Identification and characterization of migraine in pregnancy: A Norwegian registry-based cohort study.

BACKGROUND: Migraine is common in women of reproductive age. Migraine's episodic manifestation and acute and preventive pharmacological treatment options challenge studying drug safety for this condition during pregnancy. To improve such studies, we aimed to develop algorithms to identify and characterize migraines in electronic healthcare registries and to assess the level of care. METHODS: We linked four registries to detect pregnancies from 2009-2018 and used three algorithms for migraine identification: i) diagnostic codes, ii) triptans dispensed, and iii) a combination of both. We assessed migraine severity using dispensed drugs as proxies. ICD-10 diagnostic subcodes of migraine (G43) allowed the allocation of four subtypes: complicated and/or status migrainosus; with aura; without aura; other/unspecified. RESULTS: We included 535,089 pregnancies in 367,908 women with available one-year lookback. The prevalence of migraines identified was 2.9%-4.3% before, and 0.8%-1.5% during pregnancy, depending on algorithm used. Pregnant women with migraine were mostly managed in primary care. CONCLUSIONS: Primary care data in combination with drug dispensation records were instrumental for identification of migraine in electronic healthcare registries. Data from secondary care and drug dispensations allow better characterization of migraines. Jointly, these algorithms may contribute to improved perinatal pharmacoepidemiological studies in this population by addressing confounding by maternal migraine indication.

Impact of the early COVID-19 pandemic on adult mental health-related dispensed medications, hospitalizations and specialist outpatient visits in Norway and Sweden: Interrupted time series analysis.

AIMS: Norway and Sweden had different early pandemic responses that may have impacted mental health management. The aim was to assess the impact of the early COVID-19 pandemic on mental health-related care. METHODS: We used national registries in Norway and Sweden (1 January 2018-31 December 2020) to define 2 cohorts: (i) general adult population; and (ii) mental health adult population. Interrupted times series regression analyses evaluated step and slope changes compared to prepandemic levels for monthly rates of medications (antidepressants, antipsychotics, anxiolytics, hypnotics/sedatives, lithium, opioid analgesics, psychostimulants), hospitalizations (for anxiety, bipolar, depressive/mood, eating and schizophrenia/delusional disorders) and specialist outpatient visits. RESULTS: In Norway, immediate reductions occurred in the general population for medications (-12% antidepressants to -7% hypnotics/sedatives) except for antipsychotics; and hospitalizations (-33% anxiety disorders to -17% bipolar disorders). Increasing slope change occurred for all medications except psychostimulants (+1.1%/month hypnotics/sedatives to +1.7%/month antidepressants); and hospitalization for anxiety disorders (+5.5%/month), depressive/mood disorders (+1.7%/month) and schizophrenia/delusional disorders (+2%/month). In Sweden, immediate reductions occurred for antidepressants (-7%) and opioids (-10%) and depressive/mood disorder hospitalizations (-11%) only with increasing slope change in psychostimulant prescribing of (0.9%/month). In contrast to Norway, increasing slope changes occurred in specialist outpatient visits for depressive/mood disorders, eating disorders and schizophrenia/delusional disorders (+1.5, +1.9 and +2.3%/month, respectively). Similar changes occurred in the pre-existing mental health cohorts. CONCLUSION: Differences in early COVID-19 policy response may have contributed to differences in adult mental healthcare provision in Norway and Sweden.

Drug utilisation in children and adolescents before and after the start of the COVID-19 pandemic: Interrupted time-series analyses in three European countries.

