Obesity is associated with increased 11-oxyandrogen serum concentrations during puberty.

INTRODUCTION: While the influence of various factors on classical androgen synthesis in children and adolescents and its impact on puberty has been widely investigated, there appear to be gaps and contradictory findings regarding the association of overweight and obesity with the synthesis of adrenal-derived 11-oxygenated androgen (11-OA) serum levels. With this study, we aimed to examine how overweight and obesity affect 11-OA serum levels during puberty in a large cohort of children and adolescents. METHODS: Our cohort comprised 1,054 healthy children aged 6 to 19 years providing serum samples at a total of 1,734 visits. Liquid chromatography-tandem mass spectrometry was used to quantify 11-ketotestosterone (11-KT), 11-ketoandrostendione (11-KA4), 11-ß-hydroxytestosterone (11-OHT), 11-ß-hydroxyandrostendione (11-OHA4), testosterone, androstenedione, and DHEAS. In addition, we assessed BMI-SDSs; skinfold thicknesses; and Tanner stages. The significance level α was set to α=0.05. RESULTS: Increases in 11-KT, 11-KA4, 11-OHT, and 11-OHA4 levels were observed in boys and girls during puberty. 11-KT (ß=0.2, p<0.001), 11-KA4 (ß=0.16, p<0.001) and 11-OHA4 (ß=0.12, p=0.003) were positively correlated with BMI in boys age 13 and under. 11-KT (ß=0.1, p=0.047) was positively correlated with BMI in girls age 11 and under. 11-OHT was positively correlated with BMI independent of age (boys 13 and under: ß=0.17, p<0.001; over 13 years: ß=0.14, p=0.001; girls 11 and under: ß=0.17, p<0.001; over 11 years: ß=0.18, p<0.001). CONCLUSION: We found increasing 11-OA serum levels throughout all Tanner stages. 11-OAs were observed to be associated with BMI and skinfold thickness, suggesting that overweight and obesity may be associated with pubertal alterations in 11-OA serum levels.

Reference intervals and percentiles for soluble transferrin receptor and sTfR/log ferritin index in healthy children and adolescents.

OBJECTIVES: Soluble transferrin receptor (sTfR) is a marker of both erythropoiesis and iron status and is considered useful for detecting iron deficiency, especially in inflammatory conditions, but reference intervals covering the entire pediatric age spectrum are lacking. METHODS: We studied 1,064 (48.5 % female) healthy children of the entire pediatric age spectrum to determine reference values and percentiles for sTfR and the ratio of sTfR to log-ferritin (sTfR-F index) using a standard immunoturbidimetric assay. RESULTS: Soluble TfR levels were highly age-specific, with a peak in infancy and a decline in adulthood, whereas the sTfR-F index was a rather constant parameter. There were positive linear relationships for sTfR with hemoglobin (Hb) (p=0.008) and transferrin (females p<0.001; males p=0.003). A negative association was observed between sTfR and ferritin in females (p<0.0001) and for transferrin saturation and mean corpuscular volume (MCV) in both sexes (both p<0.0001). We found a positive relationship between sTfR and body height, body mass index (BMI) and inflammatory markers (CrP p<0.0001; WBC p=0.0172), while sTfR-F index was not affected by inflammation. CONCLUSIONS: Soluble TfR values appear to reflect the activity of infant erythropoiesis and to be modulated by inflammation and iron deficiency even in a healthy cohort.

Executive functions & metabolic control in phenylketonuria (PKU) and mild hyperphenylalaninemia (mHPA).

