Full Terms & Conditions of access and use can be found at https://www.tandfonline.com/action/journalInformation?journalCode=khvi20 Human Vaccines & Immunotherapeutics ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/khvi20 Temporal trends and determinants of COVID-19 vaccine series initiation after recent pregnancy Eszter Török, Tavleen Dhinsa, Sheryll Dimanlig-Cruz, Gillian D. Alton, Ann E. Sprague, Sandra I. Dunn, Prakesh S. Shah, Darine El-Chaâr, Annette K. Regan, Kumanan Wilson, Sarah A. Buchan, Jeffrey C. Kwong, Siri E. Håberg, Christopher A. Gravel, Nannette Okun, Mark C. Walker, Shannon E. MacDonald, Sarah E. Wilson, Jon Barrett & Deshayne B. Fell To cite this article: Eszter Török, Tavleen Dhinsa, Sheryll Dimanlig-Cruz, Gillian D. Alton, Ann E. Sprague, Sandra I. Dunn, Prakesh S. Shah, Darine El-Chaâr, Annette K. Regan, Kumanan Wilson, Sarah A. Buchan, Jeffrey C. Kwong, Siri E. Håberg, Christopher A. Gravel, Nannette Okun, Mark C. Walker, Shannon E. MacDonald, Sarah E. Wilson, Jon Barrett & Deshayne B. Fell (2023) Temporal trends and determinants of COVID-19 vaccine series initiation after recent pregnancy, Human Vaccines & Immunotherapeutics, 19:2, 2215150, DOI: 10.1080/21645515.2023.2215150 To link to this article: https://doi.org/10.1080/21645515.2023.2215150 © 2023 The Author(s). Published with license by Taylor & Francis Group, LLC. View supplementary material Published online: 30 May 2023. Submit your article to this journal Article views: 1172 View related articles View Crossmark data https://www.tandfonline.com/action/journalInformation?journalCode=khvi20 https://www.tandfonline.com/loi/khvi20 https://www.tandfonline.com/action/showCitFormats?doi=10.1080/21645515.2023.2215150 https://doi.org/10.1080/21645515.2023.2215150 https://www.tandfonline.com/doi/suppl/10.1080/21645515.2023.2215150 https://www.tandfonline.com/doi/suppl/10.1080/21645515.2023.2215150 https://www.tandfonline.com/action/authorSubmission?journalCode=khvi20&show=instructions https://www.tandfonline.com/action/authorSubmission?journalCode=khvi20&show=instructions https://www.tandfonline.com/doi/mlt/10.1080/21645515.2023.2215150 https://www.tandfonline.com/doi/mlt/10.1080/21645515.2023.2215150 http://crossmark.crossref.org/dialog/?doi=10.1080/21645515.2023.2215150&domain=pdf&date_stamp=30 May 2023 http://crossmark.crossref.org/dialog/?doi=10.1080/21645515.2023.2215150&domain=pdf&date_stamp=30 May 2023 RESEARCH ARTICLE Temporal trends and determinants of COVID-19 vaccine series initiation after recent pregnancy Eszter Töröka,b, Tavleen Dhinsab, Sheryll Dimanlig-Cruzb,c, Gillian D. Altona,b, Ann E. Spraguea,b, Sandra I. Dunnb,d, Prakesh S. Shahe,f,g,h, Darine El-Chaârc,i,j, Annette K. Regank,l, Kumanan Wilson i,m,n, Sarah A. Buchano,p, Jeffrey C. Kwongo,p,q,r, Siri E. Håbergs, Christopher A. Gravelc,t, Nannette Okunu, Mark C. Walkera,b,c,i,j, Shannon E. MacDonaldv,w,x, Sarah E. Wilsono,p, Jon Barretty, and Deshayne B. Fella,c aChildren’s Hospital of Eastern Ontario (CHEO) Research Institute, Ottawa, ON, Canada; bBetter Outcomes Registry and Network (BORN) Ontario, Ottawa, ON, Canada; cSchool of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, Canada; dSchool of Nursing, University of Ottawa, Ottawa, ON, Canada; eDepartment of Paediatrics, Mount Sinai Hospital, Toronto, ON, Canada; fDepartment of Paediatrics, University of Toronto, Toronto, ON, Canada; gMaternal-infant Care Research Centre, Department of Paediatrics, Mount Sinai Hospital, Toronto, ON, Canada; hInstitute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, ON, Canada; iClinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada; jDepartment of Obstetrics and Gynaecology, University of Ottawa, Ottawa, ON, Canada; kSchool of Nursing and Health Professions, University of San Francisco, San Francisco, CA, USA; lDepartment of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, CA, USA; mDepartment of Medicine, University of Ottawa, Ottawa, ON, Canada; nBruyère Research Institute, Ottawa, ON, Canada; oPublic Health Ontario, Toronto, ON, Canada; pDalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada; qICES, Toronto, ON, Canada; rDepartment of Family and Community Medicine, University of Toronto, Toronto, ON, Canada; sCentre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway; tDepartment of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, QC, Canada; uDepartment of Obstetrics and Gynaecology, University of Toronto, Toronto, ON, Canada; vFaculty of Nursing, University of Alberta, Edmonton, AB, Canada; wSchool of Public Health, University of Alberta, Edmonton, AB, Canada; xDepartment of Paediatrics, University of Calgary, Calgary, AB, Canada; yDepartment of Obstetrics and Gynaecology, McMaster University, Hamilton, ON, Canada ABSTRACT During the rapid deployment of COVID-19 vaccines in 2021, safety concerns may have led some pregnant individuals to postpone vaccination until after giving birth. This study aimed to describe temporal patterns and factors associated with COVID-19 vaccine series initiation after recent pregnancy in Ontario, Canada. Using the provincial birth registry linked with the COVID-19 vaccine database, we identified all individuals who gave birth between January 1 and December 31, 2021, and had not yet been vaccinated by the end of pregnancy, and followed them to June 30, 2022 (follow-up ranged from 6 to 18 months). We used cumulative incidence curves to describe COVID-19 vaccine initiation after pregnancy and assessed associations with sociodemographic, pregnancy-related, and health behavioral factors using Cox proportional hazards regression to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI). Among 137,198 individuals who gave birth in 2021, 87,376 (63.7%) remained unvaccinated at the end of pregnancy; of these, 65.0% initiated COVID-19 vaccination by June 30, 2022. Lower maternal age (<25 vs. 30–34 y aHR: 0.73, 95%CI: 0.70–0.77), smoking during pregnancy (vs. nonsmoking aHR: 0.68, 95%CI: 0.65–0.72), lower neighborhood income (lowest quintile vs. highest aHR: 0.79, 95%CI: 0.76–0.83), higher material deprivation (highest quintile vs. lowest aHR: 0.74, 95%CI: 0.70– 0.79), and exclusive breastfeeding (vs. other feeding aHR: 0.81, 95%CI: 0.79–0.84) were associated with lower likelihood of vaccine initiation. Among unvaccinated individuals who gave birth in 2021, COVID-19 vaccine initiation after pregnancy reached 65% by June 30, 2022, suggesting persistent issues with vaccine hesitancy and/or access to vaccination in this population. ARTICLE HISTORY Received 6 January 2023 Revised 3 May 2023 Accepted 13 May 2023 KEYWORDS COVID-19; COVID-19 vaccination; COVID-19 vaccine series initiation; pregnancy; pregnant; birth Introduction COVID-19 disease during pregnancy is a risk factor for severe maternal illness and adverse birth outcomes;1–7 COVID-19 vaccination has, thus, been recommended for pregnant indivi- duals in many countries.8 Although COVID-19 vaccination during pregnancy has been found to be effective against SARS-CoV-2 infection in pregnant individuals,9,10 has been associated with a lower incidence of SARS-CoV-2 infection in newborns,11–13 and has not been associated with adverse preg- nancy or birth outcomes (e.g., preterm birth, small-for-gesta- tional-age at birth, and stillbirth),14–19 vaccine coverage in the pregnant population in 2021 was lower than in the general population of women of reproductive age in many settings,20,21 including in Ontario, Canada.22 Lower uptake of the COVID-19 vaccine primary series by pregnant people in 2021 may have reflected safety concerns at that time,23–25 poten- tially leading some people to postpone vaccination until after giving birth. Similar to influenza vaccination during pregnancy, COVID-19 vaccine hesitancy among pregnant people is likely influenced by a variety of factors such as low perceived effec- tiveness of the vaccine, lack of confidence in vaccine safety, and misconceptions about the disease or vaccine.26 CONTACT Deshayne B. Fell dfell@cheo.on.ca Centre for Practice Changing Research, Room L1154, 401 Smyth Road, Ottawa, ON K1H 8L1, Canada. Supplemental data for this article can be accessed on the publisher’s website at https://doi.org/10.1080/21645515.2023.2215150. HUMAN VACCINES & IMMUNOTHERAPEUTICS 2023, VOL. 19, NO. 2, 2215150 https://doi.org/10.1080/21645515.2023.2215150 © 2023 The Author(s). Published with license by Taylor & Francis Group, LLC. