Temporal trends and determinants of COVID-19 vaccine series initiation after recent pregnancy.

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.

Association between SARS-CoV-2 infection and newly diagnosed hypertension during pregnancy: prospective, population based cohort study.

Objective: To study the association between SARS-CoV-2 infection and newly diagnosed hypertension during pregnancy. Design: Prospective, population based cohort study. Setting: All singleton pregnancies after 22 completed gestational weeks registered in the Swedish Pregnancy Register and the Medical Birth Registry of Norway, from 1 March 2020 to 24 May 2022. Participants: 312 456 individuals available for analysis (201 770 in Sweden and 110 686 in Norway), with pregnancies that reached 42 completed gestational weeks by the end of follow-up in the pregnancy registries, excluding individuals with SARS-CoV-2 infection before pregnancy and those with a diagnosis of pre-existing hypertension or onset of hypertension before 20 gestational weeks. Main outcome measures: Newly diagnosed hypertension during pregnancy was defined as a composite outcome of a diagnosis of gestational hypertension, pre-eclampsia, HELLP (haemolysis, elevated liver enzymes, low platelets) syndrome, or eclampsia, from gestational week 20 to one week after delivery. The association between SARS-CoV-2 infection and hypertension during pregnancy was investigated with a stratified Cox proportional hazard model, adjusting for maternal age, body mass index, parity, smoking, region of birth, education, income, coexisting medical conditions, previous hypertension during pregnancy, number of healthcare visits during the past year, and vaccination against SARS-CoV-2. Pre-eclampsia was also analysed as a separate outcome. Results: Of 312 456 individuals available for analysis, 8% (n=24 566) had SARS-CoV-2 infection any time during pregnancy, 6% (n=18 051) had a diagnosis of hypertension during pregnancy, and 3% (9899) had pre-eclampsia. SARS-CoV-2 infection during pregnancy was not associated with an increased risk of hypertension during pregnancy (adjusted hazard ratio 0.99, 95% confidence interval 0.93 to 1.04) or pre-eclampsia (0.98, 0.87 to 1.10). The results were similar for SARS-CoV-2 infection in all gestational trimesters and in different time periods that corresponded to dominance of different variants of the SARS-CoV-2 virus. Conclusions: This population based study did not find any evidence of an association between SARS-CoV-2 infection during pregnancy and an increased risk of hypertension during pregnancy or pre-eclampsia.

Current tobacco use and SARS-CoV-2 infection in two Norwegian population-based cohorts.

BACKGROUND: Clear evidence of an increased risk for SARS-CoV-2 infection among smokers has not been established. We aimed to investigate associations between cigarette smoking or use of snus (snuff) and other nicotine-containing products and a positive SARS-CoV-2 test, taking test behavior into account. METHODS: Current tobacco use and testing behavior during the pandemic were recorded by adult participants from the Norwegian Mother, Father and Child Cohort Study and The Norwegian Influenza Pregnancy Cohort. SARS-CoV-2 infection status was obtained from The Norwegian Surveillance System for Communicable Diseases (MSIS) in May 2021 (n = 78,860) and antibody measurements (n = 5581). We used logistic regression models stratified by gender and adjusted for age, education, region, number of household members, and work situation. RESULTS: Snus use was more common among men (26%) than women (9%) and more prevalent than cigarette smoking. We found no clear associations between cigarette smoking or snus and a COVID-19 diagnosis among men. Associations among women were conflicting, indicating that cigarette smoke was negatively associated with a diagnosis (OR 0.51, 95% CI 0.35, 0.75), while no association was found for snus use (OR 1.07, 95% CI 0.86, 1.34). Compared with non-users of tobacco, both cigarette smokers and snus users had increased odds of being tested for SARS-CoV-2. CONCLUSIONS: Cigarette smoking, but not snus use, was negatively associated with SARS-CoV-2 infection in women. The lack of an association between snus use and SARS-CoV-2 infection in this population with prevalent snus use does not support the hypothesis of a protective effect of nicotine.

Severe COVID-19 during pregnancy in Sweden, Norway, and Denmark.

