Preterm birth Flashcards

1
Q

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)

A
  1. 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
  2. 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
  3. Why should it be used
    -Helps predict likelihood of preterm delivery
    -Can guide toco and steroid use
    -Can guide transfer from smaller centres
  4. 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%
  5. Cause of false positives
    -semen, blood, digital cervical examination, lubricant
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2
Q

Discuss actim partus test for PTL
-What it detects
-How results are given
-Sensitivity and specificity

A
  1. What it detects
    -Qualitative test
    -Detects insulin-like growth factor binging protein one
  2. How are results given
    -Negative result shows unlikely to deliver in next 7-14 days
  3. Sensitivity - 77%, specificity 81%
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3
Q

Discuss partosure to test for PTL
-What kind of test
-What it detects
-How results are given
-Sensitivity and specificity

A
  1. What kind of test
    -Qualitative
  2. What it detects
    -Placental alpha microglobulin (PAMG-1)
  3. How results are given
    -Negative result shows reduced likelihood of delivery within 7 days
  4. Sensitivity 83% specificity 95%
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4
Q

Discuss magnesium sulphate for neuroprotection
-Dose (1)
-Monitoring (6)
-Indications (2)
-Contra-indications (3)
-Timing (5)

A
  1. Dose
    -4g bolus over 20-25mins then 1g per hr for 24 hrs or until baby is born whichever comes first.
  2. Monitoring
    -Do at least Q4H
    -HR, BP, RR, Deep tendon reflexes, UO
  3. 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
  4. Contra-indications
    -Myasthenia gravis
    -Women with myocardial compromise / conduction defects
    -Caution with impaired renal function
  5. 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
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5
Q

Discuss the evidence for magnesium sulphate as a neuroprotection

A

-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

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6
Q

Discuss mechanism of action for MgSO4 to achieve neuroprotection (5)

A

-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

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7
Q

Discuss neonatal outcomes of preterm delivery
-Percentage cause of neonatal death (1)
-Major causes of mortality (3)
-Influencing factors determining outcome (5)

A
  1. Percentage of neonatal deaths attributed to PTD
    -50%
  2. Major causes of mortality
    -NEC, RDS, IVH
  3. Influencing factors
    -Gestation
    -Gender - boys do worse
    -Growth restriction
    -Infected environment
    -Steroid cover
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8
Q

What are the rates of mortality and severe morbidity for babies born at 22,23,24,25,26 weeks

A
  1. Babies born at 22 week
    -7 die
    -1 in 3 has severe disability
  2. Babies born at 23 weeks
    -6 die
    -1 in 4 babies have severe disability
  3. Babies born at 24 weeks
    -4 babies die
    -1 in 7 babies have severe disability
  4. Babies born at 25 weeks
    -3 babies dies
    -1 in 7 have severe disability
  5. Babies born at 26 weeks
    -2 in 10 babies die
    -1 in 10 babies have severe disability
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9
Q

Discuss outcomes for babies born between 28-32 weeks

A

-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

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10
Q

Discuss complications experienced by premature newborns (12)

A
  1. Hypoglycemia
  2. Hypothermia
  3. Jaundice with increased risk of neurological effects from bilirubin
  4. Feeding difficult
  5. Hyaline membrane disease from surfactant deficiency - leads to ARDS
  6. Chronic lung disease due to pulmonary dysplasia increased risk of lifelong pulmonary dysfunction and abnormal neurodevelopment
  7. Intraventricular haemorrhage
  8. Periventricular leukomalacia - 60-90% results in CP
  9. Necrotising enterocolitis-bacterial invasion of gut wall following ischemia
  10. Persistent ductus arteriosis leading to congestive heart failure
  11. Retinopathy
  12. Intrapartum hypoxia
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11
Q

Discuss peri-viability
-Gestation range (1)
-What are the predictors of outcome in peri-viable babies (9)

A
  1. Gestation 23-24+6
  2. 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
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12
Q

Discuss peri-viability
-Interventions and timing to modify outcomes (8)

A

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

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13
Q

Discuss peri-viable delivery
-Options for management (6)

A
  1. Shared decision making with parents as not all will want the same thing. Give local data regarding outcomes
  2. Care should be individualised depending on clinical situation and family wishes
  3. Full active intervention including CS on fetal grounds and CTG
  4. Active intervention - MgSO4, steroids, transfer, Abx but no CS and intermittent ascultation.
  5. Comfort cares only - no fetal monitoring required can be transferred to tertiary site if desired
  6. As prognosis changes daily should have ongoing discussions with parents about what we are aiming for
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14
Q

