Relationship between adherence to growth hormone therapy and growth.

Adherence to growth hormone (GH) therapy in children is variable and remains a problem which can significantly affect the response to GH treatment and future health and also have economic consequences. The response to GH treatment is not predictable at the start of treatment and depends on several factors, the main one being the diagnosis. Knowing the factors associated with poor adherence before treatment initiation can improve the response to treatment. © 2022 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.

[Prevalence of overweight preschool-age children: medical examination data of schoolchildren in southwestern France]. / Prévalence du surpoids chez le jeune enfant : analyse des données des bilans de santé à 3-4ans en Haute-Garonne.

OBJECTIVE: To analyze anthropometric data in a sample of 3- to 4-year-old children examined by Mother and Infant Welfare in preschools in the Haute-Garonne area of France. PATIENTS AND METHODS: Two consecutive school years (2007-2008 and 2008-2009) were analyzed. The samples studied included 5470 children the first year (mean age ± standard deviation : 3.9±0.4 years) and 4088 children the second year (4.0±0.4 years). Prevalence of overweight (defined according to International Obesity Task Force references) and its association with various factors (sex, age, and school location) were studied. RESULTS: Prevalence of overweight (including obesity) was 8.4% for the 2 years, with a prevalence of obesity of 1.8% in 2007-2008 and of 1.6% in 2008-2009. Overweight was significantly more frequent in girls than in boys (10.2% vs. 6.8% in 2007-2008 and 9.7% vs. 7.2% in 2008-2009) and in schools located in Priority Education Zones (ZEP) compared to schools in non-ZEP schools (17.9% vs. 7.1% in 2007-2008 and 15.7% vs. 7.2% in 2008-2009). CONCLUSION: This analysis will be repeated to follow the prevalence of overweight in children. These preliminary results confirm the need to focus on preventive actions, screening and care for overweight and obesity in underprivileged populations.

Endothelial function and mechanical arterial properties in children born small for gestational age: comparison with obese children.

BACKGROUND: Early cardiovascular events preceding atherosclerosis have been reported in children born small for gestational age (SGA). AIMS: To describe in detail the mechanical and functional arterial properties of SGA children and to compare the data to those of obese children in order to gain a better understanding of the severity of the dysfunction. A control group was required to overcome the lack of normal values. METHODS: Three groups of 7- to 15-year-old children were included. Sixty children born SGA without obesity, 49 children with obesity and not SGA, and 55 controls underwent complete carotid and brachial arterial measurements using ultrasound and flow-mediated dilation. Biological measurements were performed in the obese and SGA groups. RESULTS: Mean blood pressure and intima-media thickness were lower in SGA children than in the obese group (p < 0.001 and p = 0.004, respectively), but not different from the control group. Flow-mediated dilation was lower in SGA than in obese children and in controls (p < 0.001). CONCLUSION: These data show that children born SGA have endothelial dysfunction with normal intima-media thickness.

[Age at onset of menarche: Results from the French Health Behaviour in School-aged Children study]. / Age à la ménarche : résultats français de l'étude Health Behaviour in School-aged Children.

OBJECTIVE: To describe age at onset of menarche in a large nationally representative sample of French schoolgirls. PATIENTS AND METHODS: Age at onset of menarche was assessed in the Health Behaviour in School-aged Children French cross-sectional survey. Data were collected in 2006 by anonymous self-reported standardized questionnaire. Median age at onset of menarche was estimated using Kaplan-Meier's method from a nationally representative sample of 2323 13 and 15 years old girls in school classrooms. Mean and standard deviation was also reported in the 1059 15 years old girls who had already experienced menarche. RESULTS: Median age at onset of menarche was 12.8 years (interquartile range: 12.0-13.6), as was mean age at onset of menarche (standard deviation 1.2 years). DISCUSSION AND CONCLUSION: Age at onset of menarche and its variability (as measured by standard deviation) have decreased in most developed countries and seems stabilised at 13.0+/-0.5 years: our results are in line with this trend. The age limit of 9 years seems more coherent to define early menarche in French girls. These results may have an important impact on medical management of early pubertal development.

The cumulative effect of small dietary changes may significantly improve nutritional intakes in free-living children and adults.

