COVID-19 vaccination rates and SARS-CoV-2 infection in pregnant women in Scotland

We describe SARS-CoV-2 infection and COVID-19 vaccine uptake in Scotland in a prospective cohort of all pregnant women in Scotland drawn from national databases. As of mid-October 2021, the Covid-19 in pregnancy in Scotland (COPS) cohort included linked data on a total of 139,136 pregnancies in 126,749 women. Up to September 30, 2021, a total of 22,779 COVID-19 vaccinations had been administered to 16,229 pregnant women. Vaccine coverage was substantially lower in pregnant women than in the general female population of reproductive age (23.7% of women giving birth in September 2021 were fully vaccinated compared to 74.9 % in women 18-44 years). Of the 4,274 cases of COVID-19 in pregnancy (conrmed by SARS-CoV-2 viral reverse transcriptase polymerase chain reaction) between December 2020 (the month the COVID-19 vaccination programme started in Scotland) and September 2021 inclusive, 629 women (14.7%) were admitted to hospital and 89 (2.1%) were admitted to critical care. Of the COVID-19 cases occurring in pregnant women, 81.7% (3,491/4,274; 95% CI 80.5-82.8) were in unvaccinated women. Of the COVID-19 associated hospital admissions, 93.0% (585/629; 95% CI 90.7-94.8) were in women who were unvaccinated at the time of COVID-19 diagnosis. Of the COVID-19 associated critical care admissions 98.9% (88/89; 95% CI 93.9-100) were in women who were unvaccinated at the time of COVID-19 diagnosis. The extended perinatal mortality rate for women who gave birth within 28 days of COVID-19 diagnosis was 15.9 per 1000 births (95% CI 7.8 to 31.0; background rate in 2020 6.3 per 1,000 total births [95% CI 5.7-7.1]; background rate 2019 5.7 per 1,000 total births [95% CI 5.0-6.4]). All baby deaths occurred after pregnancies in women

Here we describe SARS-CoV-2 infection and COVID-19 vaccine uptake in Scotland, using population data from a national, prospective dynamic cohort (the COVID-19 in Pregnancy in Scotland (COPS) study; 11,12 a sub-study of EAVE II (Early Pandemic Evaluation and Enhanced Surveillance of COVID-19). 13,14 COPS includes all women who were pregnant on, or became pregnant after, March 1, 2020; technical details and study ethical and governance approval details are summarized in Table S2.
In COPS, we have linked national healthcare data from women who had early pregnancy loss, termination of pregnancy, live or stillbirth, neonatal death, or antenatal care for an ongoing pregnancy with national data on COVID-19 vaccination and con rmed SARS-CoV-2 infection (positive viral reverse transcriptase polymerase chain reaction [RT-PCR] test) (details of datasets are in Table S2 and 11,12 ). As of mid-October 2021, the COPS database included linked data on a total of 139,136 pregnancies in 126,749 women.

COVID-19 rates in pregnancy in Scotland
Up to September 30, 2021, there were 4,979 cases of SARS-CoV-2 in pregnant women. Throughout the pandemic, rates of con rmed SARS-CoV-2 in pregnancy showed similar patterns to those in the general female population of reproductive age, with peaks of infection in October 2020 and January 2021, and high infection rates in July and August 2021, which continued to increase in pregnant women to the time of latest data release in September 2021 ( Figure 1) (numbers of infections presented in Table S3). Infection rates have been consistently highest in pregnant women living in the most deprived areas, and in younger, compared to older, pregnant women ( Figure S1), similar to patterns seen in the general population. 15 The percentage of SARS-CoV-2 infections that were temporally associated with a hospital admission (i.e., admission within 14 days of positive COVID-19 RT-PCR) or critical care admission (i.e. admission within 21 days of positive COVID-19 RT-PCR) was higher in pregnant women than those in the general female population age 18-44 years ( Figure 1). This is likely to re ect the fact that admission is generally more common among pregnant than non-pregnant women (due to admissions for obstetric complications, labour and birth; as well as potentially due to a lower threshold for admission for COVID-19 in pregnant women than for COVID-19 in the general population), and also that COVID-19 is more likely to cause severe disease in pregnant than non-pregnant women. 1 Although surveillance studies (mainly based on women admitted to hospital) have suggested that pregnant women are at highest risk of COVID-19 in the third trimester, 8 these Scottish population datacapturing all virologically con rmed infections in a setting where testing has been widely available in hospital and the community -show SARS-CoV-2 infections were relatively evenly spread throughout pregnancy: 1,592 (31.9% 95% CI 30. 38.6-39.9) vaccinations were given in the rst trimester of pregnancy (2 +0 to 13 +6 weeks gestation); 8,030 (35.3%; 95% CI 34.6-35.9) in the second trimester (14 +0 to 27 +6 weeks gestation); and 5,804 (25.5%; 95% CI 24.9-26.1) in the third trimester (28 +0 weeks gestation or over). 17,841 (78.3%; 95% CI 77.8-78.9) of the vaccinations given were P zer-BioNTech BNT162b2 mRNA vaccine; 2,853 (12.3%; 95% CI 12.1-13.0) were Moderna mRNA-1273 mRNA vaccine; and 2,085 (9.2%; 95% CI 8.8-9.5%) were Oxford-AstraZeneca AZD1222 viral vector vaccine.
Coverage of vaccination (de ned as the percentage of women who were vaccinated at some point prior to giving birth i.e. vaccination may have been given before or during pregnancy) increased over time, but coverage has been consistently substantially lower than coverage in the same age groups seen in the general female population ( cases associated with hospital admissions, and 98.9% (88/89; 95% CI 93.9-100) of COVID-19 cases associated with critical care admissions occurred in women who were unvaccinated at the time of COVID-19 diagnosis ( Figure 1). As of the latest data release of September 30, 2021, there had been no maternal deaths associated with COVID-19 in pregnancy in Scotland (i.e. no women with con rmed COVID-19 in pregnancy who subsequently died during pregnancy or in the six weeks following pregnancy).
By mid-October 2021, a total of 567 babies born within 28 days of maternal COVID-19 diagnosis. Of these, eight were stillbirths (deaths in utero ≥24 weeks gestation) and one was a neonatal death (death within 28 days of birth) giving an extended perinatal mortality rate in this population of 15.9 per 1000 births (95% CI 7.8 to 31.0; background rate in 2020 6.3 per 1,000 total births [95% CI 5.7-7.1]; background rate 2019 5.7 per 1,000 total births [95% CI 5.0-6.4]). 16 All perinatal deaths occurred in women who were unvaccinated at the time of COVID-19 diagnosis.

