Traumatic stress, mental health, and quality of life in adolescents with esophageal atresia.

INTRODUCTION: We aimed to investigate QoL in EA patients in relation to comparison groups and to clinical factors including experienced traumatic stress. MATERIAL AND METHODS: Adolescents with EA in Norway born between 1996 and 2002 were included. Clinical assessment and patient's characteristics were collected. Quality of life (PedsQL), traumatic stress (IES-13) and mental health (SDQ-20) were compared to groups of healthy controls, children with acute lymphoblastic leukemia (ALL) and kidney transplanted children (TX). RESULTS: 68 EA adolescents participated. Total scores for PedsQL were not different from the healthy group and ALL patients, but significantly better than the TX patients. The subscale for physical performance was significantly lower than in healthy adolescents, and nine (17%) patients had scores ≤70 indicating reduced health status. Five EA adolescents (12%) had mental health scores suggesting a psychiatric disorder, and six (9%) reported high traumatic stress scores with a significant correlation to days on ventilator in the neonatal period. The strongest predictors for quality of life among EA adolescents were self-reported mental health, posttraumatic stress and GERD symptoms. CONCLUSION: Scores for Quality of life in the EA group are good except for subscale for physical performance. Symptoms of posttraumatic stress, mental strain and gastroesophageal reflux are predictors of reduced QoL.

[Long-term consequences of esophageal atresia; esophageal and lung abnormalities in adulthood]. / Langetermijngevolgen van slokdarmatresie.

Esophageal atresia is a rare congenital anomaly. Due to increased survival rates, the population of adults born with this malformation is growing. These patients turn out to have an increased risk to develop Barrett's esophagus, esophageal carcinoma or lung abnormalities like bronchiectasis. This is illustrated by three cases: a 42-year-old man with an irresectable esophageal squamous cell carcinoma; a 23-year-old man with a Barrett's esophagus without any reflux complaints; and a 51-year-old women with a reflux esophagitis and extensive bronchiectasis due to a combination of gastroesophageal reflux with chronic aspiration and a reduced sputum clearance because of a history of tracheomalacia. It is important for healthcare providers to be aware of these risks and the possible absence of symptoms, in order to detect abnormalities at an early stage and improve quality of life of these patients.

Prediction of postnatal outcome in fetuses with congenital lung malformation: 2-year follow-up study.

OBJECTIVES: To identify, in fetuses with a congenital lung malformation (CLM), prenatal predictors of the need for postnatal respiratory support and the need for surgery by calculating the CLM volume ratio (CVR), and to evaluate the concordance between the prenatal appearance and the postnatal type of CLM. METHODS: This was an analysis of prenatal, perinatal and postnatal data from fetuses diagnosed with a CLM at the Erasmus University Medical Center - Sophia Children's Hospital in Rotterdam, The Netherlands, between January 2007 and December 2016. For all included fetuses, CVR was measured retrospectively on stored ultrasound images obtained at 18 + 1 to 24 + 6 weeks (US1), 25 + 0 to 29 + 6 weeks (US2) and/or 30 + 0 to 35 + 6 weeks' gestation (US3). Postnatal diagnosis of CLM was based on computed tomography or histology. Primary outcomes were the need for respiratory support within 24 h and surgery within 2 years after birth. RESULTS: Of the 80 fetuses with a CLM included in this study, 14 (18%) required respiratory support on the first postnatal day, and 17 (21%) required surgery within 2 years. Only the CVR at US2 was predictive of the need for respiratory support, with a cut-off value of 0.39. Four of 16 (25%) fetuses which showed full regression of the CLM prenatally required respiratory support within 24 h after birth. The CVR at US1, US2 and US3 was predictive of surgery within 2 years. Overall, the prenatal appearance of the CLM showed low concordance with the postnatal type. Prenatally suspected microcystic congenital pulmonary airway malformation (CPAM) was shown on computed tomography after birth to be congenital lobar overinflation in 15/35 (43%) cases. Respiratory support within 24 h after birth and surgical resection within 28 days after birth were needed in all cases of macrocystic CPAM. CONCLUSIONS: CVR can predict the need for respiratory support within 24 h after birth and for surgery within 2 years. Regression of a CLM prenatally does not rule out respiratory problems after birth. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. - Legal Statement: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Changes in thyroid hormone concentrations during neonatal extracorporeal membrane oxygenation.

