Concerns have been raised regarding a potential surge of COVID-19 in pregnancy, secondary to the rising numbers of COVID-19 in the community, easing of societal restrictions, and vaccine hesitancy. Although COVID-19 vaccination is now offered to all pregnant women in the United Kingdom; limited data exist on its uptake and safety.
This study aimed to investigate the uptake and safety of COVID-19 vaccination among pregnant women.
This was a cohort study of pregnant women who gave birth at St George’s University Hospitals National Health Service Foundation Trust, London, United Kingdom, between March 1, 2020, and July 4, 2021. The primary outcome was uptake of COVID-19 vaccination and its determinants. The secondary outcomes were perinatal safety outcomes. Data were collected on COVID-19 vaccination uptake, vaccination type, gestational age at vaccination, and maternal characteristics, including age, parity, ethnicity, index of multiple deprivation score, and comorbidities. Further data were collected on perinatal outcomes, including stillbirth (fetal death at ≥24 weeks’ gestation), preterm birth, fetal and congenital abnormalities, and intrapartum complications. Pregnancy and neonatal outcomes of women who received the vaccine were compared with that of a matched cohort of women with balanced propensity scores. Effect magnitudes of vaccination on perinatal outcomes were reported as mean differences or odds ratios with 95% confidence intervals. Factors associated with antenatal vaccination were assessed with logistic regression analysis.
Data were available for 1328 pregnant women of whom 140 received at least 1 dose of the COVID-19 vaccine before giving birth and 1188 women who did not; 85.7% of those vaccinated received their vaccine in the third trimester of pregnancy and 14.3% in the second trimester of pregnancy. Of those vaccinated, 127 (90.7%) received a messenger RNA vaccine and 13 (9.3%) a viral vector vaccine. There was evidence of reduced vaccine uptake in younger women ( P =.001), women with high levels of deprivation (ie, fifth quintile of the index of multiple deprivation; P =.008), and women of Afro-Caribbean or Asian ethnicity compared with women of White ethnicity ( P <.001). Women with prepregnancy diabetes mellitus had increased vaccine uptake ( P =.008). In the multivariable model the fifth deprivation quintile (most deprived) (adjusted odds ratio, 0.10; 95% confidence interval, 0.02–0.10; P =.003) and Afro-Caribbean ethnicity (adjusted odds ratio, 0.27; 95% confidence interval, 0.06–0.85; P =.044) were significantly associated with lower antenatal vaccine uptake, whereas prepregnancy diabetes mellitus was significantly associated with higher antenatal vaccine uptake (adjusted odds ratio, 10.5; 95% confidence interval, 1.74–83.2; P =.014). In a propensity score–matched cohort, the rates of adverse pregnancy outcomes of 133 women who received at least 1 dose of the COVID-19 vaccine in pregnancy were similar to that of unvaccinated pregnant women ( P >.05 for all): stillbirth (0.0% vs 0.2%), fetal abnormalities (2.2% vs 2.5%), postpartum hemorrhage (9.8% vs 9.0%), cesarean delivery (30.8% vs 34.1%), small for gestational age (12.0% vs 12.8%), maternal high-dependency unit or intensive care admission (6.0% vs 4.0%), or neonatal intensive care unit admission (5.3% vs 5.0%). Intrapartum pyrexia (3.7% vs 1.0%; P =.046) was significantly increased but the borderline statistical significance was lost after excluding women with antenatal COVID-19 infection ( P =.079). Mixed-effects Cox regression showed that vaccination was not significantly associated with birth at <40 weeks’ gestation (hazard ratio, 0.93; 95% confidence interval, 0.71–1.23; P =.624).
Of pregnant women eligible for COVID-19 vaccination, less than one-third accepted COVID-19 vaccination during pregnancy, and they experienced similar pregnancy outcomes with unvaccinated pregnant women. There was lower uptake among younger women, non-White ethnicity, and lower socioeconomic background. This study has contributed to the body of evidence that having COVID-19 vaccination in pregnancy does not alter perinatal outcomes. Clear communication to improve awareness among pregnant women and healthcare professionals on vaccine safety is needed, alongside strategies to address vaccine hesitancy. These strategies include postvaccination surveillance to gather further data on pregnancy outcomes, particularly after first-trimester vaccination, and long-term infant follow-up.
The COVID-19 pandemic has caused loss of life and poorer health outcomes, outside and in pregnancy, despite worldwide aggressive public health measures to control the spread. Mass vaccination is a key method by which countries are aiming to control the pandemic.
