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Antenatal glucocorticoid treatment is not associated with long-term metabolic risks in individuals born before 32 weeks of gestation
  1. M J J Finken1,2,
  2. M G Keijzer-Veen2,3,
  3. F W Dekker2,
  4. M Frölich4,
  5. F J Walther1,
  6. J A Romijn5,
  7. B J van der Heijden3,
  8. J M Wit1
  1. 1
    Department of Pediatrics, Leiden University Medical Center, the Netherlands
  2. 2
    Department of Clinical Epidemiology, Leiden University Medical Center, the Netherlands
  3. 3
    Department of Pediatric Nephrology, Erasmus MC-Sophia Children’s Hospital, University Medical Center Rotterdam, the Netherlands
  4. 4
    Department of Clinical Chemistry, Leiden University Medical Center, the Netherlands
  5. 5
    Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, the Netherlands
  1. Martijn J J Finken, Department of Pediatrics, Leiden University Medical Center, P. O. Box 9600, 2300 RC Leiden, The Netherlands; m.j.j.finken{at}lumc.nl

Abstract

Background: A single course of maternal glucocorticoid treatment is effective in reducing neonatal mortality after preterm birth. However, in animals, maternal glucocorticoid treatment is associated with lifelong hyperglycaemia and hypertension, and impaired nephrogenesis in offspring. Findings from studies in humans on this topic are highly contradictory due to a number of methodological flaws, and renal function after glucocorticoid exposure has never been assessed.

Objectives: To assess in individuals born <32 gestational weeks whether antenatal glucocorticoid treatment for preterm birth is associated with long-term metabolical risks, including renal function, in adulthood.

Design: Birth cohort study.

Setting: Multicentre study.

Patients: 412 19 year olds born <32 gestational weeks from the Project On Preterm and Small-for-gestational-age infants (POPS) cohort.

Interventions: Maternal betamethasone 12 mg administered twice with a 24 h interval.

Main outcome measures: Body composition, insulin resistance, the serum lipid profile, blood pressure and estimated renal function.

Results: We did not find any long-term adverse effects of antenatal betamethasone, with the exception of an effect on glomerular filtration rate (GFR). In 19-year-old survivors, GFR was lower after betamethasone: −5.2 ml/min (95% CI −8.9 to −1.4) per 1.73 m2.

Conclusions: The reduction in neonatal mortality associated with a single course of maternal betamethasone is not accompanied by long-term metabolical risks in survivors of preterm birth. The only adverse effect found was lower GFR. Although this difference was not clinically relevant at 19 years, it might predict an increased risk of chronic renal failure in prematurely born individuals who were exposed antenatally to betamethasone.

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Footnotes

  • Competing interests: None.

  • Participants in the Dutch POPS-19 Collaborative Study Group are: TNO Quality of Life, Leiden (ETM Hille, CH de Groot, H Kloosterboer-Boerrigter, AL den Ouden, A Rijpstra, SP Verloove-Vanhorick, JA Vogelaar); Emma Children’s Hospital AMC, Amsterdam (JH Kok, A Ilsen, M van der Lans, WJC Boelen-van der Loo, T Lundqvist, HSA Heymans); University Hospital Groningen, Beatrix Children’s Hospital, Groningen (EJ Duiverman, WB Geven, ML Duiverman, LI Geven, EJLE Vrijlandt); University Hospital Maastricht, Maastricht (ALM Mulder, A Gerver); University Medical Center St Radboud, Nijmegen (LAA Kollée, L Reijmers, R Sonnemans); Leiden University Medical Center, Leiden (JM Wit, FW Dekker, MJJ Finken); Erasmus MC—Sophia Children’s Hospital, University Medical Center Rotterdam (N Weisglas-Kuperus, MG Keijzer-Veen, AJ van der Heijden, JB van Goudoever); V. U. University Medical Center, Amsterdam (MM van Weissenbruch, A Cranendonk, HA Delemarre-van de Waal, L de Groot, JF Samsom); Wilhelmina Children’s Hospital, UMC, Utrecht (LS de Vries, KJ Rademaker, E Moerman, M Voogsgeerd); Máxima Medical Center, Veldhoven (MJK de Kleine, P Andriessen, CCM Dielissen-van Helvoirt, I Mohamed); Isala Clinics, Zwolle (HLM van Straaten, W Baerts, GW Veneklaas Slots-Kloosterboer, EMJ Tuller-Pikkemaat); Royal Effatha Guyot Group, Zoetermeer (MH Ens-Dokkum); Association for Parents of Premature Babies (GJ van Steenbrugge).

  • Ethics approval: Ethics approval was obtained from all participating centres.

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