Neurodevelopment in patients with biliary atresia up to toddler age: Outcomes and predictability.

AIM: To assess neurodevelopment in young patients with biliary atresia (BA) and to determine the predictive value of General Movement Assessment (GMA) at infant age for neurodevelopmental impairments at toddler age. METHOD: Infants diagnosed with BA were prospectively included in a longitudinal study. Neurodevelopmental status was previously assessed before Kasai porto-enterostomy (KPE) and one month after KPE using Prechtl's GMA, including motor optimality scores. At 2-3 years, neurodevelopment was assessed using the Bayley Scales of Infant Development, and compared to the Dutch norm population. The predictive value of GMA at infant age for motor skills and cognition at toddler age was determined. RESULTS: Neurodevelopment was assessed in 41 BA patients. At toddler age (n = 38, age 29 ± 5 months, 70 % liver transplantation), 13 (39 %) patients scored below-average on motor skills, and 6 (17 %) patients on cognition. Abnormal GMA after KPE predicted both below-average motor skills and cognitive score at toddler age (sensitivity, 91 % and 80 %; specificity 83 % and 67 %; negative predictive value, 94 % and 94 %; and, positive predictive value, 77 % and 33 %, resp.). INTERPRETATION: One-third of toddlers with BA show impaired motor skills. GMA post-KPE has a high predictive value to identify infants with BA at risk of neurodevelopmental impairments.

The Impact of the COVID-19 Outbreak on Mental Wellbeing in Children with a Chronic Condition Compared to Healthy Peers.

The aim of this study was to assess the impact of the COVID-19 pandemic on the mental wellbeing of children 8-18 years old with chronic conditions, by comparing pandemic data with pre-pandemic data and with healthy peers. Data were obtained from two ongoing longitudinal cohorts: the PROactive cohort study following children with a chronic condition, and the WHISTLER population cohort. Mental wellbeing was assessed by three indicators: life satisfaction, internalising symptoms, and psychosomatic health. The stringency of the COVID-19-related lockdown was considered a moderating factor. Data on chronic patients were recorded before (n = 934, 65% girls) and during (n = 503, 61% girls) the pandemic, and compared to healthy peers during the pandemic (n = 166, 61% girls). Children with a chronic condition reported lower life satisfaction, but no clinically relevant changes in internalising symptoms or psychosomatic health, during the pandemic compared to before. In comparison to healthy peers, children with a chronic condition experienced decreased life satisfaction and psychosomatic health, but internalising symptoms did not differ between groups during the COVID-19 pandemic. The lockdown stringency was negatively associated with all indicators of mental wellbeing-worse life satisfaction, more internalising symptoms, and more psychosomatic symptoms.

Parental wellbeing after diagnosing a child with biliary atresia: A prospective cohort study.

PURPOSE: To determine anxiety, stress, and quality of life (QoL) in parents of children who are diagnosed with biliary atresia (BA). METHODS: Parents of BA patients (0-3 years) completed validated questionnaires at three time points: at first hospitalization (T0); 1-2 months post diagnosis (T1); and 2-3 years post diagnosis (T2). Results are presented in medians (min-max). RESULTS: We included 52 parents (age 31 [24-51 y], 31 females) of 30 BA patients. In fathers, neither anxiety nor stress levels significantly differed from reference values. Mothers reported significantly higher anxiety levels compared to reference values (T0: 48 vs 35, p = 0.001; T1: 43 vs 35, p = 0.03; T2: 37 vs 35, p = 0.04), which significantly decreased over time (-23% between T0 and T2: p = 0.04). Stress in mothers was significantly higher at T1 than at T2 (+35%, p = 0.02), but was not significantly different from reference values at each time point (T0: 17 vs 14, p = 0.07; T1: 18 vs 14, p = 0.09; T2: 13 vs 14, p = 0.52).The overall QoL in mothers and fathers was rather unaffected. CONCLUSIONS: Particularly mothers of infants diagnosed with BA report high anxiety levels up to three years after diagnosis. The overall QoL of parents is rather unaffected after diagnosing BA in their child. LEVEL OF EVIDENCE: Level 2.

Early Motor Repertoire in Infants With Biliary Atresia: A Nationwide Prospective Cohort Study.

