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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.

Restricted 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

Bonnie Auyeung, Simon Baron-Cohen, Emma Chapman, Rebecca Knickmeyer, Kevin Taylor, and Gerald Hackett

This study examines foetal testosterone (fT) levels (measured in amniotic fluid) as a candidate biological factor, influencing sex differences in systemizing. Systemizing is a cognitive process, defined as the drive to analyze or construct systems. A recent model of psychological sex differences suggests that this is a major dimension in which the sexes differ, with males being more drawn to systemize than females. Participants included 204 children (93 female), age 6–9 years, taking part in a long-term study on the effects of fT. The systemizing quotient – children’s version was administered to these mothers to answer on behalf of their child. Males (mean = 27.79 ± 7.64) scored significantly higher than females (mean = 22.59 ± 7.53), confirming that boys systemize to a greater extent than girls. Stepwise regression analysis revealed that fT was the only significant predictor of systemizing preference when the sexes were examined together. Sex was not included in the final regression model, suggesting that fT levels play a greater role than the child’s sex in terms of differences in systemizing preference. This study suggests that the levels of fT are a biological factor influencing cognitive sex differences and lends support to the empathizing–systemizing theory of sex differences.

Free access

Jean-Claude Carel, Joëlle Blumberg, Christine Seymour, Catherine Adamsbaum, and Najiba Lahlou

Group-author : for the Triptorelin 3-month CPP Study Group

Objective: Depot GnRH agonists are commonly used in the treatment of central precocious puberty (CPP). The triptorelin 11.25 mg 3-month depot, currently used in adult indications, had not previously been evaluated in CPP.

Design: This was a multicenter, open-label, 12 month trial conducted in 64 CPP children (54 girls and 10 boys), treated quarterly.

Methods: Children with a clinical onset of pubertal development before the age of 8 years (girls) or 9 years (boys), pubertal response of LH to GnRH ≥7 IU/l, advanced bone age >1 year, enlarged uterus (≥36 mm) and testosterone level ≥0.5 ng/ml (boys), were included. Suppression of gonadotropic activation, as determined from serum LH, FSH, estradiol or testosterone, and pubertal signs were assessed at Months 3, 6 and 12.

Results: GnRH-stimulated peak LH ≤3 IU/l, the main efficacy criterion, was met in 53 out of 62 (85%), 60 out of 62 (97%) and 56 out of 59 (95%) of the children at Months 3, 6 and 12 respectively. Serum FSH and sex steroids were also significantly reduced, while pubertal development regressed in most patients. Mean residual triptorelin levels were stable from Month 3 through to Month 12. The triptorelin 3-month depot was well tolerated. Severe injection pain was experienced in only one instance. Five girls experienced mild-to-moderate or severe (one girl) withdrawal bleeding.

Conclusions: The triptorelin 3-month depot efficiently suppresses the pituitary–gonadal axis and pubertal development in children with CPP. This formulation allows a 3-fold reduction, over the once-a-month depot, in the number of i.m. injections required each year.

Free access

N Benhadi, W M Wiersinga, J B Reitsma, T G M Vrijkotte, and G J Bonsel

Background

To examine the relationship between maternal TSH and free thyroxine (FT4) concentrations in early pregnancy and the risk of miscarriage, fetal or neonatal death.

Method

Cohort study of 2497 Dutch women. TSH, FT4, and thyroid peroxidase antibodies concentrations were determined at first booking. Child loss was operationalized as miscarriage, fetal or neonatal death. Women with overt thyroid dysfunction were excluded.

Results

Twenty-seven cases of child loss were observed. The mean TSH and FT4 level in the women with child loss was 1.48 mU/l and 9.82 pmol/l compared with 1.11 mU/l and 9.58 pmol/l in women without child loss. The incidence of child loss increased by 60% (OR=1.60 (95% confidence interval (CI): 1.04–2.47)) for every doubling in TSH concentration. This association remained after adjustment for smoking, age, parity, diabetes mellitus, hypertension, previous preterm deliveries, and previous preterm stillbirth/miscarriage (adjusted odds ratio=1.80 (95% CI: 1.07–3.03)). This was not true for FT4 concentrations (OR=1.41 (95% CI: 0.21–9.40); P=0.724).

