title: Adverse obstetric outcomes after local treatment for cervical preinvasive and early invasive disease according to cone depth: systematic review and meta-analysis.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Systematic review and meta-analysis.
  
  
  METHODS
  CENTRAL, Medline, Embase from 1948 to April 2016 were searched for studies assessing obstetric outcomes in women with or without previous local cervical treatment.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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. :
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Reproductive and Developmental Biology, Department of Surgery and Cancer, Faculty of Medicine, Imperial College, London, UK Queen Charlotte's and Chelsea-Hammersmith Hospital, Imperial Healthcare NHS Trust, London, UK m.kyrgiou@imperial.ac.uk.
authors.forename: Maria
authors.initials: M
authors.lastname: Kyrgiou
authors.affiliation: University Hospital of Ioannina, Ioannina, Greece.
authors.forename: Antonios
authors.initials: A
authors.lastname: Athanasiou
authors.affiliation: Institute of Reproductive and Developmental Biology, Department of Surgery and Cancer, Faculty of Medicine, Imperial College, London, UK.
authors.forename: Maria
authors.initials: M
authors.lastname: Paraskevaidi
authors.affiliation: Institute of Reproductive and Developmental Biology, Department of Surgery and Cancer, Faculty of Medicine, Imperial College, London, UK Queen Charlotte's and Chelsea-Hammersmith Hospital, Imperial Healthcare NHS Trust, London, UK.
authors.forename: Anita
authors.initials: A
authors.lastname: Mitra
authors.affiliation: Institute of Reproductive and Developmental Biology, Department of Surgery and Cancer, Faculty of Medicine, Imperial College, London, UK.
authors.forename: Ilkka
authors.initials: I
authors.lastname: Kalliala
authors.affiliation: Department of Gynaecological Oncology, Lancashire Teaching Hospitals, Preston, UK Department of Biophotonics, Lancaster University, Lancaster, UK.
authors.forename: Pierre
authors.initials: P
authors.lastname: Martin-Hirsch
authors.affiliation: Unit of Cancer Epidemiology, Scientific Institute of Public Health, Brussels, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Arbyn
authors.affiliation: Institute of Reproductive and Developmental Biology, Department of Surgery and Cancer, Faculty of Medicine, Imperial College, London, UK Queen Charlotte's and Chelsea-Hammersmith Hospital, Imperial Healthcare NHS Trust, London, UK.
authors.forename: Phillip
authors.initials: P
authors.lastname: Bennett
authors.affiliation: University Hospital of Ioannina, Ioannina, Greece.
authors.forename: Evangelos
authors.initials: E
authors.lastname: Paraskevaidis
mesh_terms: D000328:Adult; D002584:Cervix Uteri / Q000473:pathology / Q000601:surgery; D019092:Conization / Q000379:methods*; D036861:Delivery, Obstetric; D005260:Female; D006801:Humans; D007752:Obstetric Labor, Premature / Q000209:etiology; D011247:Pregnancy; D011252:Pregnancy Complications, Neoplastic / Q000473:pathology / Q000601:surgery*; D011256:Pregnancy Outcome; D047928:Premature Birth / Q000209:etiology; D012307:Risk Factors; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000601:surgery*; D002578:Uterine Cervical Dysplasia / Q000473:pathology / Q000601:surgery*