BACKGROUND/OBJECTIVES: The ELPAS (Etude Longitudinale Prospective Alimentation et Santé) study was an 8-month randomized controlled dietary modification trial designed to test the hypothesis that family dietary coaching would improve nutritional intakes and weight control in 2026 free-living children and parents. It resulted in significant nutritional changes, with beneficial effects on body mass index in adults. In these ancillary analyses, we investigated dietary changes throughout the intervention. SUBJECTS/METHODS: Before the study, modeling analyses were carried out on the French Association Sucre Produits Sucrés Consommation et Communication (ASPCC) food-consumption database to identify the most efficient dietary intervention strategy. During the study, all participants performed monthly three nonconsecutive 24-h dietary recalls: this allowed for measuring changes in the number of servings per day and serving size for each targeted food category throughout the intervention. RESULTS: Modeling analyses showed that targeting only the 10 main foods contributing to fat and carbohydrate intakes did not allow for reaching the ELPAS nutritional goals. As a result, it was decided to target more foods and to propose several types of dietary advice (such as change in serving size, change in cooking method, food substitution). This strategy led to many appropriate dietary changes during the intervention, but only a few of them reached significance. The mean number of servings per day was indeed significantly modified for only 7% of the targeted food categories in children and 17% in parents. The mean serving size was modified for only 12% of targeted food categories in children and 9% in parents. CONCLUSIONS: The cumulative effect of small dietary changes may induce significant nutritional improvements, with limited burden for populations.

Prevention of overweight in preschool children: results of kindergarten-based interventions.

OBJECTIVE: Given the increasing prevalence of pediatric obesity, we evaluated two kindergarten-based strategies for reducing overweight in preschool children in the Haute-Garonne Department in France. METHODS: Kindergartens (n=79) were randomly assigned to one of the two strategies and followed for 2 years. In the first group (Epidémiologie et prévention de l'obésité infantile, EPIPOI-1), parents and teachers received basic information on overweight and health, and children underwent screening to identify those with overweight (body mass index (BMI) > or = 90th percentile) or at risk for overweight (BMI between 75 and 90th percentile), who were then followed up by their physicians. EPIPOI-2 children, in addition, received kindergarten-based education to promote healthy practices related to nutrition, physical activity and sedentary behaviors. Data on control children from non-intervention kindergartens (n=40) were retrieved from medical records at the Division of School Health. RESULTS: At baseline, groups differed significantly on age and school area (underprivileged/not). Owing to a significant interaction between school area and group, analyses were stratified by school area. At baseline, groups did not differ on overweight prevalence and BMI z-scores for any school area. After intervention, prevalence of overweight, BMI z-score and change in BMI z-score were significantly lower in intervention groups compared with controls in underprivileged areas. Using multilevel analysis adjusted for potential confounders, a significant effect on overweight prevalence at the end of the study was noted for EPIPOI-1 in underprivileged areas only (odds ratio and 95% confidence interval: 0.18 (0.07-0.51). In non-underprivileged areas, the gain in BMI z-score was lower in EPIPOI-2 group compared with control and EPIPOI-1. CONCLUSION: Our results suggest that simple measures involving increasing awareness on overweight and health, and periodic monitoring of weight and height with follow-up care when indicated, could be useful to reduce overweight in young children from underprivileged areas. A reinforced strategy with an education component, in addition, may be indicated in children in non-underprivileged areas.

User trial of Easypod, an electronic autoinjector for growth hormone.

OBJECTIVE: A new electronic injection device, the Easypod, has been developed to administer growth hormone (GH). This study assessed the use of this device in common practice. MATERIALS AND METHODS: Results are from the French arm (one centre) of an international, open-label, uncontrolled study. Subjects were children already using, or about to start, GH therapy. Children used the Easypod device for 60 days. The main outcome measures were patients' or, if appropriate, their parents' qualitative overall impression of the device and the usefulness of its features after 15 days' use, as evaluated by questionnaire. RESULTS: At day 15, all participants (20/20) described their overall impression of the Easypod device as "good" or "very good". All participants rated the display of the remaining drug in the cartridge, the preprogrammed dosing, the onscreen instructions and the automatic-needle attachment as "useful" or "very useful". The device's audible/visible signals and customisable injection depth and speed were each rated as "useful" or "very useful" by 19/20 participants and the skin sensor, customisable needle-insertion speed and dose-injection confirmation were each rated as such by 18/20 participants. Electronic display of the date and time of the last injection and the dose history were considered "useful" or "very useful" by 17/20 and 15/20 participants, respectively. At day 60, 17/17 respondents expressed a preference for continuing to use the device. CONCLUSION: These results show that the features of Easypod are considered useful in routine practice and the majority of participants expressed a desire to continue using the device.

