HEALTHx2: patient-centered approaches for studying the effectiveness and reproductive safety of antidepressant medication in perinatal women (completed)

• Wijk, Emma van; Zugic, Milica; Rostami, Sina; Gelder, Marleen van; Ahmad, Ashi Sarfraz & Sitras, Vasilis [Show all 9 contributors for this article] (2025). Gestational weight gain and postpartum weight retention: What is the role of perinatal antidepressant use? Journal of Affective Disorders. ISSN 0165-0327. 394(A). doi: 10.1016/j.jad.2025.120521. Full text in Research Archive Show summary

  Background: Little is known about the association between perinatal antidepressant use and gestational weight gain (GWG) and postpartum weight retention (PPWR). Methods: We used data from the Norwegian Mother, Father and Child Cohort Study (MoBa), linked to the Medical Birth Registry of Norway (MBRN) and the Norwegian Prescribed Drug Registry (LMR). We included singleton, live birth pregnancies with pre-pregnancy depression/anxiety. Prenatal and perinatal antidepressant use trajectories were constructed using longitudinal k-means clustering. GWG and PPWR at 6/18 months postpartum were calculated using self-reported data. We estimated weighted relative risks (wRR) and 95 % confidence intervals (CI) using modified Poisson regression with robust variance estimators and overlap weights. For a sub- population with available genetics data, we used polygenic risk scores (PRSs) to partially account for confounding by genetic component. Results: Among 3365 pregnancies included, we observed six prenatal and perinatal antidepressant use trajectories: non-users, pre-pregnancy discontinuers, early pregnancy discontinuers, late pregnancy discontinuers, continuers, and post-pregnancy initiators. Pre-pregnancy discontinuers had increased risk of inadequate GWG compared to non-users (wRR 1.34, 95 % CI 1.03–1.73). Early pregnancy discontinuers (wRR 0.89, 95 % CI 0.78–1.02), late pregnancy discontinuers (wRR 0.88, 95 % CI 0.76–1.01), and continuers (wRR 0.86, 95 % CI 0.71–1.05) had a borderline decreased risk of excessive PPWR at 6 months postpartum compared to non-users. We observed no other associations between antidepressant use trajectories and GWG or PPWR. Conclusion: These results enhance knowledge on weight-related safety concerns of antidepressant use in the prenatal and perinatal period, specifically regarding GWG and PPWR.

• Carson, Alexis Christine; Trinh, Nhung; Nordeng, Hedvig Marie Egeland; Liu, Xiaoqin; Munk-Olsen, Trine & Eberhard-Gran, Malin [Show all 8 contributors for this article] (2025). Initiating antidepressant treatment in pregnancy: Timing, intensity, and influential maternal and familial factors. Journal of Affective Disorders. ISSN 0165-0327. 388. doi: 10.1016/j.jad.2025.119726. Full text in Research Archive Show summary

  Objective: To describe the timing and intensity of antidepressant initiation in pregnancy using longitudinal trajectories of antidepressant prescription fills to identify associated sociodemographic, lifestyle, somatic, mental health, pregnancy, and paternal factors. Methods: This population-based cohort within the Norwegian Mother, Father and Child Cohort study linked to MoBa Genetics and the Prescribed Drug Registry included 1879 women with a new episode of self-reported depression/anxiety during pregnancy. Antidepressants were measured by week and average daily dose. Results: There were 87 initiators, from which we identified three prescription fill trajectories: Early-pregnancy initiators with rapid discontinuation (n = 41, 47.1 %), Early-pregnancy initiators with mid-pregnancy discontinuation (n = 30, 34.5 %), and Early-mid pregnancy initiators with continuation (n = 16, 18.4 %) and three dose trajectories: Low dose with discontinuation (n = 45, 51.7 %), High dose with discontinuation (n = 26, 29.9 %), and Medium dose with continuation (n = 16, 18.4 %). Thyroid disorder was associated with Early initiators with rapid discontinuation (adjusted relative risk ratios (aRRR): 4.15, 95 % CI: 1.56–11.03) compared to Unmedicated. Other psychotropics pre-pregnancy increased the likelihood of being Early initiators with mid-pregnancy discontinuation and High dose discontinuers compared to Unmedicated. Higher maternal genetic liability for depression was strongly associated with Early initiators with mid-pregnancy discontinuation (aRRR = 8.57, 95 % CI: 3.09–23.74), High dose discontinuers and Medium dose continuers across comparisons. Adverse reproductive history, immigration and alcohol pre-pregnancy emerged as important factors. Conclusions: Approximately 5 out of 100 women with a new episode of depression/anxiety initiated an antidepressant during pregnancy, predominantly in early pregnancy, with most discontinuing early to mid-pregnancy. Identified factors can be utilized by clinicians to provide personalized treatment guidance.

