Research
ajog.org
OBSTETRICS
The association between cervical dysplasia, a short cervix, and preterm birth Emily S. Miller, MD, MPH; Allie Sakowicz; William A. Grobman, MD, MBA OBJECTIVE: We sought to determine whether cervical dysplasia in the absence of an excisional procedure is associated with an increased risk of preterm birth (PTB) and whether that risk is independent of the presence of a short cervix. STUDY DESIGN: This is a cohort study including women with a singleton pregnancy who underwent routine cervical length assessment between 18-23 6/7 weeks of gestation, stratified by cervical dysplasia (ie, no prior dysplasia, prior dysplasia but no excisional procedure, or prior excisional procedure). The frequency of a short cervix (2.5 cm) and PTB were compared between groups and multivariable analyses were performed to identify whether: (1) dysplasia alone or a prior excisional procedure was associated with PTB; and (2) whether these factors remained independently associated with PTB after adjusting for the presence of a short cervix.
RESULTS: Of the 18,528 women who met inclusion criteria, 3023
(16.3%) had prior dysplasia alone and 1356 (7.3%) had a prior excisional procedure. The frequency of a short cervix for women without dysplasia, with prior dysplasia alone, or with a prior excisional procedure was 0.8%, 1.0%, and 2.2%, respectively (P < .001). The frequency of PTB, respectively, was 6.4%, 6.5%, and 8.4% (P < .001). After adjusting for potential confounding factors, prior excisional procedure but not prior dysplasia alone was associated with PTB. CONCLUSION: Having a prior cervical excisional procedure but not
dysplasia alone is associated with an increased risk of PTB. This association is independent of the presence of a short cervix. Key words: cervical dysplasia, excisional procedure, loop electrosurgical excision procedure, preterm birth
Cite this article as: Miller ES, Sakowicz A, Grobman WA. The association between cervical dysplasia, a short cervix, and preterm birth. Am J Obstet Gynecol 2015;213:x.ex-x.ex.
C
ervical excisional procedures, such as a loop electrosurgical excision procedure (LEEP) or a cold knife cone, excise dysplastic cells as a means to diagnose and treat cervical intraepithelial neoplasia. Having a cervical excisional procedure has been associated with an increased risk of preterm birth (PTB).1-6 Recent studies have raised the question whether it is the excision itself, the underlying dysplasia, or risk factors for dysplasia that are associated with this From the Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL. Received March 12, 2015; revised May 8, 2015; accepted June 15, 2015. The authors report no conflict of interest. Presented at the 35th annual meeting of the Society for Maternal-Fetal Medicine, San Diego, CA, Feb. 2-7, 2015. Corresponding author: Emily S. Miller, MD, MPH. [email protected] 0002-9378/$36.00 ª 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.ajog.2015.06.036
risk of PTB.7-10 Metaanalytic data suggest that women with a prior LEEP have an increased risk of PTB compared to women with no prior dysplasia but a similar risk of PTB compared to women with dysplasia.11 Prior work also has demonstrated that the cervical shortening in pregnancy associated with an excisional procedure is an independent risk factor for PTB.12 Whether the increased risk of PTB in women with prior dysplasia, but not a cervical excision procedure, is associated with cervical shortening in pregnancy has not been examined. The objective of this study was to determine whether cervical dysplasia is independently associated with an increased risk of PTB and, if so, whether this risk is independent of the presence of a short cervical length (CL).
