Obstetric

Question 1

Immediate delivery vs. expectant for PPROM near term (PPROMT).
Journal, year, author, aim

Answer 1

Lancet, 2016.
Morris et al.
To establish if immediate delivery in PPROM at 34-36+6 reduces neonatal infection without increasing morbidity

Question 2

Immediate delivery vs. expectant for PPROM near term (PPROMT).
Methodology

Answer 2

Multicentre RCT, 11 countries. 2004-2013.
1839 women.
>16y, singleton pregnancies, PPROM 34-36+6.
IOL within 24h vs. unit led monitoring

Question 3

Immediate delivery vs. expectant for PPROM near term (PPROMT).
Results

Answer 3

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

Question 4

Immediate delivery vs. expectant for PPROM near term (PPROMT).
Conclusions.

Answer 4

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.

Question 5

Immediate delivery vs. expectant for PPROM near term (PPROMT).
Strengths.

Answer 5

65 centres, 11 countries. RCT. Blinded panel who decided on primary outcome. Good follow up (only 5 women not accounted for)

Question 6

Immediate delivery vs. expectant for PPROM near term (PPROMT).
Weaknesses

Answer 6

PPROM <34/40 included once 34/40
Study duration 9y.
Expectant management not specified

Question 7

Broad-spec antibiotics for PPROM - ORACLE I.

Journal, year, author, aim

Answer 7

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?

Question 8

Broad-spec antibiotics for PPROM - ORACLE I.

Methodology

Answer 8

RCT, intention to treat, placebo controlled. UK and other international centres. 4826 women.
4 groups: Erythromycin, augmentin, both, placebo

Question 9

Broad-spec antibiotics for PPROM - ORACLE I.

Results

Answer 9

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

Question 10

Broad-spec antibiotics for PPROM - ORACLE I.

Conclusions

Answer 10

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.

Question 11

Broad-spec antibiotics for PPROM - ORACLE I.

Strengths

Answer 11

Only 2 women lost to follow-up, 15 protocol violations
379 centres participated
Large RCT-blinded
Clinically very relevant
A lot of subanalysis

Question 12

Broad-spec antibiotics for PPROM - ORACLE I.

Limitations

Answer 12

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.

Question 13

Hyperglycaemia and adverse pregnancy outcomes (HAPO)

Journal, year, author, aim

Answer 13

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

Question 14

Hyperglycaemia and adverse pregnancy outcomes (HAPO)

Methodology

Answer 14

Observational study
~23,000
75g OGTT - stratified into 7 groups depending on result
Patients and staff blinded

Question 15

Hyperglycaemia and adverse pregnancy outcomes (HAPO)

Results

Answer 15

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)

Question 16

Hyperglycaemia and adverse pregnancy outcomes (HAPO)

Strengths

Answer 16

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

Question 17

Hyperglycaemia and adverse pregnancy outcomes (HAPO)

Limitations

Answer 17

Statistically underpowered for rare severe outcomes (e.g. perinatal deaths)
Threshold effect not established
No info on BMI or weight gain of mothers

Question 18

Hyperglycaemia and adverse pregnancy outcomes (HAPO)

Conclusions

Answer 18

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

Question 19

Effect of treatment of gestational diabetes mellitus on pregnancy outcomes (ACHOIS)
Journal, year, author, aim

Answer 19

NEJM, 2005
Crowther et al
To establish that screening and treatment of women with gestational diabetes reduces the risk of perinatal complications

Question 20

Effect of treatment of gestational diabetes mellitus on pregnancy outcomes (ACHOIS)
Methodology

Answer 20

RCT
1000 women

Dietary advice, glucose monitoring and insulin treatment vs. routine care

Question 21

Effect of treatment of gestational diabetes mellitus on pregnancy outcomes (ACHOIS)
Results

Answer 21

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

Question 22

Effect of treatment of gestational diabetes mellitus on pregnancy outcomes (ACHOIS)
Conclusions

Answer 22

Treatment of mild GDM for glycaemic control reduces the rate of serious perinatal complications without increasing the rate of caesarean section

Question 23

Effect of treatment of gestational diabetes mellitus on pregnancy outcomes (ACHOIS)
Limitations

Answer 23

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)

Question 24

Magpie trial

Journal, year, author, aim

Answer 24

Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate?
Lancet, 2002
Magpie Trial Collaberative group
Aim = title

