Exposure Registries Research Articles

Surveillance of asbestos related disease among workers enrolled in an exposure registry.

Contemporary asbestos exposure occurs during construction, remediation, and maintenance involving asbestos-containing materials (ACM), as compared to the historical exposure scenarios of asbestos mining and milling. The Ontario Asbestos Workers Register (AWR) was established in 1986 to track asbestos exposure among construction workers. This study reports on the risk of asbestos-related diseases (ARD) among workers in the AWR. AWR registrants were linked probabilistically with administrative health databases (1986-2019) to identify cases of ARD including both cancer and chronic respiratory disease. Follow-up began at AWR enrollment and continued prospectively. Incidence rates were compared to the general population using standardized incidence ratios (SIRs). Associations between ACM exposure and ARD were estimated among AWR registrants using Poisson regression. In total, 26,204 (81%) registrants were linked successfully. Common industries of employment were construction (62%), manufacturing (19%) and education (8%). Among men and women mesothelioma (M:SIR 6.83 [95% CI = 5.56-8.31]; W:SIR 19.2 [3.86-56.1]) and pulmonary fibrosis (M:SIR 14.1 [12.2-16.2]; W:SIR 9.25 [2.49-23.7]) rates were higher than the general population. Asbestosis risk was elevated among men (M:SIR 11.2 [9.59-13.1]). Workers with longer reported exposures (≥140 h) had increased rates of lung cancer (RR 1.34 [1.10-1.63]), mesothelioma (RR 2.83 [1.75-4.58]), asbestosis (RR 3.07 [2.12-4.43]), chronic obstructive pulmonary disease (RR 1.42 [1.29-1.57]), and pulmonary fibrosis (RR 1.88 [1.35-2.62]). Exposure to asbestos in construction and building maintenance continues to contribute to ARD incidence. Despite a Canadian ban on asbestos in new products, exposures to existing ACM will persist from construction activities. The AWR offers an opportunity for ongoing surveillance of resulting ARD in Ontario.

Population-based prevalence of congenital defects in a routine sentinel site-based surveillance system in the Western Cape, South Africa.

Lack of data on the burden and scope of congenital disorders (CDs) in South Africa undermines resource allocation and limits the ability to detect signals from potentially teratogenic pregnancy exposures. We used routine electronic data in the Western Cape Pregnancy Exposure Registry (PER) to determine the overall and individual prevalence of CD identified on neonatal surface examination at birth in the Western Cape, South Africa, 2016-2022. CD was confirmed by record review. The contribution of late (≤24 months) and antenatal diagnoses was assessed. We compared demographic and obstetric characteristics between women with/without pregnancies affected by CD. Women with a viable pregnancy (>22 weeks gestation; birth weight ≥ 500 g) (n = 32,494) were included. Of 1106 potential CD identified, 56.1% were confirmed on folder review. When internal and minor CD were excluded the prevalence of major CD identified on surface examination at birth was 7.2/1000 births. When missed/late diagnoses on examination (16.8%) and ultrasound (6.8%) were included, the prevalence was 9.2/1000 births: 8.9/1000 livebirths and 21.5/1000 stillbirths. The PER did not detect 21.5% of major CD visible at birth. Older maternal age and diabetes mellitus were associated with an increased prevalence of CD. Women living with/without HIV (or the timing of antiretroviral therapy, before/after conception), hypertension or obesity did not significantly affect prevalence of CD. A surveillance system based on routine data successfully determined the prevalence of major CD identified on surface examination at birth at rates slightly higher than in equivalent studies. Overall rates, modeled at ~2%, are likely underestimated. Strengthening routine neonatal examination and clinical record-keeping could improve CD ascertainment.

Safety of Antiretroviral Exposure During Pregnancy: Opportunities to Close Data Gaps.

