Associations between exposure to perfluoroalkyl substances and body fat evaluated by DXA and MRI in 109 adolescent boys.

BACKGROUND: Exposure to perfluoroalkyl substances (PFASs) has been associated with changes in body mass index and adiposity, but evidence is inconsistent as study design, population age, follow-up periods and exposure levels vary between studies. We investigated associations between PFAS exposure and body fat in a cross-sectional study of healthy boys. METHODS: In 109 boys (10-14 years old), magnetic resonance imaging and dual-energy X-ray absorptiometry were performed to evaluate abdominal, visceral fat, total body, android, gynoid, android/gynoid ratio, and total fat percentage standard deviation score. Serum was analysed for perfluorooctanoic acid, perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid, perfluorononanoic acid, and perfluorodecanoic acid using liquid chromatography and triple quadrupole mass spectrometry. Data were analysed by multivariate linear regression. RESULTS: Serum concentrations of PFASs were low. Generally, no clear associations between PFAS exposure and body fat measures were found; however, PFOS was negatively associated with abdominal fat (ß = -0.18, P = 0.046), android fat (ß = -0.34, P = 0.022), android/gynoid ratio (ß = -0.21, P = 0.004), as well as total body fat (ß = -0.21, P = 0.079) when adjusting for Tanner stage. CONCLUSIONS: Overall, we found no consistent associations between PFAS exposure and body fat. This could be due to our cross-sectional study design. Furthermore, we assessed PFAS exposure in adolescence and not in utero, which is considered a more vulnerable time window of exposure.

Prenatal pesticide exposure associated with glycated haemoglobin and markers of metabolic dysfunction in adolescents.

BACKGROUND: Pesticide exposure has been associated with increased risk of diabetes mellitus in adults, but potential effects of prenatal exposure on glucose regulation have not been investigated. The aim of this study was to investigate if maternal occupational pesticide exposure in pregnancy was associated with glycated haemoglobin A1c (HbA1c) in adolescents and whether an association was modified by sex and paraoxonase-1 (PON1) Q192R polymorphism. METHODS: A prospective cohort study of children whose mothers were either occupationally exposed or unexposed to pesticides in early pregnancy. At age 10-to-16 years, the children (n = 168) underwent clinical examinations including pubertal stage assessment (accepted by 141 children) and blood sampling. PON1 Q192R genotype was available for 139 children and 103 mothers. The main outcome measure was HbA1c but other relevant biomarkers were also included. RESULTS: Prenatal pesticide exposure was associated with a 5.0% (95% confidence interval: 1.8; 8.2) higher HbA1c compared to unexposed children after adjustment for confounders. After stratification, the association remained significant for girls (6.2% (1.6; 11.1)) and if the child or the mother had the PON1 192R-allele (6.1% (1.6; 10.8) and 7.1% (2.0; 12.6), respectively). Besides, an exposure-related increase was seen for the leptin-to-adiponectin ratio, for plasminogen activator inhibitor type-1 in girls, and for interleukin-6 in children whose mothers had the R-allele. CONCLUSION: Prenatal pesticide exposure was associated with higher HbA1c and changes in related biomarkers in adolescents. Our results suggest an adverse effect on glucose homeostasis and support previous findings from this cohort of an exposure-associated metabolic risk profile with higher susceptibility related to female sex and the PON1 192R-allele.

Anthropometry, DXA, and leptin reflect subcutaneous but not visceral abdominal adipose tissue on MRI in 197 healthy adolescents.