Why was this study conducted?
Concerns have been raised regarding a potential surge of COVID-19 in pregnancy, secondary to the rising numbers of COVID-19 in the community, easing of societal restrictions, and vaccine hesitancy. Although COVID-19 vaccination is now offered to all pregnant women in the United Kingdom, limited data exist on its uptake and safety.
We found that only 28.5% of pregnant women eligible for a COVID-19 vaccine had accepted it during pregnancy. Pregnancy and neonatal outcomes of women who received the vaccine were similar to that of a propensity score–matched cohort of pregnant women who did not receive the vaccine.
What does this add to what is known?
This study showed that clear communication and targeted strategies are needed to address vaccine hesitancy, including postvaccination surveillance to gather further data on pregnancy outcomes, particularly after first-trimester vaccination, and long-term infant follow-up.
Theoretically, COVID-19 vaccines are safe for use in pregnancy, as they do not contain a live attenuated virus. For COVID-19 vaccination in pregnancy, there has been no major safety signal from animal reproductive toxicology studies, the very small number of inadvertent pregnancies in vaccine trials, the Centers for Disease Control and Prevention (CDC) V-safe postvaccination health checker (with limited data on >30,000 pregnant women, but only 827 women have given birth), or a formal pregnancy registry (>1800 enrolled to date). A recent report of American health workers who were pregnant (n=84) or lactating (n=31) when vaccinated found that compared with nonpregnant controls (n=16), vaccine-induced humoral immunity was similar, antibody titers were higher following an actual SARS-CoV-2 infection, and antibodies were present in umbilical cord blood and breast milk, suggesting that vaccination can confer maternal and perinatal immunity.
Based on vast previous experience with other vaccines in pregnancy and no hypothesized mechanism for harm, similar efficacy and side effects are anticipated with COVID-19 vaccination in (vs outside) pregnancy. However, pregnant women were excluded from the initial randomized controlled trials (RCTs) testing the safety and efficacy of COVID-19 vaccines. Although randomized trials of COVID-19 vaccination in pregnancy have now begun, , the results will not be available until 2022 at the earliest.
Pregnant women have been reluctant to receive COVID-19 vaccination and guidance for healthcare professionals has not been consistent. Some guidelines initially recommended against routine COVID-19 vaccination in pregnancy but pivoted as safety data accumulated (eg, the United Kingdom Joint Committee on Vaccination and Immunisation [JCVI] ), whereas others recommended routine vaccination from the start (eg, the International Federation of Gynecology and Obstetrics). Therefore, this study aimed to investigate the uptake and safety of COVID-19 vaccination among pregnant women. We studied the determinants of COVID-19 vaccine uptake among eligible pregnant women and compared pregnancy outcomes in women who received COVID-19 vaccination during pregnancy with that of unvaccinated and contemporaneous pregnant controls of similar risk profiles.
Materials and Methods
Study design and population
In this retrospective cohort study, the records of all women who delivered between March 1, 2021, and July 4, 2021, in St George’s University Hospitals NHS Foundation Trust, London, United Kingdom, were screened for eligibility. The first of March was chosen as pregnant women with comorbidities were offered vaccination after this date. The inclusion criteria were pregnant women with known vaccination status and complete maternal and fetal outcome data. The exclusion criteria were women who were vaccinated entirely (ie, all doses) before pregnancy or after birth or women who had pregnancies complicated by fetal aneuploidy or genetic syndromes.
Data were obtained from electronic hospital records stored in the following systems: EuroKing E3 maternity information system, Chertsey, United Kingdom; ViewPoint Bildverarbeitung GmbH, Wessling, Germany; and Health Information Exchange—Coordinate My Care, GP Partner 2, One London Hub, One London SWL, MIG Partner, and TPP SystmOne—via Cerner, North Kansas City, Missouri. The quality of data in the later database was checked for accuracy of the COVID-19 vaccination record. For 1 week, women admitted to the postnatal ward were queried about their vaccination status, and their responses were cross-checked with the electronic records. The initial quality control showed no inconsistency between patient responses and electronic records.