Pregnant persons with chronic health conditions often require pharmacotherapy to remain healthy. The Antiretroviral Pregnancy Registry is a prospective, international, voluntary, and exposure registry that collects information on antiretroviral (ARV) exposure; however, a minority of providers use the registry, leaving critical gaps to guide prescribing in this population. The Task Force for the Elimination of Perinatal HIV Transmission in the United States, funded by the Centers for Disease Control and Prevention, has identified the monitoring of ARV safety as a paramount concern in the ongoing mission to eliminate perinatal human immunodeficiency virus (HIV) transmission. As active members of this task force, we urge all healthcare providers who care for pregnant individuals to prioritize reporting all ARV exposures to the registry.

Occupational carcinogens in Italy: an overview on exposure to cadmium and its compounds.

Given the recognized carcinogenicity of cadmium, several regulatory interventions have been carried out over the years to protect exposed workers. The aim of the study is to investigate the prevalence and extent of exposure to cadmium among Italian workers. Data was collected from a nation-wide occupational exposure registry (SIREP, 1996-2022). Gender-specific statistical analysis was carried out for some exposure-related variables (cadmium compound, activity sector, occupational group, firm size). Potentially exposed workers were estimated for some industrial sectors. Concurrent exposures were investigated using cluster analysis. Overall 4,264 measurements were analyzed. Four industrial sectors were found to be most involved by cadmium exposure: base metal manufacturing, fabricated metal products, machinery and equipment, and other transport equipment (55% of measurements). Jewellery/precious-metal workers, and glass/ceramic plant operators were found to be most at exposure risk. A total of 26,470 workers potentially exposed was estimated (69% men). Concurrent exposures to other occupational carcinogens were detected quite frequently (52% of workers). Several situations of exposure and co-exposure to cadmium deserve attention and awareness in order to minimize the risks associated with workers' health. Recognition of potentially hazardous exposure conditions is an important step in prevention strategies to better protect workers against cancer-causing agents.

Analysis of Pregnancy Outcomes Following Exposure to Intramuscular Interferon Beta-1a: The AVONEX® Pregnancy Exposure Registry.

There is a lack of well-controlled US studies of intramuscular (IM) interferon beta (IFNβ)-1a use in pregnant women with multiple sclerosis; however, in the European Medicines Agency region, IFNβ formulations may be considered during pregnancy if clinically needed based on data from European Union cohort registries. The AVONEX Pregnancy Exposure Registry was established to prospectively study the effects of IM IFNβ-1a on the risk of birth defects and spontaneous pregnancy loss in a US population. Pregnant women with multiple sclerosis exposed to IM IFNβ-1a within ~ 1 week of conception or during the first trimester were included. Participants were followed until there was a pregnancy outcome, live-born infants were followed until age 8-12 weeks. Data were collected on IM IFNβ-1a exposure, demographics, patient characteristics, medical history, and pregnancy outcomes, including live births (with or without birth defect), spontaneous abortions/miscarriages and fetal death/stillbirth, elective abortions (with and without birth defect), and ectopic pregnancies. A population-based birth defect surveillance program, the Metropolitan Atlanta Congenital Defects Program (MACDP), served as the primary external control group for evaluating the risk of birth defects. Three-hundred and two patients with a median (range) age of 31.0 (16-48) years and a median (range) gestational age at the time of enrollment of 10.1 (4-39) weeks were evaluable. Most patients (n = 278/302; 92%) reported IM IFNβ-1a exposure in the week before conception and most (n = 293/302; 97%) discontinued treatment before the end of the first trimester. Of 306 pregnancy outcomes, there were 272 live births, 28 spontaneous abortions of 266 pregnancies enrolled before 22 weeks' gestation (rate 10.5%; 95% confidence interval 7.2-15.0), five elective abortions, and one stillbirth. There were 17 adjudicator-confirmed major birth defects of 272 live births (rate 6.3%; 95% confidence interval 3.8-10.0); the pattern of birth defects observed was not suggestive of a relationship to prenatal IM IFNβ-1a exposure. This large US registry study suggests IM IFNβ-1a exposure during early pregnancy was not clinically associated with adverse pregnancy outcomes in women with multiple sclerosis. These findings help inform clinicians and patients in weighing the risks and benefits of IM IFNβ-1a use during pregnancy. ClinicalTrials.gov: NCT00168714, 15 September, 2005.

