Interventions to Increase Vaccination Against COVID-19, Influenza and Pertussis During Pregnancy: A Systematic Review and Meta-Analysis

Background: Pregnant women and their babies face significant risks from three vaccine-preventable pathogens: COVID-19, influenza, and pertussis. However, despite these vaccines' proven safety and effectiveness, vaccine uptake during pregnancy remains low and there have been no systematic reviews of interventions to increase vaccination in pregnancy against COVID-19 as well as influenza and pertussis. This research is urgently needed to guide public health strategies to improve maternal and infant health outcomes. Methods: We conducted a systematic review (PROSPERO CRD42023399488; January 2012 to December 2022 following PRISMA guidelines) of interventions to increase COVID-19/influenza/pertussis vaccination in pregnancy. We searched nine databases, including grey literature, with no language restrictions. We restricted the search to high-income countries with established vaccination programmes. Two independent investigators extracted data; discrepancies were resolved by consensus. Meta-analyses were conducted using random-effects models to estimate pooled effect sizes. Heterogeneity was assessed using the I2 statistics.Findings: Out of 2681 articles, we identified 39 relevant studies (n=168,262 participants) across nine countries. Sixteen studies (41%) were randomised controlled trials (RCTs); all other studies were observational cohort, quality-improvement or cross-sectional. The quality of 21% (8/39) of studies was strong. Pooled results of interventions to increase influenza vaccine uptake (18 effect estimates from 12 RCTs) showed the interventions were effective but had a small effect (Risk ratio = 1.07, 95%CI 1.03, 1.13). However, pooled results of interventions to increase pertussis vaccine uptake (11 effect estimates from seven RCTs) showed no clear benefit (Risk ratio = 0.96, 95%CI 0.92, 1.01). Interventions addressed the “three Ps”: patient-, provider- and policy-level strategies, and 28% (11/39) were multimodal.At patient level, clear recommendations from healthcare professionals backed by text reminders/written information were strongly associated with increased vaccine uptake, especially tailored face-to-face interventions, which addressed women’s concerns, dispelled myths and highlighted the benefits of vaccinations. Provider-level interventions included educating healthcare professionals about vaccines’ safety and effectiveness and reminders to offer vaccinations routinely at antenatal visits. Policy-level interventions included financial incentives, inserting mandatory vaccination data fields in electronic health records, and ensuring easy availability of vaccinations across different healthcare facilities.Interpretation: Training healthcare providers to offer patient counselling and consistently recommend vaccinations during pregnancy is crucial. This effort can be enhanced by utilising mobile health technologies. Implementing evidence-based interventions identified in this review could improve vaccine uptake and safeguard the health of pregnant women and their babies.Funding: MSR has an In-Practice fellowship in primary care funded by the National Institute of Health (NIHR 302007). AM is supported by the NIHR Applied Research Collaboration NW London. SH is funded by the NIHR (NIHR 300072), the Academy of Medical Sciences (SBF005\1111), the Medical Research Council (MR/N013638/1), Novo Nordisk Foundation/La Caixa Foundation (LCF/PR/SP21/52930003), Research England, and WHO.Declaration of Interest: All authors report having nothing to declare.