Presented at the Neonatal Society 2001 Autumn Meeting.
Gopalakrishnan G1, Pearce S1, Dandrea J1, Mostyn A1, Walker RM2, Ramsay MM1, Stephenson T1, Symonds ME1
1 School of Human Development, University of Nottingham, Nottingham NG7 2UH
2 School of Biosciences, University of Nottingham, Nottingham NG7 2UH
Introduction: Epidemiological and experimental studies have indicated that maternal undernutrition at specific stages of pregnancy is associated with abnormal placental and fetal growth (1). For example, maternal nutrient restriction over the period of rapid placental growth (i.e. 30-80 days) followed by adequate nutrition up to term results in a longer fetus with a disproportionately larger placenta and increased glucocorticoid receptor mRNA abundance in a range of fetal tissues (2,3). These individuals could be at increased risk of adult diseases including hypertension and obesity. The aim of this study was to determine the consequences for plasma glucose and cortisol concentrations and blood pressure control in offspring born to ewes nutrient restricted (NR) between early to mid gestation.
Study design: Eighteen Welsh Mountain ewes were individually housed from 28 days gestation. Eight ewes were fed a NR diet (3.5 MJ/day) until 80 days gestation, and the remainder a control (C; n=10)) diet (6.8-7.5 MJ/day). After 80 days gestation, until term (147 days), all animals consumed 6.8-7.5 MJ/day, sufficient to meet their metabolisable energy requirements for maintenance and growth of the conceptus throughout pregnancy. Lambs were born spontaneously and at 6 months of age a carotid artery and jugular vein were surgically catheterised to allow drug administration, blood sampling and measurement of blood pressure. At least two days after surgery, mean, systolic and diastolic blood pressure were measured for a resting period of 30 minutes, before a continuous infusion of noradrenaline with dose increases (0.5-32ng/kg/min) at 10-minute intervals. Blood samples were taken before and after each infusion.
Results: Lambs born to NR ewes were heavier than those born to controls although there was no difference in body weight at 6 months. There was no difference in resting plasma cortisol between groups (NR 19.7 + 5.1; C 21.7 + 4.2 nmol/l) but the NR group of lambs with lower resting blood pressure showed a positive correlation between blood pressure and plasma cortisol (r²=0.75; P<0.026). This group also had lower basal plasma glucose concentrations compared to controls but and exhibited a non-significantly greater increase in plasma glucose (NR 1.66 + 0.69; C 0.86 + 0.16 mmol/l) following noradrenaline infusion. Blood pressure at the maximal noradrenaline dose was similar between groups, but the rise between resting and peak recordings was greater in lambs born to NR ewes (NR 45.3 + 4.8; C 32.0 + 2.0 mmHg (P=0.07)).
Conclusion: Nutrient restriction between early to mid gestation followed by adequate feeding up to term is associated with larger offspring who exhibit lower resting blood pressure and basal glucose as well as an altered blood pressure responsiveness to cortisol and noradrenaline. These adaptations may contribute to compromised blood pressure and glucose regulation in later life.
Acknowledgement: G. Gopalakrishnan is supported by a British Heart Foundation studentship.
References
1. Barker DJP. BMJ 1995; 311, 171-174.
2. Heasman L, Clarke L, Firth K, Stephenson T, Symonds ME. Pediatr. Res. 1998; 44, 546-551.
3. Whorwood, CB, Firth KM, Budge H, Symonds ME. Endocrinology 2001; 142, 2854-2864.