A Retrospective observational cohort study of the effect of antenatal influenza vaccination on birth outcomes in Cape Town, South Africa, 2015-2016

Background: There are conflicting data concerning the impact of antenatal influenza vaccination on birth outcomes including low birthweight (LBW), preterm birth, small for gestational age (SGA), and stillbirth. Methods: We conducted a retrospective observational cohort study of infants born to women residing in Mitchells Plain, Cape Town. Infants were born at 4 health facilities during May 28 – December 31, 2015 and April 15 – December 31, 2016. We performed crude and multivariable logistic regression, propensity score (PS) matching logistic regression, and inverse probability of treatment weighted (IPTW) regression to assess vaccine effectiveness (VE) against LBW, preterm birth, SGA, and stillbirth adjusting for measured confounders. Results: Maternal vaccination status, antenatal history, and ≥1 birth outcome(s) were available for 4084/5333 (76.6%) pregnancies, 2109 (51.6%) vaccinated, and 1975 (48.4%) unvaccinated. The proportion LBW was lower in vaccinated (6.9%) vs. unvaccinated (12.5%) in multivariable [VE 0.27 (95% CI 0.07-0.42)], PS [VE 0.30 (95% CI 0.09-0.51)], and IPTW [VE 0.24 (95% CI 0.04-0.45)]. Preterm birth was less frequent in vaccinated (8.6%) than unvaccinated (16.4%) in multivariable [VE 0.26 (0.09-0.40)], PS [VE 0.25 (95% CI 0.09-0.41)], and IPTW [VE 0.34 (95% CI 0.18-0.51)]. The proportion SGA was lower in vaccinated (6.0%) than unvaccinated (8.8%) but not in adjusted models. There were few stillbirths in our study population, 30/4084 (0.7%). Conclusions: Using multiple analytic approaches, we found that influenza vaccination was associated with lower prevalence of LBW (24-30%) and preterm birth (25-34%) in Cape Town during 2015-2016.