• Zugic, Milica; Trinh, Nhung; Rostami, Sina; Nordeng, Hedvig Marie Egeland; Ystrøm, Eivind & Bulik, Cynthia M [Show all 10 contributors for this article] (2025). Antenatal depressive and anxiety symptoms in women with eating disorders who continue or discontinue antidepressant treatment in pregnancy. Journal of Affective Disorders Reports. 22, p. 1–10. doi: 10.1016/j.jadr.2025.100985. Full text in Research Archive Show summary

  Background Limited evidence on antidepressant effectiveness in pregnant women with eating disorders (ED) challenges pharmacotherapy management. We examined antenatal depressive and anxiety symptoms with continued antidepressant use in women with ED. Methods We used data from the Norwegian Mother, Father and Child Cohort Study (MoBa) linked to the Medical Birth Registry of Norway and MoBa Genetics. MoBa questionnaires at weeks 17 (early) and 30 (mid-late pregnancy) measured antidepressant exposure and symptoms of depression and anxiety using the 5-item Hopkins Symptom Checklist. We fitted generalised linear models and adjusted for confounding. In a subsample, we stratified analyses by polygenic-score tertiles for antidepressant response. Results We identified 5920 pregnancies in women with ED, mainly binge-eating disorder (BED) (84.0 %) and bulimia nervosa (BN) (12.4 %). Of these, 48 (0.8 %) continued antidepressants into early pregnancy, 93 (1.6 %) discontinued during, and 85 (1.4 %) discontinued before pregnancy. At early pregnancy only, continued antidepressant was associated with lower severity of depressive and anxiety symptoms relative to discontinuation. Among women with BED, this was specific to lower anxiety symptoms (β:-0.43, 95 %CI:-0.84, -0.02). This association was not observed in women with BN. In women with higher antidepressant-response polygenic-score continued antidepressant was associated with lower symptom severity relative to discontinued (range of β:-0.86 to -1.35). Conclusions Continuing antidepressants in early but not mid-late pregnancy is associated with lower severity of depressive and anxiety symptoms in women with BED. The association observed in women with higher antidepressant-response polygenic-score calls for larger studies on personalized treatment in perinatal ED.

• Fonseca, Ana; Branquinho, Mariana; Monteiro, Fabiana; Araújo-Pedrosa, Anabela; Bjørndal, Ludvig Daae & Lupattelli, Angela (2023). Treatment options and their uptake among women with symptoms of perinatal depression: exploratory study in Norway and Portugal. BJPsych Open. 9(3), p. 1–9. doi: 10.1192/bjo.2023.56. Full text in Research Archive Show summary

  Background Perinatal depression is the most undertreated clinical condition during the perinatal period. Knowledge about women's decision-making in seeking and receiving treatment is scarce. Aims To investigate and compare treatment option uptake in perinatal women with depressive symptoms in Portugal and Norway, and to identify sociodemographic and health-related factors associated with treatment uptake. Method Participants were women resident in Portugal or Norway (≥18 years) who were pregnant or had given birth in the past 12 months, who presented with active depressive symptoms (Edinburgh Postnatal Depression Scale score ≥10). In an electronic questionnaire, women reported treatment received and sociodemographic and health-related factors. Results The sample included 416 women from Portugal and 169 from Norway, of which 79.8% and 53.9%, respectively, were not receiving any treatment. Most Portuguese women were receiving psychological treatment, either alone (45.2%) or combined with pharmacological treatment (21.4%). Most Norwegian participants were receiving only pharmacological (36.5%) or combined treatment (35.4%). Compared with the Portuguese sample, a higher proportion of Norwegian women started treatment before pregnancy (P < 0.001). In Portugal, lower depressive symptoms and self-reported psychopathology were significantly associated with higher likelihood of receiving treatment. Conclusions We found that, in both Norway and Portugal, a substantial number of perinatal women with depressive symptoms do not receive any treatment. Differences exist regarding the chosen treatment option and timing of treatment initiation in the two countries. Only mental health-related factors were associated with treatment uptake for perinatal depression in Portugal. Our results highlight the importance of implementing strategies aimed to improve help-seeking behaviours.

