Affiliations: Departments of Neonatal Medicine and Pharmacy, Women's
Hospital, Greensboro, NC, USA | Graduate Pharmacy Education, Greensboro Area Health
Education Center, NC, USA | School of Pharmacy, University of North Carolina at
Greensboro, Greensboro, NC, USA | Department of Mathematics and Statistics, University
of North Carolina at Greensboro, Greensboro, NC, USA
Note: [] Corresponding author: Peter Gal, PharmD, BCPS, Greensboro AHEC,
Department of Graduate Pharmacy Education, Suite 100, 200 E. Northwood St.,
Greensboro, NC 27401-1020, USA. Tel.: +1 336 832 7932; Fax: +1 336 832 2851;
E-mail: peter.gal@mosescone.com
Abstract: Objectives: To examine any association of necrotizing enterocolitis
(NEC) and intestinal perforation (IP) in very low birth weight neonates with
indomethacin treatment, cumulative dose or maximum plasma concentrations. Methods: This is a retrospective 9-year cohort study of very
low birth weight infants (< 1500 grams) admitted to our neonatal intensive
care unit. The incidence of NEC and IP in infants who received indomethacin for
a PDA (N = 228) were compared to control infants who did not have PDA and
received no indomethacin (N = 628). Factors which were statistically
significant in a univariate analysis were then included in a logistic
regression model to determine their significance. Results: NEC occurred in 14 (6.1%) indomethacin-treated
infants compared to 47 (7.5%) control infants. When the incidence of NEC or
IP was restricted to events occurring within 14 days of indomethacin, 4 infants
(1.7%) had NEC. IP occurred in 14 (6.1%) indomethacin-treated infants,
but 10 had concurrent steroid therapy. IP also occurred in 4 (0.6%)
controls. Multivariate logistical regression revealed a lower risk of NEC with
indomethacin. The risk for NEC and IP is not increased with higher INDO doses
or INDO concentrations. Conclusions: Indomethacin treatment for PDA does not increase
NEC risk, and may decrease the risk. Indomethacin treatment is associated with
an increased risk of IP, especially when combined with systemic
glucocorticoids.