INTRODUCTION: Pregnancy is a risk factor for severe coronavirus disease 2019 (COVID-19) and adverse pregnancy outcomes. We aimed to explore maternal characteristics, pregnancy outcomes, vaccination status, and virus variants among pregnant women admitted to intensive care units (ICU) with severe COVID-19. MATERIAL AND METHODS: We identified pregnant women admitted to ICU in Sweden (n = 96), Norway (n = 31), and Denmark (n = 16) because of severe COVID-19, from national registers and clinical databases between March 2020 and February 2022 (Denmark), August 2022 (Sweden), or December 2022 (Norway). Their background characteristics, pregnancy outcome, and vaccination status were compared with all birthing women and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test-positive pregnant women during the same time period. We calculated the number admitted to ICU per 10 000 birthing and per 1000 SARS-CoV-2 test-positive women during the Index, Alpha, Delta, and Omicron periods. RESULTS: Women admitted to ICU had a higher mean body mass index, were more often of non-Scandinavian origin, had on average lower education and income levels, had a higher proportion of chronic and pregnancy-related conditions, delivered preterm, had neonates with low Apgar scores, and had more infants admitted to neonatal care, compared with all birthing and test-positive pregnant women. Of those admitted to ICU, only 7% had been vaccinated before admission. Overall, the highest proportion of women admitted to ICU per birthing was during the Delta period (4.1 per 10 000 birthing women). In Norway, the highest proportion admitted to ICU per test-positive pregnant women was during the Delta period (17.8 per 1000 test-positive), whereas the highest proportion of admitted per test-positive in Sweden and Denmark was seen during the Index period (15.4 and 8.9 per 1000 test-positive, respectively). CONCLUSIONS: Admission to ICU because of COVID-19 in pregnancy was a rare event in the Scandinavian countries, but women who were unvaccinated, of non-Scandinavian origin, and with lower socio-economic status were at higher risk of admission to ICU. In addition, women admitted to ICU for COVID-19 had higher risk of adverse pregnancy outcomes.

Changes in preterm birth and stillbirth during COVID-19 lockdowns in 26 countries.

Preterm birth (PTB) is the leading cause of infant mortality worldwide. Changes in PTB rates, ranging from -90% to +30%, were reported in many countries following early COVID-19 pandemic response measures ('lockdowns'). It is unclear whether this variation reflects real differences in lockdown impacts, or perhaps differences in stillbirth rates and/or study designs. Here we present interrupted time series and meta-analyses using harmonized data from 52 million births in 26 countries, 18 of which had representative population-based data, with overall PTB rates ranging from 6% to 12% and stillbirth ranging from 2.5 to 10.5 per 1,000 births. We show small reductions in PTB in the first (odds ratio 0.96, 95% confidence interval 0.95-0.98, P value <0.0001), second (0.96, 0.92-0.99, 0.03) and third (0.97, 0.94-1.00, 0.09) months of lockdown, but not in the fourth month of lockdown (0.99, 0.96-1.01, 0.34), although there were some between-country differences after the first month. For high-income countries in this study, we did not observe an association between lockdown and stillbirths in the second (1.00, 0.88-1.14, 0.98), third (0.99, 0.88-1.12, 0.89) and fourth (1.01, 0.87-1.18, 0.86) months of lockdown, although we have imprecise estimates due to stillbirths being a relatively rare event. We did, however, find evidence of increased risk of stillbirth in the first month of lockdown in high-income countries (1.14, 1.02-1.29, 0.02) and, in Brazil, we found evidence for an association between lockdown and stillbirth in the second (1.09, 1.03-1.15, 0.002), third (1.10, 1.03-1.17, 0.003) and fourth (1.12, 1.05-1.19, <0.001) months of lockdown. With an estimated 14.8 million PTB annually worldwide, the modest reductions observed during early pandemic lockdowns translate into large numbers of PTB averted globally and warrant further research into causal pathways.

Pregnancy status at the time of COVID-19 vaccination and incidence of SARS-CoV-2 infection.

