The knowledge about long-term consequences of preterm birth among health professionals, educational professionals, and parents in Slovenia.

AIM: To assess the knowledge about the long-term consequences of preterm birth and the need for training and information among various professionals working with preterm children and parents of preterm children. METHODS: In February and March 2018, physicians, psychologists, special education needs teachers, teachers, preschool teachers, and parents (N=488) filled in the Preterm Birth-Knowledge Scale and a survey regarding their perceptions and attitudes toward working with preterm children. RESULTS: Physicians and psychologists were most knowledgeable among the groups about the long-term consequences of preterm birth. Teachers, preschool teachers, and parents had significantly lower knowledge (F=23.18, P<0.001). The majority of professionals indicated that they did not feel adequately equipped to support the learning and development of preterm children and that they had not received sufficient training in this area. More than half indicated that they had received no formal training. In general, the participants tended to underestimate the long-term problems of preterm children. CONCLUSION: The findings underscore the importance of integrating the issue of the long-term outcomes of preterm birth and working with preterm children into formal education, and in other forms of educational activities.

Effectiveness of psychoeducation for children, adolescents and caregivers in the treatment of eating disorders: A systematic review.

BACKGROUND: Eating disorders in childhood and adolescence negatively affect many areas of development and functioning of children, adolescents, and their families. Psychoeducation has an important role in management and treatment of eating disorders. METHODS: A systematic literature review was performed using multiple databases (PsycInfo, PubMed, and Web of Science). The inclusion criteria comprised empirical studies of psychoeducation for patients with eating disorders or their caregivers. The study reporting quality was assessed with the revised Cochrane Collaboration's risk of bias tool and the Standard Quality Assessment Criteria for Evaluating Primary Research Papers from a Variety of Fields for non-randomized studies. RESULTS: Ten studies met the inclusion criteria, in three of which the interventions were patient-centred and in seven of which the interventions were caregiver-centred. The studies differed in terms of methodology, outcome measures, and quality. The results suggest that psychoeducation is an effective intervention for children, adolescents and caregivers in the treatment of eating disorders. It may lead to weight gain, a decrease in eating disorder symptoms, and a reduction in caregiver burden. CONCLUSIONS: There is a need for more randomized controlled trials to determine the effectiveness of psychoeducation for children, adolescents and caregivers in treatment of eating disorders.

Cognitive behavioral therapy for managing obesity in patients with chronic kidney disease: Study protocol for a randomized controlled trial.

Obesity is one of the main risk factors for progression of chronic kidney disease (CKD). Weight loss interventions have limited efficacy in patients with pre-dialysis CKD. Our objective is to test the efficacy of a cognitive behavioral therapy program for obesity management in patients with CKD. We will conduct a randomized controlled intervention trial to evaluate the effects of cognitive behavioral therapy for obesity on weight loss, change in proteinuria, weight maintenance, quality of life, depression symptoms, and anxiety symptoms in patients with CKD. The duration of the intervention will be 16 weeks. The primary study outcomes will be body mass index (BMI) and proteinuria. CKD patients will be randomized into two groups: an intervention group with cognitive behavioral therapy, sessions with a dietitian and a kinesiologist, and a control group with sessions with a dietitian and a kinesiologist, without cognitive behavioral therapy. Study outcomes will be assessed at baseline, immediately after the 16-week intervention, 3 months after the end of the intervention, and 12 months after the end of the intervention. This study will be the first to evaluate the efficacy of cognitive behavioral therapy for obesity in patients with CKD. We expect that our results will contribute to new ways of non-pharmacological treatment of CKD. Clinical trial registration: ClinicalTrials.Gov, NCT05927337.

Cognitive behavioral therapy for lifestyle changes in patients with obesity and type 2 diabetes: a systematic review and meta-analysis.

