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Antenatal Glucocorticoids and BPD

Antenatal Glucocorticoids and BPD. Evidence based interventions and BPD Postgraduate Course in Neonatology Lausanne, February 28, 2002 Thomas M. Berger NeoIPS, Kinderspital Luzern. Antenatal Glucocorticoids and BPD Overview. Antenatal Glucocorticoids and BPD Small Bowel Phosphatase.

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Antenatal Glucocorticoids and BPD

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  1. Antenatal Glucocorticoids and BPD Evidence based interventions and BPD Postgraduate Course in Neonatology Lausanne, February 28, 2002 Thomas M. Berger NeoIPS, Kinderspital Luzern

  2. Antenatal Glucocorticoids and BPDOverview

  3. Antenatal Glucocorticoids and BPD Small Bowel Phosphatase Moog F The influence of the pituitary- adrenal system on the differentiation of phosphatase in the duodenum of the suckling mouse J Exp Zool 1953;124:329-246 1953

  4. Antenatal Glucocorticoids and BPD Lung Phosphatase Buckingham S, McNary WF, Sommers SC, et al. Is lung an analog of Moog‘s developing intestine? I. Phosphatases and pulmonary alveolar differentiation in fetal rabbits Fed Proc 1968;27:328 (Abstract) 1968

  5. Antenatal Glucocorticoids and BPD Preterm Lambs Liggins GC Premature delivery of foetal lambs infused with glucocorticoids J Endocrinol 1969;45:515-523 1969

  6. Antenatal Glucocorticoids and BPD Sir Graham Liggins Liggins GC, Howie RN A controlled trial of antepartum glucocorticoid treatment for the prevention of the respiratory distress syndrome in premature infants Pediatrics 1972;50:515-525 1972

  7. Antenatal Glucocorticoids and BPD NIH Concensus Statement The effect of antenatal steroids for fetal maturation on perinatal outcomes-interim draft statement. NIH Consens Statement Online 1994 Feb 28-Mar 2 1994

  8. Banks BA et al. (1999) Multiple courses of antenatal corticosteroids and outcome of premature neonates Fetal growth Brain growth Number of alveoli Antenatal Glucocorticoids and BPD Mechanisms of Action • Functional maturity • - Surfactant (PC, SP-A, SP-B) • - Antioxidant enzymes (SOD, Cat, GP) • - Endothelial NOS • Structural maturity • Alveolar wall thickness • Microvascular maturation • Extrapulmonary effects • Cardiovascular (BP stability) • Renal (GFR, tubular function) • Gastrointestinal (enzymes)

  9. Antenatal Glucocorticoids and BPD Metaanalysis - 2001 Crowley PA 2001 (18 trials) OR (95% CI) 0.60 (0.48-0.75) 0.53 (0.44-0.63) 0.48 (0.32-0.72) Comment 14 trials (n=3544) 18 trials (n=3735) 6 trials (n=596) Death RDS IVH

  10. Antenatal Glucocorticoids and BPD Metaanalysis - 2001 Crowley PA 2001 (18 trials) OR (95% CI) 1.57 (0.87-2.84) Comment 3 trials (n=411) BPD Rx Ctrl Taeusch (1979) 8/56 8/71 Kari (1994) 6/94 1/94 Silver (1995) 24/54 16/42 Total (95% CI) 38/204 25/207 0.1 0.3 0.5 2 4 10

  11. Taeusch HW et al. (1979) Kari MA et al. (1994) Silver RK et al. (1995) 40/204 38/204 78/204 37/207 25/207 62/207 (20%) (19%) (39%) (18%) (12%) (30%) Dex (n=204) PL (n=207) Mortality BPD Death or BPD Antenatal Glucocorticoids and BPD Metaanalysis - 2001 Incidence of BPD not decreased or even increased because . . . . . . survival is increased, resulting in an increased number of survivors at risk for BPD

  12. Antenatal Glucocorticoids and BPD Metaanalysis - 2001 • Strengths • Randomized controlled trials • Quality of studies verified • Limitations • Small number of RCTs (n=3) • Small number of patients (n=411, 63 with BPD) • Non-uniform diagnostic criteria for BPD used • Metaanalysis includes studies that were performed more than 15 years apart from each other

  13. Antenatal Glucocorticoids and BPD Melbourne Experience Cohort of 678 consecutive VLBW infants from a single institution (1977-1982) Doyle LW et al. (1986). Effects of antenatal steroid therapy on mortality and morbidity in very low birth weight infants Dex (n=244) 49/244 (20%) 29/244 (12%) 29/195 (15%) PL (n=434) 169/434 (39%) 56/434 (13%) 56/265 (21%) Death BPD/live born BPD/survivor BPD or death 78/244 (32%) 225/434 (52%)

  14. Antenatal Glucocorticoids and BPD Melbourne Experience • Strengths • Large number of patients • Single center study • Limitations • Treatment allocation not randomized • Diagnostic criteria for BPD not clearly specified

  15. Antenatal Glucocorticoids and BPD Single versus Multiple Courses

  16. Banks BA et al. (1999) Multiple corses of antenatal corticosteroids and outcome of premature neonates Antenatal Glucocorticoids and BPD Single versus Multiple Courses GA 25 0/7 – 27 6/7 weeks Outcome 1 2  3 Courses of ANC

  17. Banks BA et al. (1999) Multiple corses of antenatal corticosteroids and outcome of premature neonates Antenatal Glucocorticoids and BPD Single versus Multiple Courses GA 28 0/7 – 32 0/7 weeks Outcome 1 2  3 Courses of ANC

  18. Courses of ANC French NP et al. (1999) Repeated ANC: size at birth and subsequent development BPD (36 wks) Antenatal Glucocorticoids and BPD Single versus Multiple Courses • Incidence of BPD not decreased because . . . . . . ANC-induced structural lung changes enhance susceptibility for BPD development • 3 26% 1 11% 2 10%

  19. Antenatal Glucocorticoids and BPD Conclusions • Antenatal glucocorticoids decrease . . . • . . . mortality • . . . the incidence of RDS, IVH, NEC • The impact of antenatal glucocorticoids on the incidence of BPD remains to be defined • using a uniform definition • single versus multiple courses

  20. Antenatal Glucocorticoids and BPDThank you!

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