Introduction: Maternal vaccination is a promising strategy to reduce the burden of vaccine-preventable diseases for mothers and infants. We aimed to provide an up-to-date overview of the efficacy and safety of all available maternal vaccines. Methods: We searched PubMed, Embase, CENTRAL and ClinicalTrials.gov on 1 February 2022, for phase III and IV randomised controlled trials (RCTs) that compared maternal vaccination against any pathogen with placebo or no vaccination. Primary outcomes were laboratory-confirmed or clinically confirmed disease in mothers and infants. Secondary safety outcomes included intrauterine growth restriction, stillbirth, maternal death, preterm birth, congenital malformations and infant death. Random effects meta-analysis were used to calculate pooled risk ratio’s (RR). Quality appraisal was performed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE). Results: Six RCTs on four maternal vaccines, influenza, tetanus, diphtheria and pertussis (Tdap), pneumococcal and respiratory syncytial virus (RSV) were eligible. The overall risk of bias and certainty of evidence varied from low to high. Maternal influenza vaccination significantly reduced the number of laboratory-confirmed influenza cases (RR 0.58, 95% CI 0.42 to 0.79, event rate 57 vs 98, 2 RCTs, n=6003, I²=0%), and clinically confirmed influenza cases in mothers (RR 0.88, 95% CI 0.78 to 0.99, event rate 418 vs 472, 2 RCTs, n=6003, I²=0%), and laboratory-confirmed influenza in infants (RR 0.66, 95% CI 0.52 to 0.85, event rate 98 vs 148, 2 RCTs, n=5883, I²=0%), although this was not significant for clinically confirmed influenza in infants (RR 0.99, 95% CI 0.94 to 1.05, event rate 1371 vs 1378, 2 RCTs, n=5883, I²=0%). No efficacy data were available on maternal Tdap vaccination. Maternal pneumococcal vaccination did not reduce laboratory-confirmed and clinically confirmed middle ear disease (RR 0.49, 95% CI 0.24 to 1.02, event rate 9 vs 18, 1 RCT, n=133 and RR 0.88 95% CI 0.69 to 1.12, event rate 42 vs 47, 1 RCT, n=133, respectively), and clinically confirmed lower-respiratory tract infection (LRTI) (RR 1.08, 95% CI 0.82 to 1.43, event rate 18 vs 34, 1 RCT, n=70) in infants. Maternal RSV vaccination did not reduce laboratory-confirmed RSV LRTI in infants (RR 0.75, 95% CI 0.56 to 1.01, event rate 103 vs 71, 1 RCT, n=4527). There was no evidence of a significant effect of any of the maternal vaccines on the reported safety outcomes. Conclusions: The few RCTs with low event rates suggest that, depending on the type of maternal vaccine, the vaccine might effectively prevent disease and within its size does not show safety concerns in mothers and infants. PROSPERO registration number: CRD42021235115.

Introduction: The majority of data on COVID‐19 in pregnancy are not from sound population‐based active surveillance systems.Material and methods: We conducted a multi‐national study of population‐based national or regional prospective cohorts using standardized definitions within the International Network of Obstetric Survey systems (INOSS). From a source population of women giving birth between March 1 and August 31, 2020, we included pregnant women admitted to hospital with a positive SARS‐CoV‐2 PCR test ≤7 days prior to or during admission and up to 2 days after birth. The admissions were further categorized as COVID‐19‐related or non‐COVID‐19‐related. The primary outcome of interest was incidence of COVID‐19‐related hospital admission. Secondary outcomes included severe maternal disease (ICU admission and mechanical ventilation) and COVID‐19‐directed medical treatment.Results: In a source population of 816 628 maternities, a total of 2338 pregnant women were admitted with SARS‐CoV‐2; among them 940 (40%) were COVID‐19‐related admissions. The pooled incidence estimate for COVID‐19‐related admission was 0.59 (95% confidence interval 0.27–1.02) per 1000 maternities, with notable heterogeneity across countries (I² = 97.3%, P = 0.00). In the COVID‐19 admission group, between 8% and 17% of the women were admitted to intensive care, and 5%–13% needed mechanical ventilation. Thromboprophylaxis was the most frequent treatment given during COVID‐19‐related admission (range 14%–55%). Among 908 infants born to women in the COVID‐19‐related admission group, 5 (0.6%) stillbirths were reported.Conclusions: During the initial months of the pandemic, we found substantial variations in incidence of COVID‐19‐related admissions in nine European countries. Few pregnant women received COVID‐19‐directed medical treatment. Several barriers to rapid surveillance were identified. Investment in robust surveillance should be prioritized to prepare for future pandemics.

The lack of inclusion of pregnant women in clinical trials evaluating the effectiveness of medicines to treat COVID-19 has made it difficult to establish evidence-based treatment guidelines for pregnant women. Our aim was to provide a review of the evolution and updates of the national guidelines on medicines used in pregnant women with COVID-19 published by the obstetrician and gynecologists’ societies in thirteen countries in 2020–2022. Based on the results of the RECOVERY (Randomized Evaluation of COVID-19 Therapy) trial, the national societies successively recommended against prescribing hydroxychloroquine, lopinavir–ritonavir and azithromycin. Guidelines for remdesivir differed completely between countries, from compassionate or conditional use to recommendation against. Nirmatrelvir–ritonavir was authorized in Australia and the UK only in research settings and was no longer recommended in the UK at the end of 2022. After initial reluctance to use corticosteroids, the results of the RECOVERY trial have enabled the recommendation of dexamethasone in case of severe COVID-19 since mid-2020. Some societies recommended prescribing tocilizumab to pregnant patients with hypoxia and systemic inflammation from June 2021. Anti-SARS-CoV-2 monoclonal antibodies were authorized at the end of 2021 with conditional use in some countries, and then no longer recommended in Belgium and the USA at the end of 2022. The gradual convergence of the recommendations, although delayed compared to the general population, highlights the importance of the inclusion of pregnant women in clinical trials and of international collaboration to improve the pharmacological treatment of pregnant women with COVID-19.