BACKGROUND: Due to newborn screening and early treatment, patients with phenylketonuria (PKU) and mild hyperphenylalaninemia (mHPA) develop largely normal, in terms of IQ testing and academic attainment. However, the impact of metabolic control in various stages of development on more complex cognitive abilities, i.e. executive functions (EF), is still unclear. METHODS: EFs were tested in 28 patients with PKU/mHPA, aged 8-17 years, identified by newborn screening and continuously treated. The relation to current (testing day & past 10 phenylalanine (Phe) values) and long-term metabolic control (age periods: childhood <6, 6-10, adolescence >10 years, lifetime Phe) was analyzed. RESULTS: EFs were in the lower normative range (IQR of T-values: 47.35-51.00). Patients reaction time was significantly slower than the population mean (divided attention/TAP: median 40, p < 0.01). Both, long-term and current metabolic control correlated with performance in EF tests: Higher current Phe impaired reaction times (Go/No-Go, r = -0.387; working memory, r = -0.425; p < 0.05) and performance in planning ability (ToL r = -0.465, p < 0.01). Higher long-term Phe values both in childhood and adolescence mainly affected attention (omissions/TAP r = -0.357 and - 0.490, respectively, both p < 0.05) as well as planning ability (ToL r = -0.422 and - 0.387, adolescence and lifetime, p < 0.05). CONCLUSION: Current and long-term metabolic control in PKU/mHPA, including the adolescent period, influence EFs, especially affecting reaction time and planning abilities. This should be taken into account in patient counselling.

Pediatric Syncope: Is the Diagnostic Guideline Implemented and Adhered to?

BACKGROUND: We sought to investigate adherence to the current pediatric syncope guideline in the emergency department and its impact on the frequency of missed or unnecessary diagnostic measures. For the first time, in 2014 updated guideline defines indispensable basic diagnostic measures and a consecutive algorithm for safe clinical decision making. PATIENTS AND METHOD: We analyzed retrospectively 314 pediatric patients, 166 were presented before and 148 after publication of this guideline update. RESULTS: After guideline publication, 54 patients (36.5%) were not treated in accordance with the guideline and 2 (0.63%) cases caused by epileptic seizures were initially misdiagnosed as reflex syncope. Among these 54 patients, 32 (59.3%) inpatient admissions were inappropriate, as well as 11 (20.4%) electroencephalographies, 4 (7.4%) sleep-deprivation EEGs, 2 (3.7%) magnetic resonance imaging, 5 (9.3%) urine diagnostics and 32 (59.3%) blood tests. In 21 cases (38.9%), the medical history was insufficient. ECG was missed in 42 patients (77.8%). There was no significant difference between the pre- and post-guideline groups concerning diagnostic work-up (p=0,12). DISCUSSION: This non-compliance with the guideline did not cause a large number of misdiagnosed epileptic seizures (1.4%) or adverse outcomes but led to waste of resources in healthcare system and undue burdens on patients and their families. CONCLUSION: In addition to establishment of clinical guidelines, the need for additional measures and strategies to promote their implementation seems obvious.

Drug-Drug Interactions Involving High-Alert Medications that Lead to Interaction-Associated Symptoms in Pediatric Intensive Care Patients: A Retrospective Study.

