1. Prematurity and Twins Max Brinsmead MB BS PhD March 2014

2.  Affects 8-15% of our obstetric patients  Increasing in frequency  Contributes significantly to perinatal mortality and morbidity  Is a particular challenge to those who work with limited neonatal facilities Pre term Birth

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

4. 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? 6 Questions about Preterm Birth

5.  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 Is this baby premature?

6.  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 Is it Labour?

7.  A fetal connective tissue protein  Released into the cervix and upper vagina  A bedside immunoassay test  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) Fetal Fibronectin

8.  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 Ultrasound Measures of Cervical Length

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

10.  Is the baby better off in or out?  Will depend on your local resources  At the limits of viability (22 – 25w) survival with handicap is possibly the worse outcome  So you need to be aware of the wishes and resources of the family Should Labour be Suppressed?

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

12.  I prefer IV Betamimetics  Ventolin by infusion until MPR >110 but <140 bpm. Rapidly effective but maternal side effects common  Oral Nifedipine has fewer side effects  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  Not used in Australia  Gyceryl trinitrate - transdermal patch  Not commonly used  NSAIDs  Problems include premature closure ductus and renal effects  Rebound effects described after withdrawal at 32w What is the best tocolytic to Use?

13.  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 Overall, uterine tocolysis:

14.  Psychological care  Administration of steroids  Doubles survival and halves all complications  Can the patient be transferred?  Doubles survival and halves handicap  MgSO4 to prevent brain damage  When to use antibiotics What else can be done for the patient in premature labour?

15.  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) Corticosteroids

16.  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 Corticosteroids (2)

17.  Effectively reduces the risk of:  Periventricular leucomalacia  Cerebral palsy  Overall OR is 0.14 (CI 0.05 – 0.51)  Recommended for gestations <30 weeks  Must be given within 24 hrs of birth  Consider repeating if 24 hrs  Dose is the same as that used for Eclampsia Mg suphate for Neuroprotection

18.  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 confusing  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  Erythromycin or Clindamycin is useful after PROM  Best not to give antibiotics for idiopathic premature labour with intact membranes  Perhaps the source of infection is outside the genital tract? Infection and Prematurity

19.  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? Optimal Intrapartum Care for the Premature Fetus

20.  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 is a continuum  Monitor and plot on a scale against GA  Consider suture for cervix <15 mm  Vaginal progesterone gaining acceptance as the most valuable agent to use Prediction and Prevention of Preterm Birth

21. 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 Progestational Agents

22. Multiple Pregnancy

23.  Twins 1:80 in Caucasians  Assisted conception (IVF) explains most of the increasing incidence  But incidence is also affected by:  Race (1:50 Black Africans, 1:150 in Asians)  Family history (mean FSH levels)  Older maternal age  Increasing parity  Spontaneous triplets 1:6400 (Hellin’s Law) Incidence

24.  Prematurity  Risk of pre term delivery twins increased 5-fold  And 10-fold for triplets  14% twins and 41% triplets born very pre-term  Intrauterine growth restriction  Oft en manifest as discordant growth  Congenital malformations increased 2-fold  In monochorionic twins only  Increased rate of maternal pregnancy disorders  e.g. Pre eclampsia, gest. Diabetes, APH etc  Overall PN mortality increased 2 – 3-fold Twin Problems

25. is Is Chorionicity But the single most important predictor of Risk in a twin pregnancy

26.  Dizygotic – arise from two eggs.  These are non-identical twins  Monozygotic – one egg or embryo that splits  These are identical twins (clones)  But from a clinical perspective it is chorionicity that is important  Dichorionic (two chorion, separate sacs and placentas)  Monochorionic (one chorion and a shared placenta)  Monochorionic and diamniotic (separate sacs)  Monochorionic and monamniotic (only 1%)  About 1/3 twin pregnancies are monochorionic Types of twin pregnancy

27.  The early diagnosis of twins is one of the reasons to advocate universal 1 st trimester scans  AND  It is the best time to document chorionicity  By looking for and studying the gestational sac(s)  “Y” sign = dichorionic  “T” sign = monochorionic Early Diagnosis is Important

28.  Almost all share vessels in their common placenta  But for 10 – 15% unidirectional flow results in twin-to-twin transfusion (TTS) which can:  Cause discordant growth  Has cardiovascular, haematological and amniotic fluid burdens  Result in the death of one twin  And a high risk of neurological damage to the survivor  MC and MA twins  Are at high risk of cord entanglement  Or succumb to acute polyhydramnios in the 2 nd trimester Monochorionic Twins

29.  Patient counselling  Issues of prenatal diagnosis  Nutrition and rest  More frequent AN visits  Dealing with the discomforts of pregnancy Management of Twin Pregnancy

30.  Monitoring fetal growth and well being  A role for regular ultrasound with Doppler flow studies  Place of Delivery  Time of delivery  Intrapartum fetal monitoring  Method of delivery  Issues of lactation  Two for the price of one or twice as hard?  A role for Support Groups Management of Twins – Delivery & Beyond

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