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1.
N Engl J Med ; 382(6): 534-544, 2020 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-32023373

RESUMO

BACKGROUND: Worldwide, many newborns who are preterm, small or large for gestational age, or born to mothers with diabetes are screened for hypoglycemia, with a goal of preventing brain injury. However, there is no consensus on a treatment threshold that is safe but also avoids overtreatment. METHODS: In a multicenter, randomized, noninferiority trial involving 689 otherwise healthy newborns born at 35 weeks of gestation or later and identified as being at risk for hypoglycemia, we compared two threshold values for treatment of asymptomatic moderate hypoglycemia. We sought to determine whether a management strategy that used a lower threshold (treatment administered at a glucose concentration of <36 mg per deciliter [2.0 mmol per liter]) would be noninferior to a traditional threshold (treatment at a glucose concentration of <47 mg per deciliter [2.6 mmol per liter]) with respect to psychomotor development at 18 months, assessed with the Bayley Scales of Infant and Toddler Development, third edition, Dutch version (Bayley-III-NL; scores range from 50 to 150 [mean {±SD}, 100±15]), with higher scores indicating more advanced development and 7.5 points (one half the SD) representing a clinically important difference). The lower threshold would be considered noninferior if scores were less than 7.5 points lower than scores in the traditional-threshold group. RESULTS: Bayley-III-NL scores were assessed in 287 of the 348 children (82.5%) in the lower-threshold group and in 295 of the 341 children (86.5%) in the traditional-threshold group. Cognitive and motor outcome scores were similar in the two groups (mean scores [±SE], 102.9±0.7 [cognitive] and 104.6±0.7 [motor] in the lower-threshold group and 102.2±0.7 [cognitive] and 104.9±0.7 [motor] in the traditional-threshold group). The prespecified inferiority limit was not crossed. The mean glucose concentration was 57±0.4 mg per deciliter (3.2±0.02 mmol per liter) in the lower-threshold group and 61±0.5 mg per deciliter (3.4±0.03 mmol per liter) in the traditional-threshold group. Fewer and less severe hypoglycemic episodes occurred in the traditional-threshold group, but that group had more invasive diagnostic and treatment interventions. Serious adverse events in the lower-threshold group included convulsions (during normoglycemia) in one newborn and one death. CONCLUSIONS: In otherwise healthy newborns with asymptomatic moderate hypoglycemia, a lower glucose treatment threshold (36 mg per deciliter) was noninferior to a traditional threshold (47 mg per deciliter) with regard to psychomotor development at 18 months. (Funded by the Netherlands Organization for Health Research and Development; HypoEXIT Current Controlled Trials number, ISRCTN79705768.).


Assuntos
Glicemia/análise , Glucose/administração & dosagem , Hipoglicemia/terapia , Doenças do Recém-Nascido/terapia , Transtornos Psicomotores/prevenção & controle , Desenvolvimento Infantil/efeitos dos fármacos , Nutrição Enteral , Humanos , Hipoglicemia/sangue , Fenômenos Fisiológicos da Nutrição do Lactente , Recém-Nascido , Doenças do Recém-Nascido/sangue , Infusões Intravenosas , Valores de Referência
2.
ABCS health sci ; 44(2): 85-91, 11 out 2019. tab
Artigo em Português | LILACS | ID: biblio-1022335

RESUMO

INTRODUÇÃO: A prevalência da desnutrição infantil vem diminuindo em todo o mundo, mas ainda acomete milhões de crianças, especialmente indígenas. Devido ao elevado número de doenças infecciosas associadas à desnutrição, a antibioticoterapia faz parte da terapêutica recomendada. OBJETIVO: Observar os casos de desnutrição entre crianças indígenas e não indígenas hospitalizadas e a terapêutica empregada durante o tratamento. MÉTODOS: Estudo de coorte retrospectivo, farmacoepidemiológico, realizado com informações extraídas de prontuários arquivados do período de janeiro de 2012 a dezembro de 2014 de um hospital público. RESULTADOS: Participaram 166 crianças, sendo o número de crianças indígenas aproximadamente seis vezes maior do que não indígenas. Houve maior prevalência entre lactentes e crianças com idade inferior a um ano apresentaram mais chances de serem internadas por desnutrição. Os diagnósticos de desnutrição mais vistos foram os inespecíficos, com uma proporção significativa de óbitos relacionados ao diagnóstico E43. As infecções mais comuns foram do sistema digestório e respiratório. Crianças indígenas tiveram quase cinco vezes mais chances de apresentarem infecção respiratória. A maior proporção recebeu até três antibióticos, havendo crianças que receberam mais que sete antibióticos diferentes durante o período de internação. CONCLUSÃO: A população infantil deve ser acompanhada por meio de inquéritos que possam subsidiar políticas de saúde que atendam suas necessidades. É necessária a capacitação dos profissionais envolvidos no cuidado da criança desnutrida, recursos materiais e financeiros, a fim diminuir o número de diagnósticos inespecíficos e evitar o uso indiscriminado de antibióticos, sendo imprescindível uma política de controle efetiva no uso da politerapia antimicrobiana.