OBJECTIVE: Thyroid hormone concentrations can be disturbed during critical illness. Our aim was to determine changes in thyroid hormone concentrations during neonatal extracorporeal membrane oxygenation (ECMO). STUDY DESIGN: We included 21 ECMO-treated neonates. Age-specific s.d. scores (SDS) of free and total thyroxine (FT4; TT4), reverse and total triiodothyronine (rT3; TT3), thyroid-stimulating hormone (TSH) and thyroxine-binding globulin (TBG) were determined at six fixed time-points. Data were analyzed using general linear models. RESULTS: At baseline, mean SDS FT4 (-0.78, 95% CI: -1.37 to -0.19), TT4 (-1.97, 95% CI: -2.76 to -1.18), TT3 (-0.88, 95% CI: -1.13 to -0.63), TSH (-2.14, 95% CI: -2.93 to -1.35) and TBG (-3.52, 95% CI: -4.55 to -2.50) were low with high mean SDS rT3 (0.53, 95% CI: 0.28 to 0.78). One hour after start ECMO, TT4, TSH and TBG had further declined; 12 h after start ECMO TT3 had declined (all P<0.05). After this decline, mean SDS TSH increased to the baseline level 12 h after start ECMO (-2.50, 95% CI: -3.22 to -1.79), and was higher than baseline 48 h after start ECMO (-0.56, 95% CI: -1.29 to 0.17). This TSH increase was followed by increases in TT4 and TT3. FT4 remained constant within the normal range during ECMO. CONCLUSIONS: Thyroid hormone concentrations before ECMO were suggestive of non-thyroidal illness syndrome (NTIS). During ECMO, increases in TSH, TT4 and TT3 after an initial decline possibly reflect spontaneous restoration of the hypothalamic-pituitary-thyroid axis. FT4 remained constant within the normal range. This suggests that thyroxine therapy is not required during ECMO.

Cloacal malformation patients report similar quality of life as female patients with less complex anorectal malformations.

PURPOSE: Cloacal malformations are the most complex type of anorectal malformation in females. This study aimed to report quality of life (QoL) of patients with a cloacal malformation for the first time in literature. MATERIALS AND METHODS: Female patients with an anorectal malformation participating in a follow-up program for congenital malformation survivors aged 5 or older were eligible for this study. QoL was assessed with the PedsQL™ 4.0 inventory. Scores of patients with a cloacal malformation (CM) were compared with those of female patients with rectoperineal or rectovestibular fistulas (RP/RV) and with reference data. RESULTS: A total of 59 patients (67% response rate; 13 patients with cloacal malformation) were included, QoL was assessed by patient self-report at median age of 12years (8-13), and by parent proxy-report at median age of 8years (5-12). There were no differences between groups regarding the presence of associated anomalies, with also no differences regarding anomalies in the urinary tract (CM vs. RP/RV=31% vs. 15%, p=0.237). Scores of the cloacal malformations group were similar to those of the comparison group, except the proxy-reported scores on school functioning (60.0 vs. 80.0, p=0.003). Proxy-reported scores of cloacal malformation patients were significantly lower than reference values on total QoL-score, psychosocial health, and emotional and school performance. Patients (irrespective of type of ARM) who suffered from fecal soiling reported significantly lower scores with regard to psychosocial health (71.7 vs. 81.7, p=0.034) and its subscale school performance (65.0 vs. 80.0, p<0.001). QoL-scores reported by cloacal malformation patients did not differ significantly from the reference values of the healthy population. Parents of cloacal malformation patients reported significantly lower total QoL, emotional and school performances, as well as a lower general psychosocial health for their children relative to reference data of healthy children. CONCLUSION: Patients with cloacal malformations and females with less complex anorectal malformations report similar QoL. Parents of cloacal malformation patients report more problems on several psychosocial domains relative to the healthy reference group. To monitor these matters, long-term follow-up protocols should contain multidisciplinary treatment including periodical assessment of psychosocial well-being.

Exercise capacity, daily activity, and severity of fatigue in term born young adults after neonatal respiratory failure.