BACKGROUND: Children treated in a pediatric intensive care unit (PICU) often receive several drugs together, among them drugs defined as high-alert medications (HAMs). Those drugs carry a high risk of causing patient harm, for example, due to a higher potential for interactions. HAMs should therefore be administered with caution, especially in a PICU. OBJECTIVES: The objective of the current study was to identify drug-drug interactions involving HAMs that increase the risk of interaction-associated symptoms in pediatric intensive care. METHODS: In a retrospective study, we analyzed the electronic documentation of patients hospitalized for at least 48 h in a general PICU who received at least two different drugs within a 24-h interval. We assessed potential drug-drug interactions involving HAM on the basis of the two drug information databases UpToDate and drugs.com. Furthermore, we analyzed whether symptoms were observed after the administration of drug pairs that could lead to interaction-associated symptoms. For drug pairs involving HAM administered on at least 2% of patient days, and symptoms observed at least ten times after a respective drug pair, we calculated odds ratios, 95% confidence intervals, and p-values by using a univariate binary logistic regression. RESULTS: Among 315 analyzed patients, 81.3% (256/315) received drugs defined as high-alert medication for pediatric patients. Those high-alert medications were involved in 20,150 potential drug-drug interactions. In 14.0% (2830/20,150) of these, one or more symptoms were observed that could be a possible consequence of the interaction, resulting in 3203 observed symptoms affecting 56.3% (144/256) of patients receiving high-alert medication. The odds ratios for symptoms observed after a drug-drug interaction were increased for eight specific symptoms (each p ≤ 0.05), especially hemodynamic alterations and disturbances of electrolyte and fluid balance. The odds ratio was highest for decreased blood pressure observed after the administration of the drug pair fentanyl and furosemide (OR 5.06; 95% confidence interval 3.5-7.4; p < 0.001). Increased odds ratios for specific symptoms observed after drug-drug interactions resulted from eight combinations composed of eight different drugs: digoxin, fentanyl, midazolam, phenobarbital, potassium salts and vancomycin (high-alert medications), and the diuretics furosemide and hydrochlorothiazide (non-high-alert medications). The resulting drug pairs were: potassium salts-furosemide, fentanyl-furosemide, vancomycin-furosemide, digoxin-furosemide, digoxin-hydrochlorothiazide, fentanyl-phenobarbital, potassium salts-hydrochlorothiazide, and midazolam-hydrochlorothiazide. CONCLUSIONS: In a cohort of PICU patients, this study identified eight specific drug pairs involving high-alert medications that may increase the risk of interaction-associated symptoms, mainly hemodynamic alterations and electrolyte/fluid balance disturbances. If the administration of those drug pairs is unavoidable, patients should be closely monitored.

Bilirubin Levels in Infancy and Their Associations with Body Weight, Levels of Iron-Related Parameters and Steroid Hormone Levels.

It is assumed that bilirubin is hormonally regulated and influences weight development by preventing weight gain. However, studies in healthy infants are limited. The present study established reference values for bilirubin and investigated whether bilirubin levels are significantly associated with body weight, levels of ferritin and transferrin as well as steroid hormone levels in a study population of three- and six-month-old healthy infants. Data from a total of 411 study visits from the LIFE Child study (Leipzig, Germany) were analyzed. Associations were examined using linear regression analyses. Besides laboratory parameters, anthropometric data were gathered. We found statistically significant associations between body weight and bilirubin levels. In girls, we observed additional associations between bilirubin levels and both ferritin and transferrin concentrations at three months of age. At six months, steroid hormone levels were significantly associated with concentrations of total and indirect bilirubin, with effects differing by sex. Our study thus confirms associations already reported from animal studies and studies in adult populations. Furthermore, we showed that these associations already exist in the first year of life, are influenced by sex and age and, further, depend on the bilirubin type. Our results provide reference values for bilirubin and assist, therefore, in interpreting bilirubin levels in infancy.

Associations between media use at bedtime and sleep: a cross-sectional analysis on differences between girls and boys.

Objectives: This study investigated associations between the use of electronic media and sleep in children and young adolescents, with a specific focus on the moderation of associations by sex and age. Methods: Between 2021 and 2022, 453 10- to 14-year-old children participating in the LIFE Child cohort study (Germany) reported on their use of electronic media (daily screen time, use at bedtime, device ownership) and on their sleep difficulties (Sleep Self Report). Associations between media use and sleep as well as interactions with age and sex were assessed using linear regression analyses. Results: The analyses revealed significant associations between the use of media at bedtime and bedtime problems (in girls only), sleep behavior problems (in girls only), and daytime sleepiness (in girls and boys). Daily screen time, in contrast, was associated with none of the sleep difficulties. The number of media devices owned by the child was only associated with bedtime problems in girls, and this association lost statistical significance once media use at bedtime was included as further predictor. Conclusion: The findings underline the potentially sleep-disturbing role of electronic media at bedtime. Furthermore, they suggest that this effect is more pronounced in girls than in boys.

Modifiable factors influencing attention performance in healthy children: insights from a comprehensive school nutrition study.

