Modificaciones en variables antropométricas, analíticas de riesgo metabólico y composición corporal en un grupo de niños pequeños para la edad gestacional en tratamiento con hormona de crecimiento

Resumo

Se estima que entre un 3 y un 5 % de los recién nacidos son pequeños para la edad gestacional (PEG). Determinados estímulos producidos durante un periodo crítico de desarrollo como puede ser la vida fetal y neonatal, pueden implicar consecuencias a largo plazo para la salud de un individuo. En este sentido, se ha observado en numerosos estudios asociaciones entre los niños PEG y muchas enfermedades del adulto, entre las que destaca el síndrome metabólico. Es decir, que existe una relación entre el ambiente nutricional temprano, los patrones de crecimiento postnatal y la cantidad y distribución del tejido adiposo en la vida adulta. El nacer PEG se asocia a aumento en el riesgo de enfermedades cardiovasculares, todo esto explicado por la hipótesis de la “programación temprana fetal” y el “modelo ahorrador de los niños PEG”, que señala cambios en la composición del cuerpo afectando a la distribución de la grasa con depósito en las zonas tronculares. Un 80-90 % de los niños PEG efectuarán un crecimiento recuperador normalizando su altura hacia los 2 años de edad. No obstante, un 10-20 % de estos niños no lo realizarán, desconociéndose la causa. El tratamiento de los niños PEG sin crecimiento recuperador es actualmente una indicación de empleo de la hormona de crecimiento (rhGH), aprobada por la FDA y la EMA. Los estudios muestran que un 85% de ellos alcanzan una talla adulta normal superior a -2DE, y un 98% una talla dentro del rango de su talla genética. Además del efecto del tratamiento sobre el crecimiento lineal, la GH es una hormona anabólica que modifica el metabolismo de las grasas y de los hidratos de carbono, produciendo cambios en la composición corporal de los individuos. Por lo tanto, el estudio de los niños pequeños para la edad gestacional es un tema que está en auge dada la reciente indicación de tratamiento con hormona de crecimiento. Aunque se están realizando diversos estudios en relación a la eficacia y efectividad de la hormona en este tipo de pacientes, resultaría de especial interés, no solo valorar los cambios antropométricos que se producen, sino evaluar como su composición corporal va modificándose a lo largo del tratamiento. En el caso de que se detectaran cambios en la composición corporal, debería estudiarse la posible asociación entre dichos cambios y otras variables analíticas relacionadas con el riesgo metabólico. Al ser pacientes con un aumento del riesgo cardiovascular, el estudio de la morfología y función cardiacas pueden ser de utilidad para determinar posible morbilidad cardiovascular en la edad adulta. BIBLIOGRAFÍA 1.Lee PA, Chernausek SD, Hokken-Koelega ACS, Czernichow P. International Small for Gestacional Age Advisory Board Consensus Development Conference Statement: Management of Short Children Born Small for Gestational Age. Pediatrics. 2003;111:1253-61. 2. Clayton PE, Cianfarani S, Czernichow P, Jhohansson G, Rapaport R, Rogol A. Consensus Statement: Management of the Child Born Small for Gestational Age through to Adulthood: A Consensus Statement of the International Societies of Pediatric Endocrinology and the Growth Hormone Research Society. J Clin Endocrinol Metab.2007;92:804-10. 3. Romo A, Carceller R, Tobajas J. Intrauterine Growth Retardation (IUGR):Epidemiology and Etiology. Pediatr Endocrinol Rev.2009;6:332-6. 