Data collected included maternal age, parity, index of multiple deprivation (IMD) score, self-reported ethnicity, body mass index (BMI), alcohol and smoking habits, comorbidities, antenatal complications, and medications. The IMD combines multiple deprivation indices (income, employment, education, health, crime, barriers to housing and services, and living environment) into a single score and is widely used to assess deprivation in the United Kingdom. Other data variables included COVID-19 vaccination uptake, vaccination type, and gestational age (GA) at vaccination. Other data of interest included antenatal complications, including gestational diabetes mellitus, obstetrical cholestasis, and preeclampsia; venous thromboembolism (given the association with the Oxford-AstraZeneca vaccine) or myocarditis or pericarditis (given the association with the Pfizer-BioNTech vaccine); and antenatal medication, including medications for chronic prepregnancy disorders (such as hypothyroidism, epilepsy, diabetes mellitus, or depression) or pregnancy conditions (such as gestational hypertension or preeclampsia), but not nutritional supplements, multivitamins, iron replacement, antibiotics, antiemetics, analgesia or anti-D immunoglobulin.
Vaccine types included messenger RNA (mRNA) vaccines (Moderna, Pfizer-BioNTech) and viral vector vaccine (Oxford-AstraZeneca), which are approved for use in the United Kingdom. As for the general population, pregnant women were eligible for vaccination if they (1) were a health or social care worker, which increased their risk of SARS-Cov-2 infection, or (2) were at high risk of severe COVID-19 because of personal factors (eg, non-White ethnicity) or health conditions (eg, diabetes mellitus or gestational diabetes mellitus specifically). From April 16, 2021, vaccination was offered to those aged 45 years and above, with progressively younger groups offered vaccination from May 28, 2021. From April 16, 2021, the JCVI has advised that mRNA vaccines should be used in preference in the United Kingdom for pregnant women.
The primary study outcome was COVID-19 vaccine uptake during pregnancy among women eligible for vaccination. Vaccination eligibility was assessed by comparing delivery date with vaccination eligibility date based on the mother’s age and priority category. In the United Kingdom (2021), women became eligible for vaccination based on clinical risk and maternal age, with vaccination offered to pregnant women at the same time as the rest of the population, as follows: >40 years (from April 30, 2021), >30 years (May 26, 2021), >25 years (June 8, 2021), and >18 years (June 18, 2021). , Women who delivered after the vaccination eligibility date for their age category were considered eligible for antenatal vaccination. Vaccination uptake rate was calculated as the number of women who received at least 1 dose of any COVID-19 vaccine during pregnancy in a certain group divided by all women eligible for vaccination in that group.
Secondary outcomes included perinatal outcomes to assess the safety of COVID-19 vaccination, which included stillbirth (fetal death at ≥24 weeks’ gestation), neonatal death, fetal abnormalities, preterm birth before 37 weeks’ gestation, GA at birth in weeks, intrapartum complications (pyrexia, suspected chorioamnionitis, placental abruption, and postpartum hemorrhage), birthweight z score, mode of birth (cesarean delivery, instrumental delivery, or unassisted vaginal delivery), maternal high-dependency unit or intensive care unit (ICU) admission (any indication), and neonatal ICU admission (any indication). Postpartum hemorrhage was defined as an estimated blood loss of ≥1 L regardless of the mode of birth.
GA was determined in the first trimester of pregnancy according to the crown-rump length of the fetus (singleton pregnancies) or the larger fetus (twin pregnancies) in cases of spontaneous conception and according to the embryonic age in pregnancies conceived via assisted reproductive technology (ART). After 14 weeks’ gestation, GA was determined using the head circumference of the fetus (singleton pregnancies) or the larger fetus (twin pregnancies) in cases of spontaneous conception and according to the embryonic age in pregnancies conceived via ART. Birthweight z scores were calculated using a reference standard published by Poon et al.
Continuous variables were represented as median and interquartile range (IQR) regardless of the distribution assumptions. Categorical variables were represented as numbers and percentages. The Shapiro-Wilk test and visual inspection of quantile-quantile plots were used for verifying the normality of continuous variables. Mann-Whitney U test, t test, chi-square test, or Fisher-Freeman-Halton test was used for group comparisons as appropriate.
Factors associated with antenatal vaccination were assessed among all women eligible for vaccination, by logistic regression, with factors significant in univariable analyses assessed in a multivariable model to calculate the adjusted odds ratios (ORs). Results of regression analyses were reported as mean difference (MD), OR, or hazard ratio (HR).
