Dataset Information

Efficacy, duration of protection, birth outcomes, and infant growth associated with influenza vaccination in pregnancy: a pooled analysis of three randomised controlled trials.

ABSTRACT:

Background

Maternal influenza immunisation can reduce morbidity and mortality associated with influenza infection in pregnant women and young infants. We aimed to determine the vaccine efficacy of maternal influenza immunisation against maternal and infant PCR-confirmed influenza, duration of protection, and the effect of gestational age at vaccination on vaccine efficacy, birth outcomes, and infant growth up to 6 months of age.

Methods

We did a pooled analysis of three randomised controlled trials done in Nepal (2011-2014), Mali (2011-2014), and South Africa (2011-2013). Pregnant women, gestational age 17-34 weeks in Nepal, 28 weeks or more in Mali, and 20-36 weeks in South Africa, were enrolled. Women were randomly assigned 1:1 to a study group, in which they received trivalent inactivated influenza vaccine (IIV) in all three trials, or a control group, in which they received saline placebo in Nepal and South Africa or quadrivalent meningococcal conjugate vaccine in Mali. Enrolment at all sites was complete by April 24, 2013. Infants and women were assessed for respiratory illness, and samples from those that met the case definition were tested for influenza by PCR testing. Growth measurements, including length and weight, were obtained at birth at all sites, at 24 weeks in South Africa, and at 6 months in Nepal and Mali. The three trials are registered with ClinicalTrials.gov, numbers NCT01430689, NCT01034254, and NCT02465190.

Findings

10 002 women and 9800 liveborn infants were included. Pooled efficacy of maternal vaccination to prevent infant PCR-confirmed influenza up to 6 months of age was 35% (95% CI 19 to 47). The pooled estimate was 56% (28 to 73) within the first 2 months of life, 39% (11 to 58) between 2 and 4 months, and 19% (-9 to 40) between 4 and 6 months. In women, from enrolment during pregnancy to the end of follow-up at 6 months postpartum, the vaccine was 50% (95% CI 32-63) efficacious against PCR-confirmed influenza. Efficacy was 42% (12 to 61) during pregnancy and 60% (36 to 75) postpartum. In women vaccinated before 29 weeks gestational age, the estimated efficacy was 30% (-2 to 52), and in women vaccinated at or after 29 weeks, efficacy was 71% (50 to 83). Efficacy was similar in infants born to mothers vaccinated before or after 29 weeks gestation (34% [95% CI 12 to 51] vs 35% [11 to 52]). There was no overall association between maternal vaccination and low birthweight, stillbirth, preterm birth, and small for gestational age. At 6 months of age, the intervention and control groups were similar in terms of underweight (weight-for-age), stunted (length-for-age), and wasted (weight-for-length). Median centile change from birth to 6 months of age was similar between the intervention and the control groups for both weight and length.

Interpretation

The assessment of efficacy for women vaccinated before 29 weeks gestational age might have been underpowered, because the point estimate suggests that there might be efficacy despite wide CIs. Estimates of efficacy against PCR-confirmed influenza and safety in terms of adverse birth outcomes should be incorporated into any further consideration of maternal influenza immunisation recommendations.

Funding

Bill & Melinda Gates Foundation.

SUBMITTER: Omer SB

PROVIDER: S-EPMC7284303 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Studies have shown that influenza vaccination during pregnancy reduces the risk of influenza disease in pregnant women and their offspring. Some have proposed that maternal vaccination may also have beneficial effects on birth outcomes. In 2014, we conducted an observational study to test this hypothesis using data from two large hospitals in Managua, Nicaragua.We conducted a retrospective cohort study to evaluate associations between influenza vaccination and birth outcomes. We carried out interviews and reviewed medical records post-partum to collect data on demographics, influenza vaccination during pregnancy, birth outcomes and other risk factors associated with adverse neonatal outcomes. We used influenza surveillance data to adjust for timing of influenza circulation. We assessed self-reports of influenza vaccination status by further reviewing medical records of those who self-reported but did not have readily available evidence of vaccination status. We performed multiple logistic regression (MLR) and propensity score matching (PSM).A total of 3268 women were included in the final analysis. Of these, 55% had received influenza vaccination in 2014. Overall, we did not observe statistically significant associations between influenza vaccination and birth outcomes after adjusting for risk factors, with either MLR or PSM. With PSM, after adjusting for risk factors, we observed protective associations between influenza vaccination in the second and third trimester and preterm birth (aOR: 0.87; 95% confidence interval (CI): 0.75-0.99 and aOR: 0.66; 95% CI: 0.45-0.96, respectively) and between influenza vaccination in the second trimester and low birth weight (aOR: 0.80; 95% CI: 0.64-0.97).We found evidence to support an association between influenza vaccination and birth outcomes by trimester of receipt with data from an urban population in Nicaragua. The study had significant selection and recall biases. Prospective studies are needed to minimize these biases.

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