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Ibuprofen exposure in early neonatal life does not affect renal function in young adolescence
  1. Anke Raaijmakers1,2,
  2. Zhen-Yu Zhang1,2,3,
  3. Elena Levtchenko1,
  4. Sinno HP Simons4,
  5. Nicholas Cauwenberghs3,
  6. Lambertus P van den Heuvel2,
  7. Lotte Jacobs3,
  8. Jan A Staessen3,5,
  9. Karel Allegaert2,4,6
  1. 1 Department of Pediatrics and Neonatology, University Hospitals Leuven, Leuven, Belgium
  2. 2 KU Leuven Department of Development and Regeneration, University of Leuven, Leuven, Belgium
  3. 3 Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium
  4. 4 Department of Pediatrics, Division of Neonatology, Erasmus MC Sophia Children’s Hospital, Rotterdam, The Netherlands
  5. 5 R&D Group VitaK, Maastricht University, Maastricht, The Netherlands
  6. 6 Intensive Care and Department of Pediatric Surgery, Erasmus Medical Center Sophia Children’s Hospital, Rotterdam, The Netherlands
  1. Correspondence to Dr Karel Allegaert, Department of Development and Regeneration, Herestraat 49, 3000 Leuven, KU Leuven, Belgium; karel.allegaert{at}


Introduction Ibuprofen exposure results in acute transient renal dysfunction in preterm neonates, but we are unaware of data on long-term renal safety.

Methods In a previously studied cohort of extreme low birth weight (ELBW, <1000 g) cases, the PREMATurity as predictor of children’s Cardiovascular-renal Health study generated data on renal function (renal length, estimated glomerular filtration rate based on cystatin C (eGFRcysC) at the age of 11 years. This data set in 93 ELBW cases may also generate data on long-term drug safety on ibuprofen. In this post hoc analysis, we linked markers of renal function in young adolescence in ELBW cases with their perinatal (prenatal maternal, setting at birth, treatment modalities including drug prescription during neonatal stay, neonatal creatinine values, postdischarge growth) characteristics, including but not limited to ibuprofen exposure during neonatal stay.

Results Ibuprofen exposure was not associated with significant differences in renal length or eGFRcysC. Moreover, we were unable to identify any other risk factor (perinatal characteristics, postnatal creatinine trends, postdischarge growth) on renal outcome in this cohort.

Conclusions Neonatal exposure to ibuprofen did not affect renal function. Larger studies are needed to explore the confounders of variability in renal function in former ELBW cases. This matters since ELBW relates to risk for hypertension, cardiovascular events and renal disease in later life and identification of risk factors holds the promise of secondary prevention.

Trial registration number NCT02147457.

  • Cystatin C
  • drug safety
  • ibuprofen
  • preterm

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  • JAS and KA contributed equally.

  • Contributors AR developed the study protocol, contributed to data collection, data analysis, interpreting and writing, ZYZ, NC and LJ contributed to data collection, data analysis, interpreting and writing, EL, SS and LPH contributed to writing and interpreting of the study. JAS and KA were the coordinators of the study, including advices on study protocol, data collection, data analysis, interpreting and writing. All authors agreed on the final version of the paper.

  • Funding This research is supported by the Agency for Innovation, Science and Technology in Flanders (IWT) through the SAFEPEDRUG project (IWT/SBO 120033).

  • Competing interests None declared.

  • Patient consent Parental/guardian consent obtained.

  • Ethics approval The study was conducted in accordance with the Helsinki declaration for investigations in human subjects. The Ethics Committee of the University Hospitals Leuven (Belgium) approved the study.

  • Provenance and peer review Not commissioned; externally peer reviewed.