BACKGROUND: Pregnant women are recommended to receive COVID-19 vaccines; however, relative effectiveness of vaccination by pregnancy status is unclear. METHODS: We compared the relative effectiveness of mRNA COVID-19 vaccines according to whether women received both while pregnant (n= 7,412), one dose while pregnant (n = 3,538), both while postpartum (n = 1,856), or both doses while neither pregnant nor postpartum (n = 6,687). We estimated risk of SARS-CoV-2 infection starting 14 days after the second dose using Cox regression, reporting hazard ratios (HR) and 95% confidence intervals (CI). Secondly, we examined relative effectiveness of a third (booster) dose while pregnant compared to outside pregnancy. The major circulating variant during the study period was the Delta variant. RESULTS: 54% of women received two doses of the BNT162b2 vaccine, 16% received two doses of the mRNA-1273 vaccine, while 30% received one dose of both vaccines. Compared to women who received both doses while neither pregnant nor postpartum, the adjusted HR for a positive SARS-CoV-2 PCR test was similar if the woman received both doses while pregnant (1.04; 95% CI: 0.94, 1.17), one dose while pregnant and one dose before or after pregnancy (1.03; 95% CI: 0.93, 1.14), or both doses while postpartum (0.99; 95% CI: 0.92, 1.07). The findings were similar for BNT162b2 (Pfizer-BioNTech Comirnaty) and mRNA-1273 (Moderna Spikevax), and during Delta- and Omicron-dominant periods. We observed no differences in the relative effectiveness of the booster dose according to pregnancy status. CONCLUSIONS: We observed similar effectiveness of mRNA vaccines against SARS-CoV-2 infection among women regardless of pregnancy status at the time of vaccination.

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 retrospective cohort study.

BACKGROUND: Population-based COVID-19 vaccine coverage estimates among pregnant individuals are limited. We assessed temporal patterns in vaccine coverage (≥1 dose before or during pregnancy) and evaluated factors associated with vaccine series initiation (receiving dose 1 during pregnancy) in Ontario, Canada. METHODS: We linked the provincial birth registry with COVID-19 vaccination records from December 14, 2020 to December 31, 2021 and assessed coverage rates among all pregnant individuals by month, age, and neighborhood sociodemographic characteristics. Among individuals who gave birth since April 2021-when pregnant people were prioritized for vaccination-we assessed associations between sociodemographic, behavioral, and pregnancy-related factors with vaccine series initiation using multivariable regression to estimate adjusted risk ratios (aRR) and risk differences (aRD) with 95% confidence intervals (CI). RESULTS: Among 221,190 pregnant individuals, vaccine coverage increased to 71.2% by December 2021. Gaps in coverage across categories of age and sociodemographic characteristics decreased over time, but did not disappear. Lower vaccine series initiation was associated with lower age (<25 vs. 30-34 years: aRR 0.53, 95%CI 0.51-0.56), smoking (vs. non-smoking: 0.64, 0.61-0.67), no first trimester prenatal care visit (vs. visit: 0.80, 0.77-0.84), and residing in neighborhoods with the lowest income (vs. highest: 0.69, 0.67-0.71). Vaccine series initiation was marginally higher among individuals with pre-existing medical conditions (vs. no conditions: 1.07, 1.04-1.10). CONCLUSIONS: COVID-19 vaccine coverage among pregnant individuals remained lower than in the general population, and there was lower vaccine initiation by multiple characteristics.

Fetal death after the introduction of COVID-19 mitigation measures in Sweden, Denmark and Norway: a registry-based study.

It remains unclear whether the rate of fetal death has changed during the COVID-19 pandemic. We assessed the impact of COVID-19 mitigation measures on fetal death in Sweden (449,347 births), Denmark (290,857 pregnancies) and Norway (261,057 pregnancies) using robust population-based registry data. We used Cox regression to assess the impact of the implementation of pandemic mitigation measures on March 12th, 2020, on miscarriage (fetal loss before gestational week 22) and stillbirth (fetal loss after gestational week 22). A total of 11% of 551,914 pregnancies in Denmark and Norway ended in miscarriage, while the proportion of stillbirths among 937,174 births across the three countries was 0.3%. There was no difference in the risk of fetal death during the year following pandemic mitigation measures. For miscarriage, the combined hazard ratio (HR) for Norway and Denmark was 1.01 (95% CI 0.98, 1.03), and for stillbirth, the combined HR for all three countries was 0.99 (95% CI 0.89, 1.09). We observed a slightly decreased risk of miscarriage during the first 4 months, with an HR of 0.94 (95% CI 0.90, 0.99) after lockdown. In conclusion, the risk of fetal death did not change after the implementation of COVID-19 pandemic mitigation measures in the three Scandinavian countries.