The aim of this systematic review and meta-analysis was to examine the contribution of cognitive behavioral therapy (CBT) to the implementation of lifestyle changes, considering health-related and behavioral outcomes. A systematic literature review was performed using multiple databases (PsycInfo, PubMed and MEDLINE). The inclusion criteria comprised randomised controlled trials of CBT for lifestyle changes in patients with obesity and/or type 2 diabetes. The quality of study reporting was assessed with the revised Cochrane Collaboration's risk of bias tool. A meta-analysis was conducted on studies with appropriate outcomes. Nine randomised controlled trials, with a total sample size of 902 participants, met the inclusion criteria. The meta-analysis has shown a medium, significant effect size of CBT interventions for weight loss and weight maintenance, and a low, non-significant effect size of CBT interventions for reducing glycated hemoglobin (HbA1c) levels. A separate, combined, meta-analysis for all nine calculated effect sizes has yielded a medium and significant overall effect size for the model. Our review of the studies about the effectiveness of CBT in implementing lifestyle changes has, in comparison to usual control groups, proven the efficacy of CBT interventions in implementing lifestyle changes, especially for weight loss and weight maintenance.

Corrigendum: Prognostic value of various diagnostic methods for long-term outcome of newborns after hypoxic-ischemic encephalopathy treated with hypothermia.

[This corrects the article DOI: 10.3389/fped.2022.856615.].

Prognostic Value of Various Diagnostic Methods for Long-Term Outcome of Newborns After Hypoxic-Ischemic Encephalopathy Treated With Hypothermia.

Introduction: Prediction of outcome in newborns with hypoxic-ischemic encephalopathy (HIE) has been modulated by hypothermia treatment (HT). We assessed the predictive value of diagnostic methods commonly used in neonates with HIE for short-term neurodevelopmental outcome and long-term neurological outcome. Materials and Methods: This longitudinal cohort study followed up 50 term newborns who underwent HT after HIE between July 2006 and August 2015, until preschool age. We estimated sensitivity and specificity for short-term neurodevelopmental outcome at 18 months and long-term neurological outcome at five years based on Amiel-Tison Neurological Assessment (ATNA), electroencephalography (EEG), and magnetic resonance imaging (MRI) performed in the neonatal period. Results: The accuracy of all neonatal methods tested was higher for long-term neurological outcome compared to the predictive accuracy for short-term neurodevelopmental outcome at 18-24 months. Sensitivity and specificity in predicting unfavorable long-term neurological outcome were: MRI (sensitivity 1.0 [95%CI 0.96-1.0]; specificity 0.91 [95%CI 0.86-1.0]), EEG (sensitivity 0.94 [95%CI 0.71-1.0]; specificity 1.0 [95% CI 0.89-1.0]), and ATNA (sensitivity 0.94 [95%CI 0.71-1.0]; specificity 0.91 [95%CI 0.76-0.98]). Conclusion: MRI is a powerful predictor of long-term neurological outcome when performed in the first week after HIE in HT treated infants, as are EEG and ATNA performed in the second or third week postnatally.

Therapy-type related long-term outcomes in mucopolysaccaridosis type II (Hunter syndrome) - Case series.

Mucopolysaccharidosis type II (MPS II, Hunter syndrome) is a rare, X-linked recessive multisystem lysosomal storage disease due to iduronate-2-sulfatase enzyme deficiency. We presented three unrelated Slovenian patients with the severe form of MPS II that received three different management approaches: natural course of the disease without received specific treatment, enzyme replacement therapy (ERT), and hematopoietic stem cell transplantation (HSCT). The decision on the management depended on disease severity, degree of cognitive impairment, and parent's informed decision. The current benefits of MPS II treatments are limited. The lifelong costly intravenous ERT brings significant benefits but the patients with severe phenotypes and neurological involvement progress to cognitive decline and disability regardless of ERT, as demonstrated in published reviews and our case series. The patient after HSCT was the only one of the three cases reported to show a slowly progressing cognitive development. The type of information from the case series is insufficient for generalized conclusions, but with advanced myeloablative conditioning, HSCT may be a preferred treatment option in early diagnosed MPS II patients with the severe form of the disease and low disease burden at the time of presentation.

Pregnancy exposome and child psychomotor development in three European birth cohorts.