• Tauqeer, Fatima; Moen, Anne; Myhr, Kirsten; Wilson, Claire A. & Lupattelli, Angela (2023). Assessing decisional conflict and challenges in decision-making among perinatal women using or considering using antidepressants during pregnancy—a mixed-methods study. Archives of Women's Mental Health. ISSN 1434-1816. 26, p. 669–683. doi: 10.1007/s00737-023-01341-0. Full text in Research Archive Show summary

  This study aims to investigate decisional conflict and elucidate challenges in decision-making among perinatal women using or considering using antidepressant (AD) during pregnancy. A sequential, mixed-methods study was employed among pregnant and postnatal women in Norway who had been offered ADs in the last 5 years. Quantitative data were obtained through an electronic questionnaire. Decisional conflict in pregnancy was assessed using the Decisional Conflict Scale (DCS) defined as either low (

• Trinh, Nhung; Munk-Olsen, Trine; Wray, Naomi R.; Bergink, Veerle; Nordeng, Hedvig Marie Egeland & Lupattelli, Angela [Show all 7 contributors for this article] (2023). Timing of Antidepressant Discontinuation During Pregnancy and Postpartum Psychiatric Outcomes in Denmark and Norway. JAMA psychiatry. ISSN 2168-6238. 80(5), p. 441–450. doi: 10.1001/jamapsychiatry.2023.0041. Full text in Research Archive
• Bjørndal, Ludvig Daae; Tauqeer, Fatima; Heiervang, Kristin Sverdvik; Clausen, Hanne Kristin; Heitmann, Kristine & Lupattelli, Angela (2022). Perceived risk of neurodevelopmental outcomes in offspring related to psychotropic and mental illness exposures in pregnancy and breastfeeding: a cross-sectional survey of women with past or current mental illness. BMJ Open. 12(9), p. 1–11. doi: 10.1136/bmjopen-2022-061159. Full text in Research Archive Show summary

  Objectives: To investigate the perceived risk of psychotropic and mental illness exposures (1) during pregnancy or (2) while breastfeeding on offspring neurodevelopment, and factors associated with this perception in women with past/current mental illness. Design: Cross-sectional, web-based study. Setting: Nationwide in Norway, June 2020-June 2021. Participants: Women aged 18-55 years who were pregnant, recent mothers or planning a pregnancy, and had been offered antidepressants in the last 5 years. Primary and secondary outcome measures: Perceived risk of prenatal and breastmilk exposure to psychotropic medications and maternal mental illness on offspring neurodevelopmental outcomes. Results: We included 448 women: 234 pregnant, 146 mothers and 68 planning a pregnancy. On a 0-10 scale, women perceived antidepressants as least harmful both (1) in pregnancy (mean score 4.2, 95% CI 3.6 to 4.8) and (2) while breastfeeding (mean score 3.8, 95% CI 3.3 to 4.4), relative to antipsychotics, anxiety/sleeping medication or antiepileptics (mean score range: 6.3-6.5 during pregnancy, 5.5-6.2 while breastfeeding). Many participants were unfamiliar with psychotropics other than antidepressants. The perceived risk of mental illness exposure exceeded that of antidepressants (mean score range 5.6-5.9) in both exposure periods. Using general linear models, factors associated with greater antidepressant risk perception in both exposure periods included having lower education, non-Norwegian native language, and employment status (range mean score difference (β): 2.07-6.07). For pregnant women and mothers, there was an inverse association between perceived risk and the perceived antidepressant effectiveness in both exposure periods (range of β: -0.18 to -0.25). Conclusions: In women with past/current mental illness, the perceived risk of antidepressant exposure on child neurodevelopment was lower than that for maternal mental illness. Other psychotropic medications were perceived as more harmful. As medication risk perception influences the decision-making regarding treatment of mental illness, pre- and pregnancy counselling should target women with characteristics associated with higher perceived risk. Keywords: EPIDEMIOLOGY; MENTAL HEALTH; OBSTETRICS; PSYCHIATRY; THERAPEUTICS. © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

• Trinh, Nhung; Nordeng, Hedvig Marie Egeland; Bandoli, Gretchen; Eberhard-Gran, Malin Marie Cecilia & Lupattelli, Angela (2022). Antidepressant and mental health care utilization in pregnant women with depression and/or anxiety: An interrupted time-series analysis. Journal of Affective Disorders. ISSN 0165-0327. 308, p. 458–465. doi: 10.1016/j.jad.2022.04.101. Full text in Research Archive Show summary

