Surfactant does not improve survival rate in preterm infants with congenital diaphragmatic hernia

doi:10.1016/j.jpedsurg.2004.02.011

Cited by 93 publications

(12 citation statements)

References 24 publications

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“…Although exogenous surfactant was formerly reported to be effective in three high-risk newborns with CDH [32], a more recent multicentric study evidenced no benefit [34], consistent with our findings of normal surfactant content. Furthermore, another recent investigation concluded that late prenatal corticosteroids provide no significant benefit to fetuses with CDH [56], and this finding is consistent with a normal maturational rate and normal level of corticosteroid-dependent maturation factors as reported in this paper.…”

Section: Discussionsupporting

confidence: 91%

“…Clarifying this question is important insofar as decisions have to be made as to whether or not infants with CDH should be supplemented with surfactant at birth [32–34]; this issue is particularly important because the use of exogenous surfactant in CDH is routine in several neonatal centers. No actual quantitative determination of surfactant in human CDH lung tissue is available.…”

Section: Introductionmentioning

confidence: 99%

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Surfactant Maturation Is Not Delayed in Human Fetuses with Diaphragmatic Hernia

et al. 2007

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BackgroundPulmonary hypoplasia and persistent pulmonary hypertension account for significant mortality and morbidity in neonates with congenital diaphragmatic hernia (CDH). Global lung immaturity and studies in animal models suggest the presence of surfactant deficiency that may further complicate the pathophysiology of CDH. However, data about surfactant status in human fetuses with CDH at birth are contradictory. The lack of a chronological study of surfactant content in late pregnancy has been a significant limitation. The appropriateness of administering surfactant supplements to neonates with CDH is therefore a debated question.Methods and FindingsWe investigated surfactant content in human fetuses with CDH compared to age-matched fetuses with nonpulmonary diseases used as controls. Concentrations of disaturated phosphatidylcholine and surfactant proteins were found to be similar at a given stage of pregnancy, with both components showing a similar pattern of increase with progressing pregnancy in fetuses with CDH and in control fetuses. Thyroid transcription factor 1, a critical regulator of surfactant protein transcription, similarly displayed no difference in abundance. Finally, we examined the expression of three glucocorticoid-regulated diffusible mediators involved in lung epithelial maturation, namely: keratinocyte growth factor (KGF), leptin, and neuregulin 1 beta 1 (NRG1-β1). KGF expression decreased slightly with time in control fetuses, but remained unchanged in fetuses with CDH. Leptin and NRG1-β1 similarly increased in late pregnancy in control and CDH lungs. These maturation factors were also determined in the sheep fetus with surgical diaphragmatic hernia, in which surfactant deficiency has been reported previously. In contrast to the findings in humans, surgical diaphragmatic hernia in the sheep fetus was associated with decreased KGF and neuregulin expression. Fetoscopic endoluminal tracheal occlusion performed in the sheep model to correct lung hypoplasia increased leptin expression, partially restored KGF expression, and fully restored neuregulin expression.ConclusionsOur results indicate that CDH does not impair surfactant storage in human fetuses. CDH lungs exhibited no trend toward a decrease in contents, or a delay in developmental changes for any of the studied surfactant components and surfactant maturation factors. Surfactant amounts are likely to be appropriate to lung size. These findings therefore do not support the use of surfactant therapy for infants with CDH. Moreover, they raise the question of the relevance of CDH animal models to explore lung biochemical maturity.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Surfactant Maturation Is Not Delayed in Human Fetuses with Diaphragmatic Hernia

et al. 2007

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“…46–48 In our cohort, PGE1 was used in 5% of infants with CDH and did not significantly change over time. Surfactant has not been shown to improve survival in CDH 49 and may worsen outcomes, including death and need for ECMO. 4, 29 In our study, surfactant use did not change over the study period with 15–17% of infants receiving the medication.…”

Section: Discussionmentioning

confidence: 99%

Management Practice and Mortality for Infants with Congenital Diaphragmatic Hernia

Malowitz

Hornik

Laughon³

et al. 2015

Amer J Perinatol

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Objective Congenital diaphragmatic hernia (CDH) is fatal in 20–40% of cases, largely due to pulmonary dysmaturity, lung hypoplasia, and persistent pulmonary hypertension. Evidence for survival benefit of inhaled nitric oxide (iNO), extracorporeal membrane oxygenation (ECMO), and other medical interventions targeting pulmonary hypertension is lacking. We assessed medical interventions and mortality over time in a large multicenter cohort of infants with CDH. Study Design We identified all infants ≥34 weeks gestation with CDH discharged from 29 neonatal intensive care units between 1999 and 2012 with an average of ≥2 CDH admissions per year. We examined mortality and the proportion of infants exposed to medical interventions, comparing 4 periods of time: 1999–2001, 2002–2004, 2005–2007, and 2008–2012. Results We identified 760 infants with CDH. From 1999–2001 to 2008–2012, use of iNO increased from 20% of infants to 50%, sildenafil use increased from 0% to 14%, and milrinone use increased from 0% to 22% (p<0.001). Overall mortality (28%) did not significantly change over time compared with the earliest time period. Conclusions Despite changing use of iNO, sildenafil, and milrinone, CDH mortality has not significantly decreased in this population of infants.

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“…Its use in preterm infant was also associated with lower survival rate [75]. However, this trial by its retrospective nature may be biased as sicker patients may have received surfactant Although there are no increasing trends in use of surfactant, it is still being used in preterm infants with CDH across centers [76].…”

Section: Reviewmentioning

confidence: 99%

Congenital Diaphragmatic hernia – a review

Chandrasekharan

Rawat

Madappa³

et al. 2017

matern health, neonatol and perinatol

221

151

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Congenital Diaphragmatic hernia (CDH) is a condition characterized by a defect in the diaphragm leading to protrusion of abdominal contents into the thoracic cavity interfering with normal development of the lungs. The defect may range from a small aperture in the posterior muscle rim to complete absence of diaphragm.The pathophysiology of CDH is a combination of lung hypoplasia and immaturity associated with persistent pulmonary hypertension of newborn (PPHN) and cardiac dysfunction. Prenatal assessment of lung to head ratio (LHR) and position of the liver by ultrasound are used to diagnose and predict outcomes. Delivery of infants with CDH is recommended close to term gestation. Immediate management at birth includes bowel decompression, avoidance of mask ventilation and endotracheal tube placement if required. The main focus of management includes gentle ventilation, hemodynamic monitoring and treatment of pulmonary hypertension followed by surgery. Although inhaled nitric oxide is not approved by FDA for the treatment of PPHN induced by CDH, it is commonly used.Extracorporeal membrane oxygenation (ECMO) is typically considered after failure of conventional medical management for infants ≥ 34 weeks’ gestation or with weight >2 kg with CDH and no associated major lethal anomalies. Multiple factors such as prematurity, associated abnormalities, severity of PPHN, type of repair and need for ECMO can affect the survival of an infant with CDH. With advances in the management of CDH, the overall survival has improved and has been reported to be 70-90% in non-ECMO infants and up to 50% in infants who undergo ECMO.

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Surfactant does not improve survival rate in preterm infants with congenital diaphragmatic hernia

Cited by 93 publications

References 24 publications

Surfactant Maturation Is Not Delayed in Human Fetuses with Diaphragmatic Hernia

Surfactant Maturation Is Not Delayed in Human Fetuses with Diaphragmatic Hernia

Management Practice and Mortality for Infants with Congenital Diaphragmatic Hernia

Congenital Diaphragmatic hernia – a review

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