Maternal first trimester COVID-19 vaccination and risk of major non-genetic congenital anomalies.

BACKGROUND: Information regarding the risk of early pregnancy COVID-19 vaccination on the development of major congenital anomalies in the offspring is still limited. Here, we study the association between any COVID-19 vaccination during the 1st trimester and at least one major non-genetic congenital anomaly in the offspring. METHODS: We used data from the Dutch Pregnancy Drug Register, an ongoing cohort study. We selected participants with a pregnancy that ended after at least 20 weeks gestation. Pregnant participants self-reported their COVID-19 vaccination status and the presence of congenital anomalies in the offspring. We used logistic regression analyses to study the association between 1st trimester COVID-19 vaccination (gestational week 2 + 0 to 12 + 6) and the risk of at least one major non-genetic congenital anomaly in the offspring. Clustering of anomalies on the ICD10 level by 1st trimester COVID-19 vaccination status was explored using Fisher exact tests. RESULTS: We included 3721 participants of whom 795 (21.4%) were COVID-19 vaccinated during the 1st trimester. The percentage of participants who gave birth to a child with at least one major non-genetic congenital anomaly was comparable between participants who were 1st trimester vaccinated (1.1%) and participants who were not (1.2%) (adjusted odd ratio 0.78 [95% confidence interval 0.35-1.71]). We found no clustering of major non-genetic congenital anomalies by 1st trimester COVID-19 vaccination status (p > .05). CONCLUSIONS: There were no indications of an increased risk of major non-genetic congenital anomalies in the offspring after maternal 1st trimester COVID-19 vaccination. Our findings suggest COVID-19 vaccines are safe during early pregnancy.

Determinants of Vaccination and Willingness to Vaccinate against COVID-19 among Pregnant and Postpartum Women during the Third Wave of the Pandemic: A European Multinational Cross-Sectional Survey.

With COVID-19 vaccination hesitancy at around 50% in the obstetric population, it is critical to identify which women should be addressed and how. Our study aimed to assess COVID-19 vaccination willingness among pregnant and postpartum women in Europe and to investigate associated determinants. This study was a cross-sectional, web-based survey conducted in Belgium, Norway, Switzerland, The Netherlands, and United Kingdom (UK) in June-August 2021. Among 3194 pregnant women, the proportions of women vaccinated or willing to be vaccinated ranged from 80.5% in Belgium to 21.5% in Norway. The associated characteristics were country of residence, chronic illness, history of flu vaccine, trimester of pregnancy, belief that COVID-19 is more severe during pregnancy, and belief that the COVID-19 vaccine is effective and safe during pregnancy. Among 1659 postpartum women, the proportions of women vaccinated or willing to be vaccinated ranged from 86.0% in the UK to 58.6% in Switzerland. The associated determinants were country of residence, chronic illness, history of flu vaccine, breastfeeding, and belief that the COVID-19 vaccine is safe during breastfeeding. Vaccine hesitancy in the obstetric population depends on medical history and especially on the opinion that the vaccine is safe and on the country of residence.

Mental health of pregnant and postpartum women during the third wave of the COVID-19 pandemic: a European cross-sectional study.

OBJECTIVE: To describe the mental health of perinatal women in five European countries during the third pandemic wave and identify risk factors related to depressive and anxiety symptoms. DESIGN: A cross-sectional, online survey-based study. SETTING: Belgium, Norway, Switzerland, the Netherlands and the UK, 10 June 2021-22 August 2021. PARTICIPANTS: Pregnant and up to 3 months postpartum women, older than 18 years of age. PRIMARY OUTCOME MEASURE: The Edinburgh Depression Scale (EDS) and the Generalised Anxiety Disorder scale (GAD-7) were used to assess mental health status. Univariate and multivariate generalised linear models were performed to identify factors associated with poor mental health. RESULTS: 5210 women participated (including 3411 pregnant and 1799 postpartum women). The prevalence of major depressive symptoms (EDS ≥13) was 16.1% in the pregnancy group and 17.0% in the postpartum . Moderate to severe generalised anxiety symptoms (GAD ≥10) were found among 17.3% of the pregnant and 17.7% of the postpartum women. Risk factors associated with poor mental health included having a pre-existing mental illness, a chronic somatic illness, having had COVID-19 or its symptoms, smoking, unplanned pregnancy and country of residence. Among COVID-19 restrictive measures specific to perinatal care, pregnant and postpartum women were most anxious about not having their partner present at the time of delivery, that their partner had to leave the hospital early and to be separated from their newborn after the delivery. CONCLUSION: Approximately one in six pregnant or postpartum women reported major depression or anxiety symptoms during the third wave of the pandemic. These findings suggest a continued need to monitor depression and anxiety in pregnancy and postpartum populations throughout and in the wake of the pandemic. Tailored support and counselling are essential to reduce the burden of the pandemic on perinatal and infant mental health.