M ATERIALS
AND
M ETHODS
This is a retrospective cohort study of women undergoing routine CL assessment between 18-23 6/7 weeks of gestation from December 2010 through January 2014 at Northwestern Memorial
Hospital in Chicago, IL. Women were included in the cohort if they were at least 18 years of age, had a singleton gestation, and had available delivery records. CLs were measured transvaginally by staff sonographers who were educated in the context of multicenter trials.13 All ultrasounds were read by an attending sonologist. If multiple CL ultrasounds were performed on an individual patient, we incorporated the measurement taken closest to 20 weeks of gestation for analysis. A short cervix was defined as 2.5 cm.14,15 During the study period, a transvaginal CL assessment was a routine part of the fetal anatomic survey. Medical records of all women who underwent transvaginal CL screening were identified and reviewed. Demographic characteristics and baseline clinical data including maternal age, race/ ethnicity, body mass index at delivery, tobacco use, mode of conception, and obstetric history were abstracted. Any history of cervical dysplasia was a prompted field on the obstetric admission history and physical electronic medical record during the study period. This field
MONTH 2015 American Journal of Obstetrics & Gynecology FLA 5.2.0 DTD YMOB10483_proof 31 July 2015 1:37 am ce
1.e1
Research
ajog.org
Obstetrics
TABLE 1
Patient characteristics stratified by dysplasia history No prior dysplasia (n [ 14,149)
Characteristic
Prior dysplasia alone (n [ 3023)
Prior excisional procedure (n [ 1356)
P value
Gestational age at CL screen, wk
20.3 0.9
20.3 0.8
20.2 0.8
.047
Age, y
31.2 5.5
32.1 4.7
33.8 4.1
< .001
Race/ethnicity (n ¼ 16,071)
< .001
Non-Hispanic white
6546 (53.3%)
1688 (64.4%)
Non-Hispanic black
1433 (11.7%)
352 (13.4%)
92 (7.8%)
Hispanic
3011 (24.5%)
438 (16.7%)
124 (10.5%)
1283 (10.5%)
143 (5.5%)
69 (5.9%)
Other BMI at delivery, kg/m (n ¼ 18,407)
30.3 5.7
2
893 (75.8%)
30.2 5.4
29.4 4.9
< .001
Smoking in current pregnancy
115 (0.9%)
26 (0.9%)
17 (1.3%)
.301
IVF conception (n ¼ 17,662)
549 (4.2%)
104 (3.7%)
85 (6.8%)
< .001
7354 (52.0%)
1494 (49.4%)
682 (50.3%)
.026
Prior preterm birth (n ¼ 18,527)
718 (5.1%)
188 (6.2%)
82 (6.1%)
.019
Hypertensive disease (n ¼ 18,410)
429 (3.1%)
103 (3.5%)
44 (3.3%)
.376
Diabetes mellitus (n ¼ 18,526)
845 (6.8%)
164 (6.4%)
61 (5.2%)
.092
Nulliparous
Data are presented as mean SD or n (%). BMI, body mass index; CL, cervical length; IVF, in vitro fertilization. Miller. Cervical dysplasia, short cervix, and preterm birth. Am J Obstet Gynecol 2015.
is typically filled out based on information present in the patient’s prenatal records. Dysplasia was defined as any lesion requiring colposcopic evaluation or any notation of an abnormal Pap smear if no other documentation was available. Women were stratified into 3 groups according to their history of cervical dysplasia (ie, no dysplasia, dysplasia alone, or dysplasia with excisional procedure). Gestational age at delivery was recorded and a PTB was defined as a gestational age at delivery
ajog.org
OBSTETRICS
The association between cervical dysplasia, a short cervix, and preterm birth Emily S. Miller, MD, MPH; Allie Sakowicz; William A. Grobman, MD, MBA OBJECTIVE: We sought to determine whether cervical dysplasia in the absence of an excisional procedure is associated with an increased risk of preterm birth (PTB) and whether that risk is independent of the presence of a short cervix. STUDY DESIGN: This is a cohort study including women with a singleton pregnancy who underwent routine cervical length assessment between 18-23 6/7 weeks of gestation, stratified by cervical dysplasia (ie, no prior dysplasia, prior dysplasia but no excisional procedure, or prior excisional procedure). The frequency of a short cervix (2.5 cm) and PTB were compared between groups and multivariable analyses were performed to identify whether: (1) dysplasia alone or a prior excisional procedure was associated with PTB; and (2) whether these factors remained independently associated with PTB after adjusting for the presence of a short cervix.
RESULTS: Of the 18,528 women who met inclusion criteria, 3023
(16.3%) had prior dysplasia alone and 1356 (7.3%) had a prior excisional procedure. The frequency of a short cervix for women without dysplasia, with prior dysplasia alone, or with a prior excisional procedure was 0.8%, 1.0%, and 2.2%, respectively (P < .001). The frequency of PTB, respectively, was 6.4%, 6.5%, and 8.4% (P < .001). After adjusting for potential confounding factors, prior excisional procedure but not prior dysplasia alone was associated with PTB. CONCLUSION: Having a prior cervical excisional procedure but not
dysplasia alone is associated with an increased risk of PTB. This association is independent of the presence of a short cervix. Key words: cervical dysplasia, excisional procedure, loop electrosurgical excision procedure, preterm birth
Cite this article as: Miller ES, Sakowicz A, Grobman WA. The association between cervical dysplasia, a short cervix, and preterm birth. Am J Obstet Gynecol 2015;213:x.ex-x.ex.