BackgroundAbdominal fat distribution is associated with the development of cardio-metabolic disease independently of body mass index (BMI). We assessed anthropometry, serum adipokines, and DXA as markers of abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) using magnetic resonance imaging (MRI).MethodsWe performed a cross-sectional study that included 197 healthy adolescents (114 boys) aged 10-15 years nested within a longitudinal population-based cohort. Clinical examination, blood sampling, DXA, and abdominal MRI were performed. SAT% and VAT% were adjusted to total abdominal volume.ResultsGirls had a higher SAT% than did boys in early and late puberty (16 vs. 13%, P<0.01 and 20 vs. 15%, P=0.001, respectively), whereas VAT% was comparable (7% in both genders, independently of puberty). DXA android fat% (standard deviation score (SDS)), suprailiac skinfold thickness (SDS), leptin, BMI (SDS), waist-to-height ratio (WHtR), and waist circumference (SDS) correlated strongly with SAT% (descending order: r=0.90-0.55, all P<0.001) but weakly with VAT% (r=0.49-0.06). Suprailiac skinfold was the best anthropometric marker of SAT% (girls: R2=48.6%, boys: R2=65%, P<0.001) and VAT% in boys (R2=16.4%, P<0.001). WHtR was the best marker of VAT% in girls (R2=7.6%, P=0.007).ConclusionsHealthy girls have a higher SAT% than do boys, whereas VAT% is comparable, independently of puberty. Anthropometry and circulating leptin are valid markers of SAT%, but not of VAT%.

Glandular breast tissue volume by magnetic resonance imaging in 100 healthy peripubertal girls: evaluation of clinical Tanner staging.

BACKGROUND: Appearance of glandular breast tissue may be difficult to distinguish from fat tissue by palpation, especially in obese girls. To our knowledge, validation of the clinical assessment of pubertal breast stages by magnetic resonance imaging (MRI) has never been performed. Our objective was to report normative data of glandular breast tissue volume and validate the clinical evaluation of pubertal breast staging by MRI of breast tissue and to evaluate circulating reproductive hormone levels and estrogen-dependent transabdominal ultrasound (TAUS) parameters as markers of glandular breast tissue. METHODS: Glandular breast tissue volume quantified by MRI and breast stage evaluation was performed in 100 healthy peripubertal girls. Circulating levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), inhibin B, and estradiol were measured by immunoassays. Ovarian volume, uterine volume, and endometrial thickness were assessed by TAUS. RESULTS: Glandular breast tissue volume was positively associated with Tanner stages (r = 0.858, P < 0.001). The sensitivity and specificity of breast palpation to detect presence of glandular breast tissue using MRI as gold standard were 96 and 95%, respectively. The best parameters to distinguish prepubertal girls from girls with breast development were: LH (area under the curve (AUC) by receiver operating characteristic analysis = 0.871), inhibin B (AUC = 0.847) and estradiol (AUC = 0.830). CONCLUSION: Clinical palpation reliably detects the presence of glandular breast tissue.

Determination of adrenal volume by MRI in healthy children: associations with age, body size, pubertal stage and serum levels of adrenal androgens.

BACKGROUND: Adrenal disorders such as congenital adrenal hyperplasia result in abnormal adrenal size and morphology, but little is known about the clinical value of magnetic resonance imaging (MRI) in determining adrenal volume. OBJECTIVE: To evaluate the potential usefulness of MR methodology, to estimate adrenal size in healthy children and to evaluate determinants of adrenal volume such as age, gender, body size, pubic hair stage and serum levels of adrenal androgens. DESIGN: Two hundred and thirty-five healthy children (116 girls and 119 boys) (age range 10.0-14.8 years) were examined by MRI. Clinical examinations (anthropometry and pubertal staging) were performed, and five androgen metabolites were measured in blood samples by liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: It was possible to determine adrenal volume in 115/235 children using MRI. The adrenals were not measurable in 51% of children due to breathing and moving artefacts. The median volume of the right adrenal gland was 0.46 ml in girls and 0.46 ml in boys. The median volume of the left adrenal gland was 0.34 ml in girls and 0.40 ml in boys. Adrenal size was positively associated with body surface area (estimate B = 0.34 ml/year, P = 0.03), age (estimate B = 0.05 ml/year, P = 0.021) and pubic hair stage (estimate B = 0.05 ml/stage, P = 0.075). No associations between adrenal size and serum levels of adrenal androgens were observed. CONCLUSION: It was possible to determine adrenal volume by MRI in only 50% of healthy children aged 10-15 years. Adrenal volume increased with age and Tanner stage of pubic hair. Future studies will unravel whether adrenal MRI is useful when evaluating children with adrenal diseases.