Risk of preterm birth, small for gestational age at birth, and stillbirth after covid-19 vaccination during pregnancy: population based retrospective cohort study.

OBJECTIVE: To assess the risk of preterm birth, small for gestational age at birth, and stillbirth after covid-19 vaccination during pregnancy. DESIGN: Population based retrospective cohort study. SETTING: Ontario, Canada, 1 May to 31 December 2021. PARTICIPANTS: All liveborn and stillborn infants from pregnancies conceived at least 42 weeks before the end of the study period and with gestational age ≥20 weeks or birth weight ≥500 g. MAIN OUTCOME MEASURES: Using Cox regression, hazard ratios and 95% confidence intervals were estimated for preterm birth before 37 weeks (overall and spontaneous preterm birth), very preterm birth (<32 weeks), small for gestational age at birth (<10th centile), and stillbirth. Vaccination against covid-19 was treated as a time varying exposure in the outcome specific risk window, and propensity score weighting was used to adjust hazard ratios for potential confounding. RESULTS: Among 85 162 births, 43 099 (50.6%) occurred in individuals who received one dose or more of a covid-19 vaccine during pregnancy-42 979 (99.7%) received an mRNA vaccine. Vaccination during pregnancy was not associated with any increased risk of overall preterm birth (6.5% among vaccinated v 6.9% among unvaccinated; adjusted hazard ratio 1.02, 95% confidence interval 0.96 to 1.08), spontaneous preterm birth (3.7% v 4.4%; 0.96, 0.90 to 1.03), or very preterm birth (0.59% v 0.89%; 0.80, 0.67 to 0.95). No increase was found in risk of small for gestational age at birth (9.1% v 9.2%; 0.98, 0.93 to 1.03) or stillbirth (0.25% v 0.44%; 0.65, 0.51 to 0.84). Findings were similar by trimester of vaccination, mRNA vaccine product, and number of doses received during pregnancy. CONCLUSION: The findings suggest that vaccination against covid-19 during pregnancy is not associated with a higher risk of preterm birth, small for gestational age at birth, or stillbirth.

Age and sex effects on DNA methylation sites linked to genes implicated in severe COVID-19 and SARS-CoV-2 host cell entry.

Male sex and advanced age are associated with severe symptoms of COVID-19. Sex and age also exhibit substantial associations with genome-wide DNA methylation (DNAm) differences in humans. Using a random sample of Illumina EPIC-based genome-wide methylomes from peripheral whole blood of 1,976 parents, participating in The Norwegian Mother, Father and Child Cohort Study (MoBa), we explored whether DNAm in genes linked to SARS-CoV-2 host cell entry and to severe COVID-19 were associated with sex and age. This was carried out by testing 1,572 DNAm sites (CpGs) located near 45 genes for associations with age and sex. We found that DNAm in 281 and 231 of 1,572 CpGs were associated (pFDR<0.01) with sex and aging, respectively. CpGs linked to SARS-CoV-2 host cell entry genes were all associated with age and sex, except for the ACE2 receptor gene (located on the X-chromosome), which was only associated with sex (pFDR<0.01). Furthermore, we examined whether 1,487 autosomal CpGs associated with host-cell entry and severe COVID-19 were more or less associated with sex and age than what would be expected from the same number of randomly sampled genome-wide CpGs. We found that the CpGs associated with host-cell entry and severe COVID-19 were not more or less associated with sex (R2 = 0.77, p = 0.09) than the CpGs sampled from random genomic regions; age was actually found to be significantly less so (R2 = 0.36, p = 0.04). Hence, while we found wide-spread associations between sex and age at CpGs linked to genes implicated with SARS-CoV-2 host cell entry and severe COVID-19, the effect from the sum of these CpGs was not stronger than that from randomly sampled CpGs; for age it was significantly less so. These findings could suggest that advanced age and male sex may not be unsurmountable barriers for the SARS-CoV-2 virus to evolve increased infectiousness.

