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Adverse obstetrical outcomes after local treatment for cervical pre-invasive and early invasive disease according to the cone depth: a systematic review and meta-analysis.

Title: Adverse obstetrical outcomes after local treatment for cervical pre-invasive and early invasive disease according to the cone depth: a systematic review and meta-analysis.
Authors: Kyrgiou, M
Athanasiou, A
Paraskevaidi, M
Mitra, A
Kalliala, I
Martin-Hirsch, P
Arbyn, M
Bennett, P
Paraskevaidis, E
Item Type: Journal Article
Abstract:  To assess the effect of treatment for cervical intraepithelial neoplasia (CIN) on obstetric outcomes and to correlate this with cone depth and comparison group used. Systematic review and meta-analysis. CENTRAL, Medline, Embase from 1948 to April 2016 were searched for studies assessing obstetric outcomes in women with or without previous local cervical treatment. Independent reviewers extracted the data and performed quality assessment using the Newcastle-Ottawa criteria. Studies were classified according to method and obstetric endpoint. Pooled risk ratios were calculated with a random effect model and inverse variance. Heterogeneity between studies was assessed with I(2) statistics. Obstetric outcomes comprised preterm birth (including spontaneous and threatened), premature rupture of the membranes, chorioamnionitis, mode of delivery, length of labour, induction of delivery, oxytocin use, haemorrhage, analgesia, cervical cerclage, and cervical stenosis. Neonatal outcomes comprised low birth weight, admission to neonatal intensive care, stillbirth, APGAR scores, and perinatal mortality. 71 studies were included (6 338 982 participants: 65 082 treated/6 292 563 untreated). Treatment significantly increased the risk of overall (<37 weeks; 10.7% v 5.4%; relative risk 1.78, 95% confidence interval 1.60 to 1.98), severe (<32-34 weeks; 3.5% v 1.4%; 2.40, 1.92 to 2.99), and extreme (<28-30 weeks; 1.0% v 0.3%; 2.54, 1.77 to 3.63) preterm birth. Techniques removing or ablating more tissue were associated with worse outcomes. Relative risks for delivery at <37 weeks were 2.70 (2.14 to 3.40) for cold knife conisation, 2.11 (1.26 to 3.54) for laser conisation, 2.02 (1.60 to 2.55) for excision not otherwise specified, 1.56 (1.36 to 1.79) for large loop excision of the transformation zone, and 1.46 (1.27 to 1.66) for ablation not otherwise specified. Compared with no treatment, the risk of preterm birth was higher in women who had undergone more than one treatment (13.2% v 4.1%; 3.78, 2.65 to 5.39) and with increasing cone depth (≤10-12 mm; 7.1% v 3.4%; 1.54, 1.09 to 2.18; ≥10-12 mm: 9.8% v 3.4%, 1.93, 1.62 to 2.31; ≥15-17 mm: 10.1% v 3.4%; 2.77, 1.95 to 3.93; ≥20 mm: 10.2% v 3.4%; 4.91, 2.06 to 11.68). The choice of comparison group affected the magnitude of effect. This was higher for external comparators, followed by internal comparators, and ultimately women with disease who did not undergo treatment. In women with untreated CIN and in pregnancies before treatment, the risk of preterm birth was higher than the risk in the general population (5.9% v 5.6%; 1.24, 1.14 to 1.35). Spontaneous preterm birth, premature rupture of the membranes, chorioamnionitis, low birth weight, admission to neonatal intensive care, and perinatal mortality were also significantly increased after treatment. : Women with CIN have a higher baseline risk for prematurity. Excisional and ablative treatment further increases that risk. The frequency and severity of adverse sequelae increases with increasing cone depth and is higher for excision than for ablation.
Issue Date: 28-Jul-2016
Date of Acceptance: 26-Jun-2016
URI: http://hdl.handle.net/10044/1/34087
DOI: https://dx.doi.org/10.1136/bmj.i3633
ISSN: 0959-8138
Publisher: BMJ Publishing Group
Journal / Book Title: BMJ
Volume: 354
Copyright Statement: This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 3.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/3.0/.
Sponsor/Funder: Imperial College Healthcare NHS Trust- BRC Funding
British Society for Colposcopy and Cervical Pathology
Imperial College Healthcare Charity
Genesis Research Trust
Sigrid Juselius Foundation
Imperial College Healthcare Charity
Funder's Grant Number: RDD03 79560
N/A
7114/R17R
01020
N/A
Keywords: General & Internal Medicine
1117 Public Health And Health Services
Publication Status: Published
Article Number: i3633
Appears in Collections:Division of Surgery
Faculty of Medicine



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