Children with Intestinal Failure are at Risk for Psychopathology and Trauma.

OBJECTIVES: The objective of this study is to assess the psychopathology and medical traumatic stress in children with intestinal failure (IF) and identify associated risk factors. METHODS: Two-center study, performed from September 2019 until April 2022 (partly during COVID-19 pandemic), including children (1.5-17 years) with IF, dependent on parenteral nutrition (PN) or weaned off PN, treated by a multidisciplinary IF-team. Psychopathology in children was evaluated with a semi-structured interview assessing psychiatric classifications and validated questionnaires assessing emotional (internalizing) and behavioral (externalizing) problems. Medical traumatic stress was assessed with a validated questionnaire. Problem scores were compared with normative data. Associations between clinical characteristics and outcomes were analyzed with linear regression analyses. RESULTS: Forty-one (of 111 eligible) children were included [median age 8.9 years (interquartile range, IQR 5.5-11.8), 54% female, 73% born preterm]. Median PN-duration was 17.3 months (IQR 6.9-54.0); 17 children (41%) were still PN-dependent. One third of the children met criteria for at least 1 psychiatric classification (compared with 14% in age-matched general population). Anxiety disorders and attention deficit hyperactivity disorder were most common. In school-aged children (n = 29, 6-17 years), significantly increased emotional problems were consistently reported by children ( P = 0.011), parents ( P < 0.001), and teachers ( P = 0.004). In preschool children (n = 12, 1.5-5 years), no significant differences with normative data were found. Subclinical or clinical emotional problems were reported in 19 children (46%). Medical traumatic stress was present in 14%, and 22% of children had received psychological help for trauma before. Lower gastrointestinal related quality of life was associated with more emotional problems, but not PN-duration. CONCLUSIONS: Children with IF, particularly school-aged children, are at risk for psychological problems which is reflected by the high rate of received psychotherapy and the high rate of emotional problems and psychiatric classifications.

Lung function in school-aged congenital diaphragmatic hernia patients; a longitudinal evaluation.

OBJECTIVE: Children with congenital diaphragmatic hernia (CDH) are at risk for pulmonary morbidity. Data on longitudinal evaluation of lung function in CDH are scarce. We hypothesized that CDH patients would have impaired lung function that worsens over time. We evaluated lung function and its determinants at ages 8 and 12 years. METHODS: Dynamic and static lung volumes, and diffusion capacity were measured. Extracorporeal membrane oxygenation (ECMO) treatment, the standardized European neonatal treatment protocol, patch repair, duration of ventilation, type of initial mechanical ventilation, and nitric oxide treatment were entered as covariates in linear mixed models with standard deviation score (SDS) lung function parameters (FEV1 , FEF 25-75 , and K CO ) as dependent variables. RESULTS: Seventy-six children (27 ECMO-treated) born between 1999 and 2009 performed 113 reliable lung function tests. Severity of airflow obstruction deteriorated significantly from age 8 to 12 years: estimated mean difference (95% confidence interval [CI]) SDS FEV1 was -0.57 (-0.79 to -0.36) and SDS FEF25-75 was -0.63 (-0.89 to -0.37), both P < .001. Static lung volumes were within normal range and unchanged over time: estimated mean difference (95% CI) SDS TLC -0.27 (-0.58 to 0.04); P = .085. SDS KCO was below normal at 8 and 12 years and remained stable: -0.06 (-0.22 to 0.35); P = .648. These observations were irrespective of ECMO treatment. FEV1 and FEF25-75 were negatively associated with duration of ventilation (P < .001). Baseline data were not related with TLC or KCO. CONCLUSIONS: CDH patients should be followed into adulthood as they are at risk for worsening airflow obstruction and decreased diffusion capacity at school age, irrespective of ECMO treatment.

Congenital Diaphragmatic Hernia and Growth to 12 Years.

