LANDMARKS (OBS) Flashcards
Fonseca et al 2007: study question?
does progesterone reduce the risk of PTB <34/40 in asymptomatic women found to have cervical shortening in mid trimester?
Describe participants of Fonesca 2007 trial
24,620 women. Singleton and Twins. CVL 20-25w. 413 CVL <15mm.
With or without history of PTB. Excluded if major anomalies, ROM, cerclage in situ.
Intervention of Fonseca et al 2007?
progesterone pessary 24w-33+6w 200mg nocte
Rates of PTB <34w in progesterone vs. placebo group in Fonesca et al 2007?
prog = 19% placebo = 43%
aOR 0.56(0.32-0.92) p0.02
Study question for Fonesca et al 2003?
What is the effect of prophylactic vaginal progesterone in reducing PTB in a high risk population?
Study population Fonesca et al 2003?
157 asymptomatic singletons.
Previous sPTB, prophylactic cerclage, uterine malformation.
excluded multiples, anomalies, PPROM.
Intervention Fonesca et al 2003?
progesterone 100mg from 24 weeks until 34 weeks vs. placebo.
Results Fonesca 2003?
PTB 13.8% vs. 28.5%
<34/40 2.8% vs. 18.8%
Truffle trial study question?
When to deliver
- fetal ductus venosus changes (>95th or no-a wave)
- STV
Normal STV in truffle for <29/40, >29/40?
<29 = 3.5 >29 = 4
Three randomisation groups in truffle trial?
- CTG STV abnormal
- DV PI >95 centile
- DV a-wave absent or reversed.
GA and characteristics of gestations in truffle trial?
511 pregnancies
between 26-32 weeks at randomisation
EFW >500g, DV doppler normal, CTG STV normal.
Fetal growth restriction
42% UAPI EDF absent or reversed. All UAPI >95th.
Results Truffle trial?
- 2y no impairment 85% (DV no a), 84% (DV >95), 77% (STV)
- Impairment 5% (DV no a), 9% (DV p95), 15% (STV)
DV no a = better cognitive composite score, vocabulary, 0% cerebral palsy (vs. 4% STV).
Cochrane review on magnesium for PET 2010. Describe trials included.
15 trials
- 6 compared IM or IV MgSO4 with placebo or nil
- 4 compared IM or IV MgSO4 with phenytoin, diazepam, nimodipine, isosorbide
- 1 compared MgCl with methyldopa
Cochrane review MgSO4 in PET. Findings?
Maternal
death= NS reduction 46%
eclampsia RR 0.41. SS. NNT 100
abruption RR 0.64 SS.
SE of flushing, hypotension, headache NNTH 6.
No difference in SCBU, GA, death, RDS for babies.
MAGPIE Question?
do women and babies with PET benefit from MgSO4?
MAGPIE population?
10,141 women. PET (HTN and proteinuria). Antenatal or <24hrs PP.
Intervention Magpie trial?
Placebo (saline)vs.
MgSO4: loading 4g 10-15min, maintenance 1g/hr
Outcomes magpie trial?
Eclampsia RR0.42 SS. NNT 91
Abruption 12/1000 women fewer. SS.
No significant findings for maternal death, or neonatal mortality or morbidity.
Doyle et al Meta Analysis of Magnesium sulphate investigated what?
safety and effectiveness of MgSO4 as Neuroprotection for PTB
Describe studies included in Doyle et al meta analysis.
5 trials
- ACTOMgSO4 (ANZ)
- Magnet (US)
- Rouse (US)
- Premag (France)
- MAGPIE (Int)
6145 babies total. PET 15%, PPROM 10-88%
50% had steroids
Outcomes Doyle et al?
MgSO4 for PTB reduces cerebral palsy (0.68) or significant motor dysfunction (0.61)
no effect on mortality.
CLASP trial question?
what is the effect of LDA for those at risk of PET or IUGR?
Intervention of CLASP?
placebo or aspirin from 12 weeks (60mg)
However some received prophylaxis, and some were started on aspirin once PET/IUGR diagnosed.
Findings CLASP?
Reduced preterm delivery <37 weeks
no change to PET or IUGR. However trend noted.
inclusion of treatment group + average GA for prophylaxis at 18w likely reduced effect.
Betamethasone and elective caesarean section 2005 RCT question?
Do steroids reduce RDS in babies born elLSCS at term?