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent. http://orcid.org/0000-0002-1741-7705 https://doi.org/10.1080/21645515.2023.2215150 http://www.tandfonline.com https://crossmark.crossref.org/dialog/?doi=10.1080/21645515.2023.2215150&domain=pdf&date_stamp=2023-06-24 A survey conducted in the United Kingdom in late 2020 of over 1,500 participants with a current or recent pregnancy found that a higher proportion of individuals was ‘definitely’ or ‘leaning toward’ accepting a future COVID-19 vaccine once no longer pregnant (81.2%), rather than while pregnant (62.1%).24 Thus, some individuals who were reluctant to get vaccinated against COVID-19 during pregnancy, may have been more willing to get vaccinated after giving birth. The objectives of this study, therefore, were to describe COVID- 19 vaccine series initiation after pregnancy and to assess socio- demographic, pregnancy-related, and health behavioral deter- minants of COVID-19 vaccine series initiation after pregnancy in a population-based study of people who gave birth in 2021 and remained unvaccinated against COVID-19 by the time of delivery. Methods Study design, setting, and data sources We conducted this population-based retrospective cohort study in Ontario, Canada’s most populous province with approxi- mately 140,000 births each year27 and a publicly funded health- care system. The COVID-19 vaccination program in Ontario began in December 14, 2020. Initially, pregnant individuals could only access COVID-19 vaccines if they were part of an early eligibility group (e.g., healthcare workers); however, preg- nancy became prioritized in the vaccination program on April 23, 2021, as a high-risk population for COVID-19 complications.28 From May 18, 2021, all individuals over 18 y of age became eligible for COVID-19 vaccination.29 We used data from the Better Outcomes Registry & Network (BORN)30—Ontario’s birth registry – to identify the study population. BORN Ontario receives pregnancy and birth information from all hospitals with birthing units, all midwif- ery practice groups, birth centers, and prenatal screening laboratories in the province. The registry collects data on maternal demographics, health behaviors, preexisting medical health conditions, obstetric complications, pregnancy history, and birth outcomes. The registry data have been shown to be of high quality in validation studies.30,31 Using unique health card numbers, birth registry records during the study period were deterministically linked with the provincial COVID-19 immunization database, COVaxON, which contains immuni- zation records for all COVID-19 vaccines administered in the province. Maternal residential postal code was used to link the study population to Statistics Canada’s 2016 Census to obtain information on rural/urban residence and neighborhood income, and to the Ontario Marginalization Index, which provides four area-based measures reflecting social and eco- nomic marginalization.32 Additional details on data sources are provided in Table S1. Study population The source population included all Ontario residents who gave birth in the province between January 1 and December 31, 2021 (i.e., the first year of the province’s COVID-19 vaccina- tion program). We excluded individuals who had a surgical or medical termination of pregnancy, or had a documented gesta- tional age <20 weeks’ and birth weight <500 grams, because these events are not systematically captured in the birth reg- istry. We then excluded individuals who had already received one or more doses of COVID-19 vaccine before or during pregnancy (up to and including the date of delivery). To assess the determinants of COVID-19 vaccine series initiation after pregnancy, we further restricted the study population to indi- viduals who gave birth on or after May 1, 2021, when COVID- 19 vaccines were widely available to the general population of adults in Ontario.29 Measures The study outcome was COVID-19 vaccine series initiation after pregnancy, defined as receiving at least one dose of COVID-19 vaccine from 1 d after the date of delivery until the end of follow-up on June 30, 2022; follow-up time ranged from 6 to 18 months depending on calendar month of delivery (i.e., all individuals had a minimum of 6 months of follow-up after delivery). The following variables were evaluated as potential deter- minants of COVID-19 vaccine series initiation after preg- nancy: maternal age at delivery (<25, 25–29, 30–34, 35–39, ≥40 y); month of delivery; parity; multiple birth; preexisting maternal health conditions (composite of asthma, chronic hypertension, diabetes, heart disease, thyroid disease); exclu- sive breastfeeding at discharge from hospital/birth center after delivery (yes/no); healthcare provider at delivery (mid- wife, registered nurse or clinical nurse specialist/nurse prac- titioner, family physician, obstetrician, other, unattended); self-reported maternal smoking or substance use during pregnancy (yes/no); pregnancy complications (composite of gestational hypertension, eclampsia, pre-eclampsia, gesta- tional diabetes, pulmonary embolism); preterm birth (deliv- ery at <37 weeks’ gestation; yes/no); pre-pregnancy body mass index (kilograms/meter2 [kg/m2]); provincial public health unit region (seven geographic regions); rural/urban residence; neighborhood-level income quintiles; and neigh- borhood-level marginalization quintiles (four dimensions: residential instability, material deprivation, dependency, eth- nic concentration).32 Additional details on variables are available in Table S1. Statistical analysis Follow-up time began 1 d after the date of delivery and con- tinued until either the date that dose 1 was received or until follow-up ended on June 30, 2022. We first plotted descriptive cumulative incidence curves displaying time-to-COVID-19 vaccine series initiation by 6 months (24 weeks), 12 months (48 weeks), and by the end of follow-up, overall and stratified by calendar month of delivery. Plots were also stratified by maternal age group (<30 vs. ≥30 y) and newborn feeding status at discharge from hospital/birth center. Among the subgroup of individuals who gave birth between May 1 and December 31, 2021, when COVID-19 vaccines were widely available,29 we calculated unadjusted incidence rates of COVID-19 vaccine series initiation per 2 E. TÖRÖK ET AL. 1,000 person-days of follow-up by sociodemographic, preg- nancy-related, and health behavioral factors. Cox propor- tional hazards regression was used to assess associations between these factors with COVID-19 vaccine series initia- tion after pregnancy; we computed unadjusted hazard ratios (HR) and 95% confidence intervals (CI) as well as hazard ratios adjusted for a core set of important sociodemographic variables: maternal age, neighborhood income quintile, rural residence, and public health unit region. We assessed the proportional hazards assumptions by examining Schoenfeld residual plots and Wald tests for interaction between the variables in