Cold-knife conisation and large loop excision of transformation zone significantly increase the risk for spontaneous preterm birth: a population-based cohort study

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Abstract

Objectives

Our aim was to explore the association between cold-knife conisation and large loop excision of transformation zone (LLETZ) with spontaneous preterm birth in a large 10-year national sample. We wanted to explore further the association of these procedures with preterm birth according to gestation.

Study design

We conducted a population based retrospective cohort study, using data from national Medical Birth Registry. The study population consisted of all women giving birth to singletons in the period 2003–2012 in Slovenia, excluding all induced labors and elective cesarean sections before 37 weeks of gestation (N = 192 730). We compared the prevalence of spontaneous preterm births (before 28 weeks, before 32 weeks, before 34 weeks and before 37 weeks of gestation) in women with cold-knife conisation or LLETZ compared to women without history of conisation, calculating odds ratios (OR), adjusted for potential confounders. Chi-square test was used for descriptive analysis. Logistic regression analyses were performed to estimate crude odds ratio (OR) and adjusted odds ratio (aOR) and their 95% confidence intervals (95% CI) with two-sided probability (p) values.

Results

A total of 8420 (4.4%) women had a preterm birth before 37 weeks of gestation, 2250 (1.2%) before 34 weeks of gestation, 1333 (0.7%) before 32 weeks of gestation and 603 (0.3%) before 28 weeks of gestation. A total of 4580 (2.4%) women had some type of conisation in their medical history: 2083 (1.1%) had cold-knife conisation and 2498 (1.3%) had LLETZ. In women with history of cold-knife conisation, the adjusted OR for preterm birth before 37 weeks of gestation was 3.13 (95% CI; 2.74–3.57) and for preterm birth before 28 weeks of gestation 5.96 (95% CI; 4.3–8.3). In women with history of LLETZ, the adjusted OR was 1.95 (95% CI; 1.68–2.25) and 2.88 (95% CI; 1.87–4.43), respectively.

Conclusions

Women with cervical excision procedure of any kind have significantly increased odds for preterm birth, especially for preterm birth before 28 weeks and before 32 weeks of gestation.

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.

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