The Effect of Influenza Vaccination on Birth Outcomes in a Cohort of Pregnant Women in Lao PDR, 2014-2015.

BACKGROUND: Some studies suggest that maternal influenza vaccination can improve birth outcomes. However, there are limited data from tropical settings, particularly Southeast Asia. We conducted an observational study in Laos to assess the effect of influenza vaccination in pregnant women on birth outcomes. METHODS: We consented and enrolled a cohort of pregnant woman who delivered babies at 3 hospitals during April 2014-February 2015. We collected demographic and clinical information on mother and child. Influenza vaccination status was ascertained by vaccine card. Primary outcomes were the proportion of live births born small for gestational age (SGA) or preterm and mean birth weight. Multivariate models controlled for differences between vaccinated and unvaccinated women and influenza virus circulation. RESULTS: We enrolled 5103 women (2172 [43%] were vaccinated). Among the 4854 who had a live birth, vaccinated women were statistically significantly less likely than unvaccinated women to have an infant born preterm during the period of high influenza virus circulation (risk ratio [RR] = 0.56, 95% confidence interval [CI], .45-.70), and the effect remained after adjusting for covariates (adjusted RR, 0.69; 95% CI, .55-.87). There was no effect of vaccine on mean birth weight. Vaccinated mothers had a statistically significant elevated risk of having an infant born SGA (adjusted RR, 1.25; 95% CI, 1.11­1.41). CONCLUSIONS: In this observational study, we found indirect evidence of influenza vaccine safety during pregnancy, and women who received vaccine had a reduced risk of delivering a preterm infant during times of high influenza virus circulation. Vaccination may prevent 1 in 5 preterm births that occur during periods of high influenza circulation.

Measurement of birth outcomes in analyses of the impact of maternal influenza vaccination.

BACKGROUND: The estimated association of maternal influenza vaccination and birth outcomes may be sensitive to methods used to define preterm birth or small-for-gestational age (SGA). METHODS: In a cohort of pregnant women in Lao People's Democratic Republic, we estimated gestational age from: (a) date of last menstrual period (LMP), (b) any prenatal ultrasound, (c) first trimester ultrasound, (d) Ballard Score at delivery, and (e) an algorithm combining LMP and ultrasound. Infants were classified as SGA at birth using a Canadian, global, and equation-based growth reference. We estimated the association of maternal influenza vaccination and birth outcomes, by influenza activity, using multivariable log-binomial regression and Cox proportional hazards regression with vaccination as a time-varying exposure. RESULTS: The frequency of preterm birth in the cohort varied by method to estimate gestational age, from 5% using Ballard Score to 15% using any ultrasound. Using LMP, any ultrasound, or the algorithm, we found statistically significant reductions in preterm birth among vaccinated women during periods of high influenza activity and statistically significant increases in SGA, using a Canadian growth reference. We did not find statistically significant associations with SGA when using global or equation-based growth references. CONCLUSIONS: The association of maternal influenza vaccination and birth outcomes was most affected by the choice of a growth reference used to define SGA at birth. The association with pre-term birth was present and consistent across multiple statistical approaches. Future studies of birth outcomes, specifically SGA, should carefully consider the potential for bias introduced by measurement choice.