Evidence based management of preterm labour SA Walkinshaw Consultant in Maternal and Fetal Medicine

Preterm birth in Liverpool

Trends in spontaneous preterm birth in Denmark Langhoff-Roos, J. et al. BMJ 2006

Issues Prediction Prevention Diagnosis Treatment

at Various Gestational Ages Risk factors Relationship Between Maternal Characteristics and Spontaneous Preterm Birth at Various Gestational Ages Risk Factor SPTB < 32 Weeks RR (95% CI) SPTB < 35 Weeks RR (95% CI) Black race 1.5 (0.8–2.8) 1.4 (0.9–2.0) BMI < 19.8 2.6 (1.1–6.2) 3.0 (1.7–5.1) History of SPTB 7.1 (3.8–13.2) 6.4 (4.4–9.2) Contractions 2.2 (1.5–3.1) Vaginal bleeding 2.7 (1.4–5.1) 1.9 (1.2–3.0) Pelvic infection 1.1 (0.6–2.0) 1.2 (0.8–1.7) Bacterial vaginosis 2.7 (1.6–4.6) + fFN 14.1 (9.3–21.4) 6.7 (4.9–9.2) Cervix <25 mm 7.7 (4.5–13.4) 6.5 (4.5–9.3)

Screening for preterm labour Vaginal infection/colonisation Cervical length Fetal fibronectin Risk factor assessments/scores

Screening for vaginal infection Bacterial vaginosis 9-20% women Good diagnostic tests Clear evidence link with preterm birth

Bacterial vaginosis

BV Current views US Prevention Task Force Canadian college Cochrane not recommended but caveat high risk Canadian college Not enough evidence Cochrane RR less than 34 weeks 0.95 (0.38 – 2.37) BUT Kiss et al 2004 RR 0.34; early screen and treat studies

Fetal fibronectin Honest 2002

Short cervix Empty bladder Do not squeeze the cervix Watch at least 2 minutes Reduce the gain

Short cervix Lengths less than 25mm before 24w LR 4.31 if before 20w in all women LR 11 if before 20w in previous preterm birth

Cervical cerclage for prevention of preterm birth in women with short cervix 47, 123 singleton pregnancies 470 pregnancies with cervix less than 15mm Delivery <33 weeks 28 (22%) 33 (26%) PROM 23 (18%) 19 (15%) Deaths 7 (6%) 10 (8%) Intracranial bleeds 1 (1%) 2 (2%) Pulmonary dysplasia 4 (3%) 4 (3%) Caesarean Section 33 (26%) 23 (18%) Maternal Pyrexia 5 (4%) 1 (1%) To et al 2004

Cerclage – individual patient data Jorgensen et Al 2008

Cerclage and gestation Jorgensen et al 2008

Relationship between cervical length and risk of preterm birth Cervical length changes during pregnancy Salomon et al

Progesterone Fonseca et al. NEJM 2007

Progesterone

Progesterone History of previous preterm birth Secondary analysis based on cervical length In 46 women with cervical length <28mm the rate of preterm birth before 32 weeks was significantly lower (0% vs. 30%) in the PG group De Franco et al 2007 O’Brien et al 2007

Progesterone Rouss et al 2007; twins

Is it the progesterone? Vaginal progesterone Intramuscular progesterone

Spontaneous preterm birth Where is prevention? Number of reasonable predictive tests Struggling with timing of tests Struggling with treatment options awaiting definitive trials of progesterone Continuing uncertainty on therapy BV Timing of cerclage

Treatment options Tocolysis Steroids Transfer Mode of birth ? magnesium

Diagnosis of preterm labour Clinical Fetal fibronectin Cervical length Good data including trials that fFN and cervical length superior to clinical judgement

Selection for treatment 40 women Singleton pregnancy <34 weeks Decision made to use tocolysis and steroids Ultrasound Group 14 women (70%) with cervix > 15mm Antenatal steroids 6 Tocolysis 6 Control Group 20 women with suspected digital change Antenatal steroids 20 Tocolysis 20 Steroids given – Birth within 1 w - 3 Steroids not given – No birth within 1 w - 14 Steroids given – Birth within 1 w - 2 Steroids not given – No birth within 1 w - 0

Fetal fibronectin in symptomatic women Honest 2002

Steroids and tocolysis ‘Evidence based’ management protocol for threatened preterm labour in units with access to emergency ultrasound Clinical diagnosis of preterm labour Cervix <15 mm Cervix >15 mm Steroids and tocolysis Wait and see if fFN-ve discharge after 24-48 hours If contractions and clinical suspicion persists repeat scan every 2-4 hours

Tocolysis Is tocolysis better than no tocolysis for preterm labour? It is reasonable not to use tocolytic drugs, as there is no clear evidence that they improve outcome. However, tocolysis should be considered if the few days gained would be put to good use, such as completing a course of corticosteroids, or in utero transfer. Clinical Guideline No. 1(B) October 2002 RCOG

Tocolysis in 2008 – UK Survey of practice Nifedipine 49% Atosiban 43%

Use of steroids and steroid therapy to delivery interval Steroid single dose 3 (2.2%) Steroid- both doses 133 (97.8%) > 24 hours after first dose of steroid 114(84%) Delivery within 24 hours (of 1st dose) 22 (16%) Delivery within 48 hours (of 1st dose) 34 (25%) Delivery within 7 days 95 (70%) Indomethacin tocolysis < 28w; fFN for diagnosis, all born before 34 weeks Das 2006

Steroids Indications for antenatal corticosteroid therapy Every effort should be made to initiate antenatal corticosteroid therapy in women between 24 and 34 weeks of gestation with any of the following: ● threatened preterm labour ● antepartum haemorrhage ● preterm rupture of membranes ● any condition requiring elective preterm delivery. Between 35 to 36 weeks obstetricians might want to consider antenatal steroid use in any of the above conditions although the numbers needed to treat will increase significantly. RCOG 2004

Repeat steroids Cochrane 2007

Repeat steroids: every 14 days Lancet 2008

Antibiotics ORACLE : short term morbidity advantage to erythromicin in PPROM Long term follow up Antibiotics where intact membranes CP 1.93 Numbers needed to harm 64-69 Kenyon 2008

Mode of birth Where is the evidence for CS? No useful RCTs No good multivariate studies that correct for pathology leading to preterm birth CESDI data 27/28 weeks What happens if you get diagnosis of labour wrong?

Management of preterm labour Magnesium Rouse et al 2008 6g bolus then 2g/hr No difference primary outcome 1.9% v 3.5% CP at >2y (RR 0.55, 0.32-0.95)

Evidence based preterm labour Sort accurate diagnosis Too much treatment Consider tocolysis But which drug Single course corticosteroids Get timing and diagnosis right Still uncertainty for occasional repeat doses Avoid antibiotics Consider in PPROM Avoid CS unless other clinical grounds For the future – assess magnesium