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2.
Leuk Res ; 95: 106405, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32590107

RESUMO

PURPOSE: To investigate the effect of tyrosine kinase inhibitors (TKIs) on the statural growth in children with acute lymphoblastic leukemia (ALL). METHODS: We retrospectively collected data from 344 children with ALL younger than 17 years old at diagnosis identified in pediatric department of Peking University People's Hospital. The children were divided into three groups: conventional chemotherapy group, imatinib group and dasatinib group. Height was expressed as standard deviation score(HtSDS). In the three groups, we compared the HtSDS and △HtSDS at the start of treatment and during follow-up period and also compared the adult height and median parental height(MPH). We further compared the HtSDS classified by age and gender in imatinib group. At last, univariate analysis was used to analyze the influencing factors on the deceleration of height growth by imatinib. RESULTS: There were 298 children in conventional chemotherapy group, 39 in imatinib group and 7 in dasatinib group. In imatinib group, the mean HtSDS of children at follow-up time was significantly lower than that at the start of treatment (P < 0.05), regardless of age and gender. In imatinib group, the decrease of HtSDS in girls was more obvious than in boys(P = 0.031). The HtSDS gradually decreased in the first and the second year in imatinib group. After discontinuation of imatinib, the HtSDS had no obvious change. Multivariate analysis showed that the HtSDS at the start of imatinib was negatively correlated with severe growth impairment on imatinib therapy. The HtSDS in dasatinib group and conventional chemotherapy group maintained a high degree of consistency. CONCLUSION: Imatinib can affect growth velocity in children with ALL, regardless of age and gender. With the discontinuation of imatinib, the inhibitory effect will not continue. The lower HtSDS at the start of imatinib therapy, the more obvious effect of imatinib on growth impairment will be, and the effect will be more obvious in girls than boys.


Assuntos
Antineoplásicos/efeitos adversos , Estatura/efeitos dos fármacos , Mesilato de Imatinib/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Adolescente , Criança , Pré-Escolar , Dasatinibe/efeitos adversos , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Caracteres Sexuais
3.
J Clin Endocrinol Metab ; 105(3)2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31990356

RESUMO

CONTEXT: The C-type natriuretic peptide receptor encoded by the NPR2 gene is a paracrine regulator of the growth plate; heterozygous NPR2 variants cause short stature with possible presence of different signs of bone dysplasia. To date, the effect of growth hormone (GH) treatment has been described in a few individuals with NPR2 gene variants with inconsistent results. OBJECTIVES: To identify NPR2 gene variants among children with familial short stature (FSS) and to describe their phenotype, including GH treatment response. DESIGN, SETTINGS AND PATIENTS: Out of 747 patients with short stature treated with GH in a single center, 87 with FSS met the inclusion criteria (pretreatment height ≤ -2 standard deviation in both the patient and the shorter parent, unknown genetic etiology). Next-generation sequencing methods were performed to search for NPR2 gene variants. The results were evaluated using the American College of Medical Genetics and Genomics guidelines. The GH treatment response (growth velocity improvement and height standard deviation score development over the first 5 years of treatment) was evaluated. RESULTS: In 5/87 children (5.7%), a (likely) pathogenic variant in the NPR2 gene was identified (p.Ile558Thr [in 2], p.Arg205*, p.Arg557His, p.Ser603Thr). Two children had disproportionate short-limbed short stature, 1 a dysplastic 5th finger phalanx. The growth velocity in the first year of GH treatment accelerated by 3.6 to 4.2 cm/year; the height improved by 1.2 to 1.8 SD over 5 years of treatment. CONCLUSIONS: NPR2 gene variants cause FSS in a significant proportion of children. Their GH treatment response is promising. Studies including final height data are necessary to assess the long-term efficacy of this therapy.


Assuntos
Estatura/genética , Nanismo/tratamento farmacológico , Nanismo/genética , Hormônio do Crescimento Humano/administração & dosagem , Polimorfismo de Nucleotídeo Único , Receptores do Fator Natriurético Atrial/genética , Adolescente , Adulto , Biomarcadores/análise , Estatura/efeitos dos fármacos , Criança , Pré-Escolar , Estudos de Coortes , Nanismo/patologia , Feminino , Seguimentos , Humanos , Lactente , Masculino , Fenótipo , Prognóstico , Adulto Jovem
4.
Hum Exp Toxicol ; 39(5): 624-633, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31928232

RESUMO

Melamine contamination is a recent public health problem emerging globally. Present study aimed to detect the rate of melamine presence in human milk in a cohort study and to evaluate any possible differences in maternal-infant pair characteristics such as breastfeeding status, crying and sleep problems of infants, maternal postpartum depression, maternal-infant bonding, infant and maternal anthropometry, and maternal complete blood count caused by the melamine exposure. Mothers of infants born in Sanliurfa were invited to participate in 'Urfa Child Cohort Survey'. Overall, two breast milk samples were taken between 5 days and 15 days postpartum and between 4 weeks and 10 weeks. Randox Food's InfiniPlex array was used to analyse the presence of melamine. Melamine was detected in 32.2% and 24.4% of the first and the second milk samples; 16.7% of mothers had two positive samples. z Scores for birth weight and z scores for height for age were detected to be significantly lower in cases with two positive samples compared to cases with negative samples. Mean maternal white blood cells counts were found to be lower in cases with repeated melamine contact. Melamine might have a detrimental effect on birth weight, infant height and maternal blood count. Further studies should be done to detect environmental contamination in different regions and countries.


