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

Abstract

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.

Fig 1 Meta-analysis of relative risk of perinatal mortality associated with excisional treatment for cervical intraepithelial neoplasia. *0.5 added to each cell of 2×2 contingency table because no cases were found in one of comparison groups. †Excluded because no events in both groups. In subtotals relative risks are pooled by treatment procedure (only computed in absence of significant heterogeneity between studies)

Fig 2 Meta-analysis of relative risk of perinatal mortality associated with ablative treatment for cervical intraepithelial neoplasia. *0.5 added to each cell of 2×2 contingency table because no cases found in one comparison group, allowing computation of relative risk. †Excluded because no events in both groups. To compute overall relative risk, counts of control groups in reports by Bruinsma^w13 and Jakobsson^w14 were weighted proportionally to size of corresponding treated groups to avoid double counting