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Risk for Congenital Malformation With H1N1 Influenza Vaccine: A Cohort Study With Sibling Analysis
Department of Medical Epidemiology, Karolinska Institutet, Stockholm, Sweden .ORCID iD: 0000-0003-1024-5602
Department of Medical Epidemiology, Karolinska Institutet, Stockholm, Sweden .
Department of Medical Epidemiology, Karolinska Institutet, Stockholm, Sweden .
Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
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2016 (English)In: Annals of Internal Medicine, ISSN 0003-4819, E-ISSN 1539-3704, Vol. 165, no 12, 848-855 p.Article in journal (Refereed) Published
Abstract [en]

Background: Earlier studies reporting varying risk estimates for congenital malformation in offspring of mothers undergoing vaccination against H1N1 influenza during pregnancy did not consider the potential role of confounding by familial (genetic and shared environmental) factors.

Objective: To evaluate an association between maternal H1N1 vaccination during pregnancy and offspring malformation, with familial factors taken into account.

Design: Population-based prospective study.

Setting: Sweden.

Participants: Liveborn offspring born between 1 October 2009 and 1 October 2011 to mothers receiving monovalent AS03-adjuvanted H1N1 influenza vaccine (Pandemrix [GlaxoSmithKline]) during pregnancy. A total of 40 983 offspring were prenatally exposed to the vaccine, 14 385 were exposed within the first trimester (14 weeks), and 7502 were exposed during the first 8 weeks of pregnancy. Exposed offspring were compared with 197 588 unexposed offspring. Corresponding risks in exposed versus unexposed siblings were also estimated.

Measurements: Congenital malformation, with subanalyses for congenital heart disease, oral cleft, and limb deficiency.

Results: Congenital malformation was observed in 2037 (4.97%) exposed offspring and 9443 (4.78%) unexposed offspring. Adjusted risk for congenital malformation was 4.98% in exposed offspring versus 4.96% in unexposed offspring (risk difference, 0.02% [95% CI, -0.26% to 0.30%]). The corresponding risk differences were 0.16% (CI, -0.23% to 0.56%) for vaccination during the first trimester and 0.10% (CI, -0.41% to 0.62%) for vaccination in the first 8 weeks. Using siblings as comparators yielded no statistically significant risk differences.

Limitations: The study was based on live births, and the possibility that data on miscarriage or induced abortion could have influenced the findings cannot be ruled out. Study power was limited in analyses of specific malformations.

Conclusion: When intrafamilial factors were taken into consideration, H1N1 vaccination during pregnancy did not seem to be linked to overall congenital malformation in offspring, although risk increases for specific malformations could not be ruled out completely.

Primary Funding Source: Swedish Research Council and Swedish Council for Working Life and Social Research.

Place, publisher, year, edition, pages
Philadelphia, USA: American College of Physicians , 2016. Vol. 165, no 12, 848-855 p.
National Category
Medical and Health Sciences Obstetrics, Gynecology and Reproductive Medicine
URN: urn:nbn:se:oru:diva-54267DOI: 10.7326/M16-0139PubMedID: 27654505ScopusID: 2-s2.0-85007257309OAI: oai:DiVA.org:oru-54267DiVA: diva2:1061712
Available from: 2017-01-03 Created: 2017-01-03 Last updated: 2017-01-11Bibliographically approved

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