Preterm birth Flashcards
Discuss fetal fibronectin
-What is it (3)
-When should it be tested for (5)
-Why should it be used (3)
-What tests use it and what are their sensitivity and specificity (2 tests)
-Cause of false positives (4)
- What is fetal fibronectin
-Extracellular matrix glycoprotein present at the decidual-chorionic interface
-Present in cervicovaginal secretions <16 weeks and after 37 weeks
-Disruption of the interface causes a release of FFN - When should it be tested for
-Use after 22/40
-Intact membranes
-Cervical dilation <3cm
-No gross vaginal bleeding
-No vaginal penetration in last 24 hrs - Why should it be used
-Helps predict likelihood of preterm delivery
-Can guide toco and steroid use
-Can guide transfer from smaller centres - Test types
-Qualitative: >50ng/mL = increased chance of delivery in 7 days. NPV 99.7%
-Quantitative: Gives exact number. Positive predictive value increases with increase in number
-Sensitivity - 65% specificity 93% PPV 43% NPV 97% - Cause of false positives
-semen, blood, digital cervical examination, lubricant
Discuss actim partus test for PTL
-What it detects
-How results are given
-Sensitivity and specificity
- What it detects
-Qualitative test
-Detects insulin-like growth factor binging protein one - How are results given
-Negative result shows unlikely to deliver in next 7-14 days - Sensitivity - 77%, specificity 81%
Discuss partosure to test for PTL
-What kind of test
-What it detects
-How results are given
-Sensitivity and specificity
- What kind of test
-Qualitative - What it detects
-Placental alpha microglobulin (PAMG-1) - How results are given
-Negative result shows reduced likelihood of delivery within 7 days - Sensitivity 83% specificity 95%
Discuss magnesium sulphate for neuroprotection
-Dose (1)
-Monitoring (6)
-Indications (2)
-Contra-indications (3)
-Timing (5)
- Dose
-4g bolus over 20-25mins then 1g per hr for 24 hrs or until baby is born whichever comes first. - Monitoring
-Do at least Q4H
-HR, BP, RR, Deep tendon reflexes, UO - Indications
-Any woman at risk of PTD under 30 weeks where birth is imminent - within 24hrs
-Do regardless of number of babies in utero, parity, mode of delivery, whether steroids have been given, the reason for delivery - Contra-indications
-Myasthenia gravis
-Women with myocardial compromise / conduction defects
-Caution with impaired renal function - Timing
-22+6 - 23+6 consider in discussion with NICU
-24-29+6 - offer if in established labour or planed delivery within 24 hrs.
-30-33+6 - consider if in established labour or if pre-term birth is planned within 24hr
-Don’t delay birth for MgSO4
-Ideally give more than 4 hrs prior to delivery
Discuss the evidence for magnesium sulphate as a neuroprotection
-Cochrane review included 5 RCTS 2009
-Looked at effect on neuroprotection in 6145 babies
-Included PTB up to 34 weeks. Only one trial <30
-Looked at neurodevelopmental outcomes (impairment, disability, mortality and maternal SAE)
-Reduced the risk of cerebral palsy RR 0.68 NNT 63 (NNT 29 if <28 weeks)
-Reduced risk of gross motor dysfunction RR 0.61
Discuss mechanism of action for MgSO4 to achieve neuroprotection (5)
-Antagonist for NMDA receptors - reduces seizure threshold
-Down regulates excitory stimuli through blocking NMDA receptors stopping influx of Ca and neuronal death
-Cerebral vasodilation through Ca antagonism increasing cerebral blood flow and minimising hypoxic ischemia
-Prevents neuronal injury by reduction of proinflammatory cytokines
-Anti apoptotic effect
Discuss neonatal outcomes of preterm delivery
-Percentage cause of neonatal death (1)
-Major causes of mortality (3)
-Influencing factors determining outcome (5)
- Percentage of neonatal deaths attributed to PTD