The 2014 Danish references from birth to 20 years for height, weight and body mass index.

AIM: To construct new Danish growth charts for 0- to 20-year-olds and to compare them with Danish references from 1982 and with World Health Organization (WHO) standards for children aged 0-5 years from 2006, by applying similar inclusion and exclusion criteria. METHODS: Anthropometric data from three contemporary Danish population-based studies were combined. References for height were based on healthy Caucasian children born at term. A total of 12,671 height measurements (8055 in boys and 4616 in girls) were included. Reference charts were developed using the generalised additive models for location, scale and shape. RESULTS: From prepubertal ages, a secular increase in height was observed for both genders. The differences were most pronounced in puberty, and final heights were increased by 1.4 cm in boys and 2.9 cm in girls compared to 1982 references. In boys, but not girls an upward shift in body mass index (BMI) above median levels was found. Reference curves for height were superimposable with standard curves based on the selective WHO criteria. Danish children were longer/taller and heavier and they had larger head circumferences than those reported in the recent multiethnic WHO standards. CONCLUSION: We recommend national implementation of these contemporary 2014 Danish references for anthropometric measurements.

[Basic and advanced treatment of children and adults with epilepsy].

This review finds that, in children and adults with epilepsy, there are several treatment options. Multiple antiseizure medications are available and in case of drug-resistant epilepsy, a non-pharmacological approach is recommended, including epilepsy surgery, vagus nerve stimulation, or ketogenic diet treatment. The aim of the treatment is to avoid further seizures, but also to avoid negative cognitive, psychological, and social consequences of epilepsy.

[Significantly increased incidence of functional tics among children and adolescents].

During 2020, an increase of functional tics in children and adolescents has been observed. In this review, we present phenotypes, differential diagnosis and treatment for functional tics. We discuss potential contributing causes, like the COVID-19 pandemic and the focus on tics on social media. Functional tics are more complex than tics seen in Tourette syndrome and develop more suddenly in relation to stressors mainly in teenage girls. Psychosocial issues and comorbidities must be addressed and treated by a multidisciplinary team through psychoeducation and if necessary, cognitive-behavioural therapy.

Pubarche and Gonadarche Onset and Progression Are Differently Associated With Birth Weight and Infancy Growth Patterns.

CONTEXT: Controversy exists regarding associations between early-life growth patterns and timing of puberty. OBJECTIVE: This work aims to investigate associations between birth anthropometry, early growth patterns, and onset/progression of pubertal milestones in boys and girls. METHODS: Among children examined at birth (1997-2003) and at age 36 months in a mother-child cohort, pubertal Tanner stages (B1-5, PH1-5, G1-5) and testicular volume were examined by trained physicians at 1 to 5 follow-up examinations during childhood and adolescence (672 girls and 846 boys, 2006-2013).With parametric survival models we analyzed associations between birth weight, changes in SD scores (SDS) from birth to 36 months (ΔSDS 0-36 > 0.67 SD defining catch-up growth), and age at pubertal onset/attainment of late pubertal stages/menarche. RESULTS: A 1-kg higher birth weight was associated with earlier onset of B2+ (thelarche): -3.9 months (CI, -6.7 to -1.1 months), G2+ (gonadarche): -2.7 months (-5.3 to -0.1 months), Tvol3+ (testis size > 3 mL): -2.8 months (CI, -4.9 to -0.7 months), but with later G4+ and PH4+ in boys, and a slower progression from B2 to menarche (5.3 months [CI, 1.2 to 9.4 months]) in girls. Catch-up growth was associated with earlier PH2+ (pubarche) in girls (-4.1 months [CI, -7.6 to -0.6 months]), earlier PH2+ in boys (-3.4 months [CI, -6.6 to -0.2 months]), faster progression from B2 to menarche in girls (-9.1 months [CI, 14.6 to 3.5 months]), and earlier G4+ and PH4+ in boys. CONCLUSION: Associations between birthweight and infancy catch-up growth differed for gonadarche and pubarche, and for early and late pubertal markers, with similar patterns in both sexes.

