National surveillance data analysis of COVID-19 vaccine uptake in England by women of reproductive age.

Women of reproductive age are a group of particular concern with regards to vaccine uptake, related to their unique considerations of menstruation, fertility, and pregnancy. To obtain vaccine uptake data specific to this group, we obtained vaccine surveillance data from the Office for National Statistics, linked with COVID-19 vaccination status from the National Immunisation Management Service, England, from 8 Dec 2020 to 15 Feb 2021; data from 13,128,525 such women at population-level, were clustered by age (18-29, 30-39, and 40-49 years), self-defined ethnicity (19 UK government categories), and index of multiple deprivation (IMD, geographically-defined IMD quintiles). Here we show that among women of reproductive age, older age, White ethnicity and being in the least-deprived index of multiple deprivation are each independently associated with higher vaccine uptake, for first and second doses; however, ethnicity exerts the strongest influence (and IMD the weakest). These findings should inform future vaccination public messaging and policy.

WILL (When to Induce Labour to Limit risk in pregnancy hypertension): a multicentre randomised controlled trial - adaptations to deliver a timing-of-birth trial during the COVID-19 international pandemic.

BACKGROUND: As a pragmatic randomised timing-of-birth trial, WILL adapted its trial procedures in response to the COVID-19 pandemic. These are reviewed here to inform post-pandemic trial methodology. METHODS: The trial (internal pilot) paused in March 2020, re-opened in July 2020, and is currently recruiting in 37 UK NHS consultant-led maternity units. We evaluated pandemic adaptations made to WILL processes and surveyed sites for their views of these changes (20 sites, videoconference). RESULTS: Despite 88% of sites favouring an electronic investigator site file (ISF), information technology requirements and clinical trial unit (CTU) operating procedures mandated the ongoing use of paper ISFs; site start-up delays resulted from restricted access to the CTU. Site initiation visits (SIVs) were conducted remotely; 50% of sites preferred remote SIVs and 44% felt that it was trial-dependent, while few preferred SIVs in-person as standard procedure. The Central team felt remote SIVs provided scheduling and attendance flexibility (for sites and trial staff), the option of recording discussions for missing or future staff, improved efficiency by having multiple sites attend, and time and cost savings; the negative impact on rapport-building and interaction was partially mitigated over time with more familiarity with technology and new ways-of-working. Two methods of remote consent were developed and used by 30/37 sites and for 54/156 recruits. Most (86%) sites using remote consenting felt it improved recruitment. For remote data monitoring (5 sites), advantages were primarily for the monitor (e.g. flexibility, no time constraints, reduced cost), and disadvantages primarily for the sites (e.g. document and access preparation, attendance at a follow-up meeting), but 81% of sites desired having the option of remote monitoring post-pandemic. CONCLUSIONS: COVID adaptations to WILL trial processes improved the flexibility of trial delivery, for Central and site staff, and participants. Flexibility to use these strategies should be retained post-pandemic. TRIAL REGISTRATION: ISRCTN77258279. Registered on 05 December 2018.

A global view of hypertensive disorders and diabetes mellitus during pregnancy.

Two important maternal cardiometabolic disorders (CMDs), hypertensive disorders in pregnancy (HDP) (including pre-eclampsia) and gestational diabetes mellitus (GDM), result in a large disease burden for pregnant individuals worldwide. A global consensus has not been reached about the diagnostic criteria for HDP and GDM, making it challenging to assess differences in their disease burden between countries and areas. However, both diseases show an unevenly distributed disease burden for regions with a low income or middle income, or low-income and middle-income countries (LMICs), or regions with lower sociodemographic and human development indexes. In addition to many common clinical, demographic and behavioural risk factors, the development and clinical consequences of maternal CMDs are substantially influenced by the social determinants of health, such as systemic marginalization. Although progress has been occurring in the early screening and management of HDP and GDM, the accuracy and long-term effects of such screening and management programmes are still under investigation. In addition to pharmacological therapies and lifestyle modifications at the individual level, a multilevel approach in conjunction with multisector partnership should be adopted to tackle the public health issues and health inequity resulting from maternal CMDs. The current COVID-19 pandemic has disrupted health service delivery, with women with maternal CMDs being particularly vulnerable to this public health crisis.

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.

An internally validated prediction model for critical COVID-19 infection and intensive care unit admission in symptomatic pregnant women.