Aim: To estimate the prevalence of medication use in nonhospitalized pregnant women with COVID‐19. Methods: A prospective two‐stage individual patient meta‐analysis across 10 data sources in Europe and North America studied medication use among nonhospitalized pregnant women with COVID‐19 between January 2020 and December 2022. Comparisons were made between medication use within 30 days pre‐ and post‐COVID‐19 diagnosis in this cohort and two comparator groups: pregnant women without COVID‐19 and nonpregnant women with COVID‐19. Prevalence estimates were pooled using a random‐effects model stratified by trimester. Results: 50 335 nonhospitalized pregnant women with COVID‐19 were identified. The pooled prevalence of antibacterial use in the third trimester was higher post‐COVID‐19 diagnosis (6.8%, 95% confidence interval [CI] = 5.5–8.4, I ² = 94%) compared with the same women pre‐COVID‐19 (3.9%, 95% CI = 3.1–4.9, I ² = 89%). Overall, pregnant women with COVID‐19 had higher medication use compared to pregnant women without COVID‐19, although the CIs of the prevalence overlapped. Post‐COVID‐19, antithrombotic prevalence was 4.5% (95% CI = 1.1–16.5, I ² = 100%) among pregnant women with COVID‐19 in the third trimester, compared to 2.1% (95% CI = 1.2–3.6, I ² = 99%) among those without COVID‐19 in the third trimester. Compared to nonpregnant women with COVID‐19, pregnant women with COVID‐19 were less likely to be prescribed analgesics, antiprotozoals, corticosteroids, psychoanaleptics and psycholeptics, and more likely to be prescribed antithrombotics, cough and cold and nasal preparations, and drugs used in diabetes across all trimesters. High heterogeneity existed in nearly all analyses. Conclusion: This international meta‐analysis reveals low medication use and country‐specific variations, enhancing insight into the management of COVID‐19 in nonhospitalized pregnant women. Higher antithrombotic use post‐COVID‐19 suggests prophylactic treatment in this population, but variation between countries emphasizes the challenges of combining multinational data.

Background: Understanding the varied impact of COVID‐19 severity on pregnancy outcomes is crucial for informed clinical management and targeted interventions. Objective: To evaluate the impact of COVID‐19 on pregnancy outcomes, distinguishing between pregnant women managed in primary care and those requiring hospitalization. Search Strategy: Regulatory authorities actively promoted global cooperation on COVID‐19's impact during pregnancy. Data were obtained through these regulatory bodies and direct researcher communication rather than through systematic searches. Selection Criteria: Data sources required secondary population‐based data to identify pregnancies with COVID‐19, along with hospitalization, diagnostic and medication codes. Eligibility for the meta‐analysis was determined through protocol evaluation and researcher consultations. Data Collection and Analysis: PRISMA‐IPD and Cochrane guidelines for prospective meta‐analysis were followed. Protocols and definitions were standardized across sources, and a common R script was developed. Initially, crude and adjusted relative risks (aRR) with 95% confidence intervals (CI) were calculated to assess adverse outcomes in pregnant women with and without COVID‐19 in each data source. Estimates were stratified by trimester at infection and hospitalization status. Subsequently, data were pooled using a random‐effects meta‐analysis. Main Results: Data from 10 sources across seven countries contributed to the meta‐analysis, including 86 210 pregnant women diagnosed with COVID‐19, of whom 4.4% were hospitalized. Non‐hospitalized pregnant women with COVID‐19 had no increased risks of adverse outcomes compared to pregnant women without COVID‐19. However, hospitalized women with COVID‐19 in each trimester had higher risks of cesarean section, preterm birth, and LBW compared to pregnant women without COVID‐19. Hospitalization due to COVID‐19 in the third trimester was associated with increased risk of stillbirth (aRR 5.90, 95% CI: 2.22–15.71, I ² = 0%). First‐trimester hospitalizations due to COVID‐19 did not show heightened risks of GDM (aRR 2.08, 95% CI: 0.93–4.64, I ² = 65%), pre‐eclampsia (aRR 1.79, 95% CI: 0.48–6.66, I ² = 71%), or major congenital anomalies (aRR 1.30, 95% CI: 0.55–3.06, I ² = 0%). Conclusions and Relevance: COVID‐19 requiring hospitalization is associated with adverse pregnancy outcomes, emphasizing the need to prevent severe illness during pregnancy. This study also highlights the importance of international collaboration for gathering pregnancy data and shows that building global research networks is essential for responding to future health crises.

Objectives This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the effects of SARS‐CoV‐2 vaccination during pregnancy, versus placebo or no vaccination during pregnancy, for preventing COVID‐19 disease in mothers and infants.