A systematic review of progranulin concentrations in biofluids in over 7,000 people-assessing the pathogenicity of GRN mutations and other influencing factors.

BACKGROUND: Pathogenic heterozygous mutations in the progranulin gene (GRN) are a key cause of frontotemporal dementia (FTD), leading to significantly reduced biofluid concentrations of the progranulin protein (PGRN). This has led to a number of ongoing therapeutic trials aiming to treat this form of FTD by increasing PGRN levels in mutation carriers. However, we currently lack a complete understanding of factors that affect PGRN levels and potential variation in measurement methods. Here, we aimed to address this gap in knowledge by systematically reviewing published literature on biofluid PGRN concentrations. METHODS: Published data including biofluid PGRN concentration, age, sex, diagnosis and GRN mutation were collected for 7071 individuals from 75 publications. The majority of analyses (72%) had focused on plasma PGRN concentrations, with many of these (56%) measured with a single assay type (Adipogen) and so the influence of mutation type, age at onset, sex, and diagnosis were investigated in this subset of the data. RESULTS: We established a plasma PGRN concentration cut-off between pathogenic mutation carriers and non-carriers of 74.8 ng/mL using the Adipogen assay based on 3301 individuals, with a CSF concentration cut-off of 3.43 ng/mL. Plasma PGRN concentration varied by GRN mutation type as well as by clinical diagnosis in those without a GRN mutation. Plasma PGRN concentration was significantly higher in women than men in GRN mutation carriers (p = 0.007) with a trend in non-carriers (p = 0.062), and there was a significant but weak positive correlation with age in both GRN mutation carriers and non-carriers. No significant association was seen with weight or with TMEM106B rs1990622 genotype. However, higher plasma PGRN levels were seen in those with the GRN rs5848 CC genotype in both GRN mutation carriers and non-carriers. CONCLUSIONS: These results further support the usefulness of PGRN concentration for the identification of the large majority of pathogenic mutations in the GRN gene. Furthermore, these results highlight the importance of considering additional factors, such as mutation type, sex and age when interpreting PGRN concentrations. This will be particularly important as we enter the era of trials for progranulin-associated FTD.

Parent-perceived recurrent pain in children: associations with maternal pain, depressiveness, socioeconomic status, and children's behavioural difficulties.

Objectives: The current study aimed to examine the potential transgenerational associations between maternal pain and depressiveness and childhood pain, and to explore the associations between the children's difficulties and recurrent pain (defined as pain occurring at least once a month in the previous 6 month) in healthy children aged 3-13 years. Methods: We collected Data between 2015 and 2019 as part of the LIFE Child study in Germany and investigated associations of maternal pain and depressiveness, child age, sex, pubertal stage, emotional difficulties, conduct difficulties, hyperactivity/inattention, peer group difficulties, and prosocial skills, and family socioeconomic status with the frequency of parent-perceived headache, backache, and stomachache in a sample of 1,850 children (4,819 documented visits) using logistic and ordinal regression analyses. Results: Overall, 10.4%, 24.4%, and 45.2% of parents reported their children had recurrent backache, headache, and stomachache, respectively, with 5.5% of children were reported to experience all three types of pain simultaneously. Higher age, female sex, puberty, emotional difficulties, low family socioeconomic status, as well as higher maternal impairment due to pain and maternal depressiveness were significantly associated with more frequent pain. Conclusions: Our study suggests that maternal pain, maternal depressiveness, and lower family socioeconomic status as well as child's emotional difficulties are significantly associated with a higher frequency of recurrent pain in children perceived by their parents.

Malignant peritoneal mesotheliomas of rats induced by multiwalled carbon nanotubes and amosite asbestos: transcriptome and epigenetic profiles.

