Background/Aims: Term small-for-gestational-age and preterm born infants have an increased prevalence of metabolic syndrome components already in childhood. Data in very-low-birth-weight (VLBW) children are limited. We investigated the prevalence of metabolic syndrome components in VLBW infants at 2 years of corrected age. Methods: We included 38 children, participating in the Neonatal Insulin Replacement Therapy in Europe (NIRTURE) trial, a randomized controlled trial of early insulin therapy in VLBW infants. Metabolic syndrome components were defined as: body mass index SDS >2; blood pressure (systolic and/or diastolic) ≥90th percentile; triglycerides ≥0.98 mmol/l; high-density lipoprotein (HDL) cholesterol ≤1.03 mmol/l; glucose ≥5.6 mmol/l. Results: Two children (5%) had three metabolic syndrome components, 13 children (34%) had two components, and 11 children (29%) one component. 63% had raised blood pressure (prevalence higher in boys), 32% low HDL, and 30% high triglycerides (prevalence lower in early insulin group). In children with body mass index SDS <0, insulin-treated children had higher HDL than children with standard care. Systolic blood pressure was correlated with growth between term and 2 years of corrected age. Conclusions: VLBW infants already have a high prevalence of metabolic syndrome components at 2 years of corrected age. Early insulin treatment could have long-term benefits for some of these components.

Irving RJ, Belton NR, Elton RA, Walker BR: Adult cardiovascular risk factors in premature babies. Lancet 2000;355:2135-2136.
Jaquet D, Gaboriau A, Czernichow P, Levy-Marchal C: Insulin resistance early in adulthood in subjects born with intrauterine growth retardation. J Clin Endocrinol Metab 2000;85:1401-1406.
Meas T, Deghmoun S, Alberti C, Carreira E, Armoogum P, Chevenne D, Levy-Marchal C: Independent effects of weight gain and fetal programming on metabolic complications in adults born small for gestational age. Diabetologia 2010;53:907-913.
Rotteveel J, van Weissenbruch MM, Twisk JW, Delemarre-Van de Waal HA: Infant and childhood growth patterns, insulin sensitivity, and blood pressure in prematurely born young adults. Pediatrics 2008;122:313-321.
Johansson S, Iliadou A, Bergvall N, Tuvemo T, Norman M, Cnattingius S: Risk of high blood pressure among young men increases with the degree of immaturity at birth. Circulation 2005;112:3430-3436.
Arends NJ, Boonstra VH, Duivenvoorden HJ, Hofman PL, Cutfield WS, Hokken-Koelega AC: Reduced insulin sensitivity and the presence of cardiovascular risk factors in short prepubertal children born small for gestational age. Clin Endocrinol (Oxf) 2005;62:44-50.
Hofman PL, Cutfield WS, Robinson EM, Bergman RN, Menon RK, Sperling MA, Gluckman PD: Insulin resistance in short children with intrauterine growth retardation. J Clin Endocrinol Metab 1997;82:402-406.
Hofman PL, Regan F, Jackson WE, Jefferies C, Knight DB, Robinson EM, Cutfield WS: Premature birth and later insulin resistance. N Engl J Med 2004;351:2179-2186.l
Mericq V, Ong KK, Bazaes R, Pena V, Avila A, Salazar T, Soto N, Iniguez G, Dunger DB: Longitudinal changes in insulin sensitivity and secretion from birth to age three years in small- and appropriate-for-gestational-age children. Diabetologia 2005;48:2609-2614.
Singhal A, Cole TJ, Fewtrell M, Kennedy K, Stephenson T, Elias-Jones A, Lucas A: Promotion of faster weight gain in infants born small for gestational age: is there an adverse effect on later blood pressure? Circulation 2007;115:213-220.
Soto N, Bazaes RA, Pena V, Salazar T, Avila A, Iniguez G, Ong KK, Dunger DB, Mericq MV: 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;88:3645-3650.
Veening MA, Van Weissenbruch MM, Delemarre-Van De Waal HA: Glucose tolerance, insulin sensitivity, and insulin secretion in children born small for gestational age. J Clin Endocrinol Metab 2002;87:4657-4661.
Veening MA, van Weissenbruch MM, Delemarre-van de Waal HA: Sequelae of syndrome X in children born small for gestational age. Horm Res 2004;61:103-107.
Doyle LW, Faber B, Callanan C, Morley R: Blood pressure in late adolescence and very low birth weight. Pediatrics 2003;111:252-257.
Hack M, Schluchter M, Cartar L, Rahman M: Blood pressure among very low birth weight (<1.5 kg) young adults. Pediatr Res 2005;58:677-684.
Hovi P, Andersson S, Eriksson JG, Jarvenpaa AL, Strang-Karlsson S, Makitie O, Kajantie E: Glucose regulation in young adults with very low birth weight. N Engl J Med 2007;356:2053-2063.
Vohr BR, Allan W, Katz KH, Schneider KC, Ment LR: Early predictors of hypertension in prematurely born adolescents. Acta Paediatr 2010;99:1812-1818.
Beardsall K, Vanhaesebrouck S, Ogilvy-Stuart AL, Vanhole C, Palmer CR, van Weissenbruch M, Midgley P, Thompson M, Thio M, Cornette L, Ossuetta I, Iglesias I, Theyskens C, de Jong M, Ahluwalia JS, de Zegher F, Dunger DB: Early insulin therapy in very-low-birth-weight infants. N Engl J Med 2008;359:1873-1884.
