Landmark trials Flashcards

Question

200mg Progesterone and risk of preterm birth among women with a short cervix Fonesca NEJM 2007

Answer 1

Women had to be asymptomatic with a short cervix <15mm at 20-25 weeks. Multi-centre double blinded placebo trial. Results: Spontaneous delivery <34 weeks less frequent in progesterone group 19.2% vs 34.4% Especially if no history of PTB and singleton. OPPTIMUM Trial 2016 - largest trial looking for progesterone and pre-term birth showed it did not reduce risk.

Answer 2

RCT multicentre Late preterm 34 to 36+6 weeks Primary outcome composite for any respiratory support within first 72 hours, (stillbirth and neonatal death but there were none) Results: Lower neonatal composite 11.6% vs 14.4% NNT 35. Severe respiratory complications 8.1% vs 12.1% NNT 25. Less resuscitation and surfactant requirement Shorter stay in NICU Increased neonatal hypoglycemia No difference in chorio or neonatal sepsis

Answer 3

Primary outcome - Perinatal mortality, neonatal mortality <28 days, serious neonatal morbidity. In planned breech group only 56.7% delivered vaginally Results: Lower risk of combined neonatal outcome in planned c-section group NNT 14 (7 if country with low perinatal mortality) RR 0.36 serious neonatal morbidity. No significant difference in maternal outcomes.

Answer 4

Multi-centered open-label randomised trial. Primary outcome - composite measure of maternal morbidity, mortality and progression to severe disease and major PPH Results: Half of those randomised to expectant had IOL anyway (for severe PET, HELLP, fetal distress, PROM, Post-dates) Composite was better for IOL group 30% RR NNT 8 Improvement based on significant reduction for the need for anti-hypertensives and progression to severe PET. Neonatal outcome equivalent in 2 groups.

Answer 5

4 interventions: 1. Labour induced immediately with oxytocin 2. Labour induced immediately with prostaglandins 3. Expectant management with IOL if needed via oxytocin 4. Expectant management with IOL if needed via prostaglandins. Primary outcome - definite or probable neonatal infection Results - No difference in rates of neonatal infection Women induced with oxytocin had lower rates of maternal infection, less abx use and less postpartum fever No difference in c-section rate

Answer 6

C-section >37 weeks singleton Primary outcome - admission to special care unit with respiratory distress Results: RR 0.46 in favour of steroids for admission to NICU. TTN reduced in steroid group RR0.54 Incidence of RDS RR0.21 in favour of steroids Predicted probability of admission reduced with or without steroids from 37 to 39 weeks. AN Betamethasone and delayed delivery until 39 weeks both reduce admission to SCBU after elective c-section.

Answer 7

Inclusion 32 - 38+6 leading twin cephalic EFW 1500-4000g Primary outcome: Composite of neonatal death and morbidity. Composite of maternal death and morbidity. Results: No difference in neonatal or maternal outcome. Risk of EMLSCS in vaginal group 40% Risk of EmLSCS for 2nd twin 4.2%

Answer 8

Women aged 55-74 years old Had annual CA125 6 years and TVUSS 4 years Results: Simultaneous screening with CA125 and TVUSS did not reduce ovarian cancer mortality. Majority of cancer in both groups 75-80% were high grade. False positive screening results were associated with a high risk of complications ~15% at time of surgery.

Answer 9

Aim - identifying the age at which oophrectomy might be recommended to women at average risk of ovarian cancer. Retrospective cohort of 40-80 year old women followed in 5 yearly cycles from time of surgery till 80 years old. Four groups: 1. Oophrectomy + oestrogen 2. Oophrectomy - oestrogen 3. Conservation + oestrogen 4. Conservation - oestrogen Primary outcome all cause mortality. Results: Ovarian conservation - oestrogen reduces CHD and Hip fracture. Only slight 0.47% increase from ovarian cancer death. 65 years old not statistical significance favouring removal at this point.

Answer 10

Population based prospective cohort of women aged 50 years and over invited to breast cancer screening in the UK. Breast cancer: extra 5 per 1000 women after 10 years of oestrogen extra 19 cases per 1000 after 10 years of combined HRT background incidence 32 per 1000 women Endometrial cancer: 2 per 1000 less on continuous combined HRT 4 more per 1000 women on oestrogen between 50-65 years old Background incidence 5 per 1000 Criticism: Previous HRT use was not accounted for and endometrial cancer risk persists for many years after cessation of HRT.