Characterization of the exposome, the totality of all environmental factors that one is exposed to from conception onwards, has been recommended to better evaluate the role of environmental influences on developmental programming and life-course vulnerability to major chronic diseases. In the framework of the Health and Environment-wide Associations based on Large population Surveys (HEALS) project we considered the pregnancy exposome exploiting two databases (PHIME and REPRO_PL) that include birth cohorts from three EU countries (Croatia, Slovenia and Poland). The databases contained information on several chemical exposures, socio-demographic, lifestyle and health related factors from conception to child birth, and neuropsychological scores assessed by the Bayley Scales of Infant and Toddler Development in the first two years of life. Our main goal was to assess consistency of environmental influences on neurodevelopment, if any, across European countries differing for geographical, socio-demographic characteristics and levels of chemical exposures to metals such as lead (Pb), mercury (Hg), cadmium (Cd) and trace elements, including micronutrients such as zinc (Zn) and selenium (Se). To this aim, we first selected variables common to the different databases, then applied univariate and multivariate regression analyses to identify factors linked to neurodevelopment, and finally performed meta-analysis to detect potential heterogeneity among cohorts and pooled estimates. Significant differences in exposure levels among the three sub-cohorts were observed as for Hg and Se; exposure levels under study were relatively low and within the range described in existing EU biomonitoring studies. The univariate analyses did not show any common pattern of association as only in the Polish cohort chemical exposure had an impact on neuropsychological outcome. In the meta-analysis, some consistent trends were evident, relative to the adverse influence of Pb on children's language and cognition and the positive influence of Se on language abilities. The effects of the neurotoxic metal Hg positively influenced the motor scores in the Polish cohorts, while it decreased the motor scores in the Slovenia and Croatian sub-cohorts. The only socio-demographic factor consistently associated to the outcome among cohorts was child's sex, with females performing better than males on cognitive and language scores. These findings point to the need of harmonizing existing cohorts or creating prospective study designs that facilitate comparisons in the exposome over time, places and kind of environmental exposures.

Mercury speciation in prenatal exposure in Slovenian and Croatian population - PHIME study.

In recent years, several studies have addressed the issue of prenatal exposure to methylmercury (MeHg); however, few have actually analysed MeHg blood concentrations. Our study population included mothers and their new-borns from Slovenia (central region; N = 584) and Croatia (coastal region; N = 234). We have measurements of total Hg (THg) and MeHg in maternal hair, maternal peripheral blood, and cord blood. Cord blood Hg concentrations were low to moderate (median THg = 1.84 ng/g and MeHg = 1.69 ng/g). The proportion of THg as MeHg (%MeHg) in maternal and cord blood varied between 4% and 100% (coefficient of variation, CV = 32%) and between 8% and 100% (CV = 20%), respectively. Our data shows that variability of %MeHg was higher at lower blood THg levels. Concentrations of MeHg in maternal blood and cord blood were highly correlated (Rs = 0.943), in the case of inorganic Hg correlation was significant but weaker (Rs = 0.198). MeHg levels in maternal blood and cord blood were positively associated with seafood intake, maternal age, and negatively associated with pre-pregnancy BMI. Additionally, MeHg in maternal blood was positively associated with plasma selenium levels, and cord blood MeHg was negatively associated with parity. The results of multiple linear regression models showed that speciation analysis provides more defined estimation of prenatal exposure in association modelling. Associations between Hg exposure and cognitive performance of children (assessed using Bayley Scales of Infant and Toddler development) adjusted for maternal or child Apolipoprotein E genotypes showed higher model R2 and lower p-values when adjusted for MeHg compared to THg. This study demonstrates that Hg speciation improves the association between exposure and possible negative health effects.

Psychosocial functioning in adolescents: results according to Amiel-Tison neurological assessment in a group of preterm infants.

OBJECTIVE: This prospective study investigated the relationship between Amiel-Tison neurological assessment (ATNA) in preterm children and their psychosocial functioning in adolescence. METHODS: From the initial group of 45 children regularly assessed by the ATNA from term until the age of 2 years, 27 participated in the follow-up at 13 years. RESULTS: Of the three groups categorized by neurological signs as normal, intermediate or abnormal, parents of adolescents with normal ATNA reported the lowest number of executive function problems (p = 0.019) and behavioral symptoms (p = 0.011), while the adolescents themselves reported the lowest number of behavioral symptoms (p = 0.005) and the highest quality of life (p = 0.012). The number of problems reported increased with the number of abnormal neurological signs. CONCLUSION: Standardized neurological assessment may be a helpful clinical tool for the identification of children at risk for later psychosocial problems who could benefit from prevention and early intervention programs.

Prenatal mercury exposure and child neurodevelopment outcomes at 18 months: Results from the Mediterranean PHIME cohort.

