Lung eicosanoids in perinatal rats with congenital diaphragmatic hernia

Abnormal levels of pulmonary eicosanoids have been reported in infants with persistent pulmonary hypertension (PPH) and congenital diaphragmatic hernia (CDH). We hypothesized that a dysbalance of vasoconstrictive and vasodilatory eicosanoids is involved in PPH in CDH patients. The levels of several eicosanoids in lung homogenates and in bronchoalveolar lavage fluid of controls and rats with CDH were measured after caesarean section or spontaneous birth. In controls the concentration of the stable metabolite of prostacyclin (6-keto-PGF1α), thromboxane A2 (TxB2), prostaglandin E2 (PGE2), and leukotriene B4 (LTB4) decreased after spontaneous birth. CDH pups showed respiratory insufficiency directly after birth. Their lungs had higher levels of 6- keto-PGF1α, reflecting the pulmonary vasodilator prostacyclin (PGI2), than those of controls. We conclude that in CDH abnormal lung eicosanoid levels are present perinatally. The elevated levels of 6-keto-PGF1α in CDH may reflect a compensation mechanism for increased vascular resistance

Diagnosis-related deterioration of lung function after extracorporeal membrane oxygenation.

The aim of the study was to assess lung function longitudinally after neonatal extracorporeal membrane oxygenation (ECMO), and to identify any effects of diagnosis and perinatal characteristics. 121 neonatal ECMO-treated children (70 with meconium aspiration syndrome, 20 congenital diaphragmatic hernia and 31 with other diagnoses) performed a total of 191 lung function measurements at 5, 8 and/or 12 yrs. We assessed dynamic and static lung volumes, reversibility of airway obstruction and diffusion capacity. Mean SDS forced expiratory volume in 1 s (FEV(1)) at 5 yrs before and after bronchodilation (-0.51 and 0.07) was significantly higher than at 8 (-0.79 and -0.4; p<0.04) and 12 yrs (-1.10 and -0.52; p<0.003). Mean SDS for all spirometric parameters before and after bronchodilation were significantly lower in the congenital diaphragmatic hernia group compared with the other diagnostic groups (all p</=0.025). A significant volume of trapped air was observed in 86% patients with congenital diaphragmatic hernia, 50% with meconium aspiration syndrome and 58% with other diagnoses. After bronchodilation, mean SDS FEV(1) and forced vital capacity were negatively influenced by duration of ventilation (both p<0.001) and duration of ECMO (p=0.003 and p=0.02, respectively). Long-term pulmonary sequelae after neonatal ECMO-treatment mainly occur in congenital diaphragmatic hernia patients and tend to deteriorate over time

Motor-function and exercise capacity in children with major anatomical congenital anomalies

__Background:__ Children with major anatomical congenital anomalies (CA) often need prolonged hospitalization with surgical interventions in the neonatal period and thereafter. Better intensive care treatment has reduced mortality rates, but at the cost of more morbidity. __Aim:__ To study motor-function and exercise capacity in five-year-old children born with CA, and to determine whether motor-function and exercise capacity differ according to primary diagnosis. __Study design:__ Descriptive study. __Subjects:__ One-hundred-and-two children with the following CA: congenital diaphragmatic hernia (CDH) n=24, esophageal atresia (EA) n=29, small intestinal anomalies (SIA) n=25, and abdominal wall defects (AWD) n=24. __Outcome measures:__ Overall and subtest percentile scores of the Movement-Assessment Battery for Children (M-ABC) were used to measure motor skills. Endurance time on the Bruce treadmill test was used to determine maximal exercise capacity. __Results:__ Motor-function: Seventy-three children (71.6%) had an overall percentile score within the normal range, 18 (17.6%) were classified as borderline, and 11 (10.8%) had a motor problem. This distribution was different from that in the reference population (Chi square: p=0.001). Most problems were encountered in children with CDH and EA (p=0.001 and 0.013, respectively). Ball skills and balance were most affected. __Exercise capacity:__ Mean standard deviation score (SDS) endurance time=-. 0.5 (SD: 1.3); p=0.001; due to poor exercise performance in CDH and EA patients. __Conclusions:__ Children with major anatomical CA and especially those with CDH and EA are at risk for delayed motor-function and disturbed exercise capacity