Conclusion

In a cohort of pregnant women without overt thyroid dysfunction, the risk of child loss increased with higher levels of maternal TSH. Maternal FT4 concentrations and child loss were not associated.

Free access

C Evans, NJ Jordan, G Owens, D Bradley, M Ludgate, and R John

OBJECTIVE: We describe an infant with surprisingly severe neonatal hypothyroidism due to transplacental passage of thyrotrophin receptor (TSH-R)-blocking antibodies (TBAb). DESIGN AND METHODS: TBAb were detected using a cell line which stably expresses the human TSH-R and a cAMP-responsive luciferase reporter by their ability to inhibit TSH-stimulated luciferase expression. Potent TBAb were detected in maternal serum and initially in the infant's serum but, in the latter, TBAb decreased over time to within the reference range by 3-4 months of age, illustrating the transient nature of this condition. RESULTS: The thyroid function of this child did not return to normal on withdrawal of thyroxine therapy at 16 months of age when he developed transient compensated hypothyroidism. CONCLUSIONS: We propose that the presence of potent TBAb in utero and in the first weeks of life may have implications for the development of a normally sized thyroid gland. We have demonstrated the presence of TBAb in the mother's milk and, as far as we are aware, this is the first such report. However, the TBAb in the milk probably did not contribute significantly to hypothyroidism in the child, given the reducing antibody titre in his circulation.

Free access

S Bargagna, D Dinetti, A Pinchera, M Marcheschi, L Montanelli, S Presciuttini, and L Chiovato

OBJECTIVE: Evaluation of school attainments in children with congenital hypothyroidism (CH) detected by neonatal screening and treated early in life. PATIENTS AND METHODS: Text comprehension, mathematics, reading, writing and verbal and spatial memory, as indices of school learning, were evaluated in nineteen 5- to 10-year-old children with CH attending nursery or elementary school. l-Thyroxine substitution (starting dose 8-10 microg/kg body weight per day) was initiated at a mean age of 30+/-10 days of life. The control group included 298 unaffected children matched with the CH children for age and school grade. Thirty per cent of controls were classmates of CH children. Intelligence quotients (IQ), language performances and motor development were evaluated in CH children at age 5 years, and were related to their school attainments. School performances of CH children were also compared with their neonatal serum thyroxine (T4) concentration, and with the social-cultural level of the family. RESULTS: Four out of 19 (21%) children with CH, 3 in the nursery and 1 in the elementary school, displayed a generalized learning disorder. Symbol copy, geometric copy, phrase repetition, dictation writing and spontaneous writing were particularly defective in nursery school CH children, while orthographic error recognition was defective in elementary school CH children. School learning disorders in CH children were significantly correlated with a borderline-low IQ, poor language performances and a low social-cultural level of the family, but not with motor skills or neonatal T4 concentration. CONCLUSION: School attainments of early treated CH children were within the normal range in most affected cases. However, about 20% of CH children, most of them attending nursery school, showed a generalized learning disorder. Low IQ scores and poor language performances at age 5 years were associated with defective learning, mainly in CH children living in a poor social-cultural environment. In this subset of CH children, prompt initiation of speech and psychomotor rehabilitation therapy is recommended in order to prevent subsequent school learning disorders.

Free access

S Bellone, F Prodam, S Savastio, D Avanzo, A Pagani, L Trovato, G E Walker, G Genoni, and G Bona

Context

Ghrelin is a peptide with multiple functions that circulates in acylated (AG) and unacylated (UAG) forms. However, the role of ghrelin in neonates (NN) remains to be clarified.

Objective

The aim of this study was to determine ghrelin concentrations of the two forms in NN to clarify their biological roles. As such, ghrelin levels at birth were compared with those in later life.

Setting and design

Tertiary Care Center. In this cross-sectional study, we evaluated AG, UAG, AG/UAG ratio, and insulin levels in venous cord blood from NN and in fasted normal weight (NW) and obese (OB) children, both prepubertal and pubertal.

