Behavioral and neurodevelopmental outcome of children after maternal allopurinol administration during suspected fetal hypoxia: 5-year follow up of the ALLO-trial

ObjectiveTo evaluate the long-term neurodevelopmental and behavioral outcome of antenatal allopurinol treatment during suspected fetal hypoxia.Study designWe studied children born from women who participated in a randomized double-blind placebo controlled multicenter study (ALLO-trial). Labouring women in whom the fetus was suspected to have fetal hypoxia were randomly allocated to receive allopurinol or placebo. At 5 years of age, the children were assessed with 2 parent reported questionnaires, the Ages and Stages Questionnaire (ASQ) and the Child Behavior Checklist (CBCL). A child was marked abnormal for ASQ if it scored below 2 standard deviation under the normative mean of a reference population in at least one domain. For CBCL, a score above the cut-off value (95th percentile for narrowband scale, 85th percentile for broadband scale) in at least one scale was marked as abnormal.ResultsWe obtained data from 138 out of the original 222 mildly asphyxiated children included in the ALLO-trial (response rate 62%, allopurinol n = 73, placebo n = 65). At 5 years of age, the number of children that scored abnormal on the ASQ were 11 (15.1%) in the allopurinol group versus 11 (9.2%) in the placebo group (relative risk (RR) 1.64, 95% confidence interval (CI): 0.64 to 4.17, p = 0.30). On CBCL 21 children (30.4%) scored abnormal in de allopurinol group versus 12 children (20.0%) in the placebo group (RR 1.52, 95% CI: 0.82 to 2.83, p = 0.18).ConclusionWe found no proof that allopurinol administered to labouring women with suspected fetal hypoxia improved long-term developmental and behavioral outcome. These findings are limited due to the fact that the study was potentially underpowered.Trial registrationNCT00189007 Dutch Trial Register NTR1383

研究目的：评估疑似胎儿缺氧期间产前别嘌醇治疗的长期神经发育和行为结果。研究设计：本研究调查了参与随机双盲安慰剂对照多中心研究（ALLO试验）的妇女所分娩的儿童。疑似胎儿缺氧的分娩妇女被随机分配接受别嘌醇或安慰剂。在5岁时，儿童通过两种家长报告问卷进行评估，即年龄段与阶段问卷（ASQ）和儿童行为评定量表（CBCL）。若儿童在至少一个领域中的得分低于参考人群规范性平均值的2个标准差以下，则其在ASQ中被评为异常。对于CBCL，若至少一个量表得分高于截止值（窄带量表的第95百分位数，宽带量表的第85百分位数），则被评为异常。结果：我们从ALLO试验中最初包括的222名轻度窒息儿童中获得了138名儿童的数据（响应率62%，别嘌醇组n = 73，安慰剂组n = 65）。在5岁时，在别嘌醇组中，ASQ异常的儿童有11名（15.1%），而在安慰剂组中为11名（9.2%）（相对风险（RR）1.64，95%置信区间（CI）：0.64至4.17，p = 0.30）。在CBCL中，别嘌醇组中有21名儿童（30.4%）得分异常，而安慰剂组中有12名儿童（20.0%）得分异常（RR 1.52，95% CI：0.82至2.83，p = 0.18）。结论：我们发现，对于疑似胎儿缺氧的分娩妇女给予别嘌醇治疗并未改善长期发育和行为结果。这些发现受到研究可能功率不足的限制。临床试验注册号：NCT00189007 荷兰临床试验注册 NTR1383