Nature Communications  volume 13, Article number: 2414 (2022)

Smriti Prasad, Erkan Kalafat, Helena Blakeway, Rosemary Townsend, Pat O’Brien, Edward Morris, Tim Draycott, Shakila Thangaratinam, Kirsty Le Doare, Shamez Ladhani, Peter von Dadelszen, Laura A. Magee, Paul Heath & Asma Khalil

The 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.

With the first COVID-19 vaccination trials reporting the effectiveness of vaccination against COVID-19 in December 20201,2, mass vaccination started immediately in higher-income countries and has progressed at an unprecedented pace, albeit with disappointing variation in coverage, locally and globally3. One under-vaccinated group is pregnant people. Exclusion of pregnant people from initial COVID-19 vaccine trials, lack of experience with mRNA vaccine platforms outside research settings in this group, and resultant variable and ambiguous guidance on vaccination from official and professional bodies, as well as antivaccine disinformation, contributed to vaccine hesitancy among pregnant people4,5,6,7,8.

SARS-CoV-2 infection in pregnancy can have devastating effects, with evidence showing increased rates of admission to hospital and intensive care units (ICU), maternal death, stillbirth, pre-eclampsia and preterm birth9,10. In the UK, the rate of hospital and ICU admission and the associated co-morbidities has increased with each wave11. Data from the UK Obstetric Surveillance System (UKOSS) indicate that the overwhelming majority of pregnant people who required hospitalization or ICU care for COVID-19 during the delta wave were unvaccinated12. With the emergence of the Omicron variant, the pandemic appears to be far from over and the urgent need for vaccination of pregnant people cannot be overemphasised.

Emerging data from individual observational studies and large case series are consistent with pre-clinical studies that suggested that COVID-19 vaccines have no adverse effects on pregnancy or neonatal outcomes13,14,15,16,17. Clinical trials are underway to investigate the outstanding questions about COVID-19 vaccination in pregnancy, including the optimal dosing schedule, and the duration and efficacy of antibodies transferred to the neonate transplacentally and in breastmilk18. There is an immediate need for high-quality robust information to support pregnant people considering COVID-19 vaccination, pending additional updates from large national registries and the results of ongoing trials. We conducted a systematic review and meta-analysis of published data on the effects of COVID-19 vaccination in pregnancy, and on vaccine effectiveness in pregnancy.

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