OBJECTIVES: Growth problems are reported in patients with congenital diaphragmatic hernia during the first years of life. However, it is unknown if poor growth persists during childhood. We therefore evaluated growth of patients longitudinally until 12 years of age. METHODS: This prospective study included 172 patients (43 treated with extracorporeal membrane oxygenation [ECMO]) born from 1999 to 2014. Z scores of height-for-age (HFA), weight-for-height, and distance-to-target height were calculated at 6 months of age and at 1, 2, 5, 8, and 12 years of age. Data were analyzed by using general linear models. RESULTS: At 1 year of age, the mean weight-for-height z score had declined in ECMO (-1.30, 95% confidence interval: -1.62 to -0.97) and non-ECMO patients (-0.72, 95% confidence interval: -0.91 to -0.54; P < .05). Thereafter in ECMO patients, the mean HFA z score deteriorated between 1 (-0.43, 95% confidence interval: -0.73 to -0.13) and 5 years of age (-1.08, 95% confidence interval: -1.38 to -0.78; P < .01). In non-ECMO patients, the mean HFA z score deteriorated between 2 (-0.35, 95% confidence interval: -0.53 to -0.17) and 5 years of age (-0.56, 95% confidence interval: -0.75 to -0.37; P = .002). At 12 years of age, the mean HFA z score was still less than the norm in both groups: ECMO (-0.67, 95% confidence interval: -1.01 to -0.33) versus non-ECMO (-0.49, 95% confidence interval: -0.77 to -0.20; P < .01). Adjusting for target height improved the mean height z scores but did not bring them to normal range. CONCLUSIONS: Poor linear growth persisted at 12 years of age. The pattern of early deterioration of weight gain followed by a decline in linear growth is suggestive of inadequate nutrition during infancy. Therefore, nutritional assessment and intervention should be started early and should be continued during childhood.

Determinants of exercise capacity in school-aged esophageal atresia patients.

BACKGROUND AND AIMS: Data on long-term outcome of exercise capacity in school-aged children with esophageal atresia (EA) are scarce. We evaluated maximal exercise capacity and its relation to lung function. Moreover, we studied other possible determinants of exercise capacity and lung function. METHODS: Exercise capacity of 63 children with EA born 1999-2007 was evaluated at the age of 8 years with the Bruce-protocol. Dynamic and static lung volumes, bronchodilator response and diffusion capacity were measured. Furthermore, perinatal characteristics, hospital admissions for lower respiratory tract infections (RTIs), RTIs treated with antibiotics in the past year, symptoms of gastroesophageal reflux, weight-for-height, and sports participation were evaluated as other potential determinants. RESULTS: Exercise capacity was significantly below normal: mean (SD) SDS -0.91 (0.97); P < 0.001. All spirometric parameters were significantly below normal with significant reversibility of airflow obstruction in 13.5% of patients. Static lung volumes were significantly decreased (mean (SD) SDS TLChe -1.06 (1.29); P < 0.001). Diffusion capacity corrected for alveolar volume was normal (mean (SD) SDS KCO -0.12 (1.04)). Exercise capacity was positively associated with total lung capacity and negatively with SDS weight-for-height. Spirometric parameters were negatively associated with congenital cardiac malformation, duration of ventilation, and persistent respiratory morbidity. CONCLUSION: Eight-year-old children with EA had reduced exercise capacity which was only associated with the reduction in TLChe and higher SDS weight-for-height. We speculate that diminished physical activity with recurrent respiratory tract infections may also play a role in reduced exercise capacity. This should be subject to further research to optimize appropriate intervention.

Longitudinal evaluation of growth in oesophageal atresia patients up to 12†years.

