Antenatal glucocorticoid therapy is routinely used to treat mothers threatened with preterm labour (NIH Development Conference, 1995); however, little is known about the mechanisms mediating glucocorticoid-induced fetal hypertension. Direct I.V. infusion of ovine fetuses with synthetic glucocorticoids leads to a pronounced increase in fetal arterial blood pressure (FBP) associated with a rise in femoral vascular resistance (FVR) (Derks et al. 1997). However, in human clinical practice gluco-corticoids are administered by repeated, maternal I.M. injections. Whilst maternal injection of glucocorticoids is known to cause fetal hypertension in sheep (Bennet et al. 1999), the effects of this treatment on fetal vascular resistance remain unknown. This study investigated the pressor and femoral vasoconstrictor effects of repeated, maternal injection versus continuous fetal infusion with dexamethasone (dex).

Experiments were carried out in accordance with UK legislation. At 118 days of gestation (term ca 145 days), 37 fetal sheep were instrumented under halothane (1.5 % in O₂/N₂O) with catheters and a femoral Transonic flow probe. At 124 days, the animals received one of the following treatments: (1) maternal dex group (n = 5); ewes received 2 X 12 mg daily I.M. injections of dex in saline, (2) fetal dex group (n = 18); fetuses were continuously infused I.V. for 48 h with dex (2.2 ± 0.6 mg kg^-1 h^-1 in saline at 0.5 ml h^-1), and (3) fetal saline group (n = 14); fetuses were infused continuously with saline at 0.5 ml h^-1. At the end of the protocol ewes and their fetuses were killed using an overdose of sodium pentobarbitone (200 mg kg^-1).

Prior to infusion, FBP and FVR were similar in maternal dex (41.9 ± 3.7 mmHg and 1.6 ± 0.2 mmHg (ml min^-1)^-1, respectively), fetal dex (44.7 ± 2.1 and 1.5 ± 0.1) and fetal saline (42.9 ± 2.0 and 1.3 ± 0.1) groups. During administration, pronounced increases in FBP occurred in both fetal and maternal dex groups (Fig. 1). The magnitude of the maximal increase in FBP was similar in maternal dex (9.3 ± 1.9 mmHg) and fetal dex (9.9 ± 0.9) groups; however, the temporal nature of the response differed with the mode of dex administration. In the fetal dex group, glucocorticoid-induced hypertension was associated with an increase in FVR. Conversely, in the maternal dex group, an increase in FVR occurred in response to the first, but not to the second, maternal injection (Fig. 1).

In contrast to continuous fetal dex treatment, repeated maternal dex injection dissociates the fetal pressor and vasoconstrictor responses by the second injection.

This work was supported by Tommy’s Campaign, UK.

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Figure 1. Mean (± S.E.M.) change from baseline in FBP and FVR during fetal saline infusion, or dex administration by infusion of the fetus (bar) or I.M. maternal injection (arrows). a: P < 0.05 vs. fetal saline; b: P < 0.05 vs. fetal dex (two-way ANOVA + Tukey test for daily areas under the curve).