Little is known about long-term effects of neonatal intensive care on exercise capacity, physical activity, and fatigue in term borns. We determined these outcomes in 57 young adults, treated for neonatal respiratory failure; 27 of them had congenital diaphragmatic hernia with lung hypoplasia (group 1) and 30 had normal lung development (group 2). Patients in group 2 were age-matched, with similar gestational age and birth weight, and similar neonatal intensive care treatment as patients in group 1. All patients were born before the era of extracorporeal membrane oxygenation, nitric oxide administration, and high frequency ventilation. Exercise capacity was measured by cycle ergometry, daily physical activity with an accelerometry-based activity monitor, and fatigue by the fatigue severity scale. Median (range) VO2peak in mL/kg/min was 35.4 (19.6-55.0) in group 1 and 37.6 (15.7-52.7) in group 2. There was a between-group P-value of 0.65 for exercise capacity. Daily activity and fatigue were also similar in both groups. So, residual lung hypoplasia did not play an important role in this cohort. There were no significant associations between exercise capacity and perinatal characteristics. Future studies need to elucidate whether exercise capacity is impaired in patients with more severe lung hypoplasia who nowadays survive.

Esophageal atresia: long-term morbidities in adolescence and adulthood.

Survival rates in esophageal atresia (EA) patients have reached 90%. In long-term follow-up studies the focus has shifted from purely surgical or gastrointestinal evaluation to a multidisciplinary approach. We evaluated the long-term morbidity in adolescent and adult EA patients and discussed mainly nonsurgical issues. Dysphagia is common and reported in up to 85% of patients. In young adults gastroesophageal reflux disease occurs frequently with development of Barrett esophagus in 6% reported in different series. It is difficult to estimate respiratory morbidity from the literature because many different definitions, questionnaires, and study designs have been used. However, many patients seem to suffer from respiratory problems even into adulthood. In conclusion, morbidity is not only restricted to surgical problems but many different domains are involved. These are all related and together determine to a large extent the quality of life of EA patients and also of their families. We assume that a multidisciplinary care approach seems best to address their special needs.

VACTERL Association Etiology: The Impact of de novo and Rare Copy Number Variations.

Copy number variations (CNVs), either DNA gains or losses, have been found at common regions throughout the human genome. Most CNVs neither have a pathogenic significance nor result in disease-related phenotypes but, instead, reflect the normal population variance. However, larger CNVs, which often arise de novo, are frequently associated with human disease. A genetic contribution has long been suspected in VACTERL (Vertebral, Anal, Cardiac, TracheoEsophageal fistula, Renal and Limb anomalies) association. The anomalies observed in this association overlap with several monogenetic conditions associated with mutations in specific genes, e.g. Townes Brocks (SALL1), Feingold syndrome (MYCN) or Fanconi anemia. So far VACTERL association has typically been considered a diagnosis of exclusion. Identifying recurrent or de novo genomic variations in individuals with VACTERL association could make it easier to distinguish VACTERL association from other syndromes and could provide insight into disease mechanisms. Sporadically, de novo CNVs associated with VACTERL are described in literature. In addition to this literature review of genomic variation in published VACTERL association patients, we describe CNVs present in 68 VACTERL association patients collected in our institution. De novo variations (>30 kb) are absent in our VACTERL association cohort. However, we identified recurrent rare CNVs which, although inherited, could point to mechanisms or biological processes contributing to this constellation of developmental defects.

Deterioration of exercise capacity after neonatal extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation (ECMO) provides life support in acute reversible cardiorespiratory failure. Assessment of long-term morbidity is essential to confirm survival advantage. This study aimed to assess exercise capacity in the first 12 yrs of life after neonatal ECMO, and to evaluate the effect of primary diagnosis, lung function or perinatal characteristics on exercise capacity. 120 children who, as neonates, underwent ECMO performed 191 reliable exercise tests according to the Bruce treadmill protocol at ages 5, 8 and/or 12 yrs between 2001 and 2010. Primary diagnoses were meconium aspiration syndrome (n=66), congenital diaphragmatic hernia (n=18) and other diagnoses (n=36). At ages 5, 8 and 12 yrs, ANOVA resulted in mean ± se standard deviation score endurance time on the treadmill of -0.5 ± 0.1, -1.1 ± 0.1, and -1.5 ± 0.2, respectively, all significantly less than zero (p<0.001). Exercise capacity declined significantly over time irrespective of the primary diagnosis. Neonates treated with ECMO are at risk of decreased exercise capacity at school age. We therefore propose prolonged follow-up. Proactive advice on sports participation or referral to a physical therapist is recommended, especially when either the parents or the children themselves report impaired exercise capacity.

Exercise capacity in Dutch children: new reference values for the Bruce treadmill protocol.

