Reproductive Safety of Trazodone After Maternal Exposure in Early Pregnancy: A Comparative ENTIS Cohort Study.

PURPOSE/BACKGROUND: Trazodone is indicated for the treatment of major depressive disorder, but more frequently prescribed off-label at lower doses for insomnia in women of childbearing age. The aim of this study was to assess the risks linked to trazodone exposure during pregnancy for which limited safety data are available. METHODS/PROCEDURES: This multicenter, observational prospective cohort study compared pregnancy outcomes in women exposed to trazodone in early pregnancy against those in a reference group of women exposed to a selective serotonin reuptake inhibitors (SSRIs) between 1996 and 2021. FINDINGS/RESULTS: The sample included 221 trazodone and 869 SSRI-exposed pregnancies. Exposure to trazodone in the first trimester was not associated with a significant difference in the risk of major congenital anomalies (trazodone [1/169, 0.6%]; SSRI [19/730, 2.6%]; adjusted odds ratio, 0.2; 95% confidence interval, 0.03-1.77). The cumulative incidences of live birth were 61% and 73% in the trazodone and reference group, respectively (25% vs 18% for pregnancy loss and 14% vs 10% for pregnancy termination). Trazodone exposure was not associated with a significantly increased risk of pregnancy termination and pregnancy loss. The rate of small for gestational age infants did not differ between the groups. IMPLICATIONS/CONCLUSIONS: This study did not reveal a significant difference in the risk of major congenital anomalies after first trimester exposure to trazodone, compared with SSRI exposure. Although this study is the largest so far, these results call for confirmation through further studies.

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.

Use of ondansetron during pregnancy and the risk of major congenital malformations: A systematic review and meta-analysis.

AIMS: To investigate whether ondansetron use during pregnancy is associated with increased rates of major or subgroups of malformations. METHODS: PubMed/MEDLINE, Cochrane and Reprotox® databases were searched. Observational studies comprising an exposed and control group (healthy and/or disease-matched) were included. RESULTS: No significant increased risk for major malformations, heart defects, orofacial clefts, genitourinary malformations or hypospadias were identified in our primary analysis. A significant heterogeneity existed for isolated cleft palate. Elevated point estimates and altered statistical significances were present for some of the outcomes among secondary analyses. CONCLUSIONS: Ondansetron use during pregnancy was not associated with a significant increase in rate of major or selected subgroups of malformations in our primary analysis. However, results of the secondary analyses warrant the need for continued surveillance. These results may be reassuring for pregnant women in whom ondansetron use is clinically indicated since the absolute risks of possible concerns appear to be low.

Methylphenidate in Pregnancy: A Multicenter, Prospective, Comparative, Observational Study.

INTRODUCTION: Methylphenidate is a central nervous system stimulant medicinally used in the treatment of attention-deficit disorder with or without hyperactivity (ADD/ADHD). Data on its use in human pregnancy are limited. The primary objective of the study was to evaluate the risk of major congenital anomalies after pregnancy exposure to methylphenidate for medical indications. METHODS: In a prospective, comparative, multicenter observational study performed in 4 participating Teratology Information Services (in Jerusalem, Berlin, Newcastle upon Tyne, and Toronto) between 1996 and 2013, methylphenidate-exposed pregnancies were compared with pregnancies counseled for nonteratogenic exposure (NTE) after matching by maternal age, gestational age, and year at initial contact. RESULTS: 382 methylphenidate-exposed pregnancies (89.5% in the first trimester) were followed up. The overall rate of major congenital anomalies was similar between the groups (10/309 = 3.2% [methylphenidate] vs 13/358 = 3.6% [NTE], P = .780). The rates of major congenital anomalies (6/247 = 2.4% [methylphenidate] vs 12/358 = 3.4% [NTE], P = .511) and cardiovascular anomalies (2/247 = 0.8% [methylphenidate] vs 3/358 = 0.8% [NTE], P = .970) were also similar after exclusion of genetic or cytogenetic anomalies and limiting methylphenidate exposure to the period of organogenesis (weeks 4-13 after the last menstrual period). There was a higher rate of miscarriages and elective terminations of pregnancy in the methylphenidate group. Significant predictors for the miscarriages using Cox proportional hazards model were methylphenidate exposure (adjusted hazard ratio [HR] = 1.98; 95% CI, 1.23-3.20; P = .005) and past miscarriage (adjusted HR = 1.35; 95% CI, 1.18-1.55; P < .001). CONCLUSIONS: The present study suggests that methylphenidate does not seem to increase the risk for major malformations. Further studies are required to establish its pregnancy safety and its possible association with miscarriages.

An International Study of the Ability and Cost-Effectiveness of Advertising Methods to Facilitate Study Participant Self-Enrolment Into a Pilot Pharmacovigilance Study During Early Pregnancy.

BACKGROUND: Knowledge of the fetal effects of maternal medication use in pregnancy is often inadequate and current pregnancy pharmacovigilance (PV) surveillance methods have important limitations. Patient self-reporting may be able to mitigate some of these limitations, providing an adequately sized study sample can be recruited. OBJECTIVE: To compare the ability and cost-effectiveness of several direct-to-participant advertising methods for the recruitment of pregnant participants into a study of self-reported gestational exposures and pregnancy outcomes. METHODS: The Pharmacoepidemiological Research on Outcomes of Therapeutics by a European Consortium (PROTECT) pregnancy study is a non-interventional, prospective pilot study of self-reported medication use and obstetric outcomes provided by a cohort of pregnant women that was conducted in Denmark, the Netherlands, Poland, and the United Kingdom. Direct-to-participant advertisements were provided via websites, emails, leaflets, television, and social media platforms. RESULTS: Over a 70-week recruitment period direct-to-participant advertisements engaged 43,234 individuals with the study website or telephone system; 4.78% (2065/43,234) of which were successfully enrolled and provided study data. Of these 90.4% (1867/2065) were recruited via paid advertising methods, 23.0% (475/2065) of whom were in the first trimester of pregnancy. The overall costs per active recruited participant were lowest for email (€23.24) and website (€24.41) advertisements and highest for leaflet (€83.14) and television (€100.89). Website adverts were substantially superior in their ability to recruit participants during their first trimester of pregnancy (317/668, 47.5%) in comparison with other advertising methods (P<.001). However, we identified international variations in both the cost-effectiveness of the various advertisement methods used and in their ability to recruit participants in early pregnancy. CONCLUSIONS: Recruitment of a pregnant cohort using direct-to-participant advertisement methods is feasible, but the total costs incurred are not insubstantial. Future research is needed to identify advertising strategies capable of recruiting large numbers of demographically representative pregnant women, preferentially in early pregnancy.