Assuntos
Peso ao Nascer/efeitos dos fármacos , Estatura/efeitos dos fármacos , Poluentes Ambientais , Contagem de Leucócitos , Leite Humano/química , Triazinas , Adulto , Estudos de Coortes , Poluentes Ambientais/análise , Poluentes Ambientais/toxicidade , Feminino , Humanos , Recém-Nascido , Masculino , Exposição Materna/efeitos adversos , Mães , Triazinas/análise , Triazinas/toxicidade
5.
J Pediatr Endocrinol Metab ; 33(1): 53-70, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31860471

RESUMO

Background An increasing body of evidence supports the view that both an adverse intrauterine milieu and rapid postnatal weight gain in children born small for gestational age (SGA) contribute towards the risk for the development of chronic diseases in adult life. Content The aim of this review was to identify and summarize the published evidence on metabolic and cardiovascular risk, as well as risk of impaired cardiac function, intellectual capacity, quality of life, pubertal development and bone strength among children born SGA. The review will then address whether growth hormone (GH) therapy, commonly prescribed to reduce the height deficit in children born SGA who do not catch up in height, increases or decreases these risks over time. Summary Overall, there are limited data in support of a modest beneficial effect of GH therapy on the adverse metabolic and cardiovascular risk observed in short children born SGA. Evidence to support a positive effect of GH on bone strength and psychosocial outcomes is less convincing. Outlook Further evaluation into the clinical relevance of any potential long-term benefits of GH therapy on metabolic and cardiovascular endpoints is warranted.


Assuntos
Estatura/efeitos dos fármacos , Transtornos do Crescimento/prevenção & controle , Hormônio do Crescimento Humano/administração & dosagem , Doenças do Recém-Nascido/tratamento farmacológico , Qualidade de Vida , Idade Gestacional , Humanos , Recém-Nascido , Doenças do Recém-Nascido/patologia , Recém-Nascido Pequeno para a Idade Gestacional
6.
J Pediatr Hematol Oncol ; 42(4): 271-274, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31842181

RESUMO

PURPOSE: There have been few reports on height disturbance in childhood acute lymphoblastic leukemia (ALL) patients treated without cranial radiation therapy (CRT). Our study aimed to clarify the critical period of growth in pediatric patients who were treated by the Japan Childhood Leukemia Study (JACLS) ALL-02 protocol, which involved short-term intensive treatment without CRT. PATIENTS AND METHODS: A retrospective, cohort study was conducted for prepubertal children with B-precursor ALL who were diagnosed from July 2002 to November 2011 and treated by the JACLS ALL-02 protocol at Oita University Hospital. The heights were chronologically measured at pretreatment, after the intensive phase (INT), at the end of treatment (END), and at 1 to 5 year(s) posttreatment (POST 1 to 5). RESULTS: Nine boys and 4 girls were enrolled. Z score of the height was reduced at INT and END. Delta Z scores of the height and Z score of height velocity were reduced from pretreatment to INT, and they demonstrated an early recovery during maintenance treatment in INT to END. CONCLUSIONS: Early recovery of delta Z scores of the height and Z score of height velocity was observed during the INT to END period. The shortened intensive phase without CRT may result in an adequate height in prepubertal ALL patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Estatura/efeitos dos fármacos , Desenvolvimento Infantil/efeitos dos fármacos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Criança , Pré-Escolar , Irradiação Craniana , Feminino , Humanos , Lactente , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/fisiopatologia , Estudos Retrospectivos
7.
Biomed Res Int ; 2019: 2728952, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31886190

