In the Journals

Risk for preterm birth, low birth weight higher after surgeries for cervical dysplasia

Pregnant women who have undergone prior surgical treatment for cervical dysplasia demonstrated an increased risk for preterm birth and low birth weight compared with women with no history of cervical diagnostic or treatment procedures, or women with a history of diagnostic procedures but no treatment, according to a population-based, observational study published in PLOS ONE.

The study’s findings showed no significant statistical differences in cesarean deliveries and pregnancy loss.

Sheila Weinmann

“Other studies have found a link between surgery to remove precancerous cervical lesions and preterm delivery,” Sheila Weinmann, PhD, MPH, a senior investigator at the Center for Health Research at Kaiser Permanente Northwest, told HemOnc Today. “But, it was still unclear whether it was the surgery itself or the HPV virus that causes the increased risk for preterm birth. Our study shows that it is most likely the surgery itself causing the increased risk rather than the HPV virus.

“We know this because we compared women who had the surgery to women who had the HPV virus, but only a biopsy and not the surgery,” Wedinmann added. “These women did not have the increased risk for preterm birth. Our study was also quite large, involving more than 5,000 women over a 12-year period, so this gives us a lot of confidence in the findings.”

High-grade cervical intraepithelial neoplasia (CIN) is most often detected through Pap screenings. Gynecologists often recommend follow-up colposcopy or diagnostic biopsy, in which abnormal tissue is removed before it progresses to cervical cancer. Previous studies have linked cervical surgeries to preterm birth, low birth weight, premature rupture of membranes, cesarean delivery and pregnancy loss.

Weinmann and colleagues evaluated 5,476 women aged 14 to 53 years with documented pregnancies between 1998 and 2009. Of the women, 322 received prior excisional and ablative cervical procedures — colposcopy and/or biopsy. Excisional procedures included loop electrosurgical and conization — cold knife, laser or loop electrode. Ablative procedures included laser ablation cryosurgery and electro or thermal cautery.

Researchers compared women who had been treated with excisional and ablative cervical procedures with women unexposed to cervical procedures (n = 4,307) and women who had undergone diagnostic or biopsy procedures without treatment (n = 847).

Researchers stratified excisional procedures by excision thickness and evaluated for confounding by age, BMI, race, smoking history, previous preterm birth and parity.

Preterm birth

Overall, results showed about a 20% increased risk for preterm birth associated with cervical treatment.

When evaluating ablative vs. excisional treatment, only women who underwent excisional treatment had a greater risk, primarily those with excisions of 1 cm or larger (treatment

vs. unexposed, RR = 2.15; 95% CI, 1.16 ± 3.98; treatment vs. diagnosis only, RR = 1.89; 95% CI 0.99 ± 3.62).

Preterm babies were born to 5% of women with ablative treatment, 7% to 10% of women with excisional treatment smaller than 1.6 cm, and 28% of women with excisions larger than 1.6 cm. Comparatively, 7% of unexposed women and 8% of diagnostic-only women had preterm deliveries.

Risk for preterm birth in women delivering within 1 year of excisional treatment was 1.83 (95% CI, 0.9-3.71) compared with unexposed women and 1.56 (95% CI, 0.74-3.31) compared with women in the diagnostic-only group. Where excision thickness was greater than 1 cm, unadjusted RRs for preterm delivery within 1 year after treatment were 3.26 (95% CI, 1.41-7.53) compared with unexposed women and 2.78 (95% CI, 1.30-5.96) compared with diagnostic-only women.

Low birth weight

Women with surgical treatment had approximately 50% higher likelihood of having babies at low birth weight than unexposed women and those only with diagnostic procedures. Among those who had undergone excisional treatment, those with excision thickness larger than 1 cm had the greatest likelihood of low birth rate (unadjusted RR vs. unexposed = 2.3; 95% CI, 1.06-5; RR vs. diagnostic only = 2.3; 95% CI, 1.01-5.27).

Among women who received ablative or excisional treatment smaller than 1.6 cm in thickness, 6% to 7% delivered low–birth weight babies compared with 11% of women with excisions larger than 1.6 cm. In comparison, 4% of unexposed and diagnostic women delivered low–birth weight babies.

Cesarean delivery

The association between surgical treatment and cesarean delivery was modestly elevated. Risk did not vary by thickness of excision, except in women giving birth within 1 year of surgery, where RRs were higher for excisions larger than 1 cm (RR vs. unexposed = 1.42, 95% CI, 0.93-2.15; RR vs. diagnostic only = 4.3, 95% CI, 1.6-11.54).

Pregnancy loss

Researchers reported 1,043 medically attended spontaneous abortions and 22 stillbirths.

Pregnancy loss occurred in 21% of women who underwent cervical surgery (ablative treatment, 25%; excisional treatment, 19%) compared with 18% of unexposed women and 20% of women in the diagnostic-only group. For ablative treatment, RRs for pregnancy loss were 1.43 (95% CI, 1.05-1.93) compared with unexposed women and 1.38 (95% CI, 1.01-1.89) compared with women in the diagnostic-only group.