INTRODUCTION: The prevalence of child malnutrition is declining worldwide, but still affects millions of children, especially indigenous people. Due to the high number of infectious diseases associated with malnutrition, antibiotic therapy is part of the recommended therapy. OBJECTIVE: To observe the cases of malnutrition among hospitalized indigenous and non-indigenous children and the therapy used during treatment. METHODS: Retrospective cohort study, pharmacoepidemiological, carried out with information extracted from medical records filed from January 2012 to December 2014 of a public hospital. RESULTS: 166 children participated, with the number of indigenous children being approximately six times higher than that of nonindigenous children. There was a higher prevalence among infants and children under one year of age who were more likely to be hospitalized for malnutrition. The most frequent diagnoses of malnutrition were nonspecific, with a significant proportion of deaths related to diagnosis E43. The most common infections were of the digestive and respiratory system. Indigenous children were almost five times more likely to have respiratory infection. The highest proportion received up to three antibiotics, with children receiving more than seven different antibiotics during the hospitalization period. CONCLUSION: The child population must be accompanied by surveys that can subsidize health policies that meet their needs. It is necessary to train the professionals involved in the care of malnourished children, material and financial resources, in order to reduce the number of non-specific diagnoses and to avoid the indiscriminate use of antibiotics, a policy of effective control in the use of antimicrobial polytherapy is essential.


Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Índios Sul-Americanos , Desenvolvimento Infantil/efeitos dos fármacos , Desnutrição , Saúde de Populações Indígenas , Antibacterianos/uso terapêutico , Resistência Microbiana a Medicamentos , Transtornos da Nutrição Infantil/tratamento farmacológico , Saúde da Criança , Farmacorresistência Bacteriana/efeitos dos fármacos
3.
Klin Padiatr ; 231(5): 262-268, 2019 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-31505693

RESUMO

OBJECTIVE: The consumption of illegal substances during pregnancy is an increasing social and medical issue. Main substances of prenatal drug exposure are beside tehtrahydrocannabinol (THC), opioids and methamphetamine. The effect of these substances on the long-term development of children remains uncertain. METHODS: Since 2012 newborn infants born at the university hospital of children at Leipzig which were prenatal exposed to drugs were followed long-term at the out-patient clinic for child protection. For 42 children with prenatal opioid or methamphetamine exposure the developmentent was analysed using the Bayley Scales (BSID III) at the age of 2-3 years. The children were compared with 84 unexposed control children. One case matched to 2 controls, adapted by age, gender, gestational age and birth weight. RESULTS: Motoric development between prenatal methylamphetamine, opioid exposed children and the control group showed no significant difference. Methylamphetamine exposed children (n=23) At 2 exposure show significantly lower scores in cognition and language (79,1 compared 95,9 of the control group), opioid exposed children have a slight cognitive deficits with a medium score of 91,7 (n=19). 56% of the methamphetamine group were developmentally retarded at the measurement date. Additionally, children had significant lower Bayley Scores which had single parent and/ or low educational and professional qualifications of their caregiver. Both substances increased the risk of postnatal complications to 46-53% despite of similar gestational ages in all groups. CONCLUSION: Children with prenatal methamphetamine or opioid exposure seem to have cognition and language deficits at 2 and 3 years of age. Methamphetamine might have a higher negative effect than opioids. The psychosocial risk factors associated with parental drug abuse are important for achieving age-appropriate development.


Assuntos
Analgésicos Opioides/toxicidade , Desenvolvimento Infantil/efeitos dos fármacos , Cognição/efeitos dos fármacos , Metanfetamina/toxicidade , Atividade Motora/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Comportamento do Lactente/efeitos dos fármacos , Comportamento do Lactente/psicologia , Recém-Nascido , Linguagem , Gravidez , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Efeitos Tardios da Exposição Pré-Natal/psicologia
4.
Cochrane Database Syst Rev ; 9: CD000371, 2019 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-31508807

