Skip to main content
Erschienen in: Pediatric Nephrology 12/2012

01.12.2012 | Original Article

Renal function and systolic blood pressure in very-low-birth-weight infants 1–3 years of age

verfasst von: Joshua A. Frankfurt, Andrea F. Duncan, Roy J. Heyne, Charles R. Rosenfeld

Erschienen in: Pediatric Nephrology | Ausgabe 12/2012

Einloggen, um Zugang zu erhalten

Abstract

Background

Preterm very-low-birth-weight (PT-VLBW) infants are at risk of an elevated systolic blood pressure (SBP) in infancy and adulthood; however, the pathogenesis remains unclear. Altered renal development or function may be associated with increased SBP, but their contribution in PT-VLBW is unknown.

Methods

We determined renal function and its relationship to SBP in three groups of PT-VLBW at 1, 2, and 3 years of age, using serum cystatin-C to calculate the estimated glomerular filtration rate (eGFR).

Results

Cystatin-C levels decreased from 0.84 ± 0.2 (SD) within the 1-year group to 0.70 ± 0.1 mg/l (±SD; P < 0.001) at 3 years and were unrelated to gender, fetal growth, and neonatal indomethacin exposure. eGFR rose from 121 ± 59 in the 1-year group to 138 ± 21 ml/min·1.73 m2 (P < 0.001) at 3 years. At 1 year, cystatin-C levels decreased with increasing SBP (P < 0.007), and infants with SBP ≥ 90th% had lower cystatin-C and higher eGFR (P < 0.05). At 3 years, infants with lower birth weight (P < 0.03) and gestational age (P = 0.06) had reduced eGFR.