BACKGROUND: There is inconclusive evidence for the effects of various leisure activities on attention performance in children. The literature reports inconsistent associations between activities such as physical activities or media use. To date, no study has thoroughly examined the various factors influencing attentional performance in a larger cohort of healthy children. This study aims to close this research gap. METHODS: From 2018 to 2019, the Leipzig School Nutrition Study collected data from 1215 children and their families. The children report their dietary behavior (using CoCu- Questionnaire), especially their participation in school lunch and their breakfast habits, through a paper questionnaire. Furthermore, attention performance was assessed using a validated test (FAIR-2) at school. Data on physical activity, media consumption, family eating habits and socio-economic status (SES) were collected from parents using questionnaires. Associations between attention and influencing factors were estimated using hierarchical linear regression. Analyses were adjusted for age, SES, and school type. RESULTS: Attending upper secondary schools (ßadj= 23.6, p < 0.001) and having a higher SES (ß= 1.28, p < 0.001) was associated with higher attention performance. Children doing leisure-time sports (ßadj= 4.18, p = 0.046) or reading books for at least one hour/weekday showed better attention performance (ßadj= 3.8, p = 0.040). Attention performance was also better in children having no electronic devices in the bedroom (ßadj= 13.0, p = 0.005) and in children whose parents limited their children's Internet access (ßadj= 5.2, p = 0.012). We did not find any association between nutritional habits and attention performance. CONCLUSIONS: We found that fostering modifiable habits such as reading and physical activity could enhance attention performance. These findings have substantial implications for the development of prevention and intervention programs that aim to improve attention in schoolchildren. It is important to note, however, that social status as a hardly modifiable factor also impacts attention performance. Therefore, interventions should address personal habits in a systemic approach considering the child's social status. TRIAL REGISTRATION: The study is retrospectively registered with the German Clinical Trials Register (DRKS00017317, registration: 05-29-2019).

Creatine kinase serum levels in children revisited: New reference intervals from a large cohort of healthy children and adolescents.

BACKGROUND: Creatine Kinase (CK) has become increasingly important in pediatrics as a commonly used laboratory screening parameter for neuromuscular diseases. Recent research suggests that hyperCKemia in children is not always associated with pathology and can occur due to several reasons. Little is known of various clinical factors that may influence CK throughout child development. OBJECTIVE: This study aimed to establish reliable age- and sex-specific reference ranges for serum CK levels in healthy infants, children, and adolescents. In addition, the effect of puberty, oral contraceptive (OC) use as well as steroid hormones on CK was examined. MATERIALS AND METHODS: The data was collected from subjects of the longitudinal population-based "LIFE Child"-cohort between 2011 and 2016 in Leipzig, Germany. 5238 blood samples of 2707 healthy children, aged between 0.14 months and 18 years, were analyzed. RESULTS: Serum CK levels raised during the first year of life, peaking shortly after age one (P50girls = 2.7 µkat/L, P50boys = 2.90 µkat/L). There was a pronounced difference in the 97.5th percentile between boys and girls during adolescence with its maximum at age 18 (P97.5girls = 5.74 µkat/L, P97.5boys= 14.48 µkat/L). Also, mean CK serum levels were significantly higher in boys (bboys = 0.29, pboys < 0.001). Intake of oral contraceptives (OC), extreme underweight, underweight and obesity revealed a significant inverse correlation with CK serum levels. CONCLUSION: Age, sex, OC intake and weight status affect serum CK levels, particularly during infancy and puberty. We recommend the use of age- and sex-specific reference values for CK serum levels to assess the clinical relevance of measurements.

Still an Unsolved Question: The Place of Cranial Magnetic Resonance Imaging in Acute Acquired Concomitant Esotropia.