-50% - Major causes of mortality
-NEC, RDS, IVH - Influencing factors
-Gestation
-Gender - boys do worse
-Growth restriction
-Infected environment
-Steroid cover
What are the rates of mortality and severe morbidity for babies born at 22,23,24,25,26 weeks
- Babies born at 22 week
-7 die
-1 in 3 has severe disability - Babies born at 23 weeks
-6 die
-1 in 4 babies have severe disability - Babies born at 24 weeks
-4 babies die
-1 in 7 babies have severe disability - Babies born at 25 weeks
-3 babies dies
-1 in 7 have severe disability - Babies born at 26 weeks
-2 in 10 babies die
-1 in 10 babies have severe disability
Discuss outcomes for babies born between 28-32 weeks
-Mortality is <10% and decreases with increasing gestation
-Chance of severe disability - <10%
-Completely normal outcome in 65%
-Chronic lung disease and IVH most common complications
Discuss complications experienced by premature newborns (12)
- Hypoglycemia
- Hypothermia
- Jaundice with increased risk of neurological effects from bilirubin
- Feeding difficult
- Hyaline membrane disease from surfactant deficiency - leads to ARDS
- Chronic lung disease due to pulmonary dysplasia increased risk of lifelong pulmonary dysfunction and abnormal neurodevelopment
- Intraventricular haemorrhage
- Periventricular leukomalacia - 60-90% results in CP
- Necrotising enterocolitis-bacterial invasion of gut wall following ischemia
- Persistent ductus arteriosis leading to congestive heart failure
- Retinopathy
- Intrapartum hypoxia
Discuss peri-viability
-Gestation range (1)
-What are the predictors of outcome in peri-viable babies (9)
- Gestation 23-24+6
- Predictors of outcome
-Gestational age. Make sure accurate. Every day counts
-Birthweight
-Doppler wave form - severe IUGR and abnormal dopplers - poor prognosis
-Fetal gender - boys do worse
-PPROM/Chorio - Short term risk of IUFD or death within 24 hrs
-Suspected or known fetal anomaly
-Multiple pregnancy - increased death rate
-Interventions received
-Site of delivery - Tertiary centre vs other
Discuss peri-viability
-Interventions and timing to modify outcomes (8)
Interventions and timing to modify outcome
1. Antenatal corticosteroids. Give from 22+5 + rescue at 7 days if not delivered and still at high risk of delivery
2. MgSO4 give if planning delivery after 23/40
3. Mode of birth
-Aim VB unless malpresentation and active management
-Need to balance risks and benefits as will be classical CS in 67% of cases
4. Delivery in a centre with NICU - transfer
5. Treat for GBS (Amoxicilin) + Gent (Gram -ve) in active labour
6. Monitoring depends on decision of management type
7. Delayed cord clamping 60s can reduce blood transfusion by 10%
8. Consider tocolysis to enable transfer and steroids if possible.
9. Consider rescue cerclage if Cx <10mm and no PPROM, APH, TPTL or infection
Discuss peri-viable delivery
-Options for management (6)
- Shared decision making with parents as not all will want the same thing. Give local data regarding outcomes
- Care should be individualised depending on clinical situation and family wishes
- Full active intervention including CS on fetal grounds and CTG
- Active intervention - MgSO4, steroids, transfer, Abx but no CS and intermittent ascultation.
- Comfort cares only - no fetal monitoring required can be transferred to tertiary site if desired
- As prognosis changes daily should have ongoing discussions with parents about what we are aiming for
Discuss preterm birth
-Definition (1)
-Incidence (4)
-Classification (3)
-Main causes (3)
- Definition
-Delivery 20-36+6 weeks - Incidence
-5-10% of all births born before 37/40
-1-3% <34/40
-0.5% <28/40
-Leading cause of neonatal mortality and morbidity (65% of all neonatal deaths)
-Australia and NZ 7-8% - Classification