Conclusions

Preterm very-low-birth-weight infants demonstrate increasing renal function with advancing age. An elevated SBP and eGFR at 1 year suggests dysfunctional renal autoregulation and hyperfiltration, which may alter subsequent renal function and contribute to the lower eGFR seen at 3 years in infants with the lowest birth weight and gestational age.
Literatur
1.
Zurück zum Zitat Barker DJ, Osmond C, Golding J, Kuh D, Wadsworth ME (1989) Growth in utero, blood pressure in childhood and adult life, and mortality from cardiovascular disease. BMJ 298:564–567PubMedCrossRef Barker DJ, Osmond C, Golding J, Kuh D, Wadsworth ME (1989) Growth in utero, blood pressure in childhood and adult life, and mortality from cardiovascular disease. BMJ 298:564–567PubMedCrossRef
2.
Zurück zum Zitat Barker DJ, Bagby SP, Hanson MA (2006) Mechanisms of disease: in utero programming in the pathogenesis of hypertension. Nat Clin Pract Nephrol 2:700–707PubMedCrossRef Barker DJ, Bagby SP, Hanson MA (2006) Mechanisms of disease: in utero programming in the pathogenesis of hypertension. Nat Clin Pract Nephrol 2:700–707PubMedCrossRef
3.
Zurück zum Zitat Barker DJ, Osmond C, Kajantie E, Eriksson JG (2009) Growth and chronic disease: findings in the Helsinki Birth Cohort. Ann Hum Biol 36:445–458PubMedCrossRef Barker DJ, Osmond C, Kajantie E, Eriksson JG (2009) Growth and chronic disease: findings in the Helsinki Birth Cohort. Ann Hum Biol 36:445–458PubMedCrossRef
4.
Zurück zum Zitat Barker DJ (2004) Developmental origins of adult health and disease. J Epidemiol Community Health 58:114–115PubMedCrossRef Barker DJ (2004) Developmental origins of adult health and disease. J Epidemiol Community Health 58:114–115PubMedCrossRef
5.
Zurück zum Zitat McMillen IC, Robinson JS (2005) Developmental origins of the metabolic syndrome: prediction, plasticity, and programming. Physiol Rev 85:571–633PubMedCrossRef McMillen IC, Robinson JS (2005) Developmental origins of the metabolic syndrome: prediction, plasticity, and programming. Physiol Rev 85:571–633PubMedCrossRef
6.
Zurück zum Zitat Huxley RR, Shiell AW, Law CM (2000) The role of size at birth and postnatal catch-up growth in determining systolic blood pressure: a systematic review of the literature. J Hypertens 18:815–831PubMedCrossRef Huxley RR, Shiell AW, Law CM (2000) The role of size at birth and postnatal catch-up growth in determining systolic blood pressure: a systematic review of the literature. J Hypertens 18:815–831PubMedCrossRef
7.
Zurück zum Zitat Siewert-Delle A, Ljungman S (1998) The impact of birth weight and gestational age on blood pressure in adult life: a population-based study of 49-year-old men. Am J Hypertens 11:946–953PubMedCrossRef Siewert-Delle A, Ljungman S (1998) The impact of birth weight and gestational age on blood pressure in adult life: a population-based study of 49-year-old men. Am J Hypertens 11:946–953PubMedCrossRef
8.
Zurück zum Zitat Johansson S, Iliadou A, Bergvall N, Tuvemo T, Norman M, Cnattingius S (2005) Risk of high blood pressure among young men increases with the degree of immaturity at birth. Circulation 112:3430–3436PubMedCrossRef Johansson S, Iliadou A, Bergvall N, Tuvemo T, Norman M, Cnattingius S (2005) Risk of high blood pressure among young men increases with the degree of immaturity at birth. Circulation 112:3430–3436PubMedCrossRef
9.
Zurück zum Zitat Pharoah PO, Stevenson CJ, West CR (1998) Association of blood pressure in adolescence with birthweight. Arch Dis Child Fetal Neonatal Ed 79:F114–F118PubMedCrossRef Pharoah PO, Stevenson CJ, West CR (1998) Association of blood pressure in adolescence with birthweight. Arch Dis Child Fetal Neonatal Ed 79:F114–F118PubMedCrossRef
10.
Zurück zum Zitat Hack M, Schluchter M, Cartar L, Rahman M (2005) Blood pressure among very low birth weight (< 1.5 kg) young adults. Pediatr Res 58:677–684PubMedCrossRef Hack M, Schluchter M, Cartar L, Rahman M (2005) Blood pressure among very low birth weight (< 1.5 kg) young adults. Pediatr Res 58:677–684PubMedCrossRef
11.
Zurück zum Zitat Hovi P, Andersson S, Raikkonen K, Strang-Karlsson S, Jarvenpaa AL, Eriksson JG, Pesonen AK, Heinonen K, Pyhala R, Kajantie E (2010) Ambulatory blood pressure in young adults with very low birth weight. J Pediatr 156(54–59):e51 Hovi P, Andersson S, Raikkonen K, Strang-Karlsson S, Jarvenpaa AL, Eriksson JG, Pesonen AK, Heinonen K, Pyhala R, Kajantie E (2010) Ambulatory blood pressure in young adults with very low birth weight. J Pediatr 156(54–59):e51
12.