BACKGROUND: The COVID-19 pandemic has affected children and adolescents in several ways, including worsened mental health, improvement of asthma, and increases in diabetes ketoacidosis. Less is known about how medication use in children and adolescents has been affected by the pandemic. OBJECTIVES: To explore how the COVID-19 pandemic affected drug utilisation in children and adolescents in Norway, Sweden, and Italy, by child age. METHODS: We conducted a longitudinal drug utilisation study among all children and adolescents (<18 years old) in Norway and Sweden and a nationwide paediatric database covering 3% of the paediatric population in Italy. We conducted an interrupted time-series analysis from January 2018 to December 2021, with March 2020 as the interruption point. Dispensing or prescription rates of antidepressants, anxiolytics, sleep medications, attention-deficit/hyperactivity disorder (ADHD) medications, insulin, and asthma medications were examined. RESULTS: The study population in January 2018 consisted of 3,455,521 children and adolescents (136,188 from Italy, 1,160,431 from Norway, and 2,158,902 from Sweden). For sleep medications and insulin, there were only minor changes in level or trend in some age groups after March 2020. For asthma medications, the pandemic was associated with an immediate decrease in dispensing in Norway and Sweden (range of change in level: -19.2 to -3.7 dispensings per 1000 person-months), and an increasing trend in all countries afterward (range of change in trend: 0.3-6.4 dispensings per 1000 person-months), especially for the youngest age groups. Among adolescents, the pandemic was associated with an increased trend for ADHD medications, antidepressants, and anxiolytics in Norway and Sweden, but not in Italy. CONCLUSIONS: The increasing trend of psychotropic medication dispensing, especially among adolescents after the start of the pandemic, is concerning and should be investigated further. Aside from a temporary effect on asthma medication dispensing, the pandemic did not greatly affect the dispensing of the medications investigated.

COVID-19 and pregnancy: A European study on pre- and post-infection medication use.

PURPOSE: The COVID-19 pandemic has impacted medication needs and prescribing practices, including those affecting pregnant women. Our goal was to investigate patterns of medication use among pregnant women with COVID-19, focusing on variations by trimester of infection and location. METHODS: We conducted an observational study using six electronic healthcare databases from six European regions (Aragon/Spain; France; Norway; Tuscany, Italy; Valencia/Spain; and Wales/UK). The prevalence of primary care prescribing or dispensing was compared in the 30-day periods before and after a positive COVID-19 test or diagnosis. RESULTS: The study included 294,126 pregnant women, of whom 8943 (3.0%) tested positive for, or were diagnosed with, COVID-19 during their pregnancy. A significantly higher use of antithrombotic medications was observed particularly after COVID-19 infection in the second and third trimesters. The highest increase was observed in the Valencia region where use of antithrombotic medications in the third trimester increased from 3.8% before COVID-19 to 61.9% after the infection. Increases in other countries were lower; for example, in Norway, the prevalence of antithrombotic medication use changed from around 1-2% before to around 6% after COVID-19 in the third trimester. Smaller and less consistent increases were observed in the use of other drug classes, such as antimicrobials and systemic corticosteroids. CONCLUSION: Our findings highlight the substantial impact of COVID-19 on primary care medication use among pregnant women, with a marked increase in the use of antithrombotic medications post-COVID-19. These results underscore the need for further research to understand the broader implications of these patterns on maternal and neonatal/fetal health outcomes.

Partner support for women's antidepressant treatment and its association with depressive symptoms in pregnant women, mothers, and women planning pregnancy.