-Extreme preterm birth <28/40
-Very preterm 28-32/40
-Moderate to late preterm 32-37/40 - Main causes
-Iatrogenic - PET/ Severe IUGR 20%
-PPROM 30%
-Spontaneous onset of labour 50%
Discuss risk factors for preterm birth (11)
- Previous PTB (15% after 1 PTB, 45% after 3 PTB)
- Infection - intrauterine and extrauterine
- Cervical: Previous surgery / mechanical dilation / trauma
- Congenital anomalies or chromosomal anomalies
- Uterine: congenital abnormalities, overdistension, trauma
- Placental causes: PET/Abruption / insufficiency
- Low pre-pregnancy weight
- Short pregnancy interval
- Extremes of age
- Substance use/abuse
- 66% of women with PTB don’t have risk factors
Discuss investigations for threatened preterm labour (4)
- Check fetal wellbeing - CTG + USS
- Check for infection - MSU / Swabs
- FFN
- >50ng/mL = diagnose PTL - TVUSS for Cx length - offer as first line
>15mm unlikely PTL
<15mm diagnose PTL
Discuss tocolytics for TPTL
-When to use (2)
-Contraindications (4)
-Types (4)
- When to use
-To delay birth and allow administration of steroids
-To delay birth and allow for in-utero transfer - Contra-indications
-APH
-Cx >4cm dilated
-Intra-uterine infection
-PPROM - Types
Firstline: Nifedipine (CCB)
-Reduces number of women giving birth within 7 days if <34/40
-Reduced RDS, NEC, IVH, Jaundice
Second line: IV Atosiban B-mimetic
Avoid: IV salbutamol - betamimetic
-Many side effects and same efficacy as IV Atosiban
Avoid: Indomethacin: NSAIDS
-Significant impact to multiple fetal organ systems
Discuss antibiotic use in preterm labour
-Recommendations from ORACLE II (2)
-GBS prophylaxis recommendation (1)
-Treatment of BV (2)
- Recommendations from ORACLE II
-Worse neonatal outcomes for O2 requirement and NEC in intervention arm (Erythromycin/Augmentin/Both)
-Do not give routine antibiotics in PTL - GBS prophylaxis
-NZ guidelines consider PTL as RF for GBS so give penicillin - BV
-Treatment of BV in pregnancy is not associated with decreased risk of PPROM or PTL
-Treat those with other risk factors for PTB
Discuss mode of delivery in preterm labour
-General points (1)
-Vaginal delivery (2)
-CS (4)
-Instrumental (3)
-Recommendations for FBS and FSE use (2)
- General points
-MOD should be guided by gestation, presentation, fetal condition, maternal wellbeing - Vaginal delivery
-If cephalic
-Can consider if breech but be prepared for head entrapment - CS
-If VB contraindicated
-For fetal wellbeing if distress
-For rapid delivery if maternal health compromised
-Incision depends on gestation and placental location - Instrumental
-Ventouse contra-indicated <34/40
-Forceps relatively contra-indicated <34/40. Only do if certain of fetal head position.
-Rotational forceps delivery contraindicated - FSE and FBS use
-Avoid <34/40 for FBS
-Avoid FSE in <34/40 unless very difficult to monitor and benefits outweigh risks
Discuss PPROM
-Incidence (2)
-Risk factors (6)
- Incidence
-2-3% of pregnancies
-In 40% of all Preterm births - Risk factors
-Previous PPROM (OR 8.7)
-Shorter inter pregnancy interval
-Urogenital infection
-Placental abruption
-Over distension - polyhydramnios, multiple pregnancy
-Smoking or drug use
Discuss investigations for PPROM (6)
- Assess fetal well being - CTG
- USS for presentation, fluid volumes. It’s role in Dx of PPROM is unclear
- Assess for infection
-Clinical assessment
-Swabs, MSU, Bloods
-CRP sens 69% spec 77% for histological chorio - Do sterile speculum and assessment for pooling liquor. If no liquor sen for Amnisure or actim
- Amnisure
-measures placental alpha micro globulin-1
-Sens 94-98%, Spec 87-100%
-High false positive rate
-Not impacted by small amount of semen or blood - Actim PROM
-Measures insulin like growth factor binding protein 1.