BACKGROUND: Malignant mesothelioma is an aggressive cancer that often originates in the pleural and peritoneal mesothelium. Exposure to asbestos is a frequent cause. However, studies in rodents have shown that certain multiwalled carbon nanotubes (MWCNTs) can also induce malignant mesothelioma. The exact mechanisms are still unclear. To gain further insights into molecular pathways leading to carcinogenesis, we analyzed tumors in Wistar rats induced by intraperitoneal application of MWCNTs and amosite asbestos. Using transcriptomic and epigenetic approaches, we compared the tumors by inducer (MWCNTs or amosite asbestos) or by tumor type (sarcomatoid, epithelioid, or biphasic). RESULTS: Genome-wide transcriptome datasets, whether grouped by inducer or tumor type, showed a high number of significant differentially expressed genes (DEGs) relative to control peritoneal tissues. Bioinformatic evaluations using Ingenuity Pathway Analysis (IPA) revealed that while the transcriptome datasets shared commonalities, they also showed differences in DEGs, regulated canonical pathways, and affected molecular functions. In all datasets, among highly- scoring predicted canonical pathways were Phagosome Formation, IL8 Signaling, Integrin Signaling, RAC Signaling, and TREM1 Signaling. Top-scoring activated molecular functions included cell movement, invasion of cells, migration of cells, cell transformation, and metastasis. Notably, we found many genes associated with malignant mesothelioma in humans, which showed similar expression changes in the rat tumor transcriptome datasets. Furthermore, RT-qPCR revealed downregulation of Hrasls, Nr4a1, Fgfr4, and Ret or upregulation of Rnd3 and Gadd45b in all or most of the 36 tumors analyzed. Bisulfite sequencing of Hrasls, Nr4a1, Fgfr4, and Ret revealed heterogeneity in DNA methylation of promoter regions. However, higher methylation percentages were observed in some tumors compared to control tissues. Lastly, global 5mC DNA, m6A RNA and 5mC RNA methylation levels were also higher in tumors than in control tissues. CONCLUSIONS: Our findings may help better understand how exposure to MWCNTs can lead to carcinogenesis. This information is valuable for risk assessment and in the development of safe-by-design strategies.

Birth-related, medical, and diagnostic characteristics in younger versus older children with avoidant/restrictive food intake disorder (ARFID).

BACKGROUND: Although avoidant/restrictive food intake disorder (ARFID) presents the replacement and extension of feeding disorders of infancy and childhood, previous research into ARFID concentrated mainly on older patients. While birth-related characteristics play an etiologic role in feeding disorders, virtually nothing is known so far in ARFID. Therefore, the first aim of the study was to identify differences in birth-related characteristics in younger vs. older children with ARFID. Second, differences in physical and mental comorbidities, and third, diagnostic features between age groups were analysed. METHODS: Among N = 51 in- and outpatient treatment-seeking patients, n = 23 patients aged 0-5 years (30% girls) and n = 28 patients aged 6-17 years (57% girls), with an interview-based diagnosis of ARFID were included. Data on the pre- and perinatal period and mental and physical comorbidities were derived from patients' medical records, while diagnostic criteria, main ARFID presentation, and sociodemographic variables were collected through diagnostic interview. RESULTS: Significantly, younger patients with ARFID were born more often preterm and had more pre- and perinatal complications and a higher incidence of postnatal invasive procedures. Patients with ARFID aged 0-5 years presented significantly more physical comorbidities and conditions, especially congenital anomalies, while mental comorbidities, especially mood disorders, were significantly more common in patients with ARFID aged 6-17 years. No age differences were found for the distribution of diagnostic criteria and main ARFID presentation. CONCLUSION: This is the first study which aimed to identify age-specific characteristics in patients with ARFID with potential relevance for diagnosis and treatment. Especially birth-related complications, including invasive procedures postnatally, may be associated with developing ARFID, highlighting the importance of a closer view on these potential risk factors of the disorder. Future research with longitudinal design and larger samples may allow more detailed information on further age-specific associations, symptom trajectories, and age-specific risk factors for ARFID.

Avoidant/restrictive food intake disorder (ARFID) is a feeding and eating disorder characterized by a highly limited amount and/or variety of food intake accompanied by weight loss or reduced growth, nutritional deficiencies, the dependency on enteral nutrition or oral nutritional supplements, or psychosocial impairment. Although the knowledge about ARFID is currently expanding, there is still a lack of information whether the disorder presents differentially among younger and older youths. The present study examined n = 23 children aged 0­5 years in comparison to n = 28 patients aged 6­17 years in birth-related, medical, and diagnostic features. ARFID was assessed by clinical interview and questionnaire data, and medical records were used to derive clinical information. While younger patients with ARFID were more likely to be born preterm, had complications after birth and more co-occurring physical diseases, older patients with ARFID showed more mental illnesses. These findings underline the relevance of further investigations on age-dependent characteristics of ARFID to adapt diagnostic assessment and treatment of the disorder. No significant age differences were found for diagnostic criteria and presentations of ARFID, indicating that these features are applicable for patients of all child ages.

Monochromatic ocular high-order aberrations in children and adolescents.

