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Free access

Kaspar Sørensen and Anders Juul

Objective

Early pubertal timing is consistently associated with increased BMI percentile-for-age in pubertal girls, while data in boys are more ambiguous. However, higher BMI percentile-for-age may be a result of the earlier puberty per se rather than vice versa. The aim was to evaluate markers of adiposity in relation to pubertal timing and reproductive hormone levels in healthy pubertal boys and girls.

Study design

Population-based cross-sectional study (The Copenhagen Puberty Study). Eight-hundred and two healthy Caucasian children and adolescents (486 girls) aged 8.5–16.5 years participated. BMI and bioelectric impedance analyses (BIA) were used to estimate adiposity. Clinical pubertal markers (Tanner stages and testicular volume) were evaluated. LH, FSH, estradiol, testosterone, SHBG and IGF1 levels were determined by immunoassays.

Results

In all age groups, higher BMI (all 1 year age-groups, P≤0.041) was found with early compared with late maturation, despite similar BIA–estimated body fat percentage (BIA–BF%). Neither BMI nor BIA–BF% differed for a given stage of maturation. BMI percentile-for-age and prevalence of overweight/obesity were higher in the early compared with late matured pubertal children (all P≤0.038), despite similar BIA–BF%. Pubertal girls with BIA–BF >29% had significantly lower LH and FSH levels compared with normal-weight girls (P≤0.041).

Conclusions

Early maturational timing was not associated with higher adiposity for a given stage of puberty. Using BMI percentile-for-age overestimated the degree of adiposity in early pubertal compared with late pubertal children.

Free access

Katarina Sedej, Primož Kotnik, Magdalena Avbelj Stefanija, Urh Grošelj, Andreja Širca Čampa, Lara Lusa, Tadej Battelino, and Nataša Bratina

Background

Overweight/obesity in children is a worldwide public health problem. Together with hypercholesterolaemia they are associated with early atherosclerotic complications.

Objectives

In this study, we aimed to investigate the anthropometric characteristics and total cholesterol (TC) levels in a population of 5-year-old children, to determine trends in the prevalence of overweight/obesity and hypercholesterolaemia in 5-year-old children over a period of 8 years (2001–2009) and to assess the impact of modified national nutritional guidelines for kindergartens implemented in 2005.

Design

Cross-sectional studies of overweight/obesity prevalence in the years 2001, 2003–2005 and 2009, and hypercholesterolaemia in years 2001 and 2009, in 5-year-old children.

Subjects

Altogether, 12 832 (6308 girls/6524 boys) children were included.

Methods

Overweight/obesity was defined by IOTF criteria. Hypercholesterolaemia was defined by TC level >5 mmol/l. Multivariable logistic regression models were used.

Results

No correlation between BMI values and TC levels was found. Overweight and obesity prevalence were stabilised from 2001 to 2009 (odds ratio (OR) (95% CI): 1.13 (0.99–1.3) and 1.13 (0.89–1.42) respectively). Girls were more frequently overweight/obese than boys (OR (95% CI): 0.71 (0.65–0.79) and 0.75 (0.64–0.89) respectively). Prevalence of hypercholesterolaemia significantly decreased from 2001 to 2009 (OR (95% CI): 0.47 (0.41–0.55)). It was less frequent in boys than in girls (OR (95% CI): O.7 (0.61–0.8)).

Conclusions

This is the first study to describe a negative trend in the prevalence of hypercholesterolaemia in pre-pubertal children. In addition, the prevalence of overweight/obesity in these children has been stabilised. Nationwide changes in public health policies could have influenced these observations.

Open access

Anuradhaa Subramanian, Jan Idkowiak, Konstantinos A Toulis, Shakila Thangaratinam, Wiebke Arlt, and Krishnarajah Nirantharakumar

Context

The incidence of gestational diabetes mellitus (GDM) has been on the rise, driven by maternal obesity. In parallel, pubertal tempo has increased in the general population, driven by childhood obesity.

Objective

To evaluate the available evidence on pubertal timing of boys and girls born to mothers with GDM.