RESUMO

Objective: To analyse the short-term adverse effects (AEs) of propranolol in the treatment of infantile hemangiomas (IHs) and their relevant factors, as well as the relationship between child growth and propranolol. Methods: A total of 506 patients with confirmed or suspected IHs were enrolled, and a total of 439 cases were included in the study. Short-term AEs were analysed using single-factor analysis and binary logistic regression. Out of 439 patients, 292 were enrolled to examine the effect of propranolol on 2-year-olds' height and body weight (BW), by comparison with reference range and among groups. Spearman rank correlation analysis was used to determine the relationship between BW, height, and duration of propranolol treatment. Results: Among 439 patients, 70 (16.0%) experienced AEs. Among them, 48 had gastrointestinal (GI) symptoms, 23 had central nervous system (CNS) symptoms, 8 had both symptoms above, and 7 had other symptoms. Most of the AEs occurred on the starting day (day 0), and 6 children's AEs were transient. Starting age of no older than 3 months led to more CNS symptoms, and starting age of older than 3 months was a protective factor against CNS symptoms, with an OR value of 0.303 (0.117-0.783). Height and BW of 292 two-year-old children were no less than the reference levels, although those of 3 females and 1 male were less than the average -2 standard deviation (-2SD). The height and BW of the children at the age of two was not related to the length of time of propranolol treatment. Conclusion: Oral propranolol has a good tolerance in the treatment of IHs. Oral propranolol exerts more adverse effects on the CNS of lower age children, and it has exhibited no effect on the growth of two-year-old children.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Hemiplegia/tratamento farmacológico , Propranolol/administração & dosagem , Estatura/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Sistema Nervoso Central/efeitos dos fármacos , Sistema Nervoso Central/patologia , Criança , Pré-Escolar , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/classificação , Feminino , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/patologia , Hemiplegia/complicações , Hemiplegia/patologia , Humanos , Doença Iatrogênica/prevenção & controle , Lactente , Masculino , Propranolol/efeitos adversos , Resultado do Tratamento
8.
PLoS One ; 14(12): e0227120, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31887199

RESUMO

BACKGROUND: Interferon-beta (IFN-beta) is a commonly used treatment for multiple sclerosis (MS). Current guidelines recommend cessation of treatment during pregnancy, however the results of past studies on the safety of prenatal exposure to IFN-beta have been conflicting. A large scale study of a population of MS women is therefore warranted. OBJECTIVES: To assess whether, among those born to women with MS, infants prenatally exposed to IFN-beta show evidence of smaller size at birth relative to infants which were not prenatally exposed to any MS disease modifying drugs. METHODS: Swedish and Finnish register data was used. Births to women with MS in Sweden and Finland between 2005-2014 for which a birth measurement for weight, height, and head circumference was available were included. The exposure window was from 6 months prior to LMP to the end of pregnancy. RESULTS: In Sweden, 411 pregnancies were identified as exposed to IFN-beta during the exposure window, and 835 pregnancies were counted as unexposed to any MS DMD. The corresponding numbers for Finland were 232 and 331 respectively. Infants prenatally exposed to interferon-beta were on average 28 grams heavier (p = 0.17), 0.01 cm longer (p = 0.95), and had head circumferences 0.14 cm larger (p = 0.13) in Sweden. In Finland, infants were 50 grams lighter (p = 0.27), 0.02 cm shorter (p = 0.92) and had head circumferences 0.22 cm smaller (p = 0.15) relative to those unexposed. CONCLUSIONS: This study provides evidence that exposure to IFN-beta during pregnancy does not influence birth weight, length, or head circumference.


Assuntos
Peso ao Nascer/efeitos dos fármacos , Estatura/efeitos dos fármacos , Interferon beta/efeitos adversos , Esclerose Múltipla/tratamento farmacológico , Complicações na Gravidez/tratamento farmacológico , Adulto , Feminino , Finlândia , Humanos , Recém-Nascido , Troca Materno-Fetal , Esclerose Múltipla/imunologia , Gravidez , Complicações na Gravidez/imunologia , Sistema de Registros/estatística & dados numéricos , Suécia
9.
Horm Metab Res ; 51(12): 798-804, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31745940

RESUMO

To assess total cortisol levels in children being evaluating for short stature with normal cortisol reserve and to correlate this response to clinical and laboratory data. Children assessed with glucagon test in our department were recruited in this study retrospectively. Inclusion criteria were: i) age>1 year, ii) absence of chronic illness or medication interfering with ACTH-cortisol axis, iii) GH stimulation levels>3ng/mL at least in one provocation test (glucagon or clonidine), iv) absence of multiple pituitary growth hormone deficiencies, v) normal short Synacthen test in cases of low cortisol response in glucagon test.Two hundred and thirty-seven subjects (160 males, 67.5%) with a mean age of 9.02±3.19 years, were finally included in the analysis. Cortisol peak levels but not cortisol AUC were significantly increased in females compared to males (26.83±7.31 µg/dl vs. 24.04±7.20 µg/dl). When linear correlations were studied, both cortisol peak levels and cortisol AUC were linearly but inversely correlated to age (r=-0.234, p<0.001 and r=-0.315, p<0.001, respectively). Finally, cortisol AUC was inversely correlated to weight Z-scores (r=-0.160, p=0.014). When our analysis was limited only to subjects with intact GH response (GH peak> 7 ng/mL), age was still inversely correlated to cortisol AUC (r=-0.312, p<0.001), and cortisol AUC was linearly correlated to GH AUC assessed with clonidine test (r=0.223, p=0.013). Girls, younger and thinner children exhibit higher cortisol response to glucagon test.