OBJECTIVE: Previous studies reported diminished growth after oesophageal atresia (OA) repair. We evaluated long-term follow-up data on growth. METHODS: Longitudinal cohort study up to 12 years. Patients with OA, born 1999-2013, who participated in a longitudinal follow-up programme were included. Children with genetic syndromes associated with growth disorders were excluded. SD scores (SDS) for height-for-age (HFA), weight-for-height (WFH) and distance-to-target-height were calculated for routine visits (0.5/1/2/5/8/12 years). Linear mixed models were used to estimate SDS until 12 years of age and to evaluate explanatory factors for growth. RESULTS: We included 126/155 children (32% prematurely born, 20% small for gestational age), 32 reached the age of 12 years. Fundoplication surgery was performed in 24%. SDS-HFA was below normal up to 8 years but improved over these years (mean (SE) -0.48 (0.09), -0.31 (0.09) and -0.20 (0.13) at 0.5, 8 and 12 years). Scores improved after correction for target height (mean (SE) -0.29 (0.10), -0.17 (0.09) and -0.10 (0.14) at 0.5, 8 and 12 years). SDS-WFH was below normal from age 1-5 years (mean (SE) -0.53 (0.09), -0.24 (0.09) and 0.03 (0.14) at 1, 5 and 12 years). Low birth weight and fundoplication surgery were negatively associated with growth. CONCLUSIONS: The growth of patients with OA was below the reference norm during the first years of life, but normalised at 12 years. Large longitudinal cohort studies should evaluate if normal growth persists into adolescence. Early nutritional assessment with timely dietary intervention should be considered especially in those with low birth weight or following fundoplication surgery.

Pulmonary ventilation and micro-structural findings in congenital diaphragmatic hernia.

BACKGROUND: With increasing survival of patients with more severe forms of congenital diaphragmatic hernia (CDH) and risk of long-term respiratory morbidity, studies on lung morphology are needed. We used hyperpolarised (3) He MRI and anatomical (1) H MRI in a cohort of young adult CDH patients to image regional lung ventilation and microstructure, focusing on morphological and micro-structural (alveolar) abnormalities. METHODS: Nine patients with left-sided CDH, born 1975-1993, were studied. Regional ventilation was imaged with hyperpolarised (3) He MRI, and the (3) He apparent diffusion coefficient (ADC) was computed separately for the ipsilateral and contralateral lungs. (1) H MRI was used to image lung anatomy, total lung volume and motion during free-breathing. RESULTS: (3) He MRI showed ventilation abnormalities in six patients, ranging from a single ipsilateral ventilation defect (3 patients) to multiple ventilation defects in both lungs (one patient treated with extra corporeal membrane oxygenation). In eight patients, (3) He ADC values for the ipsilateral lung were significantly higher than those for the contralateral lung. CONCLUSIONS: Functional and micro-structural changes persist into adulthood in most CDH patients. Ipsilateral elevated (3) He ADC values are consistent with enlargement of mean dimensions of the confining lung micro-structure at the alveolar level.

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

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.

Lung function in young adults with congenital diaphragmatic hernia; a longitudinal evaluation.

BACKGROUND: Survival rates of patients with congenital diaphragmatic hernia (CDH) have improved to up to 80%. Little is known about long-term consequences of the disease and its treatment. We evaluated lung function and respiratory symptoms longitudinally in a previously studied cohort of CDH patients and age-matched non-CDH patients who underwent similar neonatal intensive care treatment. STUDY DESIGN: We tested 27 young adults [mean (SD) age: 26.8 years (2.9)] with CDH and 30 non-CDH patients. Dynamic and static lung volumes, midexpiratory flows, and diffusion capacity were expressed as mean (SD) standard deviation scores. Prevalence of respiratory symptoms was evaluated with the European Community Respiratory Health Survey. RESULTS: All data are expressed as mean (SD). FEF(25-75) in CDH patients had slightly deteriorated since childhood (CDH: -0.7 (1.4) vs. -1.6 (1.5), P < 0.001; non-CDH patients: 0.2 (1.4) vs. -0.3 (1.6), P = 0.038, ns). Diffusion capacity decreased in both groups (CDH: DL(CO) c 0.2 (1.1) vs. -1.5 (1.1), P <0.001; non-CDH: DL(CO) c 0.1 (0.4) vs. -1.1 (1.1), P < 0.001). Lung volumes were normal in both groups. The prevalence of asthma was higher than in the normal population (27.6% in patients and 30% in controls, P < 0.001). CONCLUSIONS: Airflow obstruction and diffusion capacity deteriorated mildly from childhood into adulthood in survivors of CDH. The improved survival of patients with more severe forms of diaphragmatic hernia calls for long-term follow-up of lung function.