Self-Reported Medication Use among Pregnant and Postpartum Women during the Third Wave of the COVID-19 Pandemic: A European Multinational Cross-Sectional Study.

Information on medication utilization among pregnant and postpartum women during the pandemic is lacking. We described the prevalence and patterns of self-reported medication use among pregnant and postpartum women during the third wave of the pandemic (June-August 2021). An online questionnaire was distributed in five European countries between June-August 2021. Pregnant women or women who had delivered in the three preceding months, and ≥18 years old, could participate. The prevalence of overall medication use, self-medication, and changes in chronic medication use were determined. A total of 2158 women out of 5210 participants (41.4%) used at least one medication. Analgesics (paracetamol), systemic antihistamines (cetirizine), and drugs for gastric disorders (omeprazole) were the three most used classes. Anti-infectives were less prevalent than during pre-pandemic times. Antidepressants and anxiety related medication use remained similar, despite a higher prevalence of these symptoms. Self-medication was reported in 19.4% of women, and 4.1% of chronic medication users reported that they changed a chronic medication on personal initiative due to the pandemic. In conclusion, medication use patterns in our cohort were mostly similar to those of the first COVID-19 wave and the pre-pandemic period. More studies are needed to explore factors associated with self-medication and changes in chronic medication use due to the pandemic in this perinatal population.

Self-Reported Medication Use among Pregnant and Breastfeeding Women during the COVID-19 Pandemic: A Cross-Sectional Study in Five European Countries.

Insight into the epidemiology of perinatal medication use during the COVID-19 pandemic is scarce. Therefore, a cross-sectional study using an anonymous web survey was performed in Ireland, Norway, Switzerland, The Netherlands, and United Kingdom (UK) to investigate the prevalence and type of medications used by pregnant and breast-feeding women during the first pandemic wave. Factors associated with medication use were estimated by logistic regression. In total, 8378 women participated (i.e., 3666 pregnant and 4712 breastfeeding women). Most responses were collected in Norway (34%) and The Netherlands (28%), followed by Switzerland (19%), Ireland (17%) and UK (2%). Participants were more often professionally active and more often had a higher educational level compared to the general birthing population in each country. Overall, approximately 60% of women reported having used at least 1 medication in the preceding 3 months. Daily and occasional use was reported by 34% and 42% of pregnant and 29% and 44% of breastfeeding women. The most prevalent ATC (Anatomical Therapeutic Chemical) categories were the nervous system, the respiratory system, the alimentary tract/metabolism, and the musculo-skeletal system. Paracetamol, ibuprofen, antacids, and cetirizine were the most frequently used medications. The rate of antibacterial use was lower than previously reported. Having a chronic illness, country, maternal age, SARS-CoV-2 testing, professional status and time since delivery were associated with medication use. In conclusion, perinatal medication use was highly prevalent during the first pandemic wave, underlining the importance of maintaining counseling efforts on medication use, even in times of disrupted healthcare services and/or limited resources.

Vaccine Willingness and Impact of the COVID-19 Pandemic on Women's Perinatal Experiences and Practices-A Multinational, Cross-Sectional Study Covering the First Wave of the Pandemic.

The COVID-19 pandemic may be of particular concern for pregnant and breastfeeding women. We aimed to explore their beliefs about the coronavirus and COVID-19 vaccine willingness and to assess the impact of the pandemic on perinatal experiences and practices. A multinational, cross-sectional, web-based study was performed in six European countries between April and July 2020. The anonymous survey was promoted via social media. In total, 16,063 women participated (including 6661 pregnant and 9402 breastfeeding women). Most responses were collected from Belgium (44%), Norway (18%) and the Netherlands (16%), followed by Switzerland (11%), Ireland (10%) and the UK (3%). Despite differences between countries, COVID-19 vaccine hesitancy was identified among 40-50% of the respondents at the end of the first wave of the pandemic and was higher among pregnant women. Education level and employment status were associated with vaccine hesitancy. The first wave had an adverse impact on pregnancy experiences and disrupted access to health services and breastfeeding support for many women. In the future, access to health care and support should be maintained at all times. Evidence-based and tailored information on COVID-19 vaccines should also be provided to pregnant and breastfeeding women to avoid unfounded concerns about the vaccines and to support shared decision making in this population.