Data sources

We searched MEDLINE, EMBASE, CINAHL Plus, Cochrane library and grey literature for observational studies up to October 2019.

Study selection and extraction

Two reviewers independently selected studies, collected data and appraised the studies for risk of bias. Results were tabulated and narratively described as reported in the primary studies.

Results

Seven articles (six for girls and four for boys) were included. Study quality score was mostly moderate (ranging from 4 to 10 out of 11). In girls born to mothers with GDM, estimates suggest earlier timing of pubarche, thelarche and menarche although for each of these outcomes only one study each showed a statistically significant association. In boys, there was some association between maternal GDM and earlier pubarche, but inconsistency in the direction of shift of age at onset of genital and testicular development and first ejaculation. Only a single study analysed growth patterns in children of mothers with GDM, describing a 3-month advancement in the age of attainment of peak height velocity and a slight increase in pubertal tempo.

Conclusions

Pubertal timing may be influenced by the presence of maternal GDM, though current evidence is sparse and of limited quality. Prospective cohort studies should be conducted, ideally coupled with objective biochemical tests.

Free access

Juho Kärkinen, Päivi J Miettinen, Taneli Raivio, and Matti Hero

Objective:

To describe the etiology of severe short stature in the Helsinki University Hospital district covering a population of 1.2 million that is subject to frequent growth monitoring and screening rules during childhood.

Design:

Retrospective cohort study.

Methods:

We identified all subjects born 1990 or later with a height SD score <−3, after the age of 3 years, from the Helsinki University Hospital district growth database. A total of 785 subjects (376 females and 409 males) fulfilled our inclusion criteria; we reviewed their medical records and growth data and report their underlying diagnoses.

Results:

A pathological cause for short stature was diagnosed in 76% of the girls and 71% of the boys (P = NS). Syndromes were the most numerous pathological cause (n = 160; 20%), followed by organ disorders (n = 127; 16%), growth hormone deficiency (GHD, n = 94; 12%), SGA without catch-up growth (n = 73; 9%), and skeletal dysplasias (n = 57; 7%). Idiopathic short stature (ISS) was diagnosed in 210 (27%) subjects. The probability of growth-related pathology, particularly of a syndrome or skeletal dysplasia, increased with the shorter height SD score and the greater deviation from the target height. Sitting height to height SDS was increased in subjects with ISS, GHD, and SGA (all P < 0.01).

Conclusions:

Height <−3 SDS after 3 years of age usually results from a pathological cause and should be thoroughly investigated in specialized health care. The chance of finding a specific etiology increased with the severity of short stature, and the mismatch with target height.

Free access

Francesca Castiello and Carmen Freire

Background

Numerous modern non-persistent pesticides have demonstrated estrogenic/anti-androgenic activity and have been classified as endocrine-disrupting chemicals (EDCs). Processes involved in puberty development are vulnerable to EDCs, such as compounds that interfere with the metabolism or activity of sex steroids.

Objective

To conduct a systematic review of epidemiological studies on the relationship between early-life exposure to non-persistent pesticides and puberty timing and/or sexual maturation in girls and boys.

Methods

A systematic search was carried out using MEDLINE and SCOPUS databases, including original articles published up to November 2020.

Results

Thirteen studies were selected after excluding non-original and non-human studies. Exposure to different types of pesticides has been associated with altered puberty timing in girls and/or boys in eight studies. In utero exposure to atrazine has been related to earlier age of menarche in girls; exposure to organophosphate (OP) pesticides has been related to delayed sexual development in boys and girls; childhood pyrethroid exposure has been associated with pubertal delay in girls and pubertal advancement in boys; and prenatal/childhood exposure to multiple pesticides has been linked to earlier puberty onset in girls and pubertal delay in boys.

Conclusions

Most of the reviewed studies describe a relationship between pesticide exposure and changes in the age of puberty onset or sex hormone levels, although the quality of the evidence is generally low. Further well-designed longitudinal studies are warranted on specific classes of pesticides and on possible interactions between different types of compounds.

