Pandemic A/H1N1 influenza vaccination during pregnancy: A comparative study using the EFEMERIS database
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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Methodologic approaches in studies using real-world data (RWD) to measure pediatric safety and effectiveness of vaccines administered to pregnant women: A scoping review
2021, VaccineCitation Excerpt :Some authors listed their data sources by naming each database (e.g.., Beau et al 2014, Fell et al 2016), others used global terms (i.e. “electronic health data”, “a centralized medical record charting system”) to describe their data source (i.e., Kharbanda et al 2017, Morgan et al 2015) and still others provided no specific information (e.g., Fabiani et al 2015 reported “different regional databases and registries”) [36,41,47,54,55]. It proved difficult to categorize databases as claims, electronic medical records, or registries because of differences in terminology (the Nordic countries using the word “registry” more broadly than it is used elsewhere).
Pharmacoepidemiology in pregnancy
2019, TherapieCitation Excerpt :Moreover such a study requires to be conducted on a large sample size to observe rare events. For example, the safety of AH1N1 vaccination in France was assessed in pregnancy through a cohort study [66]: a group of 1645 women who were administered A/H1N1 vaccine during pregnancy were compared to 3290 non-vaccinated women. The authors concluded that vaccination with a non-adjuvanted A/H1N1 vaccine during pregnancy was not significantly associated with an increased risk of adverse pregnancy outcomes.
Birth outcomes following immunization of pregnant women with pandemic H1N1 influenza vaccine 2009–2010
2018, VaccineCitation Excerpt :KPNC’s incidence for preterm, low birth weight, very preterm and very low birth weight outcomes were well below the reported incidence for United States singleton births [11]. Studies comparing pregnant women vaccinated with H1N1 vaccine with unvaccinated pregnant women have reported no increase in adverse pregnancy outcomes following H1N1 vaccination [12–17]. Another study found no difference in adverse pregnancy outcomes among pregnant women immunized with TIV during 2008–2009 influenza season compared with pregnant women who received H1N1 vaccine during 2009–2010 influenza season [18], while another found no excess adverse birth outcomes associated with H1N1 vaccine when compared with TIV [19].
No association between influenza vaccination during pregnancy and adverse birth outcomes
2017, VaccineCitation Excerpt :With the exception of one study which reported an increased risk of preterm birth following maternal influenza vaccination (mean decrease in gestational age in the exposed pregnancies was approximately three days, which is not clinically important) [22], all studies have found no increased risk of preterm births or small for gestational age after maternal influenza vaccination. Rather, the majority of studies either found no association between maternal influenza vaccination and risk of preterm birth, low birth weight or small for gestational age [10,14,17,19–21,23,24,27,28,31,35], or reported a protective effect [26,30,32–34,36]. A meta-analysis including 5 studies on seasonal influenza vaccination and 13 studies on A/H1N1pdm09 pandemic influenza vaccination reported that influenza vaccination during pregnancy decreased the likelihood of preterm birth and low birth weight but had no impact on small for gestational age birth [29].