Mental health status of pregnant and breastfeeding women during the COVID-19 pandemic-A multinational cross-sectional study.

INTRODUCTION: Evidence on perinatal mental health during the coronavirus disease 2019 (COVID-19) pandemic and its potential determinants is limited. Therefore, this multinational study aimed to assess the mental health status of pregnant and breastfeeding women during the pandemic, and to explore potential associations between depressive symptoms, anxiety, and stress and women's sociodemographic, health, and reproductive characteristics. MATERIAL AND METHODS: A cross-sectional, web-based study was performed in Ireland, Norway, Switzerland, the Netherlands, and the UK between 16 June and 14 July 2020. Pregnant and breastfeeding women up to 3 months postpartum who were older than 18 years of age were eligible. The online, anonymous survey was promoted through social media and hospital websites. The Edinburgh Depression Scale (EDS), the Generalized Anxiety Disorder seven-item scale (GAD-7), and the Perceived Stress Scale (PSS) were used to assess mental health status. Regression model analysis was used to identify factors associated with poor mental health status. RESULTS: In total, 9041 women participated (including 3907 pregnant and 5134 breastfeeding women). The prevalence of major depressive symptoms (EDS ≥ 13) was 15% in the pregnancy cohort and and 13% the breastfeeding cohort. Moderate to severe generalized anxiety symptoms (GAD ≥ 10) were found among 11% and 10% of the pregnant and breastfeeding women. The mean (±SD) PSS scores for pregnant and breastfeeding women were 14.1 ± 6.6 and 13.7 ± 6.6, respectively. Risk factors associated with poor mental health included having a chronic mental illness, a chronic somatic illness in the postpartum period, smoking, having an unplanned pregnancy, professional status, and living in the UK or Ireland. CONCLUSIONS: This multinational study found high levels of depressive symptoms and generalized anxiety among pregnant and breastfeeding women during the COVID-19 outbreak. The study findings underline the importance of monitoring perinatal mental health during pandemics and other societal crises to safeguard maternal and infant mental health.

Pregnancy outcomes in women on metformin for diabetes or other indications among those seeking teratology information services.

AIMS: Metformin is used to treat type 2 diabetes, polycystic ovary syndrome associated infertility, and gestational diabetes. This study aims to evaluate the safety of metformin in early pregnancy. METHOD: We evaluated the risk of major birth defects and pregnancy losses in a cohort of pregnant women exposed to metformin during the first trimester for different indications relative to a matched unexposed reference group. RESULTS: The risk of major birth defects was 5.1% (20/392) in pregnancies exposed to metformin during the first trimester and 2.1% (9/431) in the reference group [adjusted odds ratio (OR) 1.70; 95% CI 0.70-4.38]. Among metformin users, this risk was 7.8% (17/219) in patients with pre-gestational diabetes and 1.7% (3/173) in those without this diagnosis. Compared to the unexposed reference, the OR for metformin user with diabetes was 3.95 (95% CI 1.77-9.41) and for metformin with other indications it was 0.83 (95% CI 0.18-2.81). The risk of pregnancy losses (spontaneous abortions and stillbirths) was 20.8% in women on metformin during the first trimester and 10.8% in the reference group [adjusted hazard ratio (HR) 1.57; 95% CI 0.90-2.74]. The risks for women on metformin with and without pre-gestational diabetes were 24.0% and 16.8% respectively, with adjusted HR of 2.51 (95% CI 1.44-4.36) and 1.38 (95% CI 0.74-2.59) when compared to the reference. CONCLUSION: Pregnant women with pre-gestational diabetes on metformin are at a higher risk for adverse pregnancy outcomes than the general population. This appears to be due to the underlying diabetes since women on metformin for other indications do not present meaningfully increased risks.

Patterns and factors associated with low adherence to psychotropic medications during pregnancy--a cross-sectional, multinational web-based study.