Pubertal Onset in Boys and Girls Is Influenced by Pubertal Timing of Both Parents.

CONTEXT: Epidemiological evidence on maternal and paternal heritability of the wide normal variation within pubertal timing is sparse. OBJECTIVE: We aimed to estimate the impact of parental pubertal timing on the onset of puberty in boys and girls. DESIGN: Annual pubertal examinations of healthy children in a longitudinal cohort study. Information on parental timing of puberty (earlier, comparable to, or later compared to peers) and menarche age was retrieved from questionnaires. PARTICIPANTS: A total of 672 girls and 846 boys. MAIN OUTCOME MEASURES: Age at onset of pubic hair (PH2+), breasts (B2+), and menarche in girls; and PH2+, genital stage (G2+), and testis >3 mL with orchidometer (Tvol3+) in boys. RESULTS: In boys, pubertal onset was significantly associated with pubertal timing of both parents. PH2+ and Tvol3+ were earlier: -11.8 months (95% confidence interval, -16.8, -6.8)/-8.9 (-12.8, -4.9), and -9.5 (-13.9, -5.1)/-7.1 (-10.4, -3.7) if the father/mother, respectively, had early pubertal development compared to late. In girls, menarche was significantly associated with both parents' pubertal timing: -10.5 months (-15.9, -5.1)/-10.1 (-14.3, -6.0) if father/mother had early pubertal development compared to late. For the onset of PH2+ and B2+ in girls, estimates were -7.0 months (-12.6, -1.4) and -4.1 (-10.6, +2.4)/-6.7 (-11.0, -2.5), and -6.7 (-11.0, -2.0) for fathers/mothers, respectively. Maternal age of menarche was significantly associated with the onset of all pubertal milestones except PH2+ in girls. CONCLUSIONS: Maternal as well as paternal pubertal timing was a strong determinant of age at pubertal onset in both girls and boys. Age at breast and pubic hair development in girls, which has declined most during recent years, seemed to be least dependent on heritability.

Validity of self-assessment of pubertal maturation.

BACKGROUND AND OBJECTIVES: Studies of adolescents often use self-assessment of pubertal maturation, the reliability of which has shown conflicting results. We aimed to examine the reliability of child and parent assessments of healthy boys and girls. METHODS: A total of 898 children (418 girls, 480 boys, age 7.4-14.9 years) and 1173 parents (550 daughters, 623 sons, age 5.6-14.7 years) assessed onset of puberty or development of breasts, genitals, and pubic hair according to Tanner stages by use of a questionnaire and drawings. Physicians' assessments were blinded and set as the gold standard. Percentage agreement, κ, and Kendall's correlation were used to analyze the agreement rates. RESULTS: Breast stage was assessed correctly by 44.9% of the girls (κ = 0.28, r = 0.74, P < .001) and genital stage by 54.7% of the boys (κ = 0.33, r = 0.61, P < .001). For pubic hair stage 66.8% of girls (κ = 0.55, r = 0.80, P < .001) and 66.1% of boys (κ = 0.46, r = 0.70, P < .001) made correct assessments. Of the parents, 86.2% correctly assessed onset of puberty in girls (κ = 0.70, r = 0.71, P < .001) and 68.4% in boys (κ = 0.30, r = 0.37, P < .001). Children who underestimated were younger and children who overestimated older than their peers who made correct assessments. Girls and their parents tended to underestimate, whereas boys overestimated their pubertal stage. CONCLUSIONS: Pubertal assessment by the child or the parents is not a reliable measure of exact pubertal staging and should be augmented by a physical examination. However, for large epidemiologic studies self-assessment can be sufficiently accurate for a simple distinction between prepuberty and puberty.

Uterine volume and endometrial thickness in healthy girls evaluated by ultrasound (3-dimensional) and magnetic resonance imaging.

