Prematurity as Predictor of Children's Cardiovascular-renal Health

NCT02147457 | Completed

• 1 other identifier: PREMATCH
• Study Type: observational
• Target: 180
• Locations: 1 country
• Sites: 1

Brief Summary

Extreme preterm birth interferes with the development of the cardiovascular system. Both macro- as well as microvasculature undergoes extensive, organ specific maturation. Under normal fetal conditions, microvascular growth drives renal development and continues until 34-36 weeks of gestational age, while retinal vascular growth continues until term age. Studies show that there is association between low birth weight and cardiovascular dysfunction. According to the Barker hypothesis, this is due to nutritional shortage. In extreme preterm birth cases, this growth restriction is observed in neonatal life. In adult life, this suboptimal growth is associated with impaired renal and (micro)vascular function, hypertension, glucose intolerance and cardiovascular disease. According to the Brenner hypothesis, disrupted renal development results in hyperfiltration and hypertension, a process that subsequently promotes itself and leads to renal impairment. We will investigate macro- and microvasculature in different organs, including eye, kidney, heart and sublingual mucosa in former preterm infants, now aged 8-13 years old and age-matched controls. The expectation is that the results of this project will identify risk factors for cardiovascular-renal disease in the adult life of former preterm infants compared to the controls, while further analysis on mediators in neonatal life of this cardiovascular-renal outcome may provide new information on perinatal risk factors.

Conditions

Endothelial Dysfunction; Sublingual Capillary Glycocalyx and Density; Visual Disturbances and Blindness; Ventricular Dysfunction, Left; Renal Impairment

Keywords

Prematurity; Extremely low birth weight; Phenotyping

Outcome Measures

Primary Outcomes (1)

• Endothelial function.

  Changes in the macro- and microcirculation of the cardiovascular-renal system: * Endothelial function * Sublingual capillary glycocalyx and density * Retinal imaging and visual acuity * Left ventricular function * Renal anatomy and function * Structure and function of the carotid artery (intima-media thickness, distensibility, Young's elastic modulus), aortic pulse wave velocity and the systolic augmentation index.

  Baseline measurement. Cross-sectional study.

Study Arms (2)

ELBW (CASES)

Extremely low birth weights, born in 2000-2005, birth weight below 1000 grams, who were initially admitted (2000-2005) at the Neonatal Intensive Care Unit, UZ Leuven Belgium and have been well characterized and documented in the postnatal period.

CONTROLS

Survivors (CASES) (n = 140) will be matched with two healthy controls. One control will be matched to sex, birth year and residential area and will be suggested by the index patient (e.g. school friend, neighbor), the second control will be age and sex matched from the area of the field.

Eligibility Criteria

• Age: 8 Years - 15 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

ELBW (birth weight below 1000 g) neonates and have been well characterized and documented in the postnatal period, survivors (n = 140) will be matched with two controls. One control will be matched to sex, birth year and residential area and will be suggested by the index patient, the second control will be age and sex matched from the area of the field center. All children considered are currently between 8 and 15 years of age. Based on GCP guidance and national law, parents or custodians will provide informed written consent, while the child has to provide informed assent.

You may qualify if:

• cases are children who were initially admitted (2000-2005) at the Neonatal Intensive Care Unit, UZ Leuven Belgium as ELBW (birth weight below 1000 g) neonates and have been well characterized and documented in the postnatal period. Survivors (n = 140) will be matched with two controls.

You may not qualify if:

• If the control child is not in good health.

Sponsors & Collaborators

• Universitaire Ziekenhuizen KU Leuven: lead

Study Sites (1)

Research Center

Eksel, Limburg, 3941, Belgium

Location

Related Publications (39)

• O'Connor AR, Stephenson T, Johnson A, Tobin MJ, Moseley MJ, Ratib S, Ng Y, Fielder AR. Long-term ophthalmic outcome of low birth weight children with and without retinopathy of prematurity. Pediatrics. 2002 Jan;109(1):12-8. doi: 10.1542/peds.109.1.12.