[Growth follow-up of SGA children after 3 years of GH treatment]. / Suivi de la croissance chez les enfants de petite taille de naissance après 3 ans de traitement par hormone de croissance: l'expérience d'un centre français.

UNLABELLED: Eighty-five percent of children born with IUGR have spontaneous catch-up growth in the first 2 years of life; however, about 10 to 15% do not catch up. Numerous therapeutic trials have demonstrated the efficacy of GH treatment in these children. However, the duration of this treatment is still discussed. OBJECTIVE: The aim of this study was to describe the evolution of growth during and after the end of treatment. POPULATION AND METHODS: This study followed 33 children in our unit, treated with growth hormone under the French indication (3 years of treatment followed by 1 year off treatment) and with a mean follow-up of 3 years after cessation. RESULTS: During the 3 years of therapy, we confirmed an increase in growth velocity that resulted in a mean height above -2 standard deviation score (SDS) in 25 children at 3 years (mean height of 1.4 SDS). Among the 25 children who achieved a height above -2 SDS at three years and therefore stopped treatment, 15 resumed GH due to a secondary catch-down. Among children who didn't catch-up at 3 years, the continuation of GH treatment didn't seem to improve the growth.

Single nucleotide polymorphisms in the neuropeptide Y2 receptor (NPY2R) gene and association with severe obesity in French white subjects.

AIMS/HYPOTHESIS: Genetic variants of genes for peptide YY (PYY), neuropeptide Y2 receptor (NPY2R) and pancreatic polypeptide (PPY) were investigated for association with severe obesity. SUBJECTS AND METHODS: The initial screening of the genes for variants was performed by sequencing in a group of severely obese subjects (n=161). Case-control analysis of the common variants was then carried out in 557 severely obese adults, 515 severely obese children and 1,163 non-obese/non-diabetic control subjects. Rare variants were genotyped in 700 obese children and the non-obese/non-diabetic control subjects (n=1,163). RESULTS: Significant association was found for a 5' variant (rs6857715) in the NPY2R gene with both severe adult obesity (p=0.002) and childhood obesity (p=0.02). This significant association was further supported by a pooled allelic analysis of all obese cases (adults and children, n=928) vs the control subjects (n=938) (p=0.0004, odds ratio=1.3, 95% CI 1.1-1.5). Quantitative trait analysis of BMI and WHR was performed and significant association was observed for SNP rs1047214 in NPY2R with an increase in WHR in the severely obese children (co-dominant model p=0.005, recessive model p=0.001). Association was also observed for an intron 3 variant (rs162430) in the PYY gene with childhood obesity (p=0.04). No significant associations were observed for PPY variants. Only one rare variant in the NPY2R gene (C-5641T) was not found in lean individuals and this was found to co-segregate with obesity in one family. CONCLUSIONS/INTERPRETATION: These results provide evidence of association for NPY2R and PYY gene variants with obesity and none for PPY variants. A rare variant of the NPY2R gene showed evidence of co-segregation with obesity and its contribution to obesity should be investigated further.

Can some growth hormone (GH)-deficient children benefit from combined therapy with gonadotropin-releasing hormone analogs and GH? Results of a retrospective study.

Recombinant GH (rGH) treatment does not invariably correct height deficits in GH-deficient children once puberty has begun. The addition of GnRH analogs (GnRHa) to delay puberty has been advocated, but published results are few and sometimes conflicting. We retrospectively compared GH-deficient children treated with rGH and GnRHa for at least 1 yr after entering puberty and having attained their final height (n = 23) with a matched control group treated only with rGH. Overall, combined therapy did not significantly increase final height relative to rGH alone. However, the shortest girls at the onset of puberty (<25th percentile) benefited more than the tallest (>75th percentile) in both final height relative to predicted height and pubertal catch-up growth. In the control group, patients having experienced intrauterine growth retardation (IUGR) attained a lower mean final height than patients without IUGR (difference significant in boys, but not in girls). In the combined therapy group, IUGR did not affect the final height of either sex. Our results suggest that two populations might benefit most from combined GnRHa and rGH therapy: girls particularly short at the onset of puberty and patients who had experienced IUGR. Further prospective studies are required to confirm these preliminary hypothesis.

