An internet-based preconception cohort study in North America and Denmark

ABSTRACT The proposed supplement responds to "COVID19 Vaccination and Menstruation" (NOT-HD-21-035). Clinical trials did not evaluate the influence SARS-CoV-2 vaccine on menstruation and anecdotal reports of menstrual changes after SARS-CoV-2 vaccination have circulated widely on social media, raising concerns about vaccine safety among the public. Pregnancy Study Online (PRESTO) is an NIH-funded prospective cohort study that enrolls women trying to conceive and follows them from preconception through 6 months after delivery (R01HD086742). Eligible female participants are aged 21-45 years, residents of North America, trying to conceive, and not using contraception or fertility treatment. During 6/2013-6/2021, PRESTO has enrolled more than 15,500 female participants. All questionnaires are completed online and data collection continued during the COVID-19 pandemic. In April 2020, we added new questions on COVID-19 infection and stressors related to the pandemic, including changes in lifestyle, behaviors and health care, and in January 2021, we added questions on SARS-CoV-2 vaccination (ever vaccinated, type of vaccine, and date of each shot). Since the study's inception, women have reported baseline data about their typical menstrual characteristics while not using hormones. After enrollment, women are offered a premium membership to Kindara.com, a menstrual charting app, in which they report day-specific menstrual data in real-time. On each bimonthly questionnaire (administered for up to 12 months), women report additional data about their most recent menstrual cycles. We will use the above prospectively-collected data to examine the extent to which SARS-CoV-2 vaccination is associated with changes in menstruation during 6 cycles of follow-up. Specifically, we will evaluate the association between SARS-CoV-2 vaccination and cycle irregularity, cycle length, intensity of bleed, duration of bleed, intermenstrual spotting/bleeding, and pain associated with menses. We will consider various windows of possible effects and identify the duration of any observed changes. We will control for several confounders, including COVID-19-related stressors. Among 1,800 U.S. participants who completed ≥1 follow-up questionnaire after 12/14/2020, we will compare menstrual characteristics between vaccinated and unvaccinated groups; we will also perform a self-matched analysis among 800 vaccinated women (pre- vs. post-vaccination). In the subset of ≥400 women who reported day-specific menstrual data using Kindara, we will characterize vaccine-related changes in menstruation. Our interdisciplinary research team has published extensively on vaccine-related health effects and menstrual characteristics, many of which are based on PRESTO data, and we have the expertise necessary to study these research questions. Given our ongoing prospective data collection throughout the pandemic, our successful recruitment of a large, diverse population of women not using hormones, and our prospective collection of menstrual data, PRESTO is uniquely-positioned to analyze data on vaccination and menstruation and provide essential information to the scientific community and the public on vaccine safety.