BACKGROUND: No previous studies have explored how closely women follow their psychotropic drug regimens during pregnancy. This study aimed to explore patterns of and factors associated with low adherence to psychotropic medication during pregnancy. METHODS: Multinational web-based study was performed in 18 countries in Europe, North America, and Australia. Uniform data collection was ensured via an electronic questionnaire. Pregnant women were eligible to participate. Adherence was measured via the 8-item Morisky Medication Adherence Scale (MMAS-8). The Beliefs about Prescribed Medicines Questionnaire (BMQ-specific), the Edinburgh Postnatal Depression Scale (EPDS), and a numeric rating scale were utilized to measure women's beliefs, depressive symptoms, and antidepressant risk perception, respectively. Participants reporting use of psychotropic medication during pregnancy (n = 160) were included in the analysis. RESULTS: On the basis of the MMAS-8, 78 of 160 women (48.8%, 95% CI: 41.1-56.4%) demonstrated low adherence during pregnancy. The rates of low adherence were 51.3% for medication for anxiety, 47.2% for depression, and 42.9% for other psychiatric disorders. Smoking during pregnancy, elevated antidepressant risk perception (risk≥6), and depressive symptoms were associated with a significant 3.9-, 2.3-, and 2.5-fold increased likelihood of low medication adherence, respectively. Women on psychotropic polytherapy were less likely to demonstrate low adherence. The belief that the benefit of pharmacotherapy outweighed the risks positively correlated (r = .282) with higher medication adherence. CONCLUSIONS: Approximately one of two pregnant women using psychotropic medication demonstrated low adherence in pregnancy. Life-style factors, risk perception, depressive symptoms, and individual beliefs are important factors related to adherence to psychotropic medication in pregnancy.

Motives for reporting adverse drug reactions by patient-reporters in the Netherlands.

AIM: The aim of this study was to quantify the reasons and opinions of patients who reported adverse drug reactions (ADRs) in the Netherlands to a pharmacovigilance centre. METHOD: A web-based questionnaire was sent to 1370 patients who had previously reported an ADR to a pharmacovigilance centre. The data were analysed using descriptive statistics, χ(2) tests and Spearman's correlation coefficients. RESULTS: The response rate was 76.5% after one reminder. The main reasons for patients to report ADRs were to share their experiences (89% agreed or strongly agreed), the severity of the reaction (86% agreed or strongly agreed to the statement), worries about their own situation (63.2% agreed or strongly agreed) and the fact the ADR was not mentioned in the patient information leaflet (57.6% agreed or strongly agreed). Of the patient-responders, 93.8% shared the opinion that reporting an ADR can prevent harm to other people, 97.9% believed that reporting contributes to research and knowledge, 90.7% stated that they felt responsible for reporting an ADR and 92.5% stated that they will report a possible ADR once again in the future. CONCLUSION: The main motives for patients to report their ADRs to a pharmacovigilance centre were the severity of the ADR and their need to share experiences. The high level of response to the questionnaire shows that patients are involved when it comes to ADRs and that they are also willing to share their motivations for and opinions about the reporting of ADRs with a pharmacovigilance centre.

Reporting of adverse drug reactions by general practitioners: a questionnaire-based study in the Netherlands.

BACKGROUND: There has been a gradual decline over the years in the number of spontaneous reports of potential adverse drug reactions (ADRs) from general practitioners (GPs) in the Netherlands. OBJECTIVE: To reveal aspects of knowledge, attitudes and behaviour that can stimulate GPs to submit (more) ADRs. METHODS: Dutch GPs were divided into the following two groups based on their reporting behaviour during the period 2004-6: (i) active reporters; and (ii) non-reporters. A random selection from each group was sent a questionnaire, based on the Ajzen and Fishbein model, focussed on their reporting behaviour. The questions were subdivided into knowledge-related questions, attitude-related questions and questions about the influence of the professional environment. RESULTS: 700 questionnaires were completed, corresponding with an overall response of 47%. GPs who actively reported ADRs differed from their non-reporting colleagues: they had more knowledge on ADR reporting, were more interested in pharmacotherapy and more often had a positive example in their professional environment. Both reporting and non-reporting GPs considered it very important to comply with their professional environment. CONCLUSION: Specific education and training of GPs on pharmacotherapy, preferably with extra attention to ADR reporting, is expected to improve ADR reporting. Improved communication of GPs with their fellow GPs and pharmacists as well as with their patients may further stimulate ADR reporting.