Assuntos
Doenças do Desenvolvimento Ósseo/tratamento farmacológico , Glucagon/administração & dosagem , Hidrocortisona/sangue , Hormônio Adrenocorticotrópico/sangue , Estatura/efeitos dos fármacos , Doenças do Desenvolvimento Ósseo/sangue , Criança , Pré-Escolar , Feminino , Hormônio do Crescimento Humano/sangue , Humanos , Masculino , Estudos Retrospectivos
10.
Cochrane Database Syst Rev ; 2019(10)2019 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-31684688

RESUMO

BACKGROUND: The final adult height of untreated girls aged up to 18 years with Turner syndrome (TS) is approximately 20 cm shorter compared with healthy females. Treatment with growth hormone (GH) increases the adult height of people with TS. The effects of adding the androgen, oxandrolone, in addition to GH are unclear. Therefore, we conducted this systematic review to investigate the benefits and harms of oxandrolone as an adjuvant therapy for people with TS treated with GH. OBJECTIVES: To assess the effects of oxandrolone on growth hormone-treated girls aged up to 18 years with Turner syndrome. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, the ICTRP Search Portal and ClinicalTrials.gov. The date of the last search was October 2018. We applied no language restrictions. SELECTION CRITERIA: We included randomised controlled clinical trials (RCTs) that enrolled girls aged up to 18 years with TS who were treated with GH and oxandrolone compared with GH only treatment. DATA COLLECTION AND ANALYSIS: Three review authors independently screened titles and abstracts for relevance, selected trials, extracted data and assessed risk of bias. We resolved disagreements by consensus, or by consultation with a fourth review author. We assessed trials for overall certainty of the evidence using the GRADE instrument. MAIN RESULTS: We included six trials with 498 participants with TS, 267 participants were randomised to oxandrolone plus GH treatment and 231 participants were randomised to GH only treatment. The individual trial sample size ranged between 22 and 133 participants. The included trials were conducted in 65 different paediatric endocrinology healthcare facilities including clinics, centres, hospitals and academia in the USA and Europe. The duration of interventions ranged between 3 and 7.6 years. The mean age of participants at start of therapy ranged from 9 to 12 years. Overall, we judged only one trial at low risk of bias in all domains and another trial at high risk of bias in most domains. We downgraded the level of evidence mainly because of imprecision (low number of trials, low number of participants or both). Comparing oxandrolone plus GH with GH only for final adult height showed a mean difference (MD) of 2.7 cm in favour of oxandrolone plus GH treatment (95% confidence interval (CI) 1.3 to 4.1; P < 0.001; 5 trials, 270 participants; moderate-quality evidence). The 95% prediction interval ranged between 0.3 cm and 5.1 cm. For adverse events, we based our main analysis on reliable date from two trials with overall low risk of bias. There was no evidence of a difference between oxandrolone plus GH and GH for adverse events (RR 1.81, 95% CI 0.83 to 3.96; P = 0.14; 2 trials, 170 participants; low-quality evidence). Six out of 86 (18.6%) participants receiving oxandrolone plus GH compared with 8/84 (9.5%) participants receiving GH only reported adverse events, mainly signs of virilisation (e.g. deepening of the voice). One trial each investigated the effects of treatments on speech (voice frequency; 88 participants), cognition (51 participants) and psychological status (106 participants). The overall results for these comparisons were inconclusive (very low-quality evidence). No trial reported on health-related quality of life or all-cause mortality. AUTHORS' CONCLUSIONS: Addition of oxandrolone to the GH therapy led to a modest increase in the final adult height of girls aged up to 18 years with TS. Adverse effects identified included virilising effects such as deepening of the voice, but reporting was inadequate in some trials.


Assuntos
Estatura/efeitos dos fármacos , Hormônio do Crescimento Humano/uso terapêutico , Oxandrolona/uso terapêutico , Síndrome de Turner/tratamento farmacológico , Adolescente , Androgênios/uso terapêutico , Feminino , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Síndrome de Turner/complicações
11.
J Pediatr Endocrinol Metab ; 32(10): 1055-1063, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31573958

RESUMO

Background In congenital adrenal hyperplasia (CAH), achieving the balance between overtreatment and undertreatment remains challenging. Final height (FH) can serve as a long-term outcome measure. We aimed to identify age-dependent factors that influence FH in CAH patients, resulting in age-specific treatment goals. Methods We retrospectively evaluated longitudinal data of 39 pediatric CAH patients born between 1980 and 1997 from the Radboudumc CAH database. We analyzed height and bone age (BA) at diagnosis or 4 years of age, at the start of puberty and at FH. Height data were corrected for parental height and secular trend. Hydrocortisone (HC) use and salivary steroid concentrations were studied longitudinally throughout childhood and puberty. Results Median FH standard deviation scores (SDSs) corrected for target height SDSs (THSDSs) was -1.63. Median height SDS corrected for THSDS (HSDS-THSDS) decreased from diagnosis/age 4 years to FH in both salt wasting (SW) CAH and simple virilizing (SV) CAH, and in both male and female patients. However, when height was corrected for BA, no height loss occurred from diagnosis/age 4 years to FH in any of the subgroups, while a height gain was seen in SV males. In the combined model analyzing both HC dose and salivary steroid concentrations, in childhood the androstenedione (A) concentration was negatively associated with FH, while in puberty the HC dose was negatively associated with FH. Conclusions In CAH, loss of growth potential already occurs in early childhood. In prepubertal children, exposure to elevated androgens is associated with decreased FH. In puberty, the growth suppressing effects of HC outweigh the negative effects of elevated androgens. Therefore, we suggest different treatment approaches in prepubertal and pubertal patients.