each multivariable model and time. In a subgroup analysis, we explored whether there was any modification of associations by calendar time by stratifying according to timing of delivery (i.e., from May 1 to August 31, 2021, and from September 1 to December 31, 2021). In a sensitivity analysis, we also specifically explored COVID- 19 vaccine series initiation during the first 6 months after pregnancy descriptively (through cumulative incidence plots and a Lexis diagram) and by repeating the analyses of deter- minants of series initiation, limited to 6 months of follow-up after pregnancy. Multiple imputation was used to address variables with missing values using a fully conditional specification to gen- erate five multiple-imputation datasets using the ‘MI’ proce- dure (SAS Version 9.4, SAS Institute Inc, Cary, NC). The crude and imputed frequencies of baseline characteristics for vari- ables with missing information are shown in Table S2. We used SAS Version 9.4 (SAS Institute Inc, Cary, NC) for data imputation and all analyses and R 4.2.0 and RStudio 2022.02.1 (RStudio Boston, MA) for cumulative incidence curves and the Lexis diagram. The study was approved by the Children’s Hospital of Eastern Ontario (CHEO) Research Ethics Board (REB protocol number 21/05PE). Results Study population Among 137,198 individuals who gave birth between January 1 and December 31, 2021, 49,822 (36.3%) had already received one or more doses of COVID-19 vaccine before or during pregnancy, leaving a study population of 87,376 unvaccinated individuals (Figure 1). The monthly percentage of individuals who remained unvaccinated at the time of delivery decreased from 99.9% in January 2021 to 36.1% in December 2021 (Table S3). In addition to the decreasing number of individuals remaining unvaccinated at the time of delivery each month, the distribution of sociodemographic characteristics of these individuals also changed over time – compared to January 2021, a higher proportion of those who gave birth in December 2021 was under 25 y of age and living in neighbor- hoods with lower household incomes and higher material depri- vation (Figure S1). Between January and December 2021, there were also small increases in the proportion of individuals who smoked during pregnancy, had a BMI ≥30 kg/m2, or resided in a rural setting, while the proportion of individuals with a preexisting medical condition or who were exclusively breastfeeding their newborn at the time of discharge from hospital/birth center after delivery decreased slightly (Figure S1). Temporal trends in COVID-19 vaccine series initiation after pregnancy Overall, the cumulative incidence of COVID-19 vaccine series initiation after pregnancy increased most rapidly in the first several months after delivery, reaching 56.3% by 6 months (24 weeks) and 65.0% by the end of follow-up (Figure 2 and Table S4). When stratified by month of delivery, 6-month cumula- tive incidences of series initiation ranged from a low of 26.0% among individuals who gave birth in December 2021 to a high of 69.6% among those who gave birth in April 2021 (Figure 3 and Table S4). Among individuals who had a minimum of 12 months of follow-up (i.e., those who gave birth in January through June 2021), 12-month cumulative incidences of COVID-19 series initiation ranged from a low of 59.5% among individuals who gave birth in July 2021 to a high of 77.1% among those who gave birth in March 2021 (Figure 3; Table S4). Overall COVID-19 vaccine series initiation by 6 months after pregnancy was higher among those 30 y of age and older at delivery (60.2%) compared with those under 30 y of age (49.5%), and while this was a consistent pattern in each calendar month of delivery, the absolute differences between age groups decreased over time (Figure S2 and Table S5). The 6-month cumulative incidence of series initiation did not differ appreciably according to newborn feeding status at the time of discharge from hospital/birth center (55.1% among those who were exclusively breastfeeding; 57.2% among those who were using other methods for newborn feeding; Figure S3 and Table S5) and did not demonstrate any clear temporal patterns. Determinants of COVID-19 vaccine series initiation after pregnancy Among 44,986 individuals who gave birth between May 1 and December 31, 2021, the crude incidence rates of COVID-19 vaccine series initiation after pregnancy were lower in the lowest (<25 y of age: 2.2 per 1,000 person-days) and highest (≥40 y: 2.6 per 1,000 person-days) maternal age groups, com- pared with those 30–34 y of age (3.4 per 1,000 person-days). Even after adjustment for neighborhood income quintile, rural residence, and region of residence, COVID-19 vaccine series initiation was significantly lower in these age groups relative to those 30–34 y of age (<25 vs. 30–34 y aHR: 0.73, 95% CI: 0.70–0.77; ≥40 vs. 30–34 y aHR: 0.79, 95% CI: 0.74– 0.84) (Table 1). Vaccine series initiation was also significantly lower in each month of delivery, relative to the month of May 2021, and decreased monotonically from June until December. Compared with nonsmokers, those who smoked during pregnancy had lower likelihood of initiating vaccina- tion (smoking vs. nonsmoking aHR: 0.68, 95% CI: 0.65–0.72); a similar pattern was observed for substance use during pregnancy (vs. nonuse aHR: 0.67, 95% CI: 0.63–0.71). Other HUMAN VACCINES & IMMUNOTHERAPEUTICS 3 factors associated with a lower likelihood of COVID-19 vac- cine series initiation after delivery included rural residence (vs. urban aHR: 0.72, 95% CI: 0.69–0.74), lower neighbor- hood income (lowest quintile vs. highest aHR: 0.79, 95% CI: 0.76–0.83), higher neighborhood material deprivation (high- est quintile vs. lowest aHR: 0.74, 95% CI: 0.70–0.79), higher neighborhood social dependency (highest quintile vs. lowest aHR: 0.89, 95% CI: 0.85–0.93), and exclusive breastfeeding at time of hospital discharge (vs. other type of newborn feeding aHR: 0.81, 95% CI: 0.79–0.84). Having a preexisting chronic medical condition was associated with a higher likelihood of vaccine series initiation after pregnancy (vs. no condition aHR: 1.09, 95% CI: 1.05–1.14), as was having pregnancy complications (vs. no complication aHR: 1.18, 95% CI: 1.14–1.22) and residing in a neighborhood with the highest ethnic concentration (highest quintile vs. lowest aHR: 1.30, 95% CI: 1.24–1.37). Subgroup and sensitivity analyses Following stratification by time period of delivery, we gener- ally observed the same patterns of associations with COVID- 19 vaccine series initiation, with respect to both direction and magnitude of the hazards ratios (Table S6). However, the likelihood of COVID-19 vaccine series initiation among those ≥40 y of age compared with those 30–34 y of age was qualitatively lower between September and December 2021 (aHR: 0.69, 95% CI: 0.62–0.78) than between May and August 2021 (aHR: 0.84, 95% CI: 0.78–0.91). Conversely, COVID-19 vaccine series initiation was higher among those Figure 1. Study flow diagram. 