OBJECTIVE: To report normative data on uterine volume and endometrial thickness in girls, according to pubertal stages; to evaluate factors that affect uterine volume; and to compare transabdominal ultrasound (TAUS) and magnetic resonance imaging (MRI). DESIGN: Cross-sectional study of a nested cohort of girls participating in The Copenhagen Mother-Child Cohort. SETTING: General community. PATIENT(S): One hundred twenty-one healthy girls, aged 9.8-14.7 years. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Clinical examination, including pubertal breast stage (Tanner classification: B1-B5). Uterine volume: ellipsoid TAUS (n = 112) and 3-dimensional TAUS (n = 111); ellipsoid MRI (n = 61). Endometrial thickness: TAUS (n = 110) and MRI (n = 60). RESULT(S): Uterine volume and endometrial thickness were positively correlated with pubertal stages; e.g., ellipsoid TAUS: r = 0.753, and endometrium TAUS: 0.648. In multiple regression analyses, uterine volume was associated with the number of large follicles (TAUS >5 mm) (Beta 0.270); estradiol (E2) (Beta 0.504); and height (Beta 0.341). Volumes from ellipsoid vs. 3-dimensional TAUS were strongly correlated (r = 0.931), as were TAUS and MRI: ellipsoid volume (r = 0.891) and endometrial thickness (r = 0.540). Uterine volume was larger in TAUS compared with MRI; mean difference across the measured range: 7.7 (5.2-10.2) cm(3). Agreement was best for small uteri. CONCLUSION(S): Uterine volume and endometrial thickness increased as puberty progressed. Circulating E2 from large follicles was the main contributor to uterine and endometrial growth. The TAUS and MRI assessments of uterus and endometrium were strongly correlated.

Circulating AMH reflects ovarian morphology by magnetic resonance imaging and 3D ultrasound in 121 healthy girls.

CONTEXT: In adult women, Anti-Müllerian hormone (AMH) is produced by small growing follicles, and circulating levels of AMH reflect the number of antral follicles as well as primordial follicles. Whether AMH reflects follicle numbers in healthy girls remains to be elucidated. OBJECTIVE: This study aimed to evaluate whether serum levels of AMH reflects ovarian morphology in healthy girls. DESIGN AND SETTING: This was a population-based cohort study involving the general community. PARTICIPANTS: Included in the study were 121 healthy girls 9.8-14.7 years of age. MAIN OUTCOME MEASURES: Clinical examination, including pubertal breast stage (Tanner's classification B1-5), ovarian volume, as well as the number and size of antral follicles were assessed by two independent modalities: magnetic resonance imaging (MRI), Ellipsoid volume, follicles ≥2 mm; and Transabdominal ultrasound, Ellipsoid and 3D volume, follicles ≥1 mm. Circulating levels of AMH, inhibin B, estradiol, FSH, and LH were assessed by immunoassays; T and androstenedione were assessed by liquid chromatography-tandem mass spectrometry. RESULTS: AMH reflected the number of small (MRI 2-3 mm) and medium (4-6 mm) follicles (Pearson's Rho [r] = 0.531 and r = 0.512, P < .001) but not large follicles (≥7 mm) (r = 0.109, P = .323). In multiple regression analysis, small and medium follicles (MRI ≤ 6 mm) remained the main contributors to circulating AMH (ß, 0.501; P < .001) whereas the correlation between AMH and estradiol was negative (ß, -0.318; P = .005). In early puberty (B1-B3), the number of AMH-producing follicles (2-6 mm) correlated positively with pubertal stages (r = 0.453, P = .001), whereas AMH levels were unaffected (-0.183, P = .118). CONCLUSIONS: Similarly to adult women, small and medium antral follicles (≤6 mm) were the main contributors to circulating levels of AMH in girls.

Pubertal onset in girls is strongly influenced by genetic variation affecting FSH action.

