Congenital diaphragmatic hernia in the preterm infant.

BACKGROUND: Congenital diaphragmatic hernia (CDH) remains a significant cause of death in newborns. With advances in neonatal critical care and ventilation strategies, survival in the term infant now exceeds 80% in some centers. Although prematurity is a significant risk factor for morbidity and mortality in most neonatal diseases, its associated risk with infants with CDH has been described poorly. We sought to determine the impact of prematurity on survival using data from the Congenital Diaphragmatic Hernia Registry (CDHR). METHODS: Prospectively collected data from live-born infants with CDH were analyzed from the CDHR from January 1995 to July 2009. Preterm infants were defined as \u3c37 weeks estimated gestational age at birth. Univariate and multivariate logistic regression analysis were\u3eperformed. RESULTS: During the study period, 5,069 infants with CDH were entered in the registry. Of the 5,022 infants with gestational age data, there were 3,895 term infants (77.6%) and 1,127 preterm infants (22.4%). Overall survival was 68.7%. A higher percentage of term infants were treated with extracorporeal membrane oxygenation (ECMO) (33% term vs 25.6% preterm). Preterm infants had a greater percentage of chromosomal abnormalities (4% term vs 8.1% preterm) and major cardiac anomalies (6.1% term vs 11.8% preterm). Also, a significantly higher percentage of term infants had repair of the hernia (86.3% term vs 69.4% preterm). Survival for infants that underwent repair was high in both groups (84.6% term vs 77.2% preterm). Survival decreased with decreasing gestational age (73.1% term vs 53.5% preterm). The odds ratio (OR) for death among preterm infants adjusted for patch repair, ECMO, chromosomal abnormalities, and major cardiac anomalies was OR 1.68 (95% confidence interval [CI], 1.34-2.11). CONCLUSION: Although outcomes for preterm infants are clearly worse than in the term infant, more than 50% of preterm infants still survived. Preterm infants with CDH remain a high-risk group. Although ECMO may be of limited value in the extremely premature infant with CDH, most preterm infants that live to undergo repair will survive. Prematurity should not be an independent factor in the treatment strategies of infants with CDH

Survival Rate Changes in Neonates with Congenital Diaphragmatic Hernia and its Contributing Factors

The purpose of this study was to demonstrate survival rate changes after the introduction of inhaled nitric oxide (iNO) therapy, and to identify the factors that influence these changes in neonates with a congenital diaphragmatic hernia (CDH) at a single center. A total of 48 neonates were divided into two groups based on the time of admission, i.e., into period I (P1; n=17; before the introduction of iNO therapy) and period II (P2; n=31; after the introduction of iNO therapy). Survival rates of the 48 neonates showed a tendency to increase from 53% during P1 to 77% during P2, but without a statistical significance, but a significant difference was found between survival rates during the two periods after adjusting for initial clinical characteristics, when the postoperative survival rate increased significantly from 69% for P1 to 100% for P2. The mean duration of preoperative respiratory management was significantly longer for P2 than for P1. Seven of 12 patients who received preoperative iNO therapy due to persistent pulmonary hypertension or refractory preductal hypoxemia in P2 survived after operation. We speculate that a management strategy based on iNO therapy and delayed operation, rather than differences between the initial clinical characteristics of the two study groups, might partially contribute to the observed improvements in postoperative and overall survival rates in neonates with CDH

Diagnosing gestational diabetes

The newly proposed criteria for diagnosing gestational diabetes will result in a gestational diabetes prevalence of 17.8%, doubling the numbers of pregnant women currently diagnosed. These new diagnostic criteria are based primarily on the levels of glucose associated with a 1.75-fold increased risk of giving birth to large-for-gestational age infants (LGA) in the Hyperglycemia Adverse Pregnancy Outcome (HAPO) study; they use a single OGTT. Thus, of 23,316 pregnancies, gestational diabetes would be diagnosed in 4,150 women rather than in 2,448 women if a twofold increased risk of LGA were used. It should be recognised that the majority of women with LGA have normal glucose levels during pregnancy by these proposed criteria and that maternal obesity is a stronger predictor of LGA. The expected benefit of a diagnosis of gestational diabetes in these 1,702 additional women would be the prevention of 140 cases of LGA, 21 cases of shoulder dystocia and 16 cases of birth injury. The reproducibility of an OGTT for diagnosing mild hyperglycaemia is poor. Given that (1) glucose is a weak predictor of LGA, (2) treating these extra numbers has a modest outcome benefit and (3) the diagnosis may be based on a single raised OGTT value, further debate should occur before resources are allocated to implementing this change