4 E. TÖRÖK ET AL. living in neighborhoods with the highest ethnic concentration compared with the lowest ethnic concentration between September and December 2021 (aHR: 1.47, 95% CI: 1.34– 1.62) than between May and August 2021 (aHR: 1.22, 95% CI: 1.14–1.29). When we restricted the follow-up period to only the first 6 months after pregnancy, there were no changes in direction or magnitude of the results (Table S7). As can be seen in the Lexis diagram (Figure S4), there were no clear temporal patterns in series initiation in the first 6 months after pregnancy with respect to time since the delivery; the most intense calendar period of COVID-19 vaccine series initiation occurred from May to June 2021, corresponding to when COVID-19 vaccines became widely available to the gen- eral adult population in the province. Discussion In this population-wide study of 87,376 individuals who gave birth in 2021 and were not yet vaccinated by the end of their pregnancy, the cumulative incidence of COVID-19 vaccine series initiation after delivery reached 65.0% by the end of June 2022. Series initiation after pregnancy by June 30, 2022, was highest among those who gave birth in the first 4 months of 2021; nevertheless, it was still considerably lower among these individuals than in the general population of women of reproductive age in Ontario (92% coverage by early July 202233), despite having had 15–18 months to initiate vac- cination by the end of the study period. Factors associated with lower likelihood of COVID-19 vaccine series initiation after pregnancy included younger and older maternal age, smoking and substance use during pregnancy, rural residence, lower neighborhood income, higher material deprivation and social dependency, and exclusive breastfeeding at the time of dis- charge from hospital/birth center. Individuals with a family doctor-attended or midwife-attended delivery (vs. obstetri- cian) also had lower likelihood of initiating their COVID-19 vaccine series after giving birth. In contrast, having a preexisting chronic medical condition, having complications during pregnancy, and residing in a neighborhood with the highest ethnic concentration were associated with a higher likelihood of vaccine series initiation after pregnancy. There are few studies that have specifically assessed COVID-19 vaccine uptake among postpartum individuals – consistent with our findings, a few small studies from the U.S. have demonstrated that lower COVID-19 vaccine uptake among pregnant and postpartum individuals was associated with a number of sociodemographic characteristics, including younger age, lower education, reported substance use, and higher parity.34,35 Similar patterns of association have also been observed in studies assessing COVID-19 vaccine cover- age during pregnancy.20,22,25,36,37 Some of the sociodemo- graphic subgroups in which vaccine initiation after delivery was lowest in our study (e.g., rural residence, lower neighbor- hood income, and higher neighborhood material deprivation) may reflect individuals who have less access to health services during pregnancy, even within the context of a publicly funded healthcare system.38 Healthcare providers play a critical role in enhancing vaccination rates in the obstetric population both by providing access to vaccination, as well as by providing information and education to their patients about safety and effectiveness of vaccination during pregnancy.39,40 Figure 2. Cumulative incidence plot of time-to-COVID-19 vaccine series initiation after pregnancy among individuals who gave birth between January 1 and December 31, 2021 a,b. a Dashed line displays COVID-19 vaccine series initiation by 6 months (24 weeks). b Dash-dotted line displays COVID-19 vaccine series initiation by 12 months (48 weeks). HUMAN VACCINES & IMMUNOTHERAPEUTICS 5 A U.S. survey of pregnant and postpartum individuals related to vaccination status 3–6 months after an initial baseline assessment of intention to receive COVID-19 vaccination showed hesitancy at baseline was associated with persistent hesitancy at follow-up; only a few individuals who reported hesitancy at baseline were later vaccinated.41 In addition, sur- veys, conducted in more than 15 countries, of pregnant and postpartum individuals about perceptions and attitudes toward COVID-19 vaccination found that barriers to accessing healthcare services, negative attitudes toward other vaccina- tions routinely recommended during pregnancy, and lack of information and concerns about side effects of the vaccine for themselves or their baby – especially in this context of a newly developed vaccine – were associated with a lower likelihood of getting vaccinated against COVID-19.23–34,41–43 These factors, combined with the prominence of misinformation about COVID-19 vaccination and adverse effects on fertility, preg- nancy outcomes, and breastfeeding44,45 as well as concerns Figure 3. Cumulative incidence plots of time-to-COVID-19 vaccine series initiation after pregnancy, by calendar month of deliverya,b. a Dashed line displays COVID-19 vaccine series initiation by 6 months (24 weeks). b Dash-dotted line displays COVID-19 vaccine series initiation by 12 months (48 weeks). 6 E. TÖRÖK ET AL. Ta bl e 1. C O VI D -1 9 va cc in e se rie s in iti at io n af te r pr eg na nc y am on g in di vi du al s w ho g av e bi rt h be tw ee n M ay 1 a nd D ec em be r 31 , 2 02 1, a nd h ad n ot y et b ee n va cc in at ed b y th e en d of p re gn an cy a . Ch ar ac te ris tic Al l Re ce iv ed ≥ 1 do se o f C O VI D -1 9 va cc in e af te r pr eg na nc ya N n = 4 4, 98 6 % b N um be r va cc in at ed b y Ju ne 3 0, 2 02 2 n = 2 4, 14 1 In ci de nc e ra te o f v ac ci na tio n pe r 10 00 p er so n- da ys U na dj us te d ha za rd r at io (9 5% C I) Ad ju st ed h az ar d ra tio c (9 5% C I) M at er na l a ge (y ea rs ) < 25 5, 41 9 12 .0 2, 43 6 2. 2 0. 69 (0 .6 6 to 0 .7 2) 0. 73 (0 .7 0 to 0 .7 7) 25 –2 9 12 ,4 98 27 .8 6, 65 1 3. 0 0. 89 (0 .8 7 to 0 .9 2) 0. 92 (0 .8 9 to 0 .9 5) 30 –3 4 16 ,2 29 36 .1 9, 17 3 3. 4 1. 00 1. 00 35 –3 9 8, 69 6 19 .3 4, 83 5 3. 3 0. 97 (0 .9 3 to 1 .0 0) 0. 96 (0 .9 2 to 0 .9 9) ≥ 40 2, 14 4 4. 8 1, 04 6 2. 6 0. 79 (0 .7 5 to 0 .8 5) 0. 79 (0 .7 4 to 0 .8 4) M on th o f d el iv er y M ay 2 02 1 7, 43 9 16 .5 5, 09 5 3. 7 1. 00 1. 00 Ju ne 2 02 1 6, 69 8 14 .9 4, 17 1 3. 2 0. 86 (0 .8 3 to 0 .9 0) 0. 87 (0 .8 3 to 0 .9 0) Ju ly 2 02 1 6, 33 5 14 .1 3, 77 1 3. 2 0. 84 (0 .8 0 to 0 .8 8) 0. 84 (0 .8 1 to 0 .8 8) Au gu st 2 02 1 6, 11 7 13 .6 3, 47 5 3. 3 0. 82 (0 .7 8 to 0 .8 5) 0. 82 (0 .7 9 to 0 .8 6) Se pt em be r 20 21 5, 49 6 12 .2 2, 85 8 3. 1 0. 74 (0 .7 1 to 0 .7 8) 0. 75 (0 .7 2 to 0 .7 8) O ct ob er 2 02 1 4, 91 7 10 .9 2, 22 7 2. 7 0. 62 (0 .5 9 to 0 .6 5) 0. 62 (0 .5 9 to 0 .6 5) N ov em be r 20 21 4, 19 3 9. 3 1, 52 8 2. 2 0. 47 (0 .4 5 to 0 .5 0) 0. 48 (0 .4 5 to 0 .5 0) D ec em be r 20 21 3, 79 1 8. 4 1, 01 6 1. 7 0. 34 (0 .3 2 to 0 .3 6) 0. 34 (0 .3 2 to 0 .3 6) Pa rit y 0 (n ul lip ar ou s) 18 ,5 98 41 .3 10 ,6 30 3. 4 1. 03 (1 .0 1 to 1 .0 7) 1. 07 (1 .0 4 to 1 .1 0) 1 (p rim ip ar ou s) 14 ,7 80 32 .9 8, 27 3 3. 3 1. 00 1. 00 ≥ 2 (m ul tip ar ou s) 11 ,6 08 25 .8 5, 23 8 2. 3 0. 72 (0 .6 9 to 0 .7 4) 0. 71 (0 .6 9 to 0 .7 4) M ul tip le b irt h N o 44 ,3 07 98 .5 23 ,7 73 3. 0 1. 00 1. 00 Ye s 67 9 1. 5 36 8 3. 1 1. 02 (0 .9 2 to 1 .1 3) 1. 01 (0 .9 1 to 1 .1 2) An y pr ee xi st in g m at er na l m ed ic al c on di tio nd N o 40 ,4 63 89 .9 21 ,5 60 3. 0 1. 00 1. 00 Ye s 4, 52 3 10 .1 2, 58 1 3. 4 1. 11 (1 .0 7 to 1 .1 6) 1. 09 (1 .0 5 to 1 .1 4) Ex cl us iv e br ea st fe ed in g fr om b irt h to d is ch ar ge fr om h os pi ta l o r bi rt h ce nt er e N o 22 ,2 91 49 .6 12 ,9 44 3. 5 1. 00 1. 00 Ye s 22 ,6 95 50 .4 11 ,1 97 2. 6 0. 80 (0 .7 8 to 0 .8 3) 0. 81 (0 .7 9 to 0 .8 4) H ea lth ca re p ro vi de r w ho c au gh t/ de liv er ed b ab y M id w ife 5, 72 8 12 .7 2, 34 4 2. 0 0. 65 (0 .6 2 to 0 .6 8) 0. 67 (0 .6 4 to 0 .7 0) Re gi st er ed N ur se o r CN S/ N P 39 2 0. 9 19 7 2. 7 0. 85 (0 .7 4 to 0 .9 8) 0. 88 (0 .7 7 to 1 .0 2) Fa m ily P hy si ci an 2, 57 9 5. 7 1, 27 1 2. 6 0. 83 (0 .7 8 to 0 .8 7) 0. 87 (0 .8 2 to 0 .9 2) O bs te tr ic ia n 32 ,4 82 72 .2 18 ,2 98 3. 3 1. 00 1. 00 O th er 3, 61 8 8. 0 1, 96 8 3. 1 0. 95 (0 .9 1 to 1 .0 0) 0. 99 (0 .9 4 to 1 .0 4) U na tt en de d (N on e) 18 7 0. 4 63 1. 4 0. 49 (0 .3 8 to 0 .6 3) 0. 52 (0 .4 0 to 0 .6 6) Sm ok ed d ur in g pr eg na nc y N o 40 ,8 94 90 .9 22 ,4 54 3. 