  Background Little is known about mental health care utilization patterns in pregnant women with depression/anxiety in Norway according to antidepressant fill trajectories in pregnancy. Method We conducted a registry-linkage cohort study of pregnancies within women having outpatient visit for depression/anxiety and antidepressant fills prior to pregnancy identified from four national registries of Norway (2009–2018). Number of consultations for depression/anxiety per 100 pregnancies as proxy of mental health care utilization was modelled using interrupted time-series analysis with first month into pregnancy and first month after delivery as interruption points. We investigated the time window spanning from six months prior to one year postpartum. Antidepressant fill trajectories in the corresponding time window were identified using longitudinal k-means trajectory modelling. Results The cohort included 8460 pregnancies within 8062 women with depression/anxiety. We observed reduced mental health care utilization when pregnant women entered the course of pregnancy (negative slopes during pregnancy for psychiatric specialists and psychologists). The declines were observed for all antidepressant fill trajectories (i.e., discontinuers and continuers) except interrupters (i.e., discontinued then resumed treatment). We found increased mental health care utilization in the postpartum year, notably in interrupters (positive slopes in consultation rates with specialists of outpatient clinics and public-contracted psychiatrists). Limitations It was not possible to measure directly the use of psychosocial interventions and psychotherapy. Conclusions Pregnancy was associated with reduced mental health care utilization regardless of whether antidepressant treatment was maintained during pregnancy or not. Increases in mental health care utilization were observed in the postpartum year, especially in interrupters.

• Trinh, Nhung; Nordeng, Hedvig Marie Egeland; Bandoli, Gretchen; Palmsten, Kristin; Eberhard-Gran, Malin & Lupattelli, Angela (2022). Antidepressant Fill and Dose Trajectories in Pregnant Women with Depression and/or Anxiety: A Norwegian Registry Linkage Study. Clinical Epidemiology. 14, p. 1439–1451. doi: 10.2147/CLEP.S379370. Full text in Research Archive Show summary

  Background: Few studies investigated longitudinal antidepressant exposure during pregnancy and included dosage in the assessment. Methods: We conducted a nationwide, registry-linkage study in Norway using data on antidepressant prescription fills in pregnancies lasting ≥ 32 weeks in women with a delivery between 2009 and 2018 who had a depression/anxiety diagnosis and antidepressant fills prior to pregnancy. Information on antidepressant exposure by week (measured by filled prescriptions) and prescribed average daily dose was used in longitudinal k-means trajectory modelling for a 108-week time window from six months prior to pregnancy to one year after delivery. Factors associated with trajectory group membership were examined using multinomial logistic regression models. Results: We included 8,460 pregnancies in 8,092 women. Four antidepressant fill trajectories were identified based on filled antidepressant prescriptions: two distinct discontinuing patterns, one at around the start of pregnancy (30.4%) and one around the end of pregnancy (33.8%); one continuing pattern (20.6%); and one interrupting pattern (15.2%). Using average usual daily dose, we identified low dose discontinuing (60.3%), medium dose reducing (20.6%) and high dose continuing (15.2%) patterns. The multinomial logistic regressions showed that the fill trajectory group membership was strongly associated with: antidepressant type and dose prior to pregnancy and co-medication prior to pregnancy, maternal age, marital status, parity, previous pregnancy loss, and pregnancy planning. Conclusion: Longitudinal trajectory modelling revealed distinct antidepressant fill and dosage patterns in the period around pregnancy. Knowledge about factors associated with utilization trajectories might be useful for health-care personnel counselling women about antidepressant use in pregnancy.

• Trinh, Nhung; Semark, Birgitte Dige; Munk-Olsen, Trine; Liu, Xiaoqin; Rø, Øyvind & Bulik, Cynthia M. [Show all 9 contributors for this article] (2022). Psychiatric visits during the postpartum year in women with eating disorders who continue or discontinue antidepressant treatment in pregnancy. International Journal of Eating Disorders. ISSN 0276-3478. 56(3), p. 582–594. doi: 10.1002/eat.23877. Full text in Research Archive Show summary