PURPOSE: To examine the association between partner support for women's antidepressant treatment and depressive symptoms in pregnant women, those planning pregnancy, and mothers who ever used antidepressants. METHODS: We included 334 women (n=44 planners, n=182 pregnant, n=108 mothers) ever treated with antidepressants within the HEALTHx2 study, a web-based cross-sectional study conducted across Norway in June 2020 to June 2021. The Edinburgh Postnatal Depression Scale and two questions of the Patient Health Questionnaire measured depressive symptoms, by degree of severity and for depressed mood, anxiety, and anhedonia sub-dimensions. Partner support was measured using one item from the Antidepressant Compliance Questionnaire. Association was estimated via unadjusted and adjusted linear and logistic regression models. RESULTS: Being unsupported by the partner was associated with increased odds of reporting moderate-to-very-severe depressive symptoms in mothers (adjusted odds ratio (aOR), 3.57; 95% confidence interval (CI), 1.04-12.19) and pregnant women (aOR, 3.26; 95% CI, 0.95-11.14), relative to being supported. Pregnant women (adjusted mean difference (ß), 0.76; 95% CI, 0.14-1.38) and mothers (ß, 0.93; 95% CI, 0.23-1.64) with no support for their antidepressant treatment presented greater symptoms of anhedonia; for women planning pregnancy, this association emerged in relation to anxiety symptoms (ß among non-users of antidepressant, 2.58; 95% CI, 1.04-4.13). CONCLUSIONS: Partner support for women's antidepressant treatment may play a key role in depressive symptoms severity and the subtypes of anhedonia and anxiety, among women planning pregnancy, pregnant women, and mothers. This highlights the importance of partner inclusion in the complex decision-making process for antidepressant treatment around the time of pregnancy.

Psychiatric visits during the postpartum year in women with eating disorders who continue or discontinue antidepressant treatment in pregnancy.

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.

Assessing decisional conflict and challenges in decision-making among perinatal women using or considering using antidepressants during pregnancy-a mixed-methods study.

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 (< 25) or moderate-high ( ≥ 25) (evaluated retrospectively for postnatal women). Logistic regression was used to identify factors associated with moderate-high decisional conflict. Qualitative data were collected through focus groups with pregnant and postnatal women, and an inductive approach was used for data analysis. Among 174 pregnant and 102 postnatal women, 67.8% and 69.6%, respectively, reported moderate-high decisional conflict during pregnancy. Unsatisfactory doctor-patient relationship was associated with greater likelihood of having moderate-high decisional conflict in pregnancy, both in pregnant (aOR = 1.20, 95% CI: 1.00-1.44) and postnatal women (aOR = 1.40, 95% CI: 1.08-1.82). Reported barriers to decision-making regarding AD use in pregnancy encompassed five DCS subscales: uninformed knowledge following contradictory research and unfamiliarity with authorised resources, unclear values due to emotional blunting and fear associated with AD use, inadequate support, uncertainty in decisions and ineffective decisions due to difficulty in finding personalised treatment, and diverging recommendations by the healthcare providers (HCPs). The quality of the interaction with the HCP plays a crucial role in managing decisional conflict and supporting informed decisions in the management of perinatal mental illness. This study highlights the need for increased provision of clear, evidence-based information by HCPs to facilitate shared decision-making and create personalised treatments for perinatal women considering AD use during pregnancy.

Comparative study showed that children faced a 78% higher risk of new-onset conditions after they had COVID-19.

AIM: Children have largely been unaffected by severe COVID-19 compared to adults, but data suggest that they may have experienced new conditions after developing the disease. We compared outcomes in children who had experienced COVID-19 and healthy controls. METHODS: A retrospective nested cohort study assessed the incidence rate of new-onset conditions after COVID-19 in children aged 0-14 years. Data were retrieved from an Italian paediatric primary care database linked to Veneto Region registries. Exposed children with a positive nasopharyngeal swab were matched 1:1 with unexposed children who had tested negative. Conditional Cox regression was fitted to estimate the adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for the exposure and outcome associations after adjusting for covariates. RESULTS: We compared 1656 exposed and 1656 unexposed children from 1 February 2020 to 30 November 2021. The overall excess risk for new-onset conditions after COVID-19 was 78% higher in the exposed than unexposed children. We found significantly higher risks for some new conditions in exposed children, including mental health issues (aHR 1.8, 95% CI 1.1-3.0) and neurological problems (aHR 2.4, 95% CI 1.4-4.1). CONCLUSION: Exposed children had a 78% higher risk of developing new conditions of interest after COVID-19 than unexposed children.

Antidepressant discontinuation before or during pregnancy and risk of psychiatric emergency in Denmark: A population-based propensity score-matched cohort study.

