Obstetric Details Flashcards
CLASP
Collaborative Low-dose Aspirin Study in Pregnancy: Randomised trial of low-dose aspirin for the prevention and treatment of preeclampsia, Lancet 1994
Methodology: International Randomised controlled trial of >9300 women between 12 and 32 weeks gestation, with a history of preeclampsia or IUGR or other risk factors, or with preeclampsia or IUGR in current pregnancy, randomised to low-dose aspirin or placebo
Results: 12% reduction in incidence of proteinic preeclampsia which was not statistically significant. Significant reduction in likelihood of preterm delivery. Possible (not significant) reduction in IUGR and stillbirth. No increase in bleeding.
Conclusions: Low dose aspirin is not supported for routine prophylactic use, but may be justified when woman are at especially increased risk of early onset preeclampsia
Strengths: Large number of women
Weaknesses: Only used 60mg Aspirin, and average gestation in prophylaxis group at enrolment was 18 weeks. Also given to women who already had preeclampsia, in whom it did not help.
ACHOIS
Australian Carbohydrate Intolerance Study in pregnant women - Effect of treatment of GDM on pregnancy outcomes, NEJM 2005
Methodology: Australia and UK, Randomised controlled trial of 1000 women 16-30 weeks gestation with a positive polycose or risk factors for diabetes underwent 2hr OGTT and were included if they had glucose levels above normal range but not diagnostic of overt diabetes, then randomised to ‘Routine care’ or Treatment (dietary advice, BSL monitoring, insulin if needed)
Results: Relative Risk 0.33 for composite of serious perinatal complications. Treatment group high rate of Induction of labour lower rate of LGA. Treatment group also had improved self-rated physical and emotional scores.
Conclusions: Routine screening and treatment of GDM reduces serious perinatal outcomes including death
Strengths: Intention to treat analysis
Weaknesses: 75% caucasian
MAGPIE
MAGnesium sulphate for Prevention of Eclampsia, Lancet 2002
Methodology: International Randomised controlled trial of 10,000 women with HTN and proteinuria, and clinical uncertainty re MgSo4, either pre-delivery or within 24 hours of delivery, were randomised to either receive MgSo4 bolus + 4hr maintenance, or placebo.
Results: Eclampsia rate was significantly reduced in MgSo4 group, particularly in those with ‘severe features’ (RR 0.42) and there was also lower risk of placental abruption.
Conclusions: MgSo4 around time of delivery in preeclampsia reduces eclampsia by around half, and reduces placental abruption.
Strengths: Blinded
Weaknesses: large variation in centre characteristics
ADDIT: MAGPIE II 18 month followup, there was no significant difference in death or disability of children following MgSo4.
HYPITAT
HYpertension Preeclampsia Intervention Trial At Term
Induction of labour versus expectant monitoring for gestational hypertension or mild preeclampsia after 36 weeks gestation, Lancet 2009
Methodology: Multicentre Randomised Controlled Trial of 750 women, 36-41 weeks gestation with gestational HTN or mild preeclampsia, randomised to either IOL within 24 hours, or expectant monitoring.
Results: Composite maternal adverse outcome (mortality, eclampsia, HELLP, VTE, abruption) were significantly reduced, RR 0.7. Also significantly less severe HTN and requirement for oral or IV anti-hypertensives. No increase in rates of CS and no difference in adverse neonatal outcome.
Conclusions: IOL >36 weeks gestation for gestational hypertension and mild pre-eclampsia reduces maternal adverse outcomes and severe HTN without adverse neonatal outcome.
Strengths: Sufficiently powered study, randomised
Weaknesses: Open label, caucasian population
ACTORDS
Australasian Collaborative Trial Of Repeat Doses of Steroids for prevention of neonatal respiratory distress syndrome, Lancet 2006
Methodology: Multicentre randomised controlled trial, 980 women who were at risk of preterm birth, <32 weeks gestation, and more than 7 days after first course of steroids, received weekly corticosteroid or placebo, until delivered or >32 weeks.
Results: Repeat steroids significantly reduced rate of severe lung disease, and increased rates of ‘no lung disease’, less likely to require surfactant. No difference in adverse maternal outcomes.
Conclusions: Short term neonatal outcomes were improved with repeat weekly doses of corticosteroid prior to 32 weeks.
Strengths: Double blinded
Weaknesses: Was not powered to detect differences in subgroups of gestation or the number of doses given.
