais , Oclusão Terapêutica/métodos , Traqueia/cirurgia , Fatores Etários , Peso Corporal , Feto/anatomia & histologia , Feto/embriologia , Pulmão/anatomia & histologia , Pulmão/embriologia , Tamanho do Órgão , Reprodutibilidade dos Testes , Fatores de Tempo , Oclusão Terapêutica/efeitos adversos , Traqueia/anatomia & histologia , Traqueia/embriologiaRESUMO
PURPOSE: To evaluate the intrauterine growth restriction (IUGR) by the expression of IR-β, IRS-1, IRS-2, IGF-IRβ and Ikappaβ in experimental model of gastroschisis. METHODS: Pregnant rats at 18.5 days of gestation were submitted to surgery to create experimental fetal gastroschisis (term = 22 days) were divided in three groups: gastroschisis (G), control (C) and sham (S). Fetuses were evaluated for body weight (BW), intestinal (IW), liver (LW) and their relations IW/BW and LW/BW. IR-β and IGF-IRβ receptors, IRS-1 and IRS-2 substrates and Ikappaβ protein were analyzed by western blotting. RESULTS: BW was lower in G, the IW and IW / BW were greater than C and S (p<0.05) groups. The liver showed no differences between groups. In fetuses with gastroschisis, compared with control fetuses, the expression of IGF-IRβ (p<0.001) and Ikappaβ (p<0.001) increased in the liver and intestine, as well as IR-β (p<0.001) which decreased in both. In contrast to the intestine, IRS-1 (p<0.001) increased in the liver and IRS-2 decreased (p<0.01). CONCLUSION: The axis of the intestine liver has an important role in inflammation, with consequent changes in the metabolic pathway of glucose can contribute to the IUGR in fetuses with gastroschisis.
OBJETIVO: Avaliar a restrição de crescimento intra-uterino (RCIU) pela expressão de IR-β, IRS-1, IRS-2, IGF-IRβ e a via inflamatória do Ikappaβ no modelo de gastrosquise experimental. MÉTODOS: Ratas grávidas com 18,5 dias de gestação foram submetidas a cirurgia experimental para criar gastrosquise fetal (termo = 22 dias) e os fetos foram divididos em três grupos: gastrosquise (G), controle (C) e sham (S). Os fetos foram avaliados quanto ao peso corporal (BW), intestinal (IW), fígado (LW) e suas relações IW/BW e LW/BW. Os receptores IR-β e IGF-IRβ, os substratos IRS-1 e IRS-2 e a proteína Ikappaβ foram analisados por western blotting. RESULTADOS: O BW de G foi menor, o IW e IW/BW foram superiores a C e S (p < 0.05). O fígado não apresentou diferenças entre os grupos. Nos fetos com gastrosquise, quando comparados com fetos controles, a expressão de IGF-IRβ (p<0.001) e Ikappaβ (p<0.001) aumentou no fígado e intestino, assim como IR-β (p<0.001) que diminuiu em ambos. Inversamente ao intestino, IRS-1 (p<0.001) aumentou no fígado e IRS-2 diminuiu (p<0.01). CONCLUSÃO: O eixo do intestino fígado tem um papel importante na inflamação, com consequentes alterações na via metabólica de glicose que pode contribuir para a RCIU em fetos com gastrosquise.
Assuntos
Animais , Feminino , Gravidez , Ratos , Retardo do Crescimento Fetal/etiologia , Trato Gastrointestinal/metabolismo , Gastrosquise/complicações , Fígado/fisiopatologia , Receptor de Insulina/metabolismo , Modelos Animais de Doenças , Proteínas I-kappa B/metabolismo , Fígado/metabolismo , Ratos Sprague-DawleyRESUMO
PURPOSE: To evaluate the effect of corticosteroids on intestinal and liver interleukin profile in an experimental model of gastroschisis in fetal rats. METHODS: Sprague-Dawley rats at 19.5 days of gestation had its fetuses operated for the creation of gastroschisis. Two groups of fetuses were studied with and without maternal administration of dexamethasone. Each group was composed of fetuses who underwent gastroschisis (G), control fetuses without manipulation (C) and sham fetuses (S). A dosage of the following interleukins was carried out in fetal intestinal and liver tissues: IL-1, IL-6, IL-10, tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ). The differences between the groups and subgroups were tested by ANOVA with Tukey post-test, with significant values of p<0.05. RESULTS: Dexamethasone led to an increase in intestinal and liver IL-6 (p<0.05) and a decrease in intestinal TNF-α (p<0.001) in fetuses with gastroschisis. CONCLUSION: Corticosteroids had an effect on the intestinal interleukin profile and a small effect on the liver interleukin profile due to immunological immaturity of the fetus, and also of fetuses with gastroschisis. The steroid action may not be exclusively anti-inflammatory, but also pro-inflammatory, varying with time of pregnancy.
OBJETIVO: Avaliar a ação do corticosteroide no perfil de interleucinas intestinais e hepáticas no modelo experimental de gastrosquise em fetos de ratos. MÉTODOS: Ratas Sprague-Dawley com 19,5 dias de gestação tiveram fetos operados para criação de gastrosquise. Dois grupos de fetos foram estudados: com e sem administração materna de dexametasona. Cada grupo foi composto por fetos submetidos a gastrosquise (G), fetos controles sem manipulação (C) e fetos sham (S). Realizou-se a dosagem das seguintes interleucinas no tecido intestinal e hepático fetal: IL-1, IL-6, IL-10, fator de necrose tumoral-alfa (TNF-α) e interferon-gama (IFN-γ). As diferenças entre os grupos e subgrupos foram testadas pelo teste de ANOVA com pós-teste de Tukey, com valores significativos de p<0,05. RESULTADOS: A dexametasona levou a um aumento da IL-6 intestinal e hepática (p<0,05) e a uma diminuição do TNF-α intestinal (p<0,001) em fetos com gastrosquise. CONCLUSÃO: O corticosteróide apresentou efeito sobre o perfil de IL intestinal e pouco na hepática, devido a imaturidade imunológica dos fetos e também dos fetos com gastrosquise a ação do esteróide pode não ser exclusivamente anti-inflamatória, mas também pró inflamatória.
Assuntos
Animais , Feminino , Gravidez , Ratos , Citocinas/análise , Dexametasona/farmacologia , Gastrosquise/tratamento farmacológico , Glucocorticoides/farmacologia , Intestinos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Citocinas/metabolismo , Modelos Animais de Doenças , Gastrosquise/embriologia , Gastrosquise/metabolismo , Interferon gama/análise , Interferon gama/metabolismo , Interleucinas/análise , Interleucinas/metabolismo , Intestinos/metabolismo , Fígado/metabolismo , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/metabolismoRESUMO
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.