European Journal of Obstetrics & Gynecology and Reproductive Biology
Cold-knife conisation and large loop excision of transformation zone significantly increase the risk for spontaneous preterm birth: a population-based cohort study
Introduction
Cervical intraepithelial neoplasia (CIN) is caused by persistent Human Papillomavirus infection. CIN is most prevalent in women in their childbearing age and can, in some cases, progress to cervical cancer, if left untreated. Screening programs for cervical cancer are implemented in many countries. As a result, incidence of invasive cervical cancer has fallen substantially in countries with well-organized screening programs [1]. On the other hand, due to growing population of women attending organized screening, more low- and high-grade cervical lesions are detected.
According to national and international guidelines for management of cervical lesions, high-grade lesions, consisting of CIN grade 2 and CIN grade 3, should be treated with excision procedures except in special situations. Large loop excision of transformation zone (LLETZ) and cold-knife conisation are the most frequent procedures used to treat high-grade cervical lesions [2], [3]. Several studies and systematic reviews have shown that cervical excision procedures are associated with pregnancy complications such as spontaneous miscarriage, preterm birth and low birthweight [4], [5], [6]. Preterm birth is the most important risk factor for neonatal morbidity and mortality. Earlier the preterm birth, greater are possibilities for serious short or long-term complications [7].
Studies suggest that the risk of preterm birth is associated with more aggressive excision procedures such as cold-knife conisation [4], greater depth of the excised cone [8], [9], [10], [11], [12], [13], and the risk of miscarriage is associated with shorter time interval between procedure and pregnancy [13], [14]. With the implementation of guidelines for management and treatment of CIN and the use of less invasive excision techniques, pregnancy complications have decreased [3], [15]. Studies including women with modern excision techniques, limited to the excision of affected transformation zone and preserving as much healthy cervical tissue as possible, have shown that the risk for pregnancy complications is minimal [5], [8], [12]. Scientists are investigating a hypothesis whether mere presence of CIN increases the risk of complications in pregnancy [8], [16], [17].
Slovenia has a national screening program for early detection of precancerous lesions since 2003. There are around 1000 cases of CIN 3 reported every year. Data on CIN 2 lesions is collected by Slovenian Cancer Registry, but not reported in Annual Reports [18].
The aim of our study was to explore the association between surgical procedure for CIN and spontaneous preterm birth in singleton pregnancies in a large 10-year national sample adjusting for some already known important confounders. We wanted to calculate the odds for spontaneous preterm birth in women with a history of cold-knife conisation and women with a history of LLETZ compared to women without any procedure. We wanted to explore further the association of these procedures with preterm birth at different gestation that is before 28 weeks of gestation, before 32 weeks of gestation, and before 34 weeks of gestation.
Section snippets
Materials and methods
We conducted a population-based retrospective cohort study using data from Medical Birth Registry – the National Perinatal Information System of Slovenia (NPIS). NPIS contains data on woman, pregnancy, birth, the postpartum period and the neonate for each mother–infant/infants pair. Data is collected at the time of birth in all 14 maternal hospitals in Slovenia according to standardised methodology and pre-made definitions of variables [19]. Registration is mandatory by law since NPIS also
Results
In the period 2003–2012 there were 195 471 singleton births in Slovenia. After exclusion of 2738 (1.4%) induced labors and elective cesarean sections before 37 weeks of gestation due to maternal and fetal conditions and three cases with gestation week at the time of birth not recorded, our final sample for the analysis consisted of 192 730 (98.6%) women. Among those 8420 (4.4%) had a preterm birth before 37 weeks of gestation, 2250 (1.2%) before 34 weeks of gestation, 1333 (0.7%) before 32 weeks
Comment
The aim of this study was to investigate the risk of preterm birth after conisation in a population-based study of singleton births in Slovenia. We found significantly higher risk for spontaneous preterm birth for singleton pregnancies in women with a history of cervical excision procedure. After adjusting for maternal age, parity, smoking during pregnancy and education we found a 3-fold increase in the odds for spontaneous preterm birth before 37 weeks of gestation following cold-knife
Acknowledgements
Special thanks to Matej Vinko, M.D. who helped with the literature search and Urša Ivanuš, M.D. who provided the most recent information regarding Slovenian screening program.
References (27)
Outcomes in preterm infants
Public Health
(2014)- et al.
Pregnancy outcome after loop electrosurgical excision procedure for cervical intraepithelial neoplasia
Int J Gynecol Obstet
(2013) - et al.
Loop electrosurgical excision procedure and risk of miscarriage
Fertil Steril
(2015) - et al.
Epidemiology and causes of preterm birth
Lancet
(2008) - et al.
Cervical cancer screening in Europe: quality assurance and organisation of programmes
Eur J Cancer
(2015) - (2013)
- et al.
Smernice za celostno obravnavo žensk s predrakavimi spremembami materničnega vratu
(2011) - et al.
2012 updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors
J Low Genit Tract Dis
(2013) - et al.
Perinatal mortality and other severe adverse pregnancy outcomes associated with treatment of cervical intraepithelial neoplasia: meta-analysis
BMJ
(2008) - et al.
Cervical conisation and the risk of preterm delivery: a retrospective matched pair analysis of a German cohort
Arch Gynecol Obstet
(2015)
Fertility and early pregnancy outcomes after treatment for cervical intraepithelial neoplasia: systematic review and meta-analysis
BMJ
Risk of preterm delivery with increasing depth of excision for cervical intraepithelial neoplasia in England: nested case-control study
BMJ
Risk of preterm delivery associated with prior treatment of cervical precancerous lesion according to the depth of the cone
Disease Markers
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