Intrauterine Growth Restriction (IUGR) Induces Signs of Subclinical Atherosclerosis in 6-Year-Old Infants Despite Absence Of Excessive Growth

Abstract

Background Postnatal catch-up growth and rapid weight gain after intrauterine growth restriction (IUGR) seem to increase the risk for later disease. This study aimed to compare features of the metabolic syndrome early in life between IUGR and appropriate for gestational age (AGA) infants.

Patients Data for 9 infants with IUGR defined by a birth weight<10^th percentile and ultrasound-proven placental insufficiency and 11 AGA children were available.

Method Postnatal growth, auxological, cardiovascular, and metabolic parameters up to a chronological age of 6 years were assessed: Fasting serum concentrations of LDL-cholesterol, insulin, leptin, IGF-I, DHEAS, skinfold thicknesses, blood pressure, and mean carotid intima-media thickness (cIMT).

Results All IUGR infants showed catch-up growth, although mean BMI SDS and total subcutaneous fat mass at the age of 6 years were still slightly lower compared to the AGA cohort. Reduced serum leptin concentrations were observed in IUGR infants (p=0.02), whereas no significant difference was found for IGF-I, insulin, LDL-cholesterol and DHEAS concentrations. Mean cIMT was significantly higher in IUGR infants (p<0.05). Mean arterial pressure did no differ.

Discussion and Conclusion In 6-year-old IUGR infants with catch-up growth, who still had a slightly reduced BMI SDS compared to the AGA group, signs of subclinical atherosclerosis were detectable suggesting that cardiovascular risk in IUGR may be present even in the absence of excessive growth.

Zusammenfassung

Hintergrund Postnatales Aufholwachstum und rasche Gewichtszunahme nach intrauteriner Wachstumsrestriktion (intrauterine growth restriction, IUGR) scheinen das Risiko für spätere Folgeerkrankungen zu erhöhen. Ziel dieser Studie war es, das Auftreten von Symptomen des metabolischen Syndroms in früher Kindheit zwischen IUGR-Kindern und Kindern mit normalem Geburtsgewicht (appropriate for gestational age, AGA) zu vergleichen.

Patienten Daten von 9 Kindern nach IUGR, definiert durch ein Geburtsgewicht<10. Perzentile und eine sonografisch nachgewiesene Plazentainsuffizienz, und 11 AGA-Kindern waren verfügbar.

Methode Postnatales Wachstum sowie folgende auxologische, kardiovaskuläre und metabolische Parameter bis zu einem chronologischen Alter von 6 Jahren wurden analysiert: Nüchtern-Serumkonzentrationen von LDL-Cholesterin, Insulin, Leptin, IGF-I, DHEAS, Hautfaltendickemessungen, Blutdruck und Intima-Media-Dicke der A. carotis communis beidseits (carotid intima-media thickness, cIMT).

Ergebnisse Alle IUGR-Kinder zeigten Aufholwachstum, wobei der mittlere BMI SDS und die subkutane Fettgewebsmasse im Alter von 6 Jahren noch leicht reduziert im Vergleich zur AGA-Kohorte waren. Die Konzentration von Leptin im Serum war erniedrigt bei den IUGR Kindern (p=0.02), kein signifikanter Unterschied fand sich für IGF-I, Insulin, LDL-Cholesterin und DHEAS. Die durchschnittliche cIMT war signifikant höher bei den IUGR-Kindern (p<0,05). Der mittlere arterielle Blutdruck unterschied sich nicht.

Diskussion und Schlussfolgerung Bei 6-jährigen IUGR-Kindern mit Aufholwachstum, deren BMI SDS weiterhin leicht erniedrigt im Vergleich zur AGA-Gruppe war, fanden sich subklinische arteriosklerotische Veränderungen, was auf ein erhöhtes kardiovaskuläres Risiko bei IUGR trotz fehlenden übermäßigen Aufholwachstums hinweisen könnte.

Key words

intrauterine growth restriction - foetal programming - catch-up growth - subclinical atherosclerosis - FIPS study

Schlüsselwörter

Intrauterine Wachstumsrestriktion - fetale Programmierung - Aufholwachstum - subklinische Arteriosklerose - FIPS-Studie