OBJECTIVES: The aim of the study was to assess the neurological status in infants with biliary atresia (BA) at time of diagnosis, using Prechtl's validated General Movement Assessment. METHODS: Infants diagnosed with BA were prospectively included in a nationwide cohort study. From birth to approximately 46 weeks of postmenstrual age (PMA), general movements (GMs) are defined as "writhing movements." At 46 to 49 weeks PMA, "'fidgety movements" emerge. The infant's early motor repertoire was recorded on video before Kasai portoenterostomy. We scored GM optimality scores (min-max 5-42) or motor optimality scores (MOS, min-max 5-28) as appropriate. We defined GM optimality scores <36 and MOS <26 as atypical, and compared the results with 2 reference groups of healthy peers. RESULTS: We assessed GMs in 35 infants with BA (11/35 boys, gestational age 40 weeks [36-42], birth weight 3370 g [2015-4285]). At time of diagnosis (PMA 47 weeks [42-60]), 16 infants (46%) showed atypical GMs. The proportion of infants with atypical GMs was significantly higher in BA (46%) than in 2 reference groups of healthy infants (vs 10%, P < 0.001; vs 18%, P < 0.001). Total and direct bilirubin levels were 165 µmol/L (87-364) and 134 µmol/L (72-334), respectively, height z score was 0.05 (-2.90, 1.75), weight z score -0.52 ([-2.50, -0.20) and mean upper arm circumference z score -1.80 (-2.50, -0.20). We found no statistically significant relation between atypical GMs and clinical variables. CONCLUSIONS: Almost half of the infants with BA showed atypical GMs at time of diagnosis, suggesting neurological impairment. Close monitoring of these infants is warranted to determine their individual neurodevelopmental trajectories.

Quality of Life in Parents of Children With Biliary Atresia.

OBJECTIVES: The aim of the study was to determine quality of life (QoL), stress, and anxiety levels in parents of children with biliary atresia (BA), and to assess factors associated with parental QoL. METHODS: Parents of children (6-16 years) with BA were included in this cross-sectional study. We used validated questionnaires to assess parental QoL, stress, and anxiety levels. We compared the results with reference data from the general population and determined associated factors using generalized linear mixed model analysis. Results are given as mean ±â€ŠSD or median [min-max]. RESULTS: We included 61 parents of 39 children (aged 11 ±â€Š3 years). Thirty-one children (79%) had undergone a liver transplantation (LTx). Parents reported reduced family activities (88 [8-100] vs 95 [30-100], P = 0.002) and more emotional worry (83 [17-100] vs 92 [95-100], P < 0.001) compared with reference data, but a stronger family cohesion (85 [30-100] vs 60 [30-100], P = 0.05). Scores on parental QoL, anxiety and stress were similar to reference data. Fathers (16.0 [11-19]) and mothers (15.4 ±â€Š1.4) scored higher on the psychological domain compared with reference data (vs 14.7 ±â€Š2.2, P < 0.01). There was no significant difference in QoL of parents with children with native liver or those who had undergone LTx. Older age and high anxiety trait in parents were adversely associated with physical QoL. Household income below &OV0556;35 000/year and high anxiety trait were adversely associated with environmental QoL. CONCLUSIONS: QoL in parents of school-aged children with BA appears to be unaffected. Parents with high-anxiety personality trait, older age, and low household income are at increased risk of impaired QoL.

A systematic review and narrative synthesis of data-driven studies in schizophrenia symptoms and cognitive deficits.

To tackle the phenotypic heterogeneity of schizophrenia, data-driven methods are often applied to identify subtypes of its symptoms and cognitive deficits. However, a systematic review on this topic is lacking. The objective of this review was to summarize the evidence obtained from longitudinal and cross-sectional data-driven studies in positive and negative symptoms and cognitive deficits in patients with schizophrenia spectrum disorders, their unaffected siblings and healthy controls or individuals from general population. Additionally, we aimed to highlight methodological gaps across studies and point out future directions to optimize the translatability of evidence from data-driven studies. A systematic review was performed through searching PsycINFO, PubMed, PsycTESTS, PsycARTICLES, SCOPUS, EMBASE and Web of Science electronic databases. Both longitudinal and cross-sectional studies published from 2008 to 2019, which reported at least two statistically derived clusters or trajectories were included. Two reviewers independently screened and extracted the data. In this review, 53 studies (19 longitudinal and 34 cross-sectional) that conducted among 17,822 patients, 8729 unaffected siblings and 5520 controls or general population were included. Most longitudinal studies found four trajectories that characterized by stability, progressive deterioration, relapsing and progressive amelioration of symptoms and cognitive function. Cross-sectional studies commonly identified three clusters with low, intermediate (mixed) and high psychotic symptoms and cognitive profiles. Moreover, identified subgroups were predicted by numerous genetic, sociodemographic and clinical factors. Our findings indicate that schizophrenia symptoms and cognitive deficits are heterogeneous, although methodological limitations across studies are observed. Identified clusters and trajectories along with their predictors may be used to base the implementation of personalized treatment and develop a risk prediction model for high-risk individuals with prodromal symptoms.

