Systematic review and meta-analysis of the effectiveness and perinatal outcomes of COVID-19 vaccination in pregnancy.

Safety and effectiveness of COVID-19 vaccines during pregnancy is a particular concern affecting vaccination uptake by this vulnerable group. Here we evaluated evidence from 23 studies including 117,552 COVID-19 vaccinated pregnant people, almost exclusively with mRNA vaccines. We show that the effectiveness of mRNA vaccination against RT-PCR confirmed SARS-CoV-2 infection 7 days after second dose was 89·5% (95% CI 69·0-96·4%, 18,828 vaccinated pregnant people, I2 = 73·9%). The risk of stillbirth was significantly lower in the vaccinated cohort by 15% (pooled OR 0·85; 95% CI 0·73-0·99, 66,067 vaccinated vs. 424,624 unvaccinated, I2 = 93·9%). There was no evidence of a higher risk of adverse outcomes including miscarriage, earlier gestation at birth, placental abruption, pulmonary embolism, postpartum haemorrhage, maternal death, intensive care unit admission, lower birthweight Z-score, or neonatal intensive care unit admission (p > 0.05 for all). COVID-19 mRNA vaccination in pregnancy appears to be safe and is associated with a reduction in stillbirth.

Management and implications of severe COVID-19 in pregnancy in the UK: data from the UK Obstetric Surveillance System national cohort.

INTRODUCTION: There is a lack of population level data on risk factors and impact of severe COVID-19 in pregnancy. The aims of this study were to determine the characteristics, and maternal and perinatal outcomes associated with severe COVID-19 in pregnancy compared with those with mild and moderate COVID-19 and to explore the impact of timing of birth. MATERIAL AND METHODS: This was a secondary analysis of a national, prospective cohort study. All pregnant women admitted to hospital in the UK with symptomatic SARS-CoV-2 from March 1, 2020 to October 31, 2021 were included. The severity of maternal infection (need for high flow or invasive ventilation, intensive care admission or died), pregnancy and perinatal outcomes, and the impact of timing of birth were analyzed using multivariable logistic regression. RESULTS: Of 4436 pregnant women, 13.9% (n = 616) had severe infection. Women with severe infection were more likely to be aged ≥30 years (adjusted odds ratio [aOR] aged 30-39 1.48, 95% confidence interval [CI] 1.20-1.83), be overweight or obese (aOR 1.73, 95% CI 1.34-2.25 and aOR 2.52 95% CI 1.97-3.23, respectively), be of mixed ethnicity (aOR 1.93, 95% CI 1.17-3.21) or have gestational diabetes (aOR 1.43, 95% CI 1.09-1.87) compared with those with mild or moderate infection. Women with severe infection were more likely to have a pre-labor cesarean birth (aOR 8.84, 95% CI 6.61-11.83), a very or extreme preterm birth (28-31+ weeks' gestation, aOR 18.97, 95% CI 7.78-14.85; <28 weeks' gestation, aOR 12.35, 95% CI 6.34-24.05) and their babies were more likely to be stillborn (aOR 2.51, 95% CI 1.35-4.66) or admitted to a neonatal unit (aOR 11.61, 95% CI 9.28-14.52). Of 112 women with severe infection who were discharged and gave birth at a later admission, the majority gave birth ≥36 weeks (85.7%), noting that three women in this group (2.7%) had a stillbirth. CONCLUSIONS: Severe COVID-19 in pregnancy increases the risk of adverse outcomes. Information to promote uptake of vaccination should specifically target those at greatest risk of severe outcomes. Decisions about timing of birth should be informed by multidisciplinary team discussion; however, our data suggest that women with severe infection who do not require early delivery have mostly good outcomes but that those with severe infection at term may warrant rapid delivery.

The incidence, characteristics and outcomes of pregnant women hospitalized with symptomatic and asymptomatic SARS-CoV-2 infection in the UK from March to September 2020: A national cohort study using the UK Obstetric Surveillance System (UKOSS).