Researchers noted they could not stratify data based on trimester of pregnancy loss. In women with surgical treatment, 7% of spontaneous abortions were in the second or third trimester, compared with 4% in the unexposed arm and 6% in the diagnostic arm.

“It did surprise me that we found an increased risk for pregnancy loss after having had an ablative (burning or freezing) procedure to remove precancerous lesions,” Weinmann said. “Twenty-five percent of women who had ablative surgeries had a pregnancy loss, compared with 18% in women who didn’t have the procedure. This is the first time this association has been reported, so we need to do more studies to see if these findings are repeated. We are not sure why this would be the case.

“It was also of interest that we didn’t see the increased risk for preterm birth in women who had the ablative procedures, only in women who had the surgical or excisional procedures,” Weinmann added.

Researchers noted thickness of the excisional procedure was not always recorded and served as a limitation of the study. The study also lacked sufficient data for covariates, such as smoking, race/ethnicity, parity and BMI.

Weinmann said clinicians should be aware that the more of the cervix that is removed during a surgical procedure, the higher the likelihood of a woman delivering her baby early.

“The risk was doubled for women who had more than one centimeter of their cervix removed,” she said. “Clinicians should keep this in mind when performing the LEEP and other excisional procedures, but of course this has to be balanced with removing all of the precancerous cells.”

All women should follow screening guidelines for Pap smears and HPV testing to prevent cervical cancer and precancerous lesions, and that younger women and teenagers should get the HPV vaccine before they become sexually active to help prevent precancerous lesions and cervical cancer, Weinmann said.

“Many women experience abnormal Pap tests or test positive for HPV, and these women are often followed closely by their doctors to look for any cancerous changes,” Weinmann said. “If surgery is needed, a woman should have a discussion with her provider about the risks of each procedure. If she does have the surgery, she may want to wait a while before becoming pregnant. In our study, women who had more than one centimeter of their cervix removed and gave birth within a year after surgery had three times the risk for delivering their babies early compared with women who didn’t have the surgery. An earlier study we published in 2015 with this same patient population found that women who have the surgeries are just as likely to get pregnant as those who don’t have the surgery.” – by Chuck Gormley

For more information:

Sheila Weinmann , PhD, MPH , can be reached at sheila.weinmann@kpchr.org.

Disclosure: GlaxoSmithKline Biologicals SA funded the study. Weinmann reports funding from GlaxoSmithKline Biologicals SA. Please see the full study for a list of all other researchers’ relevant financial disclosures.

Pregnant women who have undergone prior surgical treatment for cervical dysplasia demonstrated an increased risk for preterm birth and low birth weight compared with women with no history of cervical diagnostic or treatment procedures, or women with a history of diagnostic procedures but no treatment, according to a population-based, observational study published in PLOS ONE.

The study’s findings showed no significant statistical differences in cesarean deliveries and pregnancy loss.

Sheila Weinmann

“Other studies have found a link between surgery to remove precancerous cervical lesions and preterm delivery,” Sheila Weinmann, PhD, MPH, a senior investigator at the Center for Health Research at Kaiser Permanente Northwest, told HemOnc Today. “But, it was still unclear whether it was the surgery itself or the HPV virus that causes the increased risk for preterm birth. Our study shows that it is most likely the surgery itself causing the increased risk rather than the HPV virus.

“We know this because we compared women who had the surgery to women who had the HPV virus, but only a biopsy and not the surgery,” Wedinmann added. “These women did not have the increased risk for preterm birth. Our study was also quite large, involving more than 5,000 women over a 12-year period, so this gives us a lot of confidence in the findings.”

High-grade cervical intraepithelial neoplasia (CIN) is most often detected through Pap screenings. Gynecologists often recommend follow-up colposcopy or diagnostic biopsy, in which abnormal tissue is removed before it progresses to cervical cancer. Previous studies have linked cervical surgeries to preterm birth, low birth weight, premature rupture of membranes, cesarean delivery and pregnancy loss.

Weinmann and colleagues evaluated 5,476 women aged 14 to 53 years with documented pregnancies between 1998 and 2009. Of the women, 322 received prior excisional and ablative cervical procedures — colposcopy and/or biopsy. Excisional procedures included loop electrosurgical and conization — cold knife, laser or loop electrode. Ablative procedures included laser ablation cryosurgery and electro or thermal cautery.

Researchers compared women who had been treated with excisional and ablative cervical procedures with women unexposed to cervical procedures (n = 4,307) and women who had undergone diagnostic or biopsy procedures without treatment (n = 847).

Researchers stratified excisional procedures by excision thickness and evaluated for confounding by age, BMI, race, smoking history, previous preterm birth and parity.

Preterm birth

Overall, results showed about a 20% increased risk for preterm birth associated with cervical treatment.