Zurück zum Zitat Vohr BR, Allan W, Katz KH, Schneider KC, Ment LR (2010) Early predictors of hypertension in prematurely born adolescents. Acta Paediatr 99:1812–1818PubMedCrossRef Vohr BR, Allan W, Katz KH, Schneider KC, Ment LR (2010) Early predictors of hypertension in prematurely born adolescents. Acta Paediatr 99:1812–1818PubMedCrossRef
13.
Zurück zum Zitat Duncan AF, Rosenfeld CR, Morgan JS, Ahmad N, Heyne RJ (2008) Interrater reliability and effect of state on blood pressure measurements in infants 1 to 3 years of age. Pediatrics 122:e590–e594PubMedCrossRef Duncan AF, Rosenfeld CR, Morgan JS, Ahmad N, Heyne RJ (2008) Interrater reliability and effect of state on blood pressure measurements in infants 1 to 3 years of age. Pediatrics 122:e590–e594PubMedCrossRef
14.
Zurück zum Zitat Duncan AF, Heyne RJ, Morgan JS, Ahmad N, Rosenfeld CR (2011) Elevated systolic blood pressure in preterm very-low-birth-weight infants ≤ 3 years of life. Pediatr Nephrol 26:1115–1121PubMedCrossRef Duncan AF, Heyne RJ, Morgan JS, Ahmad N, Rosenfeld CR (2011) Elevated systolic blood pressure in preterm very-low-birth-weight infants ≤ 3 years of life. Pediatr Nephrol 26:1115–1121PubMedCrossRef
15.
Zurück zum Zitat Zandi-Nejad K, Luyckx VA, Brenner BM (2006) Adult hypertension and kidney disease: the role of fetal programming. Hypertension 47:502–508PubMedCrossRef Zandi-Nejad K, Luyckx VA, Brenner BM (2006) Adult hypertension and kidney disease: the role of fetal programming. Hypertension 47:502–508PubMedCrossRef
16.
Zurück zum Zitat Brenner BM, Garcia DL, Anderson S (1988) Glomeruli and blood pressure. Less of one, more the other? Am J Hypertens 1:335–347PubMed Brenner BM, Garcia DL, Anderson S (1988) Glomeruli and blood pressure. Less of one, more the other? Am J Hypertens 1:335–347PubMed
17.
Zurück zum Zitat Bagby SP (2007) Maternal nutrition, low nephron number, and hypertension in later life: pathways of nutritional programming. J Nutr 137:1066–1072PubMed Bagby SP (2007) Maternal nutrition, low nephron number, and hypertension in later life: pathways of nutritional programming. J Nutr 137:1066–1072PubMed
18.
Zurück zum Zitat Dotsch J, Plank C, Amann K, Ingelfinger J (2009) The implications of fetal programming of glomerular number and renal function. J Mol Med 87:841–848PubMedCrossRef Dotsch J, Plank C, Amann K, Ingelfinger J (2009) The implications of fetal programming of glomerular number and renal function. J Mol Med 87:841–848PubMedCrossRef
19.
Zurück zum Zitat Baum M (2010) Role of the kidney in the prenatal and early postnatal programming of hypertension. Am J Physiol Renal Physiol 298:F235–F247PubMedCrossRef Baum M (2010) Role of the kidney in the prenatal and early postnatal programming of hypertension. Am J Physiol Renal Physiol 298:F235–F247PubMedCrossRef
20.
Zurück zum Zitat Brenner BM, Chertow GM (1994) Congenital oligonephropathy and the etiology of adult hypertension and progressive renal injury. Am J Kidney Dis 23:171–175PubMed Brenner BM, Chertow GM (1994) Congenital oligonephropathy and the etiology of adult hypertension and progressive renal injury. Am J Kidney Dis 23:171–175PubMed
21.
Zurück zum Zitat Bagby SP (2009) Developmental origins of renal disease: should nephron protection begin at birth? Clin J Am Soc Nephrol 4:10–13PubMedCrossRef Bagby SP (2009) Developmental origins of renal disease: should nephron protection begin at birth? Clin J Am Soc Nephrol 4:10–13PubMedCrossRef
22.
Zurück zum Zitat Luyckx VA, Brenner BM (2010) The clinical importance of nephron mass. J Am Soc Nephrol 21:898–910PubMedCrossRef Luyckx VA, Brenner BM (2010) The clinical importance of nephron mass. J Am Soc Nephrol 21:898–910PubMedCrossRef
23.
Zurück zum Zitat Keijzer-Veen MG, Schrevel M, Finken MJ, Dekker FW, Nauta J, Hille ET, Frolich M, van der Heijden BJ (2005) Microalbuminuria and lower glomerular filtration rate at young adult age in subjects born very premature and after intrauterine growth retardation. J Am Soc Nephrol 16:2762–2768PubMedCrossRef Keijzer-Veen MG, Schrevel M, Finken MJ, Dekker FW, Nauta J, Hille ET, Frolich M, van der Heijden BJ (2005) Microalbuminuria and lower glomerular filtration rate at young adult age in subjects born very premature and after intrauterine growth retardation. J Am Soc Nephrol 16:2762–2768PubMedCrossRef
24.
Zurück zum Zitat Bacchetta J, Harambat J, Dubourg L, Guy B, Liutkus A, Canterino I, Kassai B, Putet G, Cochat P (2009) Both extrauterine and intrauterine growth restriction impair renal function in children born very preterm. Kidney Int 76:445–452PubMedCrossRef Bacchetta J, Harambat J, Dubourg L, Guy B, Liutkus A, Canterino I, Kassai B, Putet G, Cochat P (2009) Both extrauterine and intrauterine growth restriction impair renal function in children born very preterm. Kidney Int 76:445–452PubMedCrossRef