BACKGROUND: There is a lack of population level data on risk factors, incidence and impact of SARS-CoV-2 infection in pregnant women and their babies. The primary aim of this study was to describe the incidence, characteristics and outcomes of hospitalized pregnant women with symptomatic and asymptomatic SARS-CoV-2 in the UK compared to pregnant women without SARS-CoV-2. METHODS AND FINDINGS: We conducted a national, prospective cohort study of all hospitalized pregnant women with confirmed SARS-CoV-2 from 01/03/2020 to 31/08/2020 using the UK Obstetric Surveillance System. Incidence rates were estimated using national maternity data. Overall, 1148 hospitalized women had confirmed SARS-CoV-2 in pregnancy, 63% of which were symptomatic. The estimated incidence of hospitalization with symptomatic SARS-CoV-2 was 2.0 per 1000 maternities (95% CI 1.9-2.2) and for asymptomatic SARS-CoV-2 was 1.2 per 1000 maternities (95% CI 1.1-1.4). Compared to pregnant women without SARS-CoV-2, women hospitalized with symptomatic SARS-CoV-2 were more likely to be overweight or obese (adjusted OR 1.86, (95% CI 1.39-2.48) and aOR 2.07 (1.53-2.29)), to be of Black, Asian or Other minority ethnic group (aOR 6.24, (3.93-9.90), aOR 4.36, (3.19-5.95) and aOR 12.95, (4.93-34.01)), and to have a relevant medical comorbidity (aOR 1.83 (1.32-2.54)). Hospitalized pregnant women with symptomatic SARS-CoV-2 were more likely to be admitted to intensive care (aOR 57.67, (7.80-426.70)) but the absolute risk of poor outcomes was low. Cesarean births and neonatal unit admission were increased regardless of symptom status (symptomatic aOR 2.60, (1.97-3.42) and aOR 3.08, (1.99-4.77); asymptomatic aOR 2.02, (1.52-2.70) and aOR 1.84, (1.12-3.03)). The risks of stillbirth or neonatal death were not significantly increased, regardless of symptom status. CONCLUSIONS: We have identified factors that increase the risk of symptomatic and asymptomatic SARS-CoV-2 in pregnancy. Clinicians can be reassured that the majority of women do not experience severe complications of SARS-CoV-2 in pregnancy.

Maternal and perinatal outcomes of pregnant women with SARS-CoV-2 infection at the time of birth in England: national cohort study.

BACKGROUND: Some studies have suggested that women with SARS-CoV-2 infection during pregnancy are at increased risk of adverse pregnancy and neonatal outcomes, but these associations are still not clear. OBJECTIVE: This study aimed to determine the association between SARS-CoV-2 infection at the time of birth and maternal and perinatal outcomes. STUDY DESIGN: This is a population-based cohort study in England. The inclusion criteria were women with a recorded singleton birth between May 29, 2020, and January 31, 2021, in a national database of hospital admissions. Maternal and perinatal outcomes were compared between pregnant women with a laboratory-confirmed SARS-CoV-2 infection recorded in the birth episode and those without. Study outcomes were fetal death at or beyond 24 weeks' gestation (stillbirth), preterm birth (<37 weeks' gestation), small for gestational age infant (small for gestational age; birthweight at the .05) in the rate of other maternal outcomes. The risk of neonatal adverse outcome (adjusted odds ratio, 1.45; 95% confidence interval, 1.27-1.66; P<.001), need for specialist neonatal care (adjusted odds ratio, 1.24; 95% confidence interval, 1.02-1.51; P=.03), and prolonged neonatal admission after birth (adjusted odds ratio, 1.61; 95% confidence interval, 1.49-1.75; P<.001) were all significantly higher for infants with mothers with laboratory-confirmed SARS-CoV-2 infection. When the analysis was restricted to pregnancies delivered at term (≥37 weeks), there were no significant differences in neonatal adverse outcome (P=.78), need for specialist neonatal care after birth (P=.22), or neonatal readmission within 4 weeks of birth (P=.05). Neonates born at term to mothers with laboratory-confirmed SARS-CoV-2 infection were more likely to have prolonged admission after birth (21.1% compared with 14.6%; adjusted odds ratio, 1.61; 95% confidence interval, 1.49-1.75; P<.001). CONCLUSION: SARS-CoV-2 infection at the time of birth is associated with higher rates of fetal death, preterm birth, preeclampsia, and emergency cesarean delivery. There were no additional adverse neonatal outcomes, other than those related to preterm delivery. Pregnant women should be counseled regarding risks of SARS-CoV-2 infection and should be considered a priority for vaccination.

