Oral Submitted Presentations S53

2A-4 Maternal prenatal protein-energy supplementation is not

associated with offspring blood pressure at 11 16 years

of age in rural Gambia

S. Hawkesworth1,2 *, A.J.C. Fulford1,2, A.M. Prentice1,2,

S.E. Moore2. 1MRC International Nutrition Group, London School

of Hygiene and Tropical Medicine, London, UK, 2MRC Keneba,

MRC Laboratories, Fajara, The Gambia

E-mail: sophie.hawkesworth@lshtm.ac.uk

Aims: To investigate whether protein-energy supplementation

of pregnant women is associated with blood pressure in their

offspring.

Study design: A follow-up study of a cluster randomised controlled

trial (RCT) of protein-energy supplementation during pregnancy.

Subjects: 1267 adolescents (11 16 years) in rural Gambia, whose

mothers had taken part in a cluster-RCT during their pregnancy. In

the original trial, 28 villages were randomised to receive protein-

energy biscuits from 20 weeks gestation until birth (intervention)

or for 20 weeks after birth (control). The supplement significantly

increased birth weight and perinatal survival in the intervention

arm (Ceesay, Prentice et al. 1997).

Outcome measures: Blood pressure was measured in triplicate

using the Omron 705IT automated device on a single visit, following

standard operating procedures.

Results: Using generalised estimating equations to take into

account the cluster design of the trial and adjusted for age,

sex, rural or urban location and season of birth we observed no

difference in systolic blood pressure, diastolic blood pressure, pulse

pressure or mean arterial pressure between the two groups. The

difference in systolic blood pressure between the intervention

and control groups was 0.47 mmHg (95% CI: 1.14 to 2.08) and for

diastolic blood pressure it was 0.01 mmHg (95% CI: 1.24 to 1.23).

In addition, there was no evidence of an interaction of the

treatment effect with age, sex, location or season of birth.

Conclusions: In rural Gambia there was little evidence to

suggest that protein-energy supplements given to pregnant women

influenced their offspring’s blood pressure at 11 16 years of age.

Reference(s)

Ceesay, S.M., A.M. Prentice, et al. (1997). Effects on birth weight and

perinatal mortality of maternal dietary supplements in rural Gambia:

5 year randomised controlled trial. BMJ 315: 786 90.

2A-5 Programming of energy balance alterations in early life

leptin and hypothalamic development by maternal

nutritional manipulation

E.C. Cottrell1 *, R.L. Cripps1, Z.A. Archer2, J. Duncan2,

J.G. Mercer2, S.E. Ozanne1. 1Department of Clinical Biochemistry,

University of Cambridge, Addenbrooke’s Hospital, Hills Rd,

Cambridge CB2 2QR; 2Division of Obesity and Metabolic Health,

Rowett Research Institute, Greenburn Rd, Busksburn, Aberdeen,

Scotland, UK

E-mail: ecc35@cam.ac.uk

Aim: To determine in detail the postnatal ontogeny of leptin

hormone profile and hypothalamic energy balance pathways in an

established rodent model of altered early life nutrition.

Study design: Female rat dams were fed a low-protein diet

during pregnancy or lactation, or a control diet throughout.

Crossover manipulations were employed postnatally, to generate

three groups of offspring with differing early life nutrition and

growth trajectories.

Subjects: Blood samples and whole brains were collected from

male offspring at ten timepoints over the course of lactation,

between postnatal days 3 and 18.

Outcome Measures: Plasma leptin was measured using ELISA, and

hypothalamic leptin receptor and candidate neuropeptide gene

expression by in situ hybridisation.

Results: The profile of postnatal leptin differed markedly between

groups (p < 0.05). Control offspring showed a single but prolonged

surge in leptin levels during lactation. Recuperated animals (born

to low-protein fed dams then suckled by control females) exhibited

two leptin peaks, at days 11 and 15. Postnatal low-protein (PLP)

offspring (born to control dams and suckled by low-protein fed

females) had lower leptin levels at each timepoint (p < 0.05).

Despite dramatic differences in postnatal leptin profiles, we

observed a rise in leptin receptor (ObRb) gene expression that

occurred at an equivalent time, and of similar magnitude, in each

nutritional group.

Conclusions: These findings underline how minimal our current

knowledge is of early hypothalamic development, and suggest the

presence of a leptin independent ObRb surge, the regulation and

function of which remains unknown.

2A-6 Periconceptional undernutrition of ewes decreases

glucose tolerance in their postnatal offspring

S.E. Todd*, M.H. Oliver, A.L. Jaquiery, F.H. Bloomfield,

J.E. Harding. Ngapouri Research Station, Liggins Institute,

University of Auckland, RD2, Reporoa, New Zealand

E-mail: s.todd@auckland.ac.nz

Aims: To determine whether moderate maternal undernutrition

spanning the period of conception influences glucose tolerance of

offspring before and after puberty.

Study design: Ewes were fed to maintain bodyweight (N), or were

undernourished from 60d before, to 30d after mating (UN) to

reduce weight by 10 15%.

Subjects: Glucose tolerance tests (GTT) were performed on

offspring of periconceptionally undernourished ewes at 4 months

(pre-puberty, n = 44) and 10 months of age (post-puberty, n = 49).

Outcome Measures: Glucose area under the curve (AUC) was

analysed using multiple regression. Values are mean±SEM or mean

(95% CI).

500

600

700

800

900

Pla

sm

aG

luco

se

AU

C

(mM

.min

-1)

4mthsMale

4mthsFemale

10mthsMale

10mthsFemale

* *

Glucose AUC in 4- and 10-month offspring. Open bars represent

group N, solid bars, UN. *Significant group effect at 10 months

(p < 0.005).

Results: Treatment had no effect on postnatal weight or basal

glucose at 4 or 10 months. At 4 months there was no effect

of group, sex or twinning on glucose AUC. However AUC

decreased with every kilogram increase in bodyweight at birth ( 46

[ 88 to 3] mM·min 1·kg 1; p < 0.01), and increased with current

weight (+9 [0.7 17.2] mM·min 1·kg 1; p < 0.05). At 10 months

there was no significant effect of sex, twinning, birthweight, or

current weight, but AUC was greater in UN than N animals (+93

[30 157] mM·min 1; p < 0.05).

Conclusions: Maternal periconceptional undernutrition impairs

glucose tolerance in their post-pubertal offspring. These data

suggest that maternal nutrition around the time of conception may

have important implications for glycaemic regulation in the next

generation.