Population term CS betamethasone 2005 trial?
998 women, singleton pregnancies
LSCS after 37 weeks
no blinding
Outcome of term CS betamethasone 2005?
SCBU admission RDS= RR 0.46 SS
37w= 11.4% vs 5.2% 38w = 6.2% vs 2.8% 39w = 1.5% vs 0.6%
Late preterm delivery and betamethasone 2016 question?
Does betamethasone reduce RDS in late preterm birth (34-36+6)?
Outcomes late preterm betamethasone trial 2016?
Reduction in
- CPAP or HFNC >2hrs = RR 0.77 SS
- resuscitation at del RR 0.78 SS
- TTN RR 0.68 SS
- Surfactant rx 0.59 SS
Increase in
- Hypoglycaemia RR1.6 SS
Maternal side effects of betamethasone for late preterm delivery?
Nil
ACTORDS: study question?
does repeat prenatal steroids given to women at risk of PTB reduce neonatal morbidity without harm?
Study population ACTORDS?
<32 weeks
7 or more days since first course
ongoing risk of PTB
982 women
Intervention ACTORDS
placebo vs. Celestine 11.4mg.
Double blinded, including NICU
Outcomes ACTORDS?
NS diff for mild/moderate lung disease
Reduction in
- severe lung disease RR0.6 (0.46-0.79)
- use of oxygen therapy RR 0.90 (0.81-0.99)
Increase in
- unexplained increase of CS in steroid group.
HAPO trial question?
Is maternal hyperglycaemia less severe than DM associated with increased risk of adverse pregnancy outcomes?
Population HAPO?
25,505 women
OGTT 24-32 weeks
DM diagnosis excluded.
Results of HAPO
Increase adverse primary outcomes from and above:
Category 2 = fast 4.2-4.4, 2hr 5.1-6.0
- LGA, CS, cord c-peptide
- fasting values seem to have more effect
Increase adverse secondary outcomes from and above: 1 SD above median (fast 4.8, 2hr 7.4) - PTB - Shoulder dystocia or injury - NICU - hyperbilirubinaemia - PET
Adverse outcomes associated with higher levels of maternal glucose considered ‘non-diabetic’. Current criteria for diagnosing and treating hyperglycaemia in pregnancy should be reconsidered (4.8, 7.4).
NZ (5.5, 9.0), Aus (5.1, 8.5)
ACHOIS study question?
does treatment of women with GDM reduce risk of perinatal outcomes?
ACHOIS study population?
singleton or twins, 16-30 weeks, OGTT 2hr 7.8-11 (fasting <7.8)
1000 women. Median OGTT 8.6 at 2 hrs.
BGL aims in ACHOIS?
fasting 3.5-5.5
preprandial <5.5
postprandial 2hrs <7
Triggers for insulin treatment in ACHOIS?
2x results in 2 weeks of
fasting >5.5, postprandial >7 if <35/40
postprandial >8 if >35/40
>9 at any time or gestation
Outcomes ACHOIS?
REDUCTION IN serious perinatal outcomes RR 0.33 (0.14-0.75) SS BW -145g (SS) LGA RR 0.62 SS Macrosomia >4kg RR 0.47 SS
INCREASE in
IOL RR 1.36 SS, but no difference in CS
physical and emotional role in pregnancy improved
ORACLE 1 trial study question?
benefit of antibiotics for PPROM
Intervention for ORACLE 1?
4 groups - augmentin + eryth = augmentin + eryth placebo = eryth + aug placebo = double placebo
Population group ORACLE 1?
4826 women. <37/40 PPROM.
Median 32/40.
Outcomes ORACLE 1?
Primary composite = neonatal death, morbidity, cerebral abnormality
results vs. placebo
- Erythromycin only
- REDUCTION: primary outcome (NS), del 48h and 7d, surfactant treatment, >48hr O2 requirement, positive neonatal blood culture - Augmentin only OR combined
- REDUCTION: delivery <48h and 7d, maternal PP antibiotic prescription, uterine infection
- INCREASED: NEC (4x higher than placebo)
Take home message for ORACLE 1
Erythromycin for PPROM prolongs time to delivery, reduces neonatal infection, reduces oxygen and surfactant requirement after delivery
Augmentin is associated with NEC
ORACLE I 7y FU question
long term effects of antibiotic treatment
ORACLE I 7y FU take home message?
no long term sequelae in children treated with erythromycin. Possibly underpowered.