Growth and development after oesophageal atresia surgery: Need for long-term multidisciplinary follow-up

Abstract Survival rates in oesophageal atresia patients have reached over 90%. In long-term follow-up studies the focus has shifted from purely surgical or gastrointestinal evaluation to a multidisciplinary approach. We reviewed the literature on the long-term morbidity of these patients and discuss mainly issues of physical growth and neurodevelopment. We conclude that growth problems–both stunting and wasting–are frequently seen, but that sufficient longitudinal data are lacking. Therefore, it is unclear whether catch-up growth into adolescence and adulthood occurs. Data on determinants of growth retardation are also lacking in current literature. Studies on neurodevelopment beyond preschool age are scarce but oesophageal atresia patients seem at risk for academic problems and motor function delay. Many factors contribute to the susceptibility to growth and development problems and we propose a multidisciplinary follow-up schedule into adulthood future care which may help improve quality of life

Neonatal critical illness and development: white matter and hippocampus alterations in school-age neonatal ECMO survivors

Aim: Examine the neurobiology of long-term neuropsychological deficits following neonatal extracorporeal membrane oxygenation (ECMO). Method: This cross-sectional study assessed white matter integrity and hippocampal volume of ECMO survivors (8-15yrs) and healthy controls (8-17yrs) using Diffusion Tensor Imaging and structural MRI, respectively. Neuropsychological outcome was evaluated in patients. Included clinical predictors of white matter integrity: age start ECMO, ECMO duration, highest oxygenation index before ECMO, highest mean airway pressure and mechanical ventilation duration. Results: Patients (n=23) had lower global fractional anisotropy than controls (n=54)(patients=.368; controls=.381; p=.02), but similar global mean diffusivity (p=.41). Patients had lower fractional anisotropy in the left cingulum bundle (patients=.345; controls=.399; p<.001) and higher mean diffusivity in a region of the left parahippocampal cingulum (patients=.916; controls=.871; p<.001). Higher global mean diffusivity predicted worse verbal memory in patients (n=17)(β=-.74, p=.01). Patients (n=23) had smaller bilateral hippocampal volume than controls (n=43)(left: p< .001; right: p< .001). In patients, this was related to worse verbal memory (left: β=.65, p=.02; right: β=.71, p=.01). Interpretation: Neonatal ECMO survivors are at risk for long-term brain alterations, which may partly explain long-term neuropsychological impairments. Neuroimaging may contribute to better risk stratification of long-term impairments

Prospective longitudinal evaluation of lung function during the first year of life after repair of congenital diaphragmatic hernia

OBJECTIVE: To evaluate lung function and respiratory morbidity prospectively during the first year of life in patients with congenital diaphragmatic hernia and to study the effect of extracorporeal membrane oxygenation therapy. DESIGN: Prospective longitudinal cohort study. SETTING: Outpatient clinic of a tertiary-level pediatric hospital. PATIENTS: The cohort of 43 infants included 12 patients treated with extracorporeal membrane oxygenation. Evaluation was at 6 and 12 months; 33 infants were evaluated at both time points. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Maximal expiratory flow at functional residual capacity and functional residual capacity were measured with Masterscreen Babybody. Z-scores were calculated for maximal expiratory flow at functional residual capacity. Mean maximal expiratory flow at functional residual capacity values at 6 and 12 months were significantly below the expected values (mean z-score -1.4 and -1.5, respectively) without a significant change between both time points. Values did not significantly differ between extracorporeal membrane oxygenation and nonextracorporeal membrane oxygenation-treated patients. Functional residual capacity values were generally high, 47% were above the suggested normal range, and did not change significantly over time. Mean functional residual capacity values in extracorporeal membrane oxygenation-treated patients were significantly higher than in nonextracorporeal membrane oxygenation-treated patients (p = .006). The difference (5.1 mL/kg ± 1.8 SE) did not change significantly between the two time points. Higher mean airway pressure and longer duration of ventilation were associated with higher functional residual capacity. None of the perinatal characteristics was associated with maximal expiratory flow at functional residual capacity. Mean weight z-scores were significantly below zero at both time points (p < .001). Mean weight z-score in extracorporeal membrane oxygenation-treated patients were lower than in nonextracorporeal membrane oxygenation-treated patients (p = .046). CONCLUSIONS: Infants with congenital diaphragmatic hernia have decreased expiratory flows and increased functional residual capacity within the first year of life. Extracorporeal membrane oxygenation-treated patients with congenital diaphragmatic hernia may have more respiratory morbidity and concomitant growth impairment. Close follow-up beyond the neonatal period is therefore required. Copyrigh