25.
Zurück zum Zitat Rodriguez MM, Gomez AH, Abitbol CL, Chandar JJ, Duara S, Zilleruelo GE (2004) Histomorphometric analysis of postnatal glomerulogenesis in extremely preterm infants. Pediatr Dev Pathol 7:17–25PubMedCrossRef Rodriguez MM, Gomez AH, Abitbol CL, Chandar JJ, Duara S, Zilleruelo GE (2004) Histomorphometric analysis of postnatal glomerulogenesis in extremely preterm infants. Pediatr Dev Pathol 7:17–25PubMedCrossRef
26.
Zurück zum Zitat Gubhaju L, Sutherland MR, Black MJ (2011) Preterm birth and the kidney: implications for long-term renal health. Reprod Sci 18:322–333PubMedCrossRef Gubhaju L, Sutherland MR, Black MJ (2011) Preterm birth and the kidney: implications for long-term renal health. Reprod Sci 18:322–333PubMedCrossRef
27.
Zurück zum Zitat Hughson M, Farris AB III, Douglas-Denton R, Hoy WE, Bertram JF (2003) Glomerular number and size in autopsy kidneys: The relationship to birth weight. Kidney Int 63:2113–2122PubMedCrossRef Hughson M, Farris AB III, Douglas-Denton R, Hoy WE, Bertram JF (2003) Glomerular number and size in autopsy kidneys: The relationship to birth weight. Kidney Int 63:2113–2122PubMedCrossRef
28.
Zurück zum Zitat Manalich R, Reyes L, Herrera M, Melendi C, Fundora I (2000) Relationship between weight at birth and the number and size of renal glomeruli in humans: a histomorphometric study. Kidney Int 58:770–773PubMedCrossRef Manalich R, Reyes L, Herrera M, Melendi C, Fundora I (2000) Relationship between weight at birth and the number and size of renal glomeruli in humans: a histomorphometric study. Kidney Int 58:770–773PubMedCrossRef
29.
Zurück zum Zitat Hinchliffe SA, Sargent PH, Howard CV, Chan YF, van Velzen D (1991) Human intrauterine renal growth expressed in absolute number of glomeruli assessed by the disector method and Cavalieri principle. Lab Invest 64:777–784PubMed Hinchliffe SA, Sargent PH, Howard CV, Chan YF, van Velzen D (1991) Human intrauterine renal growth expressed in absolute number of glomeruli assessed by the disector method and Cavalieri principle. Lab Invest 64:777–784PubMed
30.
Zurück zum Zitat Rodriguez-Soriano J, Aguirre M, Oliveros R, Vallo A (2005) Long-term renal follow-up of extremely low birth weight infants. Pediatr Nephrol 20:579–584PubMedCrossRef Rodriguez-Soriano J, Aguirre M, Oliveros R, Vallo A (2005) Long-term renal follow-up of extremely low birth weight infants. Pediatr Nephrol 20:579–584PubMedCrossRef
31.
Zurück zum Zitat 2004 National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents (2004) The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics 114:555–576CrossRef 2004 National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents (2004) The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics 114:555–576CrossRef
32.
Zurück zum Zitat Finney H, Newman DJ, Gruber W, Merle P, Price CP (1997) Initial evaluation of cystatin C measurement by particle-enhanced immunonephelometry on the Behring nephelometer systems (BNA, BN II). Clin Chem 43:1016–1022PubMed Finney H, Newman DJ, Gruber W, Merle P, Price CP (1997) Initial evaluation of cystatin C measurement by particle-enhanced immunonephelometry on the Behring nephelometer systems (BNA, BN II). Clin Chem 43:1016–1022PubMed
33.
Zurück zum Zitat Filler G, Lepage N (2003) Should the Schwartz formula for estimation of GFR be replaced by cystatin C formula? Pediatr Nephrol 18:981–985PubMedCrossRef Filler G, Lepage N (2003) Should the Schwartz formula for estimation of GFR be replaced by cystatin C formula? Pediatr Nephrol 18:981–985PubMedCrossRef
34.
Zurück zum Zitat Tabachnick B, Fidell L (1996) Using multivariate statistics, 5th edn. Harper Collins College, New York, pp 127–195 Tabachnick B, Fidell L (1996) Using multivariate statistics, 5th edn. Harper Collins College, New York, pp 127–195
35.
Zurück zum Zitat Grubb AO (2000) Cystatin C—properties and use as diagnostic marker. Adv Clin Chem 35:63–99PubMedCrossRef Grubb AO (2000) Cystatin C—properties and use as diagnostic marker. Adv Clin Chem 35:63–99PubMedCrossRef
36.
Zurück zum Zitat Tenstad O, Roald AB, Grubb A, Aukland K (1996) Renal handling of radiolabelled human cystatin C in the rat. Scand J Clin Lab Invest 56:409–414PubMedCrossRef Tenstad O, Roald AB, Grubb A, Aukland K (1996) Renal handling of radiolabelled human cystatin C in the rat. Scand J Clin Lab Invest 56:409–414PubMedCrossRef
38.