Increased bowel disorders in those treated with Augmentin
Hannah et al 1996 regarding PROM, study question?
Does IOL at term reduce risk of fetal and maternal infection in women with PROM.
Randomisation groups for Term PROM?
- IOL IV oxytocin
- IOL vaginal prostaglandin
- expectant management.
Outcomes Term PROM study?
Primary
- chorioamnionitis: oxytocin 4.0%, expectant 8.6%
- neonatal infection did not differ
Secondary
- rate of CS same for oxytocin + prostaglandin
- oxytocin vs. other = fewer exams, sooner active labour, shorter interval ROM, discharged earlier
Aim of PPROMT trial?
determine whether immediate birth in singletons with ROM close to term reduces neonatal infection without increasing morbidity?
Exclusion criteria PPROMT trial?
meconium, chorioamniotitis
GBS vaginal colonisation was not an exclusion criteria
Intervention PPROMT?
immediate delivery vs. expectant management
Outcomes PPROMT?
Primary outcome neonatal sepsis not significant
Secondary outcome
- increased RDS in immediate (RR1.6 SS)
- increased CS in immediate (RR1.4 SS)
Expectant management associated with reduced APH and IP fever (SS)
HYPITAT trial question?
Whether IOL in women with a singleton pregnancy and Gest HTN or mild PET reduces severe morbidity
Intervention groups for HYPITAT?
- Expectant
- Induction
- BS >6 = ARM +augmentation
- BS <6 = PG or balloon
Outcomes for Hypitat?
composite = maternal mortality, morbidity, progression severe disease, PPH
maternal composite primary outcome = RR 0.71 SS.
Reduction in
- severe Hypertension SBP RR 0.63 SS, DBP RR 0.61 NS
- need for oral antihypertensives RR 0.61 SS
- need for IV antihypertensives RR 0.34 SS
Trend towards spontaneous delivery with IOL. No increase in LSCS with IOL.
ARRIVE trial population group?
low risk nulliparous women.
6106 women. singleton, cephalic. No HTN, bleeding, FGR or ROM.
Primary outcome ARRIVE trial?
trend toward decreased neonatal morbidity and mortality, non significant. RR0.80 95% 0.64-1.00 p= 0.049
Secondary outcomes ARRIVE trial?
LSCS
- IOL 18.6%
- CS 22.2%
RR 0.84 95%CI 0.76-0.93 p<0.001
Hypertensive disorders
RR 0.64 95% CI 0.56-0.74
Term breech trial population?
2088 women. 121 centres. complete, frank, breech
Outcomes Term breech trial
Perinatal
- mort/morb RR 0.33 0.19-0.56) 5% VD vs. 1.6% CS
- mortality RR 0.23 (0.007-0.81) 0.01 NNT 175
Apgar
- <7 @5min 3.0% VD, 0.8% CS
Hospital stay
- 4d CS, 2.8d VD
Problems term breech trial?
- optional continuous CTG
- IUGR <2.5kg included
- women with previous CS in vaginal del arm
- ad hoc assignment to arms by clinicians
- accoucheur training and experience variable
- some units unable to emLSCS <30min
- some units unable to provide O2 for 10min or more OR intubation for 30min or more
Sub analysis. Perinatal morbidity increased with
- oxytocin augmentation
- prolonged second stage
- weight less than 2.8kg
Barrett 2013 study regarding twins?
Vaginal or caesarean delivery for twin pregnancy.
Exclusion for twin delivery trial?
MA twins, fetal reduction, lethal anomaly, contraindication to labour or vaginal delivery (including >1 CS)
Twin delivery: Rate of successful vaginal delivery in planned vaginal delivery group?
56% both
4.2% vaginal twin 1, caesarean twin 2
Outcomes twin delivery trial?
Primary outcome =
fetal neonatal death or morbidity
- not changed by presentation twin 2
- increased for twin 2, not altered by mode of delivery.
Maternal death or morbidity
- no significant difference
secondary outcomes not discussed.
WOMAN trial findings?
RR reduction in death RR0.69 if TXA given within 3h of delivery for bleeding.
Reduction in laparotomy RR0.64 for ongoing bleeding
No increase thrombotic events or other adverse outcomes.
No difference in hysterectomy.