Adverse events associated with vaccination
There have been no maternal deaths associated with COVID-19 vaccination in Scotland (i.e. no women who received COVID-19 vaccination and subsequently died during pregnancy or in the six weeks following pregnancy). By mid-October 2021, a total of 3,809 babies had been born to women who had received COVID-19 vaccination during pregnancy. Six of these births were stillbirths and eight babies died within 28 days of birth, giving an extended perinatal mortality rate of 3.7 per 1000 total births [95% CI 2.0-6.2], which is reassuringly in line with the background extended perinatal mortality rates of 6.3 per 1,000 total births [95% CI 5.7-7.1] in 2020 and 5.7 per 1,000 total births [95% CI 5.0-6.4]) in 2019. 16 Conclusion These data provide new national evidence of low levels of vaccine uptake in pregnancy in Scotland, at a time when the Delta variant dominated and infection rates were still increasing in pregnant women. We found that complications known to be associated with COVID-19 in pregnancy (critical care admission, perinatal mortality) were far more common in women who were unvaccinated at the time of SARS-CoV-2 diagnosis than in vaccinated pregnant women. Although COVID-19 rates were similar across all trimesters of pregnancy, and mirrored those in the general female population of reproductive age, associated hospital admissions and critical care admissions were higher in pregnant women than in the general female population of reproductive age, and highest in the third trimester. Low vaccine uptake rates in Scotland are likely to be representative of those in the U.K. and other high-income countries. 17,18 Addressing low vaccine uptake rates in pregnant women is imperative to protect the health of women and babies.   women. An episode of COVID-19 was been de ned as associated with a hospital admission if the woman was admitted to hospital ≤14 days after the date of onset of COVID-19, or if the date of onset occurred at any point during a hospital admission. Rates of COVID-19 associated hospital admissions have been consistently higher than rates in the general female population of reproductive age. General hospital admissions is incomplete for August and September due to source data latency and so these have not been included in the gure. There were very low case numbers of con rmed SARS-CoV-2 in June 2020, which may explain the very high admission rate at this point in time c. Percentage of cases of COVID-19 associated critical care admission within 21 days of diagnosis in pregnant women and the general population of women since March 2020 (month of the rst case in Scotland) per 100,000 women. An episode of COVID-19 was de ned as associated with a critical care admission if the woman was admitted to critical care ≤21 days after the date of onset of COVID-19, or if the date of onset occurred at any point during a critical care admission. Rates of COVID-19 associated critical care admissions have been higher than rates in the general female population of reproductive age since October 2020. The percentage of cases with associated admission was high early in the pandemic due to restricted testing (mainly people ill enough to require admission and healthcare workers before May 2020). in pregnant women (calculated as the number of women receiving any COVID-19 vaccination during pregnancy in the month, divided by the number of women with an ongoing pregnancy at the start of that month*100). c. Percentage of cases of COVID-19 (con rmed by SARS-2-CoV RT-PCR) in pregnancy occurring Dec 2020 to September 2021 inclusive, cases with associated hospital admission, and cases with associated critical care admission, by vaccination status at the date of rst positive RT-PCR test. Unvaccinated is de ned as no prior COVID-19 vaccination prior to the date of onset of COVID-19, or with one dose of vaccination ≤21 days prior to the date of onset. Partially vaccinated is de ned as one dose of vaccination >21 days prior to the date of onset of COVID-19, or two doses of vaccination with the second dose ≤14 days prior to the date of onset. Fully vaccinated is de ned as two doses of vaccination with the second dose >14 days prior to the date of onset of COVID-19.

Supplementary Files
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