Neonatal and fetal therapy of congenital diaphragmatic hernia-related pulmonary hypertension

Congenital diaphragmatic hernia (CDH) is a complex malformation characterised by a triad of pulmonary hypoplasia, pulmonary hypertension (PH) and cardiac ventricular dysfunction. Much of the mortality and morbidity in CDH is largely accounted for by PH, especially when persistent beyond the neonatal period and refractory to available treatment. Gentle ventilation, haemodynamic optimisation and pulmonary vasodilation constitute the foundations of neonatal treatment of CDH-related PH (CDH-PH). Moreover, early prenatal diagnosis, the ability to assess severity and the developmental nature of the condition generate the perfect rationale for fetal therapy. Shortcomings of currently available clinical therapies in combination with increased understanding of CDH pathophysiology have spurred experimental drug trials, exploring new therapeutic mechanisms to tackle CDH-PH. We herein discuss clinically available neonatal and fetal therapies specifically targeting CDH-PH and review the most promising experimental treatments and future research avenues.

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Congenital Diaphragmatic Hernia: State of the Art in Translating Experimental Research to the Bedside

European Journal of Pediatric Surgery ◽

10.1055/s-0039-1693993 ◽

2019 ◽

Vol 29 (04) ◽

pp. 317-327

Author(s):

Lina Antounians ◽

Rebeca Lopes Figueira ◽

Lourenço Sbragia ◽

Augusto Zani

Keyword(s):

Pulmonary Hypertension ◽

Congenital Diaphragmatic Hernia ◽

Diaphragmatic Hernia ◽

Vascular Remodeling ◽

Pulmonary Hypoplasia ◽

Genetic Alterations ◽

Diaphragmatic Defect ◽

Morbidity Rate ◽

Lung Growth ◽

Mortality And Morbidity

AbstractCongenital diaphragmatic hernia (CDH) is a devastating disease that still carries a high mortality and morbidity rate. Poor outcomes for fetuses and infants with CDH are mainly related to pulmonary hypoplasia (PH) and pulmonary vascular remodeling that leads to pulmonary hypertension (PHTN). Over the last five decades, research efforts have focused on modeling CDH not only to study the pathophysiology of the diaphragmatic defect, pulmonary hypoplasia, and pulmonary hypertension, but also to identify therapies that would promote lung growth and maturation, and correct vascular remodeling. As CDH is a multifactorial condition whose etiology remains unknown, there is not a single model of CDH, rather several ones that replicate different aspects of this disease. While small animals like the mouse and the rat have mainly been used to uncover biological pathways underlying the diaphragmatic defect and poor lung growth, larger animals like the lamb and the rabbit models have been instrumental for pursuing medical and surgical interventions. Overall, the use of animal models has indeed advanced our knowledge on CDH and helped us test innovative therapeutic options. For example, the lamb model of CDH has been the paradigm for testing fetal surgical procedures, including tracheal occlusion, which has been translated to clinical use. In this review, we outline the induction protocols of CDH in animals with the use of chemicals, dietary changes, genetic alterations, and surgical maneuvers, and we describe the studies that have translated experimental results to the bedside.

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NeoAPACHE II. Relationship Between Radiographic Pulmonary Area and Pulmonary Hypertension, Mortality, and Hernia Recurrence in Newborns With CDH

Frontiers in Pediatrics ◽

10.3389/fped.2021.692210 ◽

2021 ◽

Vol 9 ◽

Author(s):

Ilaria Amodeo ◽

Nicola Pesenti ◽

Genny Raffaeli ◽

Francesco Macchini ◽

Valentina Condò ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Congenital Diaphragmatic Hernia ◽

Diaphragmatic Hernia ◽

Secondary Analysis ◽

Recurrence Risk ◽

Hernia Recurrence ◽

Systolic Pulmonary Artery Pressure ◽

Clinical Trial Registration ◽

Mortality And Morbidity ◽

Lung Area

Congenital diaphragmatic hernia is a rare disease with high mortality and morbidity due to pulmonary hypoplasia and pulmonary hypertension. The aim of the study is to investigate the relationship between radiographic lung area and systolic pulmonary artery pressure (sPAP) on the first day of life, mortality, and hernia recurrence during the first year of life in infants with a congenital diaphragmatic hernia (CDH). A retrospective data collection was performed on 77 CDH newborns. Echocardiographic sPAP value, deaths, and recurrence cases were recorded. Lung area was calculated by tracing the lung's perimeter, excluding mediastinal structures, and herniated organs, on the preoperative chest X-ray performed within 24 h after birth. Logistic and linear regression analyses were performed. Deceased infants showed lower areas and higher sPAP values. One square centimeter of rising in the total, ipsilateral, and contralateral area was associated with a 22, 43, and 24% reduction in mortality risk. sPAP values showed a decreasing trend after birth, with a maximum of 1.84 mmHg reduction per unitary increment in the ipsilateral area at birth. Recurrence patients showed lower areas, with recurrence risk decreasing by 14 and 29% per unit increment of the total and ipsilateral area. In CDH patients, low lung area at birth reflects impaired lung development and defect size, being associated with increased sPAP values, mortality, and recurrence risk.Clinical Trial Registration: The manuscript is an exploratory secondary analysis of the trial registered at ClinicalTrials.gov with identifier NCT04396028.

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Study of Mortality and Morbidity in Neonates with Congenital Diaphragmatic Hernia

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2021/v33i37b32050 ◽

2021 ◽

pp. 277-282

Author(s):

Zainab Elahi ◽

Seyyed Abolfazl Afje ◽

Mohammad Kazemian ◽

Maryam Shariati ◽

Naeeme Taslimi Taleghani ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Congenital Diaphragmatic Hernia ◽

Diaphragmatic Hernia ◽

Analytical Study ◽

Place Of Birth ◽

Cross Sectional ◽

Mortality And Morbidity ◽

Relationship Of ◽

The Relationship ◽

Type Of Delivery

Introduction: Congenital diaphragmatic hernia may either lead to death or cause several complications such as increased pulmonary artery pressure. Objective: The present study aimed to compare mortality and morbidity, vasopressor intake, and visceral hernia of CDH neonates with pulmonary hypertension and without pulmonary hypertension in Mahdieh and Mofid hospitals in Tehran. Methods: This cross-sectional analytical study included 56 neonates with congenital diaphragmatic hernia who were admitted to Mofid and Mahdieh Children's Hospitals from 2014 to 2018. The sample size included 56 people selected based on census method. We compared the pulmonary hypertension and non-pulmonary hypertension groups in variables, such as gender, gestational age, birth weight, place of birth, and type of delivery and we examined relationship between pulmonary hypertension and mortality and morbidity and relationship between mortality and vasopressor intake. Results: The OR value was calculated to be 1.106, which is significant at the level of 0.004 (p < 0.01). This finding indicated that the chance of death in the group of infants with severe pulmonary hypertension was increased by 1.106. Also, the relationship of visceral hernia (stomach, intestine, liver, kidney, and spleen) to thorax was examined by logistic regression. Only the OR value of liver hernia (9.42) was significant (p < 0.001), indicating that the chance of death was higher in infants with liver hernias. It also the OR value of dopamine, dobutamine, and milrinone was significant (p < 0.01). Conclusion: In general, the results obtained in our study indicated that the mortality rate in the group of infants with pulmonary hypertension was significantly higher than the group without pulmonary hypertension. Also, liver hernia to thorax was associated with the severity of pulmonary hypertension, and the patients needed medication had a higher chance of death.

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