Stress Markers, Executive Functioning, and Resilience Among Early Adolescents With Complex Congenital Heart Disease.

Importance: Infants with complex congenital heart disease (cCHD) may experience prolonged and severe stress when undergoing open heart surgery. However, little is known about long-term stress and its role in neurodevelopmental impairments in this population. Objective: To investigate potential differences between early adolescents aged 10 to 15 years with cCHD and healthy controls in physiological stress markers by hair analysis, executive function (EF) performance, and resilience. Design, Setting, and Participants: This single-center, population-based case-control study was conducted at the University Children's Hospital Zurich, Switzerland. Patients with different types of cCHD who underwent cardiopulmonary bypass surgery during the first year of life and who did not have a genetic disorder were included in a prospective cohort study between 2004 and 2012. A total of 178 patients were eligible for assessment at ages 10 to 15 years. A control group of healthy term-born individuals was cross-sectionally recruited. Data assessment was between 2019 and 2021. Statistical analysis was performed from January to April 2023. Exposure: Patients with cCHD who underwent infant open heart surgery. Main Outcomes and Measures: Physiological stress markers were quantified by summing cortisol and cortisone concentrations measured with liquid chromatography with tandem mass spectrometry in a 3-centimeter hair strand. EFs were assessed with a neuropsychological test battery to produce an age-adjusted EF summary score. Resilience was assessed with a standardized self-report questionnaire. Results: The study included 100 patients with cCHD and 104 controls between 10 and 15 years of age (mean [SD] age, 13.3 [1.3] years); 110 (53.9%) were male and 94 (46.1%) were female. When adjusting for age, sex, and parental education, patients had significantly higher sums of hair cortisol and cortisone concentrations (ß, 0.28 [95% CI, 0.12 to 0.43]; P < .001) and lower EF scores (ß, -0.36 [95% CI, -0.49 to -0.23]; P < .001) than controls. There was no group difference in self-reported resilience (ß, -0.04 [95% CI, -0.23 to 0.12]; P = .63). A significant interaction effect between stress markers and EFs was found, indicating a stronger negative association in patients than controls (ß, -0.65 [95% CI, -1.15 to -0.15]; P = .01). The contrast effects were not significant in patients (ß, -0.21 [95% CI, -0.43 to -0.00]; P = .06) and controls (ß, 0.09 [95% CI, -0.11 to 0.30]; P = .38). Conclusions and Relevance: This case-control study provides evidence for altered physiological stress levels in adolescents with cCHD and an association with poorer EF. These results suggest that future studies are needed to better understand the neurobiological mechanisms and timing of alterations in the stress system and its role in neurodevelopment.

Benchmarking against the MOMS Trial: Zurich Results of Open Fetal Surgery for Spina Bifida.

INTRODUCTION: The Management of Myelomeningocele Study, a.k.a. the MOMS trial, was published in 2011 in the New England Journal of Medicine. This prospective randomized controlled trial proved to be a milestone publication that provided definitive evidence that fetal surgery is a novel standard of care for select fetuses with spina bifida aperta (SB). The goal of our study is to assess whether our center can match these benchmark results. MATERIALS AND METHODS: Our study was conducted according to the MOMS protocol using the same inclusion and exclusion criteria and looked at the same outcome parameters that were used in the MOMS trial. Zurich and MOMS results were compared. RESULTS: We enrolled 20 patients between December 2010 and May 2015 all of whom underwent fetal surgery for SB. Among 51 different outcome variables, there were only 3 favorable (multiplicity-adjusted) significant differences (gestational age at birth, hindbrain herniation, and psychomotor development). There were no statistically significant differences regarding any other parameters. CONCLUSION: Our findings confirm that rigorous apprenticeship, training, and comprehensive prospective data collection enable centers like the Zurich Center for Fetal Diagnosis and Therapy to achieve benchmark results for open fetal surgery for myelomeningocele and myeloschisis. These results justify the existence and continuation of our program. Outcome documentation is an essential element of quality management. It is medically and ethically fundamental for fetal medicine and surgery centers offering high-end innovative medical care.

Perinatal care at the limit of viability between 22 and 26 completed weeks of gestation in Switzerland. 2011 revision of the Swiss recommendations.