The Bruce treadmill protocol is suitable for children 4 years of age and older. Dutch reference values were established in 1987. We considered that children's exercise capacity has deteriorated due to changes in physical activity patterns and eating habits. We determined new reference values and evaluated determinants of exercise capacity. Healthy Dutch children (n=267) aged 6-13 years participated in this cross-sectional observational study. The maximal endurance time on the treadmill was the criterion of exercise capacity. Furthermore, we obtained data on anthropometry, smoking habits, socioeconomic status, ethnicity, sports participation, and school transport habits. The maximal endurance time for children aged up till 10 was lower (up to 1.6 and 1.4 min in girls and boys, respectively) than previously published. Body mass index was negatively, and intense sports participation was positively associated with endurance time (beta=-0.412 and 0.789, respectively; P<0.001). In conclusion, exercise capacity seems to have deteriorated in Dutch children aged up till 10 years whereas the values from the older children are remarkably similar to those from the previous study.

Parental satisfaction with follow-up services for children with major anatomical congenital anomalies.

BACKGROUND: Since 1999 a multidisciplinary follow-up programme for parents and children with major anatomical congenital anomalies is in place in our hospital, run by a dedicated team. The aim of the present study was to evaluate the services of this team from a parental perspective. METHODS: Parents completed a questionnaire including open and closed questions about satisfaction with the various professional disciplines involved in the follow-up, statements on usefulness of the follow-up services and suggestions for improvement. RESULTS: Four hundred and sixty-nine surveys were sent out, of which 71% were returned. Non-responding parents included significantly more parents of non-Dutch origin (P= 0.038) and parents who never responded to invitations for follow-up examinations (P < 0.001). Parental satisfaction differed for the various disciplines. Eighty per cent of the parents were (very) satisfied with the social worker, compared with 92% with nurses. More than half of the parents agreed that the follow-up services give peace of mind. Almost a quarter of parents, however, considered the follow-up services as redundant. The children of these parents had significantly shorter intensive care unit stay (P= 0.02), were older at the time of the questionnaire (P= 0.04), of higher socio-economic status (P= 0.001) and less likely to be of non-Dutch origin (P= 0.008). Sixty-one per cent of the parents had contacted the 24-h helpline. Ninety per cent of the parents were satisfied with the intensive care unit, almost 80% with the general ward. CONCLUSION: Overall, parents were satisfied with the services of the follow-up team. Some parents, however, saw room for improvement related to better communication, recognizability of the team and better planning and organization.

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.

Pulmonary function and exercise capacity in survivors of congenital diaphragmatic hernia.

Congenital diaphragmatic hernia (CDH) is associated with pulmonary hypoplasia and pulmonary hypertension. The objective of this study was to assess pulmonary function and exercise capacity and its early determinants in children and adolescents born with high-risk CDH (CDH-associated respiratory distress within the first 24 h) and to explore the relationship of these findings with CDH severity. Of 159 patients born with high-risk CDH, 84 survived. Of the 69 eligible patients, 53 children (mean+/-SD age 11.9+/-3.5 yrs) underwent spirometry, lung volume measurements and maximal cardiopulmonary exercise testing (CPET). Results of the pulmonary function tests were compared with those from a healthy control group matched for sex, age and height. CDH survivors had a significantly lower forced expiratory volume in 1 s (FEV(1)), forced vital capacity (FVC), FEV(1)/FVC, maximum mid-expiratory flow and peak expiratory flow when compared with healthy controls. The residual volume/total lung capacity ratio was significantly higher. Linear regression analysis showed that gastro-oesophageal reflux disease was an independent determinant of reduced FEV(1) and FVC. CPET results were normal in those tested. High-risk CDH survivors have mild to moderate pulmonary function abnormalities when compared with a healthy matched control group, which may be related to gastro-oesophageal reflux disease in early life. Exercise capacity and gas exchange parameters were normal in those tested, indicating that the majority of patients do not have physical impairment.

Calcitonin gene-related peptide expression is altered in pulmonary neuroendocrine cells in developing lungs of rats with congenital diaphragmatic hernia.

