Perinatal complications, morbidity and mortality are some 3- to 6-fold higher in twin relative to singleton fetuses, even after adjustment for gestational age (Cheung et al. 2000). While some studies have examined differences in the hypothalamic-pituitary-adrenal (HPA) axis between singleton and twin fetuses (Schwartz & Rose, 1998; Edwards & McMillen, 2002), no study has yet investigated basal and stimulated cardiovascular and other endocrine physiology in single vs. twin fetuses during late gestation. The present study has examined fetal cardiovascular (blood pressure, heart rate, femoral vascular resistance) and endocrine (ACTH, cortisol, catecholamines, vasopressin: AVP) variables in single and twin fetuses during baseline and during exposure to an episode of acute hypoxaemia.
Twenty sheep fetuses were chronically instrumented under general anaesthesia (1.5% halothane in O2/N2O) with vascular catheters and a flow probe around the fetal femoral artery. Of these, n = 10 were singleton and n = 10 were twin fetuses, in which only one fetus from each twin pregnancy was instrumented. At 0.9 gestation all fetuses were exposed to a single episode of acute hypoxaemia by reducing maternal Fi,O2 for 1 h. Fetal carotid blood samples were taken at appropriate intervals before, during and after the 1 h episode of acute hypoxaemia for analyses of blood gases, metabolites and concentrations of ACTH, cortisol, AVP (RIA) and catecholamines (HPLC), with assays validated for ovine plasma. All data were analysed by either one-way ANOVA or two-way ANOVA with repeated measures followed by Tukey’s test.
Basal blood gas and metabolic status was similar in singleton and twin fetuses and was appropriate for fetuses at 130 ± 3 dGA (pH 7.34 ± 0.01; Pa,O2, 22 ± 1 mmHg; blood glucose, 0.96 ± 0.10 mmol l-1). Basal heart rate was similar but mean arterial blood pressure (ABP) and femoral blood flow (FBF) tended to be lower (P = 0.07) in twin relative to singleton fetuses (HR, 166 ± 4 vs. 165 ± 5 beats min-1; ABP, 44.5 ± 2.3 vs. 51.4 ± 2.9 mmHg; FBF, 32.2 ± 3.3 vs. 38.5 ± 2.6 ml min-1). Basal ACTH (39.0 ± 4.7 vs. 30.7 ± 2.6 pg ml-1), adrenaline (98 ± 23 vs. 83 ± 13 pg ml-1) and AVP (2.4 ± 0.6 vs. 3.6 ± 0.6 pg ml-1) concentrations were similar, but basal cortisol was lower (17.2 ± 1.4 vs. 26.9 ± 3.3 ng ml-1) and noradrenaline higher (720 ± 167 vs. 359 ± 39 pg ml-1) in twin, relative to singleton, fetuses. In addition, the cardiovascular and plasma ACTH and catecholamine responses to acute hypoxaemia were similar, but there were trends for the increase in cortisol to be blunted, and that of AVP to be exacerbated, during hypoxaemia in twins relative to singleton fetuses, respectively. All ewes and fetuses were humanely killed at the end of all experiments by giving an overdose of barbiturates. At post-mortem twins were of significantly lower body weight than single fetuses (2.28 ± 0.14 vs. 2.86 ± 0.14 kg).
The data indicate that certain aspects of the physiological differences between singleton and twin fetuses may be related to body mass, such as basal blood pressure and femoral blood flow, while others reflect genuine alterations in basal and stimulated function (pituitary-adrenal axis) due to multiple pregnancy.
This work was supported by the British Heart Foundation and Tommy’s – The Baby Charity.