Perinatal care of pregnant women at high risk for preterm delivery and of preterm infants born at the limit of viability (22-26 completed weeks of gestation) requires a multidisciplinary approach by an experienced perinatal team. Limited precision in the determination of both gestational age and foetal weight, as well as biological variability may significantly affect the course of action chosen in individual cases. The decisions that must be taken with the pregnant women and on behalf of the preterm infant in this context are complex and have far-reaching consequences. When counselling pregnant women and their partners, neonatologists and obstetricians should provide them with comprehensive information in a sensitive and supportive way to build a basis of trust. The decisions are developed in a continuing dialogue between all parties involved (physicians, midwives, nursing staff and parents) with the principal aim to find solutions that are in the infant's and pregnant woman's best interest. Knowledge of current gestational age-specific mortality and morbidity rates and how they are modified by prenatally known prognostic factors (estimated foetal weight, sex, exposure or nonexposure to antenatal corticosteroids, single or multiple births) as well as the application of accepted ethical principles form the basis for responsible decision-making. Communication between all parties involved plays a central role. The members of the interdisciplinary working group suggest that the care of preterm infants with a gestational age between 22 0/7 and 23 6/7 weeks should generally be limited to palliative care. Obstetric interventions for foetal indications such as Caesarean section delivery are usually not indicated. In selected cases, for example, after 23 weeks of pregnancy have been completed and several of the above mentioned prenatally known prognostic factors are favourable or well informed parents insist on the initiation of life-sustaining therapies, active obstetric interventions for foetal indications and provisional intensive care of the neonate may be reasonable. In preterm infants with a gestational age between 24 0/7 and 24 6/7 weeks, it can be difficult to determine whether the burden of obstetric interventions and neonatal intensive care is justified given the limited chances of success of such a therapy. In such cases, the individual constellation of prenatally known factors which impact on prognosis can be helpful in the decision making process with the parents. In preterm infants with a gestational age between 25 0/7 and 25 6/7 weeks, foetal surveillance, obstetric interventions for foetal indications and neonatal intensive care measures are generally indicated. However, if several prenatally known prognostic factors are unfavourable and the parents agree, primary non-intervention and neonatal palliative care can be considered. All pregnant women with threatening preterm delivery or premature rupture of membranes at the limit of viability must be transferred to a perinatal centre with a level III neonatal intensive care unit no later than 23 0/7 weeks of gestation, unless emergency delivery is indicated. An experienced neonatology team should be involved in all deliveries that take place after 23 0/7 weeks of gestation to help to decide together with the parents if the initiation of intensive care measures appears to be appropriate or if preference should be given to palliative care (i.e., primary non-intervention). In doubtful situations, it can be reasonable to initiate intensive care and to admit the preterm infant to a neonatal intensive care unit (i.e., provisional intensive care). The infant's clinical evolution and additional discussions with the parents will help to clarify whether the life-sustaining therapies should be continued or withdrawn. Life support is continued as long as there is reasonable hope for survival and the infant's burden of intensive care is acceptable. If, on the other hand, the health care team and the parents have to recognise that in the light of a very poor prognosis the burden of the currently used therapies has become disproportionate, intensive care measures are no longer justified and other aspects of care (e.g., relief of pain and suffering) are the new priorities (i.e., redirection of care). If a decision is made to withhold or withdraw life-sustaining therapies, the health care team should focus on comfort care for the dying infant and support for the parents.

Determinants of body weight gain and association with neurodevelopmental outcome in infants operated for congenital heart disease.

The aim of this prospective study was to examine the determinants of growth failure and the association with neurodevelopmental outcome in infants undergoing open-heart surgery. In 107 infants undergoing open-heart surgery for congenital heart disease (CHD), we evaluated weight at birth, at surgery, and at one year of age (expressed as z-scores). Neurodevelopmental status was assessed before surgery and at one year of age. Median age at surgery was 3.9 months (range: 0.1-10.2). Mean [+/-standard deviation (S.D.)] weight z-score at birth was -0.27 (+/-1.45), before surgery -1.34 (+/-1.45) (P<0.001 vs. birth weight), and at one year -0.86 (+/-1.35), (P<0.001 vs. weight at surgery). Poor preoperative weight (<10th percentile) was associated with genetic disorders [odds ratio (OR) 5.9, P<0.001], preoperative neurological abnormalities (OR 3.41, P<0.05), and older age at surgery (OR 1.01, P<0.05). Weight <10th percentile at one year was associated with the same factors as poor preoperative weight, however, also with risk adjustment for congenital heart surgery-1 (RACHS) score >3 (OR 3.22, P<0.05). Neurodevelopmental outcome at one year was not determined by growth failure. In conclusion, impaired body weight gain before surgery is followed by a catch-up growth after surgery. However, there is no relationship to neurodevelopmental outcome. Genetic comorbidity is the most significant factor for poor weight gain.