INTRODUCTION: Neurotoxicity due to acute prenatal exposure to high-dose of mercury (Hg) is well documented. However, the effect of prenatal exposure to low Hg levels on child neurodevelopment and the question about "safety" of fish-eating during pregnancy remain controversial. International comparisons of Hg concentrations in mother-child biological samples and neurodevelopmental scores embedded in birth cohort studies may provide useful evidence to explore this issue. MATERIALS AND METHODS: The Mediterranean (Italy, Slovenia, Croatia, and Greece) cohort study included 1308 mother-child pairs enrolled in the Public Health Impact of long-term, low-level, Mixed Element exposure in a susceptible population EU Sixth Framework Programme (PHIME). Maternal hair and venous blood, cord blood and breast milk samples were collected, and total Hg (THg) levels were measured. Demographic and socioeconomic information, lifestyles and nutritional habits were collected through questionnaires at different phases of follow-up. Children at 18 months of age underwent neurodevelopmental testing using the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III). Multivariate linear and logistic regressions were performed, for each country, to assess the association between THg and BSID-III scores, obtaining adjusted ß coefficients and odds ratios (ORs). These values were used to conduct a meta-analysis, to explore possible heterogeneity among countries and to obtain combined estimates of the association between THg exposure and BSID-III scores. RESULTS: Median THg (ng/g) was: 704 in maternal hair, 2.4 in maternal blood, 3.6 in cord blood, and 0.6 in breast milk. THg concentrations were highest in Greece and lowest in Slovenia. BSID-III neurodevelopmental scores were higher in Croatia and Slovenia. The meta-analysis of multivariate linear models found an overall positive association between language composite score and receptive communication scaled score and increasing THg in maternal hair (n = 1086; ß = 0.55; 95%CI: 0.05-1.05 and n = 1075; ß = 0.12; 95%CI: 0.02-0.22, respectively). The meta-analysis of logistic regression models showed that the overall adjusted OR between THg in cord blood and suboptimal gross motor score was borderline significant (n = 882; OR = 1.03; 95%CI: 1.00-1.07). Heterogeneity was found across the four sub-cohorts for language composite score in maternal blood, and for fine motor scaled score in cord blood and breast milk. Language composite score and THg concentrations in maternal venous blood were positively related (n = 58; ß = 4.29; CI95% (-0.02, 8.60)) in Croatia and an increase of 1 ng/g of THg in maternal venous blood was associated with a reduced risk for children to fall in the lowest quintile of language score by 31% (n = 58; OR = 0.69; CI 95%: 0.37, 1.01). The comparison of ß coefficients obtained by multiple linear regression model showed an inverse association between fine motor score and THg concentrations in cord blood for Croatia (n = 54; ß = -0.53; CI 95%: -1.10, 0.04) and Slovenia (n = 225; ß = -0.25; CI 95%: -0.49, -0.01). In Slovenia THg level in breast milk was associated with suboptimal fine motor performance (n = 195; OR = 5.25; CI 95%: 1.36, 21.10). CONCLUSIONS: This study showed an inverse relation between THg levels and developmental motor scores at 18 months, although the evidence was weak and partially internally and externally inconsistent. No evidence of detrimental effects of THg was found for cognitive and language outcomes at these concentrations and age.

ESSENCE-Q: Slavic language versions for developmental screening in young children.

PURPOSE: The Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations - Questionnaire (ESSENCE-Q) was developed as a brief screener to identify children with developmental concerns who might have neurodevelopmental disorders (NDDs). This study aimed to translate the ESSENCE-Q into south Slavic languages, namely, Bosnian, Bulgarian, Croatian, Macedonian, Montenegrin, Serbian, and Slovenian, and to evaluate its psychometric properties for screening purposes in clinical settings. PATIENTS AND METHODS: In the study, the ESSENCE-Q was completed for 251 "typically developing" children and 200 children with 1 or more diagnosed NDDs, all aged 1-6 years. Internal consistency and construct validity were tested first, followed by generating receiver operating characteristic curves and the area under the curve. Optimal cutoff values were then explored. RESULTS: The Cronbach's α coefficients were 0.91, 0.88, and 0.86 for ESSENCE-Q parent-completed form, and the telephone and direct interview forms administered by trained nurse or specialist, respectively. The 3 versions produced area under the curve values (95% confidence interval): 0.96 (0.93-0.99), 0.91 (0.86-0.95), and 0.91 (0.86-0.97), respectively. An optimal cutoff for ESSENCE-Q parent-completed form was found to be ≥3 points, while for the telephone and direct interviews, it was ≥5 points. CONCLUSION: We found adequate measurement properties of the south Slavic languages versions of the ESSENCE-Q as a screener for NDDs in clinical settings. This study provided additional data supporting sound psychometric properties of the ESSENCE-Q.

