Elsevier

Vaccine

Volume 32, Issue 11, 5 March 2014, Pages 1254-1258
Vaccine

Pandemic A/H1N1 influenza vaccination during pregnancy: A comparative study using the EFEMERIS database

https://doi.org/10.1016/j.vaccine.2014.01.021Get rights and content

Highlights

  • Comparative study of influenza A/H1N1 vaccine effects on pregnancy outcomes.

  • No association between non-adjuvanted vaccine and pregnancy loss or preterm birth.

  • No association between non-adjuvanted vaccine and neonatal pathology.

Abstract

Objective

To evaluate the risk of adverse pregnancy outcomes following A/H1N1 vaccination in pregnant women.

Methods

This observational cohort study compared vaccinated and non-vaccinated pregnant women in EFEMERIS, a French prescription database including pregnant women. Women who ended their pregnancy in South Western France between October 21, 2009 and November 30, 2010 (the period of the French vaccination campaign) were included. Two non-vaccinated women were individually matched to each vaccinated woman by month and year of pregnancy onset. Conditional logistic regression and Cox proportional hazards regression were used to evaluate associations between each outcome (all-cause pregnancy loss, preterm delivery, small for gestational age (SGA) and neonatal pathology) and A/H1N1 vaccination during pregnancy.

Results

1645 women of the 12,120 (13.6%) in the database who were administered A/H1N1 vaccine during pregnancy were compared to 3290 non-vaccinated women. Most were vaccinated in December 2009 (61%) with a non-adjuvanted vaccine (93%). The risks of pregnancy loss (adjusted HR = 0.56; 95% CI = 0.31–1.01), of preterm birth (adjusted HR = 0.82; 95% CI = 0.64–1.06), and of neonatal pathology (adjusted OR = 0.70; 95% CI = 0.49–1.02) did not differ between the vaccinated and the non-vaccinated groups. The rate of SGA was lower in the vaccinated group than in the non-vaccinated group (0.5% vs. 1.4%; adjusted OR = 0.36; 95% CI = 0.17–0.78).

Conclusion

There was no significant association between adverse pregnancy outcomes and vaccination with a non-adjuvanted A/H1N1 vaccine during pregnancy.

Introduction

During the A/H1N1 pandemic of 2009–2010, pregnant women were at increased risk of severe illness, hospitalization, and complications, especially during the second and third trimesters [1], [2], [3], [4], [5].

The World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) initiated a worldwide vaccination campaign in 2009 for populations most at risk of severe illness with the aim of minimizing the impact and spread of the A(H1N1)v09 strain. Pregnant women were one of the main groups prioritized by the vaccination campaign [6]. Thus, during the A/H1N1 influenza outbreak in 2009, French health authority guidelines were to vaccinate all pregnant women with a non-adjuvanted vaccine during the second and third trimesters [7].

The French vaccination campaign started on October 21, 2009. Vaccination was offered free of charge at vaccination centers, first to health care workers and those in various risk groups, and then to the entire population. A two-dose vaccination was planned but from the end of November 2009 just one dose was administered to most individuals. Five vaccines were available in France: the non-adjuvanted Panenza° (Sanofi Pasteur), the AS03-adjuvanted Pandemrix° (GlaxoSmithKline), the non-adjuvanted Celvapan° (Baxter), the MF59-adjuvanted Focetria° (Novartis Vaccines and Diagnostics) and the AF03-adjuvanted Humenza° (Sanofi Pasteur).

The French National Health Insurance Fund for Salaried Workers (Caisse National de l’Assurance Maladie des Travailleurs Salariés; CNAMTS) centralized and recorded all vaccination data in order to manage and to monitor the campaign. During the A/H1N1 pandemic, vaccination centers were required to report A/H1N1 vaccinations to the CNAMTS; consequently, the vaccination data are considered to be close to complete.

Because of the emergency nature of the A/H1N1 vaccine production and of the vaccination centers used for this particular vaccination campaign, there was some mistrust in the general population about safety. Indeed, there was a lack of vaccination safety data. This led to a low rate of vaccination in general population and an even lower rate among pregnant women, despite the risks of influenza being well known for this subpopulation.

Recent retrospective comparative studies, conducted after the A/H1N1 pandemic, have provided reassuring findings about the use of A/H1N1 vaccines for pregnant woman. No increased risk of fetal death, adverse fetal outcomes or birth defects have been reported [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19]. A small number of non-comparative studies have investigated the potential effects of a non-adjuvanted vaccine [20], [21], [22]. The only comparative study was by Opperman et al. [23] including 323 women exposed to a non-adjuvanted vaccine. Their findings did not indicate any increased risk of spontaneous abortion, major malformation or preterm birth.

This first French retrolective comparative study was designed to evaluate the potential adverse effects of A/H1N1 vaccination, mainly with a non-adjuvanted vaccine, during pregnancy in France.

Section snippets

Materials and methods

This observational cohort study evaluated adverse pregnancy outcomes for pregnant women exposed or not exposed to an A/H1N1 vaccine. The study was based on EFEMERIS, a French prescription database including pregnant women, and on the CNAMTS vaccination database.

Results

In the EFEMERIS cohort, 12,120 pregnancies ended between October 21, 2009 and November 30, 2010 and had started before January 31, 2010. A total of 1645 (13.6%) of these women were vaccinated with an A/H1N1 vaccine during pregnancy. These 1645 vaccinated women were compared to 3290 unexposed women. Fifty-one per cent of them received two doses of vaccine. Thirty-five per cent received the first dose in November 2009, 61% in December 2009 and 3% in January 2010. The non-adjuvanted Panenza° was

Discussion

This study did not find any significant association between all-cause pregnancy termination, preterm delivery, or neonatal pathology and A/H1N1 vaccination during pregnancy. However, the rate of SGA was lower among A/H1N1 vaccinated than unexposed women.

Conclusion

The A/H1N1 vaccination rate among pregnant women in our region of France was relatively low (13.6%), probably because of concerns about the safety of the vaccines; this value is nevertheless similar to those in other European countries [8], [33]. Our comparative study did not find any significant association between the risk of all-cause pregnancy termination, preterm delivery or neonatal pathology and non-adjuvanted A/H1N1 vaccination during pregnancy. These results confirm previous findings

Funding

The EFEMERIS database was funded by the Agence Nationale de Sécurité du Médicament et des produits de santé (ANSM), the CNAMTS, the Mutuelle Générale de l’Education Nationale, the Clinical Research Hospital Program (PHRC) and the Unions régionales des Caisses d’Assurance Maladie. Additional funding has been received from the ANSM for the influenza medication study.

Conflict of interest statement

None.

Acknowledgments

We are grateful to the Caisse National de l’Assurance Maladie des Travailleurs Salariés (CNAMTS) for vaccination data collection.

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