Obstetric Flashcards
Immediate delivery vs. expectant for PPROM near term (PPROMT).
Journal, year, author, aim
Lancet, 2016.
Morris et al.
To establish if immediate delivery in PPROM at 34-36+6 reduces neonatal infection without increasing morbidity
Immediate delivery vs. expectant for PPROM near term (PPROMT).
Methodology
Multicentre RCT, 11 countries. 2004-2013.
1839 women.
>16y, singleton pregnancies, PPROM 34-36+6.
IOL within 24h vs. unit led monitoring
Immediate delivery vs. expectant for PPROM near term (PPROMT).
Results
Neonatal sepsis (primary outcome) 2% vs. 3% - not significant. In immediate delivery, neonates had increased respiratory distress, mechanical ventilation and NICU time. Higher CS rate for mothers. Expectant - women had higher APH rate, use of PP antibiotics and longer hospital stay
Immediate delivery vs. expectant for PPROM near term (PPROMT).
Conclusions.
Expectant management should be practised as immediate delivery was shown to increase neonatal complications and likelihood of c-section. However women need to be closely monitored as they had a higher incidence of APH and infection.
Immediate delivery vs. expectant for PPROM near term (PPROMT).
Strengths.
65 centres, 11 countries. RCT. Blinded panel who decided on primary outcome. Good follow up (only 5 women not accounted for)
Immediate delivery vs. expectant for PPROM near term (PPROMT).
Weaknesses
PPROM <34/40 included once 34/40
Study duration 9y.
Expectant management not specified
Broad-spec antibiotics for PPROM - ORACLE I.
Journal, year, author, aim
Lancet, 2001
Kenyon et al
Do antibiotics administered to the mother in PPROM improve neonatal health and long-term outcomes by preventing infectious morbidity in the fetus or delay PTB?
Broad-spec antibiotics for PPROM - ORACLE I.
Methodology
RCT, intention to treat, placebo controlled. UK and other international centres. 4826 women.
4 groups: Erythromycin, augmentin, both, placebo
Broad-spec antibiotics for PPROM - ORACLE I.
Results
Erythromycin - prolonged pregnancy, and reduced surfactant requirement, major cerebral abnormalities, positive blood culture. Composite primary outcome (NND, chronic lung disease, major cerebral abnormality on USS) when look at singleton pregnancies.
Augmentin, and both - prolonged pregnancy but increased NEC
Broad-spec antibiotics for PPROM - ORACLE I.
Conclusions
Erythromycin for women with PPROM has a myriad of health benefits for neonate and probable reduction in childhood disability, particularly in singleton pregnancy. Augmentin associated with increased risk of NEC and therefore not recommended.
Broad-spec antibiotics for PPROM - ORACLE I.
Strengths
Only 2 women lost to follow-up, 15 protocol violations 379 centres participated Large RCT-blinded Clinically very relevant A lot of subanalysis
Broad-spec antibiotics for PPROM - ORACLE I.
Limitations
11 cases had medicines revealed and data was included in analysis
Limited info of study population were collected e.g. previous obstetric history or maternal disease.