The association between maternal characteristics and SARS-CoV-2 in pregnancy: a population-based registry study in Sweden and Norway.

The objectives of the current study were to identify risk factors for SARS-CoV-2 positivity, and to address how different testing strategies, choice of comparison group, and population background characteristics may influence observed associations. National registries data for 107,627 pregnant women in Sweden and 81,195 in Norway, were used to identify risk factors for SARS-CoV-2, separately for women under non-universal testing (testing by indication) and universal testing (testing of all pregnant women in contact with a delivery ward). We also investigated underlying characteristics associated with testing for SARS-CoV-2. Overall, 2.1% of pregnant women in Sweden and 1.1% in Norway were test-positive during the pandemic's first 18 months. We show that the choice of test strategy for SARS-CoV-2 provided different associations with risk factors for the disease; for instance, women who were overweight, obese or had gestational diabetes had increased odds of being test-positive under non-universal testing, but not under universal testing. Nevertheless, a consistent pattern of association between being born in the Middle East and Africa and test-positivity was found independent of test strategy and in both countries. These women were also less likely to get tested. Our results are useful to consider for surveillance and clinical recommendations for pregnant women during the current and future pandemics.

COVID-19 vaccination in pregnant women in Sweden and Norway.

Vaccines against SARS-CoV-2 are highly effective in preventing severe disease and mortality. Although pregnant women are at increased risk of severe COVID-19, vaccination uptake among pregnant women varies. We used the Swedish and Norwegian population-based health registries to identify pregnant women and to investigate background characteristics associated with not being vaccinated. In this study of 164 560 women giving birth between May 2021 and May 2022, 78% in Sweden and 87% in Norway have been vaccinated with at least one dose at delivery. Not being vaccinated while being pregnant was associated with age below 30 years, low education and income level, birth region other than Scandinavia, smoking during pregnancy, not living with a partner, and gestational diabetes. These results can assist health authorities develop targeted vaccination information to diminish vaccination inequality and prevent severe disease in vulnerable groups.

Association of COVID-19 Vaccination During Pregnancy With Incidence of SARS-CoV-2 Infection in Infants.

Importance: Pregnant women are recommended to receive COVID-19 vaccination to reduce risk of severe COVID-19. Whether vaccination during pregnancy also provides passive protection to infants after birth remains unclear. Objective: To determine whether COVID-19 vaccination in pregnancy was associated with reduced risk of COVID-19 in infants up to age 4 months during COVID-19 pandemic periods dominated by Delta and Omicron variants. Design, Setting, and Participants: This nationwide, register-based cohort study included all live-born infants born in Norway between September 1, 2021, and February 28, 2022. Exposures: Maternal messenger RNA COVID-19 vaccination during second or third trimester compared with no vaccination before or during pregnancy. Main Outcomes and Measures: The risk of a positive polymerase chain reaction test result for SARS-CoV-2 during an infant's first 4 months of life by maternal vaccination status during pregnancy with either dose 2 or 3 was estimated, as stratified by periods dominated by the Delta variant (between September 1 and December 31, 2021) or Omicron variant (after January 1, 2022, to the end of follow-up on April 4, 2022). A Cox proportional hazard regression was used, adjusting for maternal age, parity, education, maternal country of birth, and county of residence. Results: Of 21 643 live-born infants, 9739 (45.0%) were born to women who received a second or third dose of a COVID-19 vaccine during pregnancy. The first 4 months of life incidence rate of a positive test for SARS-CoV-2 was 5.8 per 10 000 follow-up days. Infants of mothers vaccinated during pregnancy had a lower risk of a positive test compared with infants of unvaccinated mothers and lower risk during the Delta variant-dominated period (incidence rate, 1.2 vs 3.0 per 10 000 follow-up days; adjusted hazard ratio, 0.29; 95% CI, 0.19-0.46) compared with the Omicron period (incidence rate, 7.0 vs 10.9 per 10 000 follow-up days; adjusted hazard ratio, 0.67; 95% CI, 0.57-0.79). Conclusions and Relevance: The results of this Norwegian population-based cohort study suggested a lower risk of a positive test for SARS-CoV-2 during the first 4 months of life among infants born to mothers who were vaccinated during pregnancy. Maternal COVID-19 vaccination may provide passive protection to young infants, for whom COVID-19 vaccines are currently not available.