  Objective To determine the association between continued antidepressant use in pregnancy and postpartum psychiatric visits for eating (ED) or mood/anxiety disorders in women with preexisting ED. Method Using Danish health registry data (1998–2015), we identified 3529 pregnancies in women with ED prepregnancy: (i) 564 with continued antidepressant use before and during pregnancy; (ii) 778 with discontinued antidepressants before pregnancy; (iii) 2137 unexposed. Outpatient and inpatient postpartum visits for an ED or a mood/anxiety disorder constituted the outcome measures. We estimated hazard ratios (HRs) and 95% confidence intervals (CI) using Cox regression with inverse probability of treatment weighting, and performed stratified analyses by antidepressant prescription filling in the first 3 months postpartum. Results The weighted cumulative incidence for an ED visit at end of follow-up was 4.5% (continued) and 4.8% (discontinued). We found no association between continued antidepressant and postpartum ED visit, relative to discontinued (HR: 0.89, 95% CI: 0.52–1.52). The HR for postpartum mood/anxiety disorder visit was 1.27 (95% CI: 0.68–2.36) with continued antidepressants versus discontinued but decreased if more than two antidepressant prescriptions were refilled. Continued antidepressant use was associated with a 57% reduced likelihood of a postpartum ED visit versus discontinued use in pregnancies with antidepressant prescription refills in the early postpartum. Conclusion Among women with preexisting ED, there was no association between continued antidepressant use during pregnancy and the likelihood of postpartum psychiatric visits, relative to discontinued antidepressants before pregnancy. Continuation of treatment into the early postpartum is associated with reduced likelihood of postpartum ED visit. Public Significance Based on data from the Danish registries, we identified 3529 pregnancies among women with preexisting eating disorders before pregnancy. Women with continued antidepressant treatment both before and during pregnancy did not have a lower probability of having postpartum psychiatric visits for an eating disorder or for mood/anxiety disorders (often coexisting with eating disorders), relative to those who discontinued antidepressants before pregnancy. Further continuation of antidepressant treatment into the early postpartum is associated with improved maternal postpartum outcomes. However, residual confounding by disease severity limits confidence in this conclusion.

• Trønnes, Johanne Naper; Lupattelli, Angela; Ystrøm, Eivind & Nordeng, Hedvig Marie Egeland (2022). Analysis of Prenatal Exposure to Opioid Analgesics and Scholastic Skills in Children in Fifth Grade in Norway. JAMA Network Open. 5(7). doi: 10.1001/jamanetworkopen.2022.22425. Full text in Research Archive Show summary

  Importance Few studies have examined the neurodevelopmental consequences of prenatal exposure to opioid analgesics. Therefore, it is necessary to gain knowledge to inform clinical decisions for pregnant women with moderate to severe pain. Objective To investigate fifth-grade scholastic skills in children with prenatal exposure to opioid analgesics. Design, Setting, and Participants A cohort study was conducted based on data from the Norwegian Mother, Father, and Child Cohort (1999-2008). These data were linked to the Medical Birth Registry of Norway, and data from Statistics Norway included 64 256 live-born singletons, born to 54 568 mothers who reported pain during pregnancy, were analyzed. The study was conducted from July 1 to December 15, 2021. Exposures Self-reported exposure to opioid analgesics during pregnancy, characterized in terms of any exposure, the exposure timing, and the exposure duration. Main Outcomes and Measures Scores from 3 national tests for children in fifth grade. The tests measured scholastic skills in literacy, numeracy, and the English language. Test scores were standardized to z scores. Differences in z scores were compared between children of mothers exposed to opioid analgesics during pregnancy and children of mothers with only prepregnancy opioid exposure. Results Of the 64 256 children included, 32 521 were boys (50.6%), and 1483 children (2.3%) were exposed to an opioid analgesic at least once during gestation. All test scores were similar between children with any exposure to opioid analgesics in utero and children with only prepregnancy exposure. Children exposed in the first trimester and those exposed in two or three 4-week intervals during pregnancy scored lower than children of mothers with only prepregnancy exposures on tests in literacy (weighted β [wβ], −0.13; 95% CI, −0.25 to −0.01 and wβ, −0.19; 95% CI, −0.35 to −0.04) and numeracy (wβ, −0.14; 95% CI, −0.25 to −0.04 and wβ, −0.19; 95% CI, −0.34 to −0.05). These differences were small and may not be clinically relevant. Conclusions and Relevance In this large birth cohort, prenatal exposure to opioid analgesics had no substantial negative association with fifth-grade scholastic skills. However, adequate pain management in pregnancy may be addressed on an individual patient level, bearing in mind the benefits and risks of different analgesic therapies.

