• Jonas F Ludvigsson, Peter Ström, Cecilia Lundholm, Sven Cnattingius, Anders Ekbom, Åke Örtqvist, Nils Feltelius, Fredrik Granath, and Olof Stephansson.
• Department of Medical Epidemiology, Karolinska Institutet, Sweden Department of Paediatrics, Örebro University Hospital, Sweden jonasludvigsson@yahoo.com.
• BMJ. 2015 Jan 1;351:h5585.

Study QuestionWhat is the mortality in offspring of mothers who had influenza A(H1N1)pdm09 vaccination during pregnancy?MethodsThis was a prospective population based cohort study in seven healthcare regions in Sweden based on vaccinations taking place between 2 October 2009 and 26 November 2010. H1N1 vaccination data were linked with pregnancy and birth characteristics and offspring mortality data in 275,500 births (of which 1203 were stillbirths) from 137,886 mothers. Of these offspring, 41,183 had been exposed to vaccination with Pandemrix, a monovalent AS03 adjuvanted H1N1 influenza vaccine, during fetal life. A primary comparison group consisted of pregnancies of women who were not vaccinated during the same calendar period. In a second comparison, non-exposed siblings of infants prenatally exposed to vaccination were used as controls. Cox regression was used to estimate hazard ratios for stillbirth, early neonatal mortality (days 0-6 after birth), and subsequent mortality (beginning on day 7) in vaccinated versus non-vaccinated women, adjusting for mother's age at delivery, body mass index, parity, smoking, country of birth, and disposable income and for sex of offspring.Study Answer And LimitationsThe results of this study suggest that AS03 adjuvanted H1N1 vaccination during pregnancy does not affect the risk of stillbirth, early neonatal death, or later mortality in the offspring. During follow-up, 1172 stillbirths, 380 early neonatal deaths, and 706 deaths thereafter occurred. Compared with general population controls, this corresponded to adjusted hazard ratios of 0.83 (95% confidence interval 0.65 to 1.04) for stillbirth, 0.71 (0.44 to 1.14) for early neonatal death, and 0.97 (0.69 to 1.36) for later death. When siblings were used as controls, adjusted hazard ratios were 0.88 (0.59 to 1.30) for stillbirth, 0.82 (0.46 to 1.49) for early neonatal death, and 0.78 (0.52 to 1.19) for later death. Limitations of the study include lack of data on miscarriage before gestational week 22, inability to ascertain which mothers had pandemic flu during pregnancy, and lack of data on factors influencing the decision to vaccinate during pregnancy.What This Study AddsH1N1 vaccination during pregnancy is not associated with adverse fetal outcome or offspring mortality, including when familial factors are taken into account.Funding, Competing Interests, Data SharingThis project was supported by grants from the Swedish Research Council and the Swedish Council for Working Life and Social Research. NF was employed at the Swedish Medical Product Agency at the time of the study.© Ludvigsson et al 2015.

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