Use of antiepileptic drugs during pregnancy and risk of spontaneous abortion and stillbirth: population based cohort study

Abstract

Objective To determine whether use of antiepileptic drugs during pregnancy may increase the risk of spontaneous abortion or stillbirth.Design Population based cohort study.Setting Register based study in Denmark, 1997Denmark, -2008 Participants 983 305 pregnancies identified in the Danish medical birth register and the Danish national hospital discharge register from 1

Antiepileptic drugs and intrauterine death

“…Given this background, it is surprising that only one study to date (the Danish register study) has evaluated the comparative risks of intrauterine death associated with different AED treatments. 10 Our findings in a considerably larger cohort of prospectively followed pregnancies in women with epilepsy demonstrate that frequencies of intrauterine death are similar across pregnancies exposed to the 6 most frequently used AED monotherapies, in keeping with the results of the Danish study. 10 We found no relationship between occurrence of intrauterine death and AED dose, at least for LTG, CBZ, or VPA, whereas an increased occurrence was identified in women exposed to polytherapy.…”

“…10 Our findings in a considerably larger cohort of prospectively followed pregnancies in women with epilepsy demonstrate that frequencies of intrauterine death are similar across pregnancies exposed to the 6 most frequently used AED monotherapies, in keeping with the results of the Danish study. 10 We found no relationship between occurrence of intrauterine death and AED dose, at least for LTG, CBZ, or VPA, whereas an increased occurrence was identified in women exposed to polytherapy. The observation that AED monotherapy, which is the predominant treatment regimen in pregnant women with epilepsy, [7][8][9] had no apparent impact on the rate of spontaneous abortions or stillbirths is also consistent with a previous report from Rochester based on 788 pregnancies in 256 women with epilepsy.…”

“…In the general population in the Danish register study, the rate of spontaneous abortions is 11% and of stillbirths is 0.3%. 10 However, the rates of spontaneous abortions identified in our analysis cannot be compared with those of the Rochester study or the Danish register study because, in addition to using slightly different diagnostic criteria, our prospective study did not allow detection of early abortions occurring before enrollment (median gestational week 8), while the Rochester medical record linkage system and the Danish Health Care register enabled identification of abortions occurring throughout the entire duration of pregnancy. The Rochester study also found that in women with epilepsy, as in the general population, the highest rates of spontaneous abortion occur in early pregnancy, 15 which is in line with our own findings showing decreasing risk of intrauterine death with increasing gestational week (table 4).…”

“…15 The recent Danish register-based study has some advantages. 10 Because it is population-based, its results are representative of and the methodology allows a comparison with the general population. It is therefore reassuring that the absence of differences in miscarriage rates among different AEDs in our more selected population is consistent with the Danish findings.…”

“…[7][8][9] Less focus has been given to the role of AEDs regarding other adverse pregnancy outcomes, in particular spontaneous abortions and stillbirths. A recent Danish study based on data from national health registries found no association between AED use during pregnancy and spontaneous abortions in women with epilepsy (n 5 2,615) but found a significantly increased risk with AED use in women without epilepsy, 10 leading to the question of a potential impact of unmeasured confounding.…”