When evaluating ablative vs. excisional treatment, only women who underwent excisional treatment had a greater risk, primarily those with excisions of 1 cm or larger (treatment

vs. unexposed, RR = 2.15; 95% CI, 1.16 ± 3.98; treatment vs. diagnosis only, RR = 1.89; 95% CI 0.99 ± 3.62).

Preterm babies were born to 5% of women with ablative treatment, 7% to 10% of women with excisional treatment smaller than 1.6 cm, and 28% of women with excisions larger than 1.6 cm. Comparatively, 7% of unexposed women and 8% of diagnostic-only women had preterm deliveries.

Risk for preterm birth in women delivering within 1 year of excisional treatment was 1.83 (95% CI, 0.9-3.71) compared with unexposed women and 1.56 (95% CI, 0.74-3.31) compared with women in the diagnostic-only group. Where excision thickness was greater than 1 cm, unadjusted RRs for preterm delivery within 1 year after treatment were 3.26 (95% CI, 1.41-7.53) compared with unexposed women and 2.78 (95% CI, 1.30-5.96) compared with diagnostic-only women.

Low birth weight

Women with surgical treatment had approximately 50% higher likelihood of having babies at low birth weight than unexposed women and those only with diagnostic procedures. Among those who had undergone excisional treatment, those with excision thickness larger than 1 cm had the greatest likelihood of low birth rate (unadjusted RR vs. unexposed = 2.3; 95% CI, 1.06-5; RR vs. diagnostic only = 2.3; 95% CI, 1.01-5.27).

Among women who received ablative or excisional treatment smaller than 1.6 cm in thickness, 6% to 7% delivered low–birth weight babies compared with 11% of women with excisions larger than 1.6 cm. In comparison, 4% of unexposed and diagnostic women delivered low–birth weight babies.

Cesarean delivery

The association between surgical treatment and cesarean delivery was modestly elevated. Risk did not vary by thickness of excision, except in women giving birth within 1 year of surgery, where RRs were higher for excisions larger than 1 cm (RR vs. unexposed = 1.42, 95% CI, 0.93-2.15; RR vs. diagnostic only = 4.3, 95% CI, 1.6-11.54).

Pregnancy loss

Researchers reported 1,043 medically attended spontaneous abortions and 22 stillbirths.

Pregnancy loss occurred in 21% of women who underwent cervical surgery (ablative treatment, 25%; excisional treatment, 19%) compared with 18% of unexposed women and 20% of women in the diagnostic-only group. For ablative treatment, RRs for pregnancy loss were 1.43 (95% CI, 1.05-1.93) compared with unexposed women and 1.38 (95% CI, 1.01-1.89) compared with women in the diagnostic-only group.

Researchers noted they could not stratify data based on trimester of pregnancy loss. In women with surgical treatment, 7% of spontaneous abortions were in the second or third trimester, compared with 4% in the unexposed arm and 6% in the diagnostic arm.

“It did surprise me that we found an increased risk for pregnancy loss after having had an ablative (burning or freezing) procedure to remove precancerous lesions,” Weinmann said. “Twenty-five percent of women who had ablative surgeries had a pregnancy loss, compared with 18% in women who didn’t have the procedure. This is the first time this association has been reported, so we need to do more studies to see if these findings are repeated. We are not sure why this would be the case.

“It was also of interest that we didn’t see the increased risk for preterm birth in women who had the ablative procedures, only in women who had the surgical or excisional procedures,” Weinmann added.

Researchers noted thickness of the excisional procedure was not always recorded and served as a limitation of the study. The study also lacked sufficient data for covariates, such as smoking, race/ethnicity, parity and BMI.

Weinmann said clinicians should be aware that the more of the cervix that is removed during a surgical procedure, the higher the likelihood of a woman delivering her baby early.

“The risk was doubled for women who had more than one centimeter of their cervix removed,” she said. “Clinicians should keep this in mind when performing the LEEP and other excisional procedures, but of course this has to be balanced with removing all of the precancerous cells.”

All women should follow screening guidelines for Pap smears and HPV testing to prevent cervical cancer and precancerous lesions, and that younger women and teenagers should get the HPV vaccine before they become sexually active to help prevent precancerous lesions and cervical cancer, Weinmann said.

“Many women experience abnormal Pap tests or test positive for HPV, and these women are often followed closely by their doctors to look for any cancerous changes,” Weinmann said. “If surgery is needed, a woman should have a discussion with her provider about the risks of each procedure. If she does have the surgery, she may want to wait a while before becoming pregnant. In our study, women who had more than one centimeter of their cervix removed and gave birth within a year after surgery had three times the risk for delivering their babies early compared with women who didn’t have the surgery. An earlier study we published in 2015 with this same patient population found that women who have the surgeries are just as likely to get pregnant as those who don’t have the surgery.” – by Chuck Gormley

For more information:

Sheila Weinmann , PhD, MPH , can be reached at sheila.weinmann@kpchr.org.

Disclosure: GlaxoSmithKline Biologicals SA funded the study. Weinmann reports funding from GlaxoSmithKline Biologicals SA. Please see the full study for a list of all other researchers’ relevant financial disclosures.