Neurodevelopmental outcome of premature infants after exposure to antenatal indomethacin

Sanjiv B Amin, Majeeda Kamaluddeen, Madhavi Sangem
American Journal of Obstetrics and Gynecology 2008, 199 (1): 41.e1-8

OBJECTIVE: This study was undertaken to evaluate the effect of antenatal indomethacin exposure on neurodevelopmental outcomes of premature infants.

STUDY DESIGN: A retrospective cohort study was performed to compare neurodevelopmental outcomes between premature infants exposed to antenatal indomethacin and infants unexposed to antenatal indomethacin. Inclusion criteria included all 23-29 weeks' gestational age infants delivered between January 1998 and December 2002 who had neurodevelopmental evaluation performed at 16-24 months corrected age. Outborn infants and those with major congenital malformations or chromosomal problems were excluded. Continuous and categorical variables were analyzed by using t test and chi(2) test, respectively.

RESULTS: A total of 255, 23-29 weeks' gestational age infants were delivered between January 1998 and December 2002. Of the 87 infants who met inclusion criteria, 29 infants were exposed to antenatal indomethacin (mean dose 267 mg and median duration 3 days) and 58 infants were unexposed to antenatal indomethacin. There were no significant differences between the 2 groups in clinical characteristics, except for gestational age, mode of delivery, and antenatal steroid exposure. There was no significant difference in major neurosensory abnormality (cerebral palsy and/or deafness and/or blindness); however, the proportion of infants with subnormal Bayley-Mental Developmental Index (70 or less) and neurodevelopmental impairment (neurosensory abnormality and/or Mental Developmental Index 70 or less) was significantly less in the group exposed to antenatal indomethacin compared with unexposed group. When controlled for confounders including antenatal steroids, antenatal indomethacin was not associated with Mental Developmental Index 70 or less (odds ratio 0.44, 95% confidence interval 0.12-1.5) and neurodevelopmental impairment (odds ratio 0.4, 95% confidence interval 0.13-1.2) by using logistic regression. Subgroup analysis of 12 infants exposed to antenatal indomethacin within 48 hours of birth was not associated with neurodevelopmental impairment (odds ratio 0.2, 95% confidence interval 0.03-1.02) compared with unexposed group.

CONCLUSION: Antenatal indomethacin is not associated with abnormal neurodevelopmental outcome in infants 29 or less weeks' gestational age.

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