Further study of the inhibition of premature labor by indomethacin Part II double-blind study

Abstract

In the etiology of premature labor prostaglandins [PG] fulfill a significant role and indomethacin is a strong inhibitor of PG synthesis. The effect of indomethacin on premature labor was studied in a prospective randomized double-blind study in 36 patients. Eighteen patients received indomethacin and 18 received placebo; 200-300 mg of indomethacin was the total dosage in 24-h period. The activity of the uterus was monitored with a cardiotocograph. The mean duration of pregnancy and the mean birth weight in indomethecin group (36.4 wk, 2833 g) were both significantly greater (P < 0.001) than that in placebo group (31.2 wk, 2028 g). In the indomethacin group 3 children weighed < 2500 g compared with 14 in placebo group. In 15 of 18 indomethacin-treated patients (83.3%) premature labor was arrested after indomethacin treatment compared with 4 of 18 in the placebo group (22.2%). The indomethacin group had a mean 1-min APGAR score of 9.3 .+-. 0.2 whereas the placebo group showed a score of 7.8 .+-. 0.5 (P < 0.01). Three infants died from respiratory distress syndrome; 1 in the indomethacin group (1810 g) and 2 in the placebo group (600 and 1450 g). Autopsies in the infants demonstrated a typical picture of pulmonary atelectasis and hyaline membranes. There was no evidence of premature closure of the ductus arteriosus or pulmonary hypertension. Two mothers in the indomethacin group suffered minor discomfort, i.e., nausea, vomiting and vertigo. In both groups, no changes were noted, either during or after therapy in maternal blood pressure or maternal and fetal heart rate. Indomethacin was significantly more effective than placebo in inhibiting premature labor.