PURPOSE: The aim of this study was to collect further data to estimate the risk of relevant intracranial pathology and thereby better assess the need for cranial imaging in children with acute acquired comitant esotropia (AACE). To date, there is still not enough literature on this topic to enable a consensus on the diagnostic algorithm. METHODS: We analyzed data from patients with convergent strabismus who received cranial imaging via magnetic resonance imaging (MRI). Twenty-one patients received a cranial MRI for the diagnostic evaluation of AACE. The age range was from 2 to 12 years, and the mean age at the time of diagnosis was 5.5 years. Of these patients, only one exhibited insignificant MRI findings, with no therapeutic consequences. CONCLUSIONS: Our data add further evidence that AACE without neurological findings or other ophthalmologic anomalies might not be an indication for cranial MRI as a diagnostic screening tool.

Associations between gestational weight gain and weight development of the offspring: Differences depending on maternal pre-pregnancy BMI.

PURPOSE: Obesity rates are rising, and the gestational weight gain (GWG) of most women does not comply with current guidelines. This study assesses the association of pre-pregnancy BMI (ppBMI) and GWG with the child's weight development and investigates whether associations with GWG differ depending on ppBMI. METHODS: Data were obtained from the cohort study LIFE Child (Germany), comprising 691 mother-child pairs. Children's weight was followed until age five. Associations between maternal ppBMI, GWG, and children's weight were evaluated using regression analyses. RESULTS: The association between GWG and birth weight (BW) was significantly positive in normal and underweight (n/u) women (ßGWG = 0.05, p < 0.01, 95% confidence interval (CI) 0.03-0.07), but not in women with overweight or obesity (o/o) (ßGWG = 0.0002, p = 0.99, 95% CI -0.03 to 0.03). The risk of giving birth to an infant who was large for gestational age (LGA) increased with rising GWG in n/u women (OR = 1.6, p < 0.01, 95% CI 1.23-2.25). Women with o/o were at increased risk for a LGA baby regardless of GWG (OR = 3, p < 0.01, 95% CI 1.34-6.97). This trend persisted in the child's weight development during the first 5 years of life. CONCLUSION: Women with o/o might increase their offspring's risk for higher weight at birth and in early childhood. In n/u women, GWG might be the more influential factor. Women should strive for normal weight before conception and should be more attentive to GWG.

Drowning and Nonfatal Drowning in Children and Adolescents: A Subsequent Retrospective Data Analysis.

Fatal and nonfatal drowning are among the leading causes of death and lifelong severe neurological impairment among children and adolescents. This study aimed to complement research from Leipzig 1994-2008 to seek trends within risk factors, treatments, and outcomes throughout the last decade. We retrospectively investigated data of 47 inpatients aged 0-18 admitted to Leipzig University Department of Pediatrics who matched ICD-10 code T75.1 from 2008 to 2020 and compared them to a preceding study at the same institution. We also examined the prognostic value of parameters regarding the patients' outcomes. There were three median incidents per annum. The median age was 2.75 years; 76% of incidents happened in males. An accumulation was seen during the summer months and weekends. Most drowning incidents occurred in private ponds or pools (48.9%). Thirty-nine children were discharged without resulting morbidity, four showed neurological impairment, and three died. Risk factors concerning age, sex, and incident characteristics were confirmed. Special supervision needs still apply to 1-3-year-old male children or children with pre-existing health conditions around private pools and ponds. Hospitalization duration shortened, and morbidity and lethality decreased since the previous study. There was structural improvement in primary care and medical documentation. Parameters suggesting good outcomes include a submersion time < 5 min, GCS > 3 points, spontaneous movement upon admission, remaining pupillary light response, the absence of cardiovascular arrest, body temperature ≥ 32 °C, pH > 7, blood glucose < 15 mmol/L, lactate < 14 mmol/L, base excess ≥ -15 mmol/L, and the absence of ARDS. Clear legislation can contribute to improved private home water safety. Further studies should include a broad in- and outpatient spectrum and standardized incident documentation presupposing Utstein-style reporting. Regular reinvestigation of consistent geographical regions facilitates process evaluations of drowning epidemiology and therapy evolution.

Pediatric reference intervals for serum folate and cobalamin based on a European population without exposure to folic acid fortification.

The aim of the present study was to define pediatric reference intervals for serum cobalamin and folate utilizing data generated from a population not exposed to food fortified with folic acid. Folate and cobalamin results analyzed by electrochemiluminescence immunoassay (Roche Cobas) were obtained from 2375 children (2 months to 17.99 years of age). The serum samples were collected between 2011 and 2015 as part of the LIFE (Leipzig Research Centre for Civilization Diseases) Child cohort study in Germany, where folic acid fortification of food is not mandated. These results were used to generate age- and gender-specific reference intervals presented as non-parametric 2.5 and 97.5 percentiles. Because of a subsequent restandardisation of the Roche folate assay in 2016, folate values were recalculated accordingly for adaptation to results obtained using the present calibration. In both genders, folate concentrations decreased continuously with age, whereas cobalamin concentrations peaked at five years of age and then declined. Teenage females had higher concentrations of cobalamin in the age group 12-17.99 years.

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.

Pten knockout in mouse preosteoblasts leads to changes in bone turnover and strength.

Bone development and remodeling are controlled by the phosphoinositide-3-kinase (Pi3k) signaling pathway. We investigated the effects of downregulation of phosphatase and tensin homolog (Pten), a negative regulator of Pi3k signaling, in a mouse model of Pten deficiency in preosteoblasts. We aimed to identify mechanisms that are involved in the regulation of bone turnover and are linked to bone disorders. Femora, tibiae, and bone marrow stromal cells (BMSCs) isolated from mice with a conditional deletion of Pten (Pten cKO) in Osterix/Sp7-expressing osteoprogenitor cells were compared to Cre-negative controls. Bone phenotyping was performed by µCT measurements, bone histomorphometry, quantification of bone turnover markers CTX and procollagen type 1 N propeptide (P1NP), and three-point bending test. Proliferation of BMSCs was measured by counting nuclei and Ki-67-stained cells. In vitro, osteogenic differentiation capacity was determined by ALP staining, as well as by detecting gene expression of osteogenic markers. BMSCs from Pten cKO mice were functionally different from control BMSCs. Osteogenic markers were increased in BMSCs derived from Pten cKO mice, while Pten protein expression was lower and Akt phosphorylation was increased. We detected a higher trabecular bone volume and an altered cortical bone morphology in Pten cKO bones with a progressive decrease in bone and tissue mineral density. Pten cKO bones displayed fewer osteoclasts and more osteoblasts (P = .00095) per trabecular bone surface and a higher trabecular bone formation rate. Biomechanical analysis revealed a significantly higher bone strength (P = .00012 for males) and elasticity of Pten cKO femora. On the cellular level, both proliferation and osteogenic differentiation capacity of Pten cKO BMSCs were significantly increased compared to controls. Our findings suggest that Pten knockout in osteoprogenitor cells increases bone stability and elasticity by increasing trabecular bone mass and leads to increased proliferation and osteogenic differentiation of BMSCs.

Lipoprotein(a) serum concentrations in children in relation to body mass index, age and sex.

BACKGROUND: Lipoprotein(a) (Lp(a)) is an inherited risk factor for atherosclerotic cardiovascular disease (ASCVD). Limited data exist on Lp(a) values in children. We aimed to evaluate whether Lp(a) concentrations in youth are influenced by BMI. METHODS: 756 blood samples of 248 children with obesity and 264 matched healthy children aged 5 and 18 years, enrolled in the population-based LIFE Child (German civilization diseases cohort) study, were analyzed. Repeat measurements were available in 154 children (1-4 follow ups, ~1 year apart). RESULTS: The median Lp(a) concentration in the total cohort (n = 512) at first visit was 9.7 mg/dL (IQR 4.0-28.3). Lp(a) concentrations between 30-50 mg/dL were observed in 11.5%, while 12.5% exhibited Lp(a) ≧50 mg/dL. There was no association of Lp(a) with body mass index (BMI) (ß = 0.004, P = 0.49). Lp(a) levels did not correlate with age or sex, while Lp(a) was associated positively with low-density lipoprotein cholesterol (ß = 0.05, P < 0.0001). The Lp(a) risk category remained stable in 94% of all children in repeated measurements. CONCLUSIONS: The data showed no association of Lp(a) levels in children with BMI, age or sex. Measurement of Lp(a) in youth may be useful to identify children at increased lifetime risk for ASCVD. IMPACT: In youth, Lp(a) levels are not affected by age, sex and BMI. Lp(a) risk categories remain stable over time in repeated measurements in children. Measurement of Lp(a) in children may be useful as an additional factor to identify children at increased lifetime risk for ASCVD and for reverse family screening.

