TL;DR
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A Swedish national case-control study found that women vaccinated against HPV before pregnancy had modestly lower odds of preterm, very preterm and spontaneous preterm birth. The associations were stronger for some outcomes among women vaccinated before age 17, but the observational study cannot establish that vaccination caused the differences.
A Swedish national case-control study found that women who received a quadrivalent HPV vaccine before pregnancy had lower odds of several adverse birth outcomes, including preterm birth, than women who were unvaccinated. The analysis covered 624,713 singleton births from 2006 through 2023, but its observational design means it cannot show that vaccination caused the differences.
Researchers led by Jiayao Lei of the Karolinska Institute compared pregnancy outcomes among women aged 16 to 35 who had not previously given birth. In the study, vaccination was associated with lower adjusted odds of preterm birth (aOR 0.95), very preterm birth (aOR 0.85) and spontaneous preterm birth (aOR 0.95). The paper was published in The BMJ, according to MedPage Today’s account of the study.
Associations for some outcomes were stronger among women vaccinated before age 17: adjusted odds were 0.90 for preterm birth and 0.89 for spontaneous preterm birth compared with unvaccinated women. Vaccination was also associated with lower odds of preterm prelabor rupture of membranes and severe small-for-gestational-age birth. The researchers reported no significant differences for ordinary prelabor rupture of membranes, stillbirth or neonatal mortality across the vaccinated group overall.
These are adjusted odds ratios, not direct estimates of how many pregnancies vaccination would prevent from having a complication. Overall, 14.8% of eligible women had received quadrivalent HPV vaccination before pregnancy. The researchers matched cases with up to 10 controls without the same outcome to address some potential differences between groups.
Potential Benefits Beyond Cancer Prevention
HPV vaccination is used to prevent infections that can lead to cervical and other cancers. The study adds evidence about a possible association with pregnancy and birth outcomes, an area that may matter to families and to evaluations of vaccination programs. The researchers told MedPage Today that even modest differences could have population-level health and economic implications, but that is an interpretation of the findings, not a measured result of this study.
The results do not change what the study can establish: they show an association, not proof that vaccination prevents preterm birth. Still, the findings may inform future research and analyses that weigh the broader effects of HPV vaccination alongside cancer prevention. They do not establish a pregnancy-specific reason to vaccinate or replace existing guidance; people with questions about vaccination should consult a qualified health professional.
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How Vaccination Could Relate to Birth Outcomes
The analysis included women whose first HPV vaccination was quadrivalent; births among women first vaccinated with bivalent or nonavalent vaccines were excluded. The source report notes that U.S. pediatric guidance recommends a two-dose series of the nine-valent vaccine beginning between ages 9 and 12. That recommendation is separate from this Swedish study, which examined a different vaccine type and a Swedish population.
The researchers discussed two possible routes for the observed association: HPV infection might affect embryonic development or the placenta, and vaccination might reduce exposure to HPV during pregnancy. Another possibility is that preventing high-grade cervical lesions could reduce the need for cervical procedures associated with pregnancy risks. The study did not establish which, if any, explains the results.
High-grade cervical lesions had been diagnosed before childbirth in 0.6% of vaccinated women and 3.7% of unvaccinated women. When researchers adjusted for these lesions, the associations with preterm-birth outcomes weakened. The authors said this pattern may be consistent with lesion prevention contributing to the association, while cautioning that the analysis was exploratory.
“Our findings highlight the importance of timely HPV vaccination and suggest that its potential benefits may extend beyond cancer prevention to reproductive health.”
— Jiayao Lei and Zhongsong Zhang, Karolinska Institute researchers, in comments to MedPage Today
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Causation and Mechanism Remain Unclear
Because this was an observational case-control study, unmeasured differences between vaccinated and unvaccinated women may have affected the results. The authors identified possible residual confounding related to catch-up or opportunistic vaccination, prior HPV exposure, and sexual or reproductive behavior, particularly among women vaccinated at age 17 or older. The study also could not fully assess differences in preventive interventions for preterm birth.
Researchers lacked detailed information about cervical treatment, so they could not determine whether fewer lesions or procedures accounted for some of the association. The findings also concern a specific group—first-time mothers aged 16 to 35 in Sweden—and the quadrivalent vaccine. Whether the results apply to other populations or vaccine formulations is not established by this analysis.
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Further Studies Must Test the Link
The study report does not specify a next research milestone. Further research could examine whether the associations persist in other populations and with other HPV vaccine formulations, and whether cervical lesions or treatments help explain them. More detailed data on participants’ vaccination histories, HPV exposure and pregnancy care could help address limitations identified by the authors.
For now, the reported findings are evidence of a possible association, not a basis for promising an individual pregnancy outcome. The researchers said policy and cost-effectiveness analyses could take potential pregnancy-related effects into account alongside cancer prevention; whether such analyses will change policy remains unknown.
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Key Questions
What did the Swedish study find?
Among 624,713 singleton births, prior quadrivalent HPV vaccination was associated with lower adjusted odds of preterm, very preterm and spontaneous preterm birth. The study also reported associations with some other outcomes, including severe small-for-gestational-age birth.
Does the study prove HPV vaccination prevents preterm birth?
No. The study was observational and found associations. It cannot establish that vaccination caused the lower odds or rule out other differences between vaccinated and unvaccinated women.
Were the findings stronger for people vaccinated younger?
For preterm and spontaneous preterm birth, the reported associations were stronger among women vaccinated before age 17. This subgroup finding does not by itself establish why the association differed.
Did vaccination lower every pregnancy risk studied?
No. The researchers reported no significant overall differences for prelabor rupture of membranes, stillbirth or neonatal mortality. Results varied by outcome and, for some measures, by age at vaccination.
Can these results be applied to every HPV vaccine or population?
The study examined Swedish births and women whose first HPV vaccine was quadrivalent. It excluded women first vaccinated with bivalent or nonavalent vaccines, so it does not establish that the results apply to those formulations or other populations.
Source: rss
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