-Spec 98% Sens 93%
-Not impacted by small amount of semen, urine, infection or blood
Discuss PPROM
-Outcomes (3)
-Fetal risks at <34/40 (1)
-Fetal risks at >34/40 (1)
-Risks of lung hypoplasia if PPROM at 21/40 vs 29/40 (2)
- Outcomes
-Most likely outcome is labour
-80% born within 7 days
-25% deliver within 48hrs - Fetal risks at <34/40
-Risks are due to prematurity - RDS, NEC, IVH, PVL, CP - Fetal risks at >34/40
-Risks are due to infection - Risk of lung hypoplasia
-21/40 90% risk
-29/40 10% risk
Discuss management of PPROM (10)
- Admit to ward
- Q4H Obs - monitor for signs and sx of infection
- TDS CTG
- Twice weekly bloods
- Steroids if <34+6 (Not associated with increase risk of sepsis)
- Tocolysis contraindicated
-Worse apgars, more ventilation, increased chorioamnionitis - Antibiotics
- erythromycin 250-500mg PO Q6H 10/7 or until established labour. Prolongs pregnancy, reduces surfactant requirement
-Consider 48hrs IV ampicillin until GBS status known
-Avoid augmentin as increase in NEC (RR 4) - MgSO4
-If <30 weeks and delivery expected or planned - Amnioinfusion
-Not recommended routinely as poor data
-Associated with decreased: hypoplasia; neonatal sepsis; neonatal death; reduced puerperal sepsis - Meet with neonatologist
Discuss expectant management for PPROM
-Criteria (7)
-Monitoring (4)
- Criteria
-Cephalic presentation and engaged
-Clear liquor. No PVB
-Normal FM
-No signs of infection
-Not had digital VE
-Able to attend for monitoring
-Lives within 40mins of hospital - Monitoring
-2 x daily temperatures
-1-2 x weekly clinical review - bloods, CTG, vitals
-1 x weekly USS for LV
-GS fortnightly
Discuss delivery with PPROM
-Timing (1)
-Mode (2)
-Abx use (1)
- Timing
-If not in spontaneous labour then IOL at 37/40 - Mode of delivery
-Aim VB if cephalic, no fetal distress and delivery not required imminently
-If delivery before 26/40 with oligo outcomes are poor so palliative approach to delivery should be discussed - Antibiotic use
-Switch from erythromycin to GBS prophylaxis once in established labour
Discuss cervical length monitoring
-Should low risk women be screening (8)
-How should screening be done (2)
-RANZCOG statement on screening low risk women
- Requirements for screening and Cx length
-Important condition? PTB affects 8% of pregnancies
-Recognised latent phase - PTB associated with shortened cx
-Natural Hx of disease known - Multifactorial and not entirely understood
-Is there an acceptable treatment - cerclage and progesterone both effective in cx <25mm in low risk women
-Is there an accurate test - TVUSS has PPV of 20-30%
-Is the test acceptable - TVUSS acceptable to most.
-Are there facilities for diagnosis - May be an issue.
-Is it cost effective - some evidence suggests yes - How should screening be done
-TAUSS at 20 weeks scan.
-If <35mm for TVUSS. If <25mm for treatment - RANZCOG statement
-Supports universal cervical length screening
-Do at mid trimester scan by TAUSS with TVUSS if Cx <35mm or unable to totally visualise length
-First line treatment should be progesterone from 16- 24 until 34-36 weeks
Discuss the measurement technique for USS of cervical length
-TAUSS (2)
-TVUSS (5)
- TAUSS
-Scan as first line
-Make sure bladder is full - TVUSS
-Most accurate
-Empty bladder
-Probe in anterior fornix to avoid pressure on cervix
-Take shortest of 3 measurements over 5 mins
-Funnelling and shortening with fundal pressure are associated with PTB but don’t add to the predictive modelling
Discuss average cervical lengths
-Average length at 20/40 in a singleton
-10th centile length and RR for PTB
-5th centile length and RR for PTB
-2.5th centile length and RR for PTB
- Average length - 40mm
- 10% - 30mm RR 4
- 5% 27mm RR 5.4
- 2.5% 22mm RR 6.3
Discuss cerclage as treatment for shortened cervix
-Who should be offered treatment (9) - NICE guidelines 2022
- Women with a hx of 3 or more previous PTB should be offered a Hx indicated cervical cerclage
- Women with a Hx of mid-trimester loss, PTB may be offered serial sonographic surveillance 16-24 weeks (B grade evidence)
- Screened women should be offered a cerclage if their cx is <25mm on TVUSS before 24/40. Funnelling doesn’t count
- Women with no risk factors for PTB who have an incidental short cervix (<25mm) should NOT be offered a cerclage
- In women who have had a previously failed cervical cerclage abdo cerclage can be considered
- Cerclage is not indicated in women with multiple pregnancies
- In women with risk factors for PTB - uterine anomilies, LLETZ, multiple D&C the role of USS or Hx indicated cerclage is unclear.