Hyperglycaemia and adverse pregnancy outcomes (HAPO)
Journal, year, author, aim
NEJM, 2008
HAPO study cooperative research group (Metzfer et al)
To assess whether maternal hyperglycaemia below the threshold for diabetes Dx was a/w adverse pregnancy outcomes
Hyperglycaemia and adverse pregnancy outcomes (HAPO)
Methodology
Observational study
~23,000
75g OGTT - stratified into 7 groups depending on result
Patients and staff blinded
Hyperglycaemia and adverse pregnancy outcomes (HAPO)
Results
Frequency of primary outcomes (BW >90th, cord blood C peptide >90th, primary CS and neonatal hypoglycaemia) increased with increasing glucose category
- Strongest for birthweight and C peptide
Also positive associations with 5 secondary outcomes (should dystocia or birth injury, prematurity, need for NICU, PET, hyperbilirubinaemia)
Hyperglycaemia and adverse pregnancy outcomes (HAPO)
Strengths
Multi-centre observational study, OGTTs validated at single lab
Adds weight to ACHOSIS (reduced perinatal morbidity and mortality with treatment of GDM)
Clinicians and patients blinded to result of OGTT
Biologically plausible – results support the Pedersen hypothesis (maternal hyperglycaemia –> fetal hyperglycaemia –> exaggerated response to insulin)
Limited caregiver bias as patients and staff (other than lab staff) were blinded to result of OGTT
Hyperglycaemia and adverse pregnancy outcomes (HAPO)
Limitations
Statistically underpowered for rare severe outcomes (e.g. perinatal deaths)
Threshold effect not established
No info on BMI or weight gain of mothers
Hyperglycaemia and adverse pregnancy outcomes (HAPO)
Conclusions
On average, maternal glucose levels (less than those meeting the criteria for DM diagnosis at the time) are associated with increased birth weight and neonatal insulin levels
Effect of treatment of gestational diabetes mellitus on pregnancy outcomes (ACHOIS)
Journal, year, author, aim
NEJM, 2005
Crowther et al
To establish that screening and treatment of women with gestational diabetes reduces the risk of perinatal complications
Effect of treatment of gestational diabetes mellitus on pregnancy outcomes (ACHOIS)
Methodology
RCT
1000 women
Dietary advice, glucose monitoring and insulin treatment vs. routine care
Effect of treatment of gestational diabetes mellitus on pregnancy outcomes (ACHOIS)
Results
Composite serious neonatal outcomes were lower in intervention group - 1% vs 4%, NNT 34
Intervention group had more:
- NICU admissions 71 vs 61% (but no increase in secondary outcomes such as hypoglycaemia requiring IV etc)
- IOL 39 vs 29%
- Better post-partum health survey results
No difference in the rate of caesarean sections and phototherapy requirements
Effect of treatment of gestational diabetes mellitus on pregnancy outcomes (ACHOIS)
Conclusions
Treatment of mild GDM for glycaemic control reduces the rate of serious perinatal complications without increasing the rate of caesarean section
Effect of treatment of gestational diabetes mellitus on pregnancy outcomes (ACHOIS)
Limitations
OGTT those in routine told no GDM regardless of result of OGTT - ?ethics of this once
WHO guidelines changed
Nil criteria for routine care (depended on local guidelines) may have varied
?appropriateness of use of composite outcomes given rare neonatal outcomes
?power of study with numbers given rare neonatal outcomes
Outcomes measured are not unique to GDM
- 5 stillbirths in intervention group (APH, 2 unexplained, 1 lethal abnormality, 1 IUGR + PET)
Magpie trial
Journal, year, author, aim
Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate?
Lancet, 2002
Magpie Trial Collaberative group
Aim = title
Magpie trial
Methodology
International, double blind, placebo controlled, RCT
10,100 women
Intention to treat
Antenatal or <24hr post-partum
Women with PET and there was uncertainty about whether to use MgSO4
Magpie trial
Results
Primary outcomes
- Eclampsia - reduced risk by 58%. NNT 91, 63 for severe PET.