4. Carrascosa A, Ferrandez A, Yeste D, García-Dihinx J, Romo A, Copil A et al. Estudio tranversal español de crecimiento 2008. Parte I: valores de peso y longitud en recien nacidos de 26-42 semans de edad gestacional. An Pediatr (Barc).2008;68:544-51 5. Ferrandez A, Carrascosa A, Sanchez E. Estudio longitudinal español de crecimiento 1978/2000. Barcelona:Ed.Hercu; 2010 . 6. Fabre E, González de Agüero R, Sobreviela M. Dieta materna y crecimiento fetal. Prog Obstet Gynecol.1993;36:19-39. 7. Samper MP , Jiménez-Muro A, Nerín I, Marqueta A, Ventura P, Rodríguez G. Maternal active smoking and newborn body composition. Early Hum Dev.2012;88(3):141-5 8. Biosca M, Rodriguez G, Samper MP, Odriozola Grijalba M, Cuadrón L et al. Aspectos perinatales, el crecimiento y la alimentación de los niños nacidos pequeños para la edad gestacional. An Pediatr (Barc).2013;78:14-20. 9. Chard T. The myth of fetal growth retardation at term.Br J Obstet Gynaecol.1993;100:1076-81. 10. Goldenberg RI, Cutter GR, Hoffman HJ. Intrauterine growth retardation: Standards for diagnosis. Am J Obstet Gynecol.1989;161:271-7. 11. De Zegher F, Francois I, Van Helvoirt M, Van der Berghe G. Clinical review 89: small as fetus and short as child: from endogenous to exogenous growth hormone. J Clin Endocrinol Metab.1997;82:2021-6. 12. Bernstein IM, Horbar JD, Badger GJ, Ohlsson A, Golan A. Morbidity and mortality among very low-birth-weight neonates with intrauterine growth restriction. The Vermont Oxford Network. Am J Obstet Gynecol.2000;182:198- 206. 13. Giudice LC, De Zegher F, Gargosky SE, Dsupin BA, Fuentes L, Crystal RA et al. Insulin-like growth factors and their binding proteins in the term and preterm human fetus and neonate with normal and extremes of intrauterine growth.J Clin Endocrinol Metab.1995;80:1548-55. 14. Johnson LB, Dahlgren J, Leger J, Gelander L, Savage MO, Czernichow P et al. Association between insuline-like growth factor I (IGF-I) polymorphism, circulating IGF-I, and pre and postnatal growth in two European small for gestacional age populations. J Clin Endocrinol Metab.2003;88:4805-10. 15. Abuzzahab MJ, Schneider A, Goddard A, Grigorescu F, Lautier C, Keller E, et al. IGF-I receptor mutations resulting in intrauterine and postnatal growth retardation. N Engl J Med. 2003;349:2211-22. 16. Juul A, Scheike T, Davidsen M, Gyllenborg J, Jorgensen T. Low serum insulinlike growth factor I is associated with increased risk of ischemic heart disease: a population-based case-control study. Circulation.2002;106:939-44. 17. Verkauskiene R, Jaquet D, Deghmoun S, Chevenne D, Czernichow P, LeviMarchal C. Smallness for gestational age is associated with persistent change in insulin-like growth factor I (IGF-I) and the ratio of IGF-I/IGF-binding protein-3 in adulthood. J Clin Endocrinol Metab. 2005;90:5672-6. 18. Cianfarini S, Ladaki C, Geremia C. Hormonal regulation of postnatal growth in children born small for gestational age. Horm Res.2006;65:70-4. 19. Ranke MB. Sensitivity to IGF1 in short chilcren born small for gestational age. J Endocrinol Invest.2006;29:21-6. 20. Boguszewski M, Rosberg S, Albertsson-Wikland K. Spontaneus 24-hour growth hormone profiles in prepubertal small for gestational age children. J Clin Endocrinol Metab. 1995;80:2599-606. 21. Kilby MD, Verhaeg J, Gittoes N, Somerset DA, Clark PM, Frank-lyn JA. Circulating thyroid hormone concentrations and placental thyroid hormone receptor expression in normal human pregnancy and pregnancy complicated by intrauterine growth restriction (IUGR).J Clin Endocrinol Metab.1998;83:2964- 71. 