Evaluation of microcomputer nutritional teaching games in 1,876 children at school.

OBJECTIVE: We evaluated in a prospective study microcomputer nutritional teaching games and their contribution to the children's acquisition of nutritional knowledge and improvement of eating habits. MATERIAL AND METHODS: One thousand eight hundred seventy-six children aged 7-12 years took part in this study at school. All 16 schools of the same school district were randomized into two groups: games group and control group, both receiving conventional nutritional teaching by their teachers. The children in the games group played computer games during the conventional nutritional teaching period (2 hours a week for 5 weeks). At completion of the study, dietetic knowledge and dietary records were evaluated in both groups. RESULTS: Dietary knowledge tests results were better in the games group (p<0.001). The children in the games group had a significantly better balanced diet for an energy intake of about 1900 kilocalories: more carbohydrate (46.4 +/- 0.2% vs 45.7 +/- 0.2%, p<0.05), less fat (37.1 +/- 0.1% vs 37.6 +/- 0.2%, p<0.05), less protein (16.5 +/- 0.1% vs 16.7 +/- 0.1%, p<0.05), less saccharose (11.5 +/- 0.1% vs 12.2 +/- 0.2%, p<0.001), more calcium (p<0.001) and more fiber (p<0.05). The games group had a better snack at 10 a.m., a less copious lunch and less nibbling (p<0.001). CONCLUSION: The children in the games group had slightly but significantly better nutritional knowledge and dietary intake compared to children in the control group. Using our micro computer nutritional teaching games at school provides an additional and modern support to conventional teaching.

Evaluation of cutaneous modifications in seventy-seven growth hormone-deficient children.

Cutaneous parameters such as dermal thickness, stiffness, elasticity, skin surface lipid and hydration were evaluated using noninvasive methods in 77 growth hormone-deficient (GHD) children before replacement therapy and in 70 non-GHD children. We showed that in GHD children, dermis was thinner (0.70 +/- 0.10 vs. 0.80 +/- 0.10 mm, p < 0.0001 for prepubertal children and 0.81 +/- 0.10 vs. 0.94 +/- 0.11 mm, p < 0.0001 for pubertal children), stiffer (178.5 +/- 57.3 vs. 113.09 +/- 37 kPa, p < 0.0001 for prepubertal children and 172.5 +/- 61.7 vs. 117.3 +/- 42.5 kPa for pubertal children, p < 0.001) and less elastic (0.44 +/- 0.09 vs. 0.39 +/- 0.06 (nonelasticity index), p < 0.01 for prepubertal children and 0.39 +/- 0.05 vs. 0.33 +/- 0.04, p < 0.001 for pubertal children) compared to controls. Fourteen GHD children were re-evaluated after 1 year of GH treatment: dermal thickness and skin stiffness were significantly improved (p < 0.001 and p < 0.05 respectively) while elasticity was not modified. During the same period, 11 controls did not show any significant cutaneous modification. IGF-1 values, but not IGFBP-3 values, correlated positively with dermal thickness in GHD children, before and after 1 year of GH treatment. To conclude, GHD children exhibited specific cutaneous modifications. In a subset of GHD children, we showed that these modifications were influenced by GH treatment. More extensive studies are needed to see if these changes correlated with other GH effects.

Auxological and endocrine evolution of 28 children with Prader-Willi syndrome: effect of GH therapy in 14 children.

We report on the auxological and endocrine evolution of 28 patients presenting with Prader-Willi syndrome. Half of them received growth hormone (GH) therapy (group 2). The spontaneous auxological evolution was analyzed in the two groups from 2 to 8 years; the mean SDS for height remained stable (-0.6 +/- 0.6) in group 1 and decreased (from -2.0 +/- 0.9 to -2.7 +/- 0.6) in group 2. Magnetic resonance imaging showed marked pituitary hypoplasia in the two groups. In group 2, the mean GH peak after two provocative tests was 3.8 +/- 2.4 microg/l, the mean SDS values for insulin-like growth factor I levels were -2.0 +/- 1.5 (range from -0.5 to -5.0). The mean duration of GH treatment was 3.6 +/- 2.9 (range 1-9.3) years. 14 children completed 1 year of treatment. The two groups had opposite evolutions in Delta SDS for height (-0.8 +/- 0.8 vs. +1.1 +/- 0.8), for growth velocity (-1.9 +/- 2.2 vs. +2.9 +/- 2.7), and for Z score of the body mass index (+0.37 +/- 1.3 vs. -0.14 +/- 0.76; group 1 vs. group 2). This retrospective study shows that, in children with Prader-Willi syndrome and true GH deficiency, long-term GH therapy is effective in increasing growth velocity and in maintaining body mass index.

