Meeraus Wilhelmine Hadler, Petersen Irene, Gilbert Ruth
UCL Institute of Child Health, Population Policy and Practice Programme, London, United Kingdom; UCL Research Department of Primary Care and Population Health, London, United Kingdom.
UCL Research Department of Primary Care and Population Health, London, United Kingdom.
PLoS One. 2015 Mar 25;10(3):e0122034. doi: 10.1371/journal.pone.0122034. eCollection 2015.
Between 19%-44% pregnant women are prescribed antibiotics during pregnancy. A single, large randomised-controlled-trial (ORACLE Childhood Study II) found an increased risk of childhood cerebral palsy and possibly epilepsy following prophylactic antibiotic use in pregnant women with spontaneous preterm labour. We ascertained whether this outcome could be reproduced across the population of babies delivered at term and prospectively followed in primary-care using data from The Health Improvement Network.
We determined the risk of cerebral palsy or epilepsy in children whose mothers were prescribed antibiotics during pregnancy using a cohort of 195,909 women linked to their live, term-born, singleton children. We compared the effect of antibiotic class, number of courses and timing of prescribing in pregnancy. Analyses were adjusted for maternal risk factors (e.g. recorded infection, age, chronic conditions, social deprivation, smoking status). Children were followed until age seven years or cessation of registration with the primary-care practitioner.
In total, 64,623 (33.0%) women were prescribed antibiotics in pregnancy and 1,170 (0.60%) children had records indicating cerebral palsy or epilepsy. Adjusted analyses showed no association between prescribing of any antibiotic and cerebral palsy or epilepsy (adj.HR 1.04, 95%CI 0.91-1.19). However, compared with penicillins, macrolides were associated with an increased risk of cerebral palsy or epilepsy (adj.HR 1.78, 95%CI 1.18-2.69; number needed to harm 153, 95%CI 71-671).
We found no overall association between antibiotic prescribing in pregnancy and cerebral palsy and/or epilepsy in childhood. However, our finding of an increased risk of cerebral palsy or epilepsy associated with macrolide prescribing in pregnancy adds to evidence that macrolide use is associated with serious harm.
19% - 44%的孕妇在孕期会使用抗生素。一项大型随机对照试验（ORACLE儿童研究II）发现，自发性早产孕妇预防性使用抗生素后，其子女患儿童脑瘫及可能患癫痫的风险增加。我们利用健康改善网络的数据，确定在足月分娩并在初级保健机构进行前瞻性随访的婴儿群体中，这一结果是否会重现。
我们通过对195,909名与她们存活的足月单胎子女相关联的女性进行队列研究，确定其母亲在孕期使用抗生素的儿童患脑瘫或癫痫的风险。我们比较了抗生素类别、疗程数量及孕期用药时间的影响。分析针对母亲的风险因素（如记录在案的感染、年龄、慢性病、社会剥夺、吸烟状况）进行了调整。对儿童进行随访直至7岁或停止在初级保健医生处登记。
总计64,623名（33.0%）女性在孕期使用了抗生素，1,170名（0.60%）儿童有记录显示患有脑瘫或癫痫。校正分析显示，使用任何抗生素与脑瘫或癫痫之间均无关联（校正风险比1.04，95%置信区间0.91 - 1.19）。然而，与青霉素相比，大环内酯类抗生素与脑瘫或癫痫风险增加相关（校正风险比1.78，95%置信区间1.18 - 2.69；伤害所需人数153，95%置信区间71 - 671）。
我们发现孕期使用抗生素与儿童脑瘫和/或癫痫之间无总体关联。然而，我们发现孕期使用大环内酯类抗生素与脑瘫或癫痫风险增加，这进一步证明了使用大环内酯类抗生素会造成严重危害。