Answer 11

Prospective cohort study looking at general health in postmenopausal women in USA. Through RCTs assessed the effect of HRT on heart disease, fractures, breast and endometrial cancer. The duration was 6 years. Outcomes: Breast cancer 28% increase with combined HRT where as oestrogen only was non significant. VTE 18 in 10,000 additional women per year developed VTE per year when using combined HRT Coronary heart disease if HRT commenced within 10 years of menopause no increase. But is increased if started later. CVA increased with HRT. Criticisms: Average age was 62.5 and participants were not screened for co-morbidities e.g. hypertension

Answer 12

Multicentre RCT To assess whether enoxaparin and low dose aspirin after +ve pregnancy test and uss with intensive pregnancy surveillance reduced pregnancy loss rates vs intensive surveillance alone in women with a history of 2 or more consecutive miscarriages. Secondary outcome: Tolerance and safety of enoxaparin Carriage of common thrombophilias Results: 22% pregnancy loss rate in pharmocology group, 20% loss rate in surveillance group - no difference. No safety issues with LMWH. Prevalance of common thrombophilias in this group of women similar to general population.

Answer 13

RCT low dose aspirin 60mg vs placebo started at 12-32 weeks for prevention or treatment. Double blind RCT for the effects of aspirin on proteinuric pre-eclampsia developing after randomisation. Statistically significant in those that entered the study before 20 weeks for prophylaxis. NNT 100. Effect of aspirin on preterm delivery reduced likelihood by 8% No change in rates of IUGR No effects on stillbirth No safety concerns found with aspirin such as abruption APH All outcomes were statistically significant for early onset PET <32 weeks.

Answer 14

``` Whether maternal hyperglyceamia that was less severe than outright diabetes mellitus (defined at that time) was associated with an increased risk of adverse pregnancy outcomes. Multicentre, multi country observational study. Outcomes increased as per trial: - Birthweight >90th centile - Primary c-section - Clinical neonatal hypoglycaemia - Prematurity - Shoulder dystocia - PET - NICU admission - Hyperbilirubineamia ```

Answer 15

``` To establish that screening and treatment of women with gestational diabetes reduces the risk of perinatal complications. RCT intervention (dietary advice, glucose monitoring and insulin) vs routine care. Composite serious neonatal outcomes were lower in intervention group 1% vs 4% NNT 34. ```

Answer 16

Does administration of antibotics to mother in the context of pPROM improve neonatal health and long term child health by preventing infectious morbidty in the fetus or delay progression of pre-term birth. Interventions 4 groups: 250mg erythromycin 325mg Augmentin Augmentin and erythromycin Placebo Results: Fewer primary neonatal composite outcome but non significant Fewer delivered within 48 hours & 7 days Reduction in treatment with surfactant Fewer cerebral anormalities on USS before discharge Fewer positive blood culture Reduced incidence of NEC with erythromycin vs augmentin. 7 year follow up: The findings of decreased neonatal morbidity after the receipt of erythromycin in ORACLE I have not translated into long term benefit.

Answer 17

Women in spontaneous preterm labor less than 37 weeks gestation, with intact membranes without evidence of clinical infection Women were randomised to erythromycin, augmentin, both or placebo QID for 10 days. Primary outcome was a composite of neonatal death, chronic lung disease or major cerebral abnormality on USS prior to discharge from hospital. None of the antibiotic regimens were associated with lower rates of composite primary outcomes compared to placebo. No prolongation of pregnancy. Most women did not deliver with 48 hours (89.9%) or 7 days (84.6%) illustrates difficulty predicting PTL. Antibiotics should not be prescribed to women in spontaneous preterm labor without any evidence of clinical infection as they will not improve neonatal outcomes or prolong the pregnancy.

Answer 18

Aim to establish whetehr immediate delviery in singlton fetus with ruptured membranes close to term 34 - 36+6 reduces neonatal infection without increasing morbidity. Intervention: Immediate IOL within 24 hours vs expectant management until 37 weeks. Primary outcome: Definite or probable neonatal sepsis established by a review of the neonatal data by a central adjudication committee. Results: Definite or probably sepsis occured in 2% delivery vs 3% in expectant - not signifcant. Neonates in the immediate IOL group had increased rates of respiratory distress and mechanical ventilation and spent more time in intensive care. The women assigned to expectant group had higher risks of APH and use of post partum antibiotics and a longer hospital stay.

Landmark trials Flashcards

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