Comparing patients' and healthcare professionals' ADR reports after media attention: the broadcast of a Dutch television programme about the benefits and risks of statins as an example.

AIMS: To compare adverse drug reaction (ADR) reports from patients and health professionals after the broadcast of a Dutch television consumer programme about the benefits and risks of statins. METHODS: We performed a quantitative and qualitative analysis on patients' and health professionals' reports of ADRs to statins. These reports were received by the Netherlands Pharmacovigilance Centre Lareb between March 2007 and August 2007. Quantitative data consisted of patient age and gender, number of received reports and characteristics of the report (most frequently reported ADRs, seriousness, drug discontinuation and outcome of the reported reaction). Open text fields in the ADR reporting form were categorized and a content analysis was carried out. RESULTS: Media attention led to a peak in patient reporting of ADRs but not in reporting by health professionals. There were no differences between patient and health professional reports in seriousness of the ADRs and drug cessation. Patients reported nonrecovery more often than health professionals. The TV programme is mentioned as a reason for drug discontinuation in almost 30 reports. Patients often felt that they did not receive sufficient information and that their concerns were not adequately addressed by healthcare professionals. CONCLUSIONS: Media attention affects drug use and ADR reporting by patients. Patient reports can provide additional information, making them a useful source of information next to health professional reports. Content analysis provides vital insights into the impact of statins on daily life, and patients' concerns about adverse reactions should be recognized in reports to national pharmacovigilance centres.

Adverse drug reaction reporting by patients in the Netherlands: three years of experience.

BACKGROUND: There has been discussion about the acceptance of adverse drug reactions (ADRs) reported by patients to spontaneous reporting systems. Lack of experience with patient reporting in real life was one of the main drawbacks in this debate. This study covers 3 years of experience with patient reporting in daily practice. We compared patient reports with reports from healthcare professionals. Although patients have the opportunity to report ADRs in several countries, little is published in the literature about the contribution that patient reports have in practice. To our knowledge, this paper is the first to describe long-term experiences with patient reporting as part of a spontaneous reporting system. METHODS: The number of reports received, age and sex of the reporters, characteristics of the most frequently reported drugs and characteristics of the ADRs (most frequently reported ADRs, seriousness, outcome) in a 3-year period (April 2004-April 2007) were compared between patient reports and reports from healthcare professionals. FINDINGS: During this 3-year period, the Netherlands Pharmacovigilance Centre Lareb received 2522 reports directly from patients, concerning 5401 ADRs. In the same period, healthcare professionals submitted 10 635 reports, concerning 16 722 ADRs. Differences were found in the categories of seriousness and outcome of the reported ADRs between patients and healthcare professionals. Conversely, similarities between patient reports and reports from healthcare professionals were found in age, sex, most frequently reported ADRs and most frequently reported drugs. INTERPRETATION: Our study highlights clearly that valuable differences between ADR reports from patients and reports from healthcare professionals exist. Differences in interpretation by patients and healthcare professionals may cause the observed disparities in seriousness and outcome of reported ADRs. However, the similarities between patient reports and reports from healthcare professionals in most frequently reported ADRs and most frequently reported drugs are striking. After 3 years of experience with patient reporting, we conclude that patient reporting in spontaneous reporting systems is feasible and that it contributes significantly to a reliable pharmacovigilance.

Mirtazapine-induced arthralgia.

AIM: With this article, we intend to corroborate the assumed association between mirtazapine and arthralgia by presentation of eight case reports, and we describe a possible mechanism of action. METHODS AND RESULTS: The Netherlands Pharmacovigilance Centre Lareb received eight case reports on arthralgia associated with use of mirtazapine. These case reports are presented in short. We also present worldwide data on this association. CONCLUSIONS: The Lareb reports support the association between mirtazapine and arthralgia. A comparison is made between mirtazapine, mianserin and nefazodone, as these antidepressants show similarities in their mode of action and are all associated with arthralgia. We suggest that this adverse drug reaction may be induced by enhanced 5HT1-mediated neurotransmission.

Neonatal intraventricular haemorrhage associated with maternal use of paroxetine.

Selective serotonin reuptake inhibitors (SSRIs) have been reported to inhibit serotonin uptake into platelets, resulting in decreased platelet function. We report a case of a large intraventricular haemorrhage in a 6-h-old boy, whose mother used paroxetine during pregnancy.