RESUMO

BACKGROUND: The World Health Organization (WHO) recommends treating all school children at regular intervals with deworming drugs in areas where helminth infection is common. Global advocacy organizations claim routine deworming has substantive health and societal effects beyond the removal of worms. In this update of the 2015 edition we included six new trials, additional data from included trials, and addressed comments and criticisms. OBJECTIVES: To summarize the effects of public health programmes to regularly treat all children with deworming drugs on child growth, haemoglobin, cognition, school attendance, school performance, physical fitness, and mortality. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register; Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; Embase; LILACS; the metaRegister of Controlled Trials (mRCT); reference lists; and registers of ongoing and completed trials up to 19 September 2018. SELECTION CRITERIA: We included randomized controlled trials (RCTs) and quasi-RCTs that compared deworming drugs for soil-transmitted helminths (STHs) with placebo or no treatment in children aged 16 years or less, reporting on weight, height, haemoglobin, and formal tests of cognition. We also sought data on other measures of growth, school attendance, school performance, physical fitness, and mortality. DATA COLLECTION AND ANALYSIS: At least two review authors independently assessed the trials for inclusion, risk of bias, and extracted data. We analysed continuous data using the mean difference (MD) with 95% confidence intervals (CIs). Where data were missing, we contacted trial authors. We stratified the analysis based on the background burden of STH infection. We used outcomes at time of longest follow-up. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We identified 51 trials, including 10 cluster-RCTs, that met the inclusion criteria. One trial evaluating mortality included over one million children, and the remaining 50 trials included a total of 84,336 participants. Twenty-four trials were in populations categorized as high burden, including nine trials in children selected because they were helminth-stool positive; 18 with intermediate burden; and nine as low burden.First or single dose of deworming drugsFourteen trials reported on weight after a single dose of deworming drugs (4970 participants, 14 RCTs). The effects were variable. There was little or no effect in studies conducted in low and intermediate worm burden groups. In the high-burden group, there was little or no effect in most studies, except for a large effect detected from one study area in Kenya reported in two trials carried out over 30 years ago. These trials result in qualitative heterogeneity and uncertainty in the meta-analysis across all studies (I2 statistic = 90%), with GRADE assessment assessed as very low-certainty, which means we do not know if a first dose or single dose of deworming impacts on weight.For height, most studies showed little or no effect after a single dose, with one of the two trials in Kenya from 30 years ago showing a large average difference (2621 participants, 10 trials, low-certainty evidence). Single dose probably had no effect on average haemoglobin (MD 0.10 g/dL, 95% CI 0.03 lower to 0.22 higher; 1252 participants, five trials, moderate-certainty evidence), or on average cognition (1596 participants, five trials, low-certainty evidence). The data are insufficient to know if there is an effect on school attendance and performance (304 participants, one trial, low-certainty evidence), or on physical fitness (280 participants, three trials, very low-certainty evidence). No trials reported on mortality.Multiple doses of deworming drugsThe effect of regularly treating children with deworming drugs given every three to six months on weight was reported in 18 trials, with follow-up times of between six months and three years; there was little or no effect on average weight in all but two trials, irrespective of worm prevalence-intensity. The two trials with large average weight gain included one in the high burden area in Kenya carried out over 30 years ago, and one study from India in a low prevalence area where subsequent studies in the same area did not show an effect. This heterogeneity causes uncertainty in any meta-analysis (I2 = 78%). Post-hoc analysis excluding trials published prior to 2000 gave an estimate of average difference in weight gain of 0.02 kg (95%CI from 0.04 kg loss to 0.08 gain, I2 = 0%). Thus we conclude that we do not know if repeated doses of deworming drugs impact on average weight, with a fewer older studies showing large gains, and studies since 2000 showing little or no average gain.Regular treatment probably had little or no effect on the following parameters: average height (MD 0.02 cm higher, 95% CI 0.09 lower to 0.13 cm higher; 13,700 participants, 13 trials, moderate-certainty evidence); average haemoglobin (MD 0.01 g/dL lower; 95% CI 0.05 g/dL lower to 0.07 g/dL higher; 5498 participants, nine trials, moderate-certainty evidence); formal tests of cognition (35,394 participants, 8 trials, moderate-certainty evidence); school performance (34,967 participants, four trials, moderate-certainty evidence). The evidence assessing an effect on school attendance is inconsistent, and at risk of bias (mean attendance 2% higher, 95% CI 5% lower to 8% higher; 20,650 participants, three trials, very low-certainty evidence). No trials reported on physical fitness. No effect was shown on mortality (1,005,135 participants, three trials, low-certainty evidence). AUTHORS' CONCLUSIONS: Public health programmes to regularly treat all children with deworming drugs do not appear to improve height, haemoglobin, cognition, school performance, or mortality. We do not know if there is an effect on school attendance, since the evidence is inconsistent and at risk of bias, and there is insufficient data on physical fitness. Studies conducted in two settings over 20 years ago showed large effects on weight gain, but this is not a finding in more recent, larger studies. We would caution against selecting only the evidence from these older studies as a rationale for contemporary mass treatment programmes as this ignores the recent studies that have not shown benefit.The conclusions of the 2015 edition have not changed in this update.


Assuntos
Anti-Helmínticos/uso terapêutico , Helmintíase/tratamento farmacológico , Enteropatias Parasitárias , Estado Nutricional , Solo/parasitologia , Ganho de Peso , Peso Corporal , Criança , Desenvolvimento Infantil/efeitos dos fármacos , Cognição , Doenças Endêmicas , Humanos , Enteropatias Parasitárias/complicações , Enteropatias Parasitárias/tratamento farmacológico , Saúde Pública , Ensaios Clínicos Controlados Aleatórios como Assunto
5.
PLoS Med ; 16(8): e1002848, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31386659