Association of COVID-19 Vaccination in Pregnancy With Adverse Peripartum Outcomes.

Importance: There is limited comparative epidemiological evidence on outcomes associated with COVID-19 vaccination during pregnancy; monitoring pregnancy outcomes in large populations is required. Objective: To evaluate peripartum outcomes following COVID-19 vaccination during pregnancy. Design, Setting, and Participants: Population-based retrospective cohort study in Ontario, Canada, using a birth registry linked with the provincial COVID-19 immunization database. All births between December 14, 2020, and September 30, 2021, were included. Exposures: COVID-19 vaccination during pregnancy, COVID-19 vaccination after pregnancy, and no vaccination. Main Outcomes and Measures: Postpartum hemorrhage, chorioamnionitis, cesarean delivery (overall and emergency cesarean delivery), admission to neonatal intensive care unit (NICU), and low newborn 5-minute Apgar score (<7). Linear and robust Poisson regression was used to generate adjusted risk differences (aRDs) and risk ratios (aRRs), respectively, comparing cumulative incidence of outcomes in those who received COVID-19 vaccination during pregnancy with those vaccinated after pregnancy and those with no record of COVID-19 vaccination at any point. Inverse probability of treatment weights were used to adjust for confounding. Results: Among 97 590 individuals (mean [SD] age, 31.9 [4.9] years), 22 660 (23%) received at least 1 dose of COVID-19 vaccine during pregnancy (63.6% received dose 1 in the third trimester; 99.8% received an mRNA vaccine). Comparing those vaccinated during vs after pregnancy (n = 44 815), there were no significantly increased risks of postpartum hemorrhage (incidence: 3.0% vs 3.0%; aRD, -0.28 per 100 individuals [95% CI, -0.59 to 0.03]; aRR, 0.91 [95% CI, 0.82-1.02]), chorioamnionitis (0.5% vs 0.5%; aRD, -0.04 per 100 individuals [95% CI, -0.17 to 0.09]; aRR, 0.92 [95% CI, 0.70-1.21]), cesarean delivery (30.8% vs 32.2%; aRD, -2.73 per 100 individuals [95% CI, -3.59 to -1.88]; aRR, 0.92 [95% CI, 0.89-0.95]), NICU admission (11.0% vs 13.3%; aRD, -1.89 per 100 newborns [95% CI, -2.49 to -1.30]; aRR, 0.85 [95% CI, 0.80-0.90]), or low Apgar score (1.8% vs 2.0%; aRD, -0.31 per 100 newborns [95% CI, -0.56 to -0.06]; aRR, 0.84 [95% CI, 0.73-0.97]). Findings were qualitatively similar when compared with individuals who did not receive COVID-19 vaccination at any point (n = 30 115). Conclusions and Relevance: In this population-based cohort study in Ontario, Canada, COVID-19 vaccination during pregnancy, compared with vaccination after pregnancy and with no vaccination, was not significantly associated with increased risk of adverse peripartum outcomes. Study interpretation should consider that the vaccinations received during pregnancy were primarily mRNA vaccines administered in the second and third trimester.

Association of SARS-CoV-2 Vaccination During Pregnancy With Pregnancy Outcomes.