• Liu, Xiaoqin; Molenaar, Nina; Agerbo, Esben; Momen, Natalie C.; Rommel, Anna-Sophie & Lupattelli, Angela [Show all 8 contributors for this article] (2022). Antidepressant discontinuation before or during pregnancy and risk of psychiatric emergency in Denmark: A population-based propensity score-matched cohort study. PLoS Medicine. ISSN 1549-1277. 19(1). doi: 10.1371/journal.pmed.1003895. Full text in Research Archive Show summary

  Background Women prescribed antidepressants face the dilemma of whether or not to continue their treatment during pregnancy. Currently, limited evidence is available on the efficacy of continuing versus discontinuing antidepressant treatment during pregnancy to aid their decision. We aimed to estimate whether antidepressant discontinuation before or during pregnancy was associated with an increased risk of psychiatric emergency (ascertained by psychiatric admission or emergency room visit), a proxy measure of severe exacerbation of symptoms/mental health crisis. Methods and findings We carried out a propensity score–matched cohort study of women who gave birth to live-born singletons between January 1, 1997 and June 30, 2016 in Denmark and who redeemed an antidepressant prescription in the 90 days before the pregnancy, identified by Anatomical Therapeutic Chemical (ATC) code N06A. We constructed 2 matched cohorts, matching each woman who discontinued antidepressants before pregnancy (N = 2,669) or during pregnancy (N = 5,467) to one who continued antidepressants based on propensity scores. Maternal characteristics and variables related to disease severity were used to generate the propensity scores in logistic regression models. We estimated hazard ratios (HRs) of psychiatric emergency in the perinatal period (pregnancy and 6 months postpartum) using stratified Cox regression. Psychiatric emergencies were observed in 76 women who discontinued antidepressants before pregnancy and 91 women who continued. There was no evidence of higher risk of psychiatric emergency among women who discontinued antidepressants before pregnancy (cumulative incidence: 2.9%, 95% confidence interval [CI]: 2.3% to 3.6% for discontinuation versus 3.4%, 95% CI: 2.8% to 4.2% for continuation; HR = 0.84, 95% CI: 0.61 to 1.16, p = 0.298). Overall, 202 women who discontinued antidepressants during pregnancy and 156 who continued had psychiatric emergencies (cumulative incidence: 5.0%, 95% CI: 4.2% to 5.9% versus 3.7%, 95% CI: 3.1% to 4.5%). Antidepressant discontinuation during pregnancy was associated with increased risk of psychiatric emergency (HR = 1.25, 95% CI: 1.00 to 1.55, p = 0.048). Study limitations include lack of information on indications for antidepressant treatment and reasons for discontinuing antidepressants. Conclusions In this study, we found that discontinuing antidepressant medication during pregnancy (but not before) is associated with an apparent increased risk of psychiatric emergency compared to continuing treatment throughout pregnancy.

• Tauqeer, Fatima; Wood, Mollie; Andersen, Sarah Hjorth; Lupattelli, Angela & Nordeng, Hedvig (2021). Perinatal use of triptans and other drugs for migraine - A nationwide drug utilization study. PLOS ONE. 16(8). doi: 10.1371/journal.pone.0256214. Full text in Research Archive Show summary

  Objective To characterize nationwide utilization patterns of migraine pharmacotherapy before, during, and after pregnancy in women with triptan use. Methods Population-based data were obtained by linking the Medical Birth Registry of Norway and the Norwegian Prescription Database from 2006 to 2017. We included 22,940 pregnancies among 19,669 women with at least one filled triptan prescription, a proxy for migraine, in the year before pregnancy or during pregnancy. The population was classified into four groups: i) continuers; ii) discontinuers; iii) initiators, and vi) post-partum re-initiators. Participant characteristics and prescription fills for other drugs such as analgesics, antinauseants, and preventive drugs among the groups were examined, along with an array of triptan utilization parameters. Results In total, 20.0% of the women were classified as triptan continuers, 54.1% as discontinuers, 8.0% as initiators, and 17.6% as re-initiators. Extended use of triptans (�15 daily drug doses/month) occurred among 6.9% of the continuers in the first trimester. The top 10% of triptan continuers and initiators accounted for 41% (95% CI: 39.2% - 42.5%) and 33% (95% CI: 30.3% - 35.8%) of the triptan volume, respectively. Triptan continuers and initiators had similar patterns of acute co-medication during pregnancy, but use of preventive drugs was more common among the continuers before, during, and after pregnancy. Conclusion Among women using triptans before and during pregnancy, one in four continued triptan treatment during pregnancy, and extended triptan use was relatively low. Triptan discontinuation during and in the year after pregnancy was common. Use of other acute migraine treatments was higher among both continuers and initiators of triptans. Women using preventive migraine treatment were most commonly triptan continuers and re-initiators after pregnancy. Prescribing to and counseling of women with migraine should be tailored to the condition severity and their information needs to promote optimal migraine management in pregnancy. Introduction

