[Maternal and neonatal effects of indomethacin administrated during pregnancy. Apropos of 18 cases].

Background: There have been several reports that prolonged exposure of pregnant women to indomethacin for tocolysis may have significant pharmacological effects on the fetus or newborn.

Patients: Eighteen pregnant women were given indomethacin during the year 1989 for treatment of premature labor (n = 16) or polyhydramnios (n = 2). Treatment was started at gestational week 28.1 +/- 2.5 and was discontinued at gestational week 30.7 +/- 1.8. The mean age of the women at the onset of pregnancy was 30.6 +/- 5.3 years. The daily dose of indomethacin was initially 200 mg (2-3 mg/kg), then 107 +/- 59 mg. The cumulative dose was 1,820 +/- 2,370 mg. The duration of treatment was 18.1 +/- 16.4 days (less than 7 days in 8 women).

Results: The term at delivery was 33.4 +/- 3.3 weeks (11 after 32 weeks). The mean interval between discontinuation of treatment and delivery was 19.0 +/- 18.7 days. Indomethacin was effective in 10 cases of premature labor, and gestation was prolonged by 52.6 +/- 19.2 days. Among the 23 live-born neonates, 5 developed renal insufficiency attributed to indomethacin (4 premature labor, 1 hydramnios). The kidney failure with early hyperkalemia was cured within about 7 days in 4 cases. The remaining neonate also suffered from severe prolonged hypoxia and died on day 4.

Conclusions: Administration of indomethacin for premature labor places the fetus at risk because of the short drug-free interval before birth. High daily or cumulative doses of indomethacin dit not result in adverse effects.