22. Ong KL, Ahmed ML, Emmett PM, Preece MA, Dunger DB. For the Avon Longitudinal Study of Pregnancy and Chilhood Study Team. Association between postnatal catch-up growth and obesity in childhood: prospective cohort study. BMJ.2000;320:967-71. 23. Albertsson-Wikland K, Karlberg J. Postnatal growth of children born small for gestacional age. Acta Pediatr Suppl.1997;423:193-5. 24. Luo ZC, Low LC, Karlberg J. A comparison of target height estimeted and final height attained between Swedish and Hong Kong Chinese children. Acta Paediatr.1999;88:248-52. 25. Leger J, Levy-Marchal C, Bloch J. Reduced final height and indications for insuline resistance in 20 years old born small for gestacional age:regional cohort study.BMJ .1997;315:341-7. 26. Barker DJ, Winter PD, Osmond C, Margetts B, Simmonds SJ. Weight in infancy and death from ischaemic heart disease.Lancet.1989;2:577–80. 27. Eriksson JG, Forsen T, Tuomilehto J, Osmond C, Barker DJP. Early adiposity rebound in child¬hood and risk of type 2 diabetes in adult life. Diabetologia.2003;46:190-4. 28. Saenger P, Czernichow P, Hugher I, Reiter EO. Small for Gestational Age: Short Stature and Beyond. Endocrine Reviews.2007;28:219-51. 29. Dulloo AG. Regulation of fat storage via sup¬pressed thermo- genesis: a thrifty phenotype that predisposes individuals with catch-up growth to insulin resistance and obesity. Horm Res. 2006;65:90-7. 30. Soto N, Bazaes RA, Peña V, Salazar T, Avila A, Ini¬guez G et al. Insulin sensitivity and secretion are related to catch-up growth in small-for-gestational-age infants at age 1 year: results from a prospective cohort. J Clin Endocrinol Metab.2003;88:3645–50. 31. Mericq V, Ong K, Bazaes R, Peña V, Avila A, Salazar T et al. Longitudinal changes in insulina sensitivity and secretion from Barth toa ge three years in small and appropriate for gestational age children. Diabetologia.2005;48:2609-14. 32. Bazaes RA, Salazar TE, Pittaluga E. Glucose and lípido metabolismo in small for gestacio¬nal age infants at 48 hours of age. Pediatrics.2003;111:804-9. 33. Jiménez-Reina L, Cañete R, Cepeda T, Bernal G. Morphological changes to somatotroph cells and in vitro individual GH release, in male rats treated with recombinant human GH. Histol Histopathol.2000;15(2):375-83. 34. Grundy SM, Clleman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung and Blood Institute scientific statement. Circulation.2005;112:2735-52. 35. Karlberg JP, Albertsson-Wikland K, Kwan EY, Lam BC, Low LC. The timing of early postnatal catch-up growth in normal, full-terms infants born short for gestacional age. Horm Res.1997;48:17-24. 36. Danielian P, Allman A, Steer P. Is obstetric and neonatal outcome worse in fetuses who fail to reach their growth potential? Br J Obstet Gynaecol.1992;99:452-4 37. Ranke MB, Lindberg A. Observed and predic¬ted total pubertal growth during treatment with growth hormone in adolescents with idiopathic growth hormone deficiency, Turner syndrome, short stature, born small for gestational age and idiopathic short stature: KIGS analysis and re-view. Horm Res Paediatr.2011;75:423-32. 38. Sas T, de Waal W, Mulder P, Houdijk M, Jansen M, Reeser M, HokkenKoelega A. Growth hormone treatment in children with short stature born small 258 for gestational age: 5 years results of a randomized, double-blind, dose-response trial. J Clin Endocrinol Metab.1999;84:3064-70. 39. Ranke MB, Lindberg A, for the KIGS International Board. Growth hormone treatment of short children born small for gestational age or with Silver-Russell syndrome: results from KIGS, including the first report on final height. Acta Paediatr Suppl.1996;417:18-26 40. Chatelain P, Carrascosa A, Bona G, Ferrandez-Longas A, Sippell W. Growth Hormone Therapy for Short Children Born Small for Gestational Age. Horm Res.2007;68:300-9. 