Small for their age: Using metabolites to identify babies that might be born too small

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  • Published: Jul 4, 2011
  • Author: Jon Evans
  • Channels: Laboratory Informatics
thumbnail image: Small for their age: Using metabolites to identify babies that might be born too small

Poor growth or naturally small?

Being born very small can be a major risk factor for a baby. In the most extreme cases, very small babies, meaning the 10% smallest babies born at any specific gestational age, may not survive at all: up to 50% of stillbirths are associated with being small for gestational age. Even if they survive the birth, very small babies may die shortly afterwards or they may go on to suffer from numerous health problems later in life, including heart disease, high blood pressure and diabetes.

So it's important to identify fetuses that aren't growing properly as soon as possible and to determine why they aren't growing properly, so that appropriate measures can be taken. Now, you would think that with the widespread use of ultrasound scans it would be easy to identify fetuses that aren't growing properly, but it isn't.

Being born small is not in and of itself a problem: a baby may be amongst the 10% smallest babies purely because its naturally small. Being born small is only hazardous if it's due to the fetus not growing properly because it isn't receiving sufficient oxygen or nutrients from its mother.

An ultrasound scan can't be used to tell the difference between a naturally small fetus and one that's small because it's not growing properly. Understandably, doctors are reluctant to intervene in the development of a fetus unless they're certain that it's not growing properly.

Comparing metabolites 

One potential way to identify fetuses that aren't growing properly is to analyse the metabolites present in their blood or their mother's blood. Because the fetus isn't receiving sufficient nutrients or oxygen from its mother, it's blood should posses a different mix of metabolites to the blood of a fetus that is receiving sufficient amounts. Likewise, the mother's blood should contain a different mix of metabolites to mothers with fetuses that are growing well, again because sufficient nutrients and oxygen are not passing from their blood to the fetus through the placenta.

So an international team of scientists led by Louise Kenny at University College Cork in Ireland set out to find a set of metabolites able to distinguish fetuses that aren't growing properly and are at risk of being born small for gestational age. Because Kenny and her team knew that identifying such distinguishing metabolites in a complex medium such as blood would be quite a tall order, they decided to conduct three parallel studies.

Three studies

In the first study, they analysed the metabolites in blood extracted from the umbilical cords of both small and normal size babies, because they assumed that any difference in metabolite composition would be easiest to spot at birth. In the second study, they analysed the metabolites in the blood of pregnant mice where the blood supply to the fetuses was artificially restricted, preventing the fetuses from receiving sufficient oxygen and nutrients. Finally, they analysed metabolites in the blood of pregnant mothers during the 15th week of pregnancy who then went on to have either small or normal size babies. In all cases, they identified and analysed the metabolites present in the blood samples with ultra performance liquid chromatography-mass spectrometry.

Next, they employed a genetic algorithm and partial least squares discriminant analysis to compare the metabolite data produced by the three studies, eventually coming up with a suite of 19 metabolites that seemed to be differently expressed in all three studies. Interestingly, these metabolites were under-expressed in the umbilical cords but over-expressed in both the pregnant mice and women. This is because if nutrients and oxygen aren't passing properly between the mother and fetus then you would expect the baby's blood, as reflected in the umbilical cord, to contain a lack of certain metabolites that are instead building up in the mother's blood.

Because the same 19 metabolites were differently expressed in both the umbilical cords and the blood of pregnant women at 15 weeks, there's a good chance they can be used to identify those fetuses most at risk of being born small for their gestational age at an early stage in their development.

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.

Small for their age: using metabolites to identify babies due to be born too small

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