RESUMO

BACKGROUND: Metformin is increasingly offered as an acceptable and economic alternative to insulin for treatment of gestational diabetes mellitus (GDM) in many countries. However, the impact of maternal metformin treatment on the trajectory of fetal, infant, and childhood growth is unknown. METHODS AND FINDINGS: PubMed, Ovid Embase, Medline, Web of Science, ClinicalTrials.gov, and the Cochrane database were systematically searched (from database inception to 26 February 2019). Outcomes of GDM-affected pregnancies randomised to treatment with metformin versus insulin were included (randomised controlled trials and prospective randomised controlled studies) from cohorts including European, American, Asian, Australian, and African women. Studies including pregnant women with pre-existing diabetes or non-diabetic women were excluded, as were trials comparing metformin treatment with oral glucose-lowering agents other than insulin. Two reviewers independently assessed articles for eligibility and risk of bias, and conflicts were resolved by a third reviewer. Outcome measures were parameters of fetal, infant, and childhood growth, including weight, height, BMI, and body composition. In total, 28 studies (n = 3,976 participants) met eligibility criteria and were included in the meta-analysis. No studies reported fetal growth parameters; 19 studies (n = 3,723 neonates) reported measures of neonatal growth. Neonates born to metformin-treated mothers had lower birth weights (mean difference -107.7 g, 95% CI -182.3 to -32.7, I2 = 83%, p = 0.005) and lower ponderal indices (mean difference -0.13 kg/m3, 95% CI -0.26 to 0.00, I2 = 0%, p = 0.04) than neonates of insulin-treated mothers. The odds of macrosomia (odds ratio [OR] 0.59, 95% CI 0.46 to 0.77, p < 0.001) and large for gestational age (OR 0.78, 95% CI 0.62 to 0.99, p = 0.04) were lower following maternal treatment with metformin compared to insulin. There was no difference in neonatal height or incidence of small for gestational age between groups. Two studies (n = 411 infants) reported measures of infant growth (18-24 months of age). In contrast to the neonatal phase, metformin-exposed infants were significantly heavier than those in the insulin-exposed group (mean difference 440 g, 95% CI 50 to 830, I2 = 4%, p = 0.03). Three studies (n = 520 children) reported mid-childhood growth parameters (5-9 years). In mid-childhood, BMI was significantly higher (mean difference 0.78 kg/m2, 95% CI 0.23 to 1.33, I2 = 7%, p = 0.005) following metformin exposure than following insulin exposure, although the difference in absolute weights between the groups was not significantly different (p = 0.09). Limited evidence (1 study with data treated as 2 cohorts) suggested that adiposity indices (abdominal [p = 0.02] and visceral [p = 0.03] fat volumes) may be higher in children born to metformin-treated compared to insulin-treated mothers. Study limitations include heterogeneity in metformin dosing, heterogeneity in diagnostic criteria for GDM, and the scarcity of reporting of childhood outcomes. CONCLUSIONS: Following intrauterine exposure to metformin for treatment of maternal GDM, neonates are significantly smaller than neonates whose mothers were treated with insulin during pregnancy. Despite lower average birth weight, metformin-exposed children appear to experience accelerated postnatal growth, resulting in heavier infants and higher BMI by mid-childhood compared to children whose mothers were treated with insulin. Such patterns of low birth weight and postnatal catch-up growth have been reported to be associated with adverse long-term cardio-metabolic outcomes. This suggests a need for further studies examining longitudinal perinatal and childhood outcomes following intrauterine metformin exposure. This review protocol was registered with PROSPERO under registration number CRD42018117503.


Assuntos
Desenvolvimento Infantil/efeitos dos fármacos , Diabetes Gestacional/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Metformina/uso terapêutico , Pré-Escolar , Feminino , Humanos , Hipoglicemiantes/efeitos adversos , Lactente , Recém-Nascido , Insulina/efeitos adversos , Metformina/efeitos adversos , Gravidez
6.
Environ Res ; 177: 108641, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31421445

RESUMO

Lead (Pb) is a worldwide environmental contaminant that even at low levels influences brain development and affects neurobehavior later in life; nevertheless it is only a small fraction of the neurotoxicant (NT) exposome. Exposure to environmental Pb concurrent with other NT substances is often the norm, but their joint effects are challenging to study during early life. The aim of this review is to integrate studies of Pb-containing NT mixtures during the early life and neurodevelopment outcomes of children. The Pb-containing NT mixtures that have been most studied involve other metals (Mn, Al, Hg, Cd), metalloids (As), halogen (F), and organo-halogen pollutants. Co-occurring Pb-associated exposures during pregnancy and lactation depend on the environmental sources and the metabolism and half-life of the specific NT contaminant; but offspring neurobehavioral outcomes are also influenced by social stressors. Nevertheless, Pb-associated effects from prenatal exposure portend a continued burden on measurable neurodevelopment; they thus favor increased neurological health issues, decrements in neurobehavioral tests and reductions in the quality of life. Neurobehavioral test outcomes measured in the first 1000 days showed Pb-associated negative outcomes were frequently noticed in infants (<6 months). In older (preschool and school) children studies showed more variations in NT mixtures, children's age, and sensitivity and/or specificity of neurobehavioral tests; these variations and choice of statistical model (individual NT stressor or collective effect of mixture) may explain inconsistencies. Multiple exposures to NT mixtures in children diagnosed with 'autism spectrum disorders' (ASD) and 'attention deficit and hyperactivity disorders' (ADHD), strongly suggest a Pb-associated effect. Mixture potency (number or associated NT components and respective concentrations) and time (duration and developmental stage) of exposure often showed a measurable impact on neurodevelopment; however, net effects, reversibility and/or predictability of delays are insufficiently studied and need urgent attention. Nevertheless, neurodevelopment delays can be prevented and/or attenuated if public health policies are implemented to protect the unborn and the young child.