Gonadotropin treatment of hypogonadotropic hypogonadal adolescents.

Testosterone substitution, needed for normal physical development in male hypogonadal adolescents, does not induce testicular growth. We treated 37 hypogonadal adolescents with gonadotropins (hCG/hMG), to obtain complete virilization during the first two years of treatment, to avoid psychological sequellae and to allow normal sexual development. Testicular volume increased significantly during therapy (from 1.98 +/- 1.2 to 9 +/- 3.3 ml), while testosterone rose from 0.26 +/- 0.04 to 5.3 +/- 0.8 ng/ml, with worse results in adolescents with cryptorchidism. hCG/hMG treatment had a better outcome than testosterone during the induction of puberty, avoiding psychological problems induced by atrophic testes. Further long term studies are necessary to evaluate whether early hCG/hMG treatment facilitates later spermatogenesis even in patients with cryptorchidism.

[Pituitary stalk transection syndrome]. / Syndrome d'interruption de la tige pituitaire.

BACKGROUND: Pituitary stalk transection is a non-negligible cause of growth hormone (GH) deficiency. POPULATION AND METHODS: We studied 22 children (13 boys, nine girls) aged at the first clinical manifestations from 2 days to 10 years (average = 5.33 +/- 2 years). Pituitary stalk transection was assessed by the means of magnetic resonance imaging (MRI). The children's past history showed fetal distress in 12 cases (54.5%), cranial trauma in three (13%) and a midline anomaly in three (13%). The first clinical manifestations were neonatal hypoglycemia (two cases), decreased growth velocity (18 cases) and diabetes insipidus (two cases). RESULTS: GH deficiency was complete, present from the onset in 19 of 22 cases and isolated in four. Fifteen of 22 cases had adreno-corticotrophic hormone (ACTH) and thyroid stimulating hormone (TSH) deficiency. Diabetes insipidus was present in six cases and revealed the syndrome in two. All children older than normal age of puberty (n = 10) had gonadotropin deficiency. In our study, these hormonal anomalies progressed from isolated GH deficiency to multiple hormonal deficiencies. CONCLUSION: The recently described stalk transection syndrome is relatively frequent and should be suspected after cranial trauma or fetal distress syndrome. The outcome is progressive evolution towards panhypopituitarism and these patients require regular clinical survey and hormonal controls.

Growth hormone (GH) retesting and auxological data in 131 GH-deficient patients after completion of treatment.

GH state and auxological data after completion of GH therapy are reported in 131 patients (79 males, 52 females). They were treated from 1980-1994 for partial (n = 98) or complete (n = 33) GH deficiency (GHD), either idiopathic (n = 121) or organic (n = 10). A single stimulation test (clonidine+betaxolol) was used, and only 50 patients (38%) maintained a blunted response (GH peak below 10 micrograms/L). Although 9 of the 10 patients with organic GHD had an abnormal low GH peak, 67% of patients with idiopathic GHD normalized their GH secretion. This was particularly true of partial GHD patients (71% vs. 36% of complete GH-deficient patients). Based on a retest GH peak below 5 micrograms/L, only 23% of the patients were considered to be GH deficient and therefore candidates for GH treatment during adulthood. We found no significant difference between hormonal state at completion of treatment and initial GH deficiency, pubertal state, or sex, although we did find a significantly lower GH peak value before and after treatment in patients with elevated body mass index. Of the 14 obese children who were treated, 50% had an abnormally low serum insulin-like growth factor-I level, arguing for true GHD, and only two children remained obese at cessation of treatment. Auxological data showed that with a mean duration of treatment of 3.6 +/- 2.0 yr, patients classified as having complete GHD before treatment had significantly greater catch-up growth as expressed in SDS for height than patients with partial GHD (0.6 +/- 1.1 vs. 1.1 +/- 0.7 SDS, P < 0.05), and that boys grew better than girls (1.4 +/- 0.8 vs. 1.6 +/- 0.6 SDS) for height, P < 0.01). That catch-up growth was not correlated with the result of GH peak after cessation of treatment.