Laurent Storme

Standardized Postnatal Management of Infants with Congenital Diaphragmatic Hernia in Europe: The CDH EURO Consortium Consensus - 2015 Update

In 2010, the congenital diaphragmatic hernia (CDH) EURO Consortium published a standardized neonatal treatment protocol. Five years later, the number of participating centers has been raised from 13 to 22. In this article the relevant literature is updated, and consensus has been reached between the members of the CDH EURO Consortium. Key updated recommendations are: (1) planned delivery after a gestational age of 39 weeks in a high-volume tertiary center; (2) neuromuscular blocking agents to be avoided during initial treatment in the delivery room; (3) adapt treatment to reach a preductal saturation of between 80 and 95% and postductal saturation >70%; (4) target PaCO2 to be between 50 and 70 mm Hg; (5) conventional mechanical ventilation to be the optimal initial ventilation strategy, and (6) intravenous sildenafil to be considered in CDH patients with severe pulmonary hypertension. This article represents the current opinion of all consortium members in Europe for the optimal neonatal treatment of CDH.

Outcome at 2 years of infants with congenital diaphragmatic hernia: a population-based study

BACKGROUND Management of neonates with congenital diaphragmatic hernia (CDH) has undergone many changes associated with increased survival of high-risk CDH. However, little is known about the long-term outcome of CDH infants. METHODS Follow-up was performed in 85 newborn infants with CDH admitted in our neonatal intensive care unit between January 1991 and December 1998. Early (< 2 months) and late mortality (> or = 2 months), and respiratory, nutritional, musculoskeletal, and neurosensory outcome at 2 years were recorded. RESULTS Surgical repair was performed in 59 infants (69%) at a median postnatal age of 124 (range, 38 to 246) hours. Extracorporeal membrane oxygenation was used in 26 (30%) newborn infants. Survival at 2 years was 51 of 85 (60%) (early death, 28/85 [33%]; late death, 6/85 [7%]). Late deaths occurred because of persistent pulmonary hypertension or iatrogenic complications. Twelve of 51 (24%) newborn infants were oxygen dependant at the postnatal age of 28 days, and 1 of 51 (1.9%) was still oxygen dependant at 2 years. Growth failure was noted in 9 of 51 (18%), mainly related to severe gastroesophageal reflux and oral aversion. Scoliosis was diagnosed in 2 infants. Neurologic examination at 2 years was normal in 45 of 51 (88%). Cerebral palsy and developmental delay were observed in 2 and 4 infants, respectively. Four infants (8%) experienced associated problems. Respiratory, nutritional, and musculoskeletal morbidity was higher in infants treated by extracorporeal membrane oxygenation (p < 0.05). CONCLUSIONS CDH infants are at risk for adverse nutritional and respiratory outcome. Despite severe respiratory failure at birth, prolonged oxygen therapy above 2 years of age is uncommon. Conversely, failure to thrive related at least in part to gastroesophageal reflux and oral dysfunction remains the major problem at 2 years of age. However, both nutritional and respiratory problems tend to improve with age.

Standardized postnatal management of infants with congenital diaphragmatic hernia in Europe

Congenital diaphragmatic hernia (CDH) is associated with high mortality and morbidity. To date, there are no standardized protocols for the treatment of infants with this anomaly. However, protocols based on the literature and expert opinion might improve outcome. This paper is a consensus statement from the CDH EURO Consortium prepared with the aim of achieving standardized postnatal treatment in European countries. During a consensus meeting between high-volume centers with expertise in the treatment of CDH in Europe (CDH EURO Consortium), the most recent literature on CDH was discussed. Thereafter, 5 experts graded the studies according to the Scottish Intercollegiate Guidelines Network (SIGN) Criteria. Differences in opinion were discussed until full consensus was reached. The final consensus statement, therefore, represents the opinion of all consortium members. Multicenter randomized controlled trials on CDH are lacking. Use of a standardized protocol, however, may contribute to more valid comparisons of patient data in multicenter studies and identification of areas for further research.

Prenatal prediction of neonatal morbidity in survivors with congenital diaphragmatic hernia: a multicenter study

To investigate the value of the observed to expected fetal lung area to head circumference ratio (o/e LHR) and liver position in the prediction of neonatal morbidity in survivors with congenital diaphragmatic hernia (CDH).

