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Previous Volume 329:1602-1607 November 25, 1993 Number 22 Next

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ABSTRACT

Background The use of indomethacin as a tocolytic agent in pregnant women appears to be accompanied by a low incidence of neonatal complications. However, the neonatal effects of indomethacin have been studied primarily in infants born after 32 weeks' gestation. This study was designed to examine the incidence of neonatal complications in very premature infants.

Methods We identified 57 infants delivered at or before 30 weeks' gestation whose mothers had been treated with indomethacin for preterm labor and matched them with 57 infants whose mothers had not received indomethacin. The infants in the two groups were matched for sex, gestational age at delivery (mean [±SD], 27.6 ±2.0 weeks), exposure to betamethasone for 24 hours or more before delivery, and rupture of membranes 24 hours or more before delivery.

Results There were no significant differences between the two groups in birth weight, Apgar scores, cord-blood gas values, frequency of multiple gestation, or incidence of respiratory distress syndrome. The proportion of infants who required exogenous surfactant was similar, as were ventilator settings at 24 hours, the incidence of chronic lung disease, and the incidence of sepsis. The infants exposed to indomethacin had a lower urine output and higher serum creatinine concentrations during the first three days after delivery. More indomethacin-exposed infants had necrotizing enterocolitis (29 percent vs. 8 percent, P = 0.005), intracranial hemorrhage grade II to IV (28 percent vs. 9 percent, P = 0.02), and patent ductus arteriosus (62 percent vs. 44 percent, P = 0.05). More indomethacin-exposed infants with a patent ductus arteriosus required surgical ligation because of either a lack of initial response or a reopening of the duct after postnatal indomethacin therapy (50 percent vs. 20 percent of the unexposed infants, P = 0.05).

Conclusions Antenatal indomethacin therapy for preterm labor appears to increase the risk of serious neonatal complications in infants born at or before 30 weeks' gestation.

Source Information

From the Cardiovascular Research Institute (R.I.C.) and the Departments of Pediatrics (J.M., R.I.C.) and Obstetrics, Gynecology and Reproductive Sciences (M.E.N., J.A.K.), University of California, San Francisco, and the California School of Professional Psychology, Alameda, Calif. (B.A.B.C.).

Address reprint requests to Dr. Clyman at Box 0544, Rm. 1403 HSE, University of California, San Francisco, CA 94143.

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