  PMID: 11773536 BACKGROUND

• Sutherland MR, Gubhaju L, Moore L, Kent AL, Dahlstrom JE, Horne RS, Hoy WE, Bertram JF, Black MJ. Accelerated maturation and abnormal morphology in the preterm neonatal kidney. J Am Soc Nephrol. 2011 Jul;22(7):1365-74. doi: 10.1681/ASN.2010121266. Epub 2011 Jun 2.

  PMID: 21636639 BACKGROUND

• Nieuwdorp M, Meuwese MC, Mooij HL, Ince C, Broekhuizen LN, Kastelein JJ, Stroes ES, Vink H. Measuring endothelial glycocalyx dimensions in humans: a potential novel tool to monitor vascular vulnerability. J Appl Physiol (1985). 2008 Mar;104(3):845-52. doi: 10.1152/japplphysiol.00440.2007. Epub 2007 Dec 27.

  PMID: 18162484 BACKGROUND

• Takashima S, Itoh M, Oka A. A history of our understanding of cerebral vascular development and pathogenesis of perinatal brain damage over the past 30 years. Semin Pediatr Neurol. 2009 Dec;16(4):226-36. doi: 10.1016/j.spen.2009.09.004.

  PMID: 19945657 BACKGROUND

• Gien J, Kinsella JP. Pathogenesis and treatment of bronchopulmonary dysplasia. Curr Opin Pediatr. 2011 Jun;23(3):305-13. doi: 10.1097/MOP.0b013e328346577f.

  PMID: 21494147 BACKGROUND

• Abitbol CL, Rodriguez MM. The long-term renal and cardiovascular consequences of prematurity. Nat Rev Nephrol. 2012 Feb 28;8(5):265-74. doi: 10.1038/nrneph.2012.38.

  PMID: 22371245 BACKGROUND

• Barker DJ. Fetal origins of coronary heart disease. BMJ. 1995 Jul 15;311(6998):171-4. doi: 10.1136/bmj.311.6998.171.

  PMID: 7613432 BACKGROUND

• Faa G, Gerosa C, Fanni D, Nemolato S, Locci A, Cabras T, Marinelli V, Puddu M, Zaffanello M, Monga G, Fanos V. Marked interindividual variability in renal maturation of preterm infants: lessons from autopsy. J Matern Fetal Neonatal Med. 2010 Oct;23 Suppl 3:129-33. doi: 10.3109/14767058.2010.510646.

  PMID: 20836739 BACKGROUND

• Gubhaju L, Sutherland MR, Black MJ. Preterm birth and the kidney: implications for long-term renal health. Reprod Sci. 2011 Apr;18(4):322-33. doi: 10.1177/1933719111401659.

  PMID: 21427457 BACKGROUND

• Zaffanello M, Brugnara M, Bruno C, Franchi B, Talamini G, Guidi G, Cataldi L, Biban P, Mella R, Fanos V. Renal function and volume of infants born with a very low birth-weight: a preliminary cross-sectional study. Acta Paediatr. 2010 Aug;99(8):1192-8. doi: 10.1111/j.1651-2227.2010.01799.x. Epub 2010 Mar 14.

  PMID: 20337778 BACKGROUND

• Rakow A, Katz-Salamon M, Ericson M, Edner A, Vanpee M. Decreased heart rate variability in children born with low birth weight. Pediatr Res. 2013 Sep;74(3):339-43. doi: 10.1038/pr.2013.97. Epub 2013 Jun 14.

  PMID: 23770921 BACKGROUND

• Norman M, Martin H. Preterm birth attenuates association between low birth weight and endothelial dysfunction. Circulation. 2003 Aug 26;108(8):996-1001. doi: 10.1161/01.CIR.0000085069.09770.3D. Epub 2003 Aug 18.