41. Simon D, Leger J, Fjellestad-Paulsen A, Crabbe R, Czernichow P. Intermittent recombinant growth hormone treatment in short children born small for gestacional age: four-years results of a randomized trial of two different treatment regimens. Horm Res.2006;66:118-23. 42. Ranke MB, Guilbaud O, Lindberg A, Cole T. Prediction of the growth response in children with various growth disorders treated with growth hormone: analyses of data from the KIGS. Acta Pediatr Suppl.1993;391:82-8. 43. De Zegher F, Francois I, van Helvoirt M, Beckers D, Ibanez L, Chatelain P. Growth hormone treatment of short children born small for gestational age. Trends Endocrinol Metab.1998;9:233-7. 44. Hokken-Koelega AC, Van Pareren Y, Sas T, Arends N. Final height data, body composition and glucose metabolism in growth hormone-treated short children born small for gestational age. Horm Res.2003;60:113-9. 45. De Zegher F, Hokken-Koelega A. Growth hormone therapy for children born small for gestational age: height gain is less dose dependent over the long term than over the short term. Pediatrics.2005;115:e458-62. 46. Arends NJ, Boonstra VH, Mulder PG, Odink RJ, Stokvis-Brntsma WH, Rongen-Westerlaken C et al. GH treatment and its effect on bone mineral density, bone maduration and growth in short children born small for gestational age: 3-year results of a randomized, controlled GH trial. Clin Endocrinol.2003;59:779-87. 47. Sas T, Mulder P, Aanstoot HJ,k Houdijk M, Jansen M, Reeser M et al. Carbohydrate metabolism during long-term growth hormone treatment in children with short stature born small for gestational age. Clin Endocrinol.2001;54:243-51. 48. Mauras N, Attie KM, Reiter EO, Saenger P, Baptista J. High dose recombinant human growth hormone (GH) treatment of GH-deficient patients in puberty increases near-final height: a randomized, multicenter trial. J Clin Endocrinol Metab.2000;85:3653-60. 49. Christensen T, Buckland A, Bentley A, Djurhuus C, Baker-Searle R. Source Novo Nordisk A/S, Copenhagen, Denmark Cost-effectiveness of somatropin for the treatment of short children born small for gestational age. Clin Ther.2010;32:1068-82. 50. Cutfield WS, Lindberg A, Rapaport R, Wajnrajch MP, Saenger P. Safety of growth hormone treatment in children born small for gestational age: the US trial and KIGS analysis. Horm Res.2006;65:153-9. 51. Reinehr T, de Sousa G, Toschke AM, Andler W. Comparison of metabolic syndrome prevalence using eight different definitions: a critical ap¬proach. Arch Dis Child.2007;92:1067-72. 52. Olza J, Aguilera CM, Gil-Campos M, Leis R, Bueno G, Valle M et al. A Continuous Metabolic Syndrome Score Is Associated with Specific Biomarkers of Inflammation and CVD Risk in Prepubertal Children. Ann Nutr Metab.2015;66 (2-3):72-9 53. Bueno G, Moreno LA, Bueno O, J Morales, Pérez-Roche T, Garagorri JM et al. Metabolic risk-factor clustering estimation in obese children. J Physiol Biochem.2007;63(4):347-55. 54. Valle M, Gascón F, R Martos, FJ Ruz, Bermudo F, Cañete R. Metabolic cardiovascular syndrome in obese prepubertal children: the role of high fasting insulin levels. Metabolism.2002; 51(4):423-8. 55. Meas T, Deghmoun S, Alberti C, Carreira E, Ar¬moogum P, Chevenne D et al. In¬dependent effects of weight gain and fetal pro¬gramming on metabolic complications in adults born small for gestational age. Diabetologia.2010;53:907-13. 56. Forsen T, Eriksson J, Tuomilehto J, Reunanen A, Osmond C, Barker D. The fetal and childhood growth of persons who develop type 2 diabetes. Ann Intern Med. 2000;133:176-82. 