Neurodevelopmental follow-up at 36 months' corrected age of preterm infants treated with prophylactic indomethacin

Background: Previous reports have suggested that prophylactic indomethacin decreases cerebral blood flow and may play a role in the development of isc hemic brain injury and developmental handicaps. Objective: To assess the neurodevelopmental outcome of subjects at 36 month s' corrected age (CA) who, as low-birth-weight infants, received prophylact ic low-dose indomethacin within the first 24 hours of life to prevent paren t ductus arteriosus. Setting: Newborn intensive care nursery and outpatient follow-up clinic at Children's Hospitals and Clinics of Minneapolis, Minneapolis, Minn. Design: Ninety infants with birth weights of 600 to 1250 g were entered int o a prospective, randomized, controlled trial to receive either prophylacti c indomethacin, 0.1 mg/kg, or placebo in the first 24 hours and again every 24 hours for 6 doses to prevent patent ductus arteriosus. Nonresponders we re treated with standard therapeutic indomethacin or ligation. Neurodevelop mental assessment at approximately 36 months' CA included medical and devel opmental histories, physical examinations, and developmental testing using the Bayley II Scales of infant Development on subjects up to 42 months' CA. Subjects were classified as (1) normal, (2) mildly to moderately abnormal, or (3) severely impaired. Results: Forty-two (98%) of 43 subjects who received prophylactic indometha cin survived compared with 46 (98%) of 47 who received placebo. Sixty-six ( 75%) of 88 survivors were seen for neurodevelopmental assessment at 36 mont hs' CA. This group included 29 (69%) of 42 who received prophylactic indome thacin and 37 (80%) of 46 who received placebo. Twenty-three (79%) of 29 in fants in the prophylactic indomethacin group had normal neurodevelopmental assessments at 36 months' CA compared with 26 (70%) of 37 placebo-treated s ubjects (P = .68). Of 4 significantly impaired subjects treated with prophy lactic indomethacin, 1 had spastic diplegia; 1, spastic quadriplegia; 1, co gnitive delay; and 1, significant motor delay. Of 8 significantly impaired placebo-treated subjects, 7 had spastic diplegia; 1, microcephaly. Conclusion: The use of prophylactic low-dose indomethacin when initiated in the first 24 hours of life in low-birth-weight infants to prevent patent d uctus arteriosus is not associated with adverse neurodevelopmental outcome at 36 months' CA.