Effects Of Planned And Unplanned Pregnancy On Pregnant Outcomes In Women With Epilepsy

Background and Objective:The eugenics of women with epilepsy(WWE)is not only an important challenge in the field of epilepsy,but also a critical public health problem at present.Epilepsy per se and antiepileptic drugs(AEDs)are likely to cause certain adverse effects on pregnant WWE and their offspring.The choice of AEDs during pregnancy,seizure control,folic acid supplementation,pregnancy complications,breastfeeding,congenital malformation and neurodevelopmental disorders of offspring are common concerns for epileptologists and WWE of childbearing age.Therefore,preconceptual counselling and management of pregnancy,i.e.planned-pregnancy,may be an effective strategy to reduce the risk of pregnancy complications and congenital malformations of their offspring.Currently,most of the pregnancies in WWE are unplanned.A recent study has shown that unplanned pregnancies may double the risk of spontaneous fetal loss(SFL)among offspring of WWE.However,the association between planned and unplanned pregnancy and offspring’s other adverse fetal outcomes has not been studied.Here,we examined the antiepileptic drugs(AEDs)treatment patterns,seizure control,and folic acid supplementation between planned and unplanned pregnancy in WWE,and investigated the association between some modifiable risk factors and adverse fetal outcomes.Methods:From Feb 2010 to Dec 2018,consecutive cases of WWE with pregnancy registered at Xijing Hospital were retrospectively reviewed.All the enrolled WWE were divided into two groups,planned-pregnancy group and unplanned-pregnancy group.Planned pregnancy was defined as preconception counseling with epileptologists in a face-to-face manner to optimize the type and dose of AEDs and folic acid supplementation and regularly followed up according to changes of clinical status.The unplanned-pregnancy group contained all the pregnancies that were not included in the planned-pregnancy group,such as the WWE who had unexpected pregnancies thus did not have preconception counseling,the WWE who consulted epileptologists after conception,or WWE who could not be regularly followed up during pregnancy.Clinical characteristics and fetal outcomes were compared between the planned and unplanned pregnancy group by using the Mann-Whitney U test or Chi-square test with onferroni post hoc.Binary logistic regression was used to identify modifiable variables associated with adverse fetal outcomes.Results:477 pregnancies in 401 WWE were enrolled,including 188 of 477 planned pregnancies(39.4%)and 289 of 477 unplanned pregnancies(60.6%).Comparisons of clinical characteristics and pregnancy outcomes between the two groups are as follows:(1)Baseline characteristics: WWE in the planned group had a younger age of seizure onset [16(12-20)] than the unplanned-pregnancy group [18(13-22);p = 0.016];Of the two groups,the unplanned-pregnancy group had a lower education level(p = 0.003,Chi-square test),with 1.7% illiteracy and 17.6% primary school education;And in the planned group,no one was illiterate,and 91.5% of the cases of pregnancy received a middle school education or above.(2)AED treatment patterns in the first trimester: Among the planned-pregnancy group,66.0% of the pregnancies(124/188)took AED monotherapy,and 32.4% of pregnancies(61/188)received polytherapy.In the unplanned-pregnancy group,58.1%(168/289)did not take AEDs,28.0%(81/289)took AED monotherapy,and 12.8%(37/289)received polytherapy.None of the planned pregnancies took valproate(VPA)as monotherapy whereas 4.8% of the unplanned pregnancies took it(p = 0.002);(3)Seizure control during pregnancy: Compared with the unplanned-pregnancy group,the planned-pregnancy group had less frequency of generalized tonic-clonic seizures(GTCS)[ 1(1-2)vs.2(1-4);p = 0.002] and higher proportion of being seizure-free(77/188,41.0% vs.66/289,22.8%;p < 0.001);(4)Folic acid supplementation: All planned pregnancies took folic acid supplementation,but in the unplanned pregnancy group,39.8% of pregnancies(115/289)did not take folic acid(p < 0.001);The proportion of appropriate folic acid supplementation in the planned-pregnancy group was more than that of the unplanned-pregnancy group(154/188,81.9% vs.104/289,36.0%;p < 0.001);(5)Breastfeeding: No significant difference was found between planned-and unplanned-pregnancy group in regard to breastfeeding(88/188,48.4% vs.115/289,47.9%;p = 0.929);(6)Adverse fetal outcomes: The planned-pregnancy group showed significantly less adverse fetal outcomes than that of the unplanned group,including induced abortions(5/188,2.7% vs.39/289,13.5%;p < 0.001),preterm births among the live birth(6/182,3.3% vs.49/240,20.4%;p < 0.001)and major congenital malformations(MCM)among the live births within one year of delivery(3/182,1.6% vs.18/240,7.5%;p = 0.016);(7)Modifiable risk factors associated with adverse fetal outcomes: Regression analysis found that pregnancy planning was an independent protective factor of adverse fetal outcomes(adjusted odds ratio [a OR],0.14;95% confidence interval[CI],0.08-0.27;p < 0.001);Frequency of GTCS during pregnancy(a OR,1.16,95% CI,1.03-1.30;p <0.012)and whether taking VPA during pregnancy(a OR,4.34,95% CI,2.09-9.00;p< 0.001)were both independent risk factors of adverse fetal outcomes.Conclusions:1.The proportion of unplanned pregnancies was up to 60.6%,and it was related to a lower education level of WWE.2.Planned pregnancy contributes to more optimized AEDs treatment patterns,better seizure control,more appropriate folic acid supplementation and less adverse fetal outcomes,i.e.induced abortions,preterm births and MCM within 1 year of birth.3.Planned-pregnancy is an independent protective factor for reducing adverse fetal outcomes in WWE.4.Frequency of GTCS during pregnancy and whether taking VPA during pregnancy were both independent risk factors of adverse fetal outcomes.