Assuntos
Sistema Nervoso Central/efeitos dos fármacos , Exposição Ambiental/efeitos adversos , Poluentes Ambientais/toxicidade , Chumbo/toxicidade , Efeitos Tardios da Exposição Pré-Natal , Criança , Desenvolvimento Infantil/efeitos dos fármacos , Pré-Escolar , Feminino , Humanos , Lactente , Gravidez , Qualidade de Vida
7.
Pediatrics ; 144(2)2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31337693

RESUMO

OBJECTIVE: Among extremely preterm infants, we evaluated whether bevacizumab therapy compared with surgery for retinopathy of prematurity (ROP) is associated with adverse outcomes in early childhood. METHODS: This study was a retrospective analysis of prospectively collected data on preterm (22-26 + 6/7 weeks' gestational age) infants admitted to the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network centers who received bevacizumab or surgery exclusively for ROP. The primary outcome was death or severe neurodevelopmental impairment (NDI) at 18 to 26 months' corrected age (Bayley Scales of Infant and Toddler Development, Third Edition cognitive or motor composite score <70, Gross Motor Functional Classification Scale level ≥2, bilateral blindness or hearing impairment). RESULTS: The cohort (N = 405; 214 [53%] boys; median [interquartile range] gestational age: 24.6 [23.9-25.3] weeks) included 181 (45%) infants who received bevacizumab and 224 (55%) who underwent ROP surgery. Infants treated with bevacizumab had a lower median (interquartile range) birth weight (640 [541-709] vs 660 [572.5-750] g; P = .02) and longer durations of conventional ventilation (35 [21-58] vs 33 [18-49] days; P = .04) and supplemental oxygen (112 [94-120] vs 105 [84.5-120] days; P = .01). Death or severe NDI (adjusted odds ratio [aOR] 1.42; 95% confidence interval [CI] 0.94 to 2.14) and severe NDI (aOR 1.14; 95% CI 0.76 to 1.70) did not differ between groups. Odds of death (aOR 2.54 [95% CI 1.42 to 4.55]; P = .002), a cognitive score <85 (aOR 1.78 [95% CI 1.09 to 2.91]; P = .02), and a Gross Motor Functional Classification Scale level ≥2 (aOR 1.73 [95% CI 1.04 to 2.88]; P = .04) were significantly higher with bevacizumab therapy. CONCLUSIONS: In this multicenter cohort of preterm infants, ROP treatment modality was not associated with differences in death or NDI, but the bevacizumab group had higher mortality and poor cognitive outcomes in early childhood. These data reveal the need for a rigorous appraisal of ROP therapy.


Assuntos
Bevacizumab/uso terapêutico , Desenvolvimento Infantil/efeitos dos fármacos , Desenvolvimento Infantil/fisiologia , Recém-Nascido Prematuro/crescimento & desenvolvimento , Retinopatia da Prematuridade/tratamento farmacológico , Retinopatia da Prematuridade/cirurgia , Adulto , Inibidores da Angiogênese/uso terapêutico , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Masculino , Transtornos do Neurodesenvolvimento/mortalidade , Transtornos do Neurodesenvolvimento/prevenção & controle , Estudos Prospectivos , Retinopatia da Prematuridade/mortalidade , Estudos Retrospectivos
8.
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
9.
Pediatrics ; 144(2)2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31320466

RESUMO

The developmental impact of opioid use during pregnancy is a subject of ongoing debate. Short-term neonatal outcomes, such as lower birth weight and neonatal abstinence syndrome, are the most well-recognized outcomes. However, knowledge gaps exist regarding longer-term neurocognitive and mental health outcomes. In this article, we summarize an expert panel discussion that was held in April 2018 by the Substance Abuse and Mental Health Services Administration and attended by national experts in the field of perinatal opioid exposure and its impact on child development. Despite the challenges with research in this area, there is emerging literature revealing an association between neonates exposed to opioids in utero and longer-term adverse neurocognitive, behavioral, and developmental outcomes. Although adverse sequalae may not be apparent in the neonatal period, they may become more salient as children develop and reach preschool and school age. Multiple variables (genetic, environmental, and biological) result in a highly complex picture. The next steps and strategies to support families impacted by opioid use disorder are explored. Model programs are also considered, including integrated care for the child and mother, parenting supports, and augmentations to home visiting.


Assuntos
Analgésicos Opioides/efeitos adversos , Comportamento Infantil/efeitos dos fármacos , Desenvolvimento Infantil/efeitos dos fármacos , Cognição/efeitos dos fármacos , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Criança , Comportamento Infantil/fisiologia , Comportamento Infantil/psicologia , Desenvolvimento Infantil/fisiologia , Cognição/fisiologia , Congressos como Assunto , Feminino , Humanos , Masculino , Transtornos Relacionados ao Uso de Opioides/diagnóstico , Transtornos Relacionados ao Uso de Opioides/psicologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/diagnóstico , Efeitos Tardios da Exposição Pré-Natal/psicologia , Estados Unidos/epidemiologia , United States Substance Abuse and Mental Health Services Administration/tendências
10.
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
11.
Environ Pollut ; 252(Pt B): 1550-1560, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31277024

