Archives of Gynecology and Obstetrics

, Volume 298, Issue 3, pp 521–527 | Cite as

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

  • Hannes Hudalla
  • Christian Karmen
  • Thomas Bruckner
  • Stephanie Wallwiener
  • Herbert Fluhr
  • Zoe Michael
  • Alexander Freis
  • Holger Maul
  • Thomas Strowitzki
  • Johannes Pöschl
  • Ruben-J. KuonEmail author
Maternal-Fetal Medicine



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.


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.


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).


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.


Preterm birth Tocolysis β2-sympathomimetics Fenoterol Hemangioma 


Author 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.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Hannes Hudalla
    • 1
  • Christian Karmen
    • 2
  • Thomas Bruckner
    • 2
  • Stephanie Wallwiener
    • 3
  • Herbert Fluhr
    • 3
  • Zoe Michael
    • 4
  • Alexander Freis
    • 5
  • Holger Maul
    • 6
  • Thomas Strowitzki
    • 5
  • Johannes Pöschl
    • 1
  • Ruben-J. Kuon
    • 5
    Email author
  1. 1.Department of NeonatologyHeidelberg University HospitalHeidelbergGermany
  2. 2.Institute of Medical Biometry and InformaticsHeidelberg UniversityHeidelbergGermany
  3. 3.Department of Obstetrics and GynecologyHeidelberg University HospitalHeidelbergGermany
  4. 4.Department of Pediatric Newborn MedicineBrigham and Women’s Hospital, Harvard Medical SchoolBostonUSA
  5. 5.Department of Gynecological Endocrinology and Fertility DisordersHeidelberg University HospitalHeidelbergGermany
  6. 6.Department of Obstetrics and GynecologyAsklepios KlinikHamburgGermany

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