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Biological Chemistry

Spotting The Tiniest Babies

Clinical Diagnostics: Metabolites in mothers’ blood during early pregnancy could reveal growth-restricted fetuses

by Laura Cassiday
August 5, 2011

SMALL WONDER
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Credit: Shutterstock
Babies with low birth weights carry increased health risks.
Credit: Shutterstock
Babies with low birth weights carry increased health risks.

Babies who are born abnormally small carry increased risks of hypoxia, hypoglycemia, and even death. These babies also are more likely to develop cardiovascular disease and diabetes later in life. Now researchers have uncovered a chemical signature in the blood of pregnant women that appears early in pregnancy and can predict whether a baby will have an extremely low birth weight (J. Proteome Res., DOI: 10.1021/pr2002897). The researchers say the metabolite signature opens the door for diagnostic tests and therapies for small babies.

Doctors diagnose a newborn with a condition called small for gestational age when the baby’s birth weight is below the 10th percentile compared with other babies born in the same week of pregnancy. Despite being unusually small, about 30% of diminutive babies have no major health issues. But the majority of very small newborns have experienced fetal growth restriction, a condition in which a fetus fails to reach its genetically determined size and that leads to significant health problems. Scientists think a fetus’ stunted growth can arise from poor vascular development in the placenta, which hinders the flow of oxygen and nutrients from the mother’s blood.

Although doctors can use ultrasonography to estimate fetal size, the technique has a large margin of error, says Louise Kenny, a professor of obstetrics at University College Cork, in Ireland. As a result, she says, between 40 and 80% of growth-restricted fetuses go undiagnosed until birth, making clinical detection of the condition very poor. What’s more, ultrasonography can’t distinguish between growth-restricted fetuses and those who are constitutionally small but healthy.

Because fetal growth restriction is so difficult to diagnose, Kenny says, “babies that could have been saved by early delivery or proper prenatal care are often stillborn.” However, doctors risk unnecessary medical interventions and premature induction of labor if they misdiagnose small, healthy babies as being growth restricted.

Kenny and her colleagues wanted to develop a more accurate test for fetal growth restriction. They chose a group of 80 women participating in an ongoing study who had given blood during the 15th week of gestation, half of whom subsequently gave birth to unusually small babies. The researchers used mass spectrometry to identify and quantify metabolites in the women’s blood samples. The researchers identified a panel of 19 metabolites, including sphingolipids, phospholipids, carnitines, and fatty acids, whose levels differed significantly between the women who had small babies and those who gave birth to normal-weight babies. This metabolite signature allowed them to predict retrospectively which women would deliver small newborns with a sensitivity and specificity far better than current methods, Kenny says. Although the test isn’t ready for clinical use, the researchers estimate they could predict about 90% of the small for gestational age cases.

When the researchers analyzed the metabolite data further with statistical methods, they found a group of women who had given birth to small babies but whose metabolite concentrations were close to the levels of the women who had had normal-weight babies. The researchers don’t have data on which babies suffered from fetal growth restriction, but Kenny and her colleagues think that this subgroup corresponds to women who gave birth to small, but healthy, babies.

“This work gives us clues to better understand what happens in the placenta during fetal growth restriction, and in time may help us develop therapeutic strategies,” says Jane Brewin, chief executive officer at Tommy’s Baby Charity, a nonprofit organization in the U.K. that funds research on pregnancy complications. But Brewin says that the researchers must validate their results in a larger cohort. Kenny says a larger study is already under way.

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