ORACLE I
Broad spectrum antibiotics for preterm, pre labour rupture of fetal membranes, Lancet 2001
Methodology: Multicenter Randomised controlled trial of 4800 women with preterm (<37), pre-labour rupture of membranes, were randomly assigned to placebo, or Erythromycin, or Augmentin, or a combination of Erythromycin and Augmentin, QID x 10/7.
Results: The Erythromycin only group compared to placebo had a non-significant reduction in the primary composite outcome (death, lung disease, cerebral abnormality), this result was significant when they analysed the singletons only. Erythromycin also had prolonged pregnancy, fewer positive blood cultures, less oxygen requirement at 28 days of life. Similar results found in sub analyses of <32/40 and >32/40. Augmentin, or Augmentin plus Erythromycin, had an increase in rate of Necrotising enterocolitis, 4x higher than placebo.
Conclusions: In PPROM <37/40, Erythromycin results in prolonged pregnancy and reduction in neonatal adverse outcomes. Augmentin increases risk of necrotising enterocolitis.
Strengths: double blinded, intention to treat analysis
Weaknesses:
ORACLE I - 7 year follow up
Childhood outcomes after prescription of antibiotics to pregnant women with preterm rupture of the membranes: 7-year follow-up of the ORACLE I trial, Lancet 2008
Methodology: Retrospective follow up cohort study of the ORACLE I trial, almost 3300 children were included, via a parental questionnaire and national curriculum educational outcomes.
Results: There was no difference between children of those who received Erythromycin and did not, or between those who received Augmentin and did not, in functional impairment, behavioural difficulties, medical conditions, or in the level of reading, writing and mathematics. There was also no difference in the number of infant or childhood deaths. There was an increase in ‘other bowel problems’ for those who received Augmentin (and note separate study confirmed increase in bowel problems for those who had NEC).
Conclusions: At 7 years of age there was no difference in outcomes for children of those treated with Erythromycin for PPROM.
Strengths: Strength of original trial, and high follow up (75%)
Weaknesses: Parental questionnaire not formal result so risk of bias
ORACLE II
ORACLE II Trial, Kenyon et al, Lancet 2001
Methodology: Multicentre Randomised controlled trial, 6295 women with spontaneous PTL with intact membranes and without evidence clinical infection, randomised to: erythromycin QID 10/7, Augmentin QID 10/7, both OR Placebo
Results: None of ABx were associated with lower rate of composite primary outcome (NND, CLD, major cerebral abnormality on USS) when compared to placebo. ABx use was associated with lower occurrence maternal infection.
Conclusions: Antibiotics should not be routinely prescribed for women in spontaneous PTL without evidence of clinical infection
ORACLE II - 7 year follow up
Childhood outcomes after prescription of antibiotics to pregnancy with spontaneous preterm labour: 7yr FU of ORACLE II, Lancet 2008
>3000 children from the ORACLE II trial were assessed via structured parental questionnaire.
Results: Prescription of erythromycin for women in spontaneous PTL with intact membranes was associated with increase in functional impairment amongst their children at age 7yrs. Risk of
CP increased with ABx use, although overall risk of CP low.
Number needed to harm with erythromycin = 64
Conclusion: Antibiotics in preterm labour do not improve childhood outcomes
TRUFFLE
Trial of Randomized Umbilical and Fetal Flow in Europe
2 year neurodevelopment and intermediate perinatal outcomes in infants with very preterm fetal growth restriction, Lancet 2015
Methodology: Multicenter Randomised controlled trial, 500 women with fetal growth restriction at 26-31+6 weeks gestation, EFW >500g, and DV doppler <95th centile, were randomised to delivery criteria of abnormal CTG-STV, DVPI >95th centile, or DV A wave absent or reversed (although some were delivered because of maternal condition, or because of abnormal visual CTG, signs of abruption, etc - the trial had a ‘safety net’ criteria for abnormal SVT in the DV groups).
Results: 92% survived at 2 years. Primary outcome was survival without neurodevelopment impairment at 2 years of age - babies in the DV A wave group had significantly improved outcome compared to CTG-STV group, and less cerebral palsy.
Conclusions: In IUGR <32/40, waiting until late ductus venosus changes to deliver did not increase hypoxia mediated deaths and neurodevelopment impairment is reduced, rather than delivery based on computerised CTG changes, although in practice a combination of both should be utilised as many of the DV group were delivered for reasons other than an abnormal DV.