- Death of baby before discharge - no difference
Secondary outcomes:
- Not significant reduction in maternal death (45%)
- 24% experienced side effects vs. 5%
- 27% lower RR of abruption
Magpie trial
Conclusions
MgSO4 reduces the risk of eclampsia, likely reduces the risk of maternal death
At this dosage, it does not have any substantive harmful effects on the mother or child, although a quarter of women will have side effects
Magpie trial
Strengths
Multi-centre, large study Double blind Randomised Generalisabled to a large range of clinical settings (both rich and poor countries) Good follow up - 99.7% of women Intention to treat analysis
Magpie trial
Weakness
IV and IM - variable route of administration
Side effects may have allowed the allocation to be guessed
Eligibility dependent on attending clinicians’ beliefs about MgSO4 - unable to keep an accurate record of those eligible but not recruited
TRUFFLE
Journal, year, author, aim
2 year neurodevelopmental and intermediate perinatal outcomes in infants with very preterm fetal growth restriction (TRUFFLE): a randomised trial
Lees et al
The Lancet, 2015
Aim: To establish is changes in fetal ductus venosus doppler waveform could be used as indications for delivery instead of CTG short-term variation (STV)
TRUFFLE
Methodology
Multicentre, randomised management trial
Europe
Women admitted to hospital with singleton pregnancies and diagnosed with FGR
- AC <10th and abnormal UA PI >95th (+/- AREDF)
- EFW >500g
- Normal DV and short term variation
Group 1 = STV <3.5ms (<29/40), <4ms (>/=29/40)
Group 2 = early ductus changes
Group 3 = DV no A wave
TRUFFLE
Conclusions
No significant difference in the proportion of infants surviving without neuroimpairment. However timing of delivery based on late changes in DV waveform might product an improvement in developmental outcomes at 2y.
TRUFFLE
Strengths
Randomised
Intention to treat study
Independent review of data yearly
Paediatrics doing f/u were masked to allocation group
TRUFFLE
Weaknesses
Women were closely looked after by specialist MFM experts, this may be generalisable as not all women have access to this
CTG monitoring was based on computerised assessment of fetal heart STV
- Not all hospitals have this
High proportion of infants triggered safety net delivery criteria
- 38% overall
- 52% in late DV changes group
CLASP
Journal, year, author, aim
A randomised trial of low-dose aspirin for the prevention and treatment of pre-eclampsia among 9364 pregnant women.
Redman et al
Lancet, 1994
To determine the safety of LDA and if it reduces fetal / neonatal morbidity and mortality, either overall or in selected high risk groups
CLASP
Methodology
Multicentre RCT
>9000 women
Double blinded trial - 60mg Aspirin or matching placebo tablet
Inclusion criteria:
>8//40
Prophylactic: history of PET or IUGR, chronic HTN, renal disease or other risk factors e.g. maternal age
Therapeutic: signs or symptoms in current pregnancy
CLASP
Results
Statistically significant reduction in proteinuria PET if entered the study before 20/40 - NNT 100
Reduced likelihood of delivery before 37/40
No statistically significant change for:
- IUGR
- Stillbirths and neonatal deaths
For evidence for bleeding side effects (e.g. abruption)
All outcomes were more statistically significant for early onset PET <32 weeks
CLASP
Conclusions
Use low dose aspirin in those women who may be justified as high risk of early onset PET <32 weeks and start before 20 weeks gestation
CLASP
Strengths
Double blind RCT – low risk of bias
Large cohort of entrants
Intention to treat analysis
Clinically relevant in a New Zealand setting
- MMH was a trial centre as well as several Australian centres
CLASP
Weakness
PET diagnosis not standard
- E.g. rise in DBP >25mg if <90 at booking or 15mmHg is greater
ACTORDS
Journal, year, author, aim
Neonatal Respiratory Distress Syndrome after repeat exposure to antenatal corticosteroids: a randomised controlled trial (ACTORDS)
Crowther et al
Lancet, 2006
Establish if repeat prenatal corticosteroids given to women at risk of preterm birth can reduce neonatal morbidity without harm
ACTORDS
Methodology
982 women
Australia and NZ
Double-Blind RCT
Intention to treat analysis
Women at risk of preterm birth <32/40 (singleton or multiple)
≥7 days after receiving first course of steroids
Ongoing risk for PTB
IM 11.4mg Betamethasone or Placebo (Saline) given weekly, if women remained undelivered and <32/40 with ongoing risks of preterm birth
ACTORDS
Results
Primary outcomes
- Less RDS (NNT 14) - Less oxygen therapy (NNT 15) - Shorter duration of mechanical ventilation - No difference in weight/length/HCat birth or discharge
Steroid group
- Fewer severe lung disease (NNT 14) - CS birth and more minor maternal side-effects
No difference in
- Rates of NICU admission
- Length of stay
- IVH
- Necrotising enterocolitis
- Chorioamnionitis requiring intrapartum IV abx or pyrexia ≥ 38.0 ®C
ACTORDS
Conclusions
Repeat doses of antenatal corticosteroids reduced neonatal morbidity
ACTORDS
Strengths
Similar 2 groups RCT Independent data monitoring committee Blinded Given information regarding the safety profile of steroids for maternal and fetal Did follow up at 2y and 6-8y
ACTORDS
Weakness
Only studied up to 32/40
Wide range of gestational age, treatment doses and number of doses
Prophylactic administration of progesterone by vaginal suppository to reduce the incidence of spontaneous preterm birth in women at increased risk: A randomised placebo-controlled double blind study
Journal, year, author, aim
da Fonseca et al.
