title: The physiology of cervical ripening and the induction of labour: A potential role for the nitric oxide donor isosorbide mononitrate
Creators: name: Nicoll, Antony Edward
Publisher: name: University of Glasgow
Year: 2001
Subjects: subject: Physiology, Pharmacology, Obstetrics

description: The ideal agents for the induction of labour should be clinically effective, easy to administer, cost- effective and safe for both mother and fetus. Mechanical devices, oestrogens, progesterone antagonists, relaxin, and prostaglandins have all been used to induce cervical ripening, with varying rates of efficacy and adverse effects. The intra-vaginal administration of the nitric oxide donor isosorbide mononitrate (IMN) is effective at inducing cervical ripening in the first trimester of pregnancy. When used to induce cervical ripening in the first trimester, intra-vaginal IMN also has fewer adverse effects than intra-vaginal prostaglandins. Nitric oxide is a potent vasodilator. The effects of intra-vaginal IMN on maternal and fetal haemodynamics in pregnant women at term are not known. The first two chapters of this thesis provide a review of the physiology of parturition and of the agents that can be used to artificially induce cervical ripening. The final part of this thesis will present the results of a study of the maternal and fetal haemodynamic effects of intra-vaginal IMN administered to pregnant women at terra. Study Design: A double blind randomised controlled trial. 36 women were randomised to receive 20 milligrams intra-vaginal IMN (n=13), 40 milligrams intra-vaginal IMN (n=11), or no treatment (a vaginal examination only) (n=12). Maternal pulse, blood pressure and fetal heart rate were recorded before the administration of any treatment and subsequently at 30-minute intervals until 360 minutes. Umbilical artery resistance index and pulsatility index measurements were made at 0, 180 and 330 minutes. Participating women were asked to complete a symptom questionnaire immediately before the administration of the treatment and again at 360 minutes. On completion of the study cervical score was determined, and if required further cervical ripening was achieved with prostaglandins in accordance with the local protocol. Other outcome measures included mode of delivery, length of labour for those women who progressed to a vaginal delivery, volume of blood loss at delivery, umbilical cord pH, Apgar scores at 1 and 5 minutes, analgesic requirements in labour and whether or not infants required admission to the neonatal unit. Results: Mean maternal pulse rate was greater following the intra-vaginal administration of 20 and 40 milligrams IMN compared with the control group (p = 0.003 and p = 0.01 respectively). Mean maternal systolic and diastolic blood pressures were lower following the intra-vaginal administration of 40 milligrams IMN compared with the control group (p = 0.006 and p = 0.001). Mean maternal diastolic blood pressure was lower following the intra-vaginal administration of 20 milligrams IMN compared to the control group (p = 0.01). Neither dose of IMN had a significant effect on mean fetal heart rate and umbilical artery resistance or pulsatility index. 69% and 91% of participants reported a headache following the administration of 20 mg and 40 mg IMN respectively, compared to 8% of the control group (p = 0.001). None of the study participants required treatment for maternal hypotension, or maternal or fetal tachycardia. The numbers were too small to demonstrate any statistically significant change in cervical score and there were no statistically significant differences in other outcome measures. Conclusion: The intra-vaginal administration of 20 mg and 40mg IMN to pregnant women at term has an effect on maternal haemodynamics, but this effect does not appear to be of clinical significance. In this study no effect on fetal haemodynamics was demonstrated following the intra-vaginal administration of 20 mg and 40mg IMN to pregnant women at term. This thesis lays the foundation for further studies using IMN as a cervical ripening agent during the induction of labour in pregnant women at term.