Congenital diaphragmatic hernia (CDH) is associated with high neonatal mortality from lung hypoplasia and persistent pulmonary hypertension. Pulmonary neuroendocrine cells (PNEC) produce calcitonin gene-related peptide (CGRP), a potent vasodilator. We previously reported altered distribution of CGRP-positive PNEC in full-term rats with CDH, that may lead to an imbalance in vasoactive mediators. In the present study we examined the expression of CGRP-positive PNEC during lung development in rats with CDH induced by 2,4-dichlorophenyl-p-nitrophenylether (Nitrofen). Cesarean sections were performed on Days 16, 18, 20, or 22, and the lungs were immunostained for CGRP and immunoreactive cells were quantitated through image analysis. On Day 16, CGRP-immunoreactive staining was negative; on Day 18, CGRP-immunoreactive cells were found in all controls (not exposed to Nitrofen), whereas in CDH pups, CGRP-positive cells were present in only four of six cases. On Day 20, CGRP immunoreactivity was similar in CDH pups, Nitrofen-exposed pups without CDH, and controls. On Day 22 (term), significantly more CGRP-positive cells (i.e., number of positive cells per surface area [mm2] or lung volume [mm3]) were found in ipsilateral lungs of CDH pups than in controls (P < 0.05). The difference was even more striking in contralateral lungs of CDH pups (P < 0.001), ruling out nonspecific effects of Nitrofen. In CDH lungs, the proportion of immunostained epithelium and the size of the neuroendocrine cell clusters (neuroepithelial bodies [NEB]) were not significantly different from those of controls. On Day 22, supraoptimal dilution immunocytochemistry yielded similar results in CDH pups and controls. We conclude that in CDH, CGRP expression in PNEC and NEB is delayed during early stages of lung development. Because CGRP also exhibits growth factor-like properties for endothelium and epithelial cells, the lack of this factor during a crucial developmental stage (canalicular period) may be causally related to lung hypoplasia.

Prospective evaluation of surfactant composition in bronchoalveolar lavage fluid of infants with congenital diaphragmatic hernia and of age-matched controls.

OBJECTIVES: Infants with congenital diaphragmatic hernia may have biochemically immature lungs. However, normal lecithin/sphingomyelin ratios and phosphatidylglycerol concentrations have been reported in the amniotic fluid of congenital diaphragmatic hernia patients. We hypothesized that if the lungs of congenital diaphragmatic hernia patients are surfactant deficient, that this condition would be reflected in an altered surfactant composition in the bronchoalveolar lavage fluid compared with that composition in age-matched controls. DESIGN: Prospective, controlled study. SETTING: Surgical intensive care unit in a Level III pediatric university hospital. PATIENTS: Four groups were studied: two groups of congenital diaphragmatic hernia patients (conventionally ventilated, n = 13; treated with extracorporeal membrane oxygenation, n = 5); and two control groups (conventionally ventilated, n = 13; extracorporeal membrane oxygenation, n = 6). INTERVENTIONS: Bronchoalveolar lavage, using a blind, standardized technique, was performed in conventionally ventilated congenital diaphragmatic hernia patients, extracorporeal membrane oxygenation-treated congenital diaphragmatic hernia patients, age-matched conventionally ventilated controls without pulmonary abnormalities, and extracorporeal membrane oxygenation-treated infants without congenital diaphragmatic hernia. MEASUREMENTS AND MAIN RESULTS: The concentrations of different surfactant phospholipids and the fatty acid composition of phosphatidylcholine in bronchoalveolar lavage fluid were measured. No significant differences between the concentrations of phosphatidylcholine and phosphatidylglycerol, and the lecithin/sphingomyelin ratios, were found between the four groups. The fatty acid composition of phosphatidylcholine in conventionally ventilated patients showed a median percentage of palmitic acid within the normal range for age in both groups: 68% in congenital diaphragmatic hernia patients and 73% in controls (p < .001). CONCLUSIONS: Our findings indicate that the concentrations of different phospholipids are similar in congenital diaphragmatic hernia patients and controls without congenital diaphragmatic hernia. A primary surfactant deficiency is unlikely in infants with congenital diaphragmatic hernia. However, secondary surfactant deficiency after respiratory failure may be involved.

Abnormal expression of pulmonary bombesin-like peptide immunostaining cells in infants with congenital diaphragmatic hernia.

Infants with congenital diaphragmatic hernia (CDH) have a high neonatal mortality and morbidity owing to lung hypoplasia and persistent pulmonary hypertension. Pulmonary neuroendocrine cells produce bombesin-like peptide (BLP), a peptide with growth factor-like properties involved in lung development. We examined the expression of BLP immunostaining in pulmonary neuroendocrine cells (PNEC), and in clusters of these cells called neuroepithelial bodies (NEB), in the lungs of three groups of infants: patients with CDH, newborns with lung hypoplasia due to other causes, and control subjects without lung abnormalities. Morphometric analysis included: 1) percent immunostained airways; 2) percent immunostained epithelium (i.e. frequency of PNEC and NEB); and 3) NEB size. Controls and infants with lung hypoplasia did not differ with respect to BLP immunostaining. The ipsilateral and the contralateral lungs in CDH had a similar BLP immunostaining pattern of PNEC and NEB. The BLP immunostaining varied between CDH cases, possibly due to the differences in clinical presentation. The mean NEB size was significantly increased in infants with CDH compared with the other two groups (p = 0.02). Some CDH cases with large NEBs also showed a high percentage of immunostained epithelium. Lung-body weight ratio correlated positively with percent immunostained airways, and negatively with the NEB size. We conclude that in lungs of CDH patients BLP immunostaining in PNEC and NEB differs from that of infants with lung hypoplasia due to other causes and controls. The increased BLP immunostaining observed in some cases of CDH might reflect a compensatory mechanism related to impaired lung development and/or failure of neuropeptide secretion during neonatal adaptation.