The effect of COVID-19 vaccination on perinatal outcomes was assessed among women who had antenatal vaccination, compared with those who did not have the vaccine. Propensity score matching was used to match cases and controls for factors identified from between-group comparisons as potentially differing ( P <.10). Groups were matched 1:3 to simulate the observed vaccination uptake. The success of propensity score matching was assessed with propensity score histograms. After matching, the effect of vaccination was estimated using generalized estimation equations using matched group identifiers as cluster labels. Effect magnitudes of vaccination on perinatal outcomes were reported as MD or OR with 95% confidence intervals (CIs). GA at delivery was assessed in a separate cohort matched for the expected date of delivery, and confounders were identified for other perinatal outcomes. Mixed-effects Cox regression was used to estimate the effect of vaccination on GA at birth <40 weeks’ gestation. In a sensitivity analysis for pregnancy outcomes, women with antenatal COVID-19 were excluded. All analyses were performed using R for statistical computing software (version 4.0.2; R Foundation for Statistical Computing, Vienna Austria).
Between March 1, 2021, and July 4, 2021, a total of 1328 eligible women with complete vaccination records were identified ( Figure 1 ). This included 140 women who received at least 1 dose of the COVID-19 vaccine in pregnancy before birth and 1188 women who did not. Table 1 shows that women who received antenatal vaccination (vs those who did not) were slightly older, had less deprivation (ie, higher IMD scores), and were more likely to be of White ethnicity than of Afro-Caribbean ethnicity. There was no difference in maternal BMI, alcohol consumption, or smoking habits. Women with COVID-19 vaccination had significantly higher rates of pregestational diabetes mellitus, antenatal medication use, and hypertension than unvaccinated women. There was no difference in antenatal complications, including antenatal SARS-CoV-2 infection (<2% in each group), gestational diabetes mellitus ( P =.499), obstetrical cholestasis ( P =.646), or cardiac complications (ie, arrhythmia; P =.874).
|Variables||At least 1 dose during pregnancy (n=140)||Did not receive a vaccine during pregnancy (n=1188)||P value a|
|Vaccine type b|
|Pfizer-BioNTech (mRNA)||109 (77.8)||—||NA|
|Moderna (mRNA)||18 (12.9)||—||NA|
|Oxford-AstraZeneca (viral vector)||13 (9.3)||—||NA|
|Vaccination-birth interval (d)||32.3 (20.2–53.4)||—||NA|
|Trimester at vaccination|
|First trimester||0 (0.0)||—||NA|
|Second trimester||20 (14.3)||—||NA|
|Third trimester||120 (85.7)||—||NA|
|Maternal age (y)||35.0 (31.7–37.0)||33.0 (30.0–36.0)||.005|
|Parous||62 (44.3)||593 (49.9)||.207|
|IMD score||18.9 (14.0–23.7)||20.2 (14.3–27.6)||.009|
|First quintile||17 (12.1)||101 (8.5)||.152|
|Second quintile||17 (12.1)||166 (14.0)||.552|
|Third quintile||47 (33.6)||368 (31.0)||.531|
|Fourth quintile||50 (35.7)||422 (35.5)||.964|
|Fifth quintile||5 (3.6)||102 (8.6)||.039|
|Not available||4 (2.9)||29 (2.4)||.764|
|White||80 (57.1)||551 (46.4)||.015|
|Asian||17 (12.1)||205 (17.3)||.125|
|Afro-Carribean||5 (3.6)||101 (8.5)||.041|
|Mixed||13 (9.3)||156 (13.1)||.196|
|Not reported||25 (17.9)||175 (14.7)||.327|
|BMI (kg/m 2 )||23.8 (21.5–27.5)||24.2 (21.8–28.3)||.344|
|Obesity (BMI ≥30 kg/m 2 )||15 (10.7)||173 (14.6)||.216|
|Smoker||1 (0.7)||27 (2.3)||.224|
|Alcohol use||1 (0.7)||5 (0.4)||.624|
|Pregestational diabetes mellitus||6 (4.3)||7 (0.6)||<.001|
|Antenatal medication||46 (32.9)||273 (23.0)||.009|
|Hypertension on medication||13 (9.3)||46 (3.9)||.003|
|Twin pregnancy||4 (2.9)||24 (2.0)||.514|
|SARS-CoV-2 infection||2 (1.4)||16 (1.3)||.936|
|Gestational diabetes mellitus||20 (14.3)||146 (12.3)||.499|
|Obstetrical cholestasis||2 (1.4)||12 (1.0)||.646|
|Cardiac problems||1 (0.7)||10 (0.8)||.874|
|Any||25 (17.9)||175 (14.7)||.327|