AJOG (American Journal of Obstetrics and Gynaecology) , 2003
To evaluate if prophylactic administration of progesterone by pessary can reduce the risk of incidence of preterm birth in a high risk population
Prophylactic administration of progesterone by vaginal suppository to reduce the incidence of spontaneous preterm birth in women at increased risk
Methodology
Double blind RCT - 100mg of progesterone daily or placebo from 24-34/40
Brazil
142 women
Included women – 24+/40, asymptomatic at time of randomisation and had at least one of:
- Previous preterm birth
- Uterine malformation
- Prophylactic cervical cerclage in this pregnancy
Excluded multiple pregnancy and fetal malformation
Prophylactic administration of progesterone by vaginal suppository to reduce the incidence of spontaneous preterm birth in women at increased risk
Results
PTB lower in intervention group
Fewer recordable UA events
- Weekly 60 min recording of contractions
Prophylactic administration of progesterone by vaginal suppository to reduce the incidence of spontaneous preterm birth in women at increased risk
Conclusions
Prophylactic vaginal progesterone reduced the frequency of uterine contractions and rate of preterm delivery in high risk women
ACTORDS long term follow up
Administration of repeat doses of AN corticosteroids reduces neonatal morbidity without changing either survival free of major neurosensory disability or body size at 2y
Treatment with repeat dose(s) associated with neither benefit nor harm in mid-childhood (6-8y)
Prophylactic administration of progesterone by vaginal suppository to reduce the incidence of spontaneous preterm birth in women at increased risk
Strengths
Double blind RCT – low risk of bias
Most women had a previous preterm birth
- This is the single biggest risk factor
Clinically relevant in a New Zealand setting
Prophylactic administration of progesterone by vaginal suppository to reduce the incidence of spontaneous preterm birth in women at increased risk
Weaknesses
Very high risk population (baseline preterm birth rate of 25% for all women birthing at this hospital)
Small numbers
Gestation at intake was 24+/40 – would have been ideal to see if any value in starting earlier
Mechanism of action not completely understood
No comparison to cerclage alone
Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus: Intervention review
journal, year, author, aim
Doyle et al
Cochrane, 2009
To assess the effects of magnesium sulphate as a neuroprotective agent when given to women considered at risk of pre-term birth
Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus: Intervention review
methodology
5 RCTs of antenatal MgSO4 whose primary outcomes including neuroprotection
6145 babies
MAGPIE only study that looked at eclampsia
Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus: Intervention review
results
Significantly reduced risk of:
- Cerebral palsy, NNT 63 - Substantial gross motor dysfunction
No overall significant effect on:
- Paediatric morality - Serious adverse maternal events
Significantly more women in magnesium group ceased therapy due to side effects
Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus: Intervention review
conclusion
The evidence now supports a role for antenatal magnesium sulphate in women at high risk of preterm birth as a neuroprotective agent particularly noticeable for those who delivered below 34 weeks.
Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus: Intervention review
strengths
Large cohort of babies
Only one study from developing country so applicable to our population
Meta-analysis of RCTs
Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus: Intervention review
weaknesses
Babies were only followed up to 2 years old with developmental milestones
- Some cases of cerebral palsy may be missed therefore overpowering the effect of magnesium sulphate
? Diluted benefit as included babies up to 37 weeks
- Subgroup analysis showed greater effect in those <34/40
Progesterone and Risk of Preterm Birth Among Women with Short Cervix
journal, year, aim, author
Fonseca et al
The New England Journal of Medicine, 2007
To evaluate if progesterone reduces early preterm delivery in asymptomatic women found at mid-gestation to have a short cervix
Progesterone and Risk of Preterm Birth Among Women with Short Cervix
methodology
Multi-centered double-blind RCT
250 short cervix and agreed to participate
Cervical length of ≤15mm on TV USS
singleton or twin pregnancy undergoing routine USS 20-25/40 or fetal anatomy
Exclusion:
- Major fetal abnormality
- History of ruptured membranes
- Cervical cerclage
Vaginal progesterone 200mg nocte 24-33+6 vs. placebo
Progesterone and Risk of Preterm Birth Among Women with Short Cervix
results
Primary outcomes = Spontaneous delivery before 34 week
- 19.2% vs 34.4%
- lower in pv progesterone group
- Especially if no history of PTB or singleton pregnancy
Non-significant reduction in neonatal morbidity
Progesterone and Risk of Preterm Birth Among Women with Short Cervix
conclusion
In asymptomatic women with short cervix, treatment with progesterone reduces rate of spontaneous delivery before 34w
Progesterone and Risk of Preterm Birth Among Women with Short Cervix
Strengths
Screened >24,000 women
Good adherence rate
Intention-to-treat
Double-blind RCT
Progesterone and Risk of Preterm Birth Among Women with Short Cervix
Weaknesses
USS detection of cervical length- a lot of potential inconsistencies between sonographer
High number of USS required to identify asymptomatic shortened cervix ?cost-benefit
Length of <15mm - different to current practice
ARRIVE
journal, year, author, aim
Labor Induction versus Expectant Management in Low risk Nulliparous Women
Grobman et al
NEJM, 2018
Perinatal and maternal consequences of IOL at 39/40 among low risk nulliparous women are uncertain
ARRIVE
methodology
Multicentre RCT, USA
Low risk nulliparous women - randomised between 38-38+8
- Accurately dated by early USS or FAS + LMP congruent
Just over 6000 women
IOL at 39-39+4 vs. expectant management
EM - delivery initiated 40+5 to 42+2
ARRIVE
results
Primary outcomes = Composite of perinatal death or severe neonatal complications
- No difference in perinatal death / severe neonatal complications
Significantly lower rate of CS in IOL group
- NNT to avoid 1 CS - 28
Women in IOL group also significantly:
- Less likely to have hypertensive disorders of pregnancy
- Less likely to have extensions of uterine incision during CS
- Reported less pain
- More perceived control during childbirth
ARRIVE
conclusion
IOL at 39/40 in low risk P0 women did not result in a significantly lower frequency of composite adverse perinatal outcome
Did result in a significantly lower frequency of CS
ARRIVE
strengths
Large RCT
ARRIVE
weaknesses
Selection bias
Not blinded - unable to be
- Ascertainment bias
Still needs evaluation of cost-effectiveness
? comparison of early vs late indication as allowed maternal request induction from 40+5
Antenatal betamethasone for women at risk of late preterm delivery
journal, year, author, aim
Gyamfi-Bannerman et al
NEJM 2016
To assess if betamethasone given to late preterm babies reduced rate of neonatal morbidity
Antenatal betamethasone for women at risk of late preterm delivery
methodology
Randomised control trial
Intention to treat analysis
2831 participants
Singleton pregnancy at high probability of late pre-term delivery 34+0 – 36+6
- PTL, PPROM, planned IOL or CS