Zurück zum Zitat Roos JF, Doust J, Tett SE, Kirkpatrick CM (2007) Diagnostic accuracy of cystatin C compared to serum creatinine for the estimation of renal dysfunction in adults and children—a meta-analysis. Clin Biochem 40:383–391PubMedCrossRef Roos JF, Doust J, Tett SE, Kirkpatrick CM (2007) Diagnostic accuracy of cystatin C compared to serum creatinine for the estimation of renal dysfunction in adults and children—a meta-analysis. Clin Biochem 40:383–391PubMedCrossRef
39.
Zurück zum Zitat Jerums G, Premaratne E, Panagiotopoulos S, Clarke S, Power DA, MacIsaac RJ (2008) New and old markers of progression of diabetic nephropathy. Diabetes Res Clin Pract 82 [Suppl 1]:S30–S37PubMedCrossRef Jerums G, Premaratne E, Panagiotopoulos S, Clarke S, Power DA, MacIsaac RJ (2008) New and old markers of progression of diabetic nephropathy. Diabetes Res Clin Pract 82 [Suppl 1]:S30–S37PubMedCrossRef
40.
Zurück zum Zitat Andersen TB, Eskild-Jensen A, Frokiaer J, Brochner-Mortensen J (2009) Measuring glomerular filtration rate in children; can cystatin C replace established methods? A review. Pediatr Nephrol 24:929–941PubMedCrossRef Andersen TB, Eskild-Jensen A, Frokiaer J, Brochner-Mortensen J (2009) Measuring glomerular filtration rate in children; can cystatin C replace established methods? A review. Pediatr Nephrol 24:929–941PubMedCrossRef
41.
Zurück zum Zitat Finney H, Newman DJ, Thakkar H, Fell JM, Price CP (2000) Reference ranges for plasma cystatin C and creatinine measurements in premature infants, neonates, and older children. Arch Dis Child 82:71–75PubMedCrossRef Finney H, Newman DJ, Thakkar H, Fell JM, Price CP (2000) Reference ranges for plasma cystatin C and creatinine measurements in premature infants, neonates, and older children. Arch Dis Child 82:71–75PubMedCrossRef
42.
Zurück zum Zitat Guignard JP, John EG (1986) Renal function in the tiny, premature infant. Clin Perinatol 13:377–401PubMed Guignard JP, John EG (1986) Renal function in the tiny, premature infant. Clin Perinatol 13:377–401PubMed
43.
Zurück zum Zitat Heilbron DC, Holliday MA, al-Dahwi A, Kogan BA (1991) Expressing glomerular filtration rate in children. Pediatr Nephrol 5:5–11PubMedCrossRef Heilbron DC, Holliday MA, al-Dahwi A, Kogan BA (1991) Expressing glomerular filtration rate in children. Pediatr Nephrol 5:5–11PubMedCrossRef
44.
Zurück zum Zitat Rhodin MM, Anderson BJ, Peters AM, Coulthard MG, Wilkins B, Cole M, Chatelut E, Grubb A, Veal GJ, Keir MJ, Holford NH (2009) Human renal function maturation: a quantitative description using weight and postmenstrual age. Pediatr Nephrol 24:67–76PubMedCrossRef Rhodin MM, Anderson BJ, Peters AM, Coulthard MG, Wilkins B, Cole M, Chatelut E, Grubb A, Veal GJ, Keir MJ, Holford NH (2009) Human renal function maturation: a quantitative description using weight and postmenstrual age. Pediatr Nephrol 24:67–76PubMedCrossRef
45.
Zurück zum Zitat Vanpee M, Blennow M, Linne T, Herin P, Aperia A (1992) Renal function in very low birth weight infants: normal maturity reached during early childhood. J Pediatr 121:784–788PubMedCrossRef Vanpee M, Blennow M, Linne T, Herin P, Aperia A (1992) Renal function in very low birth weight infants: normal maturity reached during early childhood. J Pediatr 121:784–788PubMedCrossRef
46.
Zurück zum Zitat Hodgin JB, Rasoulpour M, Markowitz GS, D'Agati VD (2009) Very low birth weight is a risk factor for secondary focal segmental glomerulosclerosis. Clin J Am Soc Nephrol 4:71–76PubMedCrossRef Hodgin JB, Rasoulpour M, Markowitz GS, D'Agati VD (2009) Very low birth weight is a risk factor for secondary focal segmental glomerulosclerosis. Clin J Am Soc Nephrol 4:71–76PubMedCrossRef
47.
Zurück zum Zitat Moritz KM, Wintour EM, Black MJ, Bertram JF, Caruana G (2008) Factors influencing mammalian kidney development: implications for health in adult life. Adv Anat Embryol Cell Biol 196:1–78PubMedCrossRef Moritz KM, Wintour EM, Black MJ, Bertram JF, Caruana G (2008) Factors influencing mammalian kidney development: implications for health in adult life. Adv Anat Embryol Cell Biol 196:1–78PubMedCrossRef
48.
Zurück zum Zitat Simeoni U, Ligi I, Buffat C, Boubred F (2011) Adverse consequences of accelerated neonatal growth: cardiovascular and renal issues. Pediatr Nephrol 26:493–508PubMedCrossRef Simeoni U, Ligi I, Buffat C, Boubred F (2011) Adverse consequences of accelerated neonatal growth: cardiovascular and renal issues. Pediatr Nephrol 26:493–508PubMedCrossRef
Metadaten
Titel
Renal function and systolic blood pressure in very-low-birth-weight infants 1–3 years of age
verfasst von
Joshua A. Frankfurt
Andrea F. Duncan
Roy J. Heyne
Charles R. Rosenfeld
Publikationsdatum
01.12.2012
Verlag
Springer-Verlag
Erschienen in
Pediatric Nephrology / Ausgabe 12/2012
Print ISSN: 0931-041X
Elektronische ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-012-2265-y

