Safety and efficacy of the Covid-19 Pfizer-BioNTech vaccination in pregnancy: A systematic review and meta-analysis

BACKGROUND: Pregnant women continue to be excluded from clinical trials, leading to vaccine hesitancy in this vulnerable population. Pfizer-BioNTech vaccination is the primary and widely available Coronavirus disease 2019 (Covid-19) vaccine in New Zealand (NZ). No systematic reviews and meta-analyses of the safety and efficacy outcomes of the maternal, foetal or neonate have been published. OBJECTIVE: To assess the safety and efficacy of the Covid-19 Pfizer-BioNTech, also referred to as BNT162b2, Comirnaty, or Tozinameran, vaccination during pregnancy. DESIGN: Systematic review and meta-analysis. METHOD: Electronic databases were searched (Embase, Medline, Web of Science, PubMed, Scopus) to the 4th of February 2023 for the safety and efficacy of the Pfizer-BioNTech vaccination during pregnancy. Studies included had to have a control or placebo group of unvaccinated pregnant women for comparison. Maternal safety outcomes were antepartum bleeding, postpartum haemorrhage, placental abruption, meconium-stained amniotic fluid, gestational diabetes, pregnancy-related hypertension, and death. Foetal and neonatal safety outcomes were miscarriages, stillborn, infant death, preterm delivery with subgroups of <32 weeks, <35 weeks, <37 weeks of gestation, heart malformation, congenital anomalies, neonatal intensive care unit (NICU) admission, neonatal seizures, neonatal respiratory complications, neonatal meconium aspiration syndrome, abnormal foetal heart rate, one and five minute Apgar scores ≤7, small for gestational age (SGA), and birth weight. Efficacy outcomes were documented Covid-19 infection, hospitalisation, severe or critical illness, intensive care unit (ICU) admission and death. Study titles and abstracts were screened, and the full text was obtained if it met the inclusion criteria. All included studies were assessed using the Cochrane Risk of Bias in non-randomized studies of exposure (ROBINS-E). The data was analysed using Revman odds ratios (OR) and 95% confidence intervals (95%CI) for binary outcomes and weighted mean difference and 95%CI for continuous outcomes. Statistical heterogeneity was assessed using the Cochrane Q test and Higgins I² test. RESULTS: Ten cohort studies met the inclusion criteria, with 44,883 pregnant women (mean age, 30.7 years) who received one or two doses of Pfizer-BioNTech compared to the control group of 34,988 unvaccinated pregnant women (mean age 30.0 years). Four studies were judged as having a low risk of bias, four having some concerns, and two as high risk. There were no statistically significant differences for all outcomes except placental abruption (OR 0.45, 95% CI 0.27 to 0.75), meconium-stained amniotic fluid (OR 0.75 95% CI 0.64 to 0.88), preterm delivery <32 weeks of gestation (OR 0.57, 95% CI 0.39 to 0.83), neonatal respiratory complications (OR 0.65, 95% CI 0.43 to 0.99), neonatal meconium aspiration syndrome (OR 0.52, 95% CI 0.31 to 0.90) and abnormal foetal heart rate (OR 0.64, 95% CI 0.46 to 0.90), documented Covid-19 infections (OR 0.56, 95% CI 0.48 to 0.65) and pregnant women hospitalised with Covid-19 (OR 0.50, 95% CI 0.31 to 0.82) in favour of pregnant women vaccinated with Pfizer-BioNTech. CONCLUSION: There were no adverse risks associated with the Pfizer-BioNTech vaccination during any trimester of pregnancy, and a small number of maternal, foetal and neonatal outcomes had reduced risk of occurrence. The Pfizer-BioNTech vaccination is safe and effective when used during pregnancy.