Dauncey MJ, Gandy G, Gairdner D: Assessment of total body fat in infancy from skinfold thickness measurements. Arch Dis Child 1977;52:223-227.
Fredriks AM, van Buuren S, Burgmeijer RJ, Meulmeester JF, Beuker RJ, Brugman E, Roede MJ, Verloove-Vanhorick SP, Wit JM: Continuing positive secular growth change in the Netherlands 1955-1997. Pediatr Res 2000;47:316-323.
Fredriks AM, van Buuren S, Wit JM, Verloove-Vanhorick SP: Body index measurements in 1996-1997 compared with 1980. Arch Dis Child 2000;82:107-112.
Ford ES, Li C: Defining the metabolic syndrome in children and adolescents: will the real definition please stand up? J Pediatr 2008;152:160-164.
Cook S, Weitzman M, Auinger P, Nguyen M, Dietz WH: Prevalence of a metabolic syndrome phenotype in adolescents: findings from the Third National Health and Nutrition Examination Survey, 1988-1994. Arch Pediatr Adolesc Med 2003;157:821-827.
Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel iii). JAMA 2001;285:2486-2497.
Zimmet P, Alberti KG, Kaufman F, Tajima N, Silink M, Arslanian S, Wong G, Bennett P, Shaw J, Caprio S: The metabolic syndrome in children and adolescents - an IDF consensus report. Pediatr Diabetes 2007;8:299-306.
Weiss R, Dziura J, Burgert TS, Tamborlane WV, Taksali SE, Yeckel CW, Allen K, Lopes M, Savoye M, Morrison J, Sherwin RS, Caprio S: Obesity and the metabolic syndrome in children and adolescents. N Engl J Med 2004;350:2362-2374.
National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents: The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics 2004;114:555-576.
American Academy of Pediatrics. National Cholesterol Education Program: Report of the expert panel on blood cholesterol levels in children and adolescents. Pediatrics 1992;89:525-584.
Barker DJ, Hales CN, Fall CH, Osmond C, Phipps K, Clark PM: Type 2 (non-insulin-dependent) diabetes mellitus, hypertension and hyperlipidaemia (syndrome X): relation to reduced fetal growth. Diabetologia 1993;36:62-67.
Bazaes RA, Alegria A, Pittaluga E, Avila A, Iniguez G, Mericq V: Determinants of insulin sensitivity and secretion in very-low-birth-weight children. J Clin Endocrinol Metab 2004;89:1267-1272.
Taittonen L, Uhari M, Nuutinen M, Turtinen J, Pokka T, Akerblom HK: Insulin and blood pressure among healthy children. Cardiovascular risk in young Finns. Am J Hypertens 1996;9:194-199.
D'Adamo E, Santoro N, Caprio S: Metabolic syndrome in pediatrics: old concepts revised, new concepts discussed. Pediatr Clin North Am 2011;58:1241-1255, xi.
Doyle LW, Ford GW, Davis NM, Callanan C: Antenatal corticosteroid therapy and blood pressure at 14 years of age in preterm children. Clin Sci (Lond) 2000;98:137-142.
Maric-Bilkan C, Manigrasso MB: Sex differences in hypertension: contribution of the renin-angiotensin system. Gend Med 2012;9:287-291.
Winter JS, Faiman C, Hobson WC, Prasad AV, Reyes FI: Pituitary-gonadal relations in infancy. I. Patterns of serum gonadotropin concentrations from birth to four years of age in man and chimpanzee. J Clin Endocrinol Metab 1975;40:545-551.
Winter JS, Hughes IA, Reyes FI, Faiman C: Pituitary-gonadal relations in infancy. 2. Patterns of serum gonadal steroid concentrations in man from birth to two years of age. J Clin Endocrinol Metab 1976;42:679-686.
Morrison JA, Glueck CJ, Wang P: Childhood risk factors predict cardiovascular disease, impaired fasting glucose plus type 2 diabetes mellitus, and high blood pressure 26 years later at a mean age of 38 years: the Princeton-lipid research clinics follow-up study. Metabolism 2012;61:531-541.
Kamagate A, Dong HH: FoxO1 integrates insulin signaling to VLDL production. Cell Cycle 2008;7:3162-3170.
Gorbach SL, Schaefer EJ, Woods M, Longcope C, Dwyer JT, Goldin BR, Morrill-LaBrode A, Dallal G: Plasma lipoprotein cholesterol and endogenous sex hormones in healthy young women. Metabolism 1989;38:1077-1081.
Stoffers DA, Desai BM, DeLeon DD, Simmons RA: Neonatal exendin-4 prevents the development of diabetes in the intrauterine growth retarded rat. Diabetes 2003;52:734-740.
Granado M, Fuente-Martin E, Garcia-Caceres C, Argente J, Chowen JA: Leptin in early life: a key factor for the development of the adult metabolic profile. Obes Facts 2012;5:138-150.
Niklasson A, Ericson A, Fryer JG, Karlberg J, Lawrence C, Karlberg P: An update of the Swedish reference standards for weight, length and head circumference at birth for given gestational age (1977-1981). Acta Paediatr Scand 1991;80:756-762.
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