Weitere Artikel der Ausgabe 12/2012

Pediatric Nephrology 12/2012 Zur Ausgabe

Neuer Typ-1-Diabetes bei Kindern am Wochenende eher übersehen

23.04.2024 Typ-1-Diabetes Nachrichten

Wenn Kinder an Werktagen zum Arzt gehen, werden neu auftretender Typ-1-Diabetes und diabetische Ketoazidosen häufiger erkannt als bei Arztbesuchen an Wochenenden oder Feiertagen.

Neue Studienergebnisse zur Myopiekontrolle mit Atropin

22.04.2024 Fehlsichtigkeit Nachrichten

Augentropfen mit niedrig dosiertem Atropin können helfen, das Fortschreiten einer Kurzsichtigkeit bei Kindern zumindest zu verlangsamen, wie die Ergebnisse einer aktuellen Studie mit verschiedenen Dosierungen zeigen.

Spinale Muskelatrophie: Neugeborenen-Screening lohnt sich

18.04.2024 Spinale Muskelatrophien Nachrichten

Seit 2021 ist die Untersuchung auf spinale Muskelatrophie Teil des Neugeborenen-Screenings in Deutschland. Eine Studie liefert weitere Evidenz für den Nutzen der Maßnahme.

Fünf Dinge, die im Kindernotfall besser zu unterlassen sind

18.04.2024 Pädiatrische Notfallmedizin Nachrichten

Im Choosing-Wisely-Programm, das für die deutsche Initiative „Klug entscheiden“ Pate gestanden hat, sind erstmals Empfehlungen zum Umgang mit Notfällen von Kindern erschienen. Fünf Dinge gilt es demnach zu vermeiden.

Update Pädiatrie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.