2 1. 00 1. 00 Ye s 4, 09 2 9. 1 1, 68 7 1. 9 0. 65 (0 .6 2 to 0 .6 8) 0. 68 (0 .6 5 to 0 .7 2) Su bs ta nc e us e du rin g pr eg na nc yf N o 41 ,8 44 93 .0 22 ,8 86 3. 1 1. 00 1. 00 Ye s 3, 14 2 7. 0 1, 25 5 1. 9 0. 64 (0 .6 0 to 0 .6 7) 0. 67 (0 .6 3 to 0 .7 1) Pr eg na nc y co m pl ic at io ns g N o 38 ,6 26 85 .9 20 ,3 47 2. 9 1. 00 1. 00 Ye s 6, 36 0 14 .1 3, 79 4 3. 7 1. 20 (1 .1 6 to 1 .2 4) 1. 18 (1 .1 4 to 1 .2 2) Pr et er m b irt h N o (≥ 37 w ee ks ) 41 ,6 75 92 .6 22 ,4 41 3. 1 1. 00 1. 00 Ye s (< 37 W ee ks ) 3, 31 1 7. 4 1, 70 0 2. 8 0. 93 (0 .8 9 to 0 .9 8) 0. 93 (0 .8 8 to 0 .9 8) M at er na l B M I ( kg /m 2 ) ≥ 30 .0 9, 65 4 21 .5 5, 25 8 3. 1 1. 02 (0 .9 9 to 1 .0 5) 1. 04 (1 .0 0 to 1 .0 7) < 30 .0 35 ,3 32 78 .5 18 ,8 83 3. 0 1. 00 1. 00 (C on tin ue d) HUMAN VACCINES & IMMUNOTHERAPEUTICS 7 Ta bl e 1. (C on tin ue d) . Ch ar ac te ris tic Al l Re ce iv ed ≥ 1 do se o f C O VI D -1 9 va cc in e af te r pr eg na nc ya N n = 4 4, 98 6 % b N um be r va cc in at ed b y Ju ne 3 0, 2 02 2 n = 2 4, 14 1 In ci de nc e ra te o f v ac ci na tio n pe r 10 00 p er so n- da ys U na dj us te d ha za rd r at io (9 5% C I) Ad ju st ed h az ar d ra tio c (9 5% C I) N ei gh bo rh oo d m ed ia n fa m ily in co m e qu in til es 1 (L ow es t) 10 ,8 85 24 .2 5, 44 1 2. 7 0. 81 (0 .7 8 to 0 .8 5) 0. 79 (0 .7 6 to 0 .8 3) 2 9, 65 6 21 .5 5, 10 9 2. 9 0. 89 (0 .8 6 to 0 .9 3) 0. 88 (0 .8 5 to 0 .9 2) 3 9, 60 6 21 .4 5, 27 6 3. 2 0. 96 (0 .9 2 to 1 .0 0) 0. 94 (0 .9 0 to 0 .9 8) 4 8, 63 7 19 .2 4, 85 8 3. 3 1. 00 (0 .9 6 to 1 .0 5) 0. 99 (0 .9 5 to 1 .0 4) 5 (H ig he st ) 6, 20 2 13 .8 3, 45 7 3. 3 1. 00 1. 00 Ru ra l r es id en ce N o 37 ,6 63 83 .7 20 ,9 17 3. 2 1. 00 1. 00 Ye s 7, 32 3 16 .3 3, 22 4 2. 2 0. 73 (0 .7 0 to 0 .7 6) 0. 72 (0 .6 9 to 0 .7 4) PH U r eg io n of r es id en ce So ut h W es t 6, 50 3 14 .5 3, 16 9 2. 6 0. 90 (0 .8 6 to 0 .9 4) 0. 97 (0 .9 2 to 1 .0 2) Ce nt ra l W es t 9, 82 7 21 .8 5, 25 1 3. 0 1. 02 (0 .9 8 to 1 .0 7) 1. 03 (0 .9 9 to 1 .0 7) Ce nt ra l E as t 13 ,1 26 29 .2 7, 53 4 3. 4 1. 13 (1 .0 8 to 1 .1 7) 1. 09 (1 .0 5 to 1 .1 3) G re at er T or on to A re a 7, 73 6 17 .2 4, 11 0 3. 0 1. 00 1. 00 Ea st er n 5, 21 0 11 .6 2, 73 3 2. 9 1. 00 (0 .9 5 to 1 .0 5) 1. 04 (0 .9 9 to 1 .0 9) N or th W es t 81 0 1. 8 46 2 3. 3 1. 12 (1 .0 1 to 1 .2 3) 1. 25 (1 .1 4 to 1 .3 8) N or th E as t 1, 77 4 3. 9 88 2 2. 7 0. 91 (0 .8 5 to 0 .9 8) 1. 03 (0 .9 6 to 1 .1 2) M ar gi na liz at io n in di ce sh Re si de nt ia l i ns ta bi lit y qu in til e 1 (le as t un st ab le ) 8, 90 7 19 .8 4, 96 8 3. 3 1. 00 1. 00 2 8, 38 7 18 .6 4, 65 2 3. 2 0. 99 (0 .9 5 to 1 .0 3) 1. 03 (0 .9 9 to 1 .0 7) 3 8, 64 0 19 .2 4, 61 1 3. 0 0. 93 (0 .9 0 to 0 .9 7) 0. 98 (0 .9 4 to 1 .0 2) 4 8, 51 6 18 .9 4, 39 9 2. 9 0. 89 (0 .8 5 to 0 .9 3) 0. 96 (0 .9 2 to 1 .0 1) 5 (m os t un st ab le ) 10 ,5 36 23 .4 5, 51 1 2. 9 0. 90 (0 .8 6 to 0 .9 3) 1. 01 (0 .9 6 to 1 .0 6) M at er ia l d ep riv at io n qu in til e 1 (le as t de pr iv ed ) 8, 08 6 18 .0 4, 74 6 3. 6 1. 00 1. 00 2 8, 34 8 18 .6 4, 65 2 3. 3 0. 91 (0 .8 7 to 0 .9 5) 0. 91 (0 .8 7 to 0 .9 5) 3 8, 43 4 18 .7 4, 58 3 3. 1 0. 87 (0 .8 4 to 0 .9 1) 0. 88 (0 .8 4 to 0 .9 2) 4 8, 88 2 19 .7 4, 65 4 2. 9 0. 82 (0 .7 8 to 0 .8 5) 0. 82 (0 .7 8 to 0 .8 6) 5 (m os t de pr iv ed ) 11 ,2 36 25 .0 5, 50 6 2. 6 0. 73 (0 .7 0 to 0 .7 6) 0. 74 (0 .7 0 to 0 .7 9) D ep en de nc y qu in til e 1 (le as t de pe nd en t) 13 ,9 74 31 .1 8, 08 2 3. 5 1. 00 1. 00 2 9, 36 4 20 .8 5, 01 0 3. 0 0. 89 (0 .8 6 to 0 .9 2) 0. 94 (0 .9 0 to 0 .9 7) 3 7, 71 7 17 .2 3, 96 9 2. 8 0. 84 (0 .8 1 to 0 .8 7) 0. 90 (0 .8 6 to 0 .9 3) 4 7, 24 7 16 .1 3, 79 5 2. 9 0. 86 (0 .8 3 to 0 .9 0) 0. 93 (0 .8 9 to 0 .9 7) 5 (m os t de pe nd en t) 6, 68 4 14 .9 3, 28 5 2. 7 0. 80 (0 .7 7 to 0 .8 4) 0. 89 (0 .8 5 to 0 .9 3) Et hn ic c on ce nt ra tio n qu in til e 1 (lo w es t co nc en tr at io n) 7, 00 3 15 .6 3, 28 6 2. 5 1. 00 1. 00 2 7, 32 9 16 .3 3, 67 4 2. 7 1. 10 (1 .0 5 to 1 .1 6) 1. 04 (0 .9 9 to 1 .0 9) 3 7, 46 9 16 .6 3, 91 7 2. 9 1. 18 (1 .1 2 to 1 .2 4) 1. 08 (1 .0 2 to 1 .1 3) 4 9, 24 9 20 .6 5, 03 8 3. 1 1. 23 (1 .1 8 to 1 .2 9) 1. 11 (1 .0 6 to 1 .1 7) 5 (h ig he st c on ce nt ra tio n) 13 ,9 36 31 .0 8, 22 6 3. 5 1. 35 (1 .3 0 to 1 .4 1) 1. 30 (1 .2 4 to 1 .3 7) Ab br ev ia tio ns : B M I, bo dy m as s in de x; P H U , p ub lic h ea lth u ni t. a Fo llo w -u p pe rio d ex te nd ed fr om t he d ay o f d el iv er y un til J un e 30 , 2 02 2. b Co lu m n pe rc en ta ge s. c M od el s w er e ad ju st ed fo r m at er na l a ge a t de liv er y, n ei gh bo rh oo d in co m e qu in til e, r ur al r es id en ce , a nd p ub lic h ea lth u ni t re gi on . d Co m po si te o f a st hm a, c hr on ic h yp er te ns io n, d ia be te s, h ea rt d is ea se , t hy ro id d is ea se . e Ex cl us iv e br ea st fe ed in g vs . o th er m et ho ds o f ne w bo rn f ee di ng f ro m b irt h to d is ch ar ge f ro m h os pi ta l o r bi rt h ce nt er . O th er m et ho ds o f fe ed in g co m pr is ed : b re as t m ilk s ub st itu te ( fo rm ul a on ly ), br ea st m ilk s ub st itu te ( ot he r) , co m bi na tio n of b re as tm ilk a nd b re as tm ilk s ub st itu te , a nd u nk no w n fe ed in g pr ac tic es . f Se lf- re po rt ed c an na bi s, o pi oi d, o r al co ho l u se d ur in g pr eg na nc y. g Co m po si te o f g es ta tio na l h yp er te ns io n, e cl am ps ia , p re -e cl am ps ia , g es ta tio na l d ia be te s, a nd p ul m on ar y em bo lis m . h O nt ar io M ar gi na liz at io n In de x in cl ud ed n ei gh bo rh oo d- le ve l q ui nt ile s fo r r es id en tia l i ns ta bi lit y (fa m ily o r h ou si ng in st ab ili ty ), m at er ia l d ep riv at io n (in ab ili ty to a tt ai n ba si c m at er ia l n ee ds ), de pe nd en cy (r ec ei pt o f i nc om e su pp or t) , an d et hn ic c on ce nt ra tio n (g eo gr ap hi c ar ea s w ith h ig h co nc en tr at io ns o f r ec en t im m ig ra nt s an d/ or ‘v is ib le m in or iti es ;’ se e Ta bl e S1 fo r de ta ils . 8 E. TÖRÖK ET AL. about transitory changes in the menstrual cycle following COVID-19 vaccination46, may have contributed to the lower vaccination rates in this population. An additional important consideration in the postpartum population that may impact willingness to become vaccinated is breastfeeding. The World Health Organization and other pediatric associations recom- mend exclusive breastfeeding for the first 6 months of life.47,48 Although breastfeeding people might be more willing to get vaccinated against COVID-19 than pregnant people,49 there could be some reluctance to initiate vaccination while still breastfeeding if there are perceived safety concerns,24,45,50 despite recommendations for lactating individuals to get vaccinated.8 It has been suggested that immunization should become a part of routine obstetrical care to increase vaccine confidence and uptake and decrease misinformation.39,40 One small study conducted at a single hospital in mid-2021 explored willing- ness of obstetric patients admitted for delivery to initiate their COVID-19 vaccine series during their hospitalization; among 221 obstetric patients who had not yet received any doses of COVID-19 vaccine, 19.5% successfully received their first dose in that clinical setting.51 Inpatient vaccination has also been found to improve postpartum vaccination rates for other vac- cines; for example, offering human papillomavirus and pertus- sis vaccination prior to hospital discharge substantially increased vaccination rates among postpartum patients not yet vaccinated.52,53 Addressing concerns about COVID-19 vaccines by obstetrical care providers and administering vac- cines in hospital could be an efficient way to increase COVID- 19 vaccine coverage among individuals who