Discuss preterm birth
-Definition (1)
-Incidence (4)
-Classification (3)
-Main causes (3)

A
  1. Definition
    -Delivery 20-36+6 weeks
  2. 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%
  3. Classification
    -Extreme preterm birth <28/40
    -Very preterm 28-32/40
    -Moderate to late preterm 32-37/40
  4. Main causes
    -Iatrogenic - PET/ Severe IUGR 20%
    -PPROM 30%
    -Spontaneous onset of labour 50%
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15
Q

Discuss risk factors for preterm birth (11)

A
  1. Previous PTB (15% after 1 PTB, 45% after 3 PTB)
  2. Infection - intrauterine and extrauterine
  3. Cervical: Previous surgery / mechanical dilation / trauma
  4. Congenital anomalies or chromosomal anomalies
  5. Uterine: congenital abnormalities, overdistension, trauma
  6. Placental causes: PET/Abruption / insufficiency
  7. Low pre-pregnancy weight
  8. Short pregnancy interval
  9. Extremes of age
  10. Substance use/abuse
  11. 66% of women with PTB don’t have risk factors
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16
Q

Discuss investigations for threatened preterm labour (4)

A
  1. Check fetal wellbeing - CTG + USS
  2. Check for infection - MSU / Swabs
  3. FFN
    - >50ng/mL = diagnose PTL
  4. TVUSS for Cx length - offer as first line
    >15mm unlikely PTL
    <15mm diagnose PTL
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17
Q

Discuss tocolytics for TPTL
-When to use (2)
-Contraindications (4)
-Types (4)

A
  1. When to use
    -To delay birth and allow administration of steroids
    -To delay birth and allow for in-utero transfer
  2. Contra-indications
    -APH
    -Cx >4cm dilated
    -Intra-uterine infection
    -PPROM
  3. 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
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18
Q

Discuss antibiotic use in preterm labour
-Recommendations from ORACLE II (2)
-GBS prophylaxis recommendation (1)
-Treatment of BV (2)

A
  1. 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
  2. GBS prophylaxis
    -NZ guidelines consider PTL as RF for GBS so give penicillin
  3. BV
    -Treatment of BV in pregnancy is not associated with decreased risk of PPROM or PTL
    -Treat those with other risk factors for PTB
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19
Q

Discuss mode of delivery in preterm labour
-General points (1)
-Vaginal delivery (2)
-CS (4)
-Instrumental (3)
-Recommendations for FBS and FSE use (2)

A
  1. General points
    -MOD should be guided by gestation, presentation, fetal condition, maternal wellbeing
  2. Vaginal delivery
    -If cephalic
    -Can consider if breech but be prepared for head entrapment
  3. CS
    -If VB contraindicated
    -For fetal wellbeing if distress
    -For rapid delivery if maternal health compromised
    -Incision depends on gestation and placental location
  4. Instrumental
    -Ventouse contra-indicated <34/40
    -Forceps relatively contra-indicated <34/40. Only do if certain of fetal head position.
    -Rotational forceps delivery contraindicated
  5. FSE and FBS use
    -Avoid <34/40 for FBS
    -Avoid FSE in <34/40 unless very difficult to monitor and benefits outweigh risks
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20
Q

Discuss PPROM
-Incidence (2)
-Risk factors (6)

A
  1. Incidence
    -2-3% of pregnancies
    -In 40% of all Preterm births
  2. Risk factors
    -Previous PPROM (OR 8.7)
    -Shorter inter pregnancy interval
    -Urogenital infection
    -Placental abruption
    -Over distension - polyhydramnios, multiple pregnancy
    -Smoking or drug use
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21
Q

Discuss investigations for PPROM (6)

A
  1. Assess fetal well being - CTG
  2. USS for presentation, fluid volumes. It’s role in Dx of PPROM is unclear
  3. Assess for infection
    -Clinical assessment
    -Swabs, MSU, Bloods
    -CRP sens 69% spec 77% for histological chorio
  4. Do sterile speculum and assessment for pooling liquor. If no liquor sen for Amnisure or actim
  5. 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
  6. 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
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22
Q

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)

A
  1. Outcomes
    -Most likely outcome is labour
    -80% born within 7 days
    -25% deliver within 48hrs
  2. Fetal risks at <34/40
    -Risks are due to prematurity - RDS, NEC, IVH, PVL, CP
  3. Fetal risks at >34/40
    -Risks are due to infection
  4. Risk of lung hypoplasia
    -21/40 90% risk
    -29/40 10% risk
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23
Q