Global changes in maternity care provision during the COVID-19 pandemic: A systematic review and meta-analysis.

BACKGROUND: The COVID-19 pandemic has had a profound impact on healthcare systems globally, with a worrying increase in adverse maternal and foetal outcomes. We aimed to assess the changes in maternity healthcare provision and healthcare-seeking by pregnant women during the COVID-19 pandemic. METHODS: We performed a systematic review and meta-analysis of studies of the effects of the pandemic on provision of, access to and attendance at maternity services (CRD42020211753). We searched MEDLINE and Embase in accordance with PRISMA guidelines from January 1st, 2020 to April 17th 2021 for controlled observational studies and research letters reporting primary data comparing maternity healthcare-seeking and healthcare delivery during compared to before the COVID-19 pandemic. Case reports and series, systematic literature reviews, and pre-print studies were excluded. Meta-analysis was performed on comparable outcomes that were reported in two or more studies. Data were combined using random-effects meta-analysis, using risk ratios (RR) or incidence rate ratios (IRR) with 95% confidence intervals (CI). FINDINGS: Of 4743 citations identified, 56 were included in the systematic review, and 21 in the meta-analysis. We identified a significant decrease in the number of antenatal clinic visits (IRR 0614, 95% CI 0486-0776, P<00001, I2=54.6%) and unscheduled care visits (IRR 0741, 95% CI 0602-0911, P = 00046, I2=00%) per week, and an increase in virtual or remote antenatal care (IRR 4656 95% CI 7762-2794, P<00001, I2=90.6%) and hospitalisation of unscheduled attendees (RR 1214, 95% CI 1118-1319, P<00001, I2=00%). There was a decrease in the use of GA for category 1 Caesarean sections (CS) (RR 0529, 95% CI 0407-0690, P<00001, I2=00%). There was no significant change in intrapartum epidural use (P = 00896) or the use of GA for elective CS (P = 079). INTERPRETATION: Reduced maternity healthcare-seeking and healthcare provision during the COVID-19 pandemic has been global, and must be considered as potentially contributing to worsening of pregnancy outcomes observed during the pandemic.

Effects of the COVID-19 pandemic on maternal and perinatal outcomes: a systematic review and meta-analysis.