Prenatal hormones alter antioxidant enzymes and lung histology in rats with congenital diaphragmatic hernia.

Prenatal administration of dexamethasone (Dex) and thyrotropin-releasing hormone (TRH) synergistically enhances lung maturity, but TRH suppresses the antioxidant enzyme activity. Prenatal hormonal therapy improves alveolar surfactant content and lung compliance in rats with congenital diaphragmatic hernia (CDH). In full term neonatal rats with CDH we studied the effects of prenatal Dex or Dex+TRH on antioxidant enzyme activity at birth, on survival, and on lung morphometry after 4 h of ventilation with 100% O2. CDH was induced by administration of 2,4-dichlorophenyl-p-nitro-phenylether (Nitrofen) on gestational day 10. Dex+TRH-treated CDH rats had lower activity of glutathione reductase after birth than did sham-treated CDH pups. Dex-treated and sham-treated pups had similar antioxidant enzyme activity. Hormonal treatment did not change survival during ventilation. The average airspace volume increased in Dex-treated CDH pups after ventilation, with a small synergistic effect after addition of TRH. On the basis of our findings, we speculate that prenatal administration of Dex is the best choice to improve lung maturity and airspace volume in CDH patients.

Long-term pulmonary sequelae in children with congenital diaphragmatic hernia.

Neonates with congenital diaphragmatic hernia (CDH) often suffer from respiratory insufficiency due to lung hypoplasia and pulmonary hypertension. Artificial ventilation is frequently required, and this leads to a high incidence of bronchopulmonary dysplasia. Long-term follow-up studies have shown persisting airway obstruction. To evaluate the long-term pulmonary sequelae in CDH, we studied 40 CDH patients of age 7 to 18 yr (median 11.7 yr) and 65 age-matched controls without CDH and lung hypoplasia who underwent similar neonatal treatment. Mild airway obstruction was found in both groups with more peripheral airway obstruction in CDH patients than in control subjects. Both groups had normal TLC and single-breath carbon monoxide diffusion capacity (DLCO). CDH patients had increased residual volume (RV) and RV/TLC compared with controls. Increased airway responsiveness to methacholine (MCH) was common but bronchoconstriction to inhaled metabisulfite (MBS) was rare both in CDH and control subjects. We conclude that this group of CDH patients has minor residual lung function impairment. Mild airway obstruction and increased airway responsiveness to inhaled MCH but not to MBS suggest that structural changes in distal airways are involved and not autonomic nerve dysfunction. Both artificial ventilation in the neonatal period and residual lung hypoplasia seem important determinants of persistent lung function abnormalities in CDH patients.

Prostanoids in bronchoalveolar lavage fluid do not predict outcome in congenital diaphragmatic hernia patients.

Vasoactive prostanoids may be involved in persistent pulmonary hypertension (PPH) in infants with a congenital diaphragmatic hernia (CDH). We hypothesized that increased levels of prostanoids in bronchoalveolar lavage (BAL) fluid would predict clinical outcome. We measured the concentrations of 6-keto-prostaglandin F(1alpha) (6-keto-PGF(1alpha)), thromboxane B(2) (TxB(2)), protein, albumin, total cell count, and elastase-alpha1-proteinase-inhibitor complex in BAL fluid of 18 CDH patients and of 13 control subjects without PPH. We found different concentrations of prostanoids in BAL fluid of CDH patients with PPH: infants with a poor prognosis had either high levels of both 6-keto-PGF(1alpha) and TxB(2) compared to controls, or high levels of 6-keto-PGF(1alpha) only. TxB(2) levels showed a large variability in all CDH patients irrespective of outcome. We conclude that prostanoid levels in BAL fluid do not predict clinical outcome in CDH patients.