Discuss management of PPROM (10)

A
  1. Admit to ward
  2. Q4H Obs - monitor for signs and sx of infection
  3. TDS CTG
  4. Twice weekly bloods
  5. Steroids if <34+6 (Not associated with increase risk of sepsis)
  6. Tocolysis contraindicated
    -Worse apgars, more ventilation, increased chorioamnionitis
  7. 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)
  8. MgSO4
    -If <30 weeks and delivery expected or planned
  9. Amnioinfusion
    -Not recommended routinely as poor data
    -Associated with decreased: hypoplasia; neonatal sepsis; neonatal death; reduced puerperal sepsis
  10. Meet with neonatologist
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24
Q

Discuss expectant management for PPROM
-Criteria (7)
-Monitoring (4)

A
  1. 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
  2. Monitoring
    -2 x daily temperatures
    -1-2 x weekly clinical review - bloods, CTG, vitals
    -1 x weekly USS for LV
    -GS fortnightly
25
Q

Discuss delivery with PPROM
-Timing (1)
-Mode (2)
-Abx use (1)

A
  1. Timing
    -If not in spontaneous labour then IOL at 37/40
  2. 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
  3. Antibiotic use
    -Switch from erythromycin to GBS prophylaxis once in established labour
26
Q

Discuss cervical length monitoring
-Should low risk women be screening (8)
-How should screening be done (2)
-RANZCOG statement on screening low risk women

A
  1. 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
  2. How should screening be done
    -TAUSS at 20 weeks scan.
    -If <35mm for TVUSS. If <25mm for treatment
  3. 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
27
Q

Discuss the measurement technique for USS of cervical length
-TAUSS (2)
-TVUSS (5)

A
  1. TAUSS
    -Scan as first line
    -Make sure bladder is full
  2. 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
28
Q

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

A
  1. Average length - 40mm
  2. 10% - 30mm RR 4
  3. 5% 27mm RR 5.4
  4. 2.5% 22mm RR 6.3
29
Q

Discuss cerclage as treatment for shortened cervix
-Who should be offered treatment (9) - NICE guidelines 2022

A
  1. Women with a hx of 3 or more previous PTB should be offered a Hx indicated cervical cerclage
  2. Women with a Hx of mid-trimester loss, PTB may be offered serial sonographic surveillance 16-24 weeks (B grade evidence)
  3. Screened women should be offered a cerclage if their cx is <25mm on TVUSS before 24/40. Funnelling doesn’t count
  4. Women with no risk factors for PTB who have an incidental short cervix (<25mm) should NOT be offered a cerclage
  5. In women who have had a previously failed cervical cerclage abdo cerclage can be considered
  6. Cerclage is not indicated in women with multiple pregnancies
  7. In women with risk factors for PTB - uterine anomilies, LLETZ, multiple D&C the role of USS or Hx indicated cerclage is unclear.
  8. A one off Cx length between 18-22 weeks could be offered to women with cervical trauma
  9. Cerclage is effective in women with raised BMI
30
Q

When should women with risk factors for PTB be screened for cervical length (2)

A

-Screen every 2-4 weeks from 16 weeks to 24 weeks
-Screen weekly if <30mm

31
Q

Discuss prophylactic vaginal progesterone for prevention of PTB
-Mechanism (3)
-When to give (3)
-Type of progesterone (2)
-Benefits of progesterone
-Safety profile (1)

A
  1. Mechanism of action
    -Reduces myometrial sensitivity to oxytocin
    -Blocks prostaglandin synthesis
    -Progesterone insufficiency thought to trigger uterine contractility
  2. 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
  3. Type of progesterone
    -Micronized progesterone 100-200mg PV
    -17-OH progesterone IM
  4. 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
  5. Safety profile
    -No evidence of teratogenicity or adverse childhood outcomes at 2 yrs
32
Q

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)

A
  1. 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
  2. Risk of placement
    -Cervical laceration
    -Bladder trauma
    -NOT associated with ROM, Chorio, CS, second T loss (If non-emergency)
    -Intraoperative complications are rare <1%
  3. Efficacy
    -Works similarly to progesterone
    -Reduced PTB RR 0.77
    -No evidence of cerclage with multiple pregnancy
  4. 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
  5. Contra-indications
    -Active PTL
    -Clinical evidence of chorioamnionitis
    -Continuing PVB
    -PPROM
    -Evidence of fetal compromise
    -Lethal fetal defect
    -Fetal death
33
Q