PURPOSE: To investigate the prevalence and repeatability of high-order aberrations (HOAs) from non-cyclopleged eyes in 1515 children and adolescents 2.5-18 years of age. METHODS: The Leipzig Research Centre for Civilization Diseases (LIFE)-Child study is a population-based, prospective, observational single-centre study that investigates the development of children and adolescents in Germany. Wavefront measurements were repeated three times in each eye of 1515 healthy subjects. Results were described by 36 Zernike coefficients for a 5 mm reference pupil diameter. Short-term repeatability is given for each coefficient. The impact on vision is described by the root mean squared (RMS) value of the HOA Zernike coefficients. RESULTS: High-order aberrations were dominated by five contributions. For 1004 right eyes: spherical aberration (c12 = 0.06 ± 0.07 µm), coma (c7 = 0.03 ± 0.09 µm, c8 = 0.03 ± 0.06 µm) and trefoil (c6 = -0.01 ± 0.07 µm, c9 = 0.008 ± 0.06 µm). The RMS value was 0.18 ± 0.06 µm. Modes higher than fourth order do not contribute clinically to the aberrations. HOAs show no clinically significant dependency with age. Instead, HOA values agree well with previous results on aberrations in adult eyes. Spherical aberration was highly correlated between the two eyes. Repeatability was worst for coma, 0.033 µm, due to variability in the alignment of the pupil centre. The left eye showed, on average, a 0.08 mm larger pupil diameter than the right eye (p < 0.02). CONCLUSIONS: Across the age span from 2.5 to 18 years, we see the same distribution of HOA as for adults. We established that only five Zernike coefficients, spherical aberration, coma and trefoil were of clinical significance in healthy eyes. A high correlation between the two eyes for spherical aberration suggests a common blueprint for each eye in any one subject.

Distribution and clinical comparison of restrictive feeding and eating disorders using ICD-10 and ICD-11 criteria.

OBJECTIVE: Within the eleventh edition of the International Classification of Diseases (ICD-11), diagnostic criteria for feeding and eating disorders were revised and new diagnoses including avoidant/restrictive food intake disorder (ARFID) are classifiable; however, nothing is known about how these changes affect the prevalence of feeding and eating disorders. This study compared the distribution and clinical characteristics of restrictive feeding and eating disorders between ICD-10 and ICD-11. METHOD: The Eating Disorder Examination (EDE), its child version, and the EDE ARFID module were administered to N = 82 patients (0-17 years) seeking treatment for restrictive feeding and eating disorders and their parents. Clinical characteristics were derived from medical records, questionnaires, and objective anthropometrics. RESULTS: The number of residual restrictive eating disorders (rrED) significantly decreased from ICD-10 to ICD-11 due to a crossover to full-threshold disorders, especially anorexia nervosa (AN) or ARFID. Patients reclassified to ICD-11 ARFID were younger, had an earlier age of illness onset, more restrictive eating behaviors, and tended to have more somatic comorbidities compared to those reclassified to ICD-11 AN. Patients with rrED according to both ICD-10 and ICD-11 were younger, had an earlier age of illness onset, less shape concern, and more somatic comorbidities than patients who were reclassified from ICD-10 rrED to ICD-11 AN or ARFID. DISCUSSION: This study highlights the inclusive approach of ICD-11 criteria, paving the way for more targeted treatment, and ARFID's high clinical relevance. Future studies considering nonrestrictive feeding and eating disorders across the life span may allow further analyses on diagnostic crossover. PUBLIC SIGNIFICANCE: Changes in diagnostic criteria for restrictive eating disorders within the newly published ICD-11 led to an increase in full-threshold disorders, while the number of rrED was significantly lowered compared to ICD-10 criteria. The results thus highlight the diagnostic utility of ICD-11 criteria and may help providing adequate treatment to children and adolescents with rrED.

Normative data for macular and retinal nerve fibre layer thickness in healthy German children and adolescents using optical coherence tomography.

PURPOSE: To establish normative data for macular thickness, macular volume and peripapillary retinal nerve fibre layer (RNFL) thickness using Spectralis® spectral-domain optical coherence tomography (SD-OCT) in healthy German children and adolescents and investigate influencing factors. METHODS: The cross-sectional study included the right eye of 695 children with at least one complete retinal OCT scan. As part of the LIFE Child study, the children underwent an ophthalmological examination including axial length (AL), spherical equivalent (SE) and OCT measurements. Various questionnaires were answered by the children or their parents to identify media use or outdoor time. Multiple linear regression models were used to investigate the potential influencing factors. RESULTS: A total of 342 boys and 353 girls with an average age (SD) of 12.91 (3.29) years participated. The mean AL (SD) was 23.20 (0.86) mm. The mean macular thickness (SD) was 320.53 (12.29) µm and the mean RNFL thickness (SD) was 102.88 (8.79) µm. Statistical analysis revealed a significant correlation between average macular thickness and age (p < 0.001, ß = 0.77) as well as AL (p < 0.001, ß = -4.06). In addition, boys had thicker maculae (p < 0.001, ß = 5.36). The RNFL thickness showed no significant correlation with children's age (p > 0.05), but with AL (p = 0.002, ß = -2.15), birth weight (p = 0.02, ß = 0.003) and a gender-specific effect of the body mass index standard deviation score for male participants (p = 0.02, ß = 1.93). CONCLUSION: This study provides normative data and correlations between macular and RNFL thickness in healthy German children. Especially age, gender and AL must be taken into account when evaluating quantitative OCT measurements to classify them as normal.