- A one off Cx length between 18-22 weeks could be offered to women with cervical trauma
- Cerclage is effective in women with raised BMI
When should women with risk factors for PTB be screened for cervical length (2)
-Screen every 2-4 weeks from 16 weeks to 24 weeks
-Screen weekly if <30mm
Discuss prophylactic vaginal progesterone for prevention of PTB
-Mechanism (3)
-When to give (3)
-Type of progesterone (2)
-Benefits of progesterone
-Safety profile (1)
- Mechanism of action
-Reduces myometrial sensitivity to oxytocin
-Blocks prostaglandin synthesis
-Progesterone insufficiency thought to trigger uterine contractility - When to give
-16-24 weeks until 34-36 weeks
-Asx women with incidental Cx <25mm on TVUSS on mid-trimester scan
-Consider in women with a Hx of previous spontaneous preterm singleton birth - Type of progesterone
-Micronized progesterone 100-200mg PV
-17-OH progesterone IM - Benefits of progesterone
-Reduced risk of PTB by RR 0.66 NNT 11
-Reduced risk of RDS, composite neonatal mortality and morbidity score, low birth weight and admission to NICU - Safety profile
-No evidence of teratogenicity or adverse childhood outcomes at 2 yrs
Discuss cervical cerclage
-Timing of placement and removal (5)
-Risks of placement in non-rescue cerclage(1)
-Efficacy (3)
-Mechanism of action (2)
-Contraindications (7)
- Timing
-From 12-14 weeks for hx indicated (3 or more PTB)
-From 16-24 weeks based on USS findings
-Remove 36-37 weeks or if PPROM, PTL
-Do Aneuploidy screening before Hx indicated cerclage
-Do anomaly scan before USS indicated cerclage - Risk of placement
-Cervical laceration
-Bladder trauma
-NOT associated with ROM, Chorio, CS, second T loss (If non-emergency)
-Intraoperative complications are rare <1% - Efficacy
-Works similarly to progesterone
-Reduced PTB RR 0.77
-No evidence of cerclage with multiple pregnancy - Mechanism of action
-Provides a degree of structural support to a weak cervix
-More importantly allows maintenance of the cervical plug to stop ascending infection - Contra-indications
-Active PTL
-Clinical evidence of chorioamnionitis
-Continuing PVB
-PPROM
-Evidence of fetal compromise
-Lethal fetal defect
-Fetal death
Discuss cervical cerclage
-Types and method of placement (4)
-Additional treatments at placement (4)
-Types of suture
Shirodkar
-aim to place suture at level of internal os / cardinal ligaments
-Dissect rectum and bladder off cervix to level of internal os
-Suture is placed in a purse string fashion and tied tightly.
-Vaginal epithelia can be closed prior to tightening
-Make sure knot placement is documented and tagged for easy removal
MacDonald
-Cerclage is placed with out dissection first.
-Aim is for the internal os
-Purse string suture
-Tie tight and tag for easy removal with documentation of knot placement
Transabdominal cerclage
-Can be performed preconception or in early pregnancy
-Laparoscopic approach - gold standard - less complications
-Bladder is reflected down and suture is placed at level of internal os
-Birth is by CS and the suture can be left in situ
Occlusion cerclage
-Non absorbable suture placed at level of external os
-Aims to maintain cervical mucous plug
2. Additional treatments
-No need for tocolytics
-No need for antibiotics
-Can place under regional anaesthesia
-Pre and post operative progesterone not indicated
3. Types of suture
-Non-absorbable suture
-No difference between two and one purse string suture
-Addition of an occlusion suture is not routinely recommended
-No difference in braided vs monofilament - C-Stitch trial
Discuss rescue cerclage
-When to do (1)
-Contraindications (3)
-How to perform (6)
-Efficacy (2)
-Risks (5)
- When to do
-In women up to 28 weeks with a dilated cervix and bulging membranes - Contraindications
-Signs of infection
-Active bleeding
-Uterine contractions - How to perform
-Trendelenberg
-Broad spectrum abx
-Consider tocolysis
-Reduce prolapsed membranes with smooth surface device - IDC balloon
-Use MacDonald’s technique
-FU in two weeks post procedure - Efficacy
-On average increases duration of pregnancy by 34 days
-Membranes past the external os and dilation >4cm have increased risk of cerclage failure - Risks
-ROM, Chorioamnionitis, Bleeding, cervical trauma, bladder trauma
Discuss steroid administration
-Types of courses (2)
-Indications (6)
- Types of courses
-Betamethasone 11.4mg IM 2 doses 24hrs apart
Dexamethasone 24mg IM in divided doses completed in 24-40hrs - Indications
-Any woman at risk of PTD up to 34+6
-When delivery is expected or planned within 7 days even if within 24hrs
-Any woman undergoing an elective CS >34+6 where there is known lung immaturity.
