Barbara Schmidt, Kristine Sandberg Knisely Chair in Neonatology Drug Therapy to Prevent BPD

QUESTIONS • What is BPD? • Why worry about BPD? • Which drugs prevent BPD?

Shinwell et al: Arch Dis Child Fetal Neonatal Ed 2007; 92:F30 BPD 3

BPD Need for supplemental oxygen at a postmenstrual age of 36 weeks

DEFINITION OF BPD FOR INFANTS < 32 WEEKS GESTATIONAL AGE: Mild BPD Treatment with oxygen for ≥ 28 days plus Mild BPD Room air @ 36w PMA or discharge Moderate BPD <30% oxygen @ 36w PMA or discharge Severe BPD ≥30% oxygen and/or positive airway pressure @ 36w PMA or discharge NICHD/NHLBI/ORD Workshop Summary: Am J Respir Crit Care Med 2001;163:1723

Otto Dix

http://africanart. org. uk/african_art_masks_paintings_and_patterns http://africanart.org.uk/african_art_masks_paintings_and_patterns.htm

Renoir: Child with Toys

Eakins: Baby at Play

Anker: Crèche

Su Hanchen: Children playing in an Autumn Courtyard

Thoma: Der Kinderreigen

http://www.fairfield.edu/arts/art_persia.html

http://www.welt.de/wissenschaft/article1189884/Ueberleben_mit_500_Gramm_Koerpergewicht.html

QUESTIONS • What is BPD? • Why worry about BPD? • Which drugs prevent BPD?

409 (45%) BPD 194 (21%) 89 (10%) ROP Brain injury NEONATAL MORBIDITIES Total number of infants: 910

Probability of Poor 18-Month Outcome in Study Infants (N = 910) With None, 1, 2, and All 3 Neonatal Morbidities Schmidt, B. et al. JAMA 2003;289:1124-1129.

CONCLUSION In very preterm infants who survive to 36 weeks PMA, a count of BPD, brain injury and severe ROP strongly predicts the risk of a late death or survival with neurosensory impairment

QUESTIONS • What is BPD? • Why worry about BPD? • Which drugs prevent BPD?

Effects of antenatal steroids Outcome No. of patients RR 95% CI RDS Neonatal mortality IVH NEC BPD 4038 3956 2872 1675 818 0.7 0.5 0.9 0.6-0.7 0.6-0.8 0.4-0.7 0.3-0.7 0.6-1.2 Roberts D et al. Cochrane Database Syst Rev 2006

Cerebral Palsy

Effects of postnatal steroids on cerebral palsy, among all randomized infants Barrington BMC Pediatrics 2001 1:1

Effects of early postnatal steroids Outcome No. of patients RR 95% CI 3720 3286 2056 2523 1452 1.0 0.8 1.8 1.5 0.9-1.1 0.7-0.9 0.7-1.0 1.3-2.5 1.1-2.0 Mortality BPD at 36 wk Severe ROP GI perforation Cerebral palsy Halliday HL et al: Cochrane Database Syst Rev 2009

Effects of late postnatal steroids Outcome No. of patients RR 95% CI 936 471 558 621 777 0.9 0.7 1.4 0.8 1.1 0.7-1.2 0.6-0.9 1.1-1.8 0.3-2.0 0.8-1.6 Mortality BPD at 36 wk Severe ROP Blindness Cerebral palsy Halliday HL et al: Cochrane Database Syst Rev 2009

UNCERTAINTY

Dexamethasone in Tiny Babies – A Randomised Trial DART Dexamethasone in Tiny Babies – A Randomised Trial

Doyle LW et al: Pediatrics 2005; 115:655

Effects of intramuscular Vitamin A Outcome No. of patients RR 95% CI 807 693 646 570 1.0 0.9 0.7 0.7-1.3 0.7-1.0 0.4-1.3 0.6-1.2 Mortality BPD at 36 wk Severe IVH PVL Cerebral palsy N Engl J Med 1999 and Pediatrics 2005

Short Term Outcomes of the Caffeine Trial Caffeine Placebo Odds Ratio n/N n/N (95% CI) BDP Severe ROP Brain injury NEC PDA medical Tx PDA surgical Tx 350/963 49/965 126/967 63/1006 293/1001 45/1001 447/954 75/955 138/966 67/1000 381/999 126/999 0.2 0.5 1 2 5 Favors Caffeine Favors Placebo

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377 of 937 40% 431 of 932 46% DEATH OR DISABILITY Caffeine Placebo OR = 0.77 95% CI 0.64-0.93 p = 0.008

Long Term Outcomes of the Caffeine Trial Caffeine Placebo Odds Ratio n/N n/N (95% CI) Outcome Death or disability Death CP Cognitive delay Hearing loss Blindness 377/937 62/974 40/909 293/867 17/909 6/911 431/932 63/970 66/901 329/858 22/905 8/905 0.2 0.5 1 2 5 Favors Caffeine Favors Placebo

Caffeine is the drug of choice for prevention of BPD