are not yet vacci- nated by the time of delivery, particularly in settings where the majority of births take place in a hospital. Nevertheless, efforts should be made to ensure COVID-19 vaccination before or during pregnancy in order to protect individuals during their pregnancy, when they are at higher risk of serious COVID-19 disease,1–4 and also to provide passive protection to newborns.11–13 Strengths and limitations This study was population-based and included all individuals in Ontario, who gave birth in 2021 and had not yet received any doses of COVID-19 vaccine by the time of delivery. We fol- lowed these individuals until June 30, 2022, to assess COVID-19 vaccine series initiation after pregnancy, with a minimum of 6 months of follow-up for everyone in the study population (maximum follow-up was 18 months). We were able to explore associations between COVID-19 vaccine series initiation after pregnancy with a wide range of sociodemographic, pregnancy- related, and health-related factors. Nevertheless, we were unable to measure some factors that may have been important – for example, we had no information about individual or contextual factors that could have influenced individuals’ decisions about whether, or when, to initiate their primary COVID-19 vaccine series (i.e., knowledge, beliefs, attitudes, intentions, past experi- ence, confidence or trust in the healthcare system or healthcare providers, social or cultural norms and values). Although we explored COVID-19 vaccine series initiation by 6 months after pregnancy, which is a time when recommendations for new- born feeding change,47 we did not have information on the actual method of newborn feeding after discharge from hospi- tal/birth center. Conclusion This study found that among individuals not yet vaccinated against COVID-19 by the end of their pregnancy in 2021, the initiation of COVID-19 vaccination after delivery – even many months after giving birth – was lower than among women of reproductive age in the general population. This suggests that there may be persistent vaccine hesitancy among individuals experiencing a recent pregnancy or possibly reduced access to health care. Barriers to access, vaccine hesitancy, and vaccine misinformation could be addressed by targeted interventions to improve both pregnant and postpartum individuals’ awareness of the risks of COVID-19 and the benefits of COVID-19 vac- cines. Given ongoing recommendations for vaccination of preg- nant and lactating individuals, additional research is needed to better understand barriers to COVID-19 vaccination during pregnancy and after giving birth, and to monitor trends in COVID-19 vaccine coverage in these populations over time. Acknowledgments The authors thank the Ontario Ministry of Health for granting access to the COVaxON database and the Public Health Case and Contact Management Solution (CCM). The authors also thank maternal-newborn hospitals and midwifery practice groups in Ontario for providing mater- nal-newborn data to BORN Ontario. Finally, the authors thank BORN Ontario staff for their assistance with data extraction, linkage, code review, and results review. Disclosure statement K. Wilson is CEO of CANImmunize Inc, which hosts a national digital immunization record, and is a member of the independent data safety board for the Medicago COVID-19 vaccine trial; no other relationships or activities that could appear to have influenced the submitted work. Funding This study was supported by funding from the Public Health Agency of Canada, through the Vaccine Surveillance Reference Group and the COVID-19 Immunity Task Force; S. Håberg was partly supported by the Research Council of Norway (project number, 324312) and through its Centers of Excellence funding scheme (project number, 262700) and by NordForsk (project number, 105545). ORCID Kumanan Wilson http://orcid.org/0000-0002-1741-7705 Data sharing The dataset from this study is held securely by BORN Ontario. Although the dataset cannot be made publicly available, the analytic code may be available on request. HUMAN VACCINES & IMMUNOTHERAPEUTICS 9 Disclaimer The study sponsors did not participate in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication. Parts of this material are based on data and information compiled and provided by BORN Ontario and the Ontario Ministry of Health; however, the analyses, conclusions, opinions, and statements expressed herein are solely those of the authors and do not reflect those of the funding or data sources. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication. References 1. McClymont E, Albert AY, Alton GD, Boucoiran I, Castillo E, Fell DB, Kuret V, Poliquin V, Reeve T, Scott H, et al. Association of SARS-CoV-2 infection during pregnancy with maternal and perinatal outcomes. JAMA. 2022;327(20):1983–91. doi:https:// doi.org/10.1001/jama.2022.5906. 2. Centers for Disease Control and Prevention. Precautions for peo- ple with certain medical conditions. [accessed 2023 May 1]. https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precau tions/people-with-medical-conditions.html . 3. Allotey J, Stallings E, Bonet M, Yap M, Chatterjee S, Kew T, Zhou D, Coomar D, Sheikh J, Lawson H, et al. Clinical manifesta- tions, risk factors, and maternal and perinatal outcomes of coro- navirus disease 2019 in pregnancy: living systematic review and meta-analysis. BMJ. 2020;370:m3320. doi:10.1136/bmj.m3320. 4. Villar J, Ariff S, Gunier RB, Thiruvengadam R, Rauch S, Kholin A, Roggero P, Prefumo F, Do Vale MS, Cardona-Perez JA, et al. Maternal and neonatal morbidity and mortality among pregnant women with and without COVID-19 infection: the INTERCOVID multinational cohort study. JAMA Pediatr. 2021;175(8):817–26. doi:10.1001/jamapediatrics.2021.1050. 5. Regan AK, Arah OA, Fell DB, Sullivan SG. SARS-CoV-2 infection during pregnancy and associated perinatal health outcomes: a national US cohort study. J Infect Dis. 2022;225(5):759–67. doi:10.1093/infdis/jiab626. 6. Karasek D, Baer RJ, McLemore MR, Bell AJ, Blebu BE, Casey JA, Coleman-Phox K, Costello JM, Felder JN, Flowers E, Fuchs JD. The association of COVID-19 infection in pregnancy with preterm birth: a retrospective cohort study in California. Lancet Reg Heal Am. 2021;2:100027. doi:10.1016/j.lana.2021.100027. 7. DeSisto CL, Wallace B, Simeone RM, Polen K, Ko JY, Meaney- Delman D, Ellington SR. Risk for stillbirth among women with and without COVID-19 at delivery hospitalization — United States, March 2020–September 2021. Morb Mortal Wkly Rep. 2021;70(47):1640–5.10.15585/mmwr.mm7047e1 8. Berman Institute of Bioethics & Center for Immunization Research JHU. COVID-19 Maternal Immunization Tracker (COMIT): COVID-19 Vaccine policies for pregnant and lactating people worldwide. 2021 [accessed 2023 May 1]. https://www.comit global.org . 9. Dagan N, Barda N, Biron-Shental T, Makov-Assif M, Key C, Kohane IS, Hernán MA, Lipsitch M, Hernandez-Diaz S, Reis BY, et al. Effectiveness of the BNT162b2 mRNA COVID-19 vaccine in pregnancy. Nat Med. 2021;27(10):1693–5. doi:10.1038/s41591- 021-01490-8. 10. Magnus MC, Håberg SE, Carlsen EØ, Kwong JC, Buchan SA, Fell DB. Pregnancy status at the time of COVID-19 vaccination and incidence of SARS-CoV-2 infection. Clin Infect Dis. 2022: ciac739. doi:10.1093/cid/ciac739. 11. Carlsen EØ, Magnus MC, Oakley L, Fell DB, Greve-Isdahl M, Kinge JM, Håberg SE. Association of COVID-19 vaccination dur- ing pregnancy with incidence of SARS-CoV-2 infection in infants. JAMA Intern Med. 2022;182(8):825–31. doi:10.1001/jamain ternmed.2022.2442. 12. Halasa NB, Olson SM, Staat MA, Newhams MM, Price AM, Pannaraj PS, Boom JA, Sahni LC, Chiotos K, Cameron MA, et al. Maternal vaccination and risk of hospitalization for Covid-19 among infants. N Engl J Med. 2022;387(2):109–19. doi:10.1056/ NEJMoa2204399. 