C
ervical excisional procedures, such as a loop electrosurgical excision procedure (LEEP) or a cold knife cone, excise dysplastic cells as a means to diagnose and treat cervical intraepithelial neoplasia. Having a cervical excisional procedure has been associated with an increased risk of preterm birth (PTB).1-6 Recent studies have raised the question whether it is the excision itself, the underlying dysplasia, or risk factors for dysplasia that are associated with this From the Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL. Received March 12, 2015; revised May 8, 2015; accepted June 15, 2015. The authors report no conflict of interest. Presented at the 35th annual meeting of the Society for Maternal-Fetal Medicine, San Diego, CA, Feb. 2-7, 2015. Corresponding author: Emily S. Miller, MD, MPH. [email protected] 0002-9378/$36.00 ª 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.ajog.2015.06.036
risk of PTB.7-10 Metaanalytic data suggest that women with a prior LEEP have an increased risk of PTB compared to women with no prior dysplasia but a similar risk of PTB compared to women with dysplasia.11 Prior work also has demonstrated that the cervical shortening in pregnancy associated with an excisional procedure is an independent risk factor for PTB.12 Whether the increased risk of PTB in women with prior dysplasia, but not a cervical excision procedure, is associated with cervical shortening in pregnancy has not been examined. The objective of this study was to determine whether cervical dysplasia is independently associated with an increased risk of PTB and, if so, whether this risk is independent of the presence of a short cervical length (CL).
M ATERIALS
AND
M ETHODS
This is a retrospective cohort study of women undergoing routine CL assessment between 18-23 6/7 weeks of gestation from December 2010 through January 2014 at Northwestern Memorial
Hospital in Chicago, IL. Women were included in the cohort if they were at least 18 years of age, had a singleton gestation, and had available delivery records. CLs were measured transvaginally by staff sonographers who were educated in the context of multicenter trials.13 All ultrasounds were read by an attending sonologist. If multiple CL ultrasounds were performed on an individual patient, we incorporated the measurement taken closest to 20 weeks of gestation for analysis. A short cervix was defined as 2.5 cm.14,15 During the study period, a transvaginal CL assessment was a routine part of the fetal anatomic survey. Medical records of all women who underwent transvaginal CL screening were identified and reviewed. Demographic characteristics and baseline clinical data including maternal age, race/ ethnicity, body mass index at delivery, tobacco use, mode of conception, and obstetric history were abstracted. Any history of cervical dysplasia was a prompted field on the obstetric admission history and physical electronic medical record during the study period. This field
MONTH 2015 American Journal of Obstetrics & Gynecology FLA 5.2.0 DTD YMOB10483_proof 31 July 2015 1:37 am ce
1.e1
Research
ajog.org
Obstetrics
TABLE 1
Patient characteristics stratified by dysplasia history No prior dysplasia (n [ 14,149)
Characteristic
Prior dysplasia alone (n [ 3023)
Prior excisional procedure (n [ 1356)
P value
Gestational age at CL screen, wk
20.3 0.9
20.3 0.8
20.2 0.8
.047
Age, y
31.2 5.5
32.1 4.7
33.8 4.1
< .001
Race/ethnicity (n ¼ 16,071)
< .001
Non-Hispanic white
6546 (53.3%)
1688 (64.4%)
Non-Hispanic black
1433 (11.7%)
352 (13.4%)
92 (7.8%)
Hispanic
3011 (24.5%)
438 (16.7%)
124 (10.5%)
1283 (10.5%)
143 (5.5%)
69 (5.9%)
Other BMI at delivery, kg/m (n ¼ 18,407)
30.3 5.7
2
893 (75.8%)
30.2 5.4
29.4 4.9
< .001
Smoking in current pregnancy
115 (0.9%)
26 (0.9%)
17 (1.3%)
.301
IVF conception (n ¼ 17,662)
549 (4.2%)
104 (3.7%)
85 (6.8%)
< .001
7354 (52.0%)
1494 (49.4%)
682 (50.3%)
.026
Prior preterm birth (n ¼ 18,527)
718 (5.1%)
188 (6.2%)
82 (6.1%)
.019
Hypertensive disease (n ¼ 18,410)
429 (3.1%)
103 (3.5%)
44 (3.3%)
.376
Diabetes mellitus (n ¼ 18,526)
845 (6.8%)
164 (6.4%)
61 (5.2%)
.092
Nulliparous
Data are presented as mean SD or n (%). BMI, body mass index; CL, cervical length; IVF, in vitro fertilization. Miller. Cervical dysplasia, short cervix, and preterm birth. Am J Obstet Gynecol 2015.
is typically filled out based on information present in the patient’s prenatal records. Dysplasia was defined as any lesion requiring colposcopic evaluation or any notation of an abnormal Pap smear if no other documentation was available. Women were stratified into 3 groups according to their history of cervical dysplasia (ie, no dysplasia, dysplasia alone, or dysplasia with excisional procedure). Gestational age at delivery was recorded and a PTB was defined as a gestational age at delivery