Strengths: RCT
Weaknesses: Unblinded, caucasian women
ARRIVE
A RRandomised trial of Induction Vs Expectant management
Labour induction vs expectant management in low-risk nulliparous women, NEJM 2018
Methodology: Multicenter Randomised controlled trial, 6100 low-risk nulliparous women, at 38-38+6 weeks, were randomised to either IOL 39-39+4 weeks, or expectant management.
Results: Primary outcome composite of perinatal death or severe neonatal complications was slightly higher in the expectant group, but not signficantly. Caesarean delivery and hypertensive disorders of pregnancy were significantly lower in the IOL group.
Conclusions: Induction at 39 weeks of low-risk nulliparous women does not reduce risk of perinatal death or severe complications, but does reduce risk of caesarean delivery and development of hypertensive disorders compared to expectant management.
Strengths: large study, well designed
Weaknesses: unblinded
TERMPROM
Induction of labour compared with expectant management for pre labour rupture of membranes at term, NEJM 1996
Methodology: International randomised controlled trial, 5000 women with pre labour ROM >37 weeks gestation were randomised to 4 groups; 1: IOL with vaginal prostaglandin, 2: IOL with oxytocin, or expectant management with IOL if complications developed or if not spontaneously laboured after 4 days, either with 3: prostaglandin or 4: oxytocin.
Results: IOL with oxytocin significantly reduced the risk of chorioamnionitis, and postpartum fever, compared to expectant management. Neonatal infection did not significantly differ between groups. No difference in rates of CS in any of the groups. Women were more satisfied with IOL than expectant management.
Conclusions: In Term PROM, IOL with oxytocin, IOL with vaginal prostaglandin, and expectant management all have similar rates of neonatal infection and cesarean section. Induction with oxytocin results in a lower risk of maternal infection than expectant management.
Strengths: Large study, randomised. Neonatal infection panel was blinded to treatment arm.
Weaknesses:
WOMAN
Effect of early TXA administration on mortality, hysterectomy and other morbidities in women with PPH, Lancet 2017
Methodology: International Randomised controlled trial, 20,000 women with PPH (after any delivery) were randomised to either 1g IV TXA or placebo, with a second dose of TXA or placebo if bleeding was ongoing.
Results: Composite of death from all causes or hysterectomy was significantly less if TXA given within 3 hours of giving birth, in particular death from uterine atony. Also risk reduction in laparotomy for ongoing bleeding, however rates of hysterectomy and other surgical interventions were not different. There was no increase in thrombosis or adverse medical events in the TXA group, including no difference in the number of RBC units.
Conclusions: In PPH, TXA given within 3 hours of delivery reduces risk of death and death secondary to atony by about one third, without increasing risk of thrombotic events or other complications.
Strengths: Double blind
Weaknesses: Mostly developing countries
PPROMT
Immediate delivery compared with expectant management after Preterm Prelabour Rupture of Membranes close to Term, Lancet 2015
Methodology: International Randomised controlled trial, 1800 women with PPROM 34-36+6 weeks gestation were randomised to immediate delivery (by usual obstetric indications) or expectant management.
Results: Neonatal sepsis no significant difference between immediate vs expectant. Immediate delivery significantly increased risk of respiratory distress syndrome, and increased risk of CS (RR 1.4).
Conclusions: In PPROM close to Term, in the absence of infection or fetal compromise, expectant management with surveillance is appropriate, given immediate management does not reduce neonatal sepsis and increases risk of CS and RDS.
Strengths: Intention to treat analysis
Weaknesses:
HAPO
Hyperglycaemia and Adverse Pregnancy Outcomes, NEJM 2008
Methodology: International Cohort study of 25,500 women who underwent OGTT 24-32 weeks gestation and then were categorised according to BSL and pregnancy outcomes analysed
Results: Statistically significant increase in birth weight >90th centile, neonatal hypoglycaemia and hyperinsulinaemia (C-peptide), shoulder dystocia, and with the higher results an increase in rate of C-section, there was also an association with preeclampsia
Conclusions: Risk of adverse maternal and neonatal outcomes is continuous with increasing glucose level at OGTT, at levels below the overt diabetic range
Strengths: Very high number of women and data was blinded
Weaknesses: Not an RCT