Associations between Stressful Life Events and Increased Physical and Psychological Health Risks in Adolescents: A Longitudinal Study.

Stressful life events (SLEs) are understood as risk factors for mental and physical health problems, particularly in the vulnerable period of adolescence. Using a longitudinal approach, this study investigated associations between SLE and several negative health outcomes in adolescents. Moderating effects of sociodemographic factors were considered. We analyzed the data of a healthy adolescent sample from the LIFE Child study in Leipzig, Germany (n = 2024, aged 10-18 years). SLEs were measured by a questionnaire, addressing SLEs in the family and the social environment domain. Health-related quality of life (HrQoL), behavioral difficulties and BMI were compared before and after an SLE had occurred. Moderator effects of socioeconomic status (SES), age, and sex were investigated using linear regression models. All considered health parameters had, on average, deteriorated after the occurrence of an SLE in the social environment. Differences in HrQoL before and after an SLE were significantly stronger in girls. Higher SES functioned as a slight protective factor against decreased well-being after an SLE. The findings suggest that SLEs function as risk factors for mental and physical health disadvantages in adolescents. Prevention programs should seek to support adolescents in all age and SES groups affected by SLEs, with a specific focus on girls.

The relationship between myopia and near work, time outdoors and socioeconomic status in children and adolescents.

BACKGROUND: To investigate environmental and social risk factors for myopia in children and adolescents in Germany. METHODS: 1437 children aged between 3 and 18 inclusive were examined as part of the LIFE Child study based in Leipzig, Germany. Information about leisure time activities and social status was ascertained by parents and children in a questionnaire. Refractive status was attained by measuring noncycloplegic autorefraction. Myopia was defined as spherical equivalent (SE) ≤ - 0.75 D. Risk factors were identified using multiple logistic regression analysis. RESULTS: In multiple logistic regression analysis, myopia was significantly associated with less frequent outdoor activity ("once a week" vs. "twice a week or more": odds ratio (OR) 4.35, 95% confidence interval (CI) 1.89-9.98, p<0.01) and longer near work sessions (1-2 h vs. < 1 h: OR 1.83, CI 1.10-3.04, p=0.02; > 3 h vs. < 1 h: OR 3.71, CI 1.43-9.61, p<0.01) after adjustment for age, sex and socioeconomic status (SES). Duration of outdoor activity, near work frequency and SES showed no significant association with myopia (p > 0.05). Children with a lower SES were involved in longer periods of outdoor and near work activities but on fewer occasions over the course of the week, although this connection was not significant. CONCLUSION: Myopia is associated with environmental factors. The present findings suggest that daily exposure to sunlight and a restriction of long-duration near work activities might protect against pathological eye growth. Prevention strategies should be implemented for children at all ages.

Validation study on the child, adult, and parent version of the ARFID module 2.0 for the Eating Disorder Examination.

OBJECTIVE: This study presents a psychometric evaluation of the avoidant/restrictive food intake disorder (ARFID) module 2.0 for the Eating Disorder Examination (EDE), its child (ChEDE), and parent version. Within a pediatric sample seeking treatment for restrictive feeding or eating disorders and non-treatment-seeking controls, the module's interrater reliability, parent-child agreement, and its convergent, divergent, and discriminant validity were examined. METHOD: The child, adult, and/or parent version of the German ARFID module was administered to N = 176 children and adolescents (0-17 years) and their parents, as were the (Ch)EDE, well-established measures on food-avoidance behaviors, food variety, and body esteem, and objective anthropometric measures. RESULTS: Across all versions of the ARFID module, substantial to almost perfect interrater reliability was shown. Parent-child agreement for ARFID diagnosis was substantial. Based on medium-to-large associations between interview-assessed avoidant/restrictive food intake and questionnaire-assessed food-avoidance behaviors, food variety, and objective weight status, the module showed high convergent validity, especially for the child and parent version. Low associations of avoidant/restrictive food intake with weight and shape concern demonstrated divergent validity. Individuals with ARFID differed significantly from those with anorexia nervosa and individually matched controls in a range of clinical characteristics, indicating discriminant validity. DISCUSSION: This comprehensive validation supports the EDE ARFID module to be a valuable measure for the assessment and diagnosis of ARFID in 0-17-year-olds based on self- and parent-report. Validation of the ARFID module against other interview-based measures on ARFID and its evaluation in an adult sample are pending. PUBLIC SIGNIFICANCE: Based on good reliability and validity of the avoidant/restrictive food intake disorder (ARFID) module for the Eating Disorder Examination (EDE) in its child, adult, and parent version, the present study paves the way for the clinical and research use of the interview-based EDE ARFID module for assessing ARFID across childhood and adolescence.