Assuntos
Hiperplasia Suprarrenal Congênita/tratamento farmacológico , Estatura/efeitos dos fármacos , Hidrocortisona/uso terapêutico , Puberdade/efeitos dos fármacos , Maturidade Sexual/efeitos dos fármacos , Adolescente , Hiperplasia Suprarrenal Congênita/metabolismo , Hiperplasia Suprarrenal Congênita/patologia , Fatores Etários , Biomarcadores/análise , Índice de Massa Corporal , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Estudos Longitudinais , Masculino , Prognóstico , Estudos Retrospectivos
12.
Horm Res Paediatr ; 91(6): 373-379, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31480041

RESUMO

AIMS: This study aimed to evaluate final adult height (AH) after recombinant human growth hormone (GH) treatment of girls with Turner syndrome (TS) and to elucidate the predicting factors for their growth response. METHODS: We enrolled 73 patients with TS who underwent GH treatment and reached AH and 14 patients who did not undergo treatment. To assess the effectiveness of GH therapy, we evaluated final AH, height gain over the predicted AH, and height gain over the projected AH. In addition, to analyze the factors affecting final AH, we studied correlations between final AH (or height SDS, height gain) and treatment variables. RESULTS: GH therapy was started at a mean age of 8.87 ± 3.73 years, and the treatment duration was 6.47 ± 3.02 years. The patients in the treated group reached a final AH of 152.03 ± 4.66 cm (final AH SDS for the general population: -1.93 ± 1.03) with a gain over projected AH at the start of treatment of 12.21 ± 4.33 cm. The untreated control subjects had a final AH of 143.57 ± 4.06 cm with a gain over projected AH at the first visit of 3.89 ± 3.80 cm. Final AH and AH SDS were positively correlated to height SDS at the start of treatment. Thirty-five patients out of the 73 GH-treated patients (47.9%) attained to a normal range of height for Korean girls. The patients having attained to a normal height range after GH treatment had shown a higher height SDS at the start of GH treatment, a higher mid-parental height SDS, and a younger age at initiation of estrogen. CONCLUSIONS: Our findings demonstrate that GH treatment at an early age is effective in improving the final height SDS and height SDS gain in TS patients. Therefore, GH administration at an early age is important for final height gain.


Assuntos
Estatura/efeitos dos fármacos , Hormônio do Crescimento Humano/administração & dosagem , Síndrome de Turner , Adolescente , Adulto , Criança , Feminino , Humanos , Estudos Retrospectivos , Síndrome de Turner/tratamento farmacológico , Síndrome de Turner/patologia , Síndrome de Turner/fisiopatologia
13.
Growth Horm IGF Res ; 48-49: 29-35, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31493626

RESUMO

OBJECTIVE: The CERES study was a randomized, multicenter, investigator-blind trial aimed to evaluate the efficacy and safety of a recombinant human growth hormone (r-hGH) developed by Cristalia, as a biosimilar product, with analytical, functional and pharmacokinetics similarities comparable to Genotropin™, in children with growth hormone deficiency (GHD). DESIGN: A total of 135 naïve prepubertal children with GHD were recruited, of whom 97 were randomized in 14 Brazilian sites to received either r-hGH Cristalia (n = 49) or Genotropin™ (n = 48). Efficacy was evaluated considering the height standard deviation score (SDS) and growth velocity as auxological parameters, IGF-1 and IGFBP-3 were measured as pharmacodynamic parameters during 12 months treatment time. Safety was assessed by monitoring adverse events, immunogenicity, blood count with platelets, biochemical profile and hormonal levels particularly fasting glucose, insulin and HbA1C. RESULTS: The auxological parameters and IGF-1 and IGFBP-3 levels were comparable between both groups of patients. At end of study or the 12th month treatment, the means growth velocity was 9.7 cm/year and 9.5 cm/year, for r-hGH Cristalia and Genotropin™, respectively. The ANCOVA mean difference between the groups was 0.16 cm/year to Cristalia group (CI 95% = -0.72 to 1.03 cm/year). There was no difference in adherence among the treatment groups. The safety profile was comparable between groups. CONCLUSIONS: The clinical similarity between r-hGH and Genotropin™ was demonstrated within 12 month of treatment. On the basis of comparability of quality, safety, and efficacy to the reference product, r-hGH from Cristalia can be considered a cost-effective therapeutic option for patients with growth disorders.


