Abstract
BackgroundSeveral studies suggested that vaccines could have non-specific effects on mortality depending on the type of vaccine. Non-specific effects seem to be different in boys and girls. In this study we want to investigate whether there are differences in gender-specific mortality among Dutch children according to the last vaccination received. We tested the hypothesis that the mortality rate ratio for girls versus boys is more favourable for girls following MMR ± MenC vaccination (from 14 months of age) compared with the ratio following DTP-IPV vaccination (2–13 months of age). Secondarily, we investigated whether there were gender-specific changes in mortality following booster vaccination at 4 years of age.MethodsThis observational study included all Dutch children aged 0–11 years from 2000 until 2011. Age groups were classified according to the last vaccination offered. The mortality rates for all natural causes of death were calculated by gender and age group. Incidence rate ratios (IRRs) were computed using a multivariable Poisson analysis to compare mortality in boys and girls across different age groups.ResultsThe study population consisted of 6,261,472 children. During the study period, 14,038 children (0.22%) died, 91% of which were attributed to a known natural cause of death. The mortality rate for natural causes was higher among boys than girls in all age groups. Adjusted IRRs for girls compared with boys ranged between 0.81 (95% CI 0.74-0.89) and 0.91 (95% CI 0.77-1.07) over the age groups. The IRR did not significantly differ between all vaccine-related age groups (p = 0.723), between children 2–13 months (following DTP-IPV vaccination) and 14 months - 3 years (following MMR ± MenC vaccination) (p = 0.493) and between children 14 months - 3 years and 4–8 years old (following DTP-IPV vaccination) (p = 0.868).ConclusionsIn the Netherlands, a high income country, no differences in gender-specific mortality related to the type of last vaccination received were observed in DTP-IPV- and MMR ± MenC eligible age groups. The inability to detect this effect indicates that when non-specific effects were present the effects were not reflected in changes in the differences in mortality between boys and girls. The findings in this large population-based study are reassuring for the continued trust in the safety of the national vaccination programme.
Highlights
Introduction of combined vaccine DTaPHepatitis B virus (HBV)-Inactivated polio vaccine (IPV)/Haemophilus influenzae type b (Hib) at 2, 3, 4, and 11 months of age for children in specified risk groups born on or after 1st April 2006July/August 2006 January 2008Transition to combined DTaP-IPV vaccine for children at 4 years of age born from July/August 2002 onwards Hepatitis B vaccination added for children with Down syndrome born on or after 1st January 2008March 2009 January 2010Human papillomavirus (HPV) catch-up campaign for girls born 1993-1996 HPV vaccination for 12-year-old girls born on or after 1st January 1997March 2011 August 2011The 7-valent pneumococcal vaccine was replaced by the 10-valent pneumococcal vaccine for children born on or after 1st March 2011Hepatitis B vaccination introduced for all children born on or after 1st August 2011(degrees of freedom = 4)
The data were available from Statistics Netherlands, who linked demographic data of persons included in the Municipal Personal Records Database (GBA) with causes of death derived from Statistics Netherlands
Mortality rates The mortality rate due to natural causes was highest for children 0 to 1 months old
Summary
Since its introduction in 1957, the number of deaths due to diseases targeted by the NIP has drastically declined [1] Notwithstanding this important contribution of vaccinations, several studies in recent decades have suggested that vaccinations could give non-specific effects, i.e. effects on nontargeted diseases, on mortality, with differential effects in boys and girls [2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17]. Several mechanisms driving potential sex-differential effects of vaccines have been suggested, including differences in adaptive and innate immunity [2,18]
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