Women vaccinated against the human papillomavirus before becoming pregnant were less likely to deliver prematurely or face other pregnancy complications, and the benefit was greatest for those immunized before age 17, a large Swedish study published this week in The BMJ found.

Mothers who had received the HPV vaccine were 15 percent less likely than unvaccinated mothers to deliver very prematurely, between the 28th and 31st weeks of a 40-week pregnancy, according to the study. Babies born before the 37th week face higher odds of poor health and disability, CIDRAP News reported.

Vaccinated mothers were also 5 percent less likely to give birth before the 37th week, 7 percent less likely to have the amniotic membrane rupture before labor and 8 percent less likely to have a baby far smaller than expected for its stage of pregnancy.

Among women vaccinated before 17, the gaps widened: the risk of premature delivery was 10 percent lower than among unvaccinated mothers, the risk of early membrane rupture was 14 percent lower and the risk of a small-for-gestational-age baby was 9 percent lower. The researchers said the stronger effect likely reflects that girls immunized young had not yet been exposed to the virus, which spreads through sexual contact.

The study drew on more than 624,000 birth records of mothers ages 16 to 35, from 2006 through 2023. About 15 percent of the mothers had been vaccinated.

Zhongsong Zhang, the paper’s first author and a doctoral student in medical epidemiology and biostatistics at the Karolinska Institute in Stockholm, said future studies may show even greater protection. More than 90 percent of Swedish girls born in 2012 have received at least one dose. And the shots have improved: mothers in the study received a version covering four viral strains, given at a median age of 16, while today’s vaccine covers nine strains and Swedish school programs now offer it at ages 10 through 12. In the United States, the American Academy of Pediatrics recommends a first dose at ages 9 through 12, and 78 percent of teenagers had received at least one dose in 2024.

“We expect the potential reduction in adverse pregnancy outcomes to become more apparent as cohorts with higher vaccination coverage, particularly those vaccinated at younger ages, reach childbearing age,” Zhang told CIDRAP News.

Earlier population studies in Australia, Finland and Scotland had pointed the same way, but the new paper “is the largest and most comprehensive” so far, said Dr. Kevin Ault, a professor and vice chair of education at Penn State Health, who was not involved in the work. Previous research found that mothers infected with HPV were nearly twice as likely to deliver prematurely and more likely to have low-birth-weight babies.

“Getting vaccinated before pregnancy reduces this risk,” said Dr. Ault, an obstetrician-gynecologist.

The virus may threaten pregnancies in more than one way, said Dr. Rebecca Perkins, an obstetrician-gynecologist at Tufts Medical Center who was not involved in the study. Chronic HPV infection can produce cervical cancers and precancers, and removing those growths can shorten the cervix, a known risk factor. Even a cervical biopsy raises the odds of early delivery. But the study found elevated risks among unvaccinated mothers who had never been treated for cervical lesions, which Dr. Perkins said suggests “that infection alone carries risks,” perhaps through inflammation or placental dysfunction. Dr. Ault noted that studies have found HPV-infected cells in the vagina and cervix show blunted immune responses even without precancer.

Not everyone is persuaded. Dr. Mark Einstein, chair of obstetrics and gynecology and women’s health at Montefiore Medical Center in New York, said the study’s design cannot prove the vaccine caused the better outcomes, a limitation the authors acknowledged. “It could be that those that seek HPV vaccination are more likely to be from the social and racial demographics that put them at lower risk of preterm birth,” he said.

The researchers tried to strip out such influences, matching each mother who had a complication with up to 10 women of the same age and year of conception who did not, and accounting for smoking, body mass index at the first prenatal visit, maternal health, country of birth, family income, education and use of assisted reproduction.

Combined with earlier studies finding no rise in miscarriage after HPV vaccination, the authors wrote, the results counter claims that the shots harm girls’ future fertility. “Our results suggest that human papillomavirus vaccination is not only safe with respect to pregnancy outcomes, but may also confer additional benefits by reducing the risk of adverse events,” they wrote.