• Gustavson, Kristin; Ystrøm, Eivind; Ask, Helga; Torvik, Fartein Ask; Hornig, Mady & Susser, Ezra [Show all 16 contributors for this article] (2021). Acetaminophen use during pregnancy and offspring attention deficit hyperactivity disorder - a longitudinal sibling control study. JCPP Advances. 1(2). doi: 10.1002/jcv2.12020. Full text in Research Archive Show summary

  Background: Maternal acetaminophen use during pregnancy is associated with increased risk of ADHD in the child. This could reflect causal influence of acetaminophen on fetal neurodevelopment or could be due to confounding factors. The aim of the current study was to examine unmeasured familial confounding factors of this association. Methods: We used data from 26,613 children from 12,902 families participating in the prospective Norwegian Mother, Father, and Child Cohort Study (MoBa). The MoBa was linked to the Norwegian Medical Birth Register and the Norwegian Patient Registry. Siblings discordant for prenatal acetaminophen exposure were compared regarding risk of having an ADHD diagnosis. Results: Children exposed to acetaminophen up to 28 days during pregnancy did not have increased risk of receiving an ADHD diagnosis compared to unexposed children. The adjusted Hazard ratio (aHR) was 0.87 (95% C.I. = 0.70-1.08) for exposure 1 to 7 days, and 1.13 (95% C.I. = 0.82–1.49) for 8–28 days. Long-term exposure (29 days or more) was associated with a two-fold increase in risk of ADHD diagnosis (aHR = 2.02, 95% C.I = 1.17–3.25). In the sibling control model, the association between long-term acetaminophen use and ADHD in the child was aHR = 2.77 (95% C.I. = 1.48–5.05) at the between-family level, and aHR = 1.06 (95% C.I. = 0.51–2.05) at the within-family level. Conclusions: Both the exposed and the unexposed children of mothers with long-term use of acetaminophen in one of the pregnancies had increased risk of receiving an ADHD diagnosis. This indicates that the observed association between long-term acetaminophen use during pregnancy and ADHD in the child may at least partly be confounded by unobserved family factors.

• Wood, Mollie; Lupattelli, Angela; Palmsten, Kristin; Bandoli, Gretchen; Hurault-Delarue, Caroline & Damase-Michel, Christine [Show all 9 contributors for this article] (2021). Longitudinal Methods for Modeling Exposures in Pharmacoepidemiologic Studies in Pregnancy. Epidemiologic Reviews. ISSN 0193-936X. 43(1), p. 130–146. doi: 10.1093/epirev/mxab002. Full text in Research Archive Show summary

  In many perinatal pharmacoepidemiologic studies, exposure to a medication is classified as “ever exposed” versus “never exposed” within each trimester or even over the entire pregnancy. This approach is often far from real-world exposure patterns, may lead to exposure misclassification, and does not to incorporate important aspects such as dosage, timing of exposure, and treatment duration. Alternative exposure modeling methods can better summarize complex, individual-level medication use trajectories or time-varying exposures from information on medication dosage, gestational timing of use, and frequency of use. We provide an overview of commonly used methods for more refined definitions of real-world exposure to medication use during pregnancy, focusing on the major strengths and limitations of the techniques, including the potential for method-specific biases. Unsupervised clustering methods, including k-means clustering, group-based trajectory models, and hierarchical cluster analysis, are of interest because they enable visual examination of medication use trajectories over time in pregnancy and complex individual-level exposures, as well as providing insight into comedication and drug-switching patterns. Analytical techniques for time-varying exposure methods, such as extended Cox models and Robins’ generalized methods, are useful tools when medication exposure is not static during pregnancy. We propose that where appropriate, combining unsupervised clustering techniques with causal modeling approaches may be a powerful approach to understanding medication safety in pregnancy, and this framework can also be applied in other areas of epidemiology.