Having siblings promotes a more healthy weight status-Whereas only children are at greater risk for higher BMI in later childhood.

BACKGROUND: Birth order and having at least one sibling are known to be associated with an increased risk for development of overweight. However, there are no studies assessing pre- and postnatal factors for developing overweight within families. Therefore, the present study aimed to analyse the association of the mother's weight gain during pregnancy, prepregnancy BMI, mother's age at birth, breastfeeding, age gap between siblings, and physical activity together with sibling-related characteristics on the development of overweight in children and adolescents. METHODS: Data were obtained from the longitudinal LIFE Child cohort. The study sample included n = 1932 children, stratified into first-born (n = 578), second-born (n = 608), third-or-later-born single-born siblings (n = 162), only children (n = 526), and twin children (n = 58). Children with chronic or syndromic diseases, born prematurely or from mothers with gestational diabetes were excluded. Data were adjusted for multiple children per family using mixed models. Pregnancy weight gain, prepregnancy BMI and mother's age were considered prenatal co-variates. Postnatal factors included the duration of breastfeeding and the children's physical activity level. RESULTS: Particularly until the onset of puberty, the BMI-SDS differed between single-born siblings, only children and twins, and increased with birth order. Compared to children with siblings, only children exhibited a strong increase in BMI-SDS starting at age nine. A higher age gap between siblings was associated with a higher BMI-SDS in second- and third-or-later-born children. Single-born siblings had the highest rate and duration of breastfeeding. Physical activity was highest in twins and third-or-later-born children and lowest in only children. In a multivariate model, being an only child showed a highly significant association with BMI-SDS. CONCLUSION: The present study demonstrated that siblings had a lower BMI-SDS than only children did. For single-born siblings, the association between birth order and increased BMI-SDS seemed to persist only up to 11 years of age.

Age-Dependent Reference Values for hs-Troponin T and NT-proBNP and Determining Factors in a Cohort of Healthy Children (The LIFE Child Study).

This study aimed to provide reliable pediatric reference values for N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitive Troponin T (hsTnT) obtained from a population of well children and investigate for associations with sex, pubertal status, body mass index (BMI), and serum lipid levels. We analyzed hsTnT and NT-proBNP values obtained from 4826 samples provided by 2522 children aged 0.25-18 years participating in a prospective longitudinal population-based cohort study, "LIFE child" in Leipzig, Germany (Poulain et al., Eur J Epidemiol 32:145-158, 2017). NT-proBNP values decreased throughout childhood from values over 400 ng/L at 3 months to 138 ng/L in females and 65 ng/L in males by 18 years of age. Values dropped rapidly with advancing pubertal stage. We found a strong association between lower NT-proBNP values and higher BMI or elevated serum lipids, the latter effect being more pronounced in males. For hsTnT levels, approximately half of the measurements were below the detection limit. However, 76% of those aged 3 months and 21% of those aged 6 months had values exceeding the adult cut-off limit. Females had slightly higher levels in the first 2 years of life but this was reversed during puberty. In males, there was an upward trend from pubertal stage 2 onward. We identified a positive association between hsTnT and BMI but a negative association with low-density lipoprotein (LDL) cholesterol and triglyceride levels in boys but not in girls. Based on a large number of healthy children, we have established reliable reference values for NT-proBNP and hsTnT for use in everyday clinical practice. We have also identified important associations between certain metabolic and cardiac markers.Clinical Trial Registration ClinicalTrial.gov (NCT02550236).

Substance use in childhood and adolescence and its associations with quality of life and behavioral strengths and difficulties.

