Obstetrics Flashcards
What was the aim of the TRUFFLE trial? (Lancet 2015)
To assess whether changes in the fetal ductus venosus doppler waveform (DV) could be used as indications for delivery instead of CTG short-term variation (STV).
What type of the study was the TRUFFLE trial?
Prospective, European multicentre, unblinded, RCT
What was the inclusion criteria in the TRUFFLE trial?
Singleton fetuses 26-32/40 (assigned by dating scan) with very preterm fetal growth restriction (AC <10th centile and UAPI >95th)
What were the interventions in the TRUFFLE trial?
Delivery of the fetus according to the criteria of the randomisation group
1. CTG STV - delivery if reduced STV (<3.5ms <29/40 and <4.0ms >29/40)
2. DV p95 - delivery with DV >95th centile with forward flowing EDF (early changes)
3. DV no A - delivery with absent or reversed A wave on DV (late changes)
What was the primary outcome of the TRUFFLE trial?
Survival without cerebral palsy or neurosensory impairment at 2 years of age (corrected for prematurity)
or
Bayley III development score of less than 85 at 2 years of age (corrected for prematurity)
What was the secondary outcome of the TRUFFLE trial?
Composite of adverse neonatal outcome
- perinatal mortality or 1 or more of other neonatal morbidities
What were the main findings of the TRUFFLE trial?
- No statistically significant difference in the primary outcome between groups (the proportion of infants surviving without neurodevelopmental impairment).
- Off survivors, more infants in the DV no A group were free of neuroimpairment when compared to those in the CTG STV group, but this was accompanied by a non-significant increase in perinatal and infant mortality.
What was the conclusion of the TRUFFLE trial?
Although the difference in the proportion of infants surviving without neuroimpairment was non-significant at the primary endpoint, timing of delivery based on the study protocol using late changes in the DV waveform might produce an improvement in developmental outcomes at 2 years of age.
TRUFFLE study strengths
High powered/large numbers
Randomised control trial
Those assessing outcomes were blinded to intervention
Low numbers lost to follow-up
TRUFFLE study weaknesses
Randomisation not blinded
11% of women were delivered for maternal reasons (not by the randomised delivery criteria)
11% of women were delivered for fetal distress (not by the randomised delivery criteria)
What was the aim of the MAGPIE trial (Lancet 2002)?
Whether women with PET and their babies benefit from magnesium sulfate
What type of study was the MAGPIE trial?
Large (10,000), multi-centre, multi-country (33), placebo-controlled, double blinded RCT
What was the inclusion criteria for the MAGPIE trial?
Pregnant women or women within 24h postpartum with a diagnosis of PET (BP 140/90 or more and proteinuria of 1+ (30mg/dL) or more) + clinical uncertainty about magnesium sulfate
What was the intervention and comparison in the MAGPIE trial?
Intervention - 4mg loading dose MgSO4 IV bolus over 10-15 minutes, then 1g/hr infusion or 5g q4h IM
Comparison - Placebo (normal saline)
What were the primary outcomes in the MAGPIE trial?
Eclampsia
Stillbirth or neonatal death before discharge from hospital (in women randomised antenatally)
What were the secondary outcomes in the MAGPIE trial?
Composite of serious maternal morbidity
Magnesium sulfate toxicity and side effects
Labour and delivery complications
Neonatal morbidity
Maternal deaths
What were the main results of the MAGPIE trial?
Statistically significant reduction in eclampsia in the MgSO4 group - 0.8% vs 1.9%, RR 0.42, NNT 91
No difference in perinatal mortality (in women randomised prior to birth)
Statistically significant reduction in placental abruption RR 0.67
Non-significant reduction in maternal mortality (0.2% 11 vs 0.4% 20)
No statistically significant difference in severe maternal morbidity, however more side effects reported in MgSO4 group
What is the conclusion of the MAGPIE trial?
MgSO4 significantly reduces the risk of eclampsia by greater than half and probably reduces the risk of maternal death. There does not appear to be substantive harmful effects to mother or baby in the short term
MAGPIE study strengths
Double blinded RCT
High power/large numbers (10,000)
Included 33 countries, so high level of generalisability
Provided a specific dosing regimen
Low level lost to follow-up
MAGPIE study limitations
Underpowered to give statistically significant data on deaths
Variability in route of administration
What was the aim of the CLASP study (Lancet 1994)?
To establish if low dose aspirin can prevent PET and whether it is safe
What type of study was the CLASP study?
Multi-centre, placebo-controlled RCT
What was the inclusion criteria of the CLASP trial?
Prophylactic entry: Women 12-32/40 at risk of PET (prev PET/IUGR, chronic HTN, renal disease, risk factors such as AMA, FHx, multiples)
Therapeutic entry: Women 12-32/40 with signs or symptoms of PET or IUGR in current pregnancy
What was the intervention and comparison in the CLASP study?
Intervention - 60mg/day aspirin
Comparison - placebo tablet