Safety of vaccination against influenza A (H1N1) during pregnancy in the Netherlands: results on pregnancy outcomes and infant's health: cross-sectional linkage study

BJOG. 2016 Apr;123(5):709-17. doi: 10.1111/1471-0528.13329. Epub 2015 Mar 6.


Objective: This study aims to assess the safety of Influenza A(H1N1), vaccination administered during the second and third trimester and containing MF59 and thiomersal (Focetria(®) ), measured by pregnancy outcomes and infant's health.

Design: Cross-sectional linkage study.

Setting and sample: A sample of pregnant women, eligible for prenatal screening, were invited to participate.

Methods: Questionnaire data were linked with the Netherlands Perinatal Registry (n = 1920). Information on infant growth, development (n = 1739) and infection-related contacts with the general practitioner (GP) during the first year of life (n = 1671) was obtained.

Main outcome measures: Multivariate logistic regression was used to assess the association between H1N1 vaccination and small-for-gestational-age infant, preterm delivery and a composite adverse outcome, i.e. low Apgar-score, neonatal intensive care unit admission, neonatal resuscitation or perinatal death. Influence of maternal vaccination on growth, development and GP infection-related contact rates were assessed using multivariate linear mixed modelling and multivariate negative binomial regression, respectively.

Results: Response rate was 21%. Though we found differences in characteristics between unvaccinated and vaccinated women, in the multivariate analyses no association was found between H1N1 vaccination and small-for-gestational-age (odds ratio [OR] 0.84; 95% confidence interval [95% CI] 0.50-1.43), preterm delivery (OR 0.98; 95% CI 0.59-1.62) and the composite adverse outcome (OR 0.84; 95% CI 0.44-1.60). We found no differences in weight-for-age (-0.05; 95% CI -0.13 to 0.04), length-for-age (-0.01; 95% CI -0.09 to 0.06), head-circumference-for-age (-0.05; 95% CI -0.13 to 0.03), developmental scores (-0.06; 95% CI -0.28 to 0.17) and infection-related GP contact rates (incidence rate ratio 1.07; 95% CI 0.91-1.28) between infants of unvaccinated and vaccinated mothers.

Conclusion: Pregnancy outcomes did not differ between H1N1-vaccinated and unvaccinated women. Furthermore, growth, development and GP infection-related contact rates, assessed after the first year of life, were similar in offspring of vaccinated and unvaccinated mothers.

Tweetable abstract: No increased risk for adverse pregnancy outcomes and infant's health following influenza vaccination.

Keywords: Infant; influenza; pregnancy; safety; vaccination.

MeSH terms

  • Adult
  • Cross-Sectional Studies
  • Female
  • Health Surveys
  • Humans
  • Infant
  • Infant Health*
  • Infant, Newborn
  • Influenza A Virus, H1N1 Subtype*
  • Influenza Vaccines / administration & dosage
  • Influenza Vaccines / adverse effects*
  • Influenza, Human / prevention & control*
  • Information Storage and Retrieval
  • Linear Models
  • Logistic Models
  • Multivariate Analysis
  • Netherlands
  • Pregnancy
  • Pregnancy Complications, Infectious / prevention & control*
  • Pregnancy Outcome*
  • Treatment Outcome


  • Influenza Vaccines
  • focetria