A prospective comparative evaluation of persistent respiratory morbidity in esophageal atresia and congenital diaphragmatic hernia survivors

__Purpose:__ The aim of the study was to compare long-term respiratory morbidity in children after repair of esophageal atresia (EA) or congenital diaphragmatic hernia (CDH). __Patients and Methods:__ Children were seen at 6, 12, and 24 months and 5 years within a prospective longitudinal follow-up program in a tertiary children's hospital. Respiratory morbidity and physical condition were evaluated at all moments. At age 5 years, pulmonary function and maximal exercise performance were tested. __Results:__ In 3 of 23 atresia patients and 10 of 20 hernia patients, bronchopulmonary dysplasia was developed. Seventeen atresia and 11 hernia patients had recurrent respiratory tract infections mainly in the first years of life. At age 5, 25% of EA and CDH patients measured showed reduced forced expiratory volume in 1 second (z-score < -2). Both atresia and hernia patients showed impaired growth, with catch-up growth at 5 years in patients with EA but not in those with hernia. Maximal exercise performance was significantly below normal for both groups

Intrinsic Cellular Susceptibility to Barrett’s Esophagus in Adults Born with Esophageal Atresia

The prevalence of Barrett’s esophagus (BE) in adults born with esophageal atresia (EA) is four times higher than in the general population and presents at a younger age (34 vs. 60 years). This is (partly) a consequence of chronic gastroesophageal reflux. Given the overlap between genes and pathways involved in foregut and BE development, we hypothesized that EA patients have an intrinsic predisposition to develop BE. Transcriptomes of Esophageal biopsies of EA patients with BE (n = 19, EA/BE); EA patients without BE (n = 44, EA-only) and BE patients without EA (n = 10, BE-only) were compared by RNA expression profiling. Subsequently, we simulated a reflux episode by exposing fibroblasts of 3 EA patients and 3 controls to acidic conditions. Transcriptome responses were compared to the differential expressed transcripts in the biopsies. Predisposing single nucleotide polymorphisms, associated with BE, were slightly increased in EA/BE versus BE-only patients. RNA expression profiling and pathway enrichment analysis revealed differences in retinoic acid metabolism and downstream signaling pathways and inflammatory, stress response and oncological processes. There was a similar effect on retinoic acid signaling and immune response in EA patients upon acid exposure. These results indicate that epithelial tissue homeostasis in EA patients is more prone to acidic disturbances

Intrinsic Cellular Susceptibility to Barrett’s Esophagus in Adults Born with Esophageal Atresia

The prevalence of Barrett’s esophagus (BE) in adults born with esophageal atresia (EA) is four times higher than in the general population and presents at a younger age (34 vs. 60 years). This is (partly) a consequence of chronic gastroesophageal reflux. Given the overlap between genes and pathways involved in foregut and BE development, we hypothesized that EA patients have an intrinsic predisposition to develop BE. Transcriptomes of Esophageal biopsies of EA patients with BE (n = 19, EA/BE); EA patients without BE (n = 44, EA-only) and BE patients without EA (n = 10, BE-only) were compared by RNA expression profiling. Subsequently, we simulated a reflux episode by exposing fibroblasts of 3 EA patients and 3 controls to acidic conditions. Transcriptome responses were compared to the differential expressed transcripts in the biopsies. Predisposing single nucleotide polymorphisms, associated with BE, were slightly increased in EA/BE versus BE-only patients. RNA expression profiling and pathway enrichment analysis revealed differences in retinoic acid metabolism and downstream signaling pathways and inflammatory, stress response and oncological processes. There was a similar effect on retinoic acid signaling and immune response in EA patients upon acid exposure. These results indicate that epithelial tissue homeostasis in EA patients is more prone to acidic disturbances