Prenatal mercury exposure, neurodevelopment and apolipoprotein E genetic polymorphism.

The aim of the present study was to evaluate the association between prenatal exposure to mercury (Hg) and neurodevelopment of the child, taking into account genetic polymorphism of apolipoprotein E (Apoe) and other relevant confounders. Six hundred and one mother-child pairs were recruited from the central Slovenia region and 243 from Rijeka, on the Croatian coast of the northern Adriatic. The total Hg in cord blood, Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) assessment at 18 months of age and Apoe genotyping was performed on 361 children; 237 of them were from Slovenia and 124 from Croatia. The results showed negative association between low-to-moderate Hg exposure in children with normal neurodevelopmental outcome and cognitive and fine motor scores at 18 months of age as assessed by Bayley III. The Hg-related decrease in cognitive score was observed only in children carrying at least one Apoe ε4 allele, while the decrease in fine motor scores was independent of the Apoe genotype. Adjusting for selenium (Se) and lead (Pb) levels, a positive association between Se and the language score and a negative association between Pb and the motor score was observed, but not in the subgroup of children carrying the ε4 allele.

Habit reversal training and educational group treatments for children with tourette syndrome: A preliminary randomised controlled trial.

Quality of life of children with Tourette Syndrome (TS) is impacted greatly by its symptoms and their social consequences. Habit Reversal Training (HRT) is effective but has not, until now, been empirically evaluated in groups. This randomised controlled trial evaluated feasibility and preliminary efficacy of eight HRT group sessions compared to eight Education group sessions. Thirty-three children aged 9-13 years with TS or Chronic Tic Disorder took part. Outcomes evaluated were tic severity and quality of life (QoL). Tic severity improvements were found in both groups. Motor tic severity (Yale Global Tic Severity Scale) showed greatest improvements in the HRT group. Both groups showed a strong tendency toward improvements in patient reported QoL. In conclusion, group-based treatments for TS are feasible and exposure to other children with tics did not increase tic expression. HRT led to greater reductions in tic severity than Education. Implications, such as cost-effectiveness of treatment delivery, are discussed.

Levels of metals in the blood and specific porphyrins in the urine in children with autism spectrum disorders.

The aim of the present study was to determine the levels of metals in blood (zinc (Zn), copper (Cu), aluminium (Al), lead (Pb) and mercury (Hg)), as well as the specific porphyrin levels in the urine of patients with autism spectrum disorder (ASD) compared with patients with other neurological disorders. The study was performed in a group of children with ASD (N = 52, average age = 6.2 years) and a control group of children with other neurological disorders (N = 22, average age = 6.6 years), matched in terms of intellectual abilities (Mann-Whitney U = 565.0, p = 0.595). Measurement of metals in blood was performed by atomic absorption spectrometry, while the HPLC method via a fluorescence detector was used to test urinary porphyrin levels. Results were compared across groups using a multivariate analysis of covariance (MANCOVA). In addition, a generalized linear model was used to establish the impact of group membership on the blood Cu/Zn ratio. In terms of blood levels of metals, no significant difference between the groups was found. However, compared to the control group, ASD group had significantly elevated blood Cu/Zn ratio (Wald χ (2) = 6.6, df = 1, p = 0.010). Additionally, no significant difference between the groups was found in terms of uroporphyrin I, heptacarboxyporphyrin I, hexacarboxyporphyrin and pentacarboxyporphyrin I. However, the levels of coproporphyrin I and coproporphyrin III were lower in the ASD group compared to the controls. Due to observed higher Cu/Zn ratio, it is suggested to test blood levels of Zn and Cu in all autistic children and give them a Zn supplement if needed.