RESUMO

This study aimed to assess the association between exposure to chromium and neuropsychological development among children. A cross-sectional study was conducted with 393 children aged 6-11 years old randomly selected from State-funded schools in two provinces in Southern Spain (Almeria and Huelva), in 2010 and 2012. Chromium levels in urine and hair samples were analyzed by inductively coupled plasma mass spectrometry with an octopole reaction system. Neuropsychological development was evaluated using the Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV) and three computerized tests from the Behavioural Assessment and Research System (BARS): Reaction Time Test (RTT), Continuous Performance Test (CPT) and Selective Attention Test (SAT). Multivariable linear regression models adjusted for potential confounders, including heavy metals, were applied to examine the association between chromium levels and neuropsychological outcomes. A 10-fold increase in urine chromium levels was associated with a decrease of 5.99 points on the WISC-IV Full-Scale IQ (95% CI: 11.98 to -0.02). Likewise, a 10-fold increase in urine chromium levels in boys was associated with a decrease of 0.03 points in the percentage of omissions (95% CI: 0.0 to 0.05) in the SAT, with an increase of 68.35 points in latency (95% CI: 6.60 to 130.12) in the RTT, and with an increase in the number of trials with latencies > 1000 ms (ß = 37.92; 95% CI: 2.73 to 73.12) in the RTT. An inverse significant association was detected between chromium levels in hair and latency in the SAT in boys (ß = -50.53; 95% CI: 86.86 to -14.22) and girls (ß = -55.95; 95% CI: 78.93 to -32.97). Excluding trials with latencies >1000 ms in the RTT increased latency scores by 29.36 points in boys (95% CI: 0.17 to 58.57), and 39.91 points in girls (95% CI: 21.25 to 58.59). This study is the first to show the detrimental effects of postnatal chromium exposure on neuropsychological development in school-aged children.


Assuntos
Atenção/efeitos dos fármacos , Desenvolvimento Infantil/efeitos dos fármacos , Cromo/análise , Exposição Ambiental/efeitos adversos , Poluentes Ambientais/análise , Inteligência/efeitos dos fármacos , Criança , Cromo/urina , Estudos Transversais , Exposição Ambiental/análise , Poluentes Ambientais/urina , Feminino , Cabelo/química , Humanos , Masculino , Testes Neuropsicológicos , Distribuição Aleatória , Espanha
12.
J Pediatr Endocrinol Metab ; 32(8): 879-884, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31271556

RESUMO

Background There is little evidence of the effects of early treatment with growth hormone (GH) in infants with Prader-Willi syndrome (PWS). A prospective study was conducted to assess the safety of GH therapy in infants younger than 2 years of age with PWS. Methods A total of 14 patients with PWS started treatment with GH under the age of 2 years and were followed over a 2-year period. A deletion of chromosome 15 was present in nine infants (64.3%) and maternal uniparental disomy 15 in five infants (35.7%). The median age at start of GH treatment was 9.6 months (interquartile range [IQR] 9.0-18.3 months). Changes in height standard deviation score (SDS), body mass index (BMI) SDS and subcapsular and tricipital skinfolds in the follow-up period were evaluated with a mixed-model regression analysis using the Package R. Results There were no fatal adverse events. A significant decrease (p < 0.001) in tricipital and subcapsular skinfold thickness, with an upward trend of height SDS and a downward trend of BMI SDS, was observed. Infants who started GH before 15 months of age started walking at a median of 18.0 [17.0-19.5] months vs. 36.6 [36.3-37.8] months for those who began treatment with GH after 15 months of age (p = 0.024). Conclusions GH treatment in infants with PWS less than 2 years of age is safe and improved body composition. Infants who received GH before the age of 15 months started to walk earlier.


Assuntos
Composição Corporal , Estatura , Índice de Massa Corporal , Hormônio do Crescimento Humano/administração & dosagem , Síndrome de Prader-Willi/tratamento farmacológico , Desenvolvimento Infantil/efeitos dos fármacos , Cognição/efeitos dos fármacos , Feminino , Seguimentos , Humanos , Lactente , Masculino , Atividade Motora/efeitos dos fármacos , Prognóstico , Estudos Prospectivos , Segurança
13.
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
14.
Drugs ; 79(10): 1053-1063, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31183768

RESUMO

The inflammatory bowel diseases commonly affect individuals during their peak reproductive years. Patients are often concerned about the impact of medical therapies on their ability to conceive, effect on the fetus, as well as the ability to breastfeed, which has led to poor medical adherence during pregnancy. However, most medications are safe, and discontinuation may lead to active disease, which is associated with adverse materno-fetal outcomes. The anti-TNF biologic therapies, infliximab and adalimumab have been extensively studied in the context of pregnancy. They are actively transferred to the placenta during the second and third trimesters; these have not been associated with an increased rate of congenital abnormalities or fetal death. The minimal amounts of drug that are transferred to breast milk are proteolyzed by the infant's digestive system with no reported short- or long-term adverse effects. There is a paucity of clinical data for the other approved anti-TNF agents or newer anti-integrin (vedolizumab) and anti-interleukin (ustekinumab) therapies used in the management of inflammatory bowel disease; however, no significant safety signals have been documented thus far. The new oral small molecule therapy, tofacitinib is teratogenic in animal models and is contra-indicated in patients attempting pregnancy. It is important that patients, as well as physicians managing patients with these conditions, be aware of the impact of these medical therapies during pregnancy.


