Brief hypoxia in late gestation sheep causes prolonged disruption of fetal electrographic, breathing behaviours and can result in early labour.

KEY POINTS Brief episodes of severe fetal hypoxia can arise in late gestation due to interruption of normal umbilical blood flow Systemic parameters and blood chemistry indicate complete recovery within 1-2 hours, but the long-term effects on fetal brain functions are unknown Fetal sheep were subjected to umbilical cord occlusion (UCO) for 10 mins at 131 days gestation, and then monitored intensively until onset of labour or delivery (<145 days gestation) Normal patterns of fetal behaviour, including breathing movements, episodes of high and low voltage electorcortical activity, eye movements, and postural (neck) muscle activity were disrupted for 3-10 days after the UCO Preterm labour and delivery occurred in a significant number of the pregnancies after UCO, compared to the control (sham-UCO) cohort. ABSTRACT Complications arising from antepartum events such as impaired umbilical blood flow can cause significant fetal hypoxia. These complications can be unpredictable, difficult to detect, and thus we lack a detailed understanding of the (patho)physiological changes that occur between the antenatal in utero event and birth. In this study, we assessed the consequences of brief (∼10 mins) umbilical cord occlusion (UCO) in fetal sheep at ∼0.88 gestation on fetal plasma cortisol concentrations and fetal behaviour (electrocortical [ECoG], electo-oculargram [EOG], nuchal muscle electromyography [EMG] and breathing activities) in the days following UCO. UCO caused a rapid onset of fetal hypoxemia, hypercapnia, and acidosis; however, by 6h all blood parameters and cardioavascular status were normalised and not different from the control (Sham-UCO) cohort. Subsequently, the incidence of fetal breathing movements decreased compared to the control group, and abnormal behavioural patterns developed over the days following UCO and leading up to the onset of labour that included increased high voltage and sub-low voltage ECoG and EOG activities, and decreased nuchal EMG activity. Fetuses subjected to UCO went into labour 7.9 ± 3.6 days post-UCO (139.5 ± 3.2 days gestation) compared to the control group fetuses at 13.6 ± 3.3 days post-sham UCO (144 ± 2.2 days gestation; p<0.05), despite comparable increases in fetal plasma cortisol, and similar body weight at birth. Thus, a single transient episode of complete UCO late in gestation in fetal sheep can result in prolonged effects on fetal brain activity and premature labour, suggesting persisting effects on fetal cerebral metabolism. This article is protected by copyright. All rights reserved.