Lung function of infants with congenital lung lesions in the first year of life.

BACKGROUND: Several studies have evaluated short-term neonatal outcome in infants with congenital lung lesions (CLL) but clinical course and lung function in the longer term have not yet been documented. We hypothesized that clinical course and lung function would be negatively affected by surgical resection. OBJECTIVE: To evaluate respiratory symptoms and lung function longitudinally in the first year of life in infants with CLL, and to analyse differences herein between infants managed by observation only and infants whose affected lung parts were resected. METHODS: We evaluated respiratory symptoms and lung function at 6 and 12 months in 30 patients with CLL. Functional residual capacity (FRC(p)) and maximal expiratory flow at functional residual capacity (V'(max)FRC) were measured with body plethysmography. SD scores were calculated for V'(max)FRC. RESULTS: Prevalence of respiratory symptoms did not differ between the groups. Mean FRC(p) (95% CI) was 25.3 (23.3-27.3) in the group managed by observation versus 27.3 (25.1-29.6) in the group managed by surgery (p = 0.149). Mean (95% CI) SDS V'(max)FRC was -1.45 (-1.84 to -1.06) versus -1.41 (-1.90 to -0.91) (p = 0.892). Lung function did not change significantly over the 6-month period. CONCLUSION: Surgical resection did not seem to have negatively affected the clinical course and lung function. We recommend pulmonary follow-up of all CLL patients into adulthood to further identify any long-term effects of CLL and observation or surgery.

Respiratory morbidity and growth after open thoracotomy or thoracoscopic repair of esophageal atresia.

BACKGROUND: Respiratory morbidity has been described in patients who underwent repair of esophageal atresia as a neonate. We compared the influence of open thoracotomy or thoracoscopy on lung function, respiratory symptoms, and growth. METHODS: Functional residual capacity (FRC(p)), indicative of lung volume, and maximal expiratory flow at functional residual capacity (V'max(FRC)), indicative of airway patency, of 37 infants operated for esophageal atresia were measured with Masterscreen Babybody at 6 and 12 months. SD scores were calculated for V'max(FRC). RESULTS: Repair was by thoracotomy in 21 cases (57%) and by thoracoscopy in 16 cases (43%). Lung function parameters did not differ between the types of surgery (FRC(p); P = .384 and V'max(FRC); P = .241). FRC(p) values were in the upper normal range and increased from 6 to 12 months (22.5 and 25.4 mL/kg respectively, P = .010). Mean (SD) V'max(FRC) was below the norm without significant change in SD scores from 6 to 12 months (-1.9 and -2.3, respectively, P = .248). Neither lung function nor type of repair was associated with clinical evolution up to 2 years. CONCLUSION: Lung function during the first year was similar in EA infants repaired by thoracotomy or thoracoscopy. Ongoing follow-up including pulmonary function testing is needed to determine whether differences occur at a later age in this cohort.

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.

Long-term impact of infantile short bowel syndrome on nutritional status and growth.

