TL;DR
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A Swedish national case-control study found that women who received a quadrivalent HPV vaccine before pregnancy had modestly lower odds of preterm, very preterm and spontaneous preterm birth than unvaccinated women. Associations were stronger for some outcomes among those vaccinated before age 17, but the observational study cannot establish that vaccination caused the differences.
A Swedish national case-control study of 624,713 singleton births found that women vaccinated against HPV before pregnancy had lower odds of several preterm birth outcomes than women who were unvaccinated. The associations were modest overall and stronger for some outcomes among women vaccinated before age 17; the observational findings do not show that vaccination caused the differences.
The study, published in The BMJ, examined births to first-time mothers aged 16 to 35 in Sweden from 2006 through 2023. It focused on the quadrivalent HPV vaccine and excluded births where a woman’s first HPV vaccination was with a bivalent or nine-valent vaccine. Of the eligible births, 14.8% of women had received the quadrivalent vaccine before pregnancy. Researchers matched each case of an adverse outcome with as many as 10 controls without that outcome.
Compared with unvaccinated women, vaccinated women had lower adjusted odds of preterm birth (adjusted odds ratio, or aOR, 0.95), very preterm birth (aOR 0.85) and spontaneous preterm birth (aOR 0.95). The 95% confidence intervals were 0.91–0.99, 0.75–0.97 and 0.91–0.99, respectively. The estimates indicate associations in this study population, not guaranteed individual reductions in risk.
Other associations varied by outcome. Vaccinated women had lower odds of preterm prelabor rupture of membranes and of having a severely small-for-gestational-age infant. The researchers did not find significant differences for premature rupture of membranes overall, stillbirth or neonatal mortality. Among women vaccinated before age 17, estimates were also lower for preterm birth, spontaneous preterm birth, preterm prelabor rupture of membranes and severe small-for-gestational-age birth.
Potential Benefits Beyond Cancer Prevention
The findings add pregnancy outcomes to research on HPV vaccination, which is primarily used to prevent infections that can lead to cervical and other cancers. If further research confirms the associations, vaccination could have benefits relevant to reproductive health as well as cancer prevention. The authors told MedPage Today that the differences were modest for individuals but could matter at a population level.
The results do not change what this study can establish: it was observational, and vaccinated and unvaccinated women may differ in ways the analysis could not fully account for. The findings are not evidence that vaccination should be used as a treatment for pregnancy complications, nor do they establish a direct protective effect during pregnancy. They do provide a reason for researchers and health-policy analysts to examine whether any reproductive-health effects belong in broader evaluations of HPV vaccination.
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Study Scope and Possible Explanations
The researchers, led by Jiayao Lei of the Karolinska Institute in Stockholm, studied nationwide register data and compared outcomes between vaccinated and unvaccinated women. The analysis included only first births and the specified quadrivalent vaccine exposure before pregnancy, so its results should not automatically be applied to every vaccine formulation, population or pregnancy.
The authors discussed two possible pathways, while stressing that the mechanism is uncertain. HPV infection might affect embryonic development or the placenta; vaccination might reduce exposure to the virus. Another possibility is indirect: preventing HPV-related high-grade cervical lesions could reduce the need for cervical treatments associated with preterm birth. In the study, a diagnosis of a high-grade cervical lesion before childbirth was recorded in 0.6% of vaccinated women and 3.7% of unvaccinated women.
When the researchers adjusted for those lesions, the associations with preterm birth-related outcomes weakened. They said this pattern could fit the explanation involving lesions and subsequent treatment, but detailed information on cervical treatment was unavailable. The authors described that analysis as exploratory, not definitive evidence of a mechanism.
“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, speaking to MedPage Today
Causation and Missing Treatment Data
The study cannot determine whether HPV vaccination itself lowered pregnancy risks. The authors noted possible residual confounding, including differences related to catch-up or opportunistic vaccination, previous HPV exposure, and sexual or reproductive behavior—particularly among women vaccinated at age 17 or older. Differences in preventive interventions for preterm birth also could not be fully assessed.
Because the researchers lacked detailed records of cervical treatments, they could not test whether avoiding those procedures explains part of the association. The findings also concern a specific vaccine and population, and the source report does not establish whether similar associations apply to other vaccine formulations or settings. No significant differences were reported for several outcomes, including stillbirth overall and neonatal mortality.
Further Studies Must Test the Link
The study authors said policy and cost-effectiveness analyses should consider both HPV vaccination’s established cancer-prevention role and the possibility of fewer pregnancy complications. That is a proposal for further evaluation, not a finding that this study measured financial savings or established a new vaccination policy.
Further research would need to test whether the associations persist in other populations and vaccine cohorts, account more fully for cervical treatment and other potential confounders, and clarify possible biological pathways. Until then, the results are best read as evidence of an association in Swedish register data rather than proof that vaccination prevents preterm birth.
Key Questions
What did the Swedish study find?
It found lower adjusted odds of preterm, very preterm and spontaneous preterm birth among women who had received a quadrivalent HPV vaccine before pregnancy compared with unvaccinated women. These are associations from an observational study, not proof of cause and effect.
Were the associations stronger for women vaccinated younger?
For preterm and spontaneous preterm birth, the study reported lower odds among women vaccinated before age 17 than among unvaccinated women. The findings do not establish why the estimates differed by age.
Does the study prove that the HPV vaccine prevents pregnancy complications?
No. The case-control study found associations but cannot rule out differences between vaccinated and unvaccinated women that may have influenced the results. The authors said the proposed explanation involving cervical lesions and treatment remains exploratory.
Which pregnancy outcomes did not show significant differences?
The study reported no significant differences for premature rupture of membranes overall, stillbirth overall or neonatal mortality. Some other outcomes, including preterm prelabor rupture of membranes, did show lower odds among vaccinated women.
What remains to be studied?
Researchers need to test the findings in other populations and vaccine groups, better account for cervical treatments and potential confounders, and investigate possible mechanisms. The study did not establish economic benefits or a change to vaccination policy.
Source: rss
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