BACKGROUND: Substance use in childhood and adolescence continues to be a current health concern. The aims of the present study were to identify trends in the use of alcohol, cigarettes, and cannabis in children and adolescents in the last 10 years and to assess associations between substance use and quality of life and behavioral strengths and difficulties. METHODS: Substance use was examined in 1829 9- to 18-year-old German children and adolescents participating in the LIFE Child cohort study between 2011 and 2020. Quality of life was investigated using the KIDSCREEN-27 questionnaire. The Strength and Difficulties Questionnaire was used to assess behavioral strengths and difficulties. Associations were assessed using linear regression analyses. All effects were adjusted for age, gender, and family socio-economic status. RESULTS: 38.44% of participants reported drinking alcohol at least sometimes. Smoking (6.23%) and the use of cannabis (3.94%) were less frequent. While we observed no significant changes in smoking between 2011 and 2021, the consumption of cannabis and the frequent consumption of alcohol has increased in this time period. Cigarette and cannabis use were associated with additional symptoms of hyperactivity/inattention and reduced prosocial behavior. For all three substances, usage was associated with more conduct problems. We also found significant associations between substance use and a lower quality of life in the areas of physical wellbeing, psychological wellbeing, parent relation and autonomy, and school environment. One noteworthy finding was that cigarette consumption and frequent alcohol use were associated with higher quality of life in terms of social support/peer group relations. Some significant interactions between substance use and child age indicated that associations between substance use and quality of life or behavioral difficulties were stronger in younger than in older children. CONCLUSIONS: The results show that quality of life and behavioral difficulties are associated with substance use and should be considered when developing or implementing preventive measures to counter substance use. Furthermore, the findings indicate that substance use can be accompanied by improved peer relations. Therefore, the influence of peers, especially of peers who use these substances, should not be underestimated.

Associations of media use and early childhood development: cross-sectional findings from the LIFE Child study.

BACKGROUND: Excessive media usage affects children's health. This study investigated associations between children's and mother's media use, parent-child interactions, and early-childhood development outcomes. METHODS: Two hundred and ninety-six healthy 2-5-year-old preschoolers (52.4% male, mean age = 3.5 years) and 224 mothers from the LIFE Child cohort study were analyzed. Screen times and parent-child interactions were assessed using standardized parental questionnaires. Developmental skills were investigated using the standardized development test ET 6-6-R. RESULTS: High screen times in children (>1 h/day) were significantly associated with lower percentile ranks in cognition (b = -10.96, p < 0.01), language (b = -12.88, p < 0.01), and social-emotional skills (b = -7.80, p = 0.05). High screen times in mothers (>5 h/day) were significantly associated with high media use by children (OR = 3.86, p < 0.01). Higher parent-child interaction scores were significantly associated with better body motor (b = 0.41, p = 0.05), cognition (b = 0.57, p < 0.01), language (b = 0.48, p = 0.02), and social-emotional outcomes (b = 0.80, p < 0.01) in children. CONCLUSIONS: Public health strategies should seek to educate caregivers as competent mediators for their children's media habits, with focus on the need for children to have frequent parent-child interactions. IMPACT: High media usage in children is related to poorer cognition, language, and social-emotional skills. More frequent parent-child interactions are associated with better body motor, cognition, language, and social-emotional skills in children. High level of media use in mothers is not directly related to children's development outcomes but is directly related to high media usage of children. Public health strategies should seek to raise media awareness and management in both parents and children.

Maternal depressive symptoms and stress during pregnancy as predictors of gestational age at birth and standardized body mass index from birth up to 2 years of age.

BACKGROUND: While depressive symptoms and stress during pregnancy are known to affect gestational age and weight at birth, evidence on their impact on child anthropometric development in the long term remains limited, showing inconsistent effects. Importantly, previous research indicated a substantially stronger impact of categorically rather than dimensionally assessed mental health problems on birth outcomes and child development. METHODS: The Patient Health Questionnaire was used to assess depressive symptoms and stress during the 2nd trimester of pregnancy dimensionally and categorically, with scores ≥10 indicating clinical significance. Gestational age at birth and BMI-SDS from birth up to 2 years of age were examined as dependent variables. Structural equation modeling was used to examine the prediction of birth outcomes and child anthropometry by mental health problems while controlling for multiple maternal and child characteristics in 322 mother-child dyads. RESULTS: Dimensionally assessed mental health problems did not significantly predict birth outcomes. While categorical depressive symptoms significantly predicted a higher child BMI-SDS, categorical stress significantly predicted a lower gestational age at birth. Neither categorical nor dimensional mental health problems significantly predicted child BMI-SDS at 6, 12, and 24 months postpartum. CONCLUSIONS: Depressive symptoms and stress during pregnancy seem to differentially affect birth outcomes, and only if clinically relevant. The results implicate the importance to timely treat pregnant women that are greatly affected by mental health problems to potentially reduce adverse birth outcomes.

Ocular biometry in children and adolescents from 4 to 17 years: a cross-sectional study in central Germany.

