Growth hormone treatment in pediatrics: What can we improve?

OBJECTIVES: To analyze the age at which treatment with growth hormone (GH) is started in the different indications approved in our country, as well as to assess the response to it and detect points of improvement. MATERIAL AND METHODS: A descriptive, observational and retrospective study of pediatric patients receiving GH treatment in December 2020 and monitored in the pediatric Endocrinology Unit of a tertiary care hospital. RESULTS: A total of 111 patients (52 females) were included in the study. The mean age at the start of treatment was 6.6 years old, being delayed in all diagnostic groups with respect to what is approved for each indication. The indication for which they most frequently received treatment was GH deficiency (n = 60, 54%). In this diagnostic group, there is a predominance of males (39 boys vs 21 girls, and a significantly greater increase in height z score (greater height SDS) is observed in those with early start of treatment compared to those who start late (greaterheight SDS 0.93 vs 0.6; P < .05). All diagnostic groups presented a greater height SDS and height velocity. No adverse effects were observed in any patient. CONCLUSION: GH treatment is effective and safe for the approved indications. The age of initiation of treatment is a point to improve in all indications, especially in SGA patients. For this, good coordination between primary care pediatricians and pediatric endocrinologists is essential, as well as specific training to identify early signs of different pathologies.

Evaluación de la antropometría en neonatos sanos. No todas las medidas son relevantes / Anthropometry assesment in healthy neonates. Not all measurements are relevant

Resumen Las medidas antropométricas se han usado para evaluar el crecimiento fetal y neonatal, además de determinar factores de riesgo de forma temprana. Clásicamente se han tomado el peso, talla, perímetro cefálico, torácico y abdominal. Son usadas para establecer condiciones como peso bajo o elevado para la edad gestacional, y con base en esto poder definir riesgos tempranos y tardíos. Otra medida sumamente importante es el perímetro cefálico, misma que determina neonatos con potencial riesgo neurológico. Estas tres medidas son clave como parte de la evaluación inicial neonatal, además de que se incluyen en el seguimiento del crecimiento y desarrollo infantil. No obstante, otras mediciones rutinarias como el perímetro torácico y abdominal, en neonatos con adaptación espontánea y exploración física normal (neonatos sanos), puede que aporten poco acerca del estado de salud neonatal. Estas últimas medidas no forman parte de los parámetros de seguimiento del crecimiento infantil, ni cuentan con gráficas de percentiles extrapolables para género y edad gestacional. Todas estas medidas están condicionadas por múltiples factores como genética, raza y nutrición, entre otros. Es momento de analizar las medidas rutinarias al momento del nacimiento de neonatos sanos, y priorizar las extrapolables a implicaciones clínicas relevantes.

Abstract Anthropometric measurements are used to assess fetal and neonatal growth and determine early risk factors. Classically, weight, height, head circumference, thoracic and abdominal circumference are the usual measures. They are used to identify conditions such as low or high weight for gestational age and, based on this, to determine early and late risks. Another important measurement is head circumference, which determines neonates with potential neurological risk. These three measures are key as part of the initial neonatal evaluation, and they are also a part of the child's growth monitoring and development. However, other routine measurements such as chest and abdominal circumferences, in newborns with spontaneous adaptation and normal physical examination (healthy neonates) may provide little information about the neonatal health status. These last measurements are not part of the child growth monitoring parameters, nor do they have percentile graphs that can be extrapolated to gender and gestational age. All these measures are conditioned by multiple factors such as genetics, race, and nutrition, among others. It is time to analyze routine measures at the time of birth of healthy newborns and prioritize those that can be extrapolated to relevant clinical implications.

[Splanchnic oximetry in small for gestational age neonates in relation to prenatal doppler study]. / Oximetría esplácnica en neonatos pequeños para la edad gestacional en relación con el estudio doppler prenatal.

INTRODUCTION: Among small for gestational age neonates, foetal Doppler enables the identification of placental insufficency aetiology and the classification of severity in small for gestational age neonates. There are studies that associate the Doppler data with alterations in the intestinal flow of the newborn, but its relationship with intestinal oximetry has been little studied. OBJECTIVE: To assess whether there is a relationship between prenatal Doppler data and abdominal oximetry in small for gestational age neonates MATERIAL AND METHODS: A prospective observational study carried out on neonates>32 weeks with a birth weight

[Influence of neonatal anthropometry on the comorbidities of the obese patient]. / Influencia de la antropometría neonatal sobre las comorbilidades del paciente obeso.