Subjects

We studied 82 NN, 82 NW, and 58 OB children.

Results

AG levels were lower in NN than in NW and OB children (P<0.0001), more specifically the prepubertal NW and OB children (P<0.0001). UAG levels were higher in NN than in NW and OB children (P<0.0001). Therefore, the AG/UAG ratio was lower in NN than in NW and OB children (P<0.0001). NN showed insulin levels similar to NW and lower than OB children (P<0.0001). At birth UAG was positively correlated with AG (Pearson: 0.425; P<0.0001) and negatively with insulin (−0.253; P<0.02). In NW and OB, UAG and AG were positively correlated to each other and negatively correlated with insulin and body mass index (−0.566; P<0.0001).

Conclusions

NN compared with children, showed higher UAG and lower AG levels. The AG/UAG ratio showed a very different profile in NN, being lower than in NW and OB children, thus suggesting a different metabolic function for the two forms in NN. Further studies are needed to clarify the exact role of the different ghrelin forms in NN.

Free access

Nicoletta Bisacchi, Milva Orquidea Bal, Laura Nardi, Ilaria Bettocchi, Graziana D'Addabbo, Veronica Conti, Sara Monti, Franco D'Alberton, Alessandro Cicognani, and Alessandra Cassio

Objective

To compare the psychological adjustment and behaviour of congenital hypothyroidism (CH) children and their parents with a control group.

Study design

A cross-sectional study was carried out with 84 CH subjects diagnosed by neonatal screening (range 2.7–18.6 years), subdivided into four age groups: group 1 (2–5 years); group 2 (6–10 years); group 3 (11–13 years); and group 4 (14–18 years) and was compared with an age-matched control group. Patients were assessed using two questionnaires: Child Behaviour Checklist for parents and Youth Self-Report for children over 11 years of age.

Results

In groups 1, 3 and 4, total score (TS), internalising score (IS=problems within the self) and externalising score (ES=conflicts with other people) as reported by parents were not significantly different in CH patients and in controls. In group 2, parents of CH children showed values of TS (P<0.05), IS (P<0.05), ES (P<0.05) and scores on other scales significantly higher than controls. In self-reports of groups 3 and 4, the behavioural scales were not significantly different in CH patients and in controls.

Conclusions

Paediatricians should be informed about the increased risk of the development of behavioural problems at primary school age in CH patients. At this age special attention should be paid to parental worries and anxiety. However, it can be reassuring for the patients and parents to know that the problems may be related to CH, and that they may spontaneously disappear.

Free access

D Zenaty, Y Aigrain, M Peuchmaur, P Philippe-Chomette, C Baumann, F Cornelis, J P Hugot, D Chevenne, V Barbu, P J Guillausseau, M Schlumberger, J C Carel, J P Travagli, and J Léger

Context

Early prophylactic thyroidectomy in patients with multiple endocrine neoplasia (MEN) type 2 offers the best chance for a normal life expectancy.

Objective

To analyze the results of thyroidectomy performed during the first year of life in six patients with MEN 2A (codon 634) or MEN 2B (codon 918) syndrome.

Design and setting

A university hospital-based prospective study from 2001 to 2008.

Subjects and methods

Six family members affected either by MEN 2A (n=3) or MEN 2B (n=3) syndrome were identified through neonatal genetic screening.

Results

Total thyroidectomy was performed at a median age of 0.8 year in the six patients, with central lymph node dissection in five. Bilateral millimetric medullary thyroid carcinoma (MTC) was found in all patients, with a unilateral lymph node micrometastasis in two of the three MEN 2B patients. Before thyroidectomy, MEN 2B patients had much higher basal serum calcitonin levels than those with MEN 2A and controls. After thyroidectomy, with a median follow-up of 3.3 years, the six patients had no evidence of persistent MTC.

Conclusion

Bilateral millimetric MTC may be present during the first year of life in these patients, with lymph node metastases also occurring in MEN 2B patients. These results support a total thyroidectomy at the age of about one year in MEN 2A (codon 634) children with an abnormal serum calcitonin level, and a total thyroidectomy with central neck dissection within the first weeks of life in MEN 2B patients.