-NICE guidelines suggest a discussion from 37-38+6 regarding steroids for elective CS. (Not enough evidence. May have harms for neurodevlopment and hypoglycemia)
-NZ/AUS guidelines - not enough evidence for >37 term steroids
-35-36+6 discuss with fam (likely to reduce resp support requirement)
-No evidence to give untargeted steroids i.e. not about to deliver
-Treat multiple pregnancies like singletons
What are the impacts (including RR) of antenatal steroids
-Benefits (7)
-No effect (3)
-Risks (4)
- Benefits
-Reduction in neonatal death RR 0.72
-Reduction in respiratory distress RR 0.66
-Reduction in intraventricular haemorrhage RR 0.55
-Reduction in NEC RR 0.5
-Reduction in need for mechanical ventilation RR 0.68
-Reduction in systemic infection in the first 48hrs of life RR 0.6
-Reduction in developmental delay RR 0.51 - No impact
-No impact on birth weight
-No impact on chronic lung disease
-No impact on chorioamnionitis - Risks
-35-36+6 - increase in psychiatric and behavioural dx if born at term
-Risk of hypoglycemia at birth
-Reduction in BW with multiple administrations (dose response)
-Impact on educational achievement if given 37-39 weeks
Discuss steroids
-Optimum treatment to delivery interval (3)
- Optimum treatment to delivery interval
When birth is expected / planned in next 48hrs
>24hrs after second dose and within 7 days
No confirmed benefit if delivery after 7 days
Still some benefit in those delivered before 24 hrs of first dose
Discuss repeat doses of steroids
-When to give (1)
-Maximum dose (1)
-Fetal impact (3)
-Regimens (2)
- When to give
-If ongoing risk of PTB 7 days after single course - Maximum dose
-Can give up to 3 rescue doses 1 week apart until 32+6 - Fetal
-Reduced mechanical ventilation / surfactant requirement
-No reduction in serious morbidity
-Reduced BW from repeat doses - Regimens
-Betamethasome 11.4mg IM in single dose
-Bethamethasone 11.4mg IM in 2 doses 24 hrs apart (no further repeat doses after this)
Discuss Term PROM
-Incidence
-RANZCOG recommendations (6)
- Incidence of PROM >37/40
-1:12 pregnancies
-8%
-70% of women will commence labour within 24hrs - RANZCOG recommendations
-Confirm diagnosis with Hx +/- sterile speculum +/- amnisure
-If GBS positive / high risk treat and induce without delay
-IOL within 24hrs as possible for women with PROM
-Can use prostaglandin to prepare the cervix if not ready.
-In women who are GBS negative and have IOL planned within 24hrs antibiotics do not need to be part of routine care
-In women who want expectant management consider antibiotics
Discuss expectant management vs IOL for PROM (4)
- Reduced chorioamnionitis (RR 0.5) in IOL group
- Reduced CS rate in IOL group (RR 0.84)
- Reduced onset of neonatal sepsis (RR 0.73)
- Reduced need for neonatal antibiotics (RR 0.61)
- Reduced NICU admissions (RR 0.75)
Discuss the PPROMPT trial
-Aim
-Study design (5)
-Primary outcome (1)
-Secondary outcomes (7)
- Aim
To determine whether immediate delivery in singletons with PPROM close to term reduces neonatal infection without increasing other morbidity - Study design
-Multi centre RCT at 65 centres in 11 countries
-Included singleton pregnancies with PPROM 34-36+6
-2 groups EM or Immediate IOL
-Both groups managed with antibiotics
-Included GBS + women. Excluded if chorio, mec - Primary outcome
-Neonatal infection - Secondary outcomes
-Composite neonatal morbidity / mortality score
-NICU admission duration
-Respiratory distress and need for mechanical ventilation
-MOD
-Maternal fever, PP antibiotics
-Hemorrhage (antepartum / intrapartum)
Discuss the results from the PPROMPT Trial
-Number included in the study (1)
-Results from primary outcome (1)
-Results from secondary outcome (7)
-Recommendations (2)
- Number included 1800 ~ 900 per group
- Results from primary outcome
-No difference in neonatal sepsis between groups RR 0.8 2% IOL 3% EM - Results from secondary outcomes
-No difference in composite neonatal mortality and morbidity score between groups RR 1.2
-Increased respiratory distress in the intervention group RR 1.6 8% vs 5% (SS) and increased mechanical ventilation RR1.4 (NS)
-Increased admission in NICU for intervention group (SS)
-Increased risk of maternal fever (SS), PP antibiotic use in EM group (NS)
-Increase in hospital stay in EM group (SS)