Short-term bowel adaptation has been documented, but data on long-term effects are scarce. The aim of the present study was to evaluate the long-term consequences of infantile short bowel syndrome (SBS). A cross-sectional assessment (2005-7) of growth, nutritional status, defecation pattern and health status in individuals with a history of infantile SBS, born between 1975 and 2002, were performed. Data were compared with reference values of healthy controls and presented as means and standard deviations or median and ranges. A total of forty subjects (sixteen male and twenty-four female; mean age 14·8 (SD 6·8) years) had received parenteral nutrition during a median of 110 (range 43-2345) d, following small bowel resection. The mean standard deviation scores (SDS) for weight for height and target height (TH) of the children were normal; mean SDS for height for age was - 0·9 (SD 1·3). The median BMI adults was 19·9 (range 17-26) kg/m2; mean SDS for height for age was - 1·0 (range - 2·5 to 1·5). Height in general was significantly shorter than TH, and 53 % of children and 78 % of adults were below TH range. Most subjects had normal body fat percentage (%BF). SDS for total body bone mineral density were generally normal. The SDS for bone mineral content (BMC) of the children were - 1·0 (SD 1·1). Mean energy intake was 91 % of the estimated average requirements. The frequencies of defecation and bowel complaints of the subjects were significantly higher than in healthy controls. In conclusion, infantile SBS results in shorter stature than was expected from their calculated TH. BMC was lower than reference values, but the subjects had normal weight for height and %BF.

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.

Routine enteral nutrition in neonates on extracorporeal membrane oxygenation.

OBJECTIVES: To evaluate over a 5-yr period the feasibility and tolerance of a protocol of routine enteral nutrition in neonates requiring extracorporeal membrane oxygenation (ECMO). DESIGN: Retrospective medical chart review. SETTING: Level III children's hospital, pediatric surgical intensive care unit. PATIENTS: Neonates treated with venoarterial ECMO (VA-ECMO) between January 1997 and January 2002. Patients with congenital diaphragmatic hernia were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Charts of all neonates treated with VA-ECMO were reviewed. Feasibility was evaluated by recording the time period needed for enteral nutrition to reach 40% of total fluid intake; tolerance was evaluated by reviewing data on enteral nutrition related morbidity. Sixty-seven of the 77 eligible patients received enteral feeding during ECMO. Thirty-six of these patients (54%) received 40% of total fluid intake as enteral nutrition within a median of 3 (range, 2-4) days. Over the years there was a trend toward an increasing usage of enteral nutrition from 71% to 94% (p = .07). Enteral nutrition was temporarily discontinued in 16 patients, with 14 showing gastric retentions, one showing discomfort, and one showing aspiration. Symptoms of bilious vomiting, blood-stained stool, or abdominal distention were not present. CONCLUSION: Neonates on ECMO in this series tolerated enteral feeding well and did not show serious adverse effects. Overall, it is our experience that routine use of enteral feeding in critically ill neonates on VA-ECMO is feasible.

Gut hormones in preterm infants with necrotizing enterocolitis during starvation and reintroduction of enteral nutrition.

OBJECTIVES: Gastrointestinal hormones control gut functions in response to enteral nutrition. Diseases involving the gastrointestinal tract, such as necrotizing enterocolitis, may affect gut hormone secretion and therefore influence gut functions. Because bowel rest is an important part of the treatment, infants with this disease are especially at risk for an altered gut hormone secretion and thus for compromised gut functions. METHODS: In the current study, the gastrointestinal hormone profiles of eight preterm infants with an ileostomy after necrotizing enterocolitis (Bell stages 2 and 3) were evaluated during starvation and reintroduction of enteral nutrition. Basal and postprandial plasma concentrations of gastrin, cholecystokinin, and peptide YY were measured with sensitive and specific radioimmunoassays. The results were compared with those of 11 controls. RESULTS: In the patients and the controls, plasma concentrations of all hormones were higher postprandially. The increases in cholecystokinin and peptide YY were significant in the patients. Compared with the controls, all concentrations were higher in the patients, and changes were significant for basal and postprandial cholecystokinin and postprandial peptide YY. CONCLUSIONS: Enteral nutrition stimulates the secretion of gastrointestinal hormones, also in premature infants with a diseased distal small bowel and colon, as in necrotizing enterocolitis. The postprandial increase of peptide YY in patients with an ileostomy indicates that enteral substrate in the colon is not necessary for stimulation of peptide YY secretion.