Landmarks Flashcards
HAPO study Journal Year Aim Type of study Outcomes Results Limitations Strengths
New England Journal of Medicine 2009
Hyperglycaemia and adverse pregnancy outcomes
Looked at risks of adverse outcomes associated with various degrees of maternal glucose intolerance less severe than overt diabetes mellitus
23000 women
Bascially just had to do OGTT
Primary outcomes - all increased risk with increasing glucose at testing
1. Macrosomia
2. C peptide in cord blood (measure of insulin production in fetus)
3. Neonatal hypoglycaemia
4. CS rates
Secondary outcomes also altered
1. Shoulder dystocia and birth injury
2. PET
3. PTB
4. Neonatal jaundice
Gave ADIPS cutoffs of fasting 5.1, 1h 10, 2h 8.5
RR 1.75 of adverse outcome
Limitations: observation study, doesn’t report on confounders such as obesity, gestaiotnal weight gain, previous mode of delivery, previous macrosomia, no cost analysis
Strengths: very large study, heterogenous population
ACHOIS Journal Year Aim Type of study Intervention Outcomes Results Limitations Strengths
NEJM
2005
Does treating GDM improve perinatal outcomes?
RCT
Intervention: dietician, physician, BSL monitoring, +/- insulin vs placebo
blinded if positive for GDM but in placebo arm
Primary outcome
Serious perinatal outcome composite: shoulder dystocia, bone fracture, nerve injury, death, NICU admission, jaundice requiring phototherapy, IOL, CS, maternal anxiety and depression
Secondary outcomes included LGA and macrosomia
Outcome
RR 0.33 primary outcome
Also significant decrease in LGA / macrosomia
Treatment improves outcomes
NNT = 34
Strengths: RCT
Limitiation: wide variety of outcomes in perinatal composite outcome
CLASP trial -Year Journal Aim Type of study Inclusion / exclusion criteria - brief Primary outcomes Results
1994 Lancet Aim: does low dose aspirin reduce risk of PET and IUGR RCT >9000 women Pregnant with risk factors for PET or IUGR or current concern for PET or IUGR Randomised to aspirin or placebo no significnat change in outcomes - Reduced PEt but not significant Reduced PTB but average of 1 day No signifcant change in birthweight No differnece in SB or NND
Cochrane meta-analysis NNT 160 starting <16/40 with those at high risk PET
What was the hypitat study? Year Journal Aim Type of study Inclusion / exclusion criteria - brief Primary outcomes Results
Comparing IOL vs expectant management in women with mild Gest HTN or PET, did it affect serious maternal outcomes?
Lancet 2009
Multicentre open label RCT
Inclusion: singletons, >36/40, no severe PET or other serious comorbidity
Number 377 and 397
intervention: IOL within 24h vs expectant management with close surveillance
Primary outcome: Composite maternal morbidity
- Mortality
- Development of severe PET: eclampsia, HELLP, abruption, pulmonary oedema, VTE, >170/110 AN or PN, major PPH
Results: significant difference, 29% relative risk reduction, OR 0.58, NNT = 8.
No significant difference in mode of delivery or composite neonatal outcome
Offer IOL to women with PET post 3740
MAGPIE Year Journal Aim Type of study Inclusion / exclusion criteria - brief Primary outcomes Results
2002
Lancet
Does MgSO4 prevent adverse outcomes for women with PET and their babies
RCT
9996 women
ITT, blinded, multicentre
MgSO4 loading and maintenance vs placebo
Inclusion: pregnant or delivered within 24h, PET, uncertainty whether should have MgSO4
Primary outcomes: eclampsia, death, matneral morbidity
Results: halved chance of eclampsia, reduction in mortality but not signficiant, SS reduced placental abruption
TRUFFLE
Lancet 2015
Multicentre prospective RCT
500 women
Europe
26-32/40 with FGR (AC <10th with abnormal UAPI), >500g, no delivery plan or fetal anomly, normal DV and normal STV, no karyotype abnormlaity, >18y o
1:1:1 - STV (daily CTG) <3 (26-29), <4 (29-32), Early DV changes (>9th), Lat DV changes (absent or reversed A wave) - twice weekly scans
Safety: STV <2.6 or <3, maternal reason for delivery
Primary outcomes: survival at 2 years without cerebral palsy, neurosensory impairment or Bayley III score <85
Secondary outcomes: death or severe neonatal morbidity
No difference
If take away the deaths in favour of late DV changes
92% survival
2% IUFD
6% NND
ORACLE
Lancet 2001
Kenyon et al
Analysing broad spectrum antibiotic use for women with PPROM <37/40
4800 women
Randomised to erythromycin + placebo vs erythromycin + augmentin vs Augmentin + placebo vs placebo x 2
Primary outcome
- Composite of neonatal death or severe neonatal disease (respiratory or cerebral)
Secondary outcome: lots. Such as number delivered in 48h, number delivered in 7/7, RDS, NEC, birth weight, days in hospital, surfactant use, oxygen use etc. etc.
Results
Both Augmentin and Erythromycin decreased the primary outcome but wasn’t SS
Both Augmentin and Erythromycin significantly decreased number birthed within 48h, and 7/7
Augmentin 4 x risk of NEC
Both decreased chorio, neonatal infection, surfactant use, O2 use, cerebral USS abnormal results
Impression
- Erythromycin decreases composite primary outcome and prolongs gestation
- Avoid Augmentin - NEC x 4 fold.