In Vivo Evidence for a Myogenic Response in the Fetal Pulmonary Circulation

In vitro studies have suggested that pulmonary arteries can exhibit a myogenic response and that this myogenic response may be potent during the perinatal period. However, whether a myogenic response can be demonstrated to exist in vivo and the potential role of the myogenic response on the regulation of pulmonary blood flow during fetal life is unknown. We hypothesized that an acute increase in pulmonary artery pressure resulting from partial compression of the ductus arteriosus (DA) in the fetus may simultaneously activate two opposing responses: 1) blood flow-induced vasodilation (owing to shear stress); and 2) pressure-induced vasoconstriction (owing to the myogenic response). To test this hypothesis, we studied the hemodynamic response to partial DA compression with and without inhibition of shear stress-induced vasodilation by nitric oxide synthase blockade in chronically prepared late-gestation fetal lambs. Without inhibition of nitric oxide synthase, pulmonary vascular resistance progressively decreased by 39 ± 5% during the DA compression period (p < 0.05). In contrast, DA compression after nitric oxide synthase inhibition caused left pulmonary artery blood flow to initially increase and then steadily decrease toward a plateau value, and caused pulmonary vascular resistance to progressively increase by 28 ± 4% above baseline (p < 0.05). The plateau value of pulmonary vascular resistance was reached in less than 5 min after the onset of DA compression. Left pulmonary artery blood flow after 10 min of partial DA compression did not change with the rise in pulmonary artery pressure; plateau values of pulmonary vascular resistance increased linearly with the increase in pulmonary artery pressure. These results support the hypothesis that the perinatal lung circulation has a potent myogenic response, and that this response may be masked in vivo under physiologic conditions by nitric oxide synthase activity. We speculate that the myogenic response may become a predominant regulatory mechanism of pulmonary vascular resistance when endothelium-dependent vasoreactivity is impaired, such as in persistent pulmonary hypertension of the newborn.

Anastomotic stricture after surgical repair of esophageal atresia: frequency, risk factors, and efficacy of esophageal bougie dilatations

AIMS The aim of this study was to evaluate the frequency and risk factors of postoperative anastomotic stricture, and the efficacy and complications of esophageal bougie dilatations for symptomatic anastomotic stricture in a population of children with esophageal atresia. PATIENTS AND METHODS The medical records of 62 children operated on for esophageal atresia type III (Ladd and Gross) over a 5-year period were retrospectively reviewed. RESULTS Anastomotic stricture developed in 23 (37%) of patients. Anastomotic tension during primary repair of esophageal atresia was associated with subsequent stricture formation (P < .05). Patients required esophageal dilation at a mean age of 149 days (range, 30-600 days). Stricture resolution occurred after a mean of 3.2 dilatations per patient (range, 1-7). Dilation was successful in 87% of patients. Three patients continued to present mild (n = 1) to severe (n = 2) dysphagia, mainly related to esophageal dysmotility. No complications were observed during or after the dilatation sessions. CONCLUSIONS Anastomotic stricture, secondary to the surgical treatment of esophageal atresia, remains a frequent complication in patients with esophageal atresia. Esophageal dilation with Savary-Gilliard bougies is a safe and effective procedure in the management of strictures.

Pulmonary Circulatory Effects of Norepinephrine in Newborn Infants with Persistent Pulmonary Hypertension

OBJECTIVE To evaluate the respiratory and the pulmonary circulatory effects of norepinephrine in newborn infants with persistent pulmonary hypertension (PPHN)-induced cardiac dysfunction. STUDY DESIGN Inclusion criteria were: 1) Newborn infants >35 weeks gestational age; 2) PPHN treated with inhaled nitric oxide; and 3) symptoms of circulatory failure despite adequate fluid resuscitation. Lung function and pulmonary hemodynamic variables assessed with Doppler echocardiography were recorded prospectively before and after starting norepinephrine. RESULTS Eighteen newborns were included (gestational age: 37 +/- 3 weeks; birth weight: 2800 +/- 700 g). After starting norepinephrine, systemic pressure and left ventricular output increased respectively from 33 +/- 4 mm Hg to 49 +/- 4 mm Hg and from 172 +/- 79 mL/kg/min to 209+/-90 mL/kg/min (P < .05). Although the mechanical ventilatory variables have not been changed, the post-ductal transcutaneous arterial oxygen saturation increased from 89% +/- 1% to 95% +/- 4%, whereas the oxygen need decreased from 51% +/- 24% to 41% +/- 20% (P < .05). The pulmonary/systemic pressure ratio decreased from 0.98 +/- 0.1 to 0.87 +/- 0.1 (P < .05). Mean left pulmonary artery blood flow velocity increased by 20% (P < .05). CONCLUSION Norepinephrine may improve lung function in newborn infants with PPHN through a decrease in pulmonary/systemic artery pressure ratio and improved cardiac performance.