57. Ong KK, Petry CJ, Emmett PM, Sandhu MS, Kiess W, Hales CN et al. Insulin sensitivity and secretion in normal children related to size at birth, postnatal growth, and plasma insuline-like growth factor-I levels. Diabetologia.2004;47:1064-70 58. Van Dijk, Bannink EM, van Pareren YK, Mulder PG, Hokken-Koelega AC. Risk factors for diabetes mellitas type 2 and metabolic syndrome are comparable for previously growth hormone (GH)-treated young adults born small for gestational age (SGA) and untreated short SGA controls. J Clin Endocrinol Metab.2007;92:160-5. 59. Sas T, Mulder P, Hokken-Koelega A. Body composition, blood pressure, and lipid metabolism before and during long-term growth hormone (GH) treatment in children with short stature born small for gestational age either with or without GH deficiency. J Clin Endocrinol Metab.2000;85:3786-92. 60. Van Pareren Y, Mulder P, Houdijk M, Jansen M, Reser M, Hokken-Koelega A. Effect of discontinuation of growth hormone treatment on risk factors for cardiovascular disease in adolescents born small for gestacional age. J Clin Endocrinol Metab.2003;88:347-53 61. Makikalio K, Vuolteenaho O, Jouppila P, Rassanen J. Ultrasonographic and biochemical markers of human fetal cardiac dysfunction in placental insufficiency. Circulation.2002;105:2058-83. 62. Crispi F, Figueras F, Cruz-Lemini M, Bartrons J,Bijnens B, Gratacós E et al. Cardiovascular programming in children born small for gestational age and relationship with prenatal signs of severity.Am J Obstet Gynecol.2012;207:121.e1-9. 63. Pérez-Cruz M, Cruz-Lemini M, Fernández MT, Parra JA, Bartrons J, Gomez R et al.Fetal cardiac function in late-onset intrauterine growth restriction vs small-for-gestational age, as defined by estimated fetal weight, cerebroplacental ratio and uterine artery Doppler.Ultrasound Obstet Gynecol.2015;46(4):465-71. 64. Arnott C, Skilton MR, Ruohonen S, Juonala M, Viikari JS, Kähönen M et al. Subtle increases in heart size persist into adulthood in growth restricted babies: the Cardiovascular Risk in Young Finns Study. Open Heart.2015;2(1):e000265. 65. Crispi F, Bijnens B, Figueras F, Bartrons J, Eixarch E, Le Roble F et al. Fetal growth restriction results in remodeled and less efficient hearts in children. Circulation.2010;121: 2427–36. 66. Lewandowski AJ, Bradlow WM, Augustine D, Davis EF, Francis J, Singhal A et al. Rightventricular systolic dysfunction in young adults born preterm. Circulation.2013;128(7):713-20. 67. Velde SJ, Ferreira I, Twisk JWR, Stehouwer CDA, van Mechelen W, Kemper HCG. Birthweight and arterial stiffness and blood pressure in adulthood - Results from the Amsterdam Growth and Health Longitudinal Study. Int J Epidemiol.2004;33:154-61 68. Martyn CN, Greenwald SE. Impaired synthesis of elastin in walls of aorta and large conduit arteries during early development as an initiating event in pathogenesis of systemic hypertension. Lancet.1997;350:953–5. 69. Salerno M, Esposito V, Farina V, Radetti G, Umbaldo A,et al. Improvement of Cardiac Performance and Cardiovascular Risk Factors in Children with GH Deficiency after Two Years of GH Replacement Therapy: An Observational, Open, Prospective, Case-Control Study. J Clin Endocrinol Metab.2006;91(4):1288–95 70. Nygren A, Sunnegardh J, Teien D, Jonzon A, Bjorkhem G, Lindell S et al. Rapid cardiovascular effects of growth hormone treatment in short prepubertal children: impact of treatment duration. Clin Endocrinol.2012;77(6):877–84. 