PII: S0022-3476(95)70286-5

Abstract

Lemke et al. point out that other studies have not shown an increased incidence of bronchopulmonary dysplasia nor an increase in intensive care requirements after antenatal indomethacin therapy. Several factors are potentially responsible for the outcome differences among recent studies.1Norton ME Merill J Cooper BA Kuller JA Clyman RI. Neonatal complications after the administration of indomethacin for preterm labor.N Engl J Med. 1993; 329: 1602-1607Crossref PubMed Scopus (374) Google Scholar, 2Major CA Lewis DF Harding JA Porto MA Garite TJ. Tocolysis with indomethacin increases the incidence of necrotizing enterocolitis in the low-birth-weight neonate.Am J Obstet Gynecol. 1994; 170: 102-106Abstract Full Text PDF PubMed Google Scholar, 3Eronen M Pesonen E Kurki T Teramo K Ylikorkala O Hallman M Increased incidence of bronchopulmonary dysplasia after antenatal administration of indomethacin to prevent preterm labor.J PEDIATR. 1994; 124: 782-788Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar Norton et al.1Norton ME Merill J Cooper BA Kuller JA Clyman RI. Neonatal complications after the administration of indomethacin for preterm labor.N Engl J Med. 1993; 329: 1602-1607Crossref PubMed Scopus (374) Google Scholar and Major et al.2Major CA Lewis DF Harding JA Porto MA Garite TJ. Tocolysis with indomethacin increases the incidence of necrotizing enterocolitis in the low-birth-weight neonate.Am J Obstet Gynecol. 1994; 170: 102-106Abstract Full Text PDF PubMed Google Scholar reported neonatal complications in infants born during indomethacin tocolysis after retrospective cohort studies, whereas ours was a randomized trial involving a small number of infants.3Eronen M Pesonen E Kurki T Teramo K Ylikorkala O Hallman M Increased incidence of bronchopulmonary dysplasia after antenatal administration of indomethacin to prevent preterm labor.J PEDIATR. 1994; 124: 782-788Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar Median birth weights were 2217 gm (range, 630 to 4930 gm; n = 42) in the indomethacin group and 2115 gm (775 to 4100 gm; n = 45) in the nylidrin group. The corresponding gestational ages were 34.7 weeks (range, 24.4 to 41.6 weeks) and 33.7 weeks (25.4 to 40.6 weeks), respectively. Among the infants born within 120 hours of the start of tocolysis, there were no significant differences in the median birth weights: 1125 gm (range, 630 to 2390 gm; n = 11) and 1320 gm (775 to 2120 gm; n = 17), respectively (p = 0.12). Median gestational ages were 28.1 weeks (range, 24.4 to 33.3 weeks) in the indomethacin group and 29.7 weeks (range, 25.4 to 33.1 weeks) in the nylidrin group (p = 0.11). When adjusted for gestation with logistic regression, the odds of bronchopulmonary dysplasia among all recipients of indomethacin remained higher than in the nylidrin group (odds ratio, 7.2; 95% confidence interval, 1.4 to 36; p = 0.03). A similar difference was evident among the 28 infants born within 120 hours after the onset of tocolysis (odds ratio, 8.4; 95% confidence interval, 1.1 to 65; p = 0.04). Differences in treatment practices may be responsible for the observed differences in outcome. In the other studies antenatal glucocorticoid therapy was frequently used (Norton et al., 89%; Major et al., 83% to 86%).4Merrill JD Clyman RI Norton ME Indomethacin as a tocolytic agent: the controversy continues.J PEDIATR. 1994; 124: 734-736Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar In our study, few mothers received antenatal glucocorticoid therapy (10%), or surfactant in respiratory distress syndrome (41%). Antenatal glucocorticoid treatment and surfactant administration in respiratory distress syndrome5Kari A Hallman M Eronen M et al.Prenatal dexamethasone treatment in conjunction with rescue therapy of human surfactant: a randomized placebo-controlled multicenter study.Pediatrics. 1994; 93: 730-736PubMed Google Scholar were studied in parallel with the indomethacin study; there was no patient overlap between the two trials. The known beneficial effects of glucocorticoid therapy (acceleration of lung maturation, closure of ductus, improved renal water clearance, improved antioxidant defense) may compensate for the adverse effects of antenatal indomethacin therapy (delay in closure of ductus, delay of surfactant maturation, antidiuresis, generation of proinflammatory leukotrienes) contributing to the risk of bronchopulmonary dysplasia. The outcome of infants born prematurely during indomethacin tocolysis may be improved by the use of antenatal glucocorticoid therapy, by early surfactant therapy in respiratory distress syndrome, and by early closure of the ductus arteriosus. However, serious concerns about the safety of using indomethacin as a tocolytic agent remain. There is a need for experimental studies and randomized clinical trials aimed at improving the safety and efficacy of tocolytic therapy in preterm labor. 9/35/63862