July 10, 2012 — Exposure to adjuvanted influenza A(H1N1) vaccine before birth does not increase the risk for major birth defects, preterm birth, or fetal growth restriction, according to a study published in the July 10 issue of JAMA.
Pregnant women face elevated risk for severe illness, death, and poor pregnancy outcome from influenza, and the 2009 influenza A(H1N1) pandemic was no exception.
Lowered immunity during pregnancy may make women more vulnerable to the infection, which in turn adversely affects fetuses. This hypothesis has been the basis of vaccinating pregnant women against influenza, beginning in 1997. During the 2009 pandemic, pregnant women received vaccination priority, despite limited information on safety. Studies are now providing assurance that the vaccine is safe.
Björn Pasternak, MD, PhD, from the Statens Serum Institut, Copenhagen, Denmark, and coworkers conducted an observational cohort study to assess association of adjuvanted influenza A(H1N1)pdm09 vaccine during pregnancy with elevated risk for major birth defects, preterm birth, and fetal growth restriction. The team collected data on 6989 vaccinated pregnant women from several Danish national registries who delivered between November 2, 2009, and September 30, 2010.
Of 330 infants exposed to vaccine in the first trimester of pregnancy, 18 (5.5%) had a major birth defect compared with 15 (4.5%) among 330 unexposed infants (prevalence odds ratio [POR], 1.21; 95% confidence interval [CI], 0.60 – 2.45). Among the first trimester vaccine-exposed infants, 31 (9.4%) were preterm compared with 24 (7.3%) among the unexposed infants (POR, 1.32; 95% CI, 0.76 – 2.31).
For second or third trimester vaccine exposure, 302 (4.6%) of 6543 infants were born prematurely; the same percentage was seen for 295 of 6366 unexposed infants (POR, 1.00; 95% CI, 0.84 – 1.17).
The researchers also found that 25 (7.6%) of 330 infants who had been exposed during the first trimester were small for gestational age compared with 31 (9.4%) of 330 of unexposed infants (POR, 0.79; 95% CI, 0.46 – 1.37). For later exposure, 641 (9.7%) of 6642 infants were small for gestational age compared with 657 (9.9%) of 6642 of unexposed infants (POR, 0.97; 95% CI, 0.87 – 1.09).
The researchers conclude, “this nationwide cohort study in Denmark found no significant associations between exposure to…adjuvanted influenza A(H1N1)pdm09 vaccine in pregnancy and risk of adverse fetal outcomes including major birth defects, preterm birth, and growth restriction.” However, they caution that their first trimester results are preliminary and suggest investigation of specific birth defects and assessment of vaccine efficacy among the pregnant population.
“[F]uture studies with improved statistical designs including prospective follow-up studies using virological end points with adjustments for selection, seasonality, and other biases are needed to confirm these data,” write Mark C. Steinhoff, MD, from the Cincinnati Children’s Hospital Medical Center in Ohio, and Noni E. MacDonald, MD, from Dalhousie University, Halifax, Nova Scotia, Canada, in an editorial.
The study was funded by the Danish Medical Research Council. The authors have disclosed no relevant financial relationships. Dr. Steinhoff reports receipt of institutional grants or pending grants from Pfizer and from the Bill and Melinda Gates Foundation. Dr. MacDonald reports receipt of consultancy fees from the World Health Organization; receipt of institutional grants or pending grants from the Canadian Institutes of Health and the International Development Research Centre; receipt of fees for lectures or speakers bureau participation from the Ontario Public Health Association; and receipt of travel/accommodations/meeting expenses from the Canadian Paediatric Society.
— Ricki Lewis, PhD