71. Esen I,Cetin I,Demirel F, Ekici F. The Effect of Recombinant Human Growth Hormone Therapy on Left-Ventricular Chamber Size and Function in Children With Growth Hormone Deficiency. Pediatr Cardiol.2013;34:1854–9 72. Capalbo D, Vecchio A, Farina V, Spinelli L, Palladino A. Subtle Alterations of Cardiac Performance in Children with Growth Hormone Deficiency: Results of a Two-Year Prospective, Case-Control Study- J Clin Endocrinol Metab.2009;94(9):3347–55 73. Van Wassenaer A. Neurodevelopmental conse¬quences of being born SGA. Pediatr Endocrinol Rev.2005;3:372-7. 74. Dubois J, Benders M, Borradori-Tolsa, C Ca¬chia A, Lazeyras F, Ha-Vinh Leuchter R et al. Primary cortical folding in the human newborn: an early marker of later functional development. Brain.2008;131:2028-41. 75. Puga B, Ferrández-Longás A, García Rome¬ro R, Mayayo E, Labarta JI. Psychomotor and intellectual development of children born with intrauterine growth retardation (IUGR).J Pediatr Endocrinol Metab.2004;17:457-62. 76. Bergvall N, Iliadou A, Johansson S, Tuvemo T, Cnattingius S. Risks for low intellectual perfor¬mance related to being born small for gestatio¬nal age are modified by gestational age. Pedia¬trics.2006;117:460-7. 77. Puga B, Gil P, de Arriba A, Armendariz Y, Labar¬ta JI, Ferrández A. Psychomotor and intellec¬tual development (Neurocognitive Function) of children born small for gestational age (SGA). Transversal and longitudinal study. Pediatr En¬docrinol Rev.2009;6:358-70 78. Ester W, Bannink E, van Dijk M, Willemsen R. Van der Kaay D, de Ridder M, Hokken-Koelega A. Subclassification of small for gestational age children with persistent short stature: growth patterns and response to GH treatment. Horm Res.2008;69:89-98. 79. Lagrou K, Froidecoeur C, Thomas M, Massa G, Beckers D, Craen M. Concerns expecta¬tions and perception regarding stature, physi¬cal appearance and psychosocial functioning before and during high-dose growth hormo¬ne treatment of short pre-pubertal children born small for gestational age. Horm Res.2008;69:334-42. 80.Hernández MI, Mericq V. Pubertal Development in Girls Born Small for Gestational Age. J Pedia¬tr Endocrinol Metab.2008;21(3):201-8. 81. Garagorri JM , Rodríguez G, Lario-Elboj AJ, Olivares JL, Lario-Muñoz A, Orden I. Reference levels for 17-hydroxyprogesterone, 11-desoxycortisol, cortisol, testosterone, dehydroepiandrosterone sulfate and androstenedione in infants from birth to six months of age. Eur J Pediatr .2008;167(6):647-53. 82. Brown LM, Pottern LM, Hoover RN. Prenatal and Perinatal Risk Factors for Testicular Cancer. Cancer Res.1986;46:4812-6. 83. English PB, Goldberg DE, Wolff C, Smith D. Pa¬rental and birth characteristics in relation to tes¬ticular cancer risk among males born between 1960 and 1995 in California (United States). Cancer Causes Control.2003;14:815-25. 84. Hernández MI, Martínez A, Capurro T, Peña V, Trejo L, Avila A et al.Comparison of clinical, ultrasonogra¬phic, and biochemical differences at the begin¬ning of puberty in healthy girls born either small for gestational age or appropriate for gestatio¬nal age: preliminary results. J Clin Endocrinol Metab.2006;91:3377-81. 85. Ibáñez L, Lopez-Bermejo A, Diaz M, Marcos MV, de Zegher F. Early metformin therapy to delay menarche and augment height in girls with precocious pubarche. Fertility and Sterility.2011;95:727-30. 86.Albanese CV, Diessel E, Genant HK. Clinical applications of body composition measurements using DXA.J Clin Densitom.2003;6:75-85. 87. MaynardLM, Chumlea WC, Roche AF, Wisemandle WA, Zeller CM et al. Total-body and regional bone mineral content and areal bone mineral density in children aged 8-18: the Fels longitudinal study. Am J Clin Nutr.1998;68:1111-7. 