PPROM

Question 1

Proportion of preterm births associated with PPROM?

Answer 1

30-40%

Question 2

Risks of PPROM?

Answer 2

prematurity,
sepsis,
cord prolapse
pulmonary hypoplasia.

In addition, there are risks associated with chorioamnionitis and placental abruption.

Question 3

Median latency after PPROM

Answer 3

7 days, decreases as gestation increases

Question 4

How to diagnose PPROM

Answer 4

• History
• Sterile speculum examination
• If uncertain, perform IGFBP-1 or PAMG-1 test of vaginal fluid
• Clinical assessment for infection: observations, blood tests (WCC, CRP) and CTG

Question 5

Management

Answer 5

• Steroids if <35/40
• MgSO4 if in labour and <30/40
• 10/7 erythromycin 250mg QID
• Vaginal swabs
• Confirm presentation
• Admission and assessment for infection
• If managed as an outpatient- twice weekly blood and assessment in a maternity unit - take into account past obstetric hx, support at home and distance from hospital
• IOL at 37/40
• IV Ben Pen in labour
• Offer emotional support as increased rates of PTSD in women with PPROM
• Counsel re risks of PTL, risks of chorioamnionitis and features to look out for
• Offer women chance to speak with neonatologist and inform paeds of admission

Question 6

Results of cochrane review looking at use of antibiotics

Answer 6

Reduction in:

• Chorioamnionitis
• delivery rates at 48 hours and 7/7
• Neonatal infection,
• use of surfactant,
• oxygen therapy
• abnormal cerebral ultrasound prior to discharge from hospital

No reduction in:

• Neonatal mortality
• Health of children at 7 years

Question 7

Benefit of MgSO4 24 hours around delivery, in women in established preterm labour <30/40

Answer 7

Reduces:

• Cerebral palsy
• Motor dysfunction in the offspring

Question 8

Should tocolysis be offered?

Answer 8

Cochrane review found an increase in incidence of chorioamnionitis with no perinatal benefit

Question 9

Cochrane review of timing of delivery with PPROM

Answer 9

Two trials: PPROMT multicentre and the PPROMEXIL-2 randomised controlled trials

• Compared expectant versus planned early delivery
• in women with PPROM ‘with no contraindications to continuing the pregnancy, expectant management with careful monitoring is associated with better outcomes for the mother and baby’.

No differences between early birth and expectant management in:

• neonatal sepsis or infection
• Perinatal mortality
• IUFD

Early delivery increased the incidence of:

• respiratory distress syndrome
• ventilation
• Neonatal death
• increased rate of caesarean section

Question 10

Limitations when considering results of cochrane

review for delivery at 37/40

Answer 10

• Looked at late PPROM- didn’t look at gestations <34/40, therefore unclear if early PPROM benefit from expectant Rx till 37 weeks
• Exclusion criteria: active labour,
  chorioamnionitis, concerns about fetal wellbeing, monochorionic multiple pregnancy, hypertensive disorders

Question 11

Evaluate nitrazine, IGFBP-1 (Actim PROM) and PAMG-1 (amnisure) for detecting PPROM?

Answer 11

RCT 2014 compared 3 options and found the following sensitivity, specificity, PPV, NPV for each.

PAMG-1 (amnisure)

• sensitivity, specificity, PPV NPV all = 100%
• Point of care
• Quick result
• Minimally invasive
• NOT affected by semen or trace amounts of blood
• False positive of 15-30% in threatened preterm labour

IGFBP-1 (Actim PROM)

• sensitivity, specificity, PPV NPV (93%, 99%, 97% and 98%)
• NOT affected by semen or trace amounts of blood

Nitrazine

• sensitivity, specificity, PPV NPV (93%, 94%, 85% and 98%)
• Affected by any alkaline fluid: blood, semen, soap, infections - BV

Question 12

Other alternative antibiotic regimes

Answer 12

48 hours of IV ampicillin, followed by PO erythromycin and amoxicillin OR addition of azithromycin to target ureaplasmas

Question 13

RANZCOG Q: A primiparous woman presents to you at 32 weeks gestation with spontaneous rupture of membranes. Her pregnancy has been uncomplicated so far and she is well.
a) Outline what assessments you would perform. (3 marks)

Answer 13

1. History – time, amount, colour, smell of fluid.
   - confirm dates
   - associated symptoms – pain, contractions, fever
   - Recent infective symptoms – cough, dysuria etc.
   - FM’s
   - PMHx etc
2. Examination – obs
   Uterine – tenderness, contractions, lie and presentation
   Speculum – confirm diagnosis, assess cervcal dialation
3. Extra tests if uncertain – amnisure, nitrizine sticks (contentious), serial pad checks
4. FBC, CRP, swab, USS – liq volume, growth, presentation, placentation.