• References

• 1 Adair L, Dahly D. Developmental determinants of blood pressure in adults. Annu Rev Nutr 2005; 25: 407-434
• 2 Barker DJ, Osmond C, Forsen TJ. et al. Trajectories of growth among children who have coronary events as adults. N Engl J Med 2005; 353: 1802-1809
• 3 Beltrand J, Nicolescu R, Kaguelidou F. et al. Catch-up growth following fetal growth restriction promotes rapid restoration of fat mass but without metabolic consequences at one year of age. PLoS One 2009; 4: e5343
• 4 Brandt I, Reinken L. et al. Die Wachstumsgeschwindigkeit gesunder Kinder in den ersten 16 Lebensjahren: Longitudinale Entwicklungsstudie Bonn – Dortmund. Klin Pädiatr, Enke Verlag Stuttgart 1988; 200: 451-456
• 5 Cosmi E, Visentin S, Fanelli T. et al. Aortic intima media thickness in fetuses and children with intrauterine growth restriction. Obstet Gynecol 2009; 114: 1109-1114
• 6 Fliesen T, Maiter D, Gerard G. et al. Reduction of serum insulin-like growth factor-I by dietary protein restriction is age dependent. Pediatr Res 1989; 26: 415-419
• 7 Franks PW, Hanson RL, Knowler WC. et al. Childhood obesity, other cardiovascular risk factors, and premature death. N Engl J Med 2010; 362: 485-493
• 8 Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972; 18: 499-502
• 9 Gluckman PD, Hanson MA. Developmental origins of disease paradigm: a mechanistic and evolutionary perspective. Pediatr Res 2004; 56: 311-317
• 10 Gomez-Roig MD, Mazarico E, Valladares E. et al. Aortic intima-media thickness and aortic diameter in small for gestational age and growth restricted fetuses. PLoS One 2015; 10: e0126842
• 11 Gudmundsson S, Korszun P, Olofsson P. et al. New score indicating placental vascular resistance. Acta Obstet Gynecol Scand 2003; 82: 807-812
• 12 Habib S, Gattineni J, Twombley K. et al. Evidence that prenatal programming of hypertension by dietary protein deprivation is mediated by fetal glucocorticoid exposure. Am J Hypertens 2011; 24: 96-101
• 13 Hemachandra AH, Howards PP, Furth SL. et al. Birth weight, postnatal growth, and risk for high blood pressure at 7 years of age: results from the Collaborative Perinatal Project. Pediatrics 2007; 119: e1264-e1270
• 14 Jaquet D, Deghmoun S, Chevenne D. et al. Dynamic change in adiposity from fetal to postnatal life is involved in the metabolic syndrome associated with reduced fetal growth. Diabetologia 2005; 48: 849-855
• 15 Kromeyer-Hauschild KWM. GFea. Perzentile für den Body Mass Index für das Kindes- und Jugendalter unter Heranziehung verschiedener deutscher Stichproben. Monatschr Kinderheilk 2001; 149: 807-818
• 16 Law CM, de Swiet M, Osmond C. et al. Initiation of hypertension in utero and its amplification throughout life. BMJ 1993; 306: 24-27
• 17 Lee PA, Chernausek SD, Hokken-Koelega AC. et al. International Small for Gestational Age Advisory Board consensus development conference statement: management of short children born small for gestational age, April 24-October 1, 2001. Pediatrics 2003; 111: 1253-1261
• 18 Levy-Marchal C, Czernichow P. Small for gestational age and the metabolic syndrome: which mechanism is suggested by epidemiological and clinical studies?. Horm Res 2006; 65 (Suppl. 03) 123-130
• 19 Lundgren EM, Cnattingius S, Jonsson B. et al. Intellectual and psychological performance in males born small for gestational age with and without catch-up growth. Pediatr Res 2001; 50: 91-96
• 20 Milovanovic I, Njuieyon F, Deghmoun S. et al. SGA children with moderate catch-up growth are showing the impaired insulin secretion at the age of 4. PLoS One 2014; 9: e100337
• 21 Riedel C, von Kries R, Buyken AE. et al. Overweight in adolescence can be predicted at age 6 years: a CART analysis in German cohorts. PLoS One 2014; 9: e93581
• 22 Rodriguez G, Samper MP, Olivares JL. et al. Skinfold measurements at birth: sex and anthropometric influence. Arch Dis Child Fetal Neonatal Ed 2005; 90: F273-F275
• 23 Singhal A, Cole TJ, Fewtrell M. et al. 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
• 24 Tzschoppe A, Struwe E, Blessing H. et al. Placental 11beta-HSD2 gene expression at birth is inversely correlated with growth velocity in the first year of life after intrauterine growth restriction. Pediatr Res 2009; 65: 647-653
• 25 Utriainen P, Laakso S, Liimatta J. et al. Premature adrenarche – a common condition with variable presentation. Horm Res Paediatr 2015; 83: 221-231
• 26 Visentin S, Grumolato F, Nardelli GB. et al. Early origins of adult disease: low birth weight and vascular remodeling. Atherosclerosis 2014; 237: 391-399
• 27 Voigt M, Schneider KT, Jahrig K. Analysis of a 1992 birth sample in Germany. 1: New percentile values of the body weight of newborn infants. Geburtshilfe Frauenheilkd 1996; 56: 550-558
• 28 Walther FJ. Growth and development of term disproportionate small-for-gestational age infants at the age of 7 years. Early Hum Dev 1988; 18: 1-11
• 29 Willers SM, Brunekreef B, Abrahamse-Berkeveld M. et al. Serum Visfatin and Leptin in Relation to Childhood Adiposity and Body Fat Distribution: The PIAMA Birth Cohort Study. Ann Nutr Metab 2015; 66: 63-71
• 30 Woods LL, Weeks DA, Rasch R. Programming of adult blood pressure by maternal protein restriction: role of nephrogenesis. Kidney Int 2004; 65: 1339-1348