INTRODUCTION: Small for gestational age (SGA) newborns show an increased risk of several diseases such as short stature, childhood obesity, and metabolic comorbidities. PATIENTS AND METHODS: The study included 883 obese patients (47% females/53% males; mean age: 10.33±3.32 years, BMI:+3.93±1.42 SD), with prospective follow-up (5 years) of growth, recording adult height when achieved (n=104). Comparisons at diagnosis, according to their neonatal anthropometry; adequate for gestational age (AGA; n=810) vs. SGA (n=73), were performed for the following features: age at their first visit, standardised height for target height (Z-score), bone age, adult height prediction, BMI (Z-score), glycaemia, insulinaemia, HOMA, total cholesterol, HDL, LDL, triglycerides, 25-OH-vitamin D, area under the curve (AUC) for glucose and insulin in the OGTT, LDL/HDL and triglyceride/HDL ratio, insulin-like growth factor (IGF-I) and IGF-binding protein 3 (IGFBP-3) serum levels. RESULTS: Despite similar BMI-SDS, ethnic, and pubertal distribution in both groups, patients with SGA showed more severe changes in lipid profile (triglyceride and triglyceride/HDL ratio, both P<.05) and carbohydrate metabolism (higher glycaemia, glucose and insulin AUCs, HOMA, HbA1c and lower whole-body insulin sensitivity index (WBISI), all P<.05) and lower 25-OH vitamin D levels (P<.05). They also showed a poorer adult height prediction (adjusted for target height) (P<.01), despite a similar degree of advance in skeletal maturation and similar IGF-I and IGFBP-3 levels than AGA patients. CONCLUSIONS: The background of SGA neonatal anthropometry is associated with a higher prevalence and severity of metabolic comorbidities and to a poorer adult height prediction in obese children and adolescents.

[Antecedentes maternos prenatales y riesgo de complicaciones neonatales en productos de término de bajo peso para edad gestacional]. / Maternal prenatal history and neonatal risk complications for low-weight for gestacional age term newborns.

Introducción: El bajo peso neonatal (< 2.5 kg o < percentil 10) se atribuye a causas constitucionales (pequeño para la edad gestacional [PEG]) o a la restricción en el crecimiento intrauterino (RCIU), con riesgos posnatales diferentes. En ausencia de una valoración fetal-placentaria prenatal adecuada, resulta difícil establecerlo. El conocer los antecedentes maternos de enfermedades gestacionales (AMEG): hipertensión arterial (HTA), hipotiroidismo, Diabetes Mellitus (DM) gestacional y otra; pudiera orientar a la diferenciación y el manejo. El objetivo de este trabajo fue determinar si la presencia de AMEG se asocia a complicaciones neonatales en productos de bajo peso neonatal. Métodos: Se realizó un estudio de cohorte retrospectivo en un grupo de 349 recién nacidos vivos de término (≥ 37 semanas de edad gestacional [SEG]), PEG, en cunero fisiológico y agrupados según los AMEG. Se determinó la frecuencia de dificultad respiratoria (DR), hipoglucemia (HG) e hiperbilirrubinemia (HBr). Resultados: El 16.6% (58/349) presentó AMEG (58.6% HTA y 41.3% hipotiroidismo, solos o combinados). Los neonatos con AMEG fueron más limítrofes (37 SEG, 55.2% vs. 35.1%; p = 0.037). Los de 37 SEG con menor peso (diferencia de ≈100 g; p = 0.028), más riesgo de HG (13.6%; intervalo de confianza al 95% [IC 95%]: -4.08-31.2) pero menos DR (diferencia de -4.7%; IC 95%: -20.6-11.05). La HG en los de 39 SEG solo se presentó en neonatos sin AMEG (diferencia 12.7%; IC 95%: 3.9 a 31.5) igual que la HBr (tres casos). Conclusiones: Indagar sobre los AMEG en un producto PEG parece ser útil en la inferencia de RCIU. Sin embargo, es insuficiente, por lo que en conjunto con otras herramientas nos ayuda a estimar posibles complicaciones y acciones preventivas. Background: Low-birth-weight (LWB < 2.5 kg or <10 percentile) could be caused by constitutional matters or by intrauterine growth restriction (IUGR), both with different neonatal complications. Without an adequate prenatal evaluation is hard to stablish those conditions. Knowing the maternal history for gestational diseases (MHGD) such as hypertension (HTA), hypothyroidism or diabetes, among others could help clarify that difference. The aim of this work was to determine if having a MHGD is associated to neonatal complications in newborns with LWB. Methods: Retrospective cohort study, which included 349 with LWB at term (≥ 37 weeks of gestation [WG]) grouped into those with or without MHGD at a hospital nursery. The frequency of respiratory distress, hypoglycemia, and hyperbilirubinemia was determined. Results: 16.6% (58/349) had MHGD (58.6% for HTA and 41.3% hypothyroidism alone or combined). The neonate with MHGD were more borderline term (37 WGA, 55.2% vs. 35.1%; p = 0.037), and had lower weight (difference of ≈100 g; p = 0.028), had more cases with hypoglycemia (13.6%; CI 95%: −4.08 to 31.2%) but developed less respiratory distress (RD) (difference of −4.7%; CI 95%: −20.6 to 11.05%). Hypoglycemia in 39 WGA was only seen among neonates without MHGD (difference 12.7%; CI95%: 3.9 to 31.5%) just as for the hyperbilirubinemia cases (three). Conclusions: Inquiring about the MHGD on LBW term babies could be useful in the inference of IUGR, although we need other tools so that altogether can help to predict possible complications and to plan preventive actions.