0909 Pitolisant Pregnancy Registry: An Observational Study of the Safety of Pitolisant Exposure in Pregnant Women and Their Offspring

Abstract Introduction WAKIX (pitolisant) is a potent and highly selective histamine 3 receptor antagonist/inverse agonist approved for the treatment of excessive daytime sleepiness or cataplexy in adult patients with narcolepsy. The safety of pitolisant in pregnant women has not been established. Available case reports from clinical trials and postmarketing experience have not demonstrated a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. The registry is a prospective, observational cohort study designed to evaluate the association between pitolisant exposure during pregnancy and subsequent maternal, fetal, and infant outcomes. Methods The primary study population consists of 3 cohorts: pregnant women with a diagnosis of narcolepsy who are exposed to pitolisant during pregnancy, pregnant women with narcolepsy who are unexposed to pitolisant but exposed to comparator products during pregnancy, and pregnant women with narcolepsy who are neither exposed to pitolisant nor comparator products. Comparator products include modafinil, armodafinil, sodium oxybate, oxybate mixed salts, solriamfetol, methylphenidate, and amphetamines. Outcomes of interest include major congenital malformation (primary outcome), minor congenital malformation, pre-eclampsia, eclampsia, spontaneous abortion, stillbirth, elective termination, small for gestational age, preterm birth, postnatal growth deficiency, and infant developmental deficiency. Data are collected from enrolled pregnant women and healthcare providers involved in their care or the care of their infants, if applicable. Only data that are routinely documented in patients' medical records during usual care are collected. Participation in the registry is voluntary and participants may withdraw their consent to participate at any time. The registry design follows current FDA guidance for designing and implementing pregnancy exposure registries. Results The registry was initiated in May 2021. Presently, data are insufficient to assess an association between pitolisant exposure and any endpoint of interest. Study completion is planned in 2030. Conclusion Healthcare providers are encouraged to discuss this voluntary pregnancy registry with their eligible patients and assist women who are interested in enrolling. The study is registered on Clinicaltrials.gov (ID# NCT05536011). Support (if any) This study is sponsored by Harmony Biosciences LLC.

Pregnancy exposure registries for drugs and vaccines in low-income and middle-income countries: scoping review protocol

IntroductionData regarding the safety of drugs and vaccines in pregnant women are typically unavailable before licensure. Pregnancy exposure registries (PERs) are an important source of postmarketing safety information. PERs in...

Diroximel Fumarate Pregnancy Outcomes in EVOLVE-MS-1 and Study Design of Diroximel Fumarate Prospective MS Pregnancy Exposure Registry (P9-3.003)

Diroximel Fumarate Pregnancy Outcomes in EVOLVE-MS-1 and Study Design of Diroximel Fumarate Prospective MS Pregnancy Exposure Registry (P9-3.003)

Barriers and Facilitators in the Creation of a Surveillance System for Solar Radiation-Induced Skin Cancers.

Outdoor workers are exposed to many hazards, including solar ultraviolet radiation (UVR). Identifying, reporting, analyzing and tracking the exposures or health outcomes of outdoor workers have not generally been formally considered. This article aims to summarize the best practices/strategies for creating an occupational sun exposure or skin cancer surveillance system for outdoor workers and to understand the key barriers and facilitators to the development of such a system. For the design of a successful occupational safety and health (OSH) surveillance system five occupational surveillance strategies are summarized: exposure registry, disease registry, disease screening/medical surveillance, sentinel event surveillance, and disease surveillance via data linkage. Ten key considerations are identified, including identifying a clear goal, a defined target population and stakeholder involvement, five critical barriers are highlighted including underreporting and funding, and five vital facilitators are recognized including communication/collaboration and a simple reporting process.