Excluded if previous course of antenatal steroids
Betamethasone 11.4mg or placebo, dose repeated 24 hours later
Antenatal betamethasone for women at risk of late preterm delivery
results
Neonatal composite of the need for respiratory support in the first 72 hours after birth or stillbirth / neonatal death
- significantly lower in steroid group
- NNT for respiratory support = 35
- no perinatal deaths
Secondary outcomes in intervention group:
- Less resuscitation and surfactant required
- Shorter stay in NICU
- Increase in neonatal hypoglycaemia
- No difference in chorio or neonatal sepsis
Antenatal betamethasone for women at risk of late preterm delivery
strengths
RCT
Double blinded
Indications to give steroids clinically relevant to practice
High FU rate
Intention to treat method
- Only 60% (~800) patients received both doses of randomised medication, as others delivered before second dose given
Antenatal betamethasone for women at risk of late preterm delivery
weaknesses
Need longer follow up to see if decrease in bronchopulmonary dysplasia has long term benefit
Study did not allow use of tocolysis
- Might increase effects seen
BSLs not measured routinely ? missed represented effect
24 hours after medication, management guided by local guidelines
Antenatal betamethasone for women at risk of late preterm delivery
weaknesses
Need longer follow up to see if decrease in bronchopulmonary dysplasia has long term benefit
Study did not allow use of tocolysis
- Might increase effects seen
BSLs not measured routinely ? missed represented effect
24 hours after medication, management guided by local guidelines
Planned caesarean section versus planned vaginal birth for breech presentation at term: a randomised multicentre trial.
author, year, journal, aim
Hannah et al.
The Lancet, 2000
To determine whether planned caesarean section was better than planned vaginal birth for selected breech-presentation pregnancies at term
TERM BREECH
methodology
Randomised controlled trial
26 countries
2088 women
Intention to treat analysis
Followed-up until 6 weeks post partum
Singleton live fetus in a frank or complete breech presentation at >37 weeks
Excluded if:
- Evidence of fetopelvic disproportion
- Fetus clinically large or EFW >4000g
- Hyperextension of fetal head
- Fetal anomaly
- Contraindication to labour or vaginal delivery
Planned C/S - 38+ weeks
Planned vaginal birth
- Expectant, unless indication for IOL or C/S developed
TERM BREECH
results
Primary outcomes = Perinatal mortality, neonatal mortality, or serious neonatal morbidity
Significantly lower risk of combined primary outcome in planned C/S group (1.6% vs. 5%)
- NNT 14
56.7% delivered vaginally in planned vag group
No significant differences in maternal outcomes
Reduction in risk was much greater in countries with a low perinatal mortality rate
Trial was stopped early owing to a higher event rate than expected
At 2y risk of death or neurodevelopmental delay was no different between the two groups
TERM BREECH
Strengths
Large, multicentre RCT
Subsequent publication of four large European population studies all show an improved neonatal outcome after elective caesarean for breech
TERM BREECH
Weaknesses
Only 56.7% of those allocated to planned vaginal breech had a vaginal birth
Standard of care was not consistent
Hard to compare low and high perinatal mortality countries
2 stillbirths included in vaginal birth group who likely died before enrolment
High rate of protocol violations in vag group
- E.g. no USS to exclude extended neck, FGR babies included
Some of the risk is due to the earlier gestation at which elective CS is performed
TERM BREECH
Conclusion
Planned C/S is better than planned vaginal birth for the term fetus in the breech presentation, with the benefits being greater in countries that are reported to have lower perinatal mortality rates
Serious maternal complications are similar between the groups
TERMPROM
Author, aim, journal, year
Induction of labour compared with expectant management for prelabour rupture of the membranes at term
Hannah et al.