PURPOSE: To evaluate ocular biometry in a large paediatric population as a function of age and sex in children of European descent. METHODS: Children were examined as part of the LIFE Child Study (Leipzig Research Centre for Civilization Disease), a population-based study in Leipzig, Germany. Altogether, 1907 children, aged from 4 to 17 years, were examined with the Lenstar LS 900. Data from the right eye was analysed for axial length, central corneal thickness, flat and steep corneal radii, aqueous depth, lens thickness and vitreous depth. Wavefront-based autorefraction was employed for analysis. RESULTS: Axial length increased in girls from 21.6 mm (4 years) up to 23.4 mm (17 years); this increase (0.174 mm per year) was statistically significant up to age 14 (23.3 mm). Axial length increased in boys from 22.2 mm (4 years) up to 23.9 mm (17 years); this increase (0.178 mm per year) was statistically significant up to age 10 (23.3 mm). No change was observed for central corneal thickness (average: girls 550 µm; boys 554 µm). Corneal curvature in girls was somewhat flatter at age 4 (7.70 mm) compared to age 10 (7.78 mm), whereas it was constant in boys (7.89 mm). Aqueous depth at age 4 was 2.73 mm for girls and 2.86 mm for boys, with the same rate of increase per year (girls: 0.046 mm; boys: 0.047 mm) from age 4 to 10. At age 17, aqueous depth was 3.06 mm in girls and 3.20 mm in boys. Lens thickness was reduced from age 4 (3.75 mm) to age 10 (3.47 mm) in girls and from age 4 (3.73 mm) to age 10 (3.44 mm) in boys, with the same rate of decrease per year of 0.046 and 0.047 mm, respectively. At age 17, lens thickness was 3.52 mm in girls and 3.50 mm in boys. Vitreous depth at age 4 was 14.51 mm for girls and 15.08 mm for boys; with 0.156 mm (girls) or 0.140 mm (boys) increase per year until age 14 (girls: 16.08 mm; boys: 16.48 mm). At age 17, vitreous depth was 16.29 mm in girls and 16.62 mm in boys. CONCLUSIONS: Eye growth (axial length) in girls showed a lag of about four years compared to boys. Aqueous depth increase matches the lens thickness decrease from ages 4 to 10 years in girls and boys. Lens thickness minimum is reached at 11 years in girls and at 12 years in boys. All dimensions of the optical ocular components are closely correlated with axial length. These data may serve as normative values for the assessment of eye growth in central European children and will provide a basis for monitoring refractive error development.

Motor skills in relation to body-mass index, physical activity, TV-watching, and socioeconomic status in German four-to-17-year-old children.

BACKGROUND: The present study describes motor skills in a large sample of German children and adolescents and investigates associations with age, gender, body-mass index, physical activity, television time, and socioeconomic status. METHODS: 2,106 children (1076 boys, 1030 girls) aged 4 to 17 years performed five different motor tests for strength (pushups, standing long jump), coordination (backward balancing, jumping side-to-side) and flexibility (forward bend) within the framework of the LIFE Child study (Leipzig, Germany). Anthropometric parameters were assessed through standardized measurement. Data on physical activity, television time, and socioeconomic status were collected via questionnaires. Linear regression analyses were applied to assess relations. RESULTS: Strength and coordination performance were higher in older than in younger children. While boys showed a higher performance in strengths tests than girls, girls performed better in flexibility and coordination during precision tasks (backward balancing). In terms of coordination under time constraint (jumping side-to-side), both genders produced similar results. Lower body-mass index, higher physical activity, and higher socioeconomic status were significantly related to better motor skills. Longer television times were significantly associated with lower performance in long jump. CONCLUSIONS: The present findings are similar to data collected at the beginning of the century, indicating that motor skills have hardly changed in recent years. The findings furthermore suggest that children from lower social strata, children with higher body weight, and children who move little have a higher risk of developing insufficient motor skills and should therefore be given special support.

Atopic diseases in children and adolescents are associated with behavioural difficulties.

