British Medical Journal
28 August 2015 (vol 351, issue 8024)
http://www.bmj.com/content/351/8024

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Editorials
Europe’s refugee crisis: an urgent call for moral leadership
BMJ 2015; 351 doi: http://dx.doi.org/10.1136/bmj.h4833 (Published 09 September 2015) Cite this as: BMJ 2015;351:h4833
Kamran Abbasi, international editor, The BMJ,
Kiran Patel, consultant cardiologist, Heart of England NHS Trust,
Fiona Godlee, editor in chief, The BMJ
Offering asylum is a minimum standard of civilised society
Europe’s refugee crisis is the greatest test of humanity faced by the world’s rich countries this century. It isn’t a new crisis. Nor was it difficult for politicians to anticipate. Refugees have fled to Europe since at least the premature optimism of the Arab Spring in 2011. Today, optimism is replaced by desperation, a promise of freedom overshadowed by death. Western nations rushed to support the democratic principles of the Arab Spring yet are reluctant to address the root causes and the consequences, which include civil war and state brutality, most notably in Syria. Oil rich Arab States have played their part by allowing political oppression and conflict to flourish in their region. A funding crisis in UN organisations is affecting the humanitarian effort in the Middle East, driving refugees to Europe in greater numbers.1 Ignoring injustice and inequity in poorer countries and in areas of conflict has not prevented the consequences reaching the shores and borders of the rich world…

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Research
Effect of bivalent human papillomavirus vaccination on pregnancy outcomes: long term observational follow-up in the Costa Rica HPV Vaccine Trial
BMJ 2015; 351 doi: http://dx.doi.org/10.1136/bmj.h4358 (Published 07 September 2015) Cite this as: BMJ 2015;351:h4358
Orestis A Panagiotou, researcher1, Brian L Befano, senior programmer2, Paula Gonzalez, investigator34, Ana Cecilia Rodríguez, investigator3, Rolando Herrero, group head4, John T Schiller, senior investigator5, Aimée R Kreimer, investigator1, Mark Schiffman, senior investigator1, Allan Hildesheim, senior investigator1, Allen J Wilcox, senior investigator6, Sholom Wacholder, senior investigator1 on behalf of the Costa Rica HPV Vaccine Trial (CVT) Group (see end of manuscript for full list of investigators)
Abstract
Objective
To examine the effect of the bivalent human papillomavirus (HPV) vaccine on miscarriage.
Design
Observational long term follow-up of a randomized, double blinded trial combined with an independent unvaccinated population based cohort.
Setting S
ingle center study in Costa Rica.
Participants
7466 women in the trial and 2836 women in the unvaccinated cohort enrolled at the end of the randomized trial and in parallel with the observational trial component.
Intervention Women in the trial were assigned to receive three doses of bivalent HPV vaccine (n=3727) or the control hepatitis A vaccine (n=3739). Crossover bivalent HPV vaccination occurred in the hepatitis A vaccine arm at the end of the trial. Women in the unvaccinated cohort received (n=2836) no vaccination.
Main outcome measure
Risk of miscarriage, defined by the US Centers for Disease Control and Prevention as fetal loss within 20 weeks of gestation, in pregnancies exposed to bivalent HPV vaccination in less than 90 days and any time from vaccination compared with pregnancies exposed to hepatitis A vaccine and pregnancies in the unvaccinated cohort.
Results
Of 3394 pregnancies conceived at any time since bivalent HPV vaccination, 381 pregnancies were conceived less than 90 days from vaccination. Unexposed pregnancies comprised 2507 pregnancies conceived after hepatitis A vaccination and 720 conceived in the unvaccinated cohort. Miscarriages occurred in 451 (13.3%) of all exposed pregnancies, in 50 (13.1%) of the pregnancies conceived less than 90 days from bivalent HPV vaccination, and in 414 (12.8%) of the unexposed pregnancies, of which 316 (12.6%) were in the hepatitis A vaccine group and 98 (13.6%) in the unvaccinated cohort. The relative risk of miscarriage for pregnancies conceived less than 90 days from vaccination compared with all unexposed pregnancies was 1.02 (95% confidence interval 0.78 to 1.34, one sided P=0.436) in unadjusted analyses. Results were similar after adjusting for age at vaccination (relative risk 1.15, one sided P=0.17), age at conception (1.03, P=0.422), and calendar year (1.06, P=0.358), and in stratified analyses. Among pregnancies conceived at any time from bivalent HPV vaccination, exposure was not associated with an increased risk of miscarriage overall or in subgroups, except for miscarriages at weeks 13-20 of gestation (relative risk 1.35, 95% confidence interval 1.02 to 1.77, one sided P=0.017).
Conclusions
There is no evidence that bivalent HPV vaccination affects the risk of miscarriage for pregnancies conceived less than 90 days from vaccination. The increased risk estimate for miscarriages in a subgroup of pregnancies conceived any time after vaccination may be an artifact of a thorough set of sensitivity analyses, but since a genuine association cannot totally be ruled out, this signal should nevertheless be explored further in existing and future studies.
Trial registration
Clinicaltrials.gov NCT00128661 and NCT01086709.