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Perinatal mortality and other severe adverse pregnancy outcomes associated with treatment of cervical intraepithelial neoplasia: meta-analysis

BMJ 2008; 337 doi: (Published 18 September 2008) Cite this as: BMJ 2008;337:a1284
  1. M Arbyn, head of unit of cancer epidemiology1, leader, working package HPV screening2,
  2. M Kyrgiou, assistant3,
  3. C Simoens, assistant1,
  4. A O Raifu, assistant1,
  5. G Koliopoulos, senior lecturer4,
  6. P Martin-Hirsch, consultant gynaecological oncologist3,
  7. W Prendiville, associated professor5,
  8. E Paraskevaidis, head of department4
  1. 1Scientific Institute of Public Health, Brussels, Belgium
  2. 2European Cooperation on Development and Implementation of Cancer Screening and Prevention Guidelines, IARC, Lyon, France
  3. 3Department of Obstetrics and Gynaecology, Central Lancashire Teaching Hospitals, Preston, Lancashire
  4. 4Department of Obstetrics and Gynaecology, University Hospital of Ioannina, Ioannina, Greece
  5. 5Department of Obstetrics and Gynaecology, Coombe Women’s Hospital, Dublin, Ireland
  1. Correspondence to: M ArbynMarc.Arbyn{at}
  • Accepted 21 July 2008


Objective To assess the relative risk of perinatal mortality, severe preterm delivery, and low birth weight associated with previous treatment for precursors of cervical cancer.

Data sources Medline and Embase citation tracking from January 1960 to December 2007.

Selection criteria Eligible studies had data on severe pregnancy outcomes for women with and without previous treatment for cervical intraepithelial neoplasia. Considered outcomes were perinatal mortality, severe preterm delivery (<32/34 weeks), extreme preterm delivery (<28/30 weeks), and low birth weight (<2000 g, <1500 g, and <1000 g). Excisional and ablative treatment procedures were distinguished.

Results One prospective cohort and 19 retrospective studies were retrieved. Cold knife conisation was associated with a significantly increased risk of perinatal mortality (relative risk 2.87, 95% confidence interval 1.42 to 5.81) and a significantly higher risk of severe preterm delivery (2.78, 1.72 to 4.51), extreme preterm delivery (5.33, 1.63 to 17.40), and low birth weight of <2000 g (2.86, 1.37 to 5.97). Laser conisation, described in only one study, was also followed by a significantly increased chance of low birth weight of <2000 g and <1500 g. Large loop excision of the transformation zone and ablative treatment with cryotherapy or laser were not associated with a significantly increased risk of serious adverse pregnancy outcomes. Ablation by radical diathermy was associated with a significantly higher frequency of perinatal mortality, severe and extreme preterm delivery, and low birth weight below 2000 g or 1500 g.

Conclusions In the treatment of cervical intraepithelial neoplasia, cold knife conisation and probably both laser conisation and radical diathermy are associated with an increased risk of subsequent perinatal mortality and other serious pregnancy outcomes, unlike laser ablation and cryotherapy. Large loop excision of the transformation zone cannot be considered as completely free of adverse outcomes.


  • We thank F Bruinsma (Mother and Child Health Research, La Trobe University, Carlton, Victoria, Australia) and M Jakobsson (department of obstetrics and gynaecology, University Hospital, Helsinki, Finland) for the provision of additional procedure specific data; and Tini Van Dijk (Norwegian Cancer Registry) for translation help.

  • Contributors: MA, MK, PM-H, and EP were responsible for conception and design. MA, MK, CS, and PM-H acquired data. MA, CS, and AOR analysed and interpreted data and drafted the manuscript, which was critically revised and edited by MK, PMH, GK, WP, and EP. MA and AOR carried out the statistical analysis. MA is guarantor.

  • Funding: European Commission (Directorate of SANCO, Luxembourg, Grand-Duché du Luxembourg) through the ECCG (European cooperation on development and implementation of cancer screening and prevention guidelines); FP6 network of excellence “CCPRB” (cancer control using population based registries and biobanks) though the University of Lund, Sweden; DWTC/SSTC (Federal Services for Scientific, Cultural and Technical Affairs, Brussels, Belgium); Gynaecological Cancer Cochrane Review Collaboration, Bath; IWT (Institute for the Promotion of Innovation by Science and Technology in Flanders) through “SIMID,” a strategic basic research project (ref 060081); and FNRS (Fonds national de la Recherche scientifique), through TELEVIE, Brussels, Belgium (ref 7.4.628.07.F).

  • Competing interests: None declared.

  • Ethical approval: Not required.

  • Provenance and peer review: Not commissioned; externally peer reviewed.

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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