Decreased surfactant phosphatidylcholine synthesis in neonates with congenital diaphragmatic hernia during extracorporeal membrane oxygenation

Purpose: Congenital diaphragmatic hernia (CDH) may result in severe respiratory insufficiency with a high morbidity. The role of a disturbed surfactant metabolism in the pathogenesis of CDH is unclear. We therefore studied endogenous surfactant metabolism in the most severe CDH patients who required extracorporeal membrane oxygenation (ECMO). Methods: Eleven neonates with CDH who required ECMO and ten ventilated neonates without significant lung disease received a 24-h infusion of the stable isotope [U-13C] glucose. The13C-incorporation into palmitic acid in surfactant phosphatidylcholine (PC) isolated from serial tracheal aspirates was measured. Mean PC concentration in epithelial lining fluid (ELF) was measured during the first 4 days of the study. Results: Fractional surfactant PC synthesis was decreased in CDH-ECMO patients compared to controls (2.4 ± 0.33 vs. 8.0 ± 2.4%/day, p = 0.04). The control group had a higher maximal enrichment (0.18 ± 0.03 vs. 0.09 ± 0.02 APE, p = 0.04) and reached this maximal enrichment earlier (46.7 ± 3.0 vs. 69.4 ± 6.6 h, p = 0.004) compared to the CDH-ECMO group, which reflects higher and faster precursor incorporation in the control group. Surfactant PC concentration in ELF was similar in both groups. Conclusion: These results show that CDH patients who require ECMO have a decreased surfactant PC synthesis, which may be part of the pathogenesis of severe pulmonary insufficiency and has a negative impact on weaning from ECMO

Decreased surfactant phosphatidylcholine synthesis in neonates with congenital diaphragmatic hernia during extracorporeal membrane oxygenation

Purpose: Congenital diaphragmatic hernia (CDH) may result in severe respiratory insufficiency with a high morbidity. The role of a disturbed surfactant metabolism in the pathogenesis of CDH is unclear. We therefore studied endogenous surfactant metabolism in the most severe CDH patients who required extracorporeal membrane oxygenation (ECMO). Methods: Eleven neonates with CDH who required ECMO and ten ventilated neonates without significant lung disease received a 24-h infusion of the stable isotope [U-13C] glucose. The13C-incorporation into palmitic acid in surfactant phosphatidylcholine (PC) isolated from serial tracheal aspirates was measured. Mean PC concentration in epithelial lining fluid (ELF) was measured during the first 4 days of the study. Results: Fractional surfactant PC synthesis was decreased in CDH-ECMO patients compared to controls (2.4 ± 0.33 vs. 8.0 ± 2.4%/day, p = 0.04). The control group had a higher maximal enrichment (0.18 ± 0.03 vs. 0.09 ± 0.02 APE, p = 0.04) and reached this maximal enrichment earlier (46.7 ± 3.0 vs. 69.4 ± 6.6 h, p = 0.004) compared to the CDH-ECMO group, which reflects higher and faster precursor incorporation in the control group. Surfactant PC concentration in ELF was similar in both groups. Conclusion: These results show that CDH patients who require ECMO have a decreased surfactant PC synthesis, which may be part of the pathogenesis of severe pulmonary insufficiency and has a negative impact on weaning from ECMO

Can we improve outcome of congenital diaphragmatic hernia?

This review gives an overview of the disease spectrum of congenital diaphragmatic hernia (CDH). Etiological factors, prenatal predictors of survival, new treatment strategies and long-term morbidity are described. Early recognition of problems and improvement of treatment strategies in CDH patients may increase survival and prevent secondary morbidity. Multidisciplinary healthcare is necessary to improve healthcare for CDH patients. Absence of international therapy guidelines, lack of evidence of many therapeutic modalities and the relative low number of CDH patients calls for cooperation between centers with an expertise in the treatment of CDH patients. The international CDH Euro-Consortium is an example of such a collaborative network, which enhances exchange of knowledge, future research and development of treatment protocols