Discuss cervical cerclage
-Types and method of placement (4)
-Additional treatments at placement (4)
-Types of suture

A

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

34
Q

Discuss rescue cerclage
-When to do (1)
-Contraindications (3)
-How to perform (6)
-Efficacy (2)
-Risks (5)

A
  1. When to do
    -In women up to 28 weeks with a dilated cervix and bulging membranes
  2. Contraindications
    -Signs of infection
    -Active bleeding
    -Uterine contractions
  3. 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
  4. Efficacy
    -On average increases duration of pregnancy by 34 days
    -Membranes past the external os and dilation >4cm have increased risk of cerclage failure
  5. Risks
    -ROM, Chorioamnionitis, Bleeding, cervical trauma, bladder trauma
35
Q

Discuss steroid administration
-Types of courses (2)
-Indications (6)

A
  1. Types of courses
    -Betamethasone 11.4mg IM 2 doses 24hrs apart
    Dexamethasone 24mg IM in divided doses completed in 24-40hrs
  2. 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
36
Q

What are the impacts (including RR) of antenatal steroids
-Benefits (7)
-No effect (3)
-Risks (4)

A
  1. 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
  2. No impact
    -No impact on birth weight
    -No impact on chronic lung disease
    -No impact on chorioamnionitis
  3. 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
37
Q

Discuss steroids
-Optimum treatment to delivery interval (3)

A
  1. 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
38
Q

Discuss repeat doses of steroids
-When to give (1)
-Maximum dose (1)
-Fetal impact (3)
-Regimens (2)

A
  1. When to give
    -If ongoing risk of PTB 7 days after single course
  2. Maximum dose
    -Can give up to 3 rescue doses 1 week apart until 32+6
  3. Fetal
    -Reduced mechanical ventilation / surfactant requirement
    -No reduction in serious morbidity
    -Reduced BW from repeat doses
  4. Regimens
    -Betamethasome 11.4mg IM in single dose
    -Bethamethasone 11.4mg IM in 2 doses 24 hrs apart (no further repeat doses after this)
39
Q

Discuss Term PROM
-Incidence
-RANZCOG recommendations (6)

A
  1. Incidence of PROM >37/40
    -1:12 pregnancies
    -8%
    -70% of women will commence labour within 24hrs
  2. 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
40
Q

Discuss expectant management vs IOL for PROM (4)

A
  1. Reduced chorioamnionitis (RR 0.5) in IOL group
  2. Reduced CS rate in IOL group (RR 0.84)
  3. Reduced onset of neonatal sepsis (RR 0.73)
  4. Reduced need for neonatal antibiotics (RR 0.61)
  5. Reduced NICU admissions (RR 0.75)
41
Q

Discuss the PPROMPT trial
-Aim
-Study design (5)
-Primary outcome (1)
-Secondary outcomes (7)

A
  1. Aim
    To determine whether immediate delivery in singletons with PPROM close to term reduces neonatal infection without increasing other morbidity
  2. 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
  3. Primary outcome
    -Neonatal infection
  4. 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)
42
Q

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)

A
  1. Number included 1800 ~ 900 per group
  2. Results from primary outcome
    -No difference in neonatal sepsis between groups RR 0.8 2% IOL 3% EM
  3. 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
  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)
43
Q

Discuss the ACTORDS trial
-Aim (1)
-Study design
-Primary outcome (4)

A
  1. Aim
    To assess whether repeat doses of steroids for women at risk of PTB would reduce neonatal morbidity without harm
  2. 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
  3. Primary outcomes
    -Occurance of respiratory distress
    -Severity of respiratory distress
    -Need for mechanical ventilation
44
Q

Discuss the ACTORDS trial
-Number included in the study (1)
-Results of the primary outcome (5)
-2 yr follow-up results

A
  1. Number included in the study
    n = 980
  2. 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)
  3. 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)
45
Q

Discuss the antenatal betamethasone for women at risk of late PTD trial
-Aim (1)
-Study design (2)
-Primary outcomes (3)
-Secondary outcomes (3)

A
  1. Aim
    To determine if betamethasone administered to women 34-36+5/40 at risk of PTB reduces neonatal morbidity
  2. Study design
    -Multicentre RCT
    -2 x IM betamethasone vs placebo
  3. Primary outcome
    -Composite measure of respiratory treatment requirements
    -Neonatal death within 72hrs
    -Still birth
  4. Secondary outcomes
    -Neonatal hypoglycemia
    -NEC, IVH, sepsis
    -Maternal infection
46
Q