Assuntos
Medicamentos Biossimilares/uso terapêutico , Estatura/efeitos dos fármacos , Transtornos do Crescimento/tratamento farmacológico , Hormônio do Crescimento Humano/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Adolescente , Criança , Pré-Escolar , Feminino , Transtornos do Crescimento/metabolismo , Transtornos do Crescimento/patologia , Humanos , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Prognóstico
14.
Environ Health ; 18(1): 62, 2019 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-31288809

RESUMO

BACKGROUND: Children in India are exposed to high levels of ambient fine particulate matter (PM2.5). However, population-level evidence of associations with adverse health outcomes from within the country is limited. The aim of our study is to estimate the association of early-life exposure to ambient PM2.5 with child health outcomes (height-for-age) in India. METHODS: We linked nationally-representative anthropometric data from India's 2015-2016 Demographic and Health Survey (n = 218,152 children under five across 640 districts of India) with satellite-based PM2.5 exposure (concentration) data. We then applied fixed effects regression to assess the association between early-life ambient PM2.5 and subsequent height-for-age, analyzing whether deviations in air pollution from the seasonal average for a particular place are associated with deviations in child height from the average for that season in that place, controlling for trends over time, temperature, and birth, mother, and household characteristics. We also explored the timing of exposure and potential non-linearities in the concentration-response relationship. RESULTS: Children in the sample were exposed to an average of 55 µ g/m3 of PM2.5 in their birth month. After controlling for potential confounders, a 100 µg/m3 increase in PM2.5 in the month of birth was associated with a 0.05 [0.01-0.09] standard deviation reduction in child height. For an average 5 year old girl, this represents a height deficit of 0.24 [0.05-0.43] cm. We also found that exposure to PM2.5 in the last trimester in utero and in the first few months of life are significantly (p < 0.05) associated with child height deficits. We did not observe a decreasing marginal risk at high levels of exposure. CONCLUSIONS: India experiences some of the worst air pollution in the world. To our knowledge, this is the first study to estimate the association of early-life exposure to ambient PM2.5 on child height-for-age at the range of ambient pollution exposures observed in India. Because average exposure to ambient PM2.5 is high in India, where child height-for-age is a critical challenge in human development, our results highlight ambient air pollution as a public health policy priority.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Poluição do Ar/efeitos adversos , Estatura/efeitos dos fármacos , Exposição Ambiental/efeitos adversos , Material Particulado/efeitos adversos , Pré-Escolar , Feminino , Humanos , Índia , Masculino
15.
Pediatr Hematol Oncol ; 36(4): 189-197, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31298597

RESUMO

Imatinib is a preferred drug for pediatric Chronic Myeloid Leukemia (CML). Long-term use has inhibitory effects on other tyrosine kinase pathways causing off-target complications such as growth impairment. Our aim was to evaluate impact of long-term use on longitudinal growth in children with CML in Kerala. We hypothesized that the impact would be lesser compared to Northern India as Kerala has the lowest rates of underweight and stunting, with a high literacy rate and per capita income. Children ≤14 years of age, diagnosed with CML and received imatinib for at least 1 year were included. Girls >9 years of age and boys >11 years were considered pubertal. Height Z scores were derived using WHO AnthroPlus. Paired t test compared difference of Z scores in prepubertal and postpubertal age groups. Height Z scores were compared with mid-parental height and sibling height Z scores. Thirty-six children were included (M = 21; F = 15). Median duration of imatinib exposure was 84 months. Decrease in longitudinal growth affected children in both prepubertal and postpubertal age groups. Decrease in height Z scores was more in prepubertal age group when imatinib therapy was initiated (p = .0018). Of 10 patients currently above 19 years (of whom 8 were in pubertal age and 2 in prepubertal age at start of imatinib) none are stunted. Patient's height Z scores was lesser compared to sibling height Z scores (p = .027). Children on continuous imatinib showed a significant stunting when treatment was initiated during prepubertal age. There is a catch-up of growth as the final height reached is within normal limits of WHO reference values.


Assuntos
Desenvolvimento do Adolescente/efeitos dos fármacos , Estatura/efeitos dos fármacos , Desenvolvimento Infantil/efeitos dos fármacos , Mesilato de Imatinib/administração & dosagem , Leucemia Mielogênica Crônica BCR-ABL Positiva , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/fisiopatologia , Masculino
16.
J Dermatol ; 46(9): 770-776, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31270853

RESUMO

The efficacy of lauromacrogol injection therapy and intralesional triamcinolone for infantile hemangiomas (IH) has been well documented recently, but with an increase in serious or rare adverse reactions. The aim of this study is to investigate the safety concerns regarding intralesional injection of lauromacrogol combined with triamcinolone for IH and to study its effect on infant growth and development. A total of 1039 IH patients who were subjected to intralesional injection of lauromacrogol combined with triamcinolone in the Plastic Surgery Department of Shandong Provincial Hospital between 1 January 2015 and 31 May 2018 were enrolled in this study. When the dose of lauromacrogol and triamcinolone was less than 3.5 and 2.0 mg/kg respectively, no serious side-effects were observed. The adverse event rate reported was 7.7%. Among the 405 patients not subjected to propranolol before the last injection, the study included three modes of treatment response: regression (82.7%), stabilization (13.8%) and failure (3.5%). By comparing height and weight to the reference standards and also by comparisons between the same-sex groups, our results confirmed that there was no significant effect on children's height and weight, regardless of whether the injection therapy was combined with oral propranolol at the appropriate dose and with more than 4-week intervals. Intralesional injection of lauromacrogol combined with triamcinolone in the treatment of IH was highly safe and effective.