Antecedentes maternos prenatales y riesgo de complicaciones neonatales en productos de término de bajo peso para edad gestacional / Maternal prenatal history and neonatal risk complications for low-weight for gestacional age term newborns

Resumen Introducción: El bajo peso neonatal (< 2.5 kg o < percentil 10) se atribuye a causas constitucionales (pequeño para la edad gestacional [PEG]) o a la restricción en el crecimiento intrauterino (RCIU), con riesgos posnatales diferentes. En ausencia de una valoración fetal-placentaria prenatal adecuada, resulta difícil establecerlo. El conocer los antecedentes maternos de enfermedades gestacionales (AMEG): hipertensión arterial (HTA), hipotiroidismo, Diabetes Mellitus (DM) gestacional y otra; pudiera orientar a la diferenciación y el manejo. El objetivo de este trabajo fue determinar si la presencia de AMEG se asocia a complicaciones neonatales en productos de bajo peso neonatal. Métodos: Se realizó un estudio de cohorte retrospectivo en un grupo de 349 recién nacidos vivos de término (≥ 37 semanas de edad gestacional [SEG]), PEG, en cunero fisiológico y agrupados según los AMEG. Se determinó la frecuencia de dificultad respiratoria (DR), hipoglucemia (HG) e hiperbilirrubinemia (HBr). Resultados: El 16.6% (58/349) presentó AMEG (58.6% HTA y 41.3% hipotiroidismo, solos o combinados). Los neonatos con AMEG fueron más limítrofes (37 SEG, 55.2% vs. 35.1%; p = 0.037). Los de 37 SEG con menor peso (diferencia de ≈100 g; p = 0.028), más riesgo de HG (13.6%; intervalo de confianza al 95% [IC 95%]: −4.08-31.2) pero menos DR (diferencia de −4.7%; IC 95%: −20.6-11.05). La HG en los de 39 SEG solo se presentó en neonatos sin AMEG (diferencia 12.7%; IC 95%: 3.9 a 31.5) igual que la HBr (tres casos). Conclusiones: Indagar sobre los AMEG en un producto PEG parece ser útil en la inferencia de RCIU. Sin embargo, es insuficiente, por lo que en conjunto con otras herramientas nos ayuda a estimar posibles complicaciones y acciones preventivas.

