TL;DR
A Swedish case-control study of 624,713 singleton births found that women who received a quadrivalent HPV vaccine before pregnancy had modestly lower odds of preterm, very preterm and spontaneous preterm birth. Associations were stronger for some outcomes among women vaccinated before age 17, but the observational study cannot establish that vaccination caused the differences.
A national Swedish case-control study found that women vaccinated against HPV before pregnancy had lower odds of several preterm birth outcomes than unvaccinated women, based on 624,713 singleton births from 2006 to 2023. The findings, published in The BMJ, show associations rather than proof that vaccination prevents pregnancy complications.
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The study examined women aged 16 to 35 who had not previously given birth. Among the eligible births, 14.8% of women had received a quadrivalent HPV vaccine before pregnancy. Compared with unvaccinated women, vaccinated women had lower adjusted odds of preterm birth (aOR 0.95), very preterm birth (aOR 0.85) and spontaneous preterm birth (aOR 0.95). The researchers matched each case of an adverse outcome with up to 10 controls without that outcome.
For women vaccinated before age 17, the adjusted odds were lower for preterm birth (aOR 0.90) and spontaneous preterm birth (aOR 0.89) compared with women who were unvaccinated. Vaccination was also associated with lower odds of preterm prelabor rupture of membranes and severe small-for-gestational-age birth. The study found no significant differences for prelabor rupture of membranes overall, stillbirth or neonatal mortality across vaccinated and unvaccinated women.
The researchers also examined diagnoses of high-grade cervical lesions before childbirth. These were recorded for 0.6% of vaccinated women and 3.7% of unvaccinated women. When the analysis adjusted for such lesions, the associations with preterm birth outcomes weakened. The study did not include detailed information about cervical treatments, limiting what researchers could conclude about why the differences appeared.
Potential Benefits Beyond Cancer Prevention
HPV vaccination is primarily used to prevent infections that can lead to cervical and other cancers. The findings raise the possibility that vaccination may also be associated with some differences in pregnancy outcomes, adding a potential consideration for public health evaluations of vaccination programs.
The researchers, Jiayao Lei and Zhongsong Zhang of Karolinska Institute, told MedPage Today that the individual differences were relatively modest, though they said the results could have population-level and economic implications. That is an interpretation of the findings, not an outcome directly measured by the study. The research did not establish how many pregnancy complications vaccination would prevent, or whether the observed associations would hold in other populations.
For readers, the results do not change the distinction between an association and a demonstrated cause. They support further research into whether preventing HPV infection or related cervical disease could be connected to pregnancy outcomes, while offering no basis to treat HPV vaccination as a pregnancy intervention.
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How the Swedish Study Was Designed
The researchers used nationwide Swedish registers to identify births from 2006 through 2023, focusing on singleton births to women aged 16 to 35 who had not previously given birth. The analysis included recipients of the quadrivalent HPV vaccine and excluded births when the first recorded HPV vaccination was bivalent or nonavalent. The study design compared women with specific outcomes against matched controls; it was not a randomized trial.
HPV-related high-grade cervical lesions and treatment for those lesions have been linked in earlier research to greater risks of preterm birth and other adverse pregnancy outcomes. The study authors suggested that preventing lesions and subsequent cervical treatment could partly account for their results. They also raised possible biological explanations involving HPV, embryonic development and the placenta, but said the mechanisms are not established.
In the United States, the American Academy of Pediatrics recommends a two-dose nine-valent HPV vaccine series, starting between ages 9 and 12. The Swedish study assessed a different vaccine formulation and population, so its findings should not be read as a direct comparison of current U.S. 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, researchers at Karolinska Institute, speaking to MedPage Today
Cause and Mechanism Remain Unsettled
The study cannot show that HPV vaccination itself caused lower odds of the reported outcomes. Because it was observational, unmeasured differences between vaccinated and unvaccinated women could have influenced the results. The authors cited possible residual confounding from catch-up or opportunistic vaccination, prior HPV exposure, and sexual or reproductive behavior, particularly among women vaccinated at age 17 or older.
The researchers also could not fully assess differences in preventive interventions for preterm birth. Although adjusting for high-grade cervical lesions weakened some associations, the registers did not provide detailed information about cervical procedures. It remains unclear how much of the relationship, if any, might reflect prevention of lesions or treatment rather than another factor.
The findings concern a particular Swedish population, a particular vaccine formulation and births recorded over a defined period. The source report does not establish whether the same associations apply to other HPV vaccines, populations, or pregnancy outcomes beyond those analyzed.
Further Studies Must Test the Link
The study authors said policy and cost-effectiveness analyses should account for HPV vaccination’s established cancer-prevention role and investigate whether pregnancy-related complications and associated long-term health costs should also be considered. Such analyses would need to distinguish measured effects from possible benefits suggested by this study.
Further research could test whether the associations appear in other populations and vaccine programs, and examine cervical diagnoses and treatments in greater detail. Until then, the immediate finding is a set of modest observational associations; whether vaccination directly changes pregnancy risk remains unresolved.
Key Questions
What did the Swedish study find?
Women who received a quadrivalent HPV vaccine before pregnancy had lower adjusted odds of preterm, very preterm and spontaneous preterm birth than unvaccinated women in the study. The results describe associations, not proof that vaccination caused the differences.
Were the associations stronger for women vaccinated earlier?
For preterm and spontaneous preterm birth, the associations were stronger among women vaccinated before age 17 than in the overall vaccinated group. The study does not establish why timing was associated with the differences.
Does this prove HPV vaccination prevents pregnancy complications?
No. The research was an observational case-control study, not a randomized trial. Residual confounding and other limitations mean it cannot establish that vaccination caused the lower odds.
Which outcomes did not differ significantly?
The study reported no significant differences between vaccinated and unvaccinated women for prelabor rupture of membranes overall, stillbirth or neonatal mortality. Some other outcomes, including preterm prelabor rupture of membranes and severe small-for-gestational-age birth, were associated with lower odds among vaccinated women.
What remains unknown about the findings?
Researchers do not know the mechanism behind the associations or how much may relate to preventing high-grade cervical lesions and subsequent treatment. The study also could not fully account for cervical procedures, prior HPV exposure and reproductive behavior.
Source: rss