MRNA COVID-19 vaccination early in pregnancy and the risk of spontaneous abortion in an international pregnancy registry.

mRNA COVID-19 vaccines are used in pregnant populations whether advertently or inadvertently. However, evidence on the safety of these vaccines during pregnancy is limited. The objective of this study is to evaluate the effect of BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) vaccination during the first 20 weeks of gestation on the risk of spontaneous abortion (SAB). All pregnant women who received at least one dose of BNT162b2 or mRNA-1273 and enrolled in the COVID-19 Vaccines International Pregnancy Exposure Registry (C-VIPER) were prospectively followed from enrollment until 20 weeks of gestation, SAB, or loss to follow-up. Baseline demographics, vaccination information, and pregnancy outcomes were collected via monthly online self-administered questionnaires, vaccination certificates, and medical records. Life tables were used to calculate the cumulative risk of SAB. Cox regression was used to estimate the hazard ratio (HR) comparing the two vaccines groups stratified by country of residence and gestational age at enrollment. Among 6840 participants who received at least one dose of BNT162b2 or mRNA-1273 at any time in pregnancy between Jan-Sep, 2021, 2129 met the inclusion criteria (1576 received BNT162b2 and 553 mRNA-1273). The two groups were balanced in terms of baseline characteristics. There were 37 SABs, with an overall 13.4% estimated cumulative risk by 20 weeks of gestation, which is similar to the expected risk in the population. The HR of SAB comparing mRNA-1273 to BNT162b2 was 1.46 (95% CI: 0.66, 3.22). The C-VIPER data show no evidence that mRNA COVID-19 vaccines increase the risk of SAB.

Recommended Adult Immunization Schedule, United States, 2023.

Recommended Adult Immunization Schedule, United States, 2023.

The COVID-19 Vaccines International Pregnancy Exposure Registry (C-VIPER): Protocol and Methodological Considerations.

The advent of the coronavirus disease 2019 (COVID-19) pandemic has led to the development of vaccines against severe acute respiratory syndrome coronavirus 2. Prospective evidence regarding safety for pregnant people and their developing fetuses is lacking. The aim of the COVID-19 Vaccines International Pregnancy Exposure Registry (C-VIPER) is to estimate the relative risk of obstetric, neonatal, and infant outcomes by comparing participants vaccinated against COVID-19 during pregnancy to a reference group of people enrolled in the Pregistry International Pregnancy Exposure Registry (PIPER) who remained unvaccinated during pregnancy. The C-VIPER and the PIPER are international, non-interventional, real-world cohort studies. Participants receiving a COVID-19 vaccine during pregnancy will be matched in the analyses by country and gestational age at enrollment to unvaccinated individuals. Self-enrolled and self-consented participants complete online questionnaires at enrollment, during pregnancy, and for 12 months after the delivery of a live infant. Where possible, outcomes are verified by medical records. The study aims to recruit at least 500 pregnancies for each approved or authorized vaccine and will last for 5 years for each product. By collecting data for each vaccine brand, the C-VIPER will be able to determine individual safety profiles. The study design allows for analysis of the effects of exposure to COVID-19 vaccines during specific etiologically relevant periods of gestation. Although the sample size may be too small to detect associations with rare outcomes, the study will be used to generate hypotheses for future research. Ultimately, the C-VIPER should provide data that will allow pregnant people and their healthcare providers to make informed decisions about COVID-19 vaccination. ClinicalTrials.gov NCT04705116. Registered on 12 January, 2021. EU PAS EUPAS39096. Registered on 20 January, 2021.

Analysis of Circulating C19MC MicroRNA as an Early Marker of Hypertension and Preeclampsia in Pregnant Patients: A Systematic Review.

