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

2. Preterm birth in Liverpool

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

4. Issues
Prediction
Prevention
Diagnosis
Treatment

5. 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)

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

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

8. Bacterial vaginosis

9. 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

10. Fetal fibronectin
Honest 2002

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

12. 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

13. 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%) (15%)
Deaths (6%) (8%)
Intracranial bleeds 1 (1%) (2%)
Pulmonary dysplasia (3%) (3%)
Caesarean Section 33 (26%) (18%)
Maternal Pyrexia 5 (4%) (1%)
To et al 2004

14. Cerclage – individual patient data
Jorgensen et Al 2008

15. Cerclage and gestation
Jorgensen et al 2008

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

17. Progesterone
Fonseca et al. NEJM 2007

18. Progesterone

19. 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

20. Progesterone
Rouss et al 2007; twins

21. Is it the progesterone? Vaginal progesterone
Intramuscular progesterone

22. 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

23. Treatment options Tocolysis Steroids Transfer Mode of birth
? magnesium

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

25. 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

26. Fetal fibronectin in symptomatic women
Honest 2002

27. 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 hours
If contractions and clinical suspicion persists repeat scan every 2-4 hours

28. 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

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

31. 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

32. 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

33. Repeat steroids
Cochrane 2007

34. Repeat steroids: every 14 days
Lancet 2008

35. 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

36. 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?

37. 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, )

38. 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