Circulatory responses to maternal hyperoxaemia and hypoxaemia assessed non-invasively in fetal sheep at 0.3±0.5 gestation in acute experiments Torvid Kiserud * , Eric Jauniaux, Daniel West, Ozkan Ozturk, Mark A. Hanson Objectives To determine fetal haemodynamic responses to hyperoxaemia and hypoxaemia in early pregnancy. Design Repeated measurements in acute experiments. Setting Experimental physiology laboratory. Methods Non-invasive Doppler ultrasound of the umbilical vein, ductus venosus, umbilical and common carotid arteries of 12 fetal lambs (0.27±0.56 gestation) during maternal hyperoxaemia and hypoxaemia under keta- mine anaesthesia. The effect of gestational age, hyperoxaemia, and hypoxaemia were assessed based on analysis of variance for dependent measurements and P # 0.05 was considered signi®cant. Differences between groups were considered signi®cant if the 95% con®dence interval did not include zero. Results Gestational age had a signi®cant effect on the blood velocity in the umbilical vein and ductus venosus. There were no circulatory changes during hyperoxaemia, but a simultaneous increase of pCO 2 was an impor- tant confounder. However, hypoxaemia caused signi®cantly reduced heart rate, reduced maximum and weighted mean blood velocity, and augmented pulsation in the umbilical vein. Hypoxaemia also caused reduced velocities in the ductus venosus (peak velocity during systole and minimum during diastole, and time-averaged velocity) and augmented pulsation of the ¯ow velocity. Additionally, the pulsatility of blood ¯ow increased in the umbilical artery and was reduced in the common carotid artery. Conclusions Maternal hypoxaemia in early pregnancy causes similar fetal circulatory responses to those in late pregnancy: bradycardia, reduced venous ¯ow velocities, augmented pulsatility in veins and a redistributional ¯ow velocity pattern of the umbilical and common carotid arteries. INTRODUCTION One of the priorities of antenatal care and surveillance during labour is to detect insuf®cient oxygen delivery to the fetus in order to prevent subsequent damage. Doppler ultrasound of the umbilical artery applied in a high risk population has proved to be a valuable method of identi- fying fetuses at risk of having a low pO 2 and acidosis at birth 1,2 . Pronounced changes such as absent or reversed end-diastolic blood velocity in the umbilical artery iden- tify a group of fetuses with 36% perinatal mortality 2 . To interpret clinical ®ndings and understand the underlying mechanisms animal experiments have been indispensa- ble. During late pregnancy, an episode of acute hypox- aemia rapidly leads to a vagally mediated bradycardia and an increase in arterial blood pressure, followed by slower endocrine responses which maintain a high peripheral resistance in the fetus, elevated blood pressure and an increase in heart rate 3 . Fetal responses to hypox- aemia may differ in early and late gestation, but there have been very few experimental investigations of such responses in early pregnancy 4,5 in spite of the fact that early hypoxia is a possible cause of maldevelopment and perinatal morbidity. The size of the fetus in early preg- nancy is an important limitation for surgical intervention. However, using ultrasound, it is possible to gain consid- erable information about fetal responses non-invasively, even in early pregnancy. Hence the ®rst aim of the present study was to investigate fetal cardiovascular responses to acute hypoxaemia in the sheep during early gestation. In humans, treatment with hyperoxygenation has been attempted in pregnancies where the fetus had a low pO 2 or was suspected of having hypoxaemia 6 during preg- nancy or during labour 7 . It is not known whether such treatment improves outcome, or causes harm. Reduction in fetal heart rate 8 and changes in the pulsatile pattern of the blood velocity in the fetal middle cerebral artery, descending aorta and aortic isthmus 9 , and an increased blood velocity in the ductus venosus 10 were noted during maternal hyperoxaemia. Again, fetal responses are expected to be different in early gestation, but that has hardly been addressed. The aim of the present study was to determine the effect of maternal hyperoxaemia and hypoxaemia on fetal haemodynamics at 0.3±0.5 gestation in fetal sheep. q RCOG 2001 British Journal of Obstetrics and Gynaecology PII: S0306-5456(00)00096-6 British Journal of Obstetrics and Gynaecology April 2001, Vol. 108, pp. 359±364 www.bjog-elsevier.com * Correspondence: Dr T. Kiserud, Unit of Fetal Medicine, Department of Obstetrics and Gynaecology, University Hospital of Bergen, POB 1, N± 5021 Bergen, Norway. Department of Obstetrics and Gynaecology, Royal Free and University College Medical School, London, UK