BACKGROUND: Atopic diseases and behavioural difficulties in children have both been on the rise in recent decades. This study seeks to assess associations between atopic diseases and behavioural difficulties, examining the differences considering child age and how behavioural difficulties were reported (via self-report or parent-report). METHODS: Data on behavioural difficulties, assessed through the Strengths and Difficulties Questionnaire (SDQ), and on atopic diseases, assessed through the participant's medical history, were available for 2701 study participants aged 3 to 18 years. Associations between atopic diseases and behavioural difficulties were evaluated using linear regression analyses. We split the study sample into two groups. I: 3-to 10-year-olds/parent-reported SDQ (n = 1764), II: 11- to 18-year-olds/parent-reported SDQ (n = 937) and self-reported SDQ (n = 915). All analyses were adjusted for age, gender, and socioeconomic status. RESULTS: In younger children, atopic dermatitis was strongly associated with higher total difficulties scores, more emotional problems and conduct problems, and more symptoms of hyperactivity/inattention. Parents reported higher total difficulties scores, more emotional problems, and more peer-relationship problems for adolescents with bronchial asthma and other allergies, whereas the adolescents themselves reported more peer relationship problems. CONCLUSION: In younger children, atopic dermatitis is associated with internalizing and externalizing problems. In adolescents, bronchial asthma and other allergies are associated with a greater level of internalizing problems only. The findings further suggest that parents of adolescents are more likely to perceive associations between atopic diseases and behavioural difficulties than the adolescents themselves.

Pediatric Reference Intervals for Thyrotropin, Free Triiodothyronine, and Free Thyroxine and the Relevance of Body Mass Index and Puberty in Measurement Interpretation.

Background: The present study aimed to establish age- and sex-specific reference intervals for serum concentrations of thyrotropin (TSH), free triiodothyronine (fT3), and free thyroxine (fT4) in healthy children and adolescents. Additionally, we investigated the association of TSH, fT3, and fT4 with putative influencing factors, such as sex, body mass index (BMI), and puberty. Methods: A total of 9404 blood serum samples from 3140 children and adolescents without thyroid affecting diseases were included in determining TSH, fT3, and fT4 levels and age- and sex-specific reference ranges. To investigate the association of TSH, fT3, and fT4 with age, sex, weight status, and the role of puberty-based changes, the hormone levels and BMI values were converted to standard deviation scores (SDS). Results: In general, TSH, fT3, and fT4 were found to be age- and sex-dependent. Puberty was accompanied by decreased TSH, decreased fT3 with a temporary peak in males, and a temporary nadir of fT4 in Tanner stage 3 for both sexes. BMI-SDS was positively associated with TSH-SDS (ß = 0.081, p < 0.001); the effect was more pronounced in overweight subjects (ß = 0.142, p < 0.01) and insignificantly negative in underweight subjects (ß = -0.047, p > 0.05). BMI-SDS was positively associated with fT3-SDS (ß = 0.066, p < 0.001) and negatively associated with fT4-SDS (ß = -0.135, p < 0.001), with the effect insignificantly less negative in overweight children (ß = -0.055, p > 0.05). Conclusions: Age- and sex-specific reference intervals are important for the interpretation of measurements of TSH, fT3, and fT4 in children and adolescents. Influencing factors such as BMI and puberty should be taken into consideration when using measurements of TSH and thyroid hormones in the diagnosis, treatment, and monitoring of thyroid diseases. Clinical Trial Registration number: NCT02550236.

Feasibility and repeatability of ocular biometry measured with Lenstar LS 900 in a large group of children and adolescents.

PURPOSE: To evaluate the feasibility and repeatability of Lenstar LS 900 biometry measurements in a paediatric population. METHODS: Children were examined as part of the LIFE Child Study (Leipzig Research Centre for Civilization Diseases), a population-based study in Leipzig, Germany. Altogether, 1917 children, aged from 3.5 to 17.5 years, were assessed with the Haag Streit Lenstar LS 900. Three consecutive measurements of the right eye were analysed for axial length, central corneal thickness, anterior chamber depth, aqueous depth, lens thickness and flat and steep corneal radii. The number of successful measurements and repeatability were evaluated for each parameter and three age bands (3.5 to 6.5 years, 6.5 to 10.5 years and 10.5 to 17.5 years). RESULTS: Best measurement feasibility was found for axial length and central corneal thickness (91% to 100%), followed by flat and steep corneal radii (86% to 100%), anterior chamber and aqueous depth (76% to 92%) and lens thickness (50% to 81%), with higher numbers for older children. Repeatability values (in mm) were: axial length 0.025 to 0.035; central corneal thickness 0.003 to 0.027; aqueous depth 0.024 to 0.058; anterior chamber 0.024 to 0.054; lens thickness 0.034 to 0.067. An overall trend showed better repeatability for older children, especially for central corneal thickness, aqueous depth and lens thickness. CONCLUSIONS: For ocular biometry in the paediatric population, axial length, central corneal thickness, flat and steep corneal radii can be measured very reliably even in children from 4 years old onward using the Lenstar LS 900. Lens thickness can be quantified in a limited number of younger children. Repeatability was high for all variables investigated. Repeatability improved with age, reaching adult values in the adolescent age band. Established repeatability limits can be applied in future studies as a quality parameter.