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.

Longitudinal Methods for Modeling Exposures in Pharmacoepidemiologic Studies in Pregnancy.

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.

Clinical practice guidelines with recommendations for peripartum depression: A European systematic review.

OBJECTIVE: This study aims to systematically review all Clinical Practice Guidelines (CPGs) with recommendations for peripartum depression in European countries. METHODS: A systematic review according to the PRISMA statement was conducted. CPGs focussing on peripartum depression or with at least one specific recommendation for peripartum depression from European countries were selected. Searching was conducted in electronic databases (MEDLINE and PsycINFO), and by contacting professional societies and international experts until November 24th, 2021. Characteristics of the included CPGs and their recommendations were extracted. A methodological quality assessment was conducted using the AGREE-II tool. RESULTS: A total of 239 records were identified after duplicate removal. Of these, 54 were examined for full-text inspection. The final selection yielded 14 CPGs from 11 European countries in 10 languages. Of them, 11 provided recommendations on pharmacological treatments, 10 on psychological treatment (e.g., cognitive-behavioural therapy), 10 on screening, 8 on diagnosis, 6 on other treatments (e.g., physical exercise), 5 on prevention, and 5 other recommendations (e.g., provide information). Regarding the overall methodological quality, only five (35.7%) guidelines were rated as of adequate quality, reaching a score ≥ 70% in the overall assessment of the AGREE-II instrument. Of the six AGREE-II domains, applicability scored the lowest and clarity of presentation scored the highest. CONCLUSION: The absence of CPGs in most European countries, the discrepancy in recommendations and the low methodological quality of the guidelines may lead to disparities and inequalities in peripartum depression management in Europe. The COST Action Riseup-PPD highlights key considerations for future guideline developers.

Association between antidepressant use in pregnancy and gestational diabetes mellitus: Results from the Norwegian Mother, Father and Child Cohort Study.

PURPOSE: This study sought to determine the association between gestational diabetes mellitus (GDM) and antidepressant exposure during early-mid pregnancy, overall and according to antidepressant affinity to the histamine-1 (H1 ) receptor. METHODS: Data originate from the nation-wide, Norwegian Mother, Father and Child Cohort Study conducted in 1999-2008, linked to the national Medical Birth Registry. The study included 6647 pregnancies within women with depressive/anxiety disorders during and/or 6 months prior to pregnancy. Pregnancies exposed in early-mid gestation to antidepressants having low (group 1, n = 814) or high (group 2, n = 77) affinity to the H1 receptor were compared to non-medicated (n = 5756). We fit crude and weighted modified Poisson regression models using inverse probability of treatment weighting (IPTW). RESULTS: Overall, 84 (1.3%) of the pregnancies developed GDM. Relative to non-medicated pregnancies, the risk of GDM was slightly lower in antidepressant group 1 exposed (1.3% vs 1.1%), but more elevated in those exposed to group 2 antidepressants (3.9%). In the weighted analysis, there was no evidence for an association between antidepressant group 1 exposure in early-mid pregnancy and risk of GDM [relative risk (RR): 0.69, 95% confidence interval: 0.31-1.51]. CONCLUSIONS: Gestational use of antidepressants with low H1 receptor affinity, mainly SSRIs and SNRIs, does not pose a substantial risk of GDM in women with depressive/anxiety disorders in pregnancy, compared to no use.

Prenatal exposure to non-steroidal anti-inflammatory drugs and risk of attention-deficit/hyperactivity disorder: A follow-up study in the Norwegian mother, father and child cohort.

