Threatened Pre Term Birth

1. Threatened Pre Term Birth Max Brinsmead PhD FRANZCOG February 2013

2. Pre term Birth • Affects 5-9% births in Europe and 12-13% in US • Increasing in frequency in both • 1:4 is induced labour for maternal and fetal reasons • Single most common cause of perinatal mortality & morbidity • Increases risk of cerebral palsy (80-fold @ 28w compared to term) • Is a particular challenge to those who work with limited neonatal facilities

3. When confronted by possible Pre term Birth • There are 6 questions you need to ask yourself • And they need to be answered ASAP • Because time is of the essence

4. 6 Questions about Pre term Birth 1 Is the baby premature? 2 Is it really labour? 3 Why is labour occurring now? 4 Should the labour be suppressed? 5 Can the labour be suppressed? 6 What else can be done?

5. Is this baby premature? • Dates uncertain or unknown? • Be the obstetric detective! • The earliest ultrasound is best • Measure uterine size and estimate fetal weight • But there is a problem with PROM! • Use USS to measure biparietal diameter & femur length • Remember the baby that is mature before its time

6. Is it Labour? • Listen to what the patient is telling you • Has it happened before? • A warm hand is better than a tocograph! • Ruptured membranes - if it isn’t obvious then it isn’t relevant • Cervical assessment • Observation over time

7. Fetal Fibronectin • Easy to perform • Not inexpensive • High negative predictive value of delivery within seven (7) days (particularly in women who present with contractions) • Poor positive predictive value and sensitivity • Overall ~50% (Based on a 2003 BMJ meta analysis of 40 published studies)

8. Ultrasound Measures of Cervical Length • Simple and safe • Expertise and equipment required • High negative predictive value if the cervix is >15 mm and there is no beaking of membranes with straining down • The positive predictive value and sensitivity is less certain • The appropriate intervention for a short cervix is also debatable

9. Why is Labour occurring now? • Underlying maternal problem? • Is the baby normal? • Antepartum haemorrhage • Chorioamnionitis • Ruptured membranes • Cervical incompetence

10. Should Labour be suppressed? • Is the baby better off in or out? • Will depend on your local resources • At the limits of viability survival with handicap is possibly the worse outcome • But you need to be aware of the wishes and resources of the family

11. Can the labour be suppressed? In many cases the answer is YES But Advanced labour and ruptured membranes sometimes make it difficult

12. What is the best tocolytic to use? • In general, use the one you know best • I prefer IV Betamimetics • 5 mg Ventolin in 500 ml and run until MPR >110 but <140 bpm. Rapidly effective but maternal side effects common • Oral Nifedipine has fewer side effects • 2 crushed tablets (20 mg) stat and repeat in one hour if required. Then 10 – 20 mg 6 – 8 hourly PRN • Doses >60 mg over 48 hrs best avoided • RCT comparisons with betamimetics suggest improved neonatal outcomes • Atobisan = an oxytocin blocker • As effective as Ca channel blocker in delaying delivery • Questions arising from long term follow up of children • Gyceryl trinitrate - transdermal patch • NSAIDs – use with caution • Problems include premature closure ductus and renal effects • Rebound effects described after withdrawal at 32w • IV Mg sulphate - ? protects the fetal brain

13. What else can be done for the patient in premature labour? • Psychological care • Administration of steroids • Doubles survival and halves all complications • Can the patient be transferred? • Doubles survival and halves handicap • What about MgSO4 to prevent brain damage? • Are antibiotics required? • Optimal care in labour

14. Corticosteroids • Effectively reduce the risk of: • Hyaline membrane disease • Necrotising enterocolitis • Intracranial haemorrhage • Death and disability • Are safe in the short and long term • Are effective at gestations 26w – 40w • Effective for all clinical indications including: • Idiopathic pre term labour • PROM • Maternal hypertensive diseases • Twins (maybe) • Must be given within 24 hrs and 7 days • Repeat once if <34 weeks or still high risk • Optimum formulation, dose & route – uncertain • I prefer IM Betamethasone 11.2 mg 24 hours apart

15. Mg suphate for Neuroprotection • Effectively reduces the risk of: • Periventricular leucomalacia • Cerebral palsy • Overall OR is 0.14 (CI 0.05 – 0.51) • Most data arises from use of MgSO4 for eclampsia prophylaxis • In this MgSO4 has been proven to be safe • Recommended for gestations <30 weeks • Planned preterm delivery • Inevitable preterm delivery • Must be given within 24 hrs of birth • Consider repeating if <30 weeks and >24 hrs • Dose is 4G IV loading over 20 – 30 min then 1 G/hour IV infusion for 24 hrs or until delivery

16. Infection and Prematurity • Subclinical infection implicated in 40-70% of pre term labour • Also has a sinister role in the aetiology of cerebral palsy • The results of therapeutic trials of antibiotics in preventing pre term birth are conflicting • Vaginosis is a risk factor for prematurity • But screening and treatment should be reserved for those at risk • Most studies have focused on anaerobic BV but aerobic BV may be the more important • Erythromycin or Clindamycin is useful after PROM • Do not use Amoxil (Increases the risk of NEC) • Antibiotics with intact membranes may increase risk of perinatal mortality (RR 1.52, CI 0.99-2.34) and increases the risk cerebral palsy (RR 1.18, CI 1.02-1.37) • Is the source of infection outside the genital tract?

17. Overall, uterine tocolysis: • Prolongs gestation • But the gains are modest • Buys time for perinatal transfer and administration of steroids • By themselves they have no effect on perinatal mortality and morbidity • Ineffective or impractical for long term use • Ca channel blockers are safer than betamimetics but sometimes slow and unpredictable

18. Optimal intrapartum care for the premature fetus • Delivery at the optimal site the most important • Avoid hypoxia and trauma • Avoid sedatives and narcotics if possible • CS for the pre term breech? • CS for the very premature?

19. Prediction and Prevention of Preterm Birth • Prior history of preterm birth the best predictor • But also look out for overworked, stressed, abused and smoking patient • And those with other chronic diseases • Multiple pregnancy • The short & incompetent cervix continuum • Monitor and plot on a scale against GA • Consider suture for cervix <15 mm • Endocrine predictors include the measurement of CRH, steroids, AFP etc

20. Progestational Agents NEJM June 2003 • A DB PC RCT of weekly injections of 17hydroxyprogesterone caproate from 16-20w in 267 high risk women in several centres • Reduced delivery at <37w from 55% to 36% • Reduced delivery at <32w from 20% to 11% These results confirmed by a meta analysis that includes previous trials AND They have now proven effective in a wide range of patients at risk incl. twins The best agent to use is vaginal Progesterone