Abstract Background: Low-birth-weight (LWB < 2.5 kg or <10 percentile) could be caused by constitutional matters or by intrauterine growth restriction (IUGR), both with different neonatal complications. Without an adequate prenatal evaluation is hard to stablish those conditions. Knowing the maternal history for gestational diseases (MHGD) such as hypertension (HTA), hypothyroidism or diabetes, among others could help clarify that difference. The aim of this work was to determine if having a MHGD is associated to neonatal complications in newborns with LWB. Methods: Retrospective cohort study, which included 349 with LWB at term (≥ 37 weeks of gestation [WG]) grouped into those with or without MHGD at a hospital nursery. The frequency of respiratory distress, hypoglycemia, and hyperbilirubinemia was determined. Results: 16.6% (58/349) had MHGD (58.6% for HTA and 41.3% hypothyroidism alone or combined). The neonate with MHGD were more borderline term (37 WGA, 55.2% vs. 35.1%; p = 0.037), and had lower weight (difference of ≈100 g; p = 0.028), had more cases with hypoglycemia (13.6%; CI 95%: −4.08 to 31.2%) but developed less respiratory distress (RD) (difference of −4.7%; CI 95%: −20.6 to 11.05%). Hypoglycemia in 39 WGA was only seen among neonates without MHGD (difference 12.7%; CI95%: 3.9 to 31.5%) just as for the hyperbilirubinemia cases (three). Conclusions: Inquiring about the MHGD on LBW term babies could be useful in the inference of IUGR, although we need other tools so that altogether can help to predict possible complications and to plan preventive actions.

Factores de riesgo maternos asociados a recién nacidos término pequeños para la edad gestacional, Maternidad del Hospital San Felipe, 2016 / Maternal risk factors associated to newly born of term small for the gestational ag e, maternity of San Felipe hospital, 2016

La restricción del crecimiento intrauterino (RCIU) y el feto pequeño para la edad gestacional (PEG) se presentan en 4% a 15% de los embarazos, en el 2010, el 27 % de los nacimientos en países con bajo a mediano ingreso fueron PEG. Los factores de riesgo más prevalentes para un feto PEG son antecedentes de RCIU, hábito de fumar, pre eclampsia y embarazo múltiple. Los fetos pequeños para la edad gestacional, tienen mayor probabilidad de desarrollar restricción en el crecimiento lineal en la vida adulta. Se ha encontrado que pueden tener reducción de las potencialidades físicas, intelectuales e incremento de las probabilidades en relación a enfermedades crónicas. El objetivo de este estudio es determinar factores de riesgo que sean identiicables y prevenibles en el control prenatal de las madres que tuvieron recién nacidos de termino PEG. Métodos : Se realizó Estudio retrospectivo de casos y controles, durante el periodo comprendido del 1 de enero al 31 de diciembre del 2016. El total de unidades de estudio fue de 4675 pacientes, conformando 1171 casos y 3504 controles. Resultados: encontramos asociación de PEG con edad materna menor de 19 años, el estado civil, nivel de educación, talla menor de 150 cm, peso menor de 50 Kg al iniciar el embarazo, ser primigesta, antece - dente de RCIU en embarazo anterior, menos de 5 controles de embarazo, no haber recibido curso de preparación psicoproilactica para el parto.

[Effects of growth hormone treatment on anthropometrics, metabolic risk, and body composition variables in small for gestational age patients]. / Modificaciones en variables antropométricas, analíticas de riesgo metabólico y composición corporal en pequeños para la edad gestacional en tratamiento con hormona de crecimiento.

INTRODUCTION AND OBJECTIVES: Small for gestational age (SGA) children without catch-up growth can benefit from treatment with growth hormone (rhGH). However, they should be monitored very closely because they are at increased risk of metabolic syndrome. MATERIAL AND METHOD: A group of 28 SGA children with a mean age of 8.79 years and undergoing treatment with rhGH were selected for evaluation. Over the course of 4 years, an annual evaluation was performed on the anthropometric variables (weight, height, body mass index [BMI], growth rate, blood pressure and waist perimeter), metabolic risk variables (glycaemia, glycosylated haemoglobin, cholesterol ratio, insulinaemia, insulin-like growth factor 1[IGF1], IGF binding protein-3 [IGFBP-3], IGF1/IGFBP3 ratio, and HOMA index), and body composition variables. RESULTS: Treatment with rhGH was associated with a significant increase in height (-2.76±.11 SD to -1.53±.17 SD, P=.000), weight (-1.50±.09 SD to -1.21±.13 SD; P=.016), and growth rate (-1.43±.35 SD to .41±.41 SD; P=.009), without a corresponding change in the BMI. Insulinaemia (9.33±1.93mU/ml to 16.55±1.72mU/ml; P=.044) and the HOMA index (3.63±.76 to 6.43±.67; P=.042) increased, approaching insulin resistance levels. No changes were observed in the lipid profile. Body composition changes were observed, with a significant increase in lean mass (73.19±1.26 to 78.74±1.31; P=.037), and a reduction of fat mass (26.81±1.26 to 21.26±1.31; P=.021). CONCLUSION: Treatment with rhGH is effective for improving anthropometric variables in SGA patients who have not experienced a catch-up growth. It also produces changes in body composition, which may lead to a reduction in risk of metabolic syndrome. However, some insulin resistance was observed. It is important to follow up this patient group in order to find out whether these changes persist into adulthood.