BACKGROUND: Pregnant women are at an increased risk of mortality and morbidity owing to COVID-19. Many studies have reported on the association of COVID-19 with pregnancy-specific adverse outcomes, but prediction models utilizing large cohorts of pregnant women are still lacking for estimating the risk of maternal morbidity and other adverse events. OBJECTIVE: The main aim of this study was to develop a prediction model to quantify the risk of progression to critical COVID-19 and intensive care unit admission in pregnant women with symptomatic infection. STUDY DESIGN: This was a multicenter retrospective cohort study including 8 hospitals from 4 countries (the United Kingdom, Austria, Greece, and Turkey). The data extraction was from February 2020 until May 2021. Included were consecutive pregnant and early postpartum women (within 10 days of birth); reverse transcriptase polymerase chain reaction confirmed SARS-CoV-2 infection. The primary outcome was progression to critical illness requiring intensive care. The secondary outcomes included maternal death, preeclampsia, and stillbirth. The association between the primary outcome and 12 candidate predictors having a known association with severe COVID-19 in pregnancy was analyzed with log-binomial mixed-effects regression and reported as adjusted risk ratios. All the potential predictors were evaluated in 1 model and only the baseline factors in another. The predictive accuracy was assessed by the area under the receiver operating characteristic curves. RESULTS: Of the 793 pregnant women who were positive for SARS-CoV-2 and were symptomatic, 44 (5.5%) were admitted to intensive care, of whom 10 died (1.3%). The 'mini-COvid Maternal Intensive Therapy' model included the following demographic and clinical variables available at disease onset: maternal age (adjusted risk ratio, 1.45; 95% confidence interval, 1.07-1.95; P=.015); body mass index (adjusted risk ratio, 1.34; 95% confidence interval, 1.06-1.66; P=.010); and diagnosis in the third trimester of pregnancy (adjusted risk ratio, 3.64; 95% confidence interval, 1.78-8.46; P=.001). The optimism-adjusted area under the receiver operating characteristic curve was 0.73. The 'full-COvid Maternal Intensive Therapy' model included body mass index (adjusted risk ratio, 1.39; 95% confidence interval, 1.07-1.95; P=.015), lower respiratory symptoms (adjusted risk ratio, 5.11; 95% confidence interval, 1.81-21.4; P=.007), neutrophil to lymphocyte ratio (adjusted risk ratio, 1.62; 95% confidence interval, 1.36-1.89; P<.001); and serum C-reactive protein (adjusted risk ratio, 1.30; 95% confidence interval, 1.15-1.44; P<.001), with an optimism-adjusted area under the receiver operating characteristic curve of 0.85. Neither model showed signs of a poor fit. Categorization as high-risk by either model was associated with a shorter diagnosis to intensive care unit admission interval (log-rank test P<.001, both), higher maternal death (5.2% vs 0.2%; P<.001), and preeclampsia (5.7% vs 1.0%; P<.001). A spreadsheet calculator is available for risk estimation. CONCLUSION: At presentation with symptomatic COVID-19, pregnant and recently postpartum women can be stratified into high- and low-risk for progression to critical disease, even where resources are limited. This can support the nature and place of care. These models also highlight the independent risk for severe disease associated with obesity and should further emphasize that even in the absence of other comorbidities, vaccination is particularly important for these women. Finally, the model also provides useful information for policy makers when prioritizing national vaccination programs to quickly protect those at the highest risk of critical and fatal COVID-19.

COVID-19 vaccination during pregnancy: coverage and safety.

BACKGROUND: 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. OBJECTIVE: This study aimed to investigate the uptake and safety of COVID-19 vaccination among pregnant women. STUDY DESIGN: 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. RESULTS: 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). CONCLUSION: 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.

Women's experiences of maternity service reconfiguration during the COVID-19 pandemic: A qualitative investigation.

OBJECTIVE: To explore women's experiences of maternity service reconfiguration during the first wave of the SARS-CoV-2 (COVID-19) pandemic. DESIGN: Qualitative interview study. SETTING: South London, United Kingdom. PARTICIPANTS: Women (N=23) who gave birth between March and August 2020 in one of the ten South London maternity hospitals. METHODS: Semi-structured interviews were conducted (N=23), via video-conferencing software. Transcribed interviews were analysed 'by hand' using Microsoft Word. Template analysis was selected to code, analyse, and interpret data, according to the findings of a recently-published national survey of maternity service reconfiguration across the UK in response to COVID-19. FINDINGS: Three main themes emerged through analysis: (i) Disruption to In-Person Care and Increased Virtual Care Provision, (ii) Changes to Labour and Birth Preferences and Plans, (iii) Advice for Navigating Maternity Services During a Pandemic. KEY CONCLUSIONS: Women reported mixed views on the reduction in scheduled in-person appointments. The increase in remote care, especially via telephone, was not well endorsed by women. Furthermore, women reported an under-reliance on healthcare professionals for support, rather turning to family. IMPLICATIONS FOR PRACTICE: We provide insight into the experiences of women who received antenatal, intrapartum, and postnatal care during the first wave of the COVID-19 pandemic. Our findings should inform healthcare policy to build back better maternity care services after 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.

SARS-CoV-2 Infection in Pregnant Women and Their Newborns.

There remain a number of uncertainties globally about the risks posed to women who are infected with SARS-CoV-2 during pregnancy. Furthermore, our understanding of the spread of COVID-19 in Sub-Saharan Africa is limited, owing to low testing rates in many parts of the continent. PeriCOVID Africa, in conjunction with the WHO/HRP Alliance, plans to address these knowledge gaps by harnessing research infrastructures in place in five sub-Saharan African countries in order to screen more than 50,000 pregnant women and their infants for SARS-CoV-2, while monitoring pregnancy and neonatal outcomes. We anticipate that the results of this study will provide much needed information about the risks that SARS-CoV-2 poses to pregnant women and their babies, as well as establishing potential routes of mother-to-child transmission.

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.