Importance: Data about the safety of vaccines against SARS-CoV-2 during pregnancy are limited. Objective: To examine the risk of adverse pregnancy outcomes after vaccination against SARS-CoV-2 during pregnancy. Design, Setting, and Participants: This registry-based retrospective cohort study included 157 521 singleton pregnancies ending after 22 gestational weeks from January 1, 2021, until January 12, 2022 (Sweden), or January 15, 2022 (Norway). The Pregnancy Register in Sweden and the Medical Birth Registry of Norway were linked to vaccination and other registries for identification of exposure and background characteristics. Exposures: Data on mRNA vaccines-BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna)-and 1 viral vector vaccine-AZD1222 (AstraZeneca)-were collected from national vaccination registries. Main Outcomes and Measures: The risk of preterm birth and stillbirth was evaluated using Cox regression models, with gestational day as the time metric and vaccination as a time-dependent exposure variable. The risk of small for gestational age, low Apgar score, and neonatal care admission was evaluated using logistic regression. Random-effects meta-analysis was used to combine results between countries. Results: Among the 157 521 singleton births included in the study (103 409 in Sweden and 54 112 in Norway), the mean maternal age at the time of delivery was 31 years, and 28 506 (18%) were vaccinated against SARS-CoV-2 (12.9% with BNT162b2, 4.8% with mRNA-1273, and 0.3% with AZD1222) while pregnant. A total of 0.7%, 8.3%, and 9.1% of individuals delivering were vaccinated during the first, second, and third trimester, respectively. Vaccination against SARS-CoV-2 was not significantly associated with increased risk of preterm birth (6.2 vs 4.9 per 10 000 pregnancy days; adjusted hazard ratio [aHR], 0.98 [95% CI, 0.91 to 1.05]; I2 = 0%; P for heterogeneity = .60), stillbirth (2.1 vs 2.4 per 100 000 pregnancy days; aHR, 0.86 [95% CI, 0.63 to 1.17]), small for gestational age (7.8% vs 8.5%; difference, -0.6% [95% CI, -1.3% to 0.2%]; adjusted OR [aOR], 0.97 [95% CI, 0.90 to 1.04]), low Apgar score (1.5% vs 1.6%; difference, -0.05% [95% CI, -0.3% to 0.1%]; aOR, 0.97 [95% CI, 0.87 to 1.08]), or neonatal care admission (8.5% vs 8.5%; difference, 0.003% [95% CI, -0.9% to 0.9%]; aOR, 0.97 [95% CI, 0.86 to 1.10]). Conclusions and Relevance: In this population-based study conducted in Sweden and Norway, vaccination against SARS-CoV-2 during pregnancy, compared with no SARS-CoV-2 vaccination during pregnancy, was not significantly associated with an increased risk of adverse pregnancy outcomes. The majority of the vaccinations were with mRNA vaccines during the second and third trimesters of pregnancy, which should be considered in interpreting the findings.

Preterm birth after the introduction of COVID-19 mitigation measures in Norway, Sweden, and Denmark: a registry-based difference-in-differences study.

BACKGROUND: Although some studies have reported a decrease in preterm birth following the start of the COVID-19 pandemic, the findings are inconsistent. OBJECTIVE: This study aimed to compare the incidences of preterm birth before and after the introduction of COVID-19 mitigation measures in Scandinavian countries using robust population-based registry data. STUDY DESIGN: This was a registry-based difference-in-differences study using births from January 2014 through December 2020 in Norway, Sweden, and Denmark. The changes in the preterm birth (<37 weeks) rates before and after the introduction of COVID-19 mitigation measures (set to March 12, 2020) were compared with the changes in preterm birth before and after March 12 from 2014 to 2019. The differences per 1000 births were calculated for 2-, 4-, 8-, 12-, and 16-week intervals before and after March 12. The secondary analyses included medically indicated preterm birth, spontaneous preterm birth, and very preterm (<32 weeks) birth. RESULTS: A total of 1,519,521 births were included in this study. During the study period, 5.6% of the births were preterm in Norway and Sweden, and 5.7% were preterm in Denmark. There was a seasonal variation in the incidence of preterm birth, with the highest incidence during winter. In all the 3 countries, there was a slight overall decline in preterm births from 2014 to 2020. There was no consistent evidence of a change in the preterm birth rates following the introduction of COVID-19 mitigation measures, with difference-in-differences estimates ranging from 3.7 per 1000 births (95% confidence interval, -3.8 to 11.1) for the first 2 weeks after March 12, 2020, to -1.8 per 1000 births (95% confidence interval, -4.6 to 1.1) in the 16 weeks after March 12, 2020. Similarly, there was no evidence of an impact on medically indicated preterm birth, spontaneous preterm birth, or very preterm birth. CONCLUSION: Using high-quality national data on births in 3 Scandinavian countries, each of which implemented different approaches to address the pandemic, there was no evidence of a decline in preterm births following the introduction of COVID-19 mitigation measures.