[The relationship between metabolic disorders and small for gestational age with idiopathic premature adrenarche]. / Estudio de la asociación de adrenarquia prematura idiopática con la presencia de alteraciones metabólicas y con antecedente de pequeño para edad gestacional.

BACKGROUND: There is still controversy on the relationship between idiopathic premature adrenarche (IPA) and a history of small for gestational age, as well as the concomitant presence of obesity and other metabolic disturbances. An attempt is made to study these potential associations in a cohort of girls with IPA from our hospital. PATIENTS AND METHODS: A descriptive cross-sectional study was conducted that included girls with a diagnosis of IPA from the Paediatric Department of the Fundación Jiménez Díaz (Madrid, Spain) between January 2007 and May 2015. A record was made of family and personal history with perinatal data, as well as anthropometric data and biochemical values at the time of diagnosis. RESULTS: Out of a total of 76 girls with IPA, 2.7% had a history of small for gestational age. When body mass index was analysed according to modified criteria of WHO 2007/Cole 2000, 11.8% were overweight, and 11.8% were obese at diagnosis. Using the criteria set by the Spanish Ministry of Health, 6.6% were overweight and 18.4% obese, with 21.2% of the girls being insulin resistance, and 13.95% having dyslipidaemia. None of them had hypertension. From a comparative analysis between normal and overweight and obesity IPA girls, the latter had significantly higher levels of triglycerides and insulin, a higher HOMA index, and lower levels of HDL cholesterol. CONCLUSIONS: IPA girls included in the study do not have a higher prevalence of small for gestational age compared to the general population. Prevalence of overweight and obesity in girls with IPA is not higher than the prevalence in the normal population.

Valor predictivo del urocultivo en el diagnóstico de las complicaciones obstétricas y neonatales, en gestantes adolescentes y añosas atendidas en el INMP, durante el 2011 / Predictive value of urine culture in the diagnosis of obstetric and neonatal complications in adolescents and old pregnant women treated at the Instituto Nacional Materno Perinatal

Objetivo: el presente estudio, busca determinar el valor predictivo del urocultivo en el diagnóstico de las complicaciones obstétricas y neonatales, en gestantes adolescentes y añosas. Material y Métodos: estudio retrospectivo, transversal, observacional, tipo caso y control. Se revisó, 453 historias clínicas y datos de recién nacidos de gestantes atendidas en el Instituto Nacional Materno Perinatal, durante el per¡odo Enero – Diciembre, 2011. Se redujo la muestra a 338 historias, para mantener una relación 1:2 para caso y control. Se excluyó, a las pacientes con patología crónica o gestacional, aquellas con edades entre 20 y 34 años, y las que no tuvieron un urocultivo en su control prenatal. Los casos fueron identificados a través del urocultivo patológico (grupo 1) y el grupo control (grupo 2) con urocultivo normal. Resultados: de las 338 pacientes estudiadas, 160 eran gestantes adolescentes y 178 gestantes añosas. Del total, 76 presentaron complicaciones obstétricas (Grupo 1: 61 y Grupo 2: 15; p≤0.001) y 46 presentaron complicaciones en el recién nacido (Grupo 1: 34 y Grupo 2: 12; p ≤0.001). Siendo, las más afectadas las gestantes adolescentes. Conclusiones: las pacientes con urocultivo patológico, especialmente en el segundo trimestre; presentaron con mayor probabilidad ruptura prematura de membranas, amenaza de parto pretérmino, recién nacido pequeño para edad gestacional, restricción del crecimiento intrauterino, depresión neonatal y parto pretérmino. Asimismo, la presencia de un urocultivo normal, se considera factor protector para las complicaciones antes mencionadas. Siendo las gestantes adolescentes las más afectadas.