BACKGROUND: The COVID-19 pandemic has had a profound impact on health-care systems and potentially on pregnancy outcomes, but no systematic synthesis of evidence of this effect has been undertaken. We aimed to assess the collective evidence on the effects on maternal, fetal, and neonatal outcomes of the pandemic. METHODS: We did a systematic review and meta-analysis of studies on the effects of the pandemic on maternal, fetal, and neonatal outcomes. We searched MEDLINE and Embase in accordance with PRISMA guidelines, from Jan 1, 2020, to Jan 8, 2021, for case-control studies, cohort studies, and brief reports comparing maternal and perinatal mortality, maternal morbidity, pregnancy complications, and intrapartum and neonatal outcomes before and during the pandemic. We also planned to record any additional maternal and offspring outcomes identified. Studies of solely SARS-CoV-2-infected pregnant individuals, as well as case reports, studies without comparison groups, narrative or systematic literature reviews, preprints, and studies reporting on overlapping populations were excluded. Quantitative meta-analysis was done for an outcome when more than one study presented relevant data. Random-effects estimate of the pooled odds ratio (OR) of each outcome were generated with use of the Mantel-Haenszel method. This review was registered with PROSPERO (CRD42020211753). FINDINGS: The search identified 3592 citations, of which 40 studies were included. We identified significant increases in stillbirth (pooled OR 1·28 [95% CI 1·07-1·54]; I2=63%; 12 studies, 168 295 pregnancies during and 198 993 before the pandemic) and maternal death (1·37 [1·22-1·53; I2=0%, two studies [both from low-income and middle-income countries], 1 237 018 and 2 224 859 pregnancies) during versus before the pandemic. Preterm births before 37 weeks' gestation were not significantly changed overall (0·94 [0·87-1·02]; I2=75%; 15 studies, 170 640 and 656 423 pregnancies) but were decreased in high-income countries (0·91 [0·84-0·99]; I2=63%; 12 studies, 159 987 and 635 118 pregnancies), where spontaneous preterm birth was also decreased (0·81 [0·67-0·97]; two studies, 4204 and 6818 pregnancies). Mean Edinburgh Postnatal Depression Scale scores were higher, indicating poorer mental health, during versus before the pandemic (pooled mean difference 0·42 [95% CI 0·02-0·81; three studies, 2330 and 6517 pregnancies). Surgically managed ectopic pregnancies were increased during the pandemic (OR 5·81 [2·16-15·6]; I2=26%; three studies, 37 and 272 pregnancies). No overall significant effects were identified for other outcomes included in the quantitative analysis: maternal gestational diabetes; hypertensive disorders of pregnancy; preterm birth before 34 weeks', 32 weeks', or 28 weeks' gestation; iatrogenic preterm birth; labour induction; modes of delivery (spontaneous vaginal delivery, caesarean section, or instrumental delivery); post-partum haemorrhage; neonatal death; low birthweight (<2500 g); neonatal intensive care unit admission; or Apgar score less than 7 at 5 min. INTERPRETATION: Global maternal and fetal outcomes have worsened during the COVID-19 pandemic, with an increase in maternal deaths, stillbirth, ruptured ectopic pregnancies, and maternal depression. Some outcomes show considerable disparity between high-resource and low-resource settings. There is an urgent need to prioritise safe, accessible, and equitable maternity care within the strategic response to this pandemic and in future health crises. FUNDING: None.

COVID-19 in Women's health: Epidemiology.

The disease COVID-19 emerged in late 2019 in Wuhan, China, and rapidly spread, causing a pandemic that is ongoing and has resulted in more than two million deaths worldwide. COVID-19 is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which spreads effectively by direct contact with an infected person or contaminated surface, droplet or aerosol transmission. Vertical transmission, if it does occur, is rare. Among women of childbearing age, most will have mild or asymptomatic infection; severe illness is uncommon. Severe illness is more common in the later stages of pregnancy, when it is associated with complications, including intensive care admission, maternal death and an increased risk of iatrogenic preterm birth. Women who are older, from minority ethnic groups, who are overweight or obese, who have comorbidities or who live with socioeconomic deprivation are more likely to experience severe illness than women without these characteristics.

Women's perceptions of COVID-19 and their healthcare experiences: a qualitative thematic analysis of a national survey of pregnant women in the United Kingdom.

BACKGROUND: The aim of this national survey was to explore pregnant women's perceptions of COVID-19 and their healthcare experiences. METHODS: Through patient and public involvement, a questionnaire was developed and advertised via the BBC website, Twitter and other online media during May 2020. The findings were analysed by qualitative thematic analysis. Women who are currently pregnant, or who have delivered during the COVID-19 pandemic were invited to partake in a national online survey. RESULTS: One thousand four hundred fifty-one participants replied to the online questionnaire. Participants provided significant insight into the perceived barriers to seeking healthcare during this pandemic. These include 'not wanting to bother anyone', 'lack of wider support from allied healthcare workers' and the influence of the media. Other concerns included the use of virtual clinics antenatally and their acceptability to patients, the presence of birthing partners, and the way in which information is communicated about rapidly changing and evolving services. The influence of the media has also had a significant impact on the way women perceive hospital care in light of COVID-19 and for some, this has shaped whether they would seek help. CONCLUSIONS: This is the first ever reported study in the United Kingdom to explore pregnant women's perceptions of COVID-19 and their subsequent healthcare experiences. It has also provided insight into perceived barriers into seeking care as well as maternal concerns antenatally, intrapartum and postpartum.