Preeclampsia and hypertension complicate several pregnancies. Identifying women at risk of developing these conditions is essential to establish potential treatment modalities. Biomarkers such as C19MC microRNA in pregnant patients wopuld assist in defining pregnancy surveillance and implementing interventions. This study sought to analyze circulating C19MC microRNA as an early marker of hypertension and preeclampsia in pregnant patients. A systematic review was undertaken using the following registers: disease registries, pregnancy registries, and pregnancy exposure registries, and the following databases: PubMed, CINAHL, Web of Science, Scopus, and EMBASE. The risk of bias was assessed using the Cochrane technique. From the 45 publications retrieved from the registers and databases, only 21 were included in the review after the removal of duplicates, screening, and eligibility evaluation. All 210 publications had a low risk of bias and illuminated the potential use of circulating C19MC microRNA as an early marker of hypertension and preeclampsia in pregnant patients. Therefore, it was concluded that C19MC microRNA can be used as an early marker of gestational preeclampsia and hypertension.

Monitoring Drug Safety in Pregnancy with Scan Statistics: A Comparison of Two Study Designs.

Traditional surveillance of adverse infant outcomes following maternal medication exposures relies on pregnancy exposure registries, which are often underpowered. We characterize the statistical power of TreeScan, a data mining tool, to identify potential signals in the setting of perinatal medication exposures and infant outcomes. We used empirical data to inform background incidence of major congenital malformations and other birth conditions. Statistical power was calculated using two probability models compatible with TreeScan, Bernoulli and Poisson, while varying the sample size, magnitude of the risk increase, and incidence of a specified outcome. We also simulated larger referent to exposure matching ratios when using the Bernoulli model in the setting of fixed N:1 propensity score matching. Finally, we assessed the impact of outcome misclassification on power. The Poisson model demonstrated greater power to detect signals than the Bernoulli model across all scenarios and suggested a sample size of 4,000 exposed pregnancies is needed to detect a twofold increase in risk of a common outcome (approximately 8 per 1,000) with 85% power. Increasing the fixed matching ratio with the Bernoulli model did not reliably increase power. An outcome definition with high sensitivity is expected to have somewhat greater power to detect signals than an outcome definition with high positive predictive value. Use of the Poisson model with an outcome definition that prioritizes sensitivity may be optimal for signal detection. TreeScan is a viable method for surveillance of adverse infant outcomes following maternal medication use.

