Maternal H1N1 vaccination and offspring outcomes

December 3, 2015

Findings of a new prospective Swedish population-based cohort study provide further reassurance about the safety of H1N1 vaccination in pregnant women.

Findings of a new prospective Swedish population-based cohort study provide further reassurance about the safety of H1N1 vaccination in pregnant women.

Including data for 137,886 mothers and 275,500 births with offspring follow-up ranging to 4.6 years, the study confirmed previous evidence that maternal H1N1 vaccination does not adversely affect fetal outcome.1 This conclusion was strengthened by findings of a second analysis using siblings not exposed to vaccination in utero as a comparator group to control for confounding familial factors. Furthermore, the research showed for the first time that maternal H1N1 vaccination does not seem to influence offspring longer term mortality, beyond the first week of life.

Jonas F Ludvigsson, MD, PhD, is lead author of the paper, professor of clinical epidemiology, Karolinska Institutet, and a pediatrician at Örebro University Hospital, Sweden. He tells Contemporary Pediatrics, “Influenza is associated with an increased risk of stillbirth, and some studies suggest that pregnant women fare worse from influenza than nonpregnant women. In contrast, we found that vaccination against H1N1 does not influence offspring mortality or adverse pregnancy outcomes. Hence, we believe practitioners should be recommending H1N1 vaccination when counseling pregnant women.”

Sweden offers the monovalent AS03 adjuvanted H1N1 vaccine (Pandemrix) to all residents free of charge. Focusing on 7 healthcare regions throughout the country, the study identified pregnant women who received the vaccine between October 2, 2009, and November 26, 2010, and linked the information with birth characteristics using data from the Swedish Medical Birth Register.

Of the 275,500 births comprising the study sample, 1203 were stillbirths, 380 were children who died during the early neonatal period, and 706 were deaths during the available follow-up.

A history of exposure to vaccination was present for 41,183 births. Using the general population as a control group, Cox regression analysis adjusting for multiple maternal demographic and clinical features plus offspring gender found the birth cohort of the vaccinated women were not at increased risk (hazard ratio [HR]; 95% confidence interval [CI]) for stillbirth (HR, 0.83; CI, 0.65 to 1.04), early neonatal death (HR, 0.71; CI, 0.44 to 1.14), or later death (HR, 0.97; CI, 0.69 to 1.36).

The analysis comparing outcomes of vaccine-exposed offspring and their unexposed siblings similarly found no statistically significant association between maternal H1N1 influenza vaccination and the outcomes of stillbirth (HR, 0.88; CI, 0.59 to 1.30), early neonatal death (HR, 0.82; CI, 0.46 to 1.49), or later death (HR, 0.78; CI, 0.52 to 1.19).

“The ability to control for familial factors by comparing outcomes of siblings who are offspring from the same women was a unique feature of our study relative to previous research on this topic. It is an important design element minimizing the risk of selection bias in the vaccination cohort and while at the same time considering genetic and environmental factors that might otherwise influence pregnancy outcomes. Lack of adjustment for these confounders could be a source of bias in earlier studies,” Ludvigsson says.

“Furthermore, we had follow-up on children for several years after birth and therefore could rule out any long-term effects on child mortality from vaccination during fetal life. Previously there has not been any information on long-term mortality of children whose mothers received the H1N1 influenza vaccine during gestation.”

Ludvigsson believes that although vaccination against H1N1 influenza in the United States involves a trivalent versus monovalent vaccine, the findings of the Swedish study about the safety of H1N1 vaccination in pregnant women can be generalized to the United States population.


1. Ludvigsson JF, Ström P, Lundholm C, et al. Maternal vaccination against H1N1 influenza and offspring mortality: population based cohort study and sibling design. BMJ. 2015;351:h5585.

Ms Krader has 30 years’ experience as a medical writer. She has worked as both a hospital pharmacist and a clinical researcher/writer for the pharmaceutical industry and is presently a freelance writer in Deerfield, Illinois. She has nothing to disclose in regard to affiliations with or financial interests in any organizations that may have an interest in any part of this article.