Discuss the antenatal betamethasone for women at risk of late PTD trial
-Number in study (1)
-Results (5)

A
  1. Number in study
    -2800
  2. 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
47
Q

Discuss the ORACLE trial
-Aim (2)
-Study design (3)
-Primary outcomes (1)
-Secondary outcomes

A
  1. Aim
    -To investigate the health benefits for the neonate of antibiotic use in PPROM
    -To investigate the best antibiotic
  2. 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
  3. Primary outcomes
    -Composite measure of neonatal death and severe morbidity
  4. Secondary outcomes
    -Prolongation of pregnancy
    -NICU admission
    -Neonatal morbidity
    -Neonatal clinical infection
48
Q

Discuss the ORACLE trial
-Number included in study
-Primary outcome results (2)
-Secondary outcome results (7)

A
  1. Number included in the study
    -4800
  2. 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
  3. 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
49
Q

Discuss ORACLE Trial - the follow-up
-Aim (1)
-Study design (2)
-Primary outcomes (4)

A
  1. Aim
    To determine the long term effects of intrautero antibiotics / placebo for PPROM
  2. Study design
    -Followed up children in oracle one and assessed health status
    -Data from parental completed postal questionnaire
  3. Primary outcomes
    -Behavioural difficulties at 7yrs
    -Functional outcomes at 7yrs
    -Educational ability
    -Health data at 7yrs
50
Q

Discuss ORACLE trial - the follow-up
-Number included (2)
-Results (2)

A
  1. Number included
    -3300
    -FU rate 75%
  2. 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
51
Q

Discuss the trial investigating prophylactic PV progesterone and spontaneous PTB
1. Aim (1)
2. Study design (3)
3. Primary outcome (2)

A
  1. Aim
    -To evaluate the effect of prophylactic PV progesterone on decreasing PTB in high risk populations
  2. Study design
    -RCT
    -Double blinded to PV progesterone vs placebo
    -Participants between 24 and 34 weeks high risk singleton pregnancies
  3. Primary outcomes
    -Frequency of contractions
    -PTB rate
52
Q

Discuss the trial investigating prophylactic PV progesterone and spontaneous PTB
-Number included (1)
-Results (3)

A
  1. Number included
    -n = 142 70 in each arm
  2. 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)
53
Q

Discuss the trial investigating progesterone and PTB in women with a shortened cervix
-Aim (1)
-Study design (3)
-Primary outcomes (1)
-Secondary outcomes

A
  1. Aim
    -To determine if progesterone reduces PTB in women with a short cervix in the mid trimester
  2. 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
  3. Primary outcome
    -PTD
  4. Secondary outcomes
    -Fetal or neonatal death
    -Major adverse outcomes for neonate
54
Q

Discuss the trial investigating progesterone and PTB in women with a shortened cervix
-Number included (2)
-Results (6)

A
  1. Number included
    -250
    -24 were twin pregnancies
  2. 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
55
Q

Discuss MgSO4 for women at risk of PTB for fetal neuroprotection study
-Aim
-Study design
-Primary outcomes

A
  1. Aim:
    -To assess the effects of MgSO4 as fetal neuroprotection when given to women considered at risk of PTB (<37/40)
  2. Study design
    -Cochrane meta analysis including RCT
  3. Primary outcomes
    -Neurological impairment in childhood
    -Major neurological disability
    -Fetal or neonatal death
    -SAE
56
Q

Discuss MgSO4 for women at risk of PTB for fetal neuroprotection study
-Number of studies included
-Number of babies included
-Results

A
  1. Number of studies included
    -5
  2. Number of babies included
    -6000
  3. 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
57
Q

Discuss ORACLE II Trial
-Aim
-Method
-Outcomes

A
  1. Aim
    -To evaluate the effect of antibiotics on TPTL on women with intact membranes and no signs of infection
  2. Method
    -4 arm RCT or erythro / augmentin/ Both / Placebo
  3. Primary outcome
    -composite measure of neonatal death, chronic lung disease, major CP
58
Q

Discuss ORACLE II Trial
-Number included (1)
-Main findings (2)

A
  1. Number included
    -6000
  2. 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
59
Q

Discuss cochrane review findings for cerclage (1) and progesterone (2) for PTL

A
  1. Cerclage
    -Cervical cerclage for women with hx of PTB or with short cervix reduces PTB before 37/40 RR 0.77 SS
  2. 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)