Pertussis and Influenza Vaccination during Pregnancy: Maternal and Neonatal Health Outcomes

Abstract

Background and objectives Vaccination during pregnancy can enhance transplacental transfer of protective antibody to the fetus and protect the infant against disease during the first few months of life. Despite the recommendation of maternal influenza and pertussis vaccination to protect pregnant women and their infants against these serious infections, uptake of the vaccines has been suboptimal globally. This thesis aims to determine the most effective interventions used to improve maternal pertussis vaccine uptake, identify psychosocial factors influencing acceptance and uptake of maternal pertussis and seasonal influenza vaccination and evaluate evidence for the safety and benefits of these two routinely recommended vaccines during pregnancy in improving maternal and neonatal health outcomes. Methods A systematic review was conducted to identify strategies effective in improving uptake of pertussis vaccine among pregnant women. A prospective cohort study of low risk, nulliparous women with singleton pregnancies were recruited between 2015-2018 at two major maternity hospitals in Adelaide, South Australia, with the primary aim to develop screening tests to identify adverse pregnancy outcomes. Using this multicentre prospective cohort with comprehensive clinical, lifestyle, sociodemographic data, and documented maternal vaccination status, the thesis examined psychosocial predictors of maternal vaccination and evaluated the safety and impact of maternal seasonal influenza and pertussis vaccines on pregnancy and birth outcomes. Poisson regression models were used to identify psychosocial factors influencing acceptance and uptake of the two routinely recommended antenatal vaccines. To evaluate the impact of maternal influenza and pertussis vaccination on health outcomes for mothers and infants, Cox proportional-hazards and log-binomial models were applied. Results The systematic review included six original published studies that reported on interventions to increase uptake of pertussis vaccine among pregnant women. Observational studies showed i) a midwife delivered maternal vaccination program improved uptake of pertussis vaccine during pregnancy from 20% to 90%; ii) implementation of an automated reminder within the electronic medical record improved uptake from 48% to 97%; iii) an increase in maternal pertussis vaccine uptake from 36% to 61% after strategies to increase provider awareness of recommendations were introduced. In contrast, interventions in all three randomised controlled trials (RCTs) (two involved education of pregnant women, one had multi-component interventions) did not demonstrate improvement in the uptake of pertussis vaccination during pregnancy, although two of the RCT studies failed to attain their sample size estimates. Data from the prospective cohort showed that women’s willingness to receive the recommended maternal vaccines was high (90%) and independent of psychosocial factors. However, a difference in the actual receipt of pertussis (79%) and seasonal influenza vaccines (48%) during pregnancy was observed. A history of major depressive disorder was the strongest predictor of pertussis (adjusted prevalence ratios, aPR 1.16, 95% CI:1.06–1.26) and influenza vaccination uptake during pregnancy (aPR 1.32; 95% CI: 1.14–1.58). Pregnant women presenting with elevated depressive symptoms were also more likely to receive maternal pertussis vaccination (aPR 1.14, 95% CI:1.00–1.30). In contrast, women with very high-perceived stress levels (aPR 0.87; 95% CI: 0.76–0.99) were less likely to receive maternal pertussis vaccination. Women with mild depressive symptoms (aPR 1.21, 95% CI: 1.00–1.44) and mild anxiety symptoms (aPR 1.21, 95% CI: 0.99–1.48) were more likely to receive influenza vaccine during pregnancy. Data analyses of the prospective cohort found no significant difference in the risk of adverse pregnancy (spontaneous abortion, chorioamnionitis, gestational hypertension, pre-eclampsia, gestational diabetes, preterm premature rupture of the membranes, spontaneous preterm birth) and birth outcomes (congenital anomalies, small for gestational age births, low birth weight, admission to the neonatal care unit, low Apgar scores and mechanical ventilation) among women who received seasonal influenza or pertussis vaccinations in pregnancy compared with unvaccinated pregnant women. This thesis also presents evidence that maternal influenza vaccination reduces the risk of pre-delivery hospitalisation with influenza-like illness during pregnancy (adjusted hazard ratios, aHR 0.61; 95% CI: 0.39–0.97). Furthermore, the thesis findings suggest a protective effect of maternal seasonal influenza in reducing the rates of low birthweight (aHR 0.46, 95% CI: 0.23–0.94) and small for gestational age births (aHR 0.65, 95% CI: 0.40–1.04) during periods of high influenza activity. Conclusions There is limited high quality evidence for interventions to increase uptake of pertussis vaccine among pregnant women. Based on the existing research, incorporating midwife led maternal vaccination programs, increasing healthcare provider awareness of recommendations and implementation of a provider reminder system to target unvaccinated pregnant women are the most effective strategies to improve uptake of pertussis vaccine during pregnancy. The psychosocial predictors of maternal vaccination identified in this thesis can be used in designing effective interventions and maternal vaccination programs. The thesis findings on the safety of maternal pertussis and influenza vaccination and additional potential benefits of influenza vaccine during pregnancy in improving neonatal outcomes can be used to promote antenatal vaccination to expecting mothers and healthcare providers. Furthermore, these findings may aid evidence-based decision making for policy makers in countries considering implementation of universal antenatal seasonal influenza and pertussis vaccination programs.