Department of Obstetrics and Gynecology, University Medical Center Utrecht, Utrecht, The Netherlands.
Department of Obstetrics and Gynecology, Haaglanden Medical Center, The Hague, The Netherlands.
Ultrasound Obstet Gynecol. 2018 Jun;51(6):806-812. doi: 10.1002/uog.17512.
Brain injury in neonates born prematurely is associated strongly with poor neurodevelopmental outcome. The aim of this study was to evaluate whether tocolysis with nifedipine or atosiban in women with threatened preterm birth can reduce the incidence of overall brain injury in neonates born prematurely.
This was a secondary analysis of the APOSTEL-III trial (Dutch Clinical Trial Registry, no. NTR2947), a randomized clinical trial in which women with threatened preterm labor between 25 and 34 weeks of gestation were allocated to treatment with nifedipine or atosiban. In this secondary analysis, women delivered at ≤ 32 weeks of gestational age in the two main contributing centers were included. Primary outcome was the presence of neonatal brain injury, which was defined as presence of abnormalities on ultrasound investigation and classified into mild and severe. To evaluate type and severity of brain injury, all neonatal ultrasounds performed during neonatal intensive and medium care admission were analyzed. To test the robustness of our results, a sensitivity analysis was performed assessing differences in baseline or known risk factors for brain injury.
A total of 117 neonates (from 102 women) were studied, of which 51 had been exposed to nifedipine and 66 to atosiban. Brain injury was observed in 22 (43.1%) neonates in the nifedipine group compared with 37 (56.1%) in the atosiban group (OR, 0.60; 95% CI, 0.29-1.24). Presence of mild brain injury was comparable between the nifedipine (33.3%) and atosiban (48.5%) groups (OR, 0.53; 95% CI, 0.25-1.13). Severe brain injury was also comparable between the groups, observed in 9.8% of neonates in the nifedipine vs 7.6% of those in the atosiban group (OR, 1.33; 95% CI, 0.36-4.85). Intraventricular hemorrhage (≥ Grade I) was the most frequently seen ultrasound abnormality, observed in 18 (35.3%) neonates in the nifedipine group vs 25 (37.9%) in the atosiban group (OR, 0.90; 95% CI, 0.42-1.91). The sensitivity analysis, with adjustment for maternal age and gestational age at randomization, showed no statistical difference between the groups for presence of brain injury (OR, 0.58; 95% CI, 0.27-1.27).
In children born before 32 weeks of gestation after the use of tocolytics, the prevalence of brain injury was high. No significant differences were found with respect to overall brain injury between neonates exposed to nifedipine and those exposed to atosiban. However, as this study was a secondary analysis of the APOSTEL III trial, it was underpowered for brain injury. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.
早产儿脑损伤与不良神经发育结局密切相关。本研究旨在评估在有早产风险的妇女中使用硝苯地平或阿托西班进行保胎治疗是否可以降低早产儿脑损伤的总体发生率。
这是 APOSTEL-III 试验（荷兰临床试验注册处，编号 NTR2947）的二次分析，这是一项随机临床试验，其中妊娠 25 至 34 周之间有早产风险的妇女被分配接受硝苯地平或阿托西班治疗。在这项二次分析中，纳入了两个主要参与中心中在妊娠 32 周前分娩的妇女。主要结局是新生儿脑损伤的存在，其定义为超声检查存在异常，并分为轻度和重度。为了评估脑损伤的类型和严重程度，对新生儿重症监护和中级护理入院期间进行的所有新生儿超声检查进行了分析。为了检验我们结果的稳健性，进行了敏感性分析，评估了基线或已知脑损伤风险因素的差异。
共研究了 117 名新生儿（来自 102 名妇女），其中 51 名新生儿暴露于硝苯地平，66 名新生儿暴露于阿托西班。硝苯地平组中有 22 名（43.1%）新生儿出现脑损伤，阿托西班组中有 37 名（56.1%）新生儿出现脑损伤（OR，0.60；95%CI，0.29-1.24）。硝苯地平组（33.3%）和阿托西班组（48.5%）轻度脑损伤的发生率相似（OR，0.53；95%CI，0.25-1.13）。两组重度脑损伤也相似，硝苯地平组有 9.8%的新生儿出现重度脑损伤，阿托西班组有 7.6%的新生儿出现重度脑损伤（OR，1.33；95%CI，0.36-4.85）。最常见的超声异常是脑室出血（≥Ⅰ级），硝苯地平组有 18 名（35.3%）新生儿出现该异常，阿托西班组有 25 名（37.9%）新生儿出现该异常（OR，0.90；95%CI，0.42-1.91）。敏感性分析，调整随机分组时的母亲年龄和孕周，两组脑损伤的存在无统计学差异（OR，0.58；95%CI，0.27-1.27）。
在使用保胎药物的妊娠 32 周前出生的儿童中，脑损伤的发生率较高。硝苯地平组和阿托西班组之间的总体脑损伤发生率无显著差异。然而，由于本研究是 APOSTEL III 试验的二次分析，因此在脑损伤方面的研究力度不足。版权所有©2017 ISUOG。由 John Wiley & Sons Ltd 出版。
