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Case reports of thrombotic adverse events after vaccination with the Oxford–AstraZeneca COVID-19 vaccine have raised concerns. This retrospective cohort study evaluated the risk for thromboembolic and thrombocytopenia-related events after COVID-19 vaccination with the Oxford–AstraZeneca and Pfizer–BioNTech vaccines in a nationwide cohort of 365 353 Danish frontline personnel. Visual Abstract. AZD1222 and BNT162b2 Vaccines and Thrombosis and Thrombocytopenia.: Case reports of thrombotic adverse events after vaccination with the Oxford–AstraZeneca COVID-19 vaccine have raised concerns. This retrospective cohort study evaluated the risk for thromboembolic and thrombocytopenia-related events after COVID-19 vaccination with the Oxford–AstraZeneca and Pfizer–BioNTech vaccines in a nationwide cohort of 365 353 Danish frontline personnel. Background: In March 2021, several European countries suspended the use of the AZD1222 (Oxford–AstraZeneca) COVID-19 vaccine because of thromboembolic safety concerns. Reports from Norway and Germany subsequently described patients with venous thrombosis and thrombocytopenia within 5 to 16 days of vaccination. Objective: To evaluate the risk for outcomes related to thrombosis and thrombocytopenia after AZD1222 or BNT162b2 (Pfizer–BioNTech) COVID-19 vaccination. Design: Nationwide exploratory retrospective cohort study. Setting: Danish linkable registers on vaccinations, hospitalizations, occupation, and other covariates. Participants: 355 209 Danish frontline personnel designated for priority COVID-19 vaccination followed from 27 December 2020 (the day of the first COVID-19 vaccination in Denmark) to 13 April 2021. Measurements: Study outcomes were cerebral venous sinus thrombosis, splanchnic vein thrombosis, pulmonary embolism, deep venous thrombosis, arterial thrombosis, thrombocytopenia, and death. Cumulative incidences of study outcomes within 28 days of vaccination and unvaccinated risk time were compared using adjusted survival curves resulting in risk differences (RDs) at day 28 after vaccination. Adjustment for birth cohort, sex, calendar period, occupation, comorbid conditions, and prescription drug use was included. Results: Vaccination with AZD1222 versus no vaccination was associated with a significant RD at day 28 for deep venous thrombosis (RD, 8.35 [95% CI, 0.21 to 16.49] per 100 000 vaccinations). The RDs for cerebral venous sinus thrombosis (RD, 1.68 [CI, −0.64 to 4.00] per 100 000 vaccinations) and thrombocytopenia (RD, 2.39 [CI, −1.09 to 5.87] per 100 000 vaccinations) were not significant. No adverse associations were seen for BNT162b2 vaccination. Limitation: No medical record review; surveillance bias. Conclusion: In this exploratory retrospective cohort study among frontline personnel in Denmark, receipt of the AZD1222 vaccine was associated with a small excess risk for deep venous thrombosis. Although the corresponding risks for the more rare and severe thrombotic outcomes (such as cerebral venous sinus thrombosis) were not statistically significantly increased, statistical precision was low, and clinically relevant risks could not be excluded with certainty. There was no statistically significant association of BNT162b2 vaccination with thrombotic or thrombocytopenic events. Primary Funding Source: Lundbeck Foundation. [ABSTRACT FROM AUTHOR]

Background Evidence linking individual-level maternal folic acid supplementation to offspring risk of congenital heart defects is lacking. We investigated whether folic acid supplementation in early pregnancy reduces offspring risk of heart defects in 2 large birth cohort studies. Methods and Results Women recruited in early pregnancy within the DNBC (Danish National Birth Cohort), 1996-2003, and MoBa (Norwegian Mother and Child Cohort Study), 2000-2009, were followed until delivery. Information on periconceptional intake of folic acid and other supplements was linked with information on heart defects from national registers. Among 197 123 births, we identified 2247 individuals with heart defects (114/10 000). Periconceptional (4 weeks before through 8 weeks after conception) use of folic acid plus other supplements (54.8%), folic acid only (12.2%), and non-folic acid supplements (5.0%) were compared with no supplement use (28.0%); the adjusted relative risks of heart defects were 0.99 (95% CI, 0.80-1.22), 1.08 (95% CI , 0.93-1.25), and 1.07 (95% CI , 0.97-1.19), respectively. For initiation of folic acid in the preconception period weeks -4 to -1 (33.7%) and the postconception periods 0 to 4 weeks (15.5%), 5 to 8 weeks (17.8%), and 9 to 12 weeks (4.6%), compared with no or late folic acid intake (29.1%), relative risks of heart defect were 1.11 (95% CI , 1.00-1.25), 1.09 (95% CI , 0.95-1.25), 0.98 (95% CI , 0.86-1.12), and 0.97 (95% CI , 0.78-1.20), respectively. Relative risks of severe defects, conotruncal defects, and septal defects showed similar results. Conclusions Folic acid was not associated with offspring risk of heart defects, including severe defects, conotruncal defects, or septal defects.