Factors associated with hospitalization, invasive mechanical ventilation treatment and death among all confirmed COVID-19 cases in Norway: Prospective cohort study.

Aims: For everyone with a positive test for SARS-CoV-2 in Norway, we studied whether age, sex, comorbidity, continent of birth and nursing home residency were risk factors for hospitalization, invasive mechanical ventilation treatment and death. Methods: Data for everyone who had tested positive for SARS-CoV-2 in Norway by end of June 2020 (N = 8569) were linked at the individual level to hospitalization, receipt of invasive mechanical ventilation treatment and death measured to end of July 2020. Underlying comorbidity was proxied by hospital-based in- or outpatient treatment during the two months before the SARS-CoV-2 test. Multivariable generalized linear models were used to assess risk ratios (RRs). Results: Risk of hospitalization was particularly high for elderly (for those aged 90 and above: RR 9.5; 95% confidence interval (CI) 7.1-12.7; comparison group aged below 50), Norwegian residents born in Asia, Africa or Latin-America (RR 2.1; 95% CI 1.9-2.4; comparison group born in Norway), patients with underlying comorbidity (RR 1.6; 95% CI 1.4-1.8) and men (RR 1.3; 95% CI 1.2-1.5). Men and residents born in Africa, Asia and Latin-America were also at higher risk of receiving ventilation treatment and dying, but the mortality risk was especially high for the elderly (for those aged 90 and above: RR 607.9; 95% CI 145.5-2540.1; comparison group aged below 50) and residents in nursing homes (RR 4.2; 95% CI 3.1-5.7). Conclusions: High age was the most important predictor of severe disease and death if infected with SARS-CoV-2, and nursing home residents were at particularly high risk of death.

Underlying conditions in adults with COVID-19. / Underliggende tilstander hos voksne med covid-19.

BACKGROUND: Cardiovascular diseases, cancer, type-2 diabetes and chronic obstructive pulmonary disease (COPD) were initially noted as the most common diseases among individuals who were hospitalised for COVID-19. However, the evidence base is weak. The objective of this study is to describe how selected diseases were distributed among adults with confirmed COVID-19 (COVID-19 positive tests) and among those hospitalised for COVID-19 compared to the general population. MATERIAL AND METHOD: We used data from the Norwegian Patient Registry, the Norwegian Registry for Primary Health Care and the Norwegian Surveillance System for Communicable Diseases for adults from the age of 20 and older for the period 1 March 2020-13 May 2020. RESULTS: Of all those who tested positive for COVID-19, 7 632 (94 %) were aged 20 years or older, and 1 025 (13.4 %) of these had been hospitalised. Among those hospitalised with COVID-19, there was a higher proportion of individuals with cardiovascular diseases (18.3 % versus 15.6 %), cancer (6.9 % versus 5.4 %), type-2 diabetes (8.6 % versus 5.2 %) and COPD (3.8 % versus 2.7 %) than in the general population as a whole after adjusting for age. The proportion of hospitalised patients with asthma, other chronic respiratory disease, cardiovascular disease, ongoing cancer treatment, complications related to hypertension, obesity and overweight, neurological disorders and cardiac and renal failure was also higher than in the general population. There were few differences between persons who had tested positive for COVID-19 and the general population in terms of underlying conditions. INTERPRETATION: Among those hospitalised for COVID-19, there was a higher proportion of patients with underlying illnesses than in the general population. This may indicate that these patients tend to have a more severe course of disease or that they are more likely to be hospitalised compared to healthy individuals. The results must be interpreted with caution, since the sample of COVID-19 individuals is non-random.