Objective: this study aims to determine the predictive value of urine culture in the diagnosis of obstetric and neonatal complications in pregnant adolescents and aged pregnant women. Material and Methods. A retrospective, cross-sectional observational, case and control study. We reviewed 453 medical records and data of newborns of pregnant women at the National Perinatal Maternal Institute, during the period January to December 2011. The sample was reduced to 338 stories, to maintain a 1:2 ratio for cases and controls. Exclusion criteria were patients with chronic or gestational diseases, those aged between 20 and 34 years, and those who did not have a urine culture in prenatal care. Cases were identified through pathological urine culture (group 1) and control group (group 2) with standard urine culture. Results: of the 338 patients studied, 160 were pregnant adolescents and 178 aged pregnant women. Of the total, 76 had obstetric complications (Group 1: 61 and Group 2: 15, P ≤ 0.001) and 46 had complications in the newborn (Group 1: 34 and Group 2: 12, P ≤ 0.001). Pregnant teens were the most affected. Conclusions: Patients with pathological urine culture, especially in the second quarter, had more probability of premature rupture of membranes, preterm labor, a newborn small for gestational age, intrauterine growth restriction, preterm delivery and neonatal depression. Also, a normal urine culture is a protective factor for the above mentioned complications. Pregnant teens being the most affected.

Incidencia y evolución de membrana hialina en menores de 35 semanas según crecimiento intrauterino / Incidence and evolution of hyaline membrane in newborns under 35 weeks of gestational age according intrauterine growth

Introduction: It is thought that intrauterine growth restriction induces respiratory maturation. The information varies if the studies consider analysis based on birth weight or gestational age. Objective: The goal of this study is to compare the incidence and evolution of hyaline membrane disease (HMD) between small and adequate premature babies under 35 weeks of gestational age (< 35 wGA) based on data in the literature. Patients and Methods: Two databases were created and analyzed: a) 2 022 newborns < 35 wGA admitted to the Service, whose incidence of HMD was calculated, and b) 733 newborns < 35 wGA with HMD and treated with surfactant, to describe the evolution. Results: Analysis of GA group shows a higher incidence of HMD (35.2 percent) among small for GA, and less (29.1 percent) among those who are not small for GA (p: 0.026). If a subset is formed for the newborns < 1 500 g in birth weight, those small for gestational age have a lower incidence (47.5 percent) than those adequate for GA (60.7 percent). Logistic regression analysis for discharge with oxygen of newborns with HMD shows association with lower z score for birth weight, corticosteroid use and oxygen dependence at 36 weeks. Conclusions: Preterm newborns small for GA show a higher incidence of HMD and oxygen dependence when comparing for GA.

Introducción: Tradicionalmente se ha considerado que la restricción de crecimiento intrauterina produce maduración respiratoria, pero la información es diferente según si los estudios consideran el análisis por grupos de peso de nacimiento o edad gestacional. Objetivo: El objetivo de este análisis fue comparar la incidencia y evolución de membrana hialina, de los prematuros menores de 35 semanas de edad gestacional según fueran pequeños o no para edad gestacional. Pacientes y Método: Se analizaron dos bases de datos: 2 022 menores de 35 semanas hospitalizados en el Servicio para determinar incidencia de membrana hialina y 733 menores de 35 semanas tratados con surfactante con diagnóstico de membrana hialina para comparar evolución de ésta. Resultados: El análisis por grupos de edad gestacional muestra una incidencia de membrana hialina mayor, de 35,2 por ciento, en los pequeños para la edad gestacional, y de 29,1 por ciento en los no pequeños (p: 0,026). Si se analiza sólo menores de 1 500 gramos de peso de nacimiento, el grupo pequeño tiene una incidencia menor, de 47,5 por ciento, y los no pequeños de 60,7 por ciento. El análisis de regresión logística para alta con oxígeno de los que tuvieron membrana hialina, muestra asociación con menor puntaje z de peso de nacimiento, uso de corticoides y dependencia de oxígeno a las 36 semanas. Conclusiones: El recién nacido pretérmino pequeño para edad gestacional tiene mayor incidencia de membrana hialina y evoluciona con mayor dependencia de oxígeno al comparar por edad gestacional.