  PMID: 12925463 BACKGROUND

• Keijzer-Veen MG, Dulger A, Dekker FW, Nauta J, van der Heijden BJ. Very preterm birth is a risk factor for increased systolic blood pressure at a young adult age. Pediatr Nephrol. 2010 Mar;25(3):509-16. doi: 10.1007/s00467-009-1373-9. Epub 2009 Dec 15.

  PMID: 20012998 BACKGROUND

• Brenner BM, Garcia DL, Anderson S. Glomeruli and blood pressure. Less of one, more the other? Am J Hypertens. 1988 Oct;1(4 Pt 1):335-47. doi: 10.1093/ajh/1.4.335.

  PMID: 3063284 BACKGROUND

• Carmody JB, Charlton JR. Short-term gestation, long-term risk: prematurity and chronic kidney disease. Pediatrics. 2013 Jun;131(6):1168-79. doi: 10.1542/peds.2013-0009. Epub 2013 May 13.

  PMID: 23669525 BACKGROUND

• Vieux R, Hascoet JM, Merdariu D, Fresson J, Guillemin F. Glomerular filtration rate reference values in very preterm infants. Pediatrics. 2010 May;125(5):e1186-92. doi: 10.1542/peds.2009-1426. Epub 2010 Apr 5.

  PMID: 20368313 BACKGROUND

• Zandi-Nejad K, Luyckx VA, Brenner BM. Adult hypertension and kidney disease: the role of fetal programming. Hypertension. 2006 Mar;47(3):502-8. doi: 10.1161/01.HYP.0000198544.09909.1a. Epub 2006 Jan 16.

  PMID: 16415374 BACKGROUND

• Bacchetta J, Harambat J, Dubourg L, Guy B, Liutkus A, Canterino I, Kassai B, Putet G, Cochat P. Both extrauterine and intrauterine growth restriction impair renal function in children born very preterm. Kidney Int. 2009 Aug;76(4):445-52. doi: 10.1038/ki.2009.201. Epub 2009 Jun 10.

  PMID: 19516242 BACKGROUND

• Keijzer-Veen MG, Devos AS, Meradji M, Dekker FW, Nauta J, van der Heijden BJ. Reduced renal length and volume 20 years after very preterm birth. Pediatr Nephrol. 2010 Mar;25(3):499-507. doi: 10.1007/s00467-009-1371-y. Epub 2009 Dec 16.

  PMID: 20013294 BACKGROUND

• Puddu M, Fanos V, Podda F, Zaffanello M. The kidney from prenatal to adult life: perinatal programming and reduction of number of nephrons during development. Am J Nephrol. 2009;30(2):162-70. doi: 10.1159/000211324. Epub 2009 Apr 2.

  PMID: 19339773 BACKGROUND

• George I, Mekahli D, Rayyan M, Levtchenko E, Allegaert K. Postnatal trends in creatinemia and its covariates in extremely low birth weight (ELBW) neonates. Pediatr Nephrol. 2011 Oct;26(10):1843-9. doi: 10.1007/s00467-011-1883-0. Epub 2011 Apr 17.

  PMID: 21499946 BACKGROUND

• Kuznetsova T, Szczesny G, Thijs L, Jozeau D, D'hooge J, Staessen JA. Assessment of peripheral vascular function with photoplethysmographic pulse amplitude. Artery Research. 2011;5(2):58-64.

  BACKGROUND

• Hubble SM, Kyte HL, Gooding K, Shore AC. Variability in sublingual microvessel density and flow measurements in healthy volunteers. Microcirculation. 2009 Feb;16(2):183-91. doi: 10.1080/10739680802461935.

  PMID: 19206003 BACKGROUND

• Liu Y-P, Richart T, Jin Y, Struijker-Boudierc HA, Staessen JA. Retinal arteriolar and venular phenotypes in a Flemish population: Reproducibility and correlates. Artery Research. 2011;5(2):72-9.

  BACKGROUND

• Sherry LM, Wang JJ, Rochtchina E, Wong T, Klein R, Hubbard L, Mitchell P. Reliability of computer-assisted retinal vessel measurementin a population. Clin Exp Ophthalmol. 2002 Jun;30(3):179-82. doi: 10.1046/j.1442-9071.2002.00520.x.

