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Tocolysis with the β2-sympathomimetic fenoterol does not increase the occurrence of infantile hemangioma in preterm and term infants

  • Maternal-Fetal Medicine
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

β2-sympathomimetics are used in obstetrics as tocolytic agents, despite a remarkable profile of side effects. Recently, the β2-sympathomimetic tocolytic drug hexoprenaline was identified as an independent risk factor for the development of infantile hemangioma (IH) in preterm infants. The aim of this study was to evaluate whether this observed effect was applicable to other β2-mimetic tocolytic agents like fenoterol.

Methods

Clinical prospectively collected data of all infants born between 2001 and 2012 and admitted to the neonatal intensive care unit (NICU) at Heidelberg University Hospital and respective maternal data were merged. For the current retrospective cohort study, cases (IH) were matched to controls (no IH) at a ratio of 1:4, adjusting for birth weight, gestational age, gender and multiple gestations. Prenatal exposure to fenoterol and perinatal outcome were analyzed in the total cohort and in subgroups.

Results

N = 5070 infants were admitted to our neonatal department, out of which n = 172 infants with IH were identified and compared to n = 596 matched controls. Exposure to fenoterol was not associated with a higher rate of IH in the total matched population (OR 0.926, 95% CI 0.619–1.384) or in a subgroup of neonates < 32 weeks of gestation or with a birth weight < 1500 g (OR 1.127, 95% CI 0.709–1.791). In the total matched population, prenatal exposure to glucocorticoids was associated with a reduced occurrence of IH (OR 0.566, 95% CI 0.332–0.964) and neonates with IH showed a prolonged total hospital stay compared to controls (69 vs. 57 days, p = 0.0033). Known risk factors for IH were confirmed by our large study cohort and included female gender, low birth weight, preterm birth and multiple gestations (all p < 0.005).

Conclusions

Exposure to fenoterol during pregnancy does not increase the occurrence of IH. Further studies are needed to explore differences in the risk profiles of different β2-sympathomimetic tocolytic drugs.

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Author information

Author notes

  1. Hannes Hudalla and Ruben-J. Kuon contributed equally to this work.

Authors and Affiliations

  1. Department of Neonatology, Heidelberg University Hospital, Heidelberg, Germany

    Hannes Hudalla & Johannes Pöschl

  2. Institute of Medical Biometry and Informatics, Heidelberg University, Heidelberg, Germany

    Christian Karmen & Thomas Bruckner

  3. Department of Obstetrics and Gynecology, Heidelberg University Hospital, Heidelberg, Germany

    Stephanie Wallwiener & Herbert Fluhr

  4. Department of Pediatric Newborn Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Zoe Michael

  5. Department of Gynecological Endocrinology and Fertility Disorders, Heidelberg University Hospital, Im Neuenheimer Feld 440, 69120, Heidelberg, Germany

    Alexander Freis, Thomas Strowitzki & Ruben-J. Kuon

  6. Department of Obstetrics and Gynecology, Asklepios Klinik, Hamburg, Germany

    Holger Maul

Authors
  1. Hannes Hudalla
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Contributions

H Hudalla: protocol/project development, data collection or management, data analysis and manuscript writing/editing. C Karmen: data collection or management. T Bruckner: data collection or management and data analysis. S Wallwiener: manuscript editing. H Fluhr: manuscript editing. Z Michael: manuscript editing. A Freis: manuscript editing. H Maul: manuscript editing. T Strowitzki: manuscript editing. J Pöschl: manuscript editing. RJ Kuon: protocol/project development, data collection or management, data analysis and manuscript writing/editing.

Corresponding author

Correspondence to Ruben-J. Kuon.

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Conflict of interest

The authors declare that they have no conflict of interest.

Funding

None declared.

Ethical approval

The study was approved by the Heidelberg University institutional review board (Ethikkommission der Medizinischen Fakultät Heidelberg, Alte Glockengießerei 11/1, 69115 Heidelberg, Germany, IRB number: S-094/2013). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Requirement for inform consent has been waived by the Heidelberg University institutional review board (Ethikkommission der Medizinischen Fakultät Heidelberg, IRB number: S-094/2013) due to the retrospective nature of the study and pseudonymization of data.

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Hudalla, H., Karmen, C., Bruckner, T. et al. Tocolysis with the β2-sympathomimetic fenoterol does not increase the occurrence of infantile hemangioma in preterm and term infants. Arch Gynecol Obstet 298, 521–527 (2018). https://doi.org/10.1007/s00404-018-4830-5

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  • DOI: https://doi.org/10.1007/s00404-018-4830-5

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