Age at pubertal onset varies substantially in healthy girls. Although genetic factors are responsible for more than half of the phenotypic variation, only a small part has been attributed to specific genetic polymorphisms identified so far. Follicle-stimulating hormone (FSH) stimulates ovarian follicle maturation and estradiol synthesis which is responsible for breast development. We assessed the effect of three polymorphisms influencing FSH action on age at breast deveopment in a population-based cohort of 964 healthy girls. Girls homozygous for FSHR -29AA (reduced FSH receptor expression) entered puberty 7.4 (2.5-12.4) months later than carriers of the common variants FSHR -29GG+GA, p = 0.003. To our knowledge, this is the strongest genetic effect on age at pubertal onset in girls published to date.

Ovarian morphology and function during growth hormone therapy of short girls born small for gestational age.

OBJECTIVE: To study the effect of growth hormone (GH) treatment on ovarian and uterine morphology and function in short, prepubertal small-for-gestational-age (SGA) girls. DESIGN: A multinational, randomized controlled trial on safety and efficacy of GH therapy in short, prepubertal children born SGA. SETTING: Not applicable. PATIENT(S): A subgroup of 18 Danish girls born SGA included in North European SGA Study (NESGAS). INTERVENTION(S): One year of GH treatment (67 µg/kg/day) followed by 2 years of randomized GH treatment (67 µg/kg/day, 35 µg/kg/day, or IGF-I titrated). MAIN OUTCOME MEASURE(S): Data on anthropometrics, reproductive hormones, and ultrasonographic examination of the internal genitalia were collected during 36 months of GH treatment. RESULT(S): Uterine and ovarian volume increased significantly during 3 years of treatment (64% and 110%, respectively) but remained low within normal reference ranges. Ovarian follicles became visible in 58% after 1 year compared with 28% before GH therapy. Anti-Müllerian hormone increased significantly during the 3 years of GH therapy but remained within the normal range. Precocious puberty was observed in one girl; another girl developed multicystic ovaries. CONCLUSION(S): GH treatment was associated with statistically significant growth of the internal genitalia, but remained within the normal range. As altered pubertal development and ovarian morphology were found in 2 of 18 girls, monitoring of puberty and ovarian function during GH therapy in SGA girls is prudent. Altogether, the findings are reassuring. However, long-term effects of GH treatment on adult reproductive function remain unknown. CLINICAL TRIAL REGISTRATION NUMBER: EudraCT 2005-001507-19.

The physiology and timing of male puberty.

PURPOSE OF REVIEW: To describe available markers of male puberty, discuss associations between adiposity and pubertal timing and to review recent evidence of a possible secular trend in male pubertal timing. RECENT FINDINGS: An expert panel reviewing existing American pubertal data from boys in 2005 could not confirm a secular trend in male pubertal timing. National Health and Nutrition Examination Survey III findings have been confirmed by the National Institute of Child Health and Human Development study reporting a mean age of 10.4 years for Caucasian boys entering Tanner stage G2. Furthermore, the Copenhagen Puberty Study reported a 3 months decline in pubertal onset during a 15-year period (from 11.92 years in 1991 to 11.66 years in 2008).A negative association between obesity and early puberty was found in the National Institute of Child Health and Human Development study, in contrast to the positive association found in a Danish study. Other studies have not been able to document an association between prepubertal BMI and age at pubertal onset. SUMMARY: Evaluation of Tanner stage and especially assessment of testicular volume should both be used in epidemiological studies. We speculate that the association between fat mass and pubertal timing may be nonlinear and recent studies may indicate a small decline in age at pubertal onset in boys.

[Tubercular meningitis with severe hyponatraemia caused by cerebral salt wasting]. / Tuberkuløs meningitis med svær hyponatriæmi på grund af cerebralt salttab.

We describe two children, who were admitted with severe hyponatraemia and dehydration. In both children the hyponatraemia was due to cerebral salt wasting caused by tubercular meningitis. Differential diagnosis and pathophysiology is discussed. It is important to discriminate between cerebral salt wasting and inappropriate secretion of antidiuretic hormone since the therapy required is completely different in the two conditions.