Question 14

b) Assuming your investigations are normal, how would you manage her? (5 marks) (PPROM at 32/40)

Answer 14

1. Admit for observation – chance of PTL
2. Ensure unit with NICU available
3. Maternal wellbeing – temp, pulse, pad checks q4-8 hourly
4. Fetal wellbeing – CTG daily, USS 1-2 weekly
5. Antibiotics – erythromycin 250mg PO QDS, start IV ben pen if going into labour
6. Steroids – betamethasone 11.4mg IM x2

Question 15

The Oracle I trial (Kenyon et al. Lancet 2001; 357: 979-88) studied women with preterm prelabour rupture of membranes.

c) Briefly describe the study and its principle findings (numerical statistics not required) (4 marks)

Answer 15

Large multicentre double blinded placebo controlled RCT
n > 4800

Aim – to evaluate benefit of antibiotics for women with PPROM
Inclusion - <37/40, PPROM

Women randomized to:

1. augmentin + placebo
2. erythromycin + placebo
3. augmetin + erythromycin
4. placebp + placebo

1’ Outcome – composite measure of neonatal morbidity and mortality - NND, lung disease and USS evidence of CNS abnormality

Result – erythromycin:
• Prolongs pregnancy mean 10d
• Reduced 1’ outcome

Augmentin = increased NEC, did not reduce primary outcome

Question 16

The Oracle II study (Kenyon et al. Lancet 2001; 357: 989-94) used the same treatment options as Oracle I.

d) How did the group of women that was studied differ from the Oracle I group? (1 mark)

Answer 16

Women with threatened preterm delivery and membranes intact as opposed to PPROM
Demonstrated no improvement in outcomes when oral erythromycin or augmentin were given

Question 17

Both studies had their 7 year follow up data published in 2008 (Kenyon et al. Lancet 2008; 372: 1310–27).
e) What additional information did this follow up provide (numerical statistics not required)? (2 marks)

Answer 17

Neither antibiotic made a statistically significant difference to:
•	Functional impairment
•	Educational achievement
•	Behavioural difficulties
•	Specific medical conditions

In children at 7 years of age.

Question 18

Incidence of PPROM

Answer 18

3%

Question 19

Evidence for use of steroids in PPROM

Answer 19

Reduced rate of:

• Intraventricular haemorrhage
• RDS

No difference was observed for:

• necrotising enterocolitis,
• neonatal sepsis
• Apgar score of less than 7 at 5 minutes
• Perinatal mortality

No increased risk of chorioamnionitis or neonatal sepsis with maternal steroid use.

After 34/40 there is a high NNT for benefit and potential risk of giving steroids therefore decision should be made on an individual basis.

Question 20

Results of a retrospective cohort study of women with PPROM who had planned home care?

Answer 20

• membrane rupture occurring before 26+0 weeks’,
• non‐cephalic presentation and
• oligohydramnios

Associated with an increased risk of ‘complication’ (defined as fetal death, placental abruption, umbilical cord prolapse, delivery outside of hospital and neonatal death).

Hospital based care should be recommended to women who have all three of these features.

Question 21

How is PROM diagnosed?

Answer 21

1) Sterile speculum examination for pooling liquor

Additional tests if speculum findings uncertain:

2) Nitrazine paper for pH - turns blue in alkaline pH >6.0
3) Amnisure - uses immunochromatography. Monoclonal antibodies bind PAMG1 protein (high in amniotic fluid, but low in vaginal secretions at all gestations)
4) Actim PROM - detects insulin-like growth factor binding protein 1 (IGFBP-1)

Question 22

If PPROM with GBS, how does management differ?

Answer 22

IOL at 34 weeks, when risks of GBS sepsis may outweigh the risks of prematurity
(RANZCOG)

Question 23

What is the incidence of PPROM?

Answer 23

3%

RCOG

Question 24

PPROM is associated with _______ of preterm births

Answer 24

30-40%

RCOG

Question 25

What is the median latency after PPROM?

Answer 25

7 days RCOG

Question 26

What are the benefits of erythromycin in the context of PPROM?

Answer 26

Reduced Chorioamnionitis Prolonged latency Improved neonatal outcomes RCOG

Question 27

Is tocolysis recommended in PPROM?

Answer 27

No Cochrane review found that - tocolysis does not significantly improve perinatal outcome and might be associated with an increased risk of chorioamnionitis - tocolysis was associated with an increased risk of APGAR <7 and the need for ventilation support

Question 28

With PPROM, what is the delivery latency from 24-28/40 31/40

Answer 28

24-28/40: 8-10 days 31/40: 5 days

Question 29

With PPROM, what are three risk factors for complications | Fetal death, placental abruption, umbilical cord prolapse, delivery outside of hospital, neonatal death

Answer 29

PPROM <26/40 Non-cephalic presentation Oligohydramnios

Question 30

What does Amnisure test for?

Answer 30

Placental Micro Globulin PAMG-1

Question 31

What are the complications of PPROM?

Answer 31

``` Prematurity Sepsis (Chorioamnionitis) Cord prolapse Placental abruption Pulmonary hypoplasia ```

Question 32

Why is increased emotional support required in PPROM?

Answer 32

Increased rate of PTSD

Question 33

What were the findings of the Cochrane review on amnio infusion with PPROM?

Answer 33

Associated with improved outcomes in - fetal umbilical artery pH at delivery - variable decelerations in labour - neonatal death - neonatal sepsis - pulmonary hypoplasia - puerperal sepsis BUT insufficient data: further evidence required. NOT currently recommended as part of routine clinical practice

Question 34

What antibiotic should be used in PPROM, if a woman is allergic to erythromycin?

Answer 34

Penicillin | NICE guideline