COVID-19 vaccination and pregnancy: getting the word outVictoria Male, Senior Lecturer in Reproductive Immunology, Imperial College LondonPregnancy is a risk factor for severe COVID-19, doubling the likelihood that an unvaccinated individual requires intensive care, invasive ventilation, or ECMO. Between March 2020 and December 2021 in the UK, COVID-19 emerged as the leading cause of death during pregnancy: among the 33 women who succumbed to the virus, none had been fully vaccinated (Knight et al, ISBN: 978-1-7392619-4-8). Furthermore, in unvaccinated individuals, SARS-CoV-2 during pregnancy can adversely affect infants, increasing the odds of preterm birth by 1.5-fold and those of stillbirth or neonatal death by approximately 3-fold (Male, Nat Rev Immunol, 2022, 22:277-82).In the face of these concerning statistics, COVID-19 vaccination in pregnancy seems a sensible precaution. Clinical trials and subsequent observational studies demonstrated that COVID-19 vaccination is safe and effective in the general population, but expectant parents naturally have an important additional question: is it safe for my baby?In the clinical trials of the COVID-19 vaccines, pregnancy was an exclusion criterion but nonetheless 102 participants became pregnant during mRNA vaccine trials, with miscarriage rates no different between the vaccinated and control groups. Early observational studies focussed on outcomes at birth which, during the pandemic, have been somewhat better in vaccinated individuals, particularly with respect to outcomes influenced by SARS-CoV2 infection (Prasad, Nat Comms, 2022, 13:2412*). A population-based cohort study published in this issue of BJOG (please add reference) is the latest in a mounting number of observational studies that examine the risk of early pregnancy loss following COVID-19 vaccination, controlling for gestational age and relevant medical and social confounders. This is the first to formally consider termination of pregnancy at the patient’s request as a competing risk, but whether or not this was including in the analysis, the authors found no increased risk of miscarriage associated with COVID-19 vaccination either during or before pregnancy.The evidence is now clear: COVID-19 vaccination is safe in pregnancy, but infection is not. Despite this, COVID-19 booster uptake among those eligible due to pregnancy remains low, peaking at 19% in the 2022-23 booster season. Some people are not aware their pregnancy makes them eligible for a booster and, among those who are, not all are informed of the extensive evidence on the safety and benefits of COVID-19 vaccination in pregnancy. Others believe their primary course of vaccination, or a previous infection, is sufficient to protect them. Although a primary course of vaccination continues to protect against severe disease, evidence on how long protection lasts, particularly in the face of new variants, is not yet available: as time elapses the benefit of a booster is expected to increase. Pertinently, people continue to die of flu during and shortly after pregnancy, despite having been exposed to the virus throughout their lives. In the UK, two women recently died this way: neither had received the recommended flu booster during pregnancy (Knight et al, ISBN: 978-1-7392619-4-8).While ongoing research remains important for confirming the safety of COVID-19 vaccination during pregnancy, it is unlikely that any new study will overturn the wealth of evidence we have already amassed. The challenge now is to get the word out.* For a regularly updated list of studies concerning the safety of COVID-19 vaccination in pregnancy, please see http://bit.ly/pregnancysafety

Objective Assess whether coronavirus disease 2019 (COVID-19) vaccination impacts menstrual bleeding quantity. Design Retrospective cohort Setting Five global regions Populations Vaccinated and unvaccinated regularly cycling individuals using the digital fertility-awareness application “Natural Cycles”. Methods We used prospectively collected menstrual cycle data and multivariable longitudinal Poisson GEE models, multivariable multinomial logistic regression models, and calculated the adjusted difference between vaccination groups. All regression models were adjusted for confounders. Outcome measures Mean number of heavy bleeding days (fewer, no change, more) and changes in bleeding quantity (less, no change, more) at three time points (first dose, second dose, and post-exposure menses). Results We included 9,555 individuals (7,401 vaccinated, 2,154 unvaccinated). About 2/3 of individuals reported no change in the number of heavy bleeding days regardless of vaccination status. After adjusting for confounders, there were no significant differences in the number of heavy bleeding days by vaccination status. A larger proportion of vaccinated individuals experienced an increase in total bleeding quantity (34.5% unvaccinated, 38.4% vaccinated; 4.0% [0.7, 7.2%] adjusted difference). This translates to an estimated 40 additional people per 1,000 normally cycling individuals who experience more total bleeding quantity following the first vaccine dose due to vaccination. Differences resolved in the cycle post-exposure. Conclusion A small increase in the probability of more total bleeding quantity occurs following the first COVID-19 vaccine dose which resolved the cycle post-vaccination cycle. Total number of heavy bleeding days did not differ by vaccination status. Our findings can reassure the public that any changes are small and transie

Objective. Clinicians and regulators are receiving reports of changes to menstrual periods following COVID-19 vaccination. However, it is unclear if the two are biologically linked. If they are, people using hormonal contraception are predicted to be less likely to report a change and spontaneously cycling people vaccinated prior to ovulation more likely. The objective was to test these hypotheses. Design. Retrospective cohort study. Setting. UK. Population. 1273 people who had received at least one dose of a COVID-19 vaccination, have periods or withdrawal bleeds and keep a record of the dates of these. Methods. Participants reported whether they use any hormonal contraception and, for each dose of the vaccine, on which day of their menstrual cycle they were vaccinated and details of how the timing and flow of their next period compared to their normal experience. Main outcome measures. Association between 1. the use of hormonal contraception and reported changes to timing or flow of the next menstrual period, and 2. the timing of vaccination within the menstrual cycle and reported changes to timing or flow of the next menstrual period. Results. The data from this cohort did not support the pre-specified hypotheses that people using hormonal contraception would be less likely to report a change, or that spontaneously cycling people vaccinated prior to ovulation would be more likely to report a change. Conclusions. This study did not detect strong signals supporting the idea that COVID-19 vaccination is linked to menstrual changes in most people. Funding. No specific funding.