Alveolar capillary dysplasia: a cause of persistent pulmonary hypertension of the newborn

Abstract. The term alveolar capillary dysplasia refers to complex vascular abnormalities which have recently been identified in some infants with persistent pulmonary hypertension. We report four cases admitted to our institution for severe pulmonary hypertension unresponsive to maximal cardiorespiratory support, including high-frequency ventilation, inhaled nitric oxide and extracorporeal membrane oxygenation. The four infants died of refractory hypoxaemia. The diagnosis of alveolar capillary dysplasia was established by necropsy. We have used these cases as an opportunity for a thorough review of the literature containing comments regarding aetiology, pathophysiology, clinical presentation, associated malformations and treatment trials. Conclusion: alveolar capillary dysplasia should be ruled out in all newborn infants presenting severe idiopathic pulmonary hypertension associated with malformations. Open lung biopsy may prevent from using costly, invasive and probably ineffective procedures such as extracorporeal membrane oxygenation.

Newborn infant pain assessment using heart rate variability analysis.

ObjectivesSystems controlling cardiovascular function are closely coupled with the perception of pain. Heart rate variability (HRV) is a well-established noninvasive measure of cardiac autonomic control. We hypothesized that pain may alter HRV in the newborn infant and that HRV analysis could be used as an indicator of prolonged pain in the newborn infant. MethodsTo test the hypothesis, we measured the magnitude of the heart rate high-frequency variations using an innovative High Frequency Variability Index (HFVI) in newborn infants at risk of postoperative pain. We investigated newborn infants with a gestational age (GA) more than 34 weeks, and who were admitted after a major surgical procedure. Inclusions ranged from 2 to 72 hours after the surgery. The postoperative pain was scored using EDIN scale (neonatal pain and discomfort scale) at the end of the 2 hours recording period. The infants were separated in: (1) Group “Low EDIN,” when EDIN<5; and (2) Group “High EDIN,” when EDIN ≥5. Predictive positive and negative values of a threshold value of HFVI in assessing pain have been studied. ResultsTwenty-eight newborn infants were enrolled in the study (mean GA=37.8±1.5 wk) at a median delay between the surgery and the recording of 5 hours. Mean EDIN were 2±1 and 7±2 in respectively the groups “Low EDIN” and “High EDIN.” The 2 groups were similar for GA, basal heart and respiratory rates, SpO2, mean arterial blood pressure, and morphine infusion rate. HFVI was significantly lower in the group “High EDIN” than in the group “Low EDIN” (0.7±0.2 vs. 1.2±0.3, respectively; P<0.01). An HFVI <0.9 was able to predict an EDIN score ≥5, with a sensitivity of 90%, and a specificity of 75%. DiscussionThe results of this study indicate that postoperative pain is associated with a decreased high-frequency HRV in full-term newborn infants. Our findings suggest that HRV could be used as an indicator to assess prolonged pain in the newborn infants.

Placental BDNF/TrkB signaling system is modulated by fetal growth disturbances in rat and human.

The brain-derived neurotrophic factor (BDNF) has been shown to exert an important role during implantation, placental development, and fetal growth control in mice. Its expression is closely related to the nutritional status in several tissues such as in the nervous system. In a previous study, we demonstrated that maternal undernutrition (MU), during the perinatal life, modified both the BDNF and its functional receptor, the tyrosine kinase receptor B (TrkB) gene expression in the brain of growth-restricted rat offspring during sensitive developmental windows, suggesting that these early modifications may have long-lasting consequences. In the present study, we measured BDNF/TrkB mRNA and protein levels in rat placentas from mothers submitted to a 50% food restriction during gestation, and in human placentas from pregnancies with fetal growth restriction or fetal macrosomia. In the rat, two subtypes of placental TrkB receptors have been identified: the TrkB-FL and TrkB-T1 receptors. We found that MU induced intrauterine growth restriction (IUGR) of fetuses at term and decreased the placental BDNF mRNA and protein levels. Placentae from undernourished mothers exhibited an increased mRNA expression of TrkB-FL whereas both TrkB-FL and TrkB-T1 receptors proteins levels were not modified. In human IUGR placentas, both BDNF and TrkB receptor mRNA expressions were up-regulated. Finally, although neither BDNF nor TrkB mRNA levels were altered by fetal macrosomia alone, BDNF mRNA levels were decreased when macrosomia was associated with maternal type 1 diabetes. These results show that the placental BDNF/TrkB system is modulated in rats and humans during pregnancies with fetal growth perturbations and is affected by the maternal energetic status. These data suggest that this system may exert an important role for the feto-placental unit development and that it may also be implicated in the etiology of pathologies related to placental and fetal growth disturbances.