Limitations
- No data collected on past obstetric history, other fetal or maternal disease
Earliest gestaion not specified
uncertain long term imapcts
Strengths
- LArge multicentre RCT blinded trial
Not many lost to FU
Erythromycin cheap and widely available
ORACLE 2
Lancet 2008
Kenyon et al
7y FU from ORACLE trial to assess any long term benefit or adverse outcomes
75% response rate, retrospective cohort trial
Primary outcome: presence of functional impairment from a validated questionaire. Asked questions concerning hospital admissions, respiratory symptoms, neurobehavioural questions, medical conditions, convulsions
No change in primary outcome for any of the groups
No difference in death, neurobehavioural outcomes, CNS / developmental issues, diabetes, bowel issues
Strengths
- Large cohort
- Good response rate
- Validated standardised quesitonairre used
No difference in response rate between groups
Limitations
- Recall questionaire from parents. Relies on parents understanding of childrens medical conditions
- Under-represented were those from lower socioeconomic class
PPROMT
Lancet 2016
Morris
RCT, blinded to assessors, ITT
1800 women
9 year study period
Included if PPROM 34-36+6
(included into study if ROM prior to 34/40 and made it to 34/40_
Randomised 1:1 to immediate management vs expectant and IOL after 37-38/40
Primary outcome: neonatal sepsis: no difference
Secondary outcome
- Neonatal morbidity: increased RDS in immediate, increased NICU stay in immediate, increased CS in immediate
- Maternal morbidity. Decreased fever in immediate, decreased hospital stay in immediate
Interpretation: expectant better to reduce prematurity complications
Limitation: 9 yr study design, women not blinded, hospital polices differed
Strengths: RCT, multi centre, assessors blinded
FONESCA 2003
AJOG 2003
RCT, placebo controlled, double blinded
Tertiary medical centre in Brazil, high rate of PTB
High risk singletons included if at least one spontaneous PTB, previous prophylactic cerclage and therefore inferred incompetent cervix, uterine malformation
100mg PV suppository between 24-34/40
Swabs at entry and UA monitoring each week
ONLY 157 women
Primary outcome: PTB <37/40 or PTL
Half the rate of PTB - significant
Tocolysis worked better for progesterone group by >twice - delayed PTB rate <37/40
Small sample size
Very high preterm birth rate
Women had extensive follow up
Women had vaginal infections treated
FONESCA 2 2007
NEJM 2007
Multicentre, double blinded, RCT
Aim: does progesterone pessaries reduce risk of PTB pre 34/40 in asymptomatic women with demonstrated cervical shortening on mid-trimester screening
Singleton or twin pregnancies, with routine anatomy scan TVUSS cervical screening showing length <15mm
Exclusions: major fetal anomaly, painful contractions, SROM, cerclage
Progesterone PV vs placebo 24 - 33+6
Outcome spontaneous PTB <34/40
Secondary outcomes: neontal morbidity and LBW
Screened 25,000 women and entered 250 women
Outcome: OR 0.56 of PTB <34/40, significant
Progesterone protective against neonatal morbidiyt but not statistically significant
no significant difference in twins but only 26 pregnancies included
Limitations: no comment on IOL if SROM, insufficiently powered to detect secondary outcomes, relies on USS assessment
Strengths: blinded, RCT, no loss to follow up, good treatemnt adherence
ACTORDs
Lancet 2006 RCT
Use of repeated doses of corticosteroids for women at risk of PTB, and neonatal outcomes
NZ and Australia
Crowther et al
1000 women
Placebo or steroids
Women who had received 2 doses of corticosteroids >7/7 prior and are still at risk of PTB, without any contraindication
Rescue dose given weekly until 32/40 or birth if considered still at risk
Primary outcomes: RDS, intubation, oxygen use, weight at hospital discahrge
Secondary outcomes: chorio, neonatal morbidity
Reduction in RDS
Reduction in severe lung disease and no lung disease
No other differences
Safe to give - no short term harm
(FU 2y: NEJM 2007, crowther et al. possible difference in attention problems, otherwise nil differences between groups
STEROIDS - Landmark
2016 NEJM
Gyami-bannerman et al
Aim: assess whether steroids should be given to women who are at risk of late preterm birth to reduce neonatal morbidity
2800 women
RCT, blinded, placebo controlled
Steroids x 2 doses, vs placebo
Inclusion crtieria: 34 - 36+5, high risk of preterm birth e.g. contracting, 3cm dilated or 75% effaced and membranes intact, or SROM etc
Excluded if imminent delivery, already had steroids, chorio, non reassuring fetal status
Primary outcome: need for respiratory within 72h or death
Secondary outcome: lots. Basically any kind of neonatal or maternal morbidity
Primary outcome OR 0.8. Significantly less respiratory compromise
Secondary outcomes: only one which was significant was neonatal hypoglycaemia RR 1.6
Limitations: significant number of woman only got one dose
No tocolysis
No documentation of neonatal hypoglycaemia numbers over time
BEnefits
Large multicentre RCT, blinded, placebo controlled
Consistent with ASTECs
ASTECS
- Antenatal Steroids for term elective Caesarean Section
2005
BMJ
Multicentre, RCT, placebo controlled
Incidence of RDS is much higher in CS vs NVB (3.6% vs 0.5%)
Steroids vs no steroids pre term ELCS
Primary outcome: SCBU admission for respiratory support . RR 0.46
Secondary outcome: level of respiratory disease
- Incidence at all of RDS 0.21 RR
- TTN o.54 RR
Doyle et al. Cochrane. MgSO4
2009
cochrane review
Involved 5 RCTs that looked at MgSO4 vs placebo for neuroprotection or tocolysis or PET
- Included MagPIE study
- Included Crowther et al NZ study
Proven to decrease CP rates
- RR 0.68
No change in any other neonatal morbidity or mortality
NNT = 63
Limitations: large variety within the studies
Benefits: large number