NEJM, 1996
TERMPROM
methodology
Multicentre, randomised controlled trial
Intention to treat analysis
5041 women
Ruptured membranes, >37 weeks, single fetus, cephalic
- Labour induced immediately with oxytocin
- Labour induced immediately with prostaglandin gel
- Expectant (oxytocin) management (unless evidence of fetal or maternal compromise, or 4 days elapsed), with IOL if needed via oxytocin
- Expectant (PG) management
TERMPROM
results
Primary outcomes - Definite or probable neonatal infection
- no difference
Women induced with oxytocin had lower rate of maternal infection
Intervention viewed more positively by women
~10% of those in the expectant group requested IOL
No difference:
- CS
TERMPROM
conclusion
Oxytocin IOL associated with reduced risk of maternal infection
No difference in rate of neonatal infection, C/S rate
TERMPROM
Strengths
Large, multicentre, randomised
Compared different IOL methods
When reviewing data collected on babies with signs of infection, committee was blinded to group assignments
TERMPROM
weaknesses
Would need larger study to detect possible effect on perinatal mortality
Large time interval for expectant management, did not look at shorter time interval to start IOL, e.g. 24h, 48h
Did not look at effect of increasing parity (separated to 0 and >1)
Cochrane 2017
- reduced maternal infection, chorio
- less likely neonatal sepsis, antibiotics or admission to NICU
- not significant reduction in CS
ORACLE I 7y follow up
Journal, year, author, aim
Kenyon et al
Lancet, 2008
to determine any differences in functional and educational ability in childhood up to 7 years old between antibiotics and placebo groups and erythromycin vs co-amoxiclav
ORACLE I 7y f/u
outcomes
The findings of decreased neonatal morbidity after the receipt of erythromycin in ORACLE I have not translated into long term benefit
No evidence of either antibiotic effecting any functional impairment, behavioural difficulties or exam attainment
HYPITAT
journal, year, author, aim
Induction of labour versus expectant monitoring for gestational hypertension or mild pre-eclampsia after 36 weeks gestation (HYPITAT): a multicentre, open label randomised controlled trial.
Koopmans et al.
The Lancet, 2009
To assess whether induction of labour in women with gestational hypertension or mild pre-eclampsia beyond 36/40 reduces poor maternal outcomes c.f. expectant monitoring
HYPITAT
method
Multicentre, open-label randomised controlled trial
Netherlands
Intention to treat analysis
756 patients
Singleton pregnancy at 36+0 to 41+0 with gest HTN or mild PET
Induction of labour within 24h of randomisation vs. expectant monitoring (“frequent’ BP monitoring + maternal assessment of FM + CTGs)
HYPITAT
results
Primary outcomes = Composite measure of poor maternal outcome (mortality, eclampsia, HELLP, pulmonary oedema, thromboembolic disease, placental abruption, progression to severe HTN or proteinuria, major PPH)
- significantly better for IOL group
- NNT 8
- Improvement based on significant reduction in need for anti-hypertensives and progression to severe HTN
IOL tended towards less CS but not significant
Neonatal outcomes equivalent between the two groups
Subgroup analysis
- Expectant management favoured in women 36-37 weeks
HYPITAT
conclusion
Induction of labour is associated with improved maternal outcome and should be advised for women with mild hypertensive disease beyond 37 weeks’ gestation (as per study)
HYPITAT
strengths
Multi-centre RCT with intention to treat analysis
Study design reflects real world practice limitations
Biologically plausible – IOL prevents progression to severe disease by shortening time to delivery
HYPITAT
weaknesses
Composite outcome
Half of those randomised to expectant had IOLs anyway
Open label – possibility of bias
80% + white, other ethnicity data not specified
Statistically insignificant in improving severe outcomes – however may have been underpowered to do this
WOMAN
journal, year, author, aim
Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial
WOMAN Trial Collaborators
Lancet, 2017
Effects of early administration of TXA on maternal outcomes
WOMAN
method
RCT, Double-blinded
21 countries
20,000 women
Intention to treat
≥16 years old
Clinical diagnosis of PPH
Intervention
- 1g slow IV injection TXA +/- repeat at 30 mins if ongoing bleeding or bleeding restarted within 24h
- IV placebo +/- second dose
Followed up to day 42 after delivery
WOMAN
results
No difference in primary outcome = Composite of death from all causes or hysterectomy within 42 days of randomisation
Maternal death due to bleeding was significantly reduced in women given TXA
Adverse events did not different by group
No difference in
- VTE
- need for blood products
- hysterectomy
- death from all causes
WOMAN
strengths
Multicentre, double blinded, RCT
Large study population
Very few participants lost to follow up
WOMAN
weaknesses
Sample size increased midway through study
? generalisable in high income country
- In low income countries, hysterectomy is an early intervention due to more anaemia and less availablility of blood products
All-cause mortality not generalisable between countries
• Mainly low-mid income countries
Limited follow up to 42 days if still in hospital or earlier if discharged
WOMAN
conclusion
TXA reduces death due to bleeding in women with PPH with no adverse effects
In patients treated with TXA within 3 hours of birth, TXA reduced death due to bleeding by one third
ASTECS
journal, year, aim, author
Antenatal betamethasone and incidence of neonatal respiratory distress after elective caesarean section: pragmatic randomised trial (ASTECS)
Stutchfield et al.
