European Journal of Epidemiology

, Volume 28, Issue 7, pp 579–588 | Cite as

Influenza H1N1 vaccination and adverse pregnancy outcome

  • Jonas F. Ludvigsson
  • Daniela Zugna
  • Sven Cnattingius
  • Lorenzo Richiardi
  • Anders Ekbom
  • Åke Örtqvist
  • Ingemar Persson
  • Olof Stephansson


Although vaccines against influenza can reduce maternal morbidity and mortality, large-scale data on adverse effects in the offspring are scarce. Historical cohort study in Stockholm County, Sweden. We linked H1N1 vaccination data (Pandemrix®, a mono-valent AS03 adjuvanted H1N1 vaccine) with pregnancy and birth data from 21,087 women with singleton offspring conceived between February 2009 and January 2010 (vaccinated during pregnancy: n = 13,297 vs. unvaccinated: n = 7,790). Data were analysed by conceptualizing the observational cohort as a series of nested cohorts defined at each week of gestation. Logistic regression estimated odds ratios (ORs) for low birth weight (LBW, <2,500 g), preterm birth (<37 completed weeks), small-for-gestational age (SGA, <10th percentile of the gestational age-specific birth weight within the cohort), low 5-min Apgar score (<7), and caesarean section. Data were adjusted for potential confounders, including maternal age, body mass index, smoking, parity, civil status and comorbidities. Compared with infants of non-vaccinated women, infants of vaccinated women had similar adjusted ORs (95 % CI) for LBW (0.91; 0.79–1.04), preterm birth (0.99; 0.89–1.10), SGA (0.97; 0.90–1.05), low Apgar score (1.05, 0.84–1.31), and a marginal risk reduction for caesarean section (0.94, 0.89–0.99). H1N1 vaccination during pregnancy, using an AS03-adjuvanted vaccine, does not appear to adversely influence offspring risks of LBW, preterm birth, SGA, or low Apgar score. Our results suggest that this vaccine is safe for the offspring when used in different stages of pregnancy.


Child H1N1 Immunization Influenza Small-for-gestational-age Pregnancy Preterm birth Vaccination 



Confidence interval


Low birth weight


Odds ratio


Small for gestational age



This project was supported by grants from the Swedish Research Council (Medicine), and the Swedish Council for Working Life and Social Research (FAS).

Ethical approval

This project (2009/1952-31/4) was approved by the Research Ethics Committee of the Karolinska Institute, Sweden on January 13, 2010.

Conflict of interest

JFL was funded by the Swedish Research Council (Medicine), OS was funded by the Swedish Society of Medicine. LR was partially supported by grants from the Compagnia san Paolo/Firms and the Italian Association for Cancer Research.

Supplementary material

10654_2013_9813_MOESM1_ESM.doc (79 kb)
Supplementary material 1 (DOC 79 kb)


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Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Jonas F. Ludvigsson
    • 1
    • 2
  • Daniela Zugna
    • 1
    • 3
  • Sven Cnattingius
    • 1
  • Lorenzo Richiardi
    • 3
  • Anders Ekbom
    • 1
  • Åke Örtqvist
    • 4
    • 5
  • Ingemar Persson
    • 6
  • Olof Stephansson
    • 1
    • 7
  1. 1.Clinical Epidemiology Unit, Department of MedicineKarolinska InstitutetStockholmSweden
  2. 2.Department of PediatricsÖrebro University HospitalÖrebroSweden
  3. 3.Cancer Epidemiology Unit, Department of Medical SciencesUniversity of Turin and CPO-PiemonteTurinItaly
  4. 4.Unit of Infectious Diseases, Department of MedicineKarolinska InstitutetStockholmSweden
  5. 5.Department of Communicable Diseases Control and PreventionStockholm County CouncilStockholmSweden
  6. 6.Medical Product AgencyUppsalaSweden
  7. 7.Department of Women’s and Children’s HealthKarolinska Institutet and HospitalStockholmSweden

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