Evidence-Based Neonatal Drug Therapy for ...

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Jun 5, 2008 - Barbara Schmidt a, b Robin Roberts b David Millar c Haresh Kirpalani a, b. aDepartment of Pediatrics, Children's Hospital of Philadelphia and ...
11th Nils W. Svenningsen Memorial Lecture Neonatology 2008;93:284–287 DOI: 10.1159/000121453

formerly Biology of the Neonate

Published online: June 5, 2008

Evidence-Based Neonatal Drug Therapy for Prevention of Bronchopulmonary Dysplasia in Very-Low-Birth-Weight Infants Barbara Schmidt a, b Robin Roberts b David Millar c Haresh Kirpalani a, b a

Department of Pediatrics, Children’s Hospital of Philadelphia and the University of Pennsylvania, Philadelphia, Pa., USA; Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ont., Canada; c Royal Maternity Hospital, Belfast, UK b

Key Words Very-low-birth-weight infant ⴢ Vitamin A ⴢ Corticosteroids ⴢ Cerebral palsy ⴢ Caffeine ⴢ Bronchopulmonary dysplasia

should be avoided during the first few days of life. However, when given during the 2nd week of life to infants at high risk of BPD corticosteroids may have important short- and longterm benefits. These should be urgently confirmed or refuted in well-designed controlled trials.

Abstract Corticosteroids, intramuscular vitamin A and caffeine reduce the risk of bronchopulmonary dysplasia (BPD) in verylow-birth-weight infants. We compared the size of the beneficial drug effects on BPD and evaluated long-term drug safety by estimating the number needed to treat (NNT) and the number needed to harm (NNH) for the outcome of cerebral palsy (CP). When given prophylactically during the first 4 days of life, corticosteroids increase the risk of CP (NNH 22; 95% CI: 12–133). When prescribed between days 7 and 14, corticosteroids reduce the 28-day mortality rate in addition to reducing BPD. Their effect on CP remains uncertain: the limited data available are consistent with a best-case scenario (NNT 15) and a worst-case scenario (NNH 14). Although repeated intramuscular injections of vitamin A during the 1st month of life reduce BPD (NNT 12; 95% CI: 6–94), estimates for CP range from an NNT of 11 to an NNH of 33. Early use of caffeine reduces both BPD and CP. The NNT for BPD is 10 (95% CI: 7–16), while the NNT for CP is 34 (95% CI: 20–132). We conclude that caffeine is the drug of choice for the prevention of BPD in very-low-birth-weight infants. Corticosteroids

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What Is Bronchopulmonary Dysplasia?

Bronchopulmonary dysplasia (BPD) is a common morbidity of very preterm and very-low-birth-weight (VLBW !1,500 g) infants. It is a chronic respiratory disease that results from abnormal repair after acute lung injury and from impaired lung growth. Different definitions of BPD have been used over the past 40 years, but one of the most enduring has been oxygen dependency at 36 weeks’ postmenstrual age [1, 2]. More recently, efforts have been made to distinguish three different levels of disease severity [3] and to standardize the oxygen saturation target range on which a classification of oxygen dependency is based [4]. The future application of these revised definitions should make the diagnosis of BPD more precise. However, the simple definition of oxygen dependency at 36 weeks’ postmenstrual age has aged well since it was first proposed 20 years ago. Using this definition, Dr. Barbara Schmidt Division of Neonatology, Children’s Hospital of Philadelphia and the Hospital of the University of Pennsylvania Ravdin 8, 3400 Spruce Street, Philadelphia, PA 19104 (USA) Tel. +1 215 662 3228, Fax +1 215 349 8831, E-Mail [email protected]

02.06.2008 10:55:18

Table 1. Efficacy of neonatal drugs for prevention of BPD: outcome of BPD

Drug

Caffeine [6] Vitamin A [5] Corticosteroids,