S751 The Vedolizumab Pregnancy Exposure Registry: An OTIS Pregnancy Study Update

Introduction: Vedolizumab is a gut-selective immunoglobulin (Ig) G1 monoclonal antibody that binds to α4β7 integrin; it is approved for the treatment of moderately to severely active Crohn’s disease (CD) and ulcerative colitis (UC) in the U.S. and elsewhere. Published studies on the effect of vedolizumab in human pregnancy are limited. Data from the ongoing Vedolizumab Pregnancy Exposure Registry (NCT02678052) in the U.S. and Canada have been collected by the MotherToBaby Pregnancy Studies conducted by the Organization of Teratology Information Specialists (OTIS). This prospective observational pregnancy cohort study planned to enroll and analyze the outcomes of 100 vedolizumab-exposed (Vedo) participants compared to 100 disease-matched (DM) and 100 healthy comparison (HC) participants. Methods: Pregnant women treated with vedolizumab for UC or CD with at least one dose in the first trimester were enrolled in the Vedo group. Pregnant women with UC or CD but no exposure to vedolizumab were enrolled in the DM group. Pregnant women with no exposure to any biologic during pregnancy and not diagnosed with an auto-inflammatory or other exclusionary disease were enrolled in the HC group. Data were collected from telephone interviews and maternal and pediatric medical records; live-born children were followed to one year of age with a dysmorphological examination and developmental screening. The Short Quality of Life in Inflammatory Bowel Disease Questionnaire (SIBDQ) was administered to women with CD or UC. Results: Between December 2015 and March 2022, outcomes were collected for 301 women, 98 in the Vedo group, 104 in the DM group, and 99 in the HC group. SIBDQ mean scores were similar in the Vedo group, 5.8 (SD 1.0) and the DM group, 5.9 (SD 1.0). Preliminary descriptive outcome data are shown in Table. In the Vedo group 7.3% of pregnancies resulted in a fetus or infant with a major birth defect, compared to 7.8% in the DM group, and 4.7% in the HC group. No pattern of major birth defects was identified in the Vedo group. Conclusion: The proportion of pregnancies with vedolizumab exposure resulting in a major birth defect are similar to proportions in the disease comparison group, and did not represent a specific pattern. The Vedolizumab Pregnancy Exposure Registry is ongoing with formal statistical analysis planned once the study is completed in 2023. Table 1. - Pregnancy Outcomes in the Study Cohort Vedo-Total(N=98) DM-Total(N=104) HC-Total(N=99) Pregnancies ending with live born infant - n/N (%) 93/98 (94.9) 99/104 (95.2) 85/99 (85.9) Spontaneous abortion – N (Left Truncation Accounted Rate a ) 3 (8.7%) 3 (6.1%) 1 (6.4%) Termination - n/N (%) 0/98 (0.0) 0/104 (0.0) 0/99 (0.0) Stillbirth - n/N (%) 0/98 (0.0) 1/104 (1.0) 0/99 (0.0) Lost to follow-up (LTFU) - n/N (%) 2/98 (2.0) 1/104 (1.0) 13/99 (13.1) Preterm delivery – N (Rate b ) 13 (14.5%) 6 (6.1%) 6 (7.2%) Birth weight full term infants – mean g (SD) 3410.4 (436.7) 3428.8 (454.0) 3308.1 (432.3) Number of pregnancies with major birth defects among all pregnancies excluding LTFU – n/N’ (%) 7/96 (7.3) 8/103 (7.8) 4/86 (4.7) Serious infections in live born infants up to 1 year of age – n/N’(%) c 3/97 (3.1) 2/99 (2.0) 1/88 (1.1) Ages and Stages Screening at 1 year of age with concern – n/N’ (%) c 10/66 (15.2) 20/87 (23.0) 11/59 (18.6) aSpontaneous abortion rate computed using Fleming-Harrington estimate at 20 weeks' gestation, accounting for left truncation because women can enroll at various times in gestation;bComputed using Fleming-Harrington estimate at 37 weeks' gestation;cIncludes twins; % = (n/N') * 100. N' at each category: Number of pregnancies meeting the criteria specified in the row title.

Novel methods for pregnancy drug safety surveillance in the FDA Sentinel System.

It is a priority of the US Food and Drug Administration (FDA) to monitor the safety of medications used during pregnancy. Pregnancy exposure registries and cohort studies utilizing electronic health record data are primary sources of information but are limited by small sample sizes and limited outcome assessment. TreeScan™, a statistical data mining tool, can be applied within the FDA Sentinel System to simultaneously identify multiple potential adverse neonatal and infant outcomes after maternal medication exposure. We implemented TreeScan using the Sentinel analytic tools in a cohort of linked live birth deliveries and infants nested in the IBM MarketScan® Research Database. As a case study, we compared first trimester fluoroquinolone use and cephalosporin use. We used the Bernoulli and Poisson TreeScan statistics with compatible propensity score-based study designs for confounding control (matching and stratification) and used multiple propensity score models with various strategies for confounding control to inform best practices. We developed a hierarchical outcome tree including major congenital malformations and outcomes of gestational length and birth weight. A total of 1791 fluoroquinolone-exposed and 8739 cephalosporin-exposed mother-infant pairs were eligible for analysis. Both TreeScan analysis methods resulted in single alerts that were deemed to be due to uncontrolled confounding or otherwise not warranting follow-up. In this implementation of TreeScan using Sentinel analytic tools, we did not observe any new safety signals for fluoroquinolone use in the first trimester. TreeScan, with tailored or high-dimensional propensity scores for confounding control, is a valuable tool in addition to current safety surveillance methods for medications used during pregnancy.

Estimating Vaccine Effectiveness by Linking Population-Based Health Registries: Some Sources of Bias.

