Research Unit for General Practice, Department of Public Health, Aarhus University, Aarhus, Denmark.
Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark.
BMJ Open. 2017 Jan 5;7(1):e012836. doi: 10.1136/bmjopen-2016-012836.
Prenatal exposure to antiepileptic drugs (AEDs) has been associated with adverse outcomes in the offspring such as congenital malformations and neuropsychiatric disorders. The objective of this study was to investigate whether prenatal exposure to AEDs is also associated with more frequent use of primary healthcare during childhood.
Population-based cohort study.
Nationwide national registers in Denmark.
All live-born singletons in Denmark during 1997-2012 identified in the Danish National Patient Register and followed until 31 December 2013 (n=963 010). Information on prenatal exposure to AEDs for maternal indication of epilepsy and other neurological conditions was obtained from the Danish Register of Medicinal Product Statistics.
The primary outcome measure was the number and type of contacts with the general practitioner (GP), excluding routine well-child visits and vaccinations. The secondary outcome measure was specific services provided at the GP contact. The association between prenatal exposure to AEDs and contacts with the GP was estimated by using negative binomial regression adjusting for sex and date of birth of the child, maternal age, cohabitation status, income, education, substance abuse, depression, severe psychiatric disorders and use of antipsychotics, antidepressants and insulin.
Children exposed prenatally to AEDs (n=4478) had 3% (95% CI 0 to 5%) more GP contacts during the study period than unexposed children. This was primarily accounted for by the number of phone contacts. Within each year of follow-up, exposed children tended to have more contacts than unexposed children, but the differences were small. We found no difference between exposed and unexposed children with regard to specific services provided at the GP contact. For the individual AEDs, we found that exposure to valproate or oxcarbazepine was associated with more GP contacts.
We found only minor differences between prenatally AED-exposed and unexposed children in the number of GP contacts.
产前暴露于抗癫痫药物(AEDs)与后代的先天畸形和神经精神障碍等不良结局有关。本研究旨在探讨产前暴露于 AED 是否也与儿童期更频繁地使用初级保健相关。
基于人群的队列研究。
丹麦全国性国家登记处。
丹麦 1997-2012 年期间所有在丹麦出生的活产单胎,在 2013 年 12 月 31 日前进行随访(n=963010)。关于母体癫痫和其他神经疾病的 AED 产前暴露的信息来自丹麦药品统计登记处。
主要观察指标为与全科医生(GP)的接触次数和类型,不包括常规的儿童健康检查和疫苗接种。次要观察指标为 GP 接触时提供的特定服务。使用负二项回归调整儿童性别和出生日期、母亲年龄、同居状况、收入、教育、药物滥用、抑郁、严重精神障碍以及抗精神病药、抗抑郁药和胰岛素的使用,来评估产前暴露于 AED 与 GP 接触之间的关联。
暴露于 AED 的儿童(n=4478)在研究期间的 GP 接触次数比未暴露的儿童多 3%(95%CI 0 至 5%)。这主要是由于电话接触次数的增加。在随访的每一年中,暴露组的儿童比未暴露组的儿童更倾向于有更多的接触,但差异很小。我们没有发现暴露组和未暴露组儿童在 GP 接触时提供的特定服务方面存在差异。对于个别 AED,我们发现暴露于丙戊酸或奥卡西平与更多的 GP 接触相关。
我们仅发现产前 AED 暴露与未暴露儿童在 GP 接触次数方面存在微小差异。