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A Swedish register-based 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 those vaccinated before age 17, but the observational findings do not 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 odds of several preterm birth outcomes than women who were unvaccinated. The observational study, published in The BMJ, found stronger associations for some outcomes among women vaccinated before age 17, but it cannot establish that vaccination caused the differences.
The study examined births among nulliparous women aged 16 to 35 in Sweden from 2006 through 2023, using nationwide registers. Of the eligible births, 14.8% involved women who had received a quadrivalent HPV vaccine before pregnancy. The researchers compared cases with adverse outcomes with up to 10 controls without the same outcome.
Compared with unvaccinated women, vaccinated women had 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). The study also reported lower odds of preterm prelabor rupture of membranes and severe small-for-gestational-age infants. It found no significant overall differences for membrane rupture without the preterm qualifier, stillbirth or neonatal mortality.
For women vaccinated before age 17, adjusted odds were lower for preterm birth (aOR 0.90; 0.85–0.95) and spontaneous preterm birth (aOR 0.89; 0.84–0.95) than for unvaccinated women. These are relative odds estimates, not direct measures of how many births would be prevented. The researchers also found that associations with preterm outcomes weakened after accounting for high-grade cervical lesions diagnosed before childbirth.
Potential Benefits Beyond Cancer Prevention
The results add pregnancy outcomes to discussion of HPV vaccination, which is primarily used to prevent HPV infections that can lead to cervical and other cancers. If the associations are supported by further research, they could matter to public-health evaluations of vaccination programs and their costs. The researchers said assessments could account for both cancer prevention and possible reductions in pregnancy complications and related healthcare costs.
The findings do not change what the study can establish: it was an observational analysis, not a trial assigning vaccination. The differences were modest at the individual level, and other characteristics associated with vaccination may also be associated with pregnancy outcomes. The study is a reason for further investigation, not proof that an HPV shot prevents preterm birth.
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Study Scope and Vaccination Timing
The analysis focused on women receiving a quadrivalent HPV vaccine before pregnancy. Researchers excluded births where the first HPV vaccination recorded was a bivalent or nonavalent vaccine, so the results should not automatically be generalized to every vaccine formulation or population.
The authors noted that earlier vaccination may provide protection before potential HPV exposure and allow more time before reproductive years. In the United States, the American Academy of Pediatrics recommends a two-dose series of the nine-valent vaccine beginning between ages 9 and 12. That guidance is separate from this Swedish study, which assessed associations in registered births rather than testing vaccination schedules.
“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, speaking to MedPage Today
Causation and Mechanism Remain Open
The study cannot determine whether vaccination itself explains the lower odds. The researchers cited possible residual confounding, including differences in catch-up or opportunistic vaccination, prior HPV exposure, and sexual or reproductive behavior, particularly among women vaccinated at age 17 or older. The analysis also could not fully account for differences in preventive interventions for preterm birth.
High-grade cervical lesions were diagnosed before childbirth in 0.6% of vaccinated women and 3.7% of unvaccinated women. Adjusting for these diagnoses weakened the associations with preterm birth outcomes, which is consistent with a possible role for preventing lesions or subsequent cervical treatment. But the study lacked detailed records of cervical treatment, so it cannot establish that explanation. The authors also raised possible effects of HPV on embryonic development or placental function, but these remain hypotheses.
Further Research Needed
The next step is for researchers to test whether similar associations appear in other populations and in studies able to better account for vaccination history, HPV exposure, cervical lesions and treatment, and other pregnancy-related factors. Further work could also examine whether the patterns differ by vaccine type and age at vaccination.
For now, the findings do not establish a new pregnancy-related indication for HPV vaccination. The study authors said policy and cost-effectiveness analyses could consider the reported associations alongside established cancer-prevention benefits, while further evidence is gathered.
Key Questions
Does this study prove HPV vaccination prevents preterm birth?
No. It found an association in an observational study; it did not prove that vaccination caused the lower odds.
Which pregnancy outcomes were associated with vaccination?
Vaccination was associated with lower odds of preterm, very preterm and spontaneous preterm birth, as well as preterm prelabor rupture of membranes and severe small-for-gestational-age infants. No significant overall differences were reported for stillbirth, neonatal mortality or membrane rupture without the preterm qualifier.
Were the associations stronger for women vaccinated younger?
For preterm and spontaneous preterm birth, the reported associations were stronger among women vaccinated before age 17. This comparison does not show that age alone explains the differences.
Could cervical treatment explain the results?
It may account for part of the association, according to the researchers, because adjustment for high-grade cervical lesions weakened some findings. However, detailed cervical-treatment information was unavailable, so the proposed explanation remains uncertain.
Source: rss