PURPOSE: To estimate the association between Attention-Deficit/Hyperactivity Disorder (ADHD) in children in preschool and primary school, and prenatal exposure to non-steroidal anti-inflammatory drugs (NSAIDs) by timing and duration. METHODS: This study was based on the Norwegian Mother, Father and Child Cohort Study linked to the Medical Birth Registry of Norway, the Norwegian Patient Registry (NPR) and the Norwegian Prescription Database (NorPD). NSAID exposure was identified by maternal self-report in pregnancy. Child diagnosis of ADHD was obtained from NPR and NorPD. Symptoms of ADHD at age 5 years were measured using Conners' Parent Rating Scale-Revised, where higher scores correspond to more symptoms. To account for time-varying exposure and confounders, marginal structural models were fitted to estimate hazard ratios and mean difference in z-scores. RESULTS: The analyses on ADHD diagnosis and ADHD symptoms included 56 340 and 34 961 children respectively. Children exposed to NSAIDs prenatally had no increased risk of ADHD diagnosis (first trimester: HR 1.12, 95% CI 0.86;1.45, second trimester: HR 0.98, 95% CI 0.69;1.38, third trimester: HR 0.68, 95% CI 0.31; 1.46) or ADHD symptoms (first trimester: standardized mean difference 0.03, 95% CI -0.03;0.09, second trimester: standardized mean difference 0.03, 95% CI -0.04;0.11, third trimester: standardized mean difference 0.11, 95% CI -0.03; 0.25). There was no duration-response relationship for either outcome. CONCLUSION: Though non-differential misclassification of the exposure may have attenuated results, these findings are reassuring and suggest no substantially increased risk of ADHD diagnosis or symptoms in children prenatally exposed to NSAIDs, regardless of timing or duration.

Thyroid hormone replacement therapy in pregnancy and motor function, communication skills, and behavior of preschool children: The Norwegian Mother, Father, and Child Cohort Study.

PURPOSE: Limited research has focused on the association between prenatal thyroid hormone replacement therapy (THRT) and motor function, communication skills, and behavior in preschool children. Here, we estimated the association between THRT during pregnancy and the first trimester and these developmental outcomes. METHODS: This study was based on the Norwegian Mother, Father, and Child Cohort Study (MoBa) and other national registries. We included mother-child pairs exposed to THRT during pregnancy (n = 663), after delivery (n = 728), or unexposed (n = 28 040). Exposure to THRT was defined according to filled prescriptions. Child outcomes, presented as T-score differences, were parent-reported using the Ages and Stages Questionnaire, Strengths and Difficulties Questionnaire, and Child Behavior Checklist. RESULTS: Of 29 431 mother-child pairs, 2.3% were prenatally exposed to THRT. We found no difference between prenatally exposed and unexposed children in regards to gross motor function (ß: 0.17, 95% CI -1.19, 1.54), fine motor function (ß: -0.17, 95% CI -1.14, 0.80), communication (ß: -0.31, 95% CI -1.58, 0.96), externalizing (ß: -0.03, 95% CI -1.07, 1.01), internalizing (ß: 0.89, 95% CI -0.20, 1.97), or social behaviors (ß: -0.04, 95% CI -0.92, 0.84). Somatic complaints were higher in THRT-exposed children (ß: 0.98, 95% CI 0.08, 1.87), and children whose mothers were exposed after delivery had more sleep problems than unexposed children (ß: 0.99, 95% CI 0.24, 1.74). CONCLUSIONS: Children prenatally exposed to THRT have developmental outcomes as positive as unexposed children on motor function, communication, and behavior. The association with somatic complaints and sleep were not clinically relevant.

Prenatal paracetamol exposure and neurodevelopmental outcomes in preschool-aged children.