Health-Related Quality of Life in Biliary Atresia Patients with Native Liver or Transplantation.

INTRODUCTION: We aimed to assess health-related quality of life (HrQoL) in biliary atresia (BA) patients, based on original data and a literature review, and to determine factors associated with their HrQoL. MATERIALS AND METHODS: We reviewed available studies describing HrQoL in BA patients. We assessed HrQoL in Dutch BA patients (6-16 years) using the validated Child Health Questionnaire. We compared HrQoL scores in BA patients with healthy peers and with children who had undergone major surgery in infancy or children with chronic conditions. We determined the relationship between specific patient-related factors and HrQoL. RESULTS: Literature data indicated that HrQoL in children with BA is lower than in healthy peers. In Dutch BA patients (n = 38; age 10 ± 3 years), parent-proxy physical HrQoL (48 ± 11) was significantly lower compared with two reference groups of healthy peers (59 ± 4 and 56 ± 6, respectively, each p < 0.001), and lower than in children with attention deficit hyperactivity disorder (60 ± 5), asthma (54 ± 6), attending a cardiology clinic (52 ± n/r), congenital diaphragmatic hernia (53 ± 7) or D-transposition of the great arteries (54 ± 6; all p < 0.05). Psychosocial HrQoL (50 ± 9) was lower than in healthy peers (54 ± 6, p = 0.02, and 53 ± 6, p = 0.07) and children with asthma (54 ± 6, p = 0.02), and largely comparable to children with other chronic conditions. Parent-proxy physical HrQoL was adversely related to adverse medical event in the past year, special education, and motor impairments; psychosocial HrQoL was adversely related to behavioral problems. CONCLUSION: Children with BA are at risk of impaired HrQoL. Special attention is warranted for children with adverse medical events and special education.

Long-Term Neurodevelopmental Outcomes in Children with Biliary Atresia.

OBJECTIVE: To assess long-term neurodevelopmental outcomes in school-aged children with biliary atresia. STUDY DESIGN: All Dutch children (6-12 years of age) diagnosed with biliary atresia were invited to participate in this study. We used validated neurodevelopmental tests to assess motor skills and cognition, and questionnaires to assess behavior. Scores were compared with the Dutch norm population, by means of 1-sample tests. Results are given as number and percentage or mean ± SD. RESULTS: We included 46 children, with a median age of 11 years (range, 6-13 years); 36 children had undergone a liver transplantation (78%). Twelve children (26%) received special education (vs 2.4% in the norm population; P < .01). Motor outcomes were significantly affected compared with the norm population (P < .01), with 25% normal (vs 85%), 25% borderline (vs 10%), and 50% low scores (vs 5%). Total IQ was lower in patients with biliary atresia, compared with the norm population (91 ± 18 vs 100 ± 15; P < .01). There were no significant differences in test scores between children with native liver and after liver transplantation. CONCLUSIONS: School-aged children with biliary atresia show neurodevelopmental impairments compared with the norm population, especially in motor skills. Our data strongly warrant evaluation of neurodevelopmental intervention programs to assess whether long-term outcomes could be improved.

Neurodevelopmental Outcomes in Children With Liver Diseases: a Systematic Review.

OBJECTIVE: The aim of the study was to determine the neurodevelopmental outcomes of children with liver diseases based on a systematical review of the literature. METHOD: A literature search according to the PRISMA statement was conducted using predefined search terms in PubMed, Cochrane Library, and PsycINFO. The inclusion criterion was studies published from 2000 onwards that reported on the neurodevelopmental outcomes of term-born children with liver diseases. A narrative synthesis was done to appraise the studies. RESULTS: Twenty-five studies were included (1913 children), 19 of which described children after liver transplantation (LTx; 1372 children). Sixty-seven percentage of the studies on children with liver diseases who survived with their native livers showed low-average or abnormal scores on specific subscales of cognitive and behavioral measures. In studies on children after LTx, this was 82%. After LTx, 83% of studies demonstrated impaired outcomes on behavior, whereas 42% of children received special education. Motor development was impaired in 82% of studies in children with native liver and after LTx. LIMITATIONS: Studies were heterogenic because of sample sizes, etiology of liver disease and type of assessment tools used. CONCLUSIONS: More than two-third of included studies showed neurodevelopmental deficits in children with liver diseases, affecting all neurodevelopmental areas. Knowledge on risk factors for impaired neurodevelopment is limited and lack of long-term follow-up is worrying, especially considering the increasing survival rates, resulting in more at-risk patients. Studying early predictors and risk factors of abnormal developmental trajectories of children with liver diseases is indicated to assess strategies to improve their long-term neurodevelopmental outcomes.