Relationship between neurological assessments of preterm infants in the first 2 years and cognitive outcome at school age.

BACKGROUND: The risk of cognitive disability in preterm infants is higher than in general population. The Amiel-Tison neurological assessment could be a useful tool for early identification of preterm children at risk of cognitive disability in school age. This study investigated the value of categorization of neurological signs assessed by the Amiel-Tison neurological assessment in the first 2 years of life in relation to cognitive performance at school age in a group of preterm children. METHODS: Preterm children with gestational age from 23 to 36 weeks were included in the prospective study. From the initial group of 45 children, in whom the Amiel-Tison neurological assessment was performed at term age, at 3 months corrected age, and at 2 years, the Wechsler Intelligence Scale for Children-third edition was performed in 39 children after school entry. RESULTS: Full scale IQ, Verbal IQ, and Performance IQ of the whole group of preterm children were not significantly different from the normative data; most of the children had IQ scores in the normal range (≥85). The mean cognitive results of children decreased as the number of neurological signs increased. There was a significant correlation between the categories of neurological signs at 2 years and later cognitive results. CONCLUSIONS: The grade of severity of neurological signs at 2 years was associated with the cognitive results at school age. The categorization of neurological signs according to the Amiel-Tison neurological assessment in preterm children might have prognostic value for cognitive outcome at school age.

Assessment of general movements and 2.5 year developmental outcomes: pilot results in a diverse preterm group.

BACKGROUND: While the predictive value of general movements for later cerebral palsy is well known, its value to predict minor neurological and developmental impairments is less clear. AIM: To analyze the results of the assessment of general movements in relation to the developmental outcome measured by the Bayley scales of infant development in a group of preterm infants. METHODS: Twenty-six preterm infants (gestational age from 23 weeks to 36 weeks) were included. The results of the assessment of general movements at term age and at 3 months corrected age were compared to the results of the mental and psychomotor developmental index of the Bayley scales assessed between two and three years of chronological age. RESULTS: Infants with normal writhing general movements achieved the highest scores on the mental and psychomotor developmental index, and those with cramped-synchronized general movements had the lowest scores. Infants with normal general movements during the fidgety period achieved the highest scores on both scales; those with an absence of fidgety movements achieved the lowest scores. We found the sensitivity of general movements to predict cognitive impairments to be 1.00 during the writhing period and 0.83 during the fidgety period; and 0.85 and 0.54, respectively, to predict motor impairments. The differences in the mental developmental index score between the groups with different qualities of general movements were significant in the writhing period and approached significance in the fidgety period, while for the psychomotor developmental index the differences between the groups with different qualities of general movements were not significant. CONCLUSION: The quality of general movements may be predictive of later development.

Amiel-Tison Neurological Assessment at term age: clinical application, correlation with other methods, and outcome at 12 to 15 months.

The aims of this study were: (1) to perform the Amiel-Tison Neurological Assessment (ATNA) in a group of infants with different risk factors for brain damage; (2) to analyze the results of the examinations in light of the risk factors and presumed aetiology; (3) to compare results of examinations with results of cranial ultrasound, electroencephalography (EEG), and cerebral function monitoring (CFM); and (4) to evaluate neurological outcome at 12 to 15 months of age using the Amiel-Tison and Gosselin method, and developmental outcome using the Bayley Scales of Infant Development. Participants were 52 term, newborn infants (31 males, 21 females) with risk factors for brain damage. Mean birthweight was 3288g (SD 661g) and mean gestational age was 39.4wks (SD 1.2wks); range 38 to 41.3wks. Mean age at admission to a neonatal special care unit was 75h, (SD 13.7h). The group with a dynamic (evolving) clinical profile differed significantly from the group with a static (stable) profile in terms of aetiology, while the group with signs of prenatal brain damage differed from the group without these signs regarding aetiology and the level of severity of neurological signs. Sensitivity of the ATNA to detect infants with abnormal ultrasound was 0.97, with EEG 0.89, and with CFM 0.88. At follow-up at 12 to 15 months 47 children were examined: neurological examination was normal in 25 and five children had a minor, five a moderate, and 12 a severe neurological deficit. Agreement of the ATNA with neurological and developmental assessment at follow-up was very good. Our findings suggest that the ATNA is also of value in assessing aetiology and timing of brain lesions.