13. Jorgensen SC, Hernandez A, Fell DB, Austin PC, D’Souza R, Guttmann A, Brown KA, Buchan SA, Gubbay JB, Nasreen S, et al. Effectiveness of maternal mRNA COVID-19 vaccination during pregnancy against Delta and Omicron SARS-CoV-2 infec- tion and hospitalization in infants: a test-negative design study. BMJ. 2023;380:e074035. doi:10.1136/bmj-2022-074035. 14. Kharbanda EO, Haapala J, DeSilva M, Vazquez-Benitez G, Vesco KK, Naleway AL, Lipkind HS. Spontaneous abortion fol- lowing COVID-19 vaccination during pregnancy. JAMA. 2021;326 (16):1629–31. doi:https://doi.org/10.1001/jama.2021.15494. 15. Magnus MC, Gjessing HK, Eide HN, Wilcox AJ, Fell DB, Håberg SE. Covid-19 vaccination during pregnancy and first-trimester miscarriage. N Engl J Med. 2021;385(21):2008–10. doi:10.1056/NEJMc2114466. 16. Lipkind HS, Vazquez-Benitez G, DeSilva M, Vesco KK, Ackerman-Banks C, Zhu J, Boyce TG, Daley MF, Fuller CC, Getahun D, et al. Receipt of COVID-19 vaccine during pregnancy and preterm or small-for-gestational-age at birth — eight inte- grated health care organizations, United States, December 15, 2020–July 22, 2021. Morb Mortal Wkly Rep. 2022;71(1):26–30. doi:10.15585/mmwr.mm7101e1. 17. Magnus MC, Örtqvist AK, Dahlqwist E, Ljung R, Skår F, Oakley L, Macsali F, Pasternak B, Gjessing HK, Håberg SE, et al. Association of SARS-CoV-2 vaccination during pregnancy with pregnancy outcomes. JAMA. 2022;327(15):1469–77. doi:https://doi.org/10. 1001/jama.2022.3271. 18. Fell DB, Dhinsa T, Alton GD, Török E, Dimanlig-Cruz S, Regan AK, Sprague AE, Buchan SA, Kwong JC, Wilson SE, et al. Association of COVID-19 vaccination in pregnancy with adverse peripartum outcomes. JAMA. 2022;327(15):1478–87. doi:https:// doi.org/10.1001/jama.2022.4255. 19. Fell DB, Dimanlig-Cruz S, Regan AK, Håberg SE, Gravel CA, Oakley L, Alton GD, Török E, Dhinsa T, Shah PS, et al. Risk of preterm birth, small for gestational age at birth, and stillbirth after COVID-19 vaccination during pregnancy: population based retro- spective cohort study. BMJ. 2022;378:e071416. doi:10.1136/bmj- 2022-071416. 20. Razzaghi H, Meghani M, Pingali C, Crane B, Naleway A, Weintraub E, Kenigsberg TA, Lamias MJ, Irving SA, Kauffman TL, et al. COVID-19 vaccination coverage among preg- nant women during pregnancy — eight integrated health care organizations, United States, December 14, 2020–May 8, 2021. Morb Mortal Wkly Rep. 2021;70(24):895–9. doi:10.15585/mmwr. mm7024e2. 21. Stock SJ, Carruthers J, Calvert C, Denny C, Donaghy J, Goulding A, Hopcroft LEM, Hopkins L, McLaughlin T, Pan J, et al. SARS-CoV-2 infection and COVID-19 vaccination rates in pregnant women in Scotland. Nat Med. 2022;28(3):504–12. doi:10. 1038/s41591-021-01666-2. 22. Fell DB, Török E, Sprague AE, Regan AK, Dhinsa T, Alton GD, Dimanlig-Cruz S, MacDonald SE, Buchan SA, Kwong JC, et al. Temporal trends and determinants of COVID-19 vaccine coverage and series initiation during pregnancy in Ontario, Canada, December 2020 to December 2021: a population-based retrospec- tive cohort study. Vaccine. 2023;41(10):1716–25. doi:https://doi. org/10.1016/j.vaccine.2023.01.073. 23. Skjefte M, Ngirbabul M, Akeju O, Escudero D, Hernandez-Diaz S, Wyszynski DF, Wu JW. COVID-19 vaccine acceptance among pregnant women and mothers of young children: results of a survey in 16 countries. Eur J Epidemiol. 2021;36(2):197–211. doi:10.1007/s10654-021-00728-6. 24. Skirrow H, Barnett S, Bell S, Riaposova L, Mounier-Jack S, Kampmann B, Holder B. Women’s views on accepting COVID- 19 vaccination during and after pregnancy, and for their babies: a multi-methods study in the UK. BMC Pregnancy Childbirth. 2022;22(1):33. doi:10.1186/s12884-021-04321-3. 10 E. TÖRÖK ET AL. https://doi.org/10.1001/jama.2022.5906 https://doi.org/10.1001/jama.2022.5906 https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-medical-conditions.html https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-medical-conditions.html https://doi.org/10.1136/bmj.m3320 https://doi.org/10.1001/jamapediatrics.2021.1050 https://doi.org/10.1093/infdis/jiab626 https://doi.org/10.1016/j.lana.2021.100027 https://doi.org/10.15585/mmwr.mm7047e1 https://www.comitglobal.org https://www.comitglobal.org https://doi.org/10.1038/s41591-021-01490-8 https://doi.org/10.1038/s41591-021-01490-8 https://doi.org/10.1093/cid/ciac739 https://doi.org/10.1001/jamainternmed.2022.2442 https://doi.org/10.1001/jamainternmed.2022.2442 https://doi.org/10.1056/NEJMoa2204399 https://doi.org/10.1056/NEJMoa2204399 https://doi.org/10.1136/bmj-2022-074035 https://doi.org/10.1001/jama.2021.15494 https://doi.org/10.1056/NEJMc2114466 https://doi.org/10.15585/mmwr.mm7101e1 https://doi.org/10.1001/jama.2022.3271 https://doi.org/10.1001/jama.2022.3271 https://doi.org/10.1001/jama.2022.4255 https://doi.org/10.1001/jama.2022.4255 https://doi.org/10.1136/bmj-2022-071416 https://doi.org/10.1136/bmj-2022-071416 https://doi.org/10.15585/mmwr.mm7024e2 https://doi.org/10.15585/mmwr.mm7024e2 https://doi.org/10.1038/s41591-021-01666-2 https://doi.org/10.1038/s41591-021-01666-2 https://doi.org/10.1016/j.vaccine.2023.01.073 https://doi.org/10.1016/j.vaccine.2023.01.073 https://doi.org/10.1007/s10654-021-00728-6 https://doi.org/10.1186/s12884-021-04321-3 25. Bhattacharya O, Siddiquea BN, Shetty A, Afroz A, Billah B. COVID-19 vaccine hesitancy among pregnant women: a systematic review and meta-analysis. BMJ Open. 2022;12(8): e061477. doi:10.1136/bmjopen-2022-061477. 26. Schmid P, Rauber D, Betsch C, Lidolt G, Denker M-L. Barriers of influenza vaccination intention and behavior - a systematic review of influenza vaccine hesitancy, 2005 - 2016. PLos One. 2017;12(1): e0170550. doi:10.1371/journal.pone.0170550. 27. Statistics Canada. Live births and fetal deaths (stillbirths), by type of birth (single or multiple). https://doi.org/10.25318/ 1310042801-eng . 28. National Advisory Committee on Immunization. Recommendations on the use of COVID-19 vaccines. 2021 Apr 23 [accessed 2023 May 1]. https://www.canada.ca/en/public-health/services/immunization/ national-advisory-committee-on-immunization-naci/recommenda tions-use-covid-19-vaccines/april-23-2021.html . 29. Ontario Ministry of Health and Long-Term Care. COVID-19 vaccine booking expanding to Ontarians 18+ ahead of schedule. 2021 [accessed 2023 May 1]. https://news.ontario.ca/en/release/ 1000143/covid-19-vaccine-booking-expanding-to-ontarians-18- ahead-of-schedule . 30. Murphy MSQ, Fell DB, Sprague AE, Corsi DJ, Dougan S, Dunn SI, Holmberg V, Huang T, Johnson M, Kotuba M, et al. Data resource profile: better outcomes registry & network (BORN) Ontario. Int J Epidemiol. 2021;50(5):1416–25. doi:10.1093/ije/dyab033. 31. Dunn S, Lanes A, Sprague AE, Fell DB, Weiss D, Reszel J, Taljaard M, Darling EK, Graham ID, Grimshaw JM, et al. Data accuracy in the Ontario birth registry: a chart re-abstraction study. BMC Health Serv Res. 2019;19(1):1001. doi:10.1186/s12913-019- 4825-3. 32. Public Health Ontario. Ontario marginalization index (ON-Marg). [accessed 2023 May 1]. https://www.publichealthontario.ca/en/ data-and-analysis/health-equity/ontario-marginalization-index . 33. Ontario Agency for Health Protection and Promotion (Public Health Ontario). COVID-19 vaccine uptake in Ontario: December 14, 2020 to July 4, 2022. Toronto, ON: Queen’s Printer for Ontario; 2022. 34. Kiefer MK, Mehl R, Costantine MM, Johnson A, Cohen J, Summerfield TL, Landon MB, Rood KM, Venkatesh KK. Characteristics and perceptions associated with COVID-19 vacci- nation hesitancy among pregnant and postpartum individuals: a cross-sectional study. BJOG. 2022;129(8):1342–51. doi:10.1111/ 1471-0528.17110. 