Obstetric outcome following cervical treatment for CIN

1
Obstetric outcome following cervical treatment
for CIN

• By M Lokman,
• M DeLange

2
Aims and Objectives

• Aim
• To determine whether cervical conisation
  increases risk of preterm delivery and adverse
  obstetric outcome
• To develop critical appraisal skills
• Objective
• To review current evidence in published studies,
  meta-analysis
• To review RCOG advisory opinion
• To critically appraise most current study
• To discuss impact on clinical practice

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The Clinical Question

• Does cervical conisation increase risk of
  preterm delivery and adverse obstetric outcomes?
• P(women of fertile age who have had cervical
  treatment)
• I (excisional cervical treatment)
• C (Cx conisation vs none)
• O (risk of preterm delivery and adverse obstetric
  outcome)

4
Literature search

• Databases searched RCOG, Cochrane, PubMed
• Search terms Cervical (MESH selecting
  subheadings treatment, surgery, complications)
  AND (obstetric morbidity OR perinatal mortality)
• Results 1 x RCOG advisory group opinion. 1 x
  cochrane protocol. 2 x current cohort studies. 2
  x meta-analysis.

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Guidelines (RCOG)

• Background evidence show both ablative and
  excisional technique have equal efficacy and
  similar risk of invasive disease.
• 2 meta-analysis similar conclusion excisional
  method increase risk of adverse pregnancy
  outcomes but not with laser ablation.
• biological mechanism uncertain and confounding
  factors (age, smoking, socio-economic class)
• clinical practice proportionally large
  excision/high grade lesion/multiple excision -gt
  high risk pregnancy (serial TV scan/ffn).
  Intervention cx cerclage, progesterone, steroids

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Paper selected

• Pregnancy outcome after cervical conisation a
  retrospective cohort study in the Leuven
  University Hospital.
• van de Vijver A, Poppe W, Verguts J, Arbyn M.
• BJOG. 2010 Feb117(3)268-73. Epub 2009 Nov 26.
• PMID 19943824 PubMed - indexed for MEDLINE
• reason the most relevant paper, up to date,
  good methodology.

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Flow chart of the study
599 women had conisation (LLETZ, laser or cold
knife) in 5 yr period (99-03)
Control group, 55 pregnancies in 54 women matched
for age, parity and yr of delivery Had no
intervention on cervix or CIN
72 subsequent pregnancies identified (delivered
before Jan 07)
17 miscarriages before 11/40 excluded
Note 3 twin pregnancies in study gp and 1 twin
pregnancy in the control gp
study group, n55 in 43 women
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Details of the study

• objective verify strength of association
  between adverse obstetrical outcomes and prior
  excisional treatment for CIN
• study design retrospective cohort study
  setting university hosp
• population 55 pregnancies in 34 women after
  conisation, 55 pregnancies in 54 women without
  history of conisation or CIN

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Continued

• Method
• Study group - 55 pregnancies in 43 women with
  delivery after 22 weeks
• Control group - 55 pregnancies in 54 women with
  equal age, parity and year of delivery. (no
  intervention on cx or dx CIN)
• Data collection patient files and questionnaire

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• Confounding factors - smoking, socio-economic
  status, education level, number of sexual
  partners
• Obstetric outcomes duration of pregnancy,
  proportion of preterm deliveries (lt37 weeks),
  proportion with PPROM. Use of induction or
  augmentation of labour, amniotic fluid, mode of
  delivery
• Neonatal outcomes birthweight, length, hc,
  gender, apgar, pH, NICU

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Data Analysis

• 43 women (study gp) 3 laser conisation (5
  pregnancies), 40 with LLETZ (50 pregnancies). 2
  of these had reconisation and delivered at term
  (4 pregnancies).

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Table 1
Histological diagnosis Number of patients (n55)
Chronic inflammation Squamous metaplasia CIN CIN 1 CIN 2 CIN 3 GIN GIN3 5 5 4 5 34 2
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Table 2 maternal characteristics
Variable Study group Mean SD Control group Mean SD P-value
Maternal height (cm) Maternal weight at start (kg) Age at menarche (yr) Age at first sexual intercourse (yr) Number of sexual partners Ever smoked Smoked during pregnancy 166.1 6.2 63.9 12.2 12.9 1.5 17.7 1.9 4.6 3.4 Number 26/52 50.0 12/51 23.5 167.0 5.6 67.5 14.8 13.2 1.5 18.6 2.6 2.5 2.5 Number 11/54 20.4 5/54 9.3 0.44 0.28 0.41 0.12 0.01 0.002 0.057
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Table 3 pregnancy outcome
Variable Study group Mean SD Control group Mean SD P-value
Maternal characteristics Weight at end pregnancy(kg) Length of gestation(day) Neonatal characteristics Birthweight(g) Length(cm) HC (cm) pH UmA Apgar 1 min Apgar 5 min 78.6 11.8 266.0 21.2 3087.9 753.7 49.1 3.8 33.9 2.5 7.3 0.1 8.6 1.0 9.4 0.8 79.8 13.2 273.9 9.3 3380.5 430.0 50.2 2.0 34.6 1.2 7.3 0.1 8.6 1.1 9.5 0.8 0.62 0.01 0.01 0.07 0.04 0.82 0.98 0.56
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Table 4 pregnancy outcome
Variable Study group Number Control group Number P-value
Preterm delivery (lt37wk) Severe preterm delivery(lt34 wk) Complications in pregnancy PPROM Preterm contractions Oxytocin Prostaglandins Clear amniotic fl Primary C/S Secondary C/S Vacuum extraction Forceps NICU Sex of neonate Male Female 14/55 25.5 6/55 10.9 22/55 40 5/55 9.1 5/55 9.1 16/44 36.4 10/44 22.7 40/43 93.0 11/58 19.0 2/58 3.5 1/58 1.7 0/58 0 15/58 25.9 35/58 60.3 23/58 39.7 2/55 3.6 0/55 0 14/55 25.5 1/55 1.8 0/55 0 17/55 30.9 15/55 27.3 49/55 89.1 13/56 23.2 3/56 5.4 5/56 8.9 0/56 0 9/58 15.5 32/56 57.1 24/56 42.9 0.002 0.031 0.15 0.20 0.057 0.67 0.65 0.75 0.65 0.68 0.11 1 0.25 0.85 0.85
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Discussion

• Results largely confirm findings of meta-analysis
• Relative risk 7.0, severe preterm significant
  (lt34wks)
• Limitations of retrospective cohort study.
  (confounding bias not always able to correct for,
  information bias, selection bias finding
  controls.)
• Small number in study
• Critical appraisal (see CASP ppt)

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Summary and Conclusion

• Current evidence supports association between
  cervical excisional treatment and preterm
  delivery. However confounding factors
  (technique, risk factors)
• Women of fertile age with CIN best balance
  between max treatment n minimal disturbance of
  anatomy. Need to reduce over-diagnosis n
  over-treatment
• Inform patient of possible risk of excisional
  treatment

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• Ideally prospective RCT 2 gps ablative vs
  excisional n compared to untreated CIN.
• More research area dimension of cone, impact of
  CIN on pregnancy, perinatal mortality,
  pathophysiology
• Preventative measures antenatally
• Impact on current practice