• Ilic, Miljana; Nordeng, Hedvig Marie Egeland & Lupattelli, Angela (2021). Medical care contact for infertility and related medication use during pregnancy – a European, cross-sectional web-based study. Norsk Epidemiologi. ISSN 0803-2491. 29(1-2), p. 97–106. doi: 10.5324/nje.v29i1-2.4051. Full text in Research Archive Show summary

  Aims: The aim of the study was two-fold: i) to determine the prevalence of medical care contact for infertility in European countries; ii) to map overall and long-term/chronic medication use during pregnancy in women who sought medical care due to infertility. Methods: This is a sub-study of the Multinational Medication Use in Pregnancy Study, a cross-sectional, web-based study conducted from October 2011 to February 2012. We included 8097 participants from Europe who were pregnant or new mothers. We collected data on overall and long-term/chronic medication use, medical care seeking due to infertility, and whether women eventually conceived spontaneously or with the aid of infertility treatment. Results: Medical care contact for infertility was lower in Western Europe (prevalence estimate: 10.0-15.3%), compared with Northern (15.2-17.5%) or Eastern (17.4-20.9%), but Poland had the lowest estimate (8.0%). Overall, 660 (8.2%) women sought medical care due to infertility but conceived spontaneously; 548 (6.8%) conceived aided by fertility treatment, and 6889 (85.0%) women did not seek help. Use of any medication was comparable across the three groups (range 80.4-82.5%), but women seeking help for infertility (21.8-24.6%) took more often long-term/chronic medications than women who did not (14.8%). Conclusion: Medical care contacts for infertility varies greatly across European countries. Women who had medical contact due to infertility used more often chronic medications in pregnancy than women who did not, pointing to more co-morbidities and risk pregnancies.

• Lupattelli, Angela & Nordeng, Hedvig Marie Egeland (2021). Does antidepressant use in pregnancy increase the risk of ADHD in children? BestPractice nordic. Full text in Research Archive
• Vallee, Jennifer; Wong, Yih; Mannino, Eline; Nordeng, Hedvig Marie Egeland & Lupattelli, Angela (2020). Association between Antidepressant Treatment during Pregnancy and Postpartum Self-Harm Ideation in Women with Psychiatric Disorders: A Cross-Sectional, Multinational Study. International Journal of Environmental Research and Public Health (IJERPH). ISSN 1661-7827. 18(1), p. 1–15. doi: 10.3390/ijerph18010046. Full text in Research Archive Show summary

  This study sought to estimate whether there is a preventative association between antidepressants during pregnancy and postpartum self-harm ideation (SHI), as this knowledge is to date unknown. Using the Multinational Medication Use in Pregnancy Study, we included a sample of mothers who were in the five weeks to one year postpartum period at the time of questionnaire completion, and reported preexisting or new onset depression and/or anxiety during pregnancy (n = 187). Frequency of postpartum SHI (‘often/sometimes’ = frequent, ‘hardly ever’ = sporadic, ‘never’) was measured via the Edinburgh Postnatal Depression Scale (EPDS) item 10, which reads “The thought of harming myself has occurred to me”. Mothers reported their antidepressant use in pregnancy retrospectively. Overall, 52.9% of women took an antidepressant during pregnancy. Frequent SHI postpartum was reported by 15.2% of non-medicated women and 22.0% of women on past antidepressant treatment in pregnancy; this proportion was higher following a single trimester treatment compared to three trimesters (36.3% versus 18.0%). There was no preventative association of antidepressant treatment in pregnancy on reporting frequent SHI postpartum (weighted RR: 1.90, 95% CI: 0.79, 4.56), relative to never/hardly ever SHI. In a population of women with antenatal depression/anxiety, there was no preventative association between past antidepressant treatment in pregnancy and reporting frequent SHI in the postpartum year. This analysis is only a first step in providing evidence to inform psychiatric disorder treatment decisions for pregnant women.

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• Lupattelli, Angela (2022). Prenatal Exposure to Antidepressants and Risk of Overweight and Obesity in Offspring at Age 8 Years. Full text in Research Archive
• Lupattelli, Angela (2022). Decisional conflict about antidepressant treatment in pregnant women with a mental illness in Norway. Full text in Research Archive
• Lupattelli, Angela (2022). Long-term safety of antidepressants in pregnancy on metabolic health outcomes in offspring. Full text in Research Archive
• Lupattelli, Angela (2022). Antidepressant Continuation and Adherence in Pregnancy and Risk of Antenatal Hospital Admission for Depression and/or Anxiety. Full text in Research Archive
• Lupattelli, Angela (2022). Association of Prenatal Antidepressant Exposure with Trajectories and Acceleration of Body Mass Index in Children from 6 Weeks to 8 Years of Age. Full text in Research Archive

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