Question

• In premature infants, do the benefits of prophylactic indomethacin outweigh the risks?

Clinical Bottom Lines

1. Prophylactic indomethacin reduces the occurrence of Grade 3 and 4 IVH in preterm infants.¹
2. Prophylactic indomethacin reduces symptomatic PDA and PDA requiring surgical ligation in preterm infants.¹
3. Prophylactic indomethacin does not significantly affect neonatal mortality, long-term neurodevelopmental outcomes, pulmonary status, platelet counts, or renal function.
4. Prophylactic indomethacin does not significantly increase the risk of necrotizing enterocolitis, clinical bleeding, sepsis, or retinopathy of prematurity.

Summary of Key Evidence

1. Meta-analysis of 19 studies randomizing 2782 preterm infants (<37 weeks gestation).¹
2. Prophylactic indomethacin reduces the occurrence of Grade 3 and 4 IVH in preterm infants.  2588 patients studied, RR 0.66 (95% CI 0.53-0.82), NNT = 20.
3. 2193 patients were evaluated for symptomatic PDA with a RR 0.44 ( 95% CI 0.38-0.50),  NNT = 4.  1791 infants were followed for  PDA requiring surgical ligation with a RR of 0.51 (95% CI 0.37-0.71), NNT = 20.
4. 2115 infants were monitored for oliguria with a RR of 1.90 (95% CI 1.45-2.47), number needed to harm 16.  However, 618 infants were studied for elevated serum creatinine with a RR of 1.09 (95% CI 0.47-2.51).

Additional Comments

• Indomethacin is contraindicated in preterm neonates with necrotizing enterocolitis, thrombocytopenia, clinical bleeding, impaired renal function, or IVH.
• Based on data from 2001-2005, rates of IVH and PDA in Holden are higher than those in this meta-analysis, thus making the NNT even lower for both outcomes.
• A 1-mg vial of indomethacin costs $483 per UM pharmacy. Infants treated with prophylactic indomethacin had an average hospital cost of $95,175 vs. $99,955 in the control group.²

Citation

1. Fowlie PW, Davis PG. Prophylactic intravenous indomethacin for preventing mortality and morbidity in preterm infants. Cochrane Database for Systematic Reviews 2002, Issue 3. Art. No. CD000174. DOI: 10.1002/14651858.CD00174.
2. Rushing SB, Ment LR. Preterm birth: a cost benefit analysis. Semin Perinatol 28:444-450.

CAT Author: Katie Bates, MD

CAT Appraisers: Cynthia Chi, MD

Date appraised: February 14, 2007