-Increased risk of haemorrhage in EM group (SS)
-Decreased risk of CS in EM group RR1.4 - Recommendations
-EM is preferred over Immediate IOL for PPROM between 34 to 36+6
-EM is OK for women with GBS (RANZCOG support immediate IOL. PPROMEXIL trial found should do IOL in GBS)
Discuss the ACTORDS trial
-Aim (1)
-Study design
-Primary outcome (4)
- Aim
To assess whether repeat doses of steroids for women at risk of PTB would reduce neonatal morbidity without harm - Study design
-RCT 23 hospitals NZ and Australia
-Women under 32/40
-Steroids every 7 days until delivered if <32/40 if still at risk of PTB
-Placebo / blinded - Primary outcomes
-Occurance of respiratory distress
-Severity of respiratory distress
-Need for mechanical ventilation
Discuss the ACTORDS trial
-Number included in the study (1)
-Results of the primary outcome (5)
-2 yr follow-up results
- Number included in the study
n = 980 - Primary outcome results
-Respiratory distress in steroid group 33% cf 41% in control group RR 0.82 (SS) NNT 14
-Severe lung disease in steroid group 12% cf 20% in control group RR 0.6 (SS) NNT 14
-Less need for O2 and less duration of mechanical ventilation in treatment group (SS)
-No difference in neonatal weight or HC between groups
-No difference between groups for other neonatal morbidity (NEC, IVH, Periventriuclar leucomalacia, infection) - 2 yr follow-up results
-No difference in body size, health service use, respiratory morbidity, behaviour scores
-Increased risk of child requiring attention assessment in treatment group (SS)
Discuss the antenatal betamethasone for women at risk of late PTD trial
-Aim (1)
-Study design (2)
-Primary outcomes (3)
-Secondary outcomes (3)
- Aim
To determine if betamethasone administered to women 34-36+5/40 at risk of PTB reduces neonatal morbidity - Study design
-Multicentre RCT
-2 x IM betamethasone vs placebo - Primary outcome
-Composite measure of respiratory treatment requirements
-Neonatal death within 72hrs
-Still birth - Secondary outcomes
-Neonatal hypoglycemia
-NEC, IVH, sepsis
-Maternal infection
Discuss the antenatal betamethasone for women at risk of late PTD trial
-Number in study (1)
-Results (5)
- Number in study
-2800 - Results
-Less respiratory issues in treatment group compared to placebo 11% vs 14% RR 0.8 (SS) NNT 35
-Less severe respiratory complications in treatment group 8% vs 12% RR 0.8 (SS) NNT 25
-Less resus and surfactant use in treatment group
-Higher neonatal hypoglycemia in the treatment group 24% vs 15% RR 1.6 (SS)
-No other secondary outcomes met significance
Discuss the ORACLE trial
-Aim (2)
-Study design (3)
-Primary outcomes (1)
-Secondary outcomes
- Aim
-To investigate the health benefits for the neonate of antibiotic use in PPROM
-To investigate the best antibiotic - Study design
-Double blinded
-Included those with PPROM (<37/40) but no signs of infection
-RCT with 4 arms (Erythromycin, Augmentin, Erythromycin + Augmentin, placebo)
-Regimen given for 10 days or until delivery - Primary outcomes
-Composite measure of neonatal death and severe morbidity - Secondary outcomes
-Prolongation of pregnancy
-NICU admission
-Neonatal morbidity
-Neonatal clinical infection
Discuss the ORACLE trial
-Number included in study
-Primary outcome results (2)
-Secondary outcome results (7)
- Number included in the study
-4800 - Primary outcome results
-Erythromycin had reduced composite outcome events cf placebo 13% vs 15% (NS) was in singletons 11% vs 14% (SS)
-No difference in the erythromycin + Augmentin or Augmentin alone group and placebo for composite outcome - Results of secondary outcomes
-Erythromycin prolonged pregnancy (SS)
-Augmentin prolonged pregnancy (SS)
-Erythromycin had reductions in need for surfactant, and oxygen dependance (SS)
-Erythromycin less neonatal infections (SS)
-Erythromycin reduced cerebral abnormalities
-Augmentin and Augmentin + erythro groups had SS increase in NEC (4 times higher)
-Use of any Abx SS associated with reduced intrauterine infection
-Augmentin better at prolonging pregnancy and avoiding intrauterine infection cf erythromycin but caused neonatal harm where erytho doesn’t
Discuss ORACLE Trial - the follow-up
-Aim (1)
-Study design (2)
-Primary outcomes (4)
- Aim
To determine the long term effects of intrautero antibiotics / placebo for PPROM - Study design
