The Fetal Response to Infection, with Particular Reference to Alterations of Tryptophan Metabolism

Funded Activity Summary

Infection in pregnancy has long been known to be associated with a high risk for brain damage in the baby. There is now good evidence that the brain can be damaged before birth, and in other babies where the brain is damaged after birth there is reason to say that these infants were factors associated with the pregnancy that rendered them vulnerable to risk factors postnatally. Very little is known about the effects of infection on the fetus. Some recent work has shown that substances released from bacteria induce cells in the uterus and placenta to produce inflammatory chemicals that can damage the brain. In this project we propose the following model: 1), infection causes the release of substances from the uterus and placenta that disrupt the blood-brain barrier in the fetal brain; and, 2), infection alters the metabolism of the essential amino acid tryptophan in the fetus, causing greater production of metabolites that have toxic effects on the developing brain. We have preliminary evidence to support these two proposals. If the idea is proven correct, it should be possible to administer simple analogues of tryptophan to prevent the toxic metabolites of this amino acid from increasing in the fetus when either the mother or the uterus becomes infected. Because these substances can be given by mouth, this would allow a simple treatment to be developed for women at risk of infection, or who are already infected. This would be particularly useful wherever medical services and resources are limited, as for under-priviledged groups and in Third World countries.

Funded Activity Details

Start Date: 01-01-2001

End Date: 01-01-2005

Funding Scheme: NHMRC Project Grants

Funding Amount: $410,616.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Public health nutrition

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

Excitotoxicity and neuroprotection | Fetal hypoxia and birth trauma | Fetal response to infection | Maternal infection | Neuroactive metabolites of tryptophan catabolism | Perinatal brain damage | Pregnancy complications and newborn health

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