Safety aspects and patterns of medication use in pregnancy. With special focus on psychotropic medication and mental health

Use of medications, including psychotropics, is common during pregnancy. Indeed, many women might be in need of pharmacotherapy during pregnancy in order to ensure maternalfetal health. However, discordant findings or lack of information about neonatal and maternal safety after use of psychotropics, in particular antidepressants, have so far posed significant challenges on practicing clinicians when assessing the risk of pharmacotherapy versus the risk of not medicated maternal illness. In addition, women's unrealistic risk perception of exposure to antidepressants during pregnancy and individuals' beliefs about prescribed medicines may influence women's adherence to needed medications during pregnancy. \n \nThus, the aims of this doctoral work were: I) to explore from a multinational perspective patterns of and factors associated with use of medications during pregnancy, with particular focus on psychotropics for treatment of depression and/or anxiety; II) to investigate patterns of and associations between use of psychotropics and other relevant medications in the time around pregnancy and eating disorders; III) to explore patterns of and risk factors for low adherence to psychotropics during pregnancy; IV) to determine whether gestational exposure to antidepressants increases the risk of obstetric bleeding complications during pregnancy and postpartum. \n \nIn order to address these research questions, data from two studies were utilized. The Multinational Medication Use in Pregnancy Study, providing information about psychiatric and other disorders during pregnancy, related medications use and adherence during pregnancy as reported by participating women, was used to address aims nos. I and III. The Norwegian Mother and Child Cohort Study, comprising information on medication exposures and maternal characteristics during pregnancy, linked to the Medical Birth Registry of Norway providing information about birth outcomes, were utilized to address aims nos. II and IV. Study I showed that about eight out of ten women used at least one medication during the course of the pregnancy, whereas five out of ten did so during the first trimester. There was a high degree of self-medication with OTC drugs (67%) during pregnancy. About 3% of women reported use of psychotropic medications during pregnancy, mostly SSRIs. Disadvantaged women (e.g. single or divorced, older, with low education, smokers and alcohol consumers during pregnancy) or with an unplanned pregnancy were more likely to use psychotropics during pregnancy. \n \nStudy II showed that use of psychotropics is high among women with eating disorders before, during, and after pregnancy, particularly among women with AN or EDNOS-P. Having BN was found to be significantly directly associated with use (1.8-fold magnitude) and incident use (2.3-fold magnitude) of psychotropics during pregnancy. Having AN or EDNOS-P were found to be significantly directly associated with use of anxiolytics/sedatives postpartum (5.1- and 6.8-fold risk magnitude, respectively). In study III, about 5% of the sample reported having a psychiatric disorder during pregnancy, mainly depression and/or anxiety, and within this group about 50% presented symptoms of depression. Of the women with a psychiatric disorder, 62% were medicated with psychotropics during pregnancy. About one out of two women medicated with psychotropics demonstrated low adherence during pregnancy. Risk factors for low medication adherence were smoking in pregnancy, ongoing symptoms of depression, elevated antidepressant risk perception, and women's individual beliefs about their prescribed psychotropics. \n \nStudy IV showed that exposure to antidepressants during the first or second trimester is not associated with an increased likelihood of vaginal bleeding in early or midpregnancy, respectively. Contrarily, women with depressive symptoms but not exposed to antidepressants during pregnancy had a moderate significant increased likelihood to experience these outcomes. Exposure to SSRIs/SNRIs between gestational week 30 and childbirth did not confer any increased odds for postpartum hemorrhage, compared to non-exposure; however, exposure to TCAs/OADs during this time window conferred a significant 3.8-fold increased odds of postpartum hemorrhage overall, but low statistical power impeded the analysis by mode of delivery. \n \nThe findings of this work highlight the need to increase awareness among healthcare providers that a large proportion of pregnant women will be in need of tailored evidence-based information about the fetal and maternal risks of medication exposures during pregnancy, but also about the risk of untreated psychiatric illness during pregnancy and postpartum.

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