-Followed up children in oracle one and assessed health status
-Data from parental completed postal questionnaire - Primary outcomes
-Behavioural difficulties at 7yrs
-Functional outcomes at 7yrs
-Educational ability
-Health data at 7yrs
Discuss ORACLE trial - the follow-up
-Number included (2)
-Results (2)
- Number included
-3300
-FU rate 75% - Results
-No difference between any groups and behavioural outcomes, functional outcomes, health outcomes or educational achievement
-Overall lower educational achievement when compared to normal population
Discuss the trial investigating prophylactic PV progesterone and spontaneous PTB
1. Aim (1)
2. Study design (3)
3. Primary outcome (2)
- Aim
-To evaluate the effect of prophylactic PV progesterone on decreasing PTB in high risk populations - Study design
-RCT
-Double blinded to PV progesterone vs placebo
-Participants between 24 and 34 weeks high risk singleton pregnancies - Primary outcomes
-Frequency of contractions
-PTB rate
Discuss the trial investigating prophylactic PV progesterone and spontaneous PTB
-Number included (1)
-Results (3)
- Number included
-n = 142 70 in each arm - Results
-Less uterine activity in progesterone group 23 vs 54% (SS)
-Less PTB in the progesterone group 14% vs 29% (SS) >50% reduction
-More deliveries <34 weeks in the placebo group 18% vs 3% (SS)
Discuss the trial investigating progesterone and PTB in women with a shortened cervix
-Aim (1)
-Study design (3)
-Primary outcomes (1)
-Secondary outcomes
- Aim
-To determine if progesterone reduces PTB in women with a short cervix in the mid trimester - Study design
-Multi centre RCT double blinded
-Screened for cervical length at mid-trimester
-If cervix less than 15mm randomised to progesterone PV 200mg or placebo from 24-34 weeks - Primary outcome
-PTD - Secondary outcomes
-Fetal or neonatal death
-Major adverse outcomes for neonate
Discuss the trial investigating progesterone and PTB in women with a shortened cervix
-Number included (2)
-Results (6)
- Number included
-250
-24 were twin pregnancies - Results
-Reduced number of deliveries before 34 weeks in progesterone group 19% vs 34% RR 0.56 (SS)
-Less neonatal morbidity in progesterone group (NS)
-No difference in composite neonatal poor outcomes between groups but all favoured progesterone as protective
-Less deliveries before 34 weeks in the progesterone group HR 0.57 (SS)
-No serious adverse events associated with progesterone use
-No difference for twins between groups for PTD
Discuss MgSO4 for women at risk of PTB for fetal neuroprotection study
-Aim
-Study design
-Primary outcomes
- Aim:
-To assess the effects of MgSO4 as fetal neuroprotection when given to women considered at risk of PTB (<37/40) - Study design
-Cochrane meta analysis including RCT - Primary outcomes
-Neurological impairment in childhood
-Major neurological disability
-Fetal or neonatal death
-SAE
Discuss MgSO4 for women at risk of PTB for fetal neuroprotection study
-Number of studies included
-Number of babies included
-Results
- Number of studies included
-5 - Number of babies included
-6000 - Results
-MgSO4 reduced the risk of CP in children born preterm RR 0.7 (SS) NNT 63 risk reduction2%
-MgSO4 reduced gross motor dysfunction RR 0.6 (SS)
-MgSO4 had no impact on mortality at any stage
-MgSO4 had no impact on other neurological abnormalities or impairments
Discuss ORACLE II Trial
-Aim
-Method
-Outcomes
- Aim
-To evaluate the effect of antibiotics on TPTL on women with intact membranes and no signs of infection - Method
-4 arm RCT or erythro / augmentin/ Both / Placebo - Primary outcome
-composite measure of neonatal death, chronic lung disease, major CP
Discuss ORACLE II Trial
-Number included (1)
-Main findings (2)
- Number included
-6000 - Main findings
-64% of women delivered after 48hrs
-None of the arms were associated with reduction in the composite outcome
-Antibiotic use was associated with lower maternal infection
Discuss cochrane review findings for cerclage (1) and progesterone (2) for PTL
- Cerclage
-Cervical cerclage for women with hx of PTB or with short cervix reduces PTB before 37/40 RR 0.77 SS - Progesterone
-Progesterone given to women with a past hx of PTB reduces PTD <37/40 RR 0.5 (SS)
-Progesterone given to women with a short cervix <25mm reduces PTB <34/40 (RR 0.64 SS)