BMJ, 2005
To test whether steroids reduce respiratory distress in babies born by elective caesarean section at term
ASTECS
method
Multicentre, pragmatic randomised trial
942 babies available for intention-to-treat analysis
Women having elective C/S planned >37/40, singleton pregnancies
Two IM doses of 12mg betamethasone in the 48h before delivery (24h apart)
Control group received treatment as usual
ASTECS
results
Primary outcomes = admission to SCBU with respiratory distress
- Reduced in intervention group
Intervention group had:
- Less TTN
- Less RDS
- Less ICU care
Adverse effects in 7 mothers in treatment group (flushing, nausea, pain, insomnia)
ASTECS
strengths
RCT
Found that steroids reduced TTN - authors thought this was the first report of this
Generalisable to our population
Biological plausibility
ASTECS
weaknesses
Unblinded
ASTECS
conclusion
AN betamethasone and delayed delivery until 39 weeks both reduce admissions to SCBU with respiratory distress after elective C/S at term
A Randomised Trial of Planned Caesarean or Vaginal Delivery for Twin Pregnancy.
journal, year, author, aim
Barret et al
New England Journal of Medicine, 2013
To assess if twins have better perinatal outcomes with vaginal delivery vs caesarean section
A Randomised Trial of Planned Caesarean or Vaginal Delivery for Twin Pregnancy.
method
Multicentre international randomised control trial
2804 participants
32+0 - 38+6 live twins, leading twin cephalic, EFW 1500-4000g
Exclusion:
- Selective IUGR - Contraindication to NVD
Planned caesarean section vs vaginal delivery.
A Randomised Trial of Planned Caesarean or Vaginal Delivery for Twin Pregnancy.
results
No significant difference in neonatal death or morbidity or maternal composite outcome (2.2 vs 1.9%)
Higher risk of adverse perinatal outcome for second twin than first twin
- Planned caesarean section did not reduce this risk
4.2% had combined vaginal + c/s for second twin
The rate of caesarean delivery was:
- 90.7% in the planned CS group
- 43.8% in the planned vaginal delivery group
Women in the planned CS group delivered earlier
Post hoc subgroup analysis
- No significant interaction of chorionicity with the primary outcome
A Randomised Trial of Planned Caesarean or Vaginal Delivery for Twin Pregnancy.
conclusions
Planned caesarean section when the first twin is cephalic did not significantly reduce the risk of adverse perinatal outcomes
A Randomised Trial of Planned Caesarean or Vaginal Delivery for Twin Pregnancy.
strengths
Randomised controlled trial with high follow up rate
A Randomised Trial of Planned Caesarean or Vaginal Delivery for Twin Pregnancy.
weaknesses
Only generalisable to units where obstetrician available for birth (most)
No standardised approach to delivery planning
High rate of caesarean section in vaginal delivery group- 40%
Need further study into outcomes for 37-38 week subgroup
- limited number of infants in this group
- Not appropriately powered for subgroup analysis
No comparison of IOL vs. CS
