TORONTO — Transdermal nitroglycerin improved neonatal outcome but did not significantly delay delivery according to the results of the Canadian Preterm Labour Nitroglycerin Trial.
“Given that there is no standard of care [for the management of preterm labor] and that no tocolytic has been shown to improve outcome, this is potentially very exciting,” said principal investigator Dr. Graeme N. Smith of Queen's University in Kingston, Ontario. His center and several others have already adopted this approach as standard, he said in an interview.
The study, which he presented at the annual meeting of the Society for Gynecologic Investigation, randomized 158 women between 24 and 32 weeks' gestation and in preterm labor either to placebo (81 patients) or a transdermal nitroglycerin, or glyceryl trinitrate (GTN), patch (77).
The primary outcome measured was a neonatal morbidity composite which included one or more of the following: chronic lung disease, necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), and perinatal mortality. The secondary outcome was the time to delivery.
Upon entry into the study and before randomization, all women received a 500-mL saline bolus (0.9%) to offset the potentially dehydrating effects of GTN. The GTN patch delivered a dose of 0.4 mg/hr and was replaced once after 24 hours.
In the 153 women left in the final analysis, neonatal outcome was significantly improved in those receiving the GTN patch, with a composite score of 3, compared with a score of 11 in the placebo group, for a relative risk of 0.29. This effect was limited to those who were at 28 weeks' gestation or less. There was one case of chronic lung disease in the GTN group, compared with seven in placebo; two cases of IVH in the GTN group, compared with one in placebo; and no cases of NEC, PVL, or perinatal mortality in the GTN group, compared with two, two, and three cases, respectively, in the placebo group.
Although there was no significant effect of GTN on time to delivery, the medication resulted in a nonsignificant 7-day prolongation of pregnancy, said Dr. Smith, suggesting that the effect might have reached significance with higher numbers.
GTN is a smooth muscle relaxant and thus might relax the smooth muscle of the uterus, he said. This effect was not observed, so he suggested the improvement in neonatal outcome might result from improved blood flow to the placenta or uterus. Side effects were seen more in the GTN group, with a relative risk of 1.41, headache being the most common.