Assuntos
Desenvolvimento Infantil/efeitos dos fármacos , Hemangioma/tratamento farmacológico , Polidocanol/efeitos adversos , Soluções Esclerosantes/efeitos adversos , Antagonistas Adrenérgicos beta/administração & dosagem , Antagonistas Adrenérgicos beta/efeitos adversos , Estatura/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Feminino , Seguimentos , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Humanos , Lactente , Injeções Intralesionais , Masculino , Polidocanol/administração & dosagem , Propranolol/administração & dosagem , Propranolol/efeitos adversos , Estudos Retrospectivos , Soluções Esclerosantes/administração & dosagem , Resultado do Tratamento , Triancinolona/administração & dosagem , Triancinolona/efeitos adversos
17.
N Engl J Med ; 381(1): 25-35, 2019 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-31269546

RESUMO

BACKGROUND: Achondroplasia is a genetic disorder that inhibits endochondral ossification, resulting in disproportionate short stature and clinically significant medical complications. Vosoritide is a biologic analogue of C-type natriuretic peptide, a potent stimulator of endochondral ossification. METHODS: In a multinational, phase 2, dose-finding study and extension study, we evaluated the safety and side-effect profile of vosoritide in children (5 to 14 years of age) with achondroplasia. A total of 35 children were enrolled in four sequential cohorts to receive vosoritide at a once-daily subcutaneous dose of 2.5 µg per kilogram of body weight (8 patients in cohort 1), 7.5 µg per kilogram (8 patients in cohort 2), 15.0 µg per kilogram (10 patients in cohort 3), or 30.0 µg per kilogram (9 patients in cohort 4). After 6 months, the dose in cohort 1 was increased to 7.5 µg per kilogram and then to 15.0 µg per kilogram, and in cohort 2, the dose was increased to 15.0 µg per kilogram; the patients in cohorts 3 and 4 continued to receive their initial doses. At the time of data cutoff, the 24-month dose-finding study had been completed, and 30 patients had been enrolled in an ongoing long-term extension study; the median duration of follow-up across both studies was 42 months. RESULTS: During the treatment periods in the dose-finding and extension studies, adverse events occurred in 35 of 35 patients (100%), and serious adverse events occurred in 4 of 35 patients (11%). Therapy was discontinued in 6 patients (in 1 because of an adverse event). During the first 6 months of treatment, a dose-dependent increase in the annualized growth velocity was observed with vosoritide up to a dose of 15.0 µg per kilogram, and a sustained increase in the annualized growth velocity was observed at doses of 15.0 and 30.0 µg per kilogram for up to 42 months. CONCLUSIONS: In children with achondroplasia, once-daily subcutaneous administration of vosoritide was associated with a side-effect profile that appeared generally mild. Treatment resulted in a sustained increase in the annualized growth velocity for up to 42 months. (Funded by BioMarin Pharmaceutical; ClinicalTrials.gov numbers, NCT01603095, NCT02055157, and NCT02724228.).


Assuntos
Acondroplasia/tratamento farmacológico , Crescimento/efeitos dos fármacos , Peptídeo Natriurético Tipo C/análogos & derivados , Osteogênese/efeitos dos fármacos , Acondroplasia/fisiopatologia , Adolescente , Biomarcadores/análise , Estatura/efeitos dos fármacos , Criança , Pré-Escolar , Colágeno/sangue , GMP Cíclico/urina , Relação Dose-Resposta a Droga , Feminino , Gráficos de Crescimento , Humanos , Injeções Subcutâneas , Masculino , Peptídeo Natriurético Tipo C/administração & dosagem , Peptídeo Natriurético Tipo C/efeitos adversos , Peptídeo Natriurético Tipo C/uso terapêutico
18.
J Clin Res Pediatr Endocrinol ; 11(4): 329-340, 2019 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-31284701

RESUMO

It is over sixty years since the first administration of human growth hormone (GH) to children with GH deficiency, and over thirty years since recombinant human GH has been available for treatment of GH deficiency and a wider range of non-GH deficiency disorders. From a diagnostic perspective, genetic analysis, using single gene or Sanger sequencing and more recently next generation or whole exome sequencing, has brought advances in the diagnosis of specific causes of short stature, which has enabled therapy to be targeted more accurately. Genetic discoveries have ranged from defects of pituitary development and GH action to abnormalities in intracellular mechanisms, paracrine regulation and cartilage matrix formation. The strategy of GH therapy using standard doses has evolved to individualised GH dosing, depending on diagnosis and predictors of growth response. Evidence of efficacy of GH in GH deficiency, Turner syndrome and short children born small for gestational age is reviewed. The importance of critical assessment of growth response is discussed, together with the recognition and management of a poor or unsatisfactory growth response and the organisational issues related to prevention, detection and intervention regarding suboptimal adherence to GH therapy.


