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Original article
Genetic background of high blood pressure is associated with reduced mortality in premature neonates
  1. Wolfgang Göpel1,
  2. Mirja Müller1,
  3. Heike Rabe2,
  4. Johannes Borgmann1,
  5. Tanja K Rausch3,
  6. Kirstin Faust1,
  7. Angela Kribs4,
  8. Jörg Dötsch5,
  9. David Ellinghaus6,
  10. Christoph Härtel1,
  11. Claudia Roll7,
  12. Miklos Szabo8,
  13. Peter Nürnberg9,
  14. Andre Franke6,
  15. Inke R König3,
  16. Mark A Turner10,
  17. Egbert Herting1
  1. 1 Paediatrics, University of Lübeck, Lübeck, Germany
  2. 2 Neonatology, Brighton Sussex University Hospitals NHS Trust, Brighton, UK
  3. 3 Institute for Medical Biometry and Statistics Lübeck, Lübeck, Germany
  4. 4 Neonatology and Pediatric Intensive Care, University Hospital of Cologne, Cologne, Germany
  5. 5 Department of Paediatrics, University of Cologne, Cologne, Germany
  6. 6 Institute of Clinical Molecular Biology, Christian-Albrechts-Universitat zu Kiel, Kiel, Germany
  7. 7 Neonatology, Universitat Witten/Herdecke, Witten, Germany
  8. 8 Neonatology, Semmelweis University, Budapest, Hungary
  9. 9 Cologne Center for Genomics, University Hospital of Cologne, Cologne, Germany
  10. 10 Division of Perinatal Reproductive Medicine, University of Liverpool, Liverpool, UK
  1. Correspondence to Professor Wolfgang Göpel, Paediatrics, University of Lübeck, Lübeck 23538, Germany; wolfgang.goepel{at}uksh.de

Abstract

Objective The aim of our study was to determine if a genetic background of high blood pressure is a survival factor in preterm infants.

Design Prospective cohort study.

Setting Patients were enrolled in 53 neonatal intensive care units.

Patients Preterm infants with a birth weight below 1500 g.

Exposures Genetic score blood pressure estimates were calculated based on adult data. We compared infants with high genetic blood pressure estimates (>75th percentile of the genetic score) to infants with low genetic blood pressure estimates (<25th percentile of the genetic score).

Main outcome measures Lowest blood pressure on the first day of life and mortality.

Results 5580 preterm infants with a mean gestational age of 28.1±2.2 weeks and a mean birth weight of 1022±299 g were genotyped and analysed. Infants with low genetic blood pressure estimates had significantly lower blood pressure if compared with infants with high genetic blood pressure estimates (27.3±6.2vs 27.9±6.4, p=0.009, t-test). Other risk factors for low blood pressure included low gestational age (−1.26 mm Hg/week) and mechanical ventilation (−2.24 mm Hg, p<0.001 for both variables, linear regression analysis). Mortality was significantly reduced in infants with high genetic blood pressure estimates (28-day mortality: 21/1395, 1.5% vs 44/1395, 3.2%, p=0.005, Fisher’s exact test). This survival advantage was independent of treatment with catecholamines.

Conclusions Our study provides first evidence that a genetic background of high blood pressure may be beneficial with regard to survival of preterm infants.

  • neonatology
  • genetics
  • hypotension
  • mortality

http://dx.doi.org/10.1136/archdischild-2019-317131

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    Footnotes

    • Contributors WG, MM, JB, KF, AK, JD, CH, CR and EH designed data collection tools, were responsible for the overall design of the study and patient enrolment. WG, TJ, DE, PN, AF and IRK were responsible for chip-genotyping, imputation and data analysis. WG, HR, MS, CH, MAT and EH were responsible for the analysis of clinical data. All authors contributed to the initial manuscript and revised the draft paper.

    • Funding This study was funded by the German Federal Ministry of Education and Research (GNN, BMBF 01ER0805 and BMBF 01ER1501) and European Union (NEO-CIRC, FP7-282533).

    • Competing interests None declared.

    • Ethics approval The German Neonatal Network study was approved by the ethics committee at the University of Lübeck and at each participating centre.

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

    • Patient consent for publication Not required.