Free access

Aristeidis Giannakopoulos, Alexandra Efthymiadou, and Dionisios Chrysis

Objective

The diagnosis of growth hormone deficiency (GHD) in children is not always straightforward because insulin-like growth factor 1 (IGF-I) or GH stimulation tests may not be able to discriminate GHD from constitutional delay of growth and puberty (CDGP) or other causes of short stature.

Design

Boys and girls (n = 429, 0.7–16 years) who attended our department for short stature participated in this study. They were followed up for an average period of 9 years. At the end of follow-up after reaching the final height, a definitive diagnosis was assigned, and all the components of ternary complex (IGF-I, IGF-binding protein-3 (IGFBP-3), acid-labile subunit (ALS), and IGF-I/IGFBP-3 ratio) were evaluated as biomarkers for the respective diagnosis.

Results

All the components of the ternary complex were tightly correlated with each other and were positively related to age. IGF-I, IGFBP-3, ALS, and IGF-I/IGFBP-3 ratio differed significantly between GHD and normal groups. IGF-I and ALS levels were lower in GHD compared to children with familial short stature, while IGF-I and IGF-I/IGFBP-3 ratio was significantly lower in GHD compared to children with CDGP. IGF-I and IGF-I/IGFBP-3 receiver operating curve cutoff points were unable to discriminate between GHD and normal groups or between GHD and CDGP groups.

Conclusion

Despite the tight correlation among all the components of the ternary complex, each one shows a statistically significant diagnosis-dependent alteration. There is a superiority of IGF-I, ALS, and IGF-I/IGFBP-3 ratio in the distinction between GHD and CDGP or between GHD and normal groups but without usable discriminating power, making auxology as the primary criterion for establishing the diagnosis.

Free access

Selmen Wannes, Monique Elmaleh-Bergès, Dominique Simon, Delphine Zénaty, Laetitia Martinerie, Caroline Storey, Georges Gelwane, Anne Paulsen, Emmanuel Ecosse, Nicolas De Roux, Jean Claude Carel, and Juliane Léger

Objective

Non-idiopathic CPP is caused by acquired or congenital hypothalamic lesions visible on MRI or is associated with various complex genetic and/or syndromic disorders. This study investigated the different types and prevalence of non-isolated CPP phenotypes.

Design and Methods

This observational cohort study included all patients identified as having non-idiopathic CPP in the database of a single academic pediatric care center over a period of 11.5 years. Patients were classified on the basis of MRI findings for the CNS as having either hypothalamic lesions or complex syndromic phenotypes without structural lesions of the hypothalamus.

Results

In total, 63 consecutive children (42 girls and 21 boys) with non-isolated CPP were identified. Diverse diseases were detected, and the hypothalamic lesions visible on MRI (n = 28, 45% of cases) included hamartomas (n = 17; either isolated or with an associated syndromic phenotype), optic gliomas (n = 8; with or without neurofibromatosis type 1), malformations (n = 3) with interhypothalamic adhesions (n = 2; isolated or associated with syndromic CNS midline abnormalities, such as optic nerve hypoplasia, ectopic posterior pituitary) or arachnoid cysts (n = 1). The patients with non-structural hypothalamic lesions (n = 35, 55% of cases) had narcolepsy (n = 9), RASopathies (n = 4), encephalopathy or autism spectrum disorders with or without chromosomal abnormalities (n = 15) and other complex syndromic disorders (n = 7).

Conclusion

Our findings suggest that a large proportion (55%) of patients with non-isolated probable non-idiopathic CPP may have complex disorders without structural hypothalamic lesions on MRI. Future studies should explore the pathophysiological relevance of the mechanisms underlying CPP in these disorders.

Free access

Ying Sun, Jiao Fang, Yuhui Wan, Puyu Su, and Fangbiao Tao

Objective

Previous finding suggests that children growing up under chronic stress tend to experience earlier sexual maturity. The present study aims to examine polygenic risk by experience interaction in predicting pubertal timing, as well as provide insight regarding the relevance of two G × E paradigms.