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.

Associations between sleep problems and emotional/behavioural difficulties in healthy children and adolescents.

OBJECTIVE: This study aimed to (1) characterise sleep disturbances and emotional/behavioural difficulties among healthy German children and adolescents aged 3 to 13 years, (2) examine the association between parent-reported sleep problems and emotional/behavioural difficulties, (3) point out possible relations between specific kinds of sleep disturbances and different behavioural difficulties. METHODS: Data were collected between 2011 and 2015 within the LIFE Child study in Germany. The sample included 1101 3- to 13-year-old children and adolescents. Information on sleep disturbances-assessed via the Children's Sleep Habits Questionnaire (CSHQ), emotional/behavioural difficulties-assessed via the Strengths and Difficulties Questionnaire (SDQ), and socioeconomic status was provided by participants' parents. Multiple regressions were applied to analyse the associations between general and specific sleep disturbances (independent variables) and emotional/behavioural difficulties (dependent variables). RESULTS: The total CSHQ score was positively associated with the total SDQ score and all SDQ subscales (emotional problems, conduct problems, hyperactivity/inattention, peer relationship problems). Most of the CSHQ subscales were related to SDQ subscale scores, except for a few non-significant relations with hyperactivity/inattention and conduct problems. The CSHQ total score, daytime sleepiness, sleep duration and parasomnias showed the strongest associations with the SDQ total score. CONCLUSION: This study confirms an association between children's and adolescents' sleep habits and psychological health. We were able to demonstrate the association between sleep problems and emotional/behavioural difficulties in a large sample of healthy participants. In particular, we observed a significant relation between parasomnias and hyperactive/inattentive behaviour as well as a significant association between emotional problems and sleep problems, especially daytime sleepiness, sleep anxiety and parasomnias.

Relation between socioeconomic status and maternal serum lipids to infant lipid concentrations and anthropometry in the first year of life.

PURPOSE: The physical health and development of an individual are influenced by multiple parameters and shaped by internal and external factors during pregnancy. However, it is unclear whether there is an association between maternal lipid concentrations in the third trimester of pregnancy and infant serum lipids as well as anthropometric growth, and whether these factors are influenced by the socioeconomic status (SES) of the mothers. METHODS: Between 2011 and 2021, 982 mother-child pairs were recruited in the LIFE-Child study. To investigate the influence of prenatal factors, pregnant women at the 24th and 36th week of gestation as well as children at the age of 3, 6 and 12 months were examined and serum lipids determined. Socioeconomic status (SES) was assessed using the validated Winkler Index. RESULTS: A higher maternal BMI was associated with a significantly lower Winkler score and a higher infant weight, height, head circumference and BMI from birth up to the 4th-5th week of life. In addition, the Winkler Index correlates with maternal HDL cholesterol and ApoA1 levels. There was no relation between the delivery mode and the maternal BMI or SES. For the maternal HDL cholesterol concentration in the third trimester, an inverse relation to children's height, weight, head circumference and BMI up to the first year of life as well as the chest and abdominal circumference to an age of 3 months was found. Children born to mothers with dyslipidemia in pregnancy tended to have a worse lipid profile than those born to normolipidemic mothers. CONCLUSION: Serum lipid concentrations and anthropometric parameters of children in the first year of life are affected by multiple factors like maternal BMI, lipid levels and SES.