Assuntos
Adalimumab/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/administração & dosagem , Ustekinumab/administração & dosagem , Adalimumab/efeitos adversos , Administração Oral , Anticorpos Monoclonais Humanizados/efeitos adversos , Aleitamento Materno , Desenvolvimento Infantil/efeitos dos fármacos , Feminino , Humanos , Recém-Nascido , Infliximab/efeitos adversos , Leite Humano/química , Leite Humano/metabolismo , Gravidez , Transdução de Sinais , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Ustekinumab/efeitos adversos
15.
Chemosphere ; 233: 387-395, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31176902

RESUMO

Polybrominated diphenylethers (PBDEs) are persistent organic pollutants (POPs), they are considered endocrine disruptors and can bioaccumulate in nature, and in living tissue. Human exposure to and the presence of PBDEs in human samples is of concern due to their potential health risks. Young children are one of the most vulnerable populations to PBDE's potential health effects. Ninety-one serum samples of 6-year-old children, residing in a contaminated location, due to former production of polychlorinated biphenyls (PCBs), were analysed to examine children's exposure to PBDEs in Slovakia. Median serum concentrations found for individual PBDE congeners BDE-28+33, -47, -99, -100, -153, -154 and -183 were 0.015, 0.184, 0.079, 0.046, 0.176, 0.014, and 0.097 ng g-1 lipid weight, respectively. Children's preschool maturity was measured using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III) test. In multivariate analyses BDE-153 serum concentrations were significantly inversely associated with WPPSI-III composite score (p = 0.011, ß = -23.6), while adjusting for PCB-153 and sex. Significant negative associations were observed for BDE-153 serum concentrations (p = 0.002, ß = -29.8) and WPPSI-III composite score, after controlling for PCB-118 and sex. Negative associations were also observed for BDE-47, BDE-100 and BDE-153, with different individual WPPSI subtest scores, after adjustment with PCB-153 and/or PCB-118 and sex. Serum concentrations of PCB-153 and PCB-118 were not statistically significantly associated with WPPSI-III composite score and individual subtest scores. These findings demonstrate adverse effects of PBDE serum exposure on preschool maturity of children, and PBDEs potentially negative impact on child neuropsychological development.


Assuntos
Desenvolvimento Infantil/efeitos dos fármacos , Disruptores Endócrinos/sangue , Poluentes Ambientais/sangue , Éteres Difenil Halogenados/sangue , Bifenil Polibromatos/sangue , Pré-Escolar , Feminino , Humanos , Masculino , Eslováquia
16.
Environ Sci Pollut Res Int ; 26(18): 18267-18290, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31041704

RESUMO

Exposure to pesticides is a major factor in the cause of dysfunction in the nervous system and neurodevelopment disorders in children at critical periods of great vulnerability. The aim of this study was to review scientific evidence published on neurodevelopmental effects of prenatal and postnatal exposure to organophosphate pesticides (OPs) in different stages, including neonates, infants, toddlers, preschool children, and school-age children. Full-text articles published in PubMed, Scopus, and ISI databases between 1973 and 2019 were reviewed and the scientific evidence was evaluated. Results: Fifty studies were eligible for inclusion in this quantitative synthesis. Fifteen of these papers evaluated the effects on neonates and infants, 18 on the effects on toddlers and preschool children, and 24 the effects on school-age children. Considerable evidence suggests that prenatal exposure to OPs contributes to child neurodevelopment disorders in all stages, whereas data about the effects of postnatal exposure are limited. Therefore, the available evidence supports the theory that sensitive time-windows occur prenatally rather than postnatally. Although 45 out of the total 50 selected articles found an association between OP exposure and child neurodevelopment, some of the evidence is controversial. A standardized methodology is needed to enable the comparison of the results in several studies, and further research studies are needed to warrant firmer conclusions. A systematic review of this evidence should be performed continuously to update the state of knowledge regarding neurodevelopmental effects associated with OP exposure.


Assuntos
Poluentes Ambientais/toxicidade , Sistema Nervoso/efeitos dos fármacos , Organofosfatos/toxicidade , Praguicidas/toxicidade , Adolescente , Criança , Desenvolvimento Infantil/efeitos dos fármacos , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Sistema Nervoso/crescimento & desenvolvimento , Praguicidas/farmacologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal
17.
Depress Anxiety ; 36(8): 753-765, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31066992

RESUMO

BACKGROUND: Prenatal maternal depression (PMD) and selective serotonin reuptake inhibitor (SSRI) antidepressants are associated with increased developmental risk in infants. Reports suggest that PMD is associated with hyperconnectivity of the insula and the amygdala, while SSRI exposure is associated with hyperconnectivity of the auditory network in the infant brain. However, associations between functional brain organization and PMD and/or SSRI exposure are not well understood. METHODS: We examined the relation between PMD or SSRI exposure and neonatal brain functional organization. Infants of control (n = 17), depressed SSRI-treated (n = 20) and depressed-only (HAM-D ≥ 8) (n = 16) women, underwent resting-state functional magnetic resonance imaging at postnatal Day 6. At 6 months, temperament was assessed using Infant Behavioral Questionnaire (IBQ). We applied GTA and partial least square regression (PLSR) to the resting-state time series to assess group differences in modularity, and connector and provincial hubs. RESULTS: Modularity was similar across all groups. The depressed-only group showed higher connector hub values in the left anterior cingulate, insula, and caudate as well as higher provincial hub values in the amygdala compared to the control group. The SSRI group showed higher provincial hub values in Heschl's gyrus relative to the depressed-only group. PLSR showed that newborns' hub values predicted 10% of the variability in infant temperament at 6 months, suggesting different developmental patterns between groups. CONCLUSIONS: Prenatal exposures to maternal depression and SSRIs have differential impacts on neonatal functional brain organization. Hub values at 6 days predict variance in temperament between infant groups at 6 months of age.