35. Siegel MR, Lumbreras-Marquez MI, James K, McBay BR, Gray KJ, Schantz-Dunn J, Diouf K, Goldfarb IT. Perceptions and attitudes toward COVID-19 vaccination among pregnant and postpartum individuals. Am J Perinatol. 2022. doi:10.1055/a-1877-5880. 36. Blakeway H, Prasad S, Kalafat E, Heath PT, Ladhani SN, Le Doare K, Magee LA, O’Brien P, Rezvani A, von Dadelszen P, et al. COVID-19 vaccination during pregnancy: coverage and safety. Am J Obstet Gynecol. 2022;226(2):236.e1-236.e14. doi: 10. 1016/j.ajog.2021.08.007. 37. Örtqvist AK, Dahlqwist E, Magnus MC, Ljung R, Jonsson J, Aronsson B, Pasternak B, Håberg SE, Stephansson O. COVID-19 vaccination in pregnant women in Sweden and Norway. Vaccine. 2022;40(33):4686–92. doi:https://doi.org/10.1016/j.vaccine.2022. 06.083. 38. Origlia P, Jevitt C, Sayn-Wittgenstein FZ, Cignacco E. Experiences of antenatal care among women who are socioeconomically deprived in high-income industrialized countries: an integrative review. J Midwifery Women's Health. 2017;62(5):589–98. doi:10. 1111/jmwh.12627. 39. Alhendyani F, Jolly K, Jones LL. Views and experiences of mater- nal healthcare providers regarding influenza vaccine during pregnancy globally: a systematic review and qualitative evidence synthesis. PLos One. 2022;17(2):e0263234. doi:10.1371/journal. pone.0263234. 40. MacDougall DM, Halperin SA. Improving rates of maternal immunization: challenges and opportunities. Hum Vaccines Immunother. 2016;12(4):857–65. doi:10.1080/21645515.2015. 1101524. 41. Germann K, Kiefer MK, Rood KM, Mehl R, Wu J, Pandit R, Lynch CD, Landon MB, Grobman WA, Costantine MM, et al. Association of initial COVID-19 vaccine hesitancy with subse- quent vaccination among pregnant and postpartum individuals. BJOG. 2022;129(8):1352–60. doi:10.1111/1471- 0528.17189. 42. Huang L, Riggan KA, Ashby GB, Rivera-Chiauzzi EY, Allyse MA. Pregnant and postpartum patients’ views of COVID-19 vaccina- tion. J Community Health. 2022;47(5):871–8. doi:10.1007/s10900- 022-01118-z. 43. Oluklu D, Goncu Ayhan S, Menekse Beser D, Uyan Hendem D, Ozden Tokalioglu E, Turgut E, Sahin D. Factors affecting the acceptability of COVID-19 vaccine in the postpartum period. Hum Vaccin Immunother. 2021;17(11):4043–7. doi:10.1080/ 21645515.2021.1972710. 44. Abbasi J. Widespread misinformation about infertility continues to create COVID-19 vaccine hesitancy. JAMA. 2022;327 (11):1013–15. doi:https://doi.org/10.1001/jama.2022.2404. 45. Oliver J, Gibney Z, Danchin C, Bradfield KB, Homer M, Gibney KB, Danchin M. Drivers of COVID-19 vaccine hesitancy among women of childbearing age in Victoria, Australia: a descriptive qualitative study. Vaccine: X. 2022;12:100240. doi:10.1016/j.jvacx.2022.100240. 46. Dellino M, Vimercati A, D’Amato A, Damiani GR, Laganà AS, Cicinelli E, Pinto V, Malvasi A, Scacco S, Ballini A, et al. “GONE with the WIND”: the transitory effects of COVID-19 on the gynecological system. J Pers Med. 2023;13(2):312. doi:10.3390/ jpm13020312. 47. World Health Organization. Breastfeeding. 2022 [accessed 2023 May 1]. https://www.who.int/health-topics/breastfeeding#tab= tab_2 . 48. Critch JN, Canadian Paediatric Society N and GC. Nutrition for healthy term infants, birth to six months: an overview. Paediatr Child Health. 2013;18(4):206–7. doi:10.1093/pch/18. 4.206. 49. Schaal NK, Zöllkau J, Hepp P, Fehm T, Hagenbeck C. Pregnant and breastfeeding women’s attitudes and fears regarding the COVID-19 vaccination. Arch Gynecol Obstet. 2022;306 (2):365–72. doi:10.1007/s00404-021-06297-z. 50. Sutton D, D’Alton M, Zhang Y, Kahe K, Cepin A, Goffman D, Staniczenko A, Yates H, Burgansky A, Coletta J, et al. COVID-19 vaccine acceptance among pregnant, breastfeeding, and nonpreg- nant reproductive-aged women. Am J Obstet Gynecol MFM. 2021;3(5):100403. doi:10.1016/j.ajogmf.2021.100403. 51. Perez MJ, Paul R, Hirshberg JS, Aibangbee E, Ford T, Cooke E, Carter EB, Odibo AO, Raghuraman N, Kelly JC. Administration of the coronavirus disease 2019 (COVID-19) vaccine to hospitalized postpartum patients. Obstet Gynecol. 2021;138(6):885–7. doi:10. 1097/AOG.0000000000004590. 52. Berenson AB, Rahman M, Hirth JM, Rupp RE, Sarpong KO. A human papillomavirus vaccination program for low-income post- partum women. Am J Obstet Gynecol. 2016;215(3):318.e1–e9. doi:10.1016/j.ajog.2016.02.032. 53. Bernstein HH, Monty M, Yang P, Cohen A. Increasing Tdap coverage among postpartum women: a quality improvement intervention. Pediatrics. 2017;139(3):e20160607. doi:https://doi. org/10.1542/peds.2016-0607. HUMAN VACCINES & IMMUNOTHERAPEUTICS 11 https://doi.org/10.1136/bmjopen-2022-061477 https://doi.org/10.1371/journal.pone.0170550 https://doi.org/10.25318/1310042801-eng https://doi.org/10.25318/1310042801-eng https://www.canada.ca/en/public-health/services/immunization/national-advisory-committee-on-immunization-naci/recommendations-use-covid-19-vaccines/april-23-2021.html https://www.canada.ca/en/public-health/services/immunization/national-advisory-committee-on-immunization-naci/recommendations-use-covid-19-vaccines/april-23-2021.html https://www.canada.ca/en/public-health/services/immunization/national-advisory-committee-on-immunization-naci/recommendations-use-covid-19-vaccines/april-23-2021.html https://news.ontario.ca/en/release/1000143/covid-19-vaccine-booking-expanding-to-ontarians-18-ahead-of-schedule https://news.ontario.ca/en/release/1000143/covid-19-vaccine-booking-expanding-to-ontarians-18-ahead-of-schedule https://news.ontario.ca/en/release/1000143/covid-19-vaccine-booking-expanding-to-ontarians-18-ahead-of-schedule https://doi.org/10.1093/ije/dyab033 https://doi.org/10.1186/s12913-019-4825-3 https://doi.org/10.1186/s12913-019-4825-3 https://www.publichealthontario.ca/en/data-and-analysis/health-equity/ontario-marginalization-index https://www.publichealthontario.ca/en/data-and-analysis/health-equity/ontario-marginalization-index https://doi.org/10.1111/1471-0528.17110 https://doi.org/10.1111/1471-0528.17110 https://doi.org/10.1055/a-1877-5880 https://doi.org/10.1016/j.ajog.2021.08.007 https://doi.org/10.1016/j.ajog.2021.08.007 https://doi.org/10.1016/j.vaccine.2022.06.083 https://doi.org/10.1016/j.vaccine.2022.06.083 https://doi.org/10.1111/jmwh.12627 https://doi.org/10.1111/jmwh.12627 https://doi.org/10.1371/journal.pone.0263234 https://doi.org/10.1371/journal.pone.0263234 https://doi.org/10.1080/21645515.2015.1101524 https://doi.org/10.1080/21645515.2015.1101524 https://doi.org/10.1111/1471-0528.17189 https://doi.org/10.1111/1471-0528.17189 https://doi.org/10.1007/s10900-022-01118-z https://doi.org/10.1007/s10900-022-01118-z https://doi.org/10.1080/21645515.2021.1972710 https://doi.org/10.1080/21645515.2021.1972710 https://doi.org/10.1001/jama.2022.2404 https://doi.org/10.1016/j.jvacx.2022.100240 https://doi.org/10.3390/jpm13020312 https://doi.org/10.3390/jpm13020312 https://www.who.int/health-topics/breastfeeding#tab=tab_2 https://www.who.int/health-topics/breastfeeding#tab=tab_2 https://doi.org/10.1093/pch/18.4.206 https://doi.org/10.1093/pch/18.4.206 https://doi.org/10.1007/s00404-021-06297-z https://doi.org/10.1016/j.ajogmf.2021.100403 https://doi.org/10.1097/AOG.0000000000004590 https://doi.org/10.1097/AOG.0000000000004590 https://doi.org/10.1016/j.ajog.2016.02.032 https://doi.org/10.1542/peds.2016-0607 https://doi.org/10.1542/peds.2016-0607 Abstract Introduction Methods Study design, setting, and data sources Study population Measures Statistical analysis Results Study population Temporal trends in COVID-19 vaccine series initiation after pregnancy Determinants of COVID-19 vaccine series initiation after pregnancy Subgroup and sensitivity analyses Discussion Strengths and limitations Conclusion Acknowledgments Disclosure statement Funding ORCID Data sharing Disclaimer References