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Women treated for grade 3 cervical intraepithelial neoplasia (CIN3) had greater risks of preterm birth and other adverse pregnancy outcomes, but this risk may be decreasing over time, researchers found.

Women treated for CIN3 were twice as likely to experience preterm birth (OR 2.09, 95% CI 2.03-2.15) and three times as likely to experience extremely preterm birth (OR 3.00, 95% CI 2.69-3.34) compared to the general population, reported Wei He, PhD, of Zhejiang University in Hangzhou, and colleagues.

Treatment for CIN3 was also associated with higher risks of chorioamnionitis, infant sepsis, and early neonatal death, the researchers wrote in .

However, many pregnancy-related risks decreased among women with CIN3 over the study period from 1973 to 2018, suggesting that "more conservative treatment methods may minimize subsequent adverse birth outcomes," He and colleagues wrote.

They cited a shift from the use of more aggressive surgical methods to less invasive procedures, such as loop electrosurgical excisions, which may have contributed to the decrease in risk.

As women treated for CIN3, which is typically caused by human papillomavirus (HPV) infection, are still at risk for preterm birth and other infection-related pregnancy outcomes, He and co-authors said that these patients should be "recognized as high risk and managed accordingly."

In an , Rebecca Perkins, MD, MsC, of Boston University, and colleagues, said that although this research concludes that pregnancies after treatment for CIN3 should be considered high risk, "optimal clinical care remains unclear."

While this study controlled for possible genetic factors, "it could not further disentangle the effects of treatment from those of CIN3 or HPV itself, which limits the ability to inform clinical care," the editorialists stated. They added that primary prevention through HPV vaccination will likely lead to a substantial reduction in poor obstetric outcomes.

In this study, He and colleagues investigated the association between treatment for CIN3 and preterm birth, as well as other birth-related outcomes. They analyzed data from five national databases in Sweden, collecting information on all births, cancer diagnoses, family information, and education from 1973 to 2018.

The researchers compared birth outcomes among women with CIN3 to the general population, assuming that all women with CIN3 were treated for it, according to Swedish standards of practice. Additionally, the researchers conducted a sibling-matched analysis, linking all women with CIN3 to their sisters without a diagnosis in order to control for possible genetic factors.

He's group controlled for covariates including calendar period of delivery, region, maternal age, parity, preeclampsia, smoking during pregnancy, and prepregnancy BMI.

Overall, there were more than 4.6 million births in the study cohort, 78,450 of which took place after a maternal CIN3 diagnosis. In the sibling analysis, around 23,000 women with a CIN3 diagnosis were linked to their sisters without CIN3.

Women who were treated for CIN3 were more likely to experience preterm birth, with the association primarily for spontaneous rather than iatrogenic preterm birth. These patients also faced higher risks of chorioamnionitis (OR 3.23, 95% CI 2.89-3.62), infant sepsis (OR 1.72, 95% CI 1.60-1.86), and early neonatal death (OR 1.83, 95% CI 1.61-2.09).

In all maternal subgroups, women with CIN3 were more likely to have a preterm birth, chorioamnionitis, or infant sepsis. These associations were stronger among mothers with lower education levels, higher parity, and a lower pre-pregnancy BMI. The researchers did not find an association between CIN3 and stillbirth.

Risks of all adverse pregnancy outcomes associated with CIN3 treatment decreased over time. The odds ratio of preterm birth declined from 3.69 (95% CI 3.41-3.99) in 1973-1979, to 1.78 (95% CI 1.69-1.88) in 2010-2018. The risks also declined for infant sepsis and early neonatal death across the study time period.

He and colleagues acknowledged that this study lacks data on treatment of CIN3 and spontaneous abortion, which could affect the findings. This study may be subject to misclassification of CIN2 and CIN3. Additionally, the researchers stated that they may not have been able to control for all confounders, and these results may not be generalizable to low-income countries.

"Our results indicate that caution should be taken when applying a screen-and-treat approach to women of reproductive age, given that overtreatment of the cervix may have a detrimental effect on future pregnancies," the study authors said.

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