Hudalla Hannes, Karmen Christian, Bruckner Thomas, Wallwiener Stephanie, Fluhr Herbert, Michael Zoe, Freis Alexander, Maul Holger, Strowitzki Thomas, Pöschl Johannes, Kuon Ruben-J
Department of Neonatology, Heidelberg University Hospital, Heidelberg, Germany.
Institute of Medical Biometry and Informatics, Heidelberg University, Heidelberg, Germany.
Arch Gynecol Obstet. 2018 Sep;298(3):521-527. doi: 10.1007/s00404-018-4830-5. Epub 2018 Jun 25.
β-sympathomimetics are used in obstetrics as tocolytic agents, despite a remarkable profile of side effects. Recently, the β-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 β-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 β-sympathomimetic tocolytic drugs.
β-拟交感神经药尽管有显著的副作用，但仍被用作产科的宫缩抑制剂。最近，β-拟交感神经药宫缩抑制剂海索那林被确定为早产儿发生婴儿血管瘤（IH）的独立危险因素。本研究的目的是评估这种观察到的效应是否适用于其他β-拟交感神经药宫缩抑制剂，如非诺特罗。
临床前瞻性收集了2001年至2012年间出生并入住海德堡大学医院新生儿重症监护病房（NICU）的所有婴儿的数据，并将相应的母亲数据进行合并。对于当前的回顾性队列研究，将病例（IH）与对照（无IH）按1:4的比例进行匹配，并对出生体重、胎龄、性别和多胎妊娠进行调整。在整个队列和亚组中分析产前暴露于非诺特罗的情况和围产期结局。
共有5070名婴儿入住我们的新生儿科，其中确定了172名患有IH的婴儿，并与596名匹配的对照进行比较。在整个匹配人群中，暴露于非诺特罗与较高的IH发生率无关（OR 0.926，95%CI 0.619 - 1.384），在胎龄<32周或出生体重<1500 g的新生儿亚组中也无关（OR 1.127，95%CI 0.709 - 1.791）。在整个匹配人群中，产前暴露于糖皮质激素与IH发生率降低有关（OR 0.566，95%CI 0.332 - 0.964），与对照相比，患有IH的新生儿住院总天数延长（69天对57天，p = 0.0033）。我们的大型研究队列证实了IH的已知危险因素，包括女性性别、低出生体重、早产和多胎妊娠（所有p < 0.005）。
孕期暴露于非诺特罗不会增加IH的发生率。需要进一步研究以探索不同β-拟交感神经药宫缩抑制剂风险概况的差异。
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