A national case-control study from Sweden, published in The BMJ, has suggested that women vaccinated against human papillomavirus (HPV) were significantly less likely to have a range of adverse outcomes during pregnancy, reports MedPage Today.
The scientists said the links were even stronger in those receiving the jab before they were 17.
Among nearly 625 000 births from 2006 to 2023, those who’d received a quadrivalent HPV shot had significantly lower odds of preterm birth (adjusted odds ratio [aOR] 0.95, 95% CI 0.91-0.99), very preterm birth (aOR 0.85, 95% CI 0.75-0.97), and spontaneous preterm birth (aOR 0.95, 95% CI 0.91-0.99) compared with those who were unvaccinated, reported Jiayao Lei, PhD, of Karolinska Institute in Stockholm, and colleagues.
They found the links were emphasised when HPV vaccination happened before 17 for both preterm birth (aOR 0.90, 95% CI 0.85-0.95) and spontaneous preterm birth (aOR 0.89, 95% CI 0.84-0.95) compared with those who were unvaccinated.
“Our findings highlight the importance of timely HPV vaccination and suggest its potential benefits may extend beyond cancer prevention to reproductive health,” Lei and co-author Zhongsong Zhang, a PhD student at Karolinska Institute, told MedPage Today.
“Although the observed differences were relatively modest at the individual level, they could translate into meaningful public health and economic benefits at the population level.”
Given the results, policy and cost-effectiveness analyses should include HPV vaccination’s cancer prevention benefits and reductions in pregnancy-related complications and resulting lifelong healthcare costs, they noted.
The potential pregnancy advantages linked to earlier HPV jabs may show that the shots deliver greater benefits when they’re given before sexual debut and potential HPV exposure, Lei and Zhang noted. “Vaccination at an earlier age may also allow women to benefit from this protection for a longer period before entering their reproductive years,” they said.
The reasons why HPV and pregnancy outcomes may be linked aren’t entirely certain, though Lei and Zhang highlighted two potential explanations.
HPV may interfere with embryonic development, which could lead to placental problems and greater preterm birth risk, while maternal vaccination could also reduce the risk of embryonic HPV exposure and consequent pregnancy complications.
Research has also linked treatment for HPV-related high-grade cervical lesions with greater risks of preterm birth and other adverse pregnancy outcomes. In the current study population, 0.6% of vaccinated women and 3.7% of unvaccinated women had a diagnosis of high-grade cervical lesion before they gave birth. When the researchers adjusted for high-grade lesions before childbirth, the associations between HPV vaccination and preterm birth-related outcomes weakened.
“This pattern is consistent with the possibility that preventing high-grade cervical lesions and subsequent cervical treatments may partly explain the observed associations,” Lei and Zhang said.
But the study didn’t have detailed information on study participants’ cervical treatment, they cautioned, meaning “the analysis should be interpreted as exploratory rather than definitive evidence of an underlying mechanism”.
In the US, a two-dose series of the nine-valent HPV vaccine (Gardasil 9) is recommended by the American Academy of Paediatrics, starting between the ages of nine and 12 years, though recent research has suggested a single shot may offer similar levels of protection.
The study included 624 713 singleton births in Sweden among nulliparous women age 16 to 35, with data drawn from nationwide registers. Among eligible births, 14.8% of women had quadrivalent HPV vaccination before pregnancy. The researchers excluded births from women whose first HPV vaccination was bivalent or nonavalent. To help counter confounding, the researchers matched each adverse pregnancy outcome case with up to 10 controls without the same adverse outcomes.
Vaccinated women were significantly less likely to have preterm prelabour rupture of membranes (preterm PROM; aOR 0.93, 95% CI 0.87-1.00) or severe small for gestational age infant (aOR 0.92, 95% CI 0.87-0.97), while no significant differences were observed when it came to PROM, stillbirth, or neonatal mortality.
Women who got a shot before age 17 were significantly less likely to have preterm PROM (aOR 0.86, 95% CI 0.78-0.94) and severe small for gestational age infants (aOR 0.91, 95% CI 0.84-0.97) compared with the unvaccinated while those vaccinated at 17 or older had lower odds of severe small for gestational age infants (aOR 0.93, 95% CI 0.87-0.99) and stillbirth (aOR 0.79, 95% CI 0.63-0.99).
Study limitations included potential residual confounding from catch-up or opportunistic vaccination, prior HPV exposure, or sexual or reproductive behaviour, particularly in women 17 and older. Differences in preventive interventions for preterm birth couldn’t be fully assessed.
Study details
Quadrivalent human papillomavirus vaccination before pregnancy and pregnancy outcomes: nationwide, population based case-control study
Zhongsong Zhang, Alexander Ploner, Verena Sengpiel et al.
Published in The BMJ on 7 October 2026
Abstract
Objective
To evaluate the association between quadrivalent human papillomavirus vaccination before pregnancy and subsequent risk of adverse pregnancy outcomes.
Design
Nationwide, population based matched case-control study.
Setting
Population of Sweden, from 1 January 2006 to 31 December 2023.
Participants
A total of 624 713 singleton births among nulliparous women aged 16-35 years in Sweden between 2006 and 2023; 92 620 (14.8%) women had received quadrivalent human papillomavirus vaccination before pregnancy.
Main outcome measures
Risk of adverse pregnancy outcomes associated with quadrivalent human papillomavirus vaccination, with preterm birth (<37 weeks), including its subtypes, and spontaneous preterm birth as primary outcomes and preterm prelabour rupture of membranes, prelabour rupture of membranes, small for gestational age infant (<10th centile), severe small for gestational age infant (<3rd centile), stillbirth, and neonatal mortality as secondary outcomes. Effect modification by age at human papillomavirus vaccination was assessed. Conditional logistic regression was used to estimate odds ratios and adjusted odds ratios with 95% confidence intervals (CIs).
Results
After adjustment for confounders, quadrivalent human papillomavirus vaccination was associated with lower odds of all included adverse pregnancy outcomes. Statistically significant associations were observed for preterm birth (<37 weeks) (adjusted odds ratio 0.95, 95% CI 0.91 to 0.99), very preterm birth (28 weeks to 31 weeks) (0.85, 0.75 to 0.97), spontaneous preterm birth (0.95, 0.91 to 0.99), preterm prelabour rupture of membranes (0.93, 0.87 to 1.00), and severe small for gestational age infant (0.92, 0.87 to 0.97). Risk reduction was generally more pronounced among women vaccinated at younger ages.
Conclusions
Quadrivalent human papillomavirus vaccination before pregnancy was associated with a lower risk of adverse pregnancy outcomes, particularly among women vaccinated at earlier ages, extending benefits of human papillomavirus vaccination beyond cancer prevention.
MedPage Today article – Study Finds Lower Pregnancy Risks in HPV-Vaccinated Women (Open access)
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