Design and methods

Data were analyzed from a 3-year prospective puberty cohort in Anhui Province, China. Breast Tanner stage and testicular volume (TV) of 997 children were annually assessed. The polygenic risk score (PRS) was computed based on 17 SNPs for early pubertal timing. Hair cortisol concentrations (HCC) were assessed in the first 3 cm hair segment as a biological marker of chronic stress.

Results

Comparing with participants under moderate levels of stress as measured by HCC, the puberty-accelerating effects of chronic stress were only observed among girls with moderate (1.7 months earlier, P = 0.007) and low genetic susceptibility (2.2 months earlier, P < 0.001) and among boys with high genetic susceptibility (2.0 months earlier, P = 0.005). Polygenic differences (PRSs) in age at thelarche was most prominent in those with low levels of stress by HCC (9.06, 9.36 and 9.53 years for high, moderate and low PRS, respectively; F = 105.06, P < 0.0001), while polygenic differences in age at TV ≥4 mL was strongest in those under chronic stress (10.91, 11.06 and 11.17 years for high, moderate and low PRS, respectively; F = 100.48, P < 0.0001).

Conclusion

Chronic stress predicts earlier age at pubertal onset in a sex-specific and genetic background-dependent manner. The bioecological G × E model for girls and diathesis stress model for boys in pubertal timing warrants further investigation.

Restricted access

George W. Clayton

Abstract

Patterns of growth of 30 children with Congenital Adrenal Hyperplasia of the 21-hydroxylase type were studied from infancy to maturity. These children were compliant as to therapy. Intramuscular (I.M.) Cortisone (40mg/M2) given every three days resulted in growth failure after the first year of life. A marked increase in height velocity occurred when oral Cortisone (20-25mg/M2) was given at approximate] 3 years. Growth was relatively normal during childhood in both boys and girls but there was a marked increase in mean weight in both sexes.

Pubertal growth spurt occurred normally in males but was delayed in females. Weight decreased in both sexes at puberty but not to normal. Better methods of monitoring this condition should result in therapeutic regimes which allow normal growth patterns as well as normal mature height.

Free access

Tilman Rohrer, Eva Stierkorb, Sabine Heger, Beate Karges, Klemens Raile, K Otfried Schwab, Reinhard W Holl, and on behalf of the Diabetes-Patienten-Verlaufsdaten (DPV) Initiative

Abstract

Objective

To investigate the effect of type 1 diabetes on pubertal onset and development, and to identify factors potentially affecting puberty, including glycemic control, relative diabetes duration, body mass index standard delta score (BMI SDS), insulin dose, and intensity of insulin therapy.

Research design and methods

Initiated in 1990, the Diabetes-Patienten-Verlaufsdaten (DPV) is an ongoing, prospective longitudinal follow-up program to benchmark the quality of diabetes care provided to, predominantly, pediatric patients. Data collection for this non-interventional audit was carried out at 202 German diabetes treatment centers. Patient recruitment was done by referral, clinic/hospital ascertainment, or self-report. Data were analyzed for subcohorts of 1218–2409 boys and 579–2640 girls from a cohort of 24 385 pediatric type 1 diabetic patients. Selection was based on ethnicity and availability of data on Tanner stage 2, or higher, of genital and pubic hair development (boys) or breast and pubic hair development, and menarche (girls).

Results

Boys showed significant (P<0.05) delay (years) in mean ages at onset of genital development (12.0 (±0.9) years) and pubarche (12.2 (±0.4) years). In girls, mean ages at thelarche (11.4 (±0.5) years), pubarche (11.5 (±0.1) years), and menarche (13.2 (±0.5) years) were significantly delayed compared with the general population. Sexual maturity (Tanner stage 5) was not delayed in either sex. Elevated glycohemoglobin and decreased BMI SDS were associated with significantly delayed pubertal onset, whereas relative diabetes duration and insulin dose were not.

Conclusions

Pubertal onset, but not sexual maturity, is delayed in children with type 1 diabetes. Delay increases with higher glycohemoglobin and lower BMI SDS.