Assuntos
Desenvolvimento do Adolescente/efeitos dos fármacos , Estatura/efeitos dos fármacos , Desenvolvimento Infantil/efeitos dos fármacos , Transtornos do Crescimento/tratamento farmacológico , Terapia de Reposição Hormonal , Hormônio do Crescimento Humano/administração & dosagem , Adolescente , Fatores Etários , Estatura/genética , Criança , Pré-Escolar , Feminino , Predisposição Genética para Doença , Transtornos do Crescimento/genética , Transtornos do Crescimento/fisiopatologia , Terapia de Reposição Hormonal/efeitos adversos , Hormônio do Crescimento Humano/efeitos adversos , Hormônio do Crescimento Humano/deficiência , Humanos , Masculino , Fatores de Tempo , Resultado do Tratamento
19.
Arch Pediatr ; 26(6): 320-323, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31353150

RESUMO

Anorchia, the absence of testes in 46,XY boys, is a very rare condition. It has been suggested that the testicular tissue disappears during pregnancy, as a result of a vascular accident associated with torsion or a genetic cause. Because pubertal growth spurt is directly influenced by androgen exposure, we decided to evaluate the pubertal height gain in nine patients with anorchia who were followed up at the pediatric endocrinology unit of Bicêtre University Hospital. We retrospectively included nine patients with bilateral anorchia whose puberty had been induced by androgen replacement therapy and for whom final height measurements were available. Data were obtained from medical records. Mean gain in pubertal height was 21.7±2.3cm, lower than the expected gain during puberty (25cm, P<0.005). Despite limited experience in this rare condition, androgen replacement therapy seems to allow for good pubertal growth spurt in adolescents with anorchia. However, formal protocols for androgen therapy during puberty may need to be optimized.


Assuntos
Androgênios/uso terapêutico , Estatura/efeitos dos fármacos , Disgenesia Gonadal 46 XY/tratamento farmacológico , Terapia de Reposição Hormonal , Puberdade/fisiologia , Testículo/anormalidades , Testosterona/uso terapêutico , Adolescente , Androgênios/farmacologia , Estudos de Casos e Controles , Criança , Seguimentos , Disgenesia Gonadal 46 XY/fisiopatologia , Humanos , Masculino , Estudos Retrospectivos , Testículo/fisiopatologia , Testosterona/farmacologia , Resultado do Tratamento
20.
PLoS Negl Trop Dis ; 13(6): e0007442, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31166952

RESUMO

BACKGROUND: Mass azithromycin distributions have been shown to reduce mortality among pre-school children in sub-Saharan Africa. It is unclear what mediates this mortality reduction, but one possibility is that antibiotics function as growth promoters for young children. METHODS AND FINDINGS: 24 rural Ethiopian communities that had received biannual mass azithromycin distributions over the previous four years were enrolled in a parallel-group, cluster-randomized trial. Communities were randomized in a 1:1 ratio to either continuation of biannual oral azithromycin (20mg/kg for children, 1 g for adults) or to no programmatic antibiotics over the 36 months of the study period. All community members 6 months and older were eligible for the intervention. The primary outcome was ocular chlamydia; height and weight were measured as secondary outcomes on children less than 60 months of age at months 12 and 36. Study participants were not masked; anthropometrists were not informed of the treatment allocation. Anthropometric measurements were collected for 282 children aged 0-36 months at the month 12 assessment and 455 children aged 0-59 months at the month 36 assessment, including 207 children who had measurements at both time points. After adjusting for age and sex, children were slightly but not significantly taller in the biannually treated communities (84.0 cm, 95%CI 83.2-84.8, in the azithromycin-treated communities vs. 83.7 cm, 95%CI 82.9-84.5, in the untreated communities; mean difference 0.31 cm, 95%CI -0.85 to 1.47, P = 0.60). No adverse events were reported. CONCLUSIONS: Periodic mass azithromycin distributions for trachoma did not demonstrate a strong impact on childhood growth. TRIAL REGISTRATION: The TANA II trial was registered on clinicaltrials.gov #NCT01202331.


Assuntos
Antibacterianos/uso terapêutico , Azitromicina/uso terapêutico , Estatura/efeitos dos fármacos , Quimioprevenção/métodos , Desenvolvimento Infantil/efeitos dos fármacos , Administração Massiva de Medicamentos , Tracoma/prevenção & controle , Animais , Antropometria , Peso Corporal/efeitos dos fármacos , Pré-Escolar , Etiópia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , População Rural
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