TL;DR
A Swedish case-control study covering 624,713 singleton births from 2006 to 2023 found lower adjusted odds of preterm, very preterm and spontaneous preterm birth among women vaccinated against HPV before pregnancy. 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 study of 624,713 singleton births found that women vaccinated against human papillomavirus (HPV) before pregnancy had lower adjusted odds of preterm birth, including very preterm and spontaneous preterm birth, than unvaccinated women. The observational findings, published in The BMJ, do not show that vaccination itself caused the differences, and the associations were modest for several outcomes.
The national case-control study used Swedish register data on nulliparous women aged 16 to 35 who gave birth between 2006 and 2023. It examined births after quadrivalent HPV vaccination; women whose first HPV dose was a bivalent or nonavalent vaccine were excluded. Among eligible births, 14.8% of women had been vaccinated before pregnancy. For each case with an adverse outcome, researchers matched up to 10 controls without that outcome.
Compared with no vaccination, vaccination was associated with lower adjusted odds of preterm birth (adjusted odds ratio, or aOR, 0.95; 95% confidence interval 0.91–0.99), very preterm birth (aOR 0.85; 0.75–0.97) and spontaneous preterm birth (aOR 0.95; 0.91–0.99). Women vaccinated before age 17 had lower odds of preterm birth (aOR 0.90; 0.85–0.95) and spontaneous preterm birth (aOR 0.89; 0.84–0.95) than unvaccinated women. These are relative odds estimates, not percentage-point reductions in the number of births affected.
The researchers also reported lower odds of preterm prelabor rupture of membranes and severe small-for-gestational-age birth among vaccinated women. No significant differences were observed for rupture of membranes overall, stillbirth or neonatal mortality in the main vaccinated-versus-unvaccinated comparison. Some outcome associations differed by age at vaccination. The authors said adjustment for high-grade cervical lesions before childbirth weakened associations with preterm-birth outcomes.
Possible Benefits Beyond Cancer Prevention
The results add pregnancy outcomes to discussion of HPV vaccination, which is chiefly given to prevent HPV infections and related cancers. If further research supports the association, prevention of cervical lesions or related treatments could be one route by which vaccination might relate to birth outcomes. The study does not establish that mechanism or prove a direct protective effect during pregnancy.
The authors told MedPage Today that the observed differences were relatively modest for individuals but could have public-health and economic relevance across a population. They argued that policy and cost-effectiveness analyses could account for possible reductions in pregnancy complications alongside cancer prevention. That is a proposed implication, not an effect measured directly by this study.
How Researchers Interpreted the Association
HPV can affect cervical tissue, and treatment for high-grade cervical lesions has previously been linked in research to increased risks of preterm birth and other pregnancy outcomes. In this study, a diagnosis of a high-grade cervical lesion before delivery was recorded in 0.6% of vaccinated women and 3.7% of unvaccinated women. When the researchers accounted for such lesions, the associations with preterm-birth outcomes weakened.
Lead researcher Jiayao Lei and co-author Zhongsong Zhang said that pattern was consistent with the possibility that preventing lesions and subsequent cervical treatment may partly explain the findings. They also described possible biological pathways involving HPV, embryonic development and the placenta. The study did not establish those explanations. In the United States, the source report says pediatric guidance recommends a two-dose series of the nine-valent vaccine beginning between ages 9 and 12; the Swedish analysis itself examined quadrivalent vaccination.
“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, researchers at Karolinska Institute, speaking to MedPage Today
Causation and Mechanism Remain Unsettled
This was an observational case-control study, so differences between vaccinated and unvaccinated women could reflect factors beyond vaccination. The authors noted possible residual confounding related to catch-up or opportunistic vaccination, previous HPV exposure, and sexual or reproductive behavior, particularly among women vaccinated at age 17 or later. The analysis also could not fully assess differences in preventive interventions for preterm birth.
Researchers did not have detailed records of cervical treatment, so they could not determine whether fewer lesions or treatments explain part of the association. The study population was restricted to first births among women aged 16 to 35 in Sweden, and the vaccine analysis was limited to the quadrivalent shot. It remains unclear whether the findings apply to other vaccine formulations or populations, or whether vaccination directly changes pregnancy risks.
Further Studies Must Test the Findings
The findings point to questions for further research, rather than a change to vaccination guidance based on pregnancy outcomes alone. Studies with more detailed information on cervical lesions and their treatment could test whether those factors account for part of the association. Research that better measures prior HPV exposure, vaccination timing and reproductive behavior may also help address confounding.
For now, the reported outcomes should be read as associations from Swedish register data, not proof that HPV vaccination prevents pregnancy complications. The source report does not identify a scheduled follow-up study or a specific next research milestone.
Key Questions
What did the Swedish study find?
Among 624,713 singleton births, HPV-vaccinated women had lower adjusted odds of preterm, very preterm and spontaneous preterm birth than unvaccinated women. The study found associations, not proof that the vaccine caused lower risks.
Were the associations stronger for women vaccinated before age 17?
Yes, for preterm birth and spontaneous preterm birth. Vaccination before age 17 was associated with adjusted odds ratios of 0.90 and 0.89, respectively, compared with no vaccination.
Does this prove HPV vaccination prevents preterm birth?
No. The study was observational, and differences in prior HPV exposure, reproductive behavior, vaccination circumstances or other factors could influence the results. The authors also said the proposed explanation involving cervical lesions and treatment remains exploratory.
Which vaccine did the study examine?
The analysis examined the quadrivalent HPV vaccine. It excluded births where the woman’s first HPV vaccination was bivalent or nonavalent, so the results do not directly establish effects for those formulations.
Did vaccination reduce every pregnancy outcome studied?
No. The study reported lower odds for several outcomes, including some preterm-birth measures, but found no significant differences in the main comparison for rupture of membranes overall, stillbirth or neonatal mortality.
Source: rss
