A randomized double-blind study comparing the fetal effects of sulindac to terbutaline during the management of preterm labor.
OBJECTIVE
The object of this study was to compare the fetal effects of sulindac and terbutaline used in the management of preterm labor on the ductus arteriosus, middle cerebral artery, renal artery, umbilical artery, fetal urine production, and amniotic fluid index.


METHODS
In a randomized, double-blind study 20 patients with preterm labor and no evidence of fetal structural anomalies or intra-amniotic infection received either sulindac (200 mg orally every 12 hours for 6 doses) or terbutaline (5 mg orally every 4 hours) for 72 hours of therapy. All medications were administered from identical blister packs. Opaque glucose base tablets were given at 4-hour intervals in the sulindac treatment arm to mimic the dosing interval in the terbutaline arm of the study. The Doppler pulsatility indices for the ductus arteriosus, middle cerebral artery, renal artery and umbilical artery and also the fetal urinary output were obtained at baseline and 5, 12, 24, 48, and 72 hours after the medication was started. Doppler data were analyzed within each group with raw data and between groups with the change in pulsatility indices from baseline. Statistical analysis was performed with the Kolmogorov-Smirnov test for normality, repeated measures analysis of variance, Mann-Whitney rank sum test, and Student t test as appropriate. P <.05 (2-tailed) was used to denote statistical significance.


RESULTS
There were 10 patients in each group, with no difference in gestational age between the 2 groups (32.3 vs 31.7 weeks). Sulindac was stopped in 2 patients after severe ductal constriction was noted, in 1 at 12 hours and in the other at 24 hours. One patient at 33 weeks' gestation was delivered because of fetal distress after 46 hours of sulindac therapy. When analyzed across time within groups, the pulsatility index in the ductus arteriosus decreased significantly at 12 and 24 hours in the sulindac group but not the terbutaline group. No significant differences were noted in the middle cerebral artery, umbilical artery, renal artery, or fetal urinary output within either group over time. Significant differences in the change from baseline in pulsatility index of the ductus arteriosus between the sulindac and terbutaline groups were noted at 5, 12, 24, and 48 hours. A similar effect was noted in the change from baseline in pulsatility index of the middle cerebral artery at 48 and 72 hours. There was a significant decrease in the amniotic fluid index in both groups at 24, 48, and 72 hours. The amniotic fluid index in the sulindac group was significantly lower than that in the terbutaline group at 48 and 72 hours of therapy.


CONCLUSIONS
Sulindac constricted the fetal ductus arteriosus, with an effect noted within 5 hours of starting therapy. The constriction, which resolved in all cases within 48 hours of discontinuing therapy, had minimal effects on the pulsatility index of the middle cerebral artery, renal artery, and umbilical artery. Sulindac and terbutaline both resulted in a significant reduction in the amniotic fluid index, with sulindac having a greater effect.
Kramer
W B
WB
Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas, USA.
Saade
G R
GR
Belfort
M
M
Dorman
K
K
Mayes
M
M
Moise
K J
KJ
D000653:Amniotic Fluid; D002536:Cerebral Arteries / Q000503:physiopathology; D016861:Cyclooxygenase Inhibitors; D004311:Double-Blind Method; D004373:Ductus Arteriosus / Q000503:physiopathology; D005260:Female; D005333:Fetus / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology; D005865:Gestational Age; D006801:Humans; D007752:Obstetric Labor, Premature / Q000188:drug therapy* / Q000503:physiopathology; D011247:Pregnancy; D011673:Pulsatile Flow; D013467:Sulindac / Q000009:adverse effects* / Q000627:therapeutic use; D013726:Terbutaline / Q000009:adverse effects* / Q000627:therapeutic use; D015149:Tocolytic Agents; D014469:Umbilical Arteries / Q000503:physiopathology; D014556:Urine