SARS-CoV-2 infection in pregnancy: A systematic review and meta-analysis of clinical features and pregnancy outcomes.

BACKGROUND: Perform a systematic review and meta-analysis of SARS-CoV-2 infection and pregnancy. METHODS: Databases (Medline, Embase, Clinicaltrials.gov, Cochrane Library) were searched electronically on 6th April and updated regularly until 8th June 2020. Reports of pregnant women with reverse transcription PCR (RT-PCR) confirmed COVID-19 were included. Meta-analytical proportion summaries and meta-regression analyses for key clinical outcomes are provided. FINDINGS: 86 studies were included, 17 studies (2567 pregnancies) in the quantitative synthesis; other small case series and case reports were used to extract rarely-reported events and outcome. Most women (73.9%) were in the third trimester; 52.4% have delivered, half by caesarean section (48.3%). The proportion of Black, Asian or minority ethnic group membership (50.8%); obesity (38.2%), and chronic co-morbidities (32.5%) were high. The most commonly reported clinical symptoms were fever (63.3%), cough (71.4%) and dyspnoea (34.4%). The commonest laboratory abnormalities were raised CRP or procalcitonin (54.0%), lymphopenia (34.2%) and elevated transaminases (16.0%). Preterm birth before 37 weeks' gestation was common (21.8%), usually medically-indicated (18.4%). Maternal intensive care unit admission was required in 7.0%, with intubation in 3.4%. Maternal mortality was uncommon (~1%). Maternal intensive care admission was higher in cohorts with higher rates of co-morbidities (beta=0.007, p<0.05) and maternal age over 35 years (beta=0.007, p<0.01). Maternal mortality was higher in cohorts with higher rates of antiviral drug use (beta=0.03, p<0.001), likely due to residual confounding. Neonatal nasopharyngeal swab RT-PCR was positive in 1.4%. INTERPRETATION: The risk of iatrogenic preterm birth and caesarean delivery was increased. The available evidence is reassuring, suggesting that maternal morbidity is similar to that of women of reproductive age. Vertical transmission of the virus probably occurs, albeit in a small proportion of cases. FUNDING: N/A.

Characteristics and outcomes of pregnant women admitted to hospital with confirmed SARS-CoV-2 infection in UK: national population based cohort study.

OBJECTIVES: To describe a national cohort of pregnant women admitted to hospital with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the UK, identify factors associated with infection, and describe outcomes, including transmission of infection, for mothers and infants. DESIGN: Prospective national population based cohort study using the UK Obstetric Surveillance System (UKOSS). SETTING: All 194 obstetric units in the UK. PARTICIPANTS: 427 pregnant women admitted to hospital with confirmed SARS-CoV-2 infection between 1 March 2020 and 14 April 2020. MAIN OUTCOME MEASURES: Incidence of maternal hospital admission and infant infection. Rates of maternal death, level 3 critical care unit admission, fetal loss, caesarean birth, preterm birth, stillbirth, early neonatal death, and neonatal unit admission. RESULTS: The estimated incidence of admission to hospital with confirmed SARS-CoV-2 infection in pregnancy was 4.9 (95% confidence interval 4.5 to 5.4) per 1000 maternities. 233 (56%) pregnant women admitted to hospital with SARS-CoV-2 infection in pregnancy were from black or other ethnic minority groups, 281 (69%) were overweight or obese, 175 (41%) were aged 35 or over, and 145 (34%) had pre-existing comorbidities. 266 (62%) women gave birth or had a pregnancy loss; 196 (73%) gave birth at term. Forty one (10%) women admitted to hospital needed respiratory support, and five (1%) women died. Twelve (5%) of 265 infants tested positive for SARS-CoV-2 RNA, six of them within the first 12 hours after birth. CONCLUSIONS: Most pregnant women admitted to hospital with SARS-CoV-2 infection were in the late second or third trimester, supporting guidance for continued social distancing measures in later pregnancy. Most had good outcomes, and transmission of SARS-CoV-2 to infants was uncommon. The high proportion of women from black or minority ethnic groups admitted with infection needs urgent investigation and explanation. STUDY REGISTRATION: ISRCTN 40092247.