The COVID-19 pandemic has underscored the importance of observational studies of real-world vaccine effectiveness to help answer urgent public health questions. One approach to rapidly answering questions about real-world vaccine effectiveness relies on linking data from a population-based registry of vaccinations with a population-based registry of health outcomes. Here we consider some potential sources of bias in linked registry studies including: incomplete reporting to the registries; errors in linking individuals between registries; and errors in the assumed population size of the catchment area of the registries. We show that the direction of the bias resulting from one source of error by itself is predictable. However, if multiple sources of error are present, the direction of the bias can be either upward or downward. The biases can be so strong as to make harmful vaccines appear effective. We provide explicit formulas to quantify and adjust for multiple biases in estimates of vaccine effectiveness which could be used in sensitivity analyses. While this work was motivated by COVID-19 vaccine questions, the results are generally applicable to studies that link population-based exposure registries with population-based case registries to estimate relative risks of exposures.

Lipid-Lowering Therapy in Women of Childbearing Age: a Review and Stepwise Clinical Approach.

Women are less often recognized to have cardiovascular disease (CVD) risk and are underrepresented in randomized trials of lipid-lowering therapy. Here, we summarize non-pharmacologic and pharmacologic strategies for lipid-lowering in women of childbearing age, lipid changes during pregnancy and lactation, discuss sex-specific outcomes in currently available literature, and discuss future areas of research. While lifestyle interventions form the backbone of CVD prevention, some women of reproductive age have an indication for pharmacologic lipid-lowering. Sex-based evidence is limited but suggests that both statin and non-statin lipid-lowering agents are beneficial regardless of sex, especially at high cardiovascular risk. Pharmacologic lipid-lowering therapies, both during the pregnancy period and during lactation, have historically been and continue to be limited by safety concerns. This oftentimes limits lipid-lowering options in women of childbearing age. In this review, we summarize lipid-lowering strategies in women of childbearing age and the impact of therapies during pregnancy and lactation. The limited sex-specific data regarding efficacy, adverse events, and cardiovascular outcomes underscore the need for a greater representation of women in randomized controlled trials. More data on lipid-lowering teratogenicity are needed, and through increased clinician awareness and reporting to incidental exposure registries, more data can be harvested.

Cohort profile: the Western Cape Pregnancy Exposure Registry (WCPER)

PurposeThe Western Cape Pregnancy Exposure Registry (PER) was established at two public sector healthcare sentinel sites in the Western Cape province, South Africa, to provide ongoing surveillance of drug exposures...

Pregnancy outcomes in a dimethyl fumarate exposure registry

IntroductionThe delayed-release dimethyl fumarate (DMF) label recommends use during pregnancy only if potential benefit justifies the potential risk. Given limited pregnancy data, United Kingdom (UK) and Ireland are enrolling DMF-exposed pregnant women into an ongoing international registry assessing pregnancy outcomes. Pregnancies end in live birth (62%), abortion (22%), and fetal loss (16%) in general, with similar rates in MS patients.MethodsPregnant women with MS exposed to DMF since the first day of their last menstrual period prior to conception/during pregnancy were included. The UK/Ireland Coordinating Centres liaise directly with patients and HCPs.ResultsAs of April 2019, 263 patients (14 patients from UK/Ireland) were enrolled. Of the 214 pregnancy outcomes (12 UK/Ireland) reported to date, 197(92%) were live births (12 UK/Ireland) and 17(8%) foetal loss. Of infants with known gestational age (n=197), 176(89%) births were full-term (12 UK/Ireland) and 18(9%) premature (<37 weeks). There were 16 spontaneous abortions (1 ectopic pregnancy), and 1 foetal death at ≥28 weeks of gestation. No molar pregnancies or infant or maternal deaths were reported. Seven(4%) infants (1 UK/Ireland) had confirmed birth defects.ConclusionNo safety signal was observed, consistent with MS and general populations. Support: Biogen; disclosures detailed on poster.david.rog@srft.nhs.uk