BACKGROUND: Recent studies have suggested an association between prenatal paracetamol exposure and adverse neurodevelopmental outcomes in children. However, these findings may be confounded by unmeasured factors related to maternal use of paracetamol and child outcomes. OBJECTIVE: To examine the association between duration and timing of prenatal paracetamol exposure on parent-reported communication skills, behaviour, and temperament in preschool-aged children, with focus on the role of unmeasured confounding. METHODS: We used data from the Norwegian Mother and Child Cohort Study. Linear and generalised linear models with inverse probability weights and robust standard errors were used to quantify the association between prenatal paracetamol exposure and continuous and categorical outcomes. RESULTS: Of the 32 934 children included in our study, 8374 (25.4%), 4961 (15.1%), and 1791 (5.4%) were prenatally exposed to paracetamol in one, two, and three trimesters, respectively. Children exposed to paracetamol in two trimesters scored lower on shyness compared with unexposed children (ß -0.62, 95% confidence interval [CI] -1.05, -0.19). Children exposed to paracetamol in three trimesters had a moderate increased risk of internalising behaviour problems (relative risk (RR) 1.36, 95% CI 1.02, 1.80) and borderline externalising behaviour problems (RR 1.22, 95% CI 0.93, 1.60) compared with unexposed children. Children exposed to paracetamol in 2nd/3rd trimester scored lower on shyness (ß -0.32, 95% CI -0.66, 0.02) compared with unexposed children. Sensitivity analyses indicated that unmeasured confounders play an important role and may potentially bias the effect estimates away from the null. CONCLUSIONS: Timing of exposure and short-term use of paracetamol during pregnancy do not seem to pose any substantial risk of the outcomes examined. Although we found an association between paracetamol use in multiple trimesters and lower shyness and greater internalising behaviour in preschool-aged children, we cannot rule out chance or unmeasured confounding as possible explanations for these findings.

Risk factors for discontinuation of thyroid hormone replacement therapy in early pregnancy: a study from the Norwegian Mother and Child Cohort Study and the Medical Birth Registry of Norway.

INTRODUCTION: Approximately 3-5% of pregnant women have hypothyroidism. Despite the potential impact of untreated hypothyroidism on infant neurodevelopment, few studies have investigated the risk factors associated with discontinuation of thyroid hormone replacement therapy (THRT) in pregnancy. We aimed to identify such factors in a population of women using THRT prior to pregnancy. MATERIAL AND METHODS: Data from the Norwegian Mother and Child Cohort Study were linked to records in the Medical Birth Registry of Norway. Pregnant women with hypothyroidism prior to pregnancy were categorized as discontinuers or continuers of THRT in pregnancy. The main analysis used generalized estimating equations based on multiply imputed data. RESULTS: Of 86 848 enrolled pregnant women, 2720 (3.2%) had a medically confirmed thyroid disorder and/or reported use of thyroid therapy. More than half (n = 1587; 57.8%) used THRT prior to pregnancy; of these, 207 (13.0%) discontinued and 1380 (86.9%) continued THRT during early pregnancy. Having a non-medicated mental disorder [odds ratio (OR) 1.64, 95% CI 1.03-2.63] and non-compliance with recommended nutritional supplementation (OR 2.51, 95% CI 1.82-3.47) increased the odds of discontinuing THRT. Women medicated for somatic comorbidities (OR 0.56, 95% CI 0.33-0.98) had a 44% decreased odds of discontinuing THRT. CONCLUSIONS: In Norway, around 13% of women with hypothyroidism discontinue THRT in early pregnancy. For discontinuers, non-medicated mental comorbidity and non-compliance with nutritional supplements presented increased risk, whereas having a medicated somatic disorder was protective. Health professionals advising women with hypothyroidism should be aware of risk factors associated with THRT discontinuation.

Safety profile of medication used during pregnancy: results of a multinational European study.

