Effects of antenatal dexamethasone and hyperglycemia on cardiovascular adaptation to asphyxia in preterm fetal sheep

Abstract

Antenatal glucocorticoids improve outcomes among premature infants but are associated with hyperglycemia, which can exacerbate hypoxic-ischemic injury. It is still unclear how antenatal glucocorticoids or hyperglycemia modulate fetal cardiovascular adaptations to severe asphyxia. In this study, preterm fetal sheep received either saline or 12 mg i.m. maternal dexamethasone, followed 4 h later by complete umbilical cord occlusion (UCO) for 25 min. An additional cohort of fetuses received titrated glucose infusions followed 4 h later by UCO, to control for the possibility that hyperglycemia contributed to the cardiovascular effects of dexamethasone. Fetuses were studied for 7 d after UCO. Maternal dexamethasone was associated with fetal hyperglycemia (p<0.001), increased arterial pressure (p<0.001) and reduced femoral (p<0.005) and carotid (p<0.05) vascular conductance before UCO. UCO was associated with bradycardia, femoral vasoconstriction and transient hypertension. For the first 5 min of UCO, fetal blood pressure in the dexamethasone-asphyxia group was greater than saline-asphyxia (p<0.001). However, the relative increase in arterial pressure was not different from saline-asphyxia. Fetal heart rate and femoral vascular conductance fell to similar nadirs in both saline and dexamethasone-asphyxia groups. Dexamethasone did not affect the progressive decline in femoral vascular tone or arterial pressure during continuing UCO. By contrast, there were no effects of glucose infusions on the response to UCO. In summary, maternal dexamethasone but not fetal hyperglycemia increased fetal arterial pressure before and for the first 5 min of prolonged UCO but did not augment the cardiovascular adaptations to acute asphyxia.

Physiological control of fetal heart rate variability during labour: implications and controversies

“…Two doses of 12 mg of maternal dexamethasone augmented the cardiovascular response during 1 h of moderate hypoxaemia in near-term fetal sheep, including a more persistent deceleration, greater hypertension and increased femoral vasoconstriction (Jellyman et al 2004;Jellyman et al 2005). In contrast, 12 mg of dexamethasone given 4 h earlier did not materially alter the cardiovascular adaptation to severe hypoxaemia induced by 25 min of complete UCO in preterm fetal sheep (Lear et al 2020c), but worsened the severity of brain injury due to the independent effects of dexamethasone-induced hyperglycaemia (Lear et al 2018a). Dexamethasone did not alter time-domain measures of FHRV nor fetal body movements during 25 min of UCO (Lear et al 2020c).…”

“…In contrast, 12 mg of dexamethasone given 4 h earlier did not materially alter the cardiovascular adaptation to severe hypoxaemia induced by 25 min of complete UCO in preterm fetal sheep (Lear et al . 2020c), but worsened the severity of brain injury due to the independent effects of dexamethasone‐induced hyperglycaemia (Lear et al . 2018a).…”

“…In contrast, 12 mg of dexamethasone given 4 h earlier did not materially alter the cardiovascular adaptation to severe hypoxaemia induced by 25 min of complete UCO in preterm fetal sheep (Lear et al 2020c), but worsened the severity of brain injury due to the independent effects of dexamethasone-induced hyperglycaemia (Lear et al 2018a). Dexamethasone did not alter time-domain measures of FHRV nor fetal body movements during 25 min of UCO (Lear et al 2020c). The disparity between these findings supports the concept that glucocorticoids have a time-dependent effect on the fetal adaptation to hypoxaemia, which is additionally modulated by the severity of hypoxaemia.…”

“…2004; Lear et al . 2020c). It is unknown whether such patterns occur during labour‐like hypoxaemia, but there is some suggestion that they may occur in human fetal compromise (Hems, 1973).…”

“…The decrease in body movements is most likely associated with a reduction in FHRV and accelerations, but there is some evidence that this is not the full story. Fetal sheep exposed to prolonged severe UCO initially suppress fetal body movements before transiently performing high-amplitude 'jerking' movements (George et al 2004;Bennet, 2017) in association with increased time-domain measures of FHRV (George et al 2004;Lear et al 2020c). It is unknown whether such patterns occur during labour-like hypoxaemia, but there is some suggestion that they may occur in human fetal compromise (Hems, 1973).…”