Evaluating the Hazard of Foetal Death following H1N1 Influenza Vaccination; A Population Based Cohort Study in the UK GPRD

<div><h3>Background</h3><p>To evaluate the risk of foetal loss associated with pandemic influenza vaccination in pregnancy. Retrospective cohort study. UK General Practice Research Database Pregnancies ending in delivery or spontaneous foetal death after 21 October 2009 and starting before 01 January 2010.</p> <h3>Methodology/Principal Findings</h3><p>Hazard ratios of foetal death for vaccinated compared to unvaccinated pregnancies were estimated for gestational weeks 9 to 12, 13 to 24 and 25 to 43 using discrete-time survival analysis. Separate models were specified to evaluate whether the potential effect of vaccination on foetal loss might be transient (for ∼4 weeks post vaccination only) or more permanent (for the duration of the pregnancy). 39,863 pregnancies meeting our inclusion criteria contributed a total of 969,322 gestational weeks during the study period. 9,445 of the women were vaccinated before or during pregnancy. When the potential effect of vaccination was assumed to be transient, the hazard of foetal death during gestational weeks 9 through 12 (HR_unadj 0.56; CI₉₅ 0.43 to 0.73) and 13 through 24 (HR_unadj 0.45; CI₉₅ 0.28 to 0.73) was lower in the 4 weeks after vaccination than in other weeks. Where the more permanent exposure definition was specified, vaccinated pregnancies also had a lower hazard of foetal loss than unvaccinated pregnancies in gestational weeks 9 through 12 (HR_unadj 0.74; CI₉₅ 0.62 to 0.88) and 13 through 24 (HR_unadj 0.59; CI₉₅ 0.45 to 0.77). There was no difference in the hazard of foetal loss during weeks 25 to 43 in either model. Sensitivity analyses suggest the strong protective associations observed may be due in part to unmeasured confounding.</p> <h3>Conclusions/Significance</h3><p>Influenza vaccination during pregnancy does not appear to increase the risk of foetal death. This study therefore supports the continued recommendation of influenza vaccination of pregnant women.</p> </div

Population characteristics of pregnant women eligible for influenza vaccination during the influenza A(H1N1)pdm09 pandemic.

<p>Population characteristics of pregnant women eligible for influenza vaccination during the influenza A(H1N1)pdm09 pandemic.</p

Time periods for inclusion of pregnancies in the study.

<p>Time periods for inclusion of pregnancies in the study.</p

Percentage of pregnancies surviving (blue) and vaccinated (red) by each gestational week.

<p>The drop in survival at 10 weeks is an artefact of the defaulting process. In reality the losses contributing to this curve would be more evenly distributed across weeks 9–12 resulting in a more gradual drop in survival.</p

Sensitivity analysis 1.

<p>All hazard ratios are for gestational weeks 9–12 only. **same as effect estimates in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0051734#pone-0051734-t002" target="_blank">table 2</a>.</p><p>Effect of varying the default length of first trimester spontaneous losses.</p

Sensitivity analysis 2.

<p>One and two week post vaccination time periods coded as unexposed to account for a delay between vaccination and onset of immunity.</p

Hazard ratios and 95% confidence intervals for association between pandemic influenza vaccination and foetal death in different gestational periods.

<p>Hazard ratios and 95% confidence intervals for association between pandemic influenza vaccination and foetal death in different gestational periods.</p

Asthma Management in Pregnancy

<div><p>Background</p><p>Asthma is common during pregnancy, however research is limited regarding the extent and timing of changes in asthma management associated with pregnancy.</p> <p>Objective</p><p>To determine the prevalence of asthma during pregnancy and identify changes in treatment and asthma exacerbation rates associated with pregnancy, while controlling for seasonal influences.</p> <p>Methods</p><p>Pregnant women with asthma were identified from the UK General Practice Research Database between 2000 and 2008. For each woman asthma medication prescribed during the study period was identified; for each product combination the British Thoracic Society medication-defined asthma treatment step was identified. Asthma exacerbations were identified during pregnancy and in the corresponding 12 months prior. Analyses of changes in asthma treatment and exacerbation rates during pregnancy relative to the corresponding period 12 months prior, to control for seasonality, were stratified by trimester and asthma treatment intensity level.</p> <p>Results</p><p>The prevalence of treated asthma in pregnancies resulting in a delivery was 8.3%. From 14,141 pregnancies, in 12,828 women with asthma, 68.4% received prescriptions for a short-acting β₂-agonist and 41.2% for inhaled corticosteroids; 76.5% were managed with asthma treatment Step 1 or 2. Poor persistence to inhaled corticosteroids, defined as a gap of up to 60 days between prescriptions, was common. In 45.0% of pregnancies, an increase in average treatment step was observed whereas in 25.6% the treatment step decreased. Treatment intensity remained the same in 29.5% of pregnancies. Exacerbations occurred in 4.8% of pregnancies compared to 5.9% in the same season the year before (p<0.001).</p> <p>Conclusion</p><p>Exacerbation rates during pregnancy were slightly lower than in the year before. However, treatment patterns and exacerbation rates in this study suggest asthma control during pregnancy is variable, and women may require close monitoring especially in those with evidence of poor control before pregnancy.</p> </div

Population characteristics for the final asthma-pregnancy cohort.

<p>Population characteristics for the final asthma-pregnancy cohort.</p

Sensitivity analysis 3.

<p>Pregnancy weeks stratified as being either during influenza season or post-influenza season; no causal protective associations are expected in the post-influenza season period.</p