Posters S141

glucose tolerance, whereas strong weight growth throughout

childhood was associated with protection (chi-sq = 12.73, df = 4,

p = 0.01). By regression of the GTT score upon the probabilistic

assignment to clusters, the statistical evidence is emphasized

[F(4,603) = 5.28, p < 0.0005).

Conclusions: Evidence that poor childhood development is

associated with impaired glucose tolerance has been revealed

by examining the natural clustering of weight trajectories. This

approach avoids issues of collinearity that would be evident if the

health outcome were regressed upon multiple childhood weights.

P2-43 Birth weight and risk of type 2 diabetes: a quantitative

systematic review of published evidence

P.H. Whincup1 *, S. Kaye1, C.G. Owen1, R. Huxley2, D.G. Cook1,

for the EARLYREAD (Early Risk Exposures in Adult Disease)

Collaboration. 1Division of Community Health Sciences, St

George’s, University of London, UK, 2George Institute, University

of Sydney, Australia

E-mail: p.whincup@sgul.ac.uk

Aim: To review published evidence relating birth weight and type

2 diabetes (T2DM).

Study design: Systematic review and meta-analysis of published

studies relating birth weight and T2DM in adults.

Subjects: Data were available for 31 of 32 relevant studies (6,172

cases, 208,464 individuals, 32 populations).

Outcome measures: Relative risk of T2DM associated with a 1 kg

increase in birth weight. Where possible, the effects of adjustment

(body mass index, social class) and exclusion (macrosomia,

maternal diabetes) were examined.

Results: There was considerable heterogeneity between studies

(c231 = 89.6, p < 0.0001) largely due to positive birth weight-

T2DM associations in 3 populations with high rates of maternal

diabetes and/or macrosomia. The remaining studies showed little

heterogeneity (c228 = 33.9, p = 0.21) and a graded inverse association

between birth weight and T2DM (pooled age and sex adjusted

relative risk 0.78, 95% CI 0.74 0.82 per kg), with no evidence

of publication bias. Among these studies, the association was

strengthened by approximately one third by adjustment for BMI or

the exclusion of macrosomic infants and was unaffected by social

class adjustment. The proportional reduction in T2DM incidence

predicted from an SD increase in birth weight (0.58 kg) was

13% (95% CI 11 16%), increasing to 16% (95% CI 13 0%) after the

exclusion of macrosomic infants.

Conclusions: In most populations studied, lower birth weight was

independently related to an increased risk of T2DM. However, the

potential for reducing T2DM incidence by interventions increasing

birth weight appears likely to be limited.

P2-44 Maternal fatty acid intake in pregnancy may affect

lymphoid organ development of offspring in a

gender-specific manner

A.L. Fear *, P.C. Calder. Institute of Developmental Sciences &

Institute of Human Nutrition, University of Southampton, UK

E-mail: alf1@soton.ac.uk

Aims: The study aimed to determine whether altered maternal

fatty acid intake during gestation in the rat affects immune status

of male or female offspring post-parturition, and if so, whether this

change is maintained into adulthood.

Subjects: 12 ten-week old nulliparous Wistar rats.

Study design: Following conception, dams were randomised into

one of two dietary groups. The diets contained salmon oil (rich in

n-3 PUFAs) or sunflower oil (rich in n-6 PUFAs). At birth, litters were

reduced to 8 pups and dams received a standard chow diet. Pups

were weaned onto chow at 3 weeks of age.

Outcome measures: Spleen and thymus weights were measured in

offspring at 3, 6, 9 and 12 weeks of age.

Results: At 3 weeks, females in the salmon oil group had

significantly heavier thymuses than those in the sunflower oil group

(P= 0.024). There was no effect of diet at any other time point on

thymus or spleen weight in males or females.

Conclusions: There may be an effect of gender on short-term

susceptibility to foetal programming of thymus weight. However,

there does not appear to be any lasting effect on the offspring

of altering balance of n-3 and n-6 PUFAs in pregnancy on spleen

or thymus weight. Further analysis is required to determine the

relative abundance of different immune cells and T-cell responses

in lymphoid organs, and whether these parameters are affected by

gender.

P2-45 Exposure to repeated intraamniotic endotoxin causes

pulmonary and systemic endotoxin tolerance in the

preterm sheep fetus

S. Kallapur *. Cincinnati Childrens Hospital, USA

Background: The occurrence of chorioamnionitis (inflammation of

the fetal membranes) induced bronchopulmonary dysplasia (BPD)

is variable in preterm infants. Chorioamnionitis induced in the

pre-term sheep fetuses by one injection of intra-amniotic (IA)

endotoxin (Endo) results in lung injury responses resembling BPD,

but repeated exposures to IA Endo do not result in a persistent lung

injury response.

Hypothesis: Repeated exposure to IA Endo induces endotoxin

tolerance.

Design and Methods: IA saline (control) or E. coli lipo-

polysaccharide O55:B5 (10 mg) (LPS) was given either 2d (2d group),

7d (7d group) or 2&7d (2+7d group) prior to preterm delivery

at 125 d gestation (Term = 150d). Responses to endotoxin were

measured in vivo (lung IL-1b, liver serum amyloid A3 mRNA) or

in vitro (lung, blood monocyte production of IL-6 in response to

100 ng/ml LPS for 16 h.

Results: See the figure.

Conclusions: Prior exposure of endotoxin decreased in vivo and

in vitro lung and systemic endo responsiveness, consistent with

endotoxin tolerance.

Speculation: Endotoxin tolerance may be one mechanism by which

a preterm infant may have relative protection to lung injury in the

face of prolonged or repeat exposures to antenatal inflammation.

Fetal endotoxin tolerance may modulate postnatal innate immune

responses.

Funded by NIH K08 HL70711, HD12714, HL65397, NHRMC.

P2-46 Multiple pro-inflammatory signalling pathways are

affected when fetal immune modulation is induced by

repetitive intra-amniotic endotoxin injection in sheep

B.W. Kramer1 *, S.G. Kallapur2, I. Nitsos3, T.J.M. Moss3,

J.P. Newnham3, A.H. Jobe2. 1University Hospital Maastricht,

Maastricht, The Netherlands, 2Cincinnati Children’s Hospital

Medical Center, Division of Pulmonary Biology, Cincinnati, Ohio,

USA, 3School of Women’s and Infants‘ Health, University of

Western Australia, Perth, Australia

Background: Intra-uterine exposure to antigens may affect

fetal and postnatal immune responses. Intra-amniotic injection

of endotoxin in pregnant sheep, induced chorioamnionitis,

inflammation in the fetal lung, a modest systemic inflammation,

and endotoxin tolerance in fetal blood monocytes.

Hypothesis: Chorioamnionitis-induced immunomodulation affects

the responses to other Toll-like receptor (TLR) ligands, such as

flagellin (TLR5) and double-stranded (ds) RNA (TLR3).

Methods: Time-mated ewes with singletons were assigned to

groups of 5 7 animals to undergo ultrasound-guided intra-amniotic

injection of endotoxin (10 mg, E. coli 055:B5) or saline. Responses