Late morbidity during childhood and adolescence in previously premature neonates after patent ductus arteriosus closure.

The health status of previously premature neonates after closure of a patent ductus arteriosus (PDA) was analyzed in childhood and adolescence. Physician questionnaires were used to study 180 hospital survivors among 210 consecutive premature neonates who underwent PDA closure between 1985 and 2005. Complete follow-up data were obtained for 129 patients (72%). During a median follow-up period of 7 years (range, 2-22 years), three late deaths (2.3%) had occurred. Only 45% of the patients were considered healthy. Morbidity included developmental delay (41.1%), pulmonary illness (12.4%), neurologic impairment (14.7%), hearing impairment (3.9%), gastrointestinal disease (3.1%), and thoracic deformity (1.2%). None of the adverse variables during the neonatal period (intraventricular hemorrhage, bradycardia apnea syndrome, bronchopulmonary dysplasia, pulmonary bleeding, hyaline membrane disease, artificial respiration time [continuous positive airway pressure + intubation], or necrotizing enterocolitis) statistically predicted respective system morbidity at the follow-up evaluation. Hyaline membrane disease (odds ratio, 2.5; p = 0.026) and longer hospitalization time (odds ratio, 1.2 days per 10 hospitalization days; p = 0.032) in the newborn period were significant predictors of an unhealthy outcome at the last follow-up evaluation. Survival until childhood after closure of a hemodynamically significant PDA in premature neonates is satisfactory. However, physical and neurodevelopmental co-morbidity persist for half of the patients, perhaps as a sequela of prematurity unrelated to ductus closure.

Intellectual and motor performance, quality of life and psychosocial adjustment in children with cystinosis.

Cystinosis is a rare multisystemic progressive disorder mandating lifelong medical treatment. Knowledge on the intellectual and motor functioning, health-related quality of life and psychosocial adjustment in children with cystinosis is limited. We have investigated nine patients (four after renal transplantation) at a median age of 9.7 years (range 5.3-19.9 years). Intellectual performance (IP) was analysed with the Wechsler Intelligence Scale for Children-III (seven children) and the Kaufman Assessment Battery for Children (two children). Motor performance (MP) was evaluated using the Zurich Neuromotor Assessment Test, and quality of life (QOL) was studied by means of the Netherlands Organization for Applied Scientific Research Academical Medical Center Child Quality of Life Questionnaire. Psychosocial adjustment was assessed by the Child Behavior Checklist. The overall intelligence quotient (IQ) of our patient cohort (median 92, range 71-105) was significantly lower than that of the healthy controls (p = 0.04), with two patients having an IQ < 85. Verbal IQ (93, range 76-118) was significantly higher than performance IQ (90, range 68-97; p = 0.03). The MP was significantly below the norm for pure motor, pegboard and static balance, as well as for movement quality. The patients' QOL was normal for six of seven dimensions (exception being positive emotions), whereas parents reported significant impairment in positive emotions, autonomy, social and cognitive functions. Significant disturbance was noted in terms of psychosocial adjustment. Based on the results from our small patient cohort, we conclude that intellectual and motor performance, health-related QOL and psychosocial adjustment are significantly impaired in children and adolescents with cystinosis.

Health-related quality of life in children and adolescents after open-heart surgery.

OBJECTIVE: To assess health-related quality of life (HRQOL) in children with congenital heart disease (CHD) after open-heart surgery and to identify medical, individual, and family-related predictors of outcome. STUDY DESIGN: Cross-sectional cohort study. 155 children with CHD (40% cyanotic type) who underwent open-heart surgery between 1995 and 1998 were eligible. One hundred and ten patients (response rate 71%) were investigated at a mean age of 10.4 years. Mean age at operation was 2.3 years (range, 0-8.7 years), mean duration of cardiopulmonary bypass was 95 minutes (range, 5-206 minutes), and circulatory arrest was performed in 9% of the children. Child- and parent-rated HRQOL was evaluated by the TNO-AZL Child Quality of Life Questionnaire. Scores were compared with healthy references. RESULTS: Most dimensions of self-reported HRQOL were impaired, including autonomy and motor, social, and emotional functioning. In addition to the children's ratings, parents rated cognitive functioning of their children as diminished. Multivariate analyses revealed that duration of cardiopulmonary bypass, length of hospitalization, need for current cardiac medication, and adverse family relationships had a negative impact on parent- but not on child-rated HRQOL. CONCLUSIONS: HRQOL is impaired in children with CHD after open-heart surgery. Medical variables and the quality of family relationships are important determinants.