88. Coin A, Sergi G, Minicuci N, Giannini S, Barbiero E, Manzato E et al. Fat-free mass and fat mass referente values by dualenergy X-ray absorptiometry (DEXA) in a 20-80 year-old italian population. Clin Nutr.2008;27:87-94. 89. Demura S, Sato S. Non-linear relationships between visceral fat area and percent regional fat mass in the trunk and the lower limbs in Japanese adults. Eur J Clin Nutr.2008;62:1395-404. 90. Bozkirli E, Ertorer ME, Bakiner O, Tutuncu NB, Demirag NG. The validity of the World Health Organisation ıs obesity body-mass index criteria in a Turkish population: a hospital-based study. Asia Pac J Clin Nutr.2007;16:443-7. 91. Moreno LA, Mesana MI, González-Gross M, Gil CM, Ortega FB, Fleta J et al. Body fat distribution reference standards in Spanish adolescents: the AVENA Study. Int J Obes (Lond).2007;31(12):1798-805 92. Baim S, Leonard MB, Bianchi ML, Hans DB, Kalkwarf HJ, Langman CB et al. Official positions of the International Society for Clinical Densitometry and executive summary of the 2007 ISCD pediatric position development conference. J Clin Densitom.2008;11:6-21. 93. Rauch F, Plotkin H, DiMeglio L, Engelbert RH, Henderson RC, Munns C et al. Fracture prediction and the definition of osteoporosis in children and adolescents: the ISCD 2007 pediatric official positions. J Clin Densitom.2008;11:22-8. 94. Lorente RM, Azpeitia J, Arévalo J, Muñoz A, García JM, Gredilla J. Absorciometría con rayos X de doble energía. Fundamentos, metodología y aplicaciones clínicas. Radiología. 2012; 54(5):410-23. 95. Gordon CM, Bachrach LK, Carpenter TO. Dual energy X-ray absorptiometry interpretation and reporting in children and adolescents: the 2007 ISCD pediatric official positions. J Clin Densitom.2008;11:43-6. 96. Rodríguez G, Moreno LA, Blay MG, Blay VA, Garagorri JM , Sarría A et al. Body composition in adolescents: measurements and metabolic aspects. Int J Obes Relat Metab Disorders.2004;28:54-8 97. Martin DD, Schweizer R, Schönau E, Binder G, Ranke MB. Growth hormone-induced increases in skeletal muscle mass alleviates the asso¬ciated insulin resistance in short children born small for gestational age, but not with growth hormone deficiency. Horm Res.2009;72:38-45. 98. Gormaz M. Pequeño para la Edad Gestacional en el período neonatal. Rev Esp Endocrinol Pediatr.2012; 3(2):90-2 99. Kulseng S, Jennekens-Schinkel A, Naess P. Defects in cognitive function were seen in very low birthweight, but not in term SGA adolescents. Acta Paediatr.2006;95:224-30. 100. Dulloo AG, Jacquet J, Montani JP. Pathways from weight fluctuations to metabolic diseases: focus on maladaptive thermogenesis during catch-up fat. Int J Obes Relat Metab Disord.2002;26:46–57. 101. Moreno LA, Moliner Urdiales-D, Ruiz JR, Mesana MI, Vicente Rodríguez-G, Rodríguez G et al. Five year trends on total and abdominal adiposity in Spanish adolescents. Nutr Hosp .2012; 27(3):731-8 102. Wells JCK, Chomtho S, Fewtrell MS. Program¬ming of body composition by early growth and nutrition. Proceedings of the Nutrition Society.2007;66:423-34. 103. Berndtc C , Schweizer R , Ranke MB , Carpeta T , Martin DD .Height, muscle, fat and bone response to growth hormone in short children with very low birth weight born appropriate for gestational age and small for gestational age. Horm Res Paediatr. 2014;82(2):81-8. 104. Ibáñez L, López-Bermejo A, Díaz M, Jaramillo A, Marín S, de Zegher F. Growth hormone therapy in short children born small for gestational age: effects on abdominal fat partitioning and circulating follistatin and high-molecular-weight adiponectin.J Clin Endocrinol Metab.2010;95(5):2234-9. 