1. PVL_COUNTRY_DATE00/1 Département santé et recherche génésiquesDepartment of reproductive health and research Day 3 - Session 2 DAY (3) Session 2 Presentation: Prophylactic corticosteroids for preterm birth

2. PVL_COUNTRY_DATE00/2 Département santé et recherche génésiquesDepartment of reproductive health and research Day 3 - Session 2 Learning objectives To recognise the dangers of reading a report without looking at all available evidence. To recognise the dangers of reading a report without looking at all available evidence. To learn the importance of critical appraisal (of a systematic review). To learn the importance of critical appraisal (of a systematic review).

3. PVL_COUNTRY_DATE00/3 Département santé et recherche génésiquesDepartment of reproductive health and research Day 3 - Session 2 Prophylactic corticosteroids for preterm birth It is August 1982. It is August 1982. You are a keen young midwife caring for a patient who has just been admitted in premature labour. You are a keen young midwife caring for a patient who has just been admitted in premature labour. Your patient is 30 weeks pregnant. Your patient is 30 weeks pregnant.

4. PVL_COUNTRY_DATE00/4 Département santé et recherche génésiquesDepartment of reproductive health and research Day 3 - Session 2 Prophylactic corticosteroids for preterm birth You wonder whether corticosteroids are indicated for the prevention of respiratory distress syndrome in the baby. You wonder whether corticosteroids are indicated for the prevention of respiratory distress syndrome in the baby.

5. PVL_COUNTRY_DATE00/5 Département santé et recherche génésiquesDepartment of reproductive health and research Day 3 - Session 2 Steps in EBRHC Asking the question Asking the question Searching for the answer Searching for the answer Finding the evidence Finding the evidence Interpreting the evidence Interpreting the evidence

6. PVL_COUNTRY_DATE00/6 Département santé et recherche génésiquesDepartment of reproductive health and research Day 3 - Session 2 Exercise Take 5 minutes to compose a three-part clinical question that would help you to find the necessary evidence. Take 5 minutes to compose a three-part clinical question that would help you to find the necessary evidence.

7. PVL_COUNTRY_DATE00/7 Département santé et recherche génésiquesDepartment of reproductive health and research Day 3 - Session 2 Searching for the answer Would you: Would you: – visit the local medical library? – do a computer search? – consult an expert (your consultant)?

8. PVL_COUNTRY_DATE00/8 Département santé et recherche génésiquesDepartment of reproductive health and research Day 3 - Session 2 Searching for the answer look for an answer in look for an answer in – textbooks? – practice guidelines? – RCTs? – systematic reviews?

9. PVL_COUNTRY_DATE00/9 Département santé et recherche génésiquesDepartment of reproductive health and research Day 3 - Session 2 “MEDLINE” citation Liggins GC, Howie RN. A controlled trial of antepartum glucocorticoid treatment for prevention of the respiratory distress syndrome in premature infants. Pediatrics, 1972;50:515-525. Liggins GC, Howie RN. A controlled trial of antepartum glucocorticoid treatment for prevention of the respiratory distress syndrome in premature infants. Pediatrics, 1972;50:515-525.

10. PVL_COUNTRY_DATE00/10 Département santé et recherche génésiquesDepartment of reproductive health and research Day 3 - Session 2 A later citation: Block MF, Kling OR, Crosby WM. Antenatal glucocorticoid therapy for the prevention of respiratory distress syndrome in the premature infant. Obstet Gynecol, 1977;50:186-90. Block MF, Kling OR, Crosby WM. Antenatal glucocorticoid therapy for the prevention of respiratory distress syndrome in the premature infant. Obstet Gynecol, 1977;50:186-90.

11. PVL_COUNTRY_DATE00/11 Département santé et recherche génésiquesDepartment of reproductive health and research Day 3 - Session 2 A more recent citation: published in the BMJ as a “Leading article” published in the BMJ as a “Leading article” Robertson NR. Advances in respiratory distress syndrome. British Medical Journal, 1982;284:917-918 Robertson NR. Advances in respiratory distress syndrome. British Medical Journal, 1982;284:917-918

12. PVL_COUNTRY_DATE00/12 Département santé et recherche génésiquesDepartment of reproductive health and research Day 3 - Session 2 What would you do? Work through the trials and try to synthesise a summary of their results? Work through the trials and try to synthesise a summary of their results? Read the above-mentioned article in the BMJ? Read the above-mentioned article in the BMJ?