  PMID: 12010210 BACKGROUND

• Richart T, Thijs L, Nawrot T, Yu J, Kuznetsova T, Balkestein EJ, Struijker-Boudier HA, Staessen JA. The metabolic syndrome and carotid intima-media thickness in relation to the parathyroid hormone to 25-OH-D(3) ratio in a general population. Am J Hypertens. 2011 Jan;24(1):102-9. doi: 10.1038/ajh.2010.124. Epub 2010 Jul 1.

  PMID: 20596035 BACKGROUND

• Seidlerova J, Bochud M, Staessen JA, Cwynar M, Dolejsova M, Kuznetsova T, Nawrot T, Olszanecka A, Stolarz K, Thijs L, Wojciechowska W, Struijker-Boudier HA, Kawecka-Jaszcz K, Elston RC, Fagard R, Filipovsky J; EPOGH investigators. Heritability and intrafamilial aggregation of arterial characteristics. J Hypertens. 2008 Apr;26(4):721-8. doi: 10.1097/HJH.0b013e3282f4d1e7.

  PMID: 18327082 BACKGROUND

• Seidlerova J, Staessen JA, Nawrot T, Brand E, Brand-Herrmann SM, Casamassima N, Citterio L, Hasenkamp S, Kuznetsova T, Li Y, Manunta P, Richart T, Struijker-Boudier HA, Fagard R, Filipovsk Ygrave J. Arterial properties in relation to genetic variation in alpha-adducin and the renin-angiotensin system in a White population. J Hum Hypertens. 2009 Jan;23(1):55-64. doi: 10.1038/jhh.2008.113. Epub 2008 Sep 18.

  PMID: 18800139 BACKGROUND

• Mischak H, Kolch W, Aivaliotis M, Bouyssie D, Court M, Dihazi H, Dihazi GH, Franke J, Garin J, Gonzalez de Peredo A, Iphofer A, Jansch L, Lacroix C, Makridakis M, Masselon C, Metzger J, Monsarrat B, Mrug M, Norling M, Novak J, Pich A, Pitt A, Bongcam-Rudloff E, Siwy J, Suzuki H, Thongboonkerd V, Wang LS, Zoidakis J, Zurbig P, Schanstra JP, Vlahou A. Comprehensive human urine standards for comparability and standardization in clinical proteome analysis. Proteomics Clin Appl. 2010 Apr;4(4):464-78. doi: 10.1002/prca.200900189. Epub 2010 Feb 3.

  PMID: 21137064 BACKGROUND

• Pearson TA, Mensah GA, Alexander RW, Anderson JL, Cannon RO 3rd, Criqui M, Fadl YY, Fortmann SP, Hong Y, Myers GL, Rifai N, Smith SC Jr, Taubert K, Tracy RP, Vinicor F; Centers for Disease Control and Prevention; American Heart Association. Markers of inflammation and cardiovascular disease: application to clinical and public health practice: A statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation. 2003 Jan 28;107(3):499-511. doi: 10.1161/01.cir.0000052939.59093.45. No abstract available.

  PMID: 12551878 BACKGROUND

• Marcelis M, Suckling J, Hofman P, Woodruff P, Bullmore E, van Os J. Evidence that brain tissue volumes are associated with HVA reactivity to metabolic stress in schizophrenia. Schizophr Res. 2006 Sep;86(1-3):45-53. doi: 10.1016/j.schres.2006.05.001. Epub 2006 Jun 27.

  PMID: 16806836 BACKGROUND

• Yeon JY, Kim HS, Sung MK. Diets rich in fruits and vegetables suppress blood biomarkers of metabolic stress in overweight women. Prev Med. 2012 May;54 Suppl:S109-15. doi: 10.1016/j.ypmed.2011.12.026. Epub 2011 Dec 29.