Assuntos
Encéfalo/fisiopatologia , Transtorno Depressivo/tratamento farmacológico , Mães/psicologia , Complicações na Gravidez/fisiopatologia , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Inibidores de Captação de Serotonina/uso terapêutico , Adulto , Antidepressivos/uso terapêutico , Encéfalo/efeitos dos fármacos , Mapeamento Encefálico/métodos , Desenvolvimento Infantil/efeitos dos fármacos , Transtorno Depressivo/fisiopatologia , Transtorno Depressivo/psicologia , Feminino , Humanos , Lactente , Recém-Nascido , Imagem por Ressonância Magnética/métodos , Vias Neurais/diagnóstico por imagem , Vias Neurais/efeitos dos fármacos , Gravidez , Complicações na Gravidez/tratamento farmacológico , Complicações na Gravidez/psicologia , Temperamento/efeitos dos fármacos
19.
Chemosphere ; 228: 204-211, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31029966

RESUMO

BACKGROUND: Chlorophenols (CPs), suspected as endocrine disrupting chemicals, exposure during early life may contribute to body size. However, limited human data with inconsistent findings have examined the developmental effects of CPs exposure. OBJECTIVE: To explore associations between prenatal and postnatal CPs exposure and anthropometric parameters in children aged 3 years. METHODS: A subset of 377 mother-child pairs with urinary five CP concentrations were enrolled from a prospective birth cohort. Generalized linear models were conducted to evaluate associations of CPs exposure with children's anthropometric measures. RESULTS: Maternal urinary 2,4,6-trichlorophenol (2,4,6-TCP) concentrations were significantly negatively associated with weight z scores [regression coefficient (ß) = -0.51, 95% confidence interval (CI): -0.96, -0.05; p = 0.01], weight for height z scores (ß = -0.54, 95% CI: -1.02, -0.06; p = 0.01) and body mass index (BMI) z scores (ß = -0.53, 95% CI: -1.03, -0.03; p = 0.01) of children aged 3 years, after adjustment for potential confounders and postnatal CPs exposure. In the sex-stratified analyses, these inverse associations remained among boys, while in girls, positive associations of prenatal 2,4,6-TCP exposure with weight for height z scores and BMI z scores were observed. Postnatal exposure to 2,5-diclorophenol (2,5-DCP) was positively associated with weight z scores (ß = 0.26, 95% CI: 0.02, 0.50; p = 0.04), after controlling for possible confounders and maternal CPs exposure during pregnancy. Considering potential sex-specific effects, these associations were only observed in girls. CONCLUSIONS: Our findings indicate that prenatal 2,4,6-TCP exposure and postnatal 2,5-DCP exposure may have adverse and sex-specific effects on children's physical development.


Assuntos
Pesos e Medidas Corporais , Desenvolvimento Infantil/efeitos dos fármacos , Clorofenóis/farmacologia , Exposição Ambiental/efeitos adversos , Exposição Materna/efeitos adversos , Adulto , Pré-Escolar , Clorofenóis/efeitos adversos , Clorofenóis/urina , Disruptores Endócrinos/efeitos adversos , Feminino , Humanos , Masculino , Gravidez , Estudos Prospectivos
20.
Horm Res Paediatr ; 91(1): 46-55, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30939478

RESUMO

BACKGROUND/AIMS: There is little information how rhGH treatment affects height in NS. This study aims to analyze data from the NS patients assembled in KIGS over 25 years. PATIENTS/METHODS: Of 613 (389 m/224 f) NS patients documented, 476 (302 m/174 f) were treated for 1 year, 237 (160 m/77 f) of which served to develop a 1st year height velocity (HV) prediction algorithm. One-hundred and forty (74 m/66 f) had reached near adult height (NAH). Factors affecting NAH on rhGH were determined. RESULTS: At the start of rhGH, the NAH groups were (median, m, f) 11.0 and 10.3 years, with a height SDS of -3.2 and -3.8 SDS (Prader), respectively. The total gain after 6.3 and 5.6 years on rhGH (0.27 and 0.30 mg/kg/week) was 1.2 and 1.3 SDS. Age at the start of rhGH (negative), height at the start of rhGH, rhGH dose, number of rhGH injections/wk and birth weight (all positive) explained 36% of the variability of 1st year HV. Height at the start of rhGH, 1st year growth on rhGH, birth weight, and gender explained 74% of the variability of NAH. Causes for rhGH treatment discontinuation and adverse events were also analyzed. CONCLUSION: rhGH treatment increases NAH in NS. Prediction algorithms may optimize treatment in the future.


Assuntos
Desenvolvimento do Adolescente/efeitos dos fármacos , Estatura/efeitos dos fármacos , Desenvolvimento Infantil/efeitos dos fármacos , Hormônio do Crescimento Humano/administração & dosagem , Síndrome de Noonan , Adolescente , Adulto , Fatores Etários , Criança , Feminino , Seguimentos , Humanos , Masculino , Síndrome de Noonan/tratamento farmacológico , Síndrome de Noonan/patologia , Síndrome de Noonan/fisiopatologia
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