13. PVL_COUNTRY_DATE00/13 Département santé et recherche génésiquesDepartment of reproductive health and research Day 3 - Session 2 BMJ 1982 article conclusion “The evidence suggests that antenatal steroids are of value only in white males, and even for them the benefit is mainly in those of 30–32 weeks’ gestation, when in our experience serious morbidity and mortality from respiratory distress syndrome is rare. In black males and in girls treatment has not been proven to be of benefit.” “The evidence suggests that antenatal steroids are of value only in white males, and even for them the benefit is mainly in those of 30–32 weeks’ gestation, when in our experience serious morbidity and mortality from respiratory distress syndrome is rare. In black males and in girls treatment has not been proven to be of benefit.” Robertson NR. Advances in respiratory distress syndrome. British Medical Journal, 1982;284:917-918

14. PVL_COUNTRY_DATE00/14 Département santé et recherche génésiquesDepartment of reproductive health and research Day 3 - Session 2 Exercise: Take 20 minutes to study the table titled: “Results of the trials done pre-1980” which is printed in your manuals and to answer the questions which are printed below the table. Take 20 minutes to study the table titled: “Results of the trials done pre-1980” which is printed in your manuals and to answer the questions which are printed below the table.

15. PVL_COUNTRY_DATE00/15 Département santé et recherche génésiquesDepartment of reproductive health and research Day 3 - Session 2 Results of early trials published before 1980 Trial N Odds Ratio CI a 197210700.55 0.38 - 0.80 b 1977 1300.32 0.11 - 0.97 c 1978 1260.32 0.11 - 0.89 d 1979 1270.58 0.22 - 1.56 e 1979 1460.25 0.10 - 0.62

16. PVL_COUNTRY_DATE00/16 Département santé et recherche génésiquesDepartment of reproductive health and research Day 3 - Session 2 Systematic review Crowley P, Chalmers I, Keirse MJNC. The effects of corticosteroid administration before preterm delivery: an overview of the evidence from controlled trials. British Journal of Obstetrics and Gynaecology 1990;97:11-25. Crowley P, Chalmers I, Keirse MJNC. The effects of corticosteroid administration before preterm delivery: an overview of the evidence from controlled trials. British Journal of Obstetrics and Gynaecology 1990;97:11-25.

17. PVL_COUNTRY_DATE00/17 Département santé et recherche génésiquesDepartment of reproductive health and research Day 3 - Session 2 Results of systematic review The occurrence of neonatal respiratory distress is the principal outcome reported in the 12 eligible trials identified. Antenatal corticosteroid administration is associated with an overall reduction of about 50% in the odds of this form of neonatal morbidity (typical odds ratio 0.49, 95% CI 0.41-0.60) The occurrence of neonatal respiratory distress is the principal outcome reported in the 12 eligible trials identified. Antenatal corticosteroid administration is associated with an overall reduction of about 50% in the odds of this form of neonatal morbidity (typical odds ratio 0.49, 95% CI 0.41-0.60)

18. PVL_COUNTRY_DATE00/18 Département santé et recherche génésiquesDepartment of reproductive health and research Day 3 - Session 2 Cochrane systematic review: Main results Antenatal administration of corticosteroids (individual doses given in review) to women expected to give birth preterm was associated with a significant reduction in respiratory distress syndrome (odds ratio 0.53, 95% confidence interval 0.44 to 0.63) in preterm infants. Antenatal administration of corticosteroids (individual doses given in review) to women expected to give birth preterm was associated with a significant reduction in respiratory distress syndrome (odds ratio 0.53, 95% confidence interval 0.44 to 0.63) in preterm infants.

19. PVL_COUNTRY_DATE00/19 Département santé et recherche génésiquesDepartment of reproductive health and research Day 3 - Session 2 Cochrane systematic review “Despite repeated randomised trials throughout the 1970s and 1980s and a systematic review of randomised trials in 1987 providing incontrovertible evidence in favour of antenatal corticosteroid therapy, obstetricians all over the world have been slow to adopt this treatment.” “Despite repeated randomised trials throughout the 1970s and 1980s and a systematic review of randomised trials in 1987 providing incontrovertible evidence in favour of antenatal corticosteroid therapy, obstetricians all over the world have been slow to adopt this treatment.” Crowley P, author of the Cochrane review

20. PVL_COUNTRY_DATE00/20 Département santé et recherche génésiquesDepartment of reproductive health and research Day 3 - Session 2 Cochrane review (continued) “The causes of this reluctance are unclear. A possible explanation is that the use of antenatal corticosteroids has not been promoted by any pharmaceutical company. “The causes of this reluctance are unclear. A possible explanation is that the use of antenatal corticosteroids has not been promoted by any pharmaceutical company.

21. PVL_COUNTRY_DATE00/21 Département santé et recherche génésiquesDepartment of reproductive health and research Day 3 - Session 2 Cochrane SR (continued) Obstetricians may have been influenced by informal reviews that suggested that corticosteroids are effective only in certain small sub-groups of women and babies.” Obstetricians may have been influenced by informal reviews that suggested that corticosteroids are effective only in certain small sub-groups of women and babies.”