  PMID: 22226662 BACKGROUND

• Rao VS, Nagaraj RK, Hebbagodi S, Kadarinarasimhiah NB, Kakkar VV. Association of inflammatory and oxidative stress markers with metabolic syndrome in asian indians in India. Cardiol Res Pract. 2010 Dec 28;2011:295976. doi: 10.4061/2011/295976.

  PMID: 21234321 BACKGROUND

• Sharma JB, Sharma A, Bahadur A, Vimala N, Satyam A, Mittal S. Oxidative stress markers and antioxidant levels in normal pregnancy and pre-eclampsia. Int J Gynaecol Obstet. 2006 Jul;94(1):23-7. doi: 10.1016/j.ijgo.2006.03.025. Epub 2006 May 30.

  PMID: 16730727 BACKGROUND

• Luzardo L, Lujambio I, Sottolano M, da Rosa A, Thijs L, Noboa O, Staessen JA, Boggia J. 24-h ambulatory recording of aortic pulse wave velocity and central systolic augmentation: a feasibility study. Hypertens Res. 2012 Oct;35(10):980-7. doi: 10.1038/hr.2012.78. Epub 2012 May 24.

  PMID: 22622282 BACKGROUND

• Salaets T, Raaijmakers A, Zhang ZY, Yu YL, Wei DM, Staessen JA, Allegaert K. QTc intervals are not prolonged in former ELBW infants at pre-adolescent age. Pediatr Res. 2022 Sep;92(3):848-852. doi: 10.1038/s41390-021-01877-w. Epub 2021 Dec 2.

  PMID: 34857877 DERIVED

• Wei FF, Raaijmakers A, Melgarejo JD, Cauwenberghs N, Thijs L, Zhang ZY, Yu CG, Levtchenko E, Struijker-Boudier HAJ, Yang WY, Kuznetsova T, Kennedy S, Verhamme P, Allegaert K, Staessen JA. Retinal and Renal Microvasculature in Relation to Central Hemodynamics in 11-Year-Old Children Born Preterm or At Term. J Am Heart Assoc. 2020 Aug 4;9(15):e014305. doi: 10.1161/JAHA.119.014305. Epub 2020 Jul 31.

  PMID: 32750311 DERIVED

• Raaijmakers A, Zhang ZY, Levtchenko E, Simons SH, Cauwenberghs N, Heuvel LPVD, Jacobs L, Staessen JA, Allegaert K. Ibuprofen exposure in early neonatal life does not affect renal function in young adolescence. Arch Dis Child Fetal Neonatal Ed. 2018 Mar;103(2):F107-F111. doi: 10.1136/archdischild-2017-312922. Epub 2017 Jun 14.

  PMID: 28615304 DERIVED

• Raaijmakers A, Zhang ZY, Claessens J, Cauwenberghs N, van Tienoven TP, Wei FF, Jacobs L, Levtchenko E, Pauwels S, Kuznetsova T, Allegaert K, Staessen JA. Does Extremely Low Birth Weight Predispose to Low-Renin Hypertension? Hypertension. 2017 Mar;69(3):443-449. doi: 10.1161/HYPERTENSIONAHA.116.08643. Epub 2017 Jan 23.

  PMID: 28115515 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Urine collection Blood collection

MeSH Terms

Conditions

Blindness; Ventricular Dysfunction, Left; Renal Insufficiency; Premature Birth

Condition Hierarchy (Ancestors)

Vision Disorders; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Eye Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Ventricular Dysfunction; Heart Diseases; Cardiovascular Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications

Study Officials

• Karel M Allegaert, PhD, MD

  UZ Leuven, Belgium

  STUDY DIRECTOR

• Lotte Jacobs, PhD

  UZ Leuven

  STUDY CHAIR

• Anke MJ Raaijmakers, MD

  UZ Leuven, Belgium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 9, 2014
• First Posted: May 26, 2014
• Study Start: October 1, 2014
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: May 25, 2016

Record last verified: 2015-11

Locations

BE (1)