105. Rodríguez G, Collado MP, MP Samper, Biosca M, Bueno O, S Valle et al. Subcutaneous fat distribution in small for gestational age newborns. J Perinat Med .2011;39(3):355-7. 106. Pallas CR. Programa de Actividades Preventivas y de Promoción de la Salud para Niños PREMATUROS con una edad gestacional menor de 32 semanas o un peso inferior a 1.500 gramos. Del alta hospitalaria a los 7 años. [Disponible en http:// www.aepap.org/previnfad/pdfs/ previnfad_menor32-1500.pdf]consultado March 2010]. 107. Díez I, de Arriba A, Bosch J, Cabanas P, Gallego E, Martínez-Aedo MJ et al.Pautas para el seguimiento clínico del niño pequeño para la edad gestacional.An Pediatr.2012;76:104.e1-7 187. Lama RA, Alonso A, Gil-Campos M, Leis R y Comité de Nutrición de la AEP. Obesidad Infantil. Recomendaciones del Comité de Nu¬trición de la Asociación Española de Pediatría. Parte I. Prevención. Deteccion precoz. Papel del pediatra. An Pediatr (Barc).2006;65:607-15. 109. Vohr BR, Poindexter BB, Dusick AM McKinley LT. Persistent beneficial effects of breast milk ingested en the neonatal intensive care unit on aoutcomes of extremely low birth weight infants at 30 months of age. Pediatrics.2007;120:953-9. 110. Gómez-Sanchiz M, R Cañete, Rodero I, JE Baeza, Ávila O. Influence of breast-feeding on mental and psychomotor development. Clin Pediatr (Phila).2003;42(1):35-42. 111. American Academy of Pediatrics.Preventing childhood obesity.A National Conference Fo-cusing on Pregnancy, Infancy and Early Child¬hood Factors. Pediatrics.2004;114:1139-73. 112. Labayen I, Ortega FB, Moreno LA, Gonzalez- Gross M. On behalf of the HELENA Study Group. Physical activity attenuates the negative effect of low birth weight on leptin levels in Eu-ropean adolescents; The HELENA study. Nutr Metab Cardiovasc Dis. 2012. 113. Olza J, Gil-Campos M, Leis R, Bueno G, Agu¬ilera CM, Valle M et al Presence of the metabolic syndrome in obese children at prepubertal age. Ann Nutr Metab.2011;58:343-50. 114. Bhargava SK, Sachdev HPS, Fall CHD. Relation of serial changes in childhood body mass index to impaired glucose tolerance in young adult¬hood.N Engl J Med.2004;350:865-75. 115. Tin W, Fritz S, Wariyar UK, Hey E. Outcome of very preterm birth: Children reviewed with ease at two years differ from those followed up with difficulty. Arch Dis Child Fetal Neonatal Ed.1998;79:F83-7. 116. Ibañez L, de Zegher F. Puberty after Prenatal Growth Restraint. Horm Res.2006;65:112-5. 117. Larraz A. ORDEN de 11 de diciembre de 2004, del Departamento de Salud, Consumo y Servicios Sociales, por la que se crea el Comité Asesor del Servicio Aragonés de Salud para la utilización terapéutica de hormona de crecimiento y sustancias relacionadas.[ Disponible en: http://www.boa.aragon.es/cgibin/EBOA/BRSCGI?CMD=VERDOC&BASE=BOLE&DOCN=000075344&SEC. Consultado Septiembre 2015] 118. Tanner JM, Whitehouse RH.Clinical longitudinal standards for height, weight, height velocity, weight velocity, and stages of puberty.Arch Dis Child.1976;51(3):170-9. 119.Seidell JC, Cigolini M, Charzewska J, Contaldo F, Ellsinger BM, Björntorp P. Measurement of regional distribution of adipose tissue. En: Björntorp P, Rösner S, editores. Obesity in Europe 88. Proceedings of the 1st European Congress on Obesity. Estocolmo: John Libbey;1988. p. 351-7 120. The Fourth Report on the Diagnosis, Evaluation and Treatment of High Blood Pressure in Children and Adolescent. National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents.Pediatrics.2004;114:555-76