Question 25

Magpie trial | Methodology

Answer 25

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

Question 26

Magpie trial | Results

Answer 26

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

Question 27

Magpie trial | Conclusions

Answer 27

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

Question 28

Magpie trial | Strengths

Answer 28

``` 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 ```

Question 29

Magpie trial | Weakness

Answer 29

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

Question 30

TRUFFLE | Journal, year, author, aim

Answer 30

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)

Question 31

TRUFFLE | Methodology

Answer 31

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

Question 32

TRUFFLE | Conclusions

Answer 32

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.

Question 33

TRUFFLE | Strengths

Answer 33

Randomised Intention to treat study Independent review of data yearly Paediatrics doing f/u were masked to allocation group

Question 34

TRUFFLE | Weaknesses

Answer 34

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

Question 35

CLASP | Journal, year, author, aim

Answer 35

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

Question 36

CLASP | Methodology

Answer 36

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

Question 37

CLASP | Results

Answer 37

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

Question 38

CLASP | Conclusions

Answer 38

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

Question 39

CLASP | Strengths

Answer 39

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

Question 40

CLASP | Weakness

Answer 40

PET diagnosis not standard | - E.g. rise in DBP >25mg if <90 at booking or 15mmHg is greater

Question 41

ACTORDS | Journal, year, author, aim

Answer 41

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

Question 42

ACTORDS | Methodology

Answer 42

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

Question 43

ACTORDS | Results

Answer 43

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

Question 44

ACTORDS | Conclusions

Answer 44

Repeat doses of antenatal corticosteroids reduced neonatal morbidity

Question 45

ACTORDS | Strengths

Answer 45

``` 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 ```

Question 46

ACTORDS | Weakness

Answer 46

Only studied up to 32/40 | Wide range of gestational age, treatment doses and number of doses

Question 47

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

Answer 47

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

Question 48

Prophylactic administration of progesterone by vaginal suppository to reduce the incidence of spontaneous preterm birth in women at increased risk Methodology

Answer 48

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

Question 49

Prophylactic administration of progesterone by vaginal suppository to reduce the incidence of spontaneous preterm birth in women at increased risk Results

Answer 49

PTB lower in intervention group Fewer recordable UA events - Weekly 60 min recording of contractions

Question 50

Prophylactic administration of progesterone by vaginal suppository to reduce the incidence of spontaneous preterm birth in women at increased risk Conclusions

Answer 50

Prophylactic vaginal progesterone reduced the frequency of uterine contractions and rate of preterm delivery in high risk women

Question 51

ACTORDS long term follow up

Answer 51

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)

Question 52

Prophylactic administration of progesterone by vaginal suppository to reduce the incidence of spontaneous preterm birth in women at increased risk Strengths

Answer 52

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

Question 53

Prophylactic administration of progesterone by vaginal suppository to reduce the incidence of spontaneous preterm birth in women at increased risk Weaknesses

Answer 53

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

Question 54

Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus: Intervention review journal, year, author, aim

Answer 54

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

Question 55

Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus: Intervention review methodology

Answer 55

5 RCTs of antenatal MgSO4 whose primary outcomes including neuroprotection 6145 babies MAGPIE only study that looked at eclampsia

Question 56

Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus: Intervention review results

Answer 56

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

Question 57

Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus: Intervention review conclusion

Answer 57

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.

Question 58

Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus: Intervention review strengths

Answer 58

Large cohort of babies Only one study from developing country so applicable to our population Meta-analysis of RCTs

Question 59

Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus: Intervention review weaknesses

Answer 59

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

Question 60

Progesterone and Risk of Preterm Birth Among Women with Short Cervix journal, year, aim, author

Answer 60

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

Question 61

Progesterone and Risk of Preterm Birth Among Women with Short Cervix methodology

Answer 61

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

Question 62

Progesterone and Risk of Preterm Birth Among Women with Short Cervix results

Answer 62

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

Question 63

Progesterone and Risk of Preterm Birth Among Women with Short Cervix conclusion

Answer 63

In asymptomatic women with short cervix, treatment with progesterone reduces rate of spontaneous delivery before 34w

Question 64

Progesterone and Risk of Preterm Birth Among Women with Short Cervix Strengths

Answer 64

Screened >24,000 women Good adherence rate Intention-to-treat Double-blind RCT

Question 65

Progesterone and Risk of Preterm Birth Among Women with Short Cervix Weaknesses

Answer 65

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

Question 66

ARRIVE journal, year, author, aim

Answer 66

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

Question 67

ARRIVE methodology

Answer 67

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

Question 68

ARRIVE results

Answer 68

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

Question 69

ARRIVE conclusion

Answer 69

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

Question 70

ARRIVE strengths

Answer 70

Large RCT

Question 71

ARRIVE weaknesses

Answer 71

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

Question 72

Antenatal betamethasone for women at risk of late preterm delivery journal, year, author, aim

Answer 72

Gyamfi-Bannerman et al NEJM 2016 To assess if betamethasone given to late preterm babies reduced rate of neonatal morbidity