PURPOSE: The present study describes the safety profile of medications used during pregnancy across European countries and examines maternal factors associated with the use of risky medications during pregnancy. METHODS: This study is based on a multinational, web-based study conducted in 15 European countries from October 2011 to February 2012. Information about maternal demographics, illnesses, and medication use during pregnancy was collected via an electronic questionnaire. Pregnant women and new mothers with a child less than 1-year-old could participate. The Swedish, Australian, and U.S. risk classification systems were used to evaluate medication safety. Descriptive statistics and generalized estimating equation models were used. RESULTS: A total of 587 medications were reported by the study sample (n = 6657). Sixty-nine percent of the women used medications classified as safe, 28% used medications classified as risky, and 3% used medications with no classification available. Both socio-demographic and medical factors were associated with the use of risky medications during pregnancy. Having a chronic disorder was the factor with the strongest association with the use of risky medications during pregnancy (adjusted odds ratio = 3.99, 95% confidence interval 3.54-4.49). CONCLUSIONS: The majority of women used medications classified as safe to use during pregnancy. However, a considerable proportion of women still used medications classified as risky. Having a chronic disorder was an important driver for using risky medications. Such use may still be appropriate when considering the woman's underlying condition. Pre-pregnancy counselling is important to ensure safe medication use for both mother and child. © 2017 The Authors. Pharmacoepidemiology & Drug Safety Published by John Wiley & Sons Ltd.

Risk of preeclampsia after gestational exposure to selective serotonin reuptake inhibitors and other antidepressants: A study from The Norwegian Mother and Child Cohort Study.

PURPOSE: To describe the risk of early- and late-onset preeclampsia across pregnancies exposed to antidepressants and to evaluate the impact of timing and length of gestational exposure to antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs), on preeclampsia. METHODS: The Norwegian Mother and Child Cohort, a prospective population-based study, and the Medical Birth Registry of Norway provided information on antidepressant exposure, depression, and anxiety symptoms in pregnancy, preeclampsia diagnoses, and important covariates. Within a pregnancy cohort of depressed women, we compared the risk of late-onset preeclampsia between SSRI-exposed and nonmedicated pregnancies using marginal structural models (weighted) and modified Poisson regression models. RESULTS: Of the 5887 pregnancies included, 11.1% were exposed at any time before week 34 to SSRIs, 1.3% to serotonin-norepinephrine reuptake inhibitors, 0.4% to tricyclic antidepressants, and 0.5% to other antidepressants. The risks of early- and late-onset preeclampsia by exposure status in pregnancy were 0.3% and 3.6% (nonmedicated), 0.4% and 3.7% (SSRIs), 1.5% and 4.1% (serotonin-norepinephrine reuptake inhibitors), and 7.1% and 10.0% (tricyclic antidepressants). Compared with nonmedicated pregnancies, SSRI-exposed in mid and late gestation had adjusted relative risks for late-onset mild preeclampsia of 0.76 (95% confidence interval, 0.38-1.53) and 1.56 (0.71-3.44) (weighted models), respectively. There was no association between SSRI exposure in pregnancy and severe late-onset preeclampsia. CONCLUSIONS: We have provided evidence that SSRI use in early and midpregnancy does not substantially increase the risk of late-onset preeclampsia.

[Drugs and pregnancy: A survey of 374 women in France]. / Médicaments et grossesse : une enquête menée auprès de 374 femmes en France.

OBJECTIVES: The objectives of this study were to describe drug use during pregnancy in a context of acute and chronic diseases during pregnancy. An additional aim was to analyze the maternal socio-demographic and lifestyle factors associated with medication use in pregnancy. METHODS: Cross-sectional, web-based descriptive study conducted among French women using a 33-item web-based questionnaire. Multiple logistic regression analyzes were performed to assess the association between socio-demographic/lifestyle factors and medication use in pregnancy. RESULTS: A total of 374 women completed the questionnaire. Of these, 75.1% (n=280) and 12.6% (n=47) used medication for treatment for acute and chronic diseases, respectively. A total of 68.9% (n=258) of women surveyed have deliberately avoided taking non-prescribed drugs when they were pregnant. Non-users of folic acid were less often taking medications (78.9%) than folic acid users (89.5%) OR=0.44 [0.24; 0.79]. CONCLUSION: More than eight out of ten women have taken medication during pregnancy especially analgesics. The maternal socio-demographic and lifestyle factors do not seem to impact on the use of medication during pregnancy.