[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.

METHODS

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.