Impact of delayed LEEP on preterm birth risk in CIN2 patients


A recent study examined the heightened risk of preterm birth associated with delayed loop electrosurgical excision procedure (LEEP) compared to immediate LEEP among women with cervical intraepithelial neoplasia grade 2.

Impact of delayed LEEP on preterm birth risk in CIN2 patients | Image Credit: © Wanmongkhol - © Wanmongkhol -

Impact of delayed LEEP on preterm birth risk in CIN2 patients | Image Credit: © Wanmongkhol - © Wanmongkhol -

The risk of preterm birth is increased by delayed loop electrosurgical excision procedure (LEEP) vs immediate LEEP, according to a recent study published in JAMA Network Open.


  1. Delayed loop electrosurgical excision procedure (LEEP) for treating CIN2 is associated with a higher risk of preterm birth compared to immediate LEEP, highlighting the importance of timing in surgical interventions for cervical conditions.
  2. Active surveillance, an alternative to immediate surgical treatment, shows comparable preterm birth risks to immediate LEEP, suggesting it as a viable option for managing CIN2 in selected cases, particularly for younger women.
  3. Women undergoing delayed LEEP within 28 months of diagnosis exhibit a substantially increased risk of preterm birth compared to those undergoing immediate LEEP or active surveillance without delay, emphasizing the need for careful monitoring and management of this subgroup.
  4. Various factors such as age at diagnosis, cytology results, and timing of LEEP influence the risk of preterm birth, indicating the importance of individualized risk assessment and management strategies for women with CIN2.
  5. These findings underscore the importance of risk stratification at the time of CIN2 diagnosis to identify patients at higher risk of preterm birth and guide appropriate treatment decisions, potentially reducing adverse pregnancy outcomes in this population.

Surgical excision is used to treat cervical intraepithelial neoplasia grade 2 (CIN2), reducing cervical cancer risk. However, spontaneous regression within 2 years is reported in 50% to 60% of CIN2 cases. Surgical treatment has also been linked to increased preterm birth and preterm premature rupture of membranes (PPROM) risk.

Active surveillance is available for younger women in many higher income countries to reduce adverse outcomes associated with surgical treatment. This involves follow-up visits for 2 years to evaluate potential progression to CIN grade 3 or greater (CIN3+) or persistent CIN2.

Currently, there is limited data about preterm birth risk following the introduction of active surveillance. To determine preterm birth risk among women with CIN2 receiving active surveillance vs surgical treatment, investigators conducted a historical nationwide population-based cohort study.

Data was obtained from Danish health care registries. Nationwide screening guidelines were first implemented in Denmark in 1986 and involved women aged 23 to 59 years.

Women with CIN2 have the option of immediate surgical excision with LEEP or active surveillance including regular follow-up visits with colposcopy, cytology, and cervical biopsies. Participants included women aged 18 to 40 years with a singleton birth after a first time CIN2 diagnosis from January 1, 1998, to December 31, 2018.

Exclusion criteria included prior CIN3+ diagnosis or LEEP. Utilization of active surveillance or LEEP was determined using the Danish Pathology Registry. A cervical biopsy or cytology as the first recorded sample within 10 months after CIN2 diagnosis was considered active surveillance, while a first subsequent record of LEEP was considered immediate LEEP.

Subgroups included women in the active surveillance group with delayed LEEP within 28 months of diagnosis and women with no LEEP record. Preterm birth was the primary outcome of the analysis.

Secondary outcomes included moderately preterm birth, extremely preterm birth, and PPROM. Covariates included age, residing region, calendar year, smoking status, parity, prior preterm birth, body mass index, index cytology, and repeated LEEP.

There were 10,537 women included in the analysis, 42% of whom received active surveillance and 58% received immediate LEEP. Most patients were aged 23 to 29 years at CIN2 diagnosis, with a median age of 26 years reported. A high-grade abnormal index cytology was reported in 46% of the active surveillance group and 54% of the immediate LEEP group.

Preterm birth was reported in 8% of patients, moderately preterm birth in 3%, and extremely preterm birth in 1%. There was not a difference in risk reported between the active surveillance and immediate LEEP groups, with an adjusted odds ratio (aRR) of 1.03 for preterm birth, 0.99 for moderately preterm birth, and 0.63 for extremely preterm birth.

While a slight increase in risk was found from active surveillance vs immediate LEEP in women with high-grade index cytology, this increase was not statistically significant. No differences were observed in stratified analyses.

Delayed LEEP within 28 months was reported in 35% of the active surveillance group. A high-grade index cytology was reported in 53% of women with delayed LEEP, and LEEP within 1 year in 79%.

Active surveillance without delayed risk had a slightly lower risk of preterm birth than immediate LEEP, with an ARR of 0.88. However, women with delayed LEEP were nearly 30% more likely to experience preterm birth than those with immediate LEEP.

The risk was especially noticed among women giving birth over 5 years after CIN2 diagnosis or over 2 years after LEEP, with a high-grade index cytology, a repeated LEEP, or diagnosed with CIN2 from 2013 to 2018.

PPROM was reported in 4% of births. The risk did not differ significantly between groups but was increased by nearly 30% among women with delayed LEEP vs immediate LEEP.

These results indicated an increased risk of preterm birth among women with delayed LEEP vs immediate LEEP. Investigators recommended risk stratification at CIN2 diagnosis to identify progression risk in patients.


Lycke KD, Kahlert J, Eriksen DO, et al. Preterm birth following active surveillance vs loop excision for cervical intraepithelial neoplasia grade 2. JAMA Netw Open. 2024;7(3):e242309. doi:10.1001/jamanetworkopen.2024.2309

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