Question 73

Antenatal betamethasone for women at risk of late preterm delivery methodology

Answer 73

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

Question 74

Antenatal betamethasone for women at risk of late preterm delivery results

Answer 74

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

Question 75

Antenatal betamethasone for women at risk of late preterm delivery strengths

Answer 75

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

Question 76

Antenatal betamethasone for women at risk of late preterm delivery weaknesses

Answer 76

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

Question 77

Antenatal betamethasone for women at risk of late preterm delivery weaknesses

Answer 77

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

Question 78

Planned caesarean section versus planned vaginal birth for breech presentation at term: a randomised multicentre trial. author, year, journal, aim

Answer 78

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

Question 79

TERM BREECH methodology

Answer 79

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

Question 80

TERM BREECH results

Answer 80

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

Question 81

TERM BREECH Strengths

Answer 81

Large, multicentre RCT Subsequent publication of four large European population studies all show an improved neonatal outcome after elective caesarean for breech

Question 82

TERM BREECH Weaknesses

Answer 82

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

Question 83

TERM BREECH Conclusion

Answer 83

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

Question 84

TERMPROM Author, aim, journal, year

Answer 84

Induction of labour compared with expectant management for prelabour rupture of the membranes at term Hannah et al. NEJM, 1996

Question 85

TERMPROM methodology

Answer 85

Multicentre, randomised controlled trial Intention to treat analysis 5041 women Ruptured membranes, >37 weeks, single fetus, cephalic 1. Labour induced immediately with oxytocin 2. Labour induced immediately with prostaglandin gel 3. Expectant (oxytocin) management (unless evidence of fetal or maternal compromise, or 4 days elapsed), with IOL if needed via oxytocin 4. Expectant (PG) management

Question 86

TERMPROM results

Answer 86

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

Question 87

TERMPROM conclusion

Answer 87

Oxytocin IOL associated with reduced risk of maternal infection No difference in rate of neonatal infection, C/S rate

Question 88

TERMPROM Strengths

Answer 88

Large, multicentre, randomised Compared different IOL methods When reviewing data collected on babies with signs of infection, committee was blinded to group assignments

Question 89

TERMPROM weaknesses

Answer 89

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

Question 90

ORACLE I 7y follow up Journal, year, author, aim

Answer 90

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

Question 91

ORACLE I 7y f/u | outcomes

Answer 91

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

Question 92

HYPITAT journal, year, author, aim

Answer 92

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

Question 93

HYPITAT method

Answer 93

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)

Question 94

HYPITAT results

Answer 94

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

Question 95

HYPITAT conclusion

Answer 95

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)

Question 96

HYPITAT strengths

Answer 96

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

Question 97

HYPITAT weaknesses

Answer 97

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

Question 98

WOMAN journal, year, author, aim

Answer 98

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

Question 99

WOMAN method

Answer 99

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

Question 100

WOMAN results

Answer 100

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

Question 101

WOMAN strengths

Answer 101

Multicentre, double blinded, RCT Large study population Very few participants lost to follow up

Question 102

WOMAN weaknesses

Answer 102

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

Question 103

WOMAN conclusion

Answer 103

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

Question 104

ASTECS journal, year, aim, author

Answer 104

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

Question 105

ASTECS method

Answer 105

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

Question 106

ASTECS results

Answer 106

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)

Question 107

ASTECS strengths

Answer 107

RCT Found that steroids reduced TTN - authors thought this was the first report of this Generalisable to our population Biological plausibility

Question 108

ASTECS weaknesses

Answer 108

Unblinded

Question 109

ASTECS conclusion

Answer 109

AN betamethasone and delayed delivery until 39 weeks both reduce admissions to SCBU with respiratory distress after elective C/S at term

Question 110

A Randomised Trial of Planned Caesarean or Vaginal Delivery for Twin Pregnancy. journal, year, author, aim

Answer 110

Barret et al New England Journal of Medicine, 2013 To assess if twins have better perinatal outcomes with vaginal delivery vs caesarean section

Question 111

A Randomised Trial of Planned Caesarean or Vaginal Delivery for Twin Pregnancy. method

Answer 111

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.

Question 112

A Randomised Trial of Planned Caesarean or Vaginal Delivery for Twin Pregnancy. results

Answer 112

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

Question 113

A Randomised Trial of Planned Caesarean or Vaginal Delivery for Twin Pregnancy. conclusions

Answer 113

Planned caesarean section when the first twin is cephalic did not significantly reduce the risk of adverse perinatal outcomes

Question 114

A Randomised Trial of Planned Caesarean or Vaginal Delivery for Twin Pregnancy. strengths

Answer 114

Randomised controlled trial with high follow up rate

Question 115

A Randomised Trial of Planned Caesarean or Vaginal Delivery for Twin Pregnancy. weaknesses

Answer 115

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