Born too soon  pg. 4

But which conserved molecules are most important, where they are produced, and whether the signals are fetal, maternal, or both, are open questions, he says.

“We feel that the signals in birth timing and the physiological pathways are poorly enough known right now that we want to take an open-ended approach to understanding the critical determinants of regular pregnancy, and which of those are disrupted that lead to preterm birth,” Muglia says.

Muglia suggests two general “models” for prematurity.

In one model, something acute (like an infection) triggers a baby to be born too early.

In the other model, genetic programming sets a variable window for birth timing, and some women are genetically predisposed to having a relatively earlier birth. Muglia and colleagues opted to pursue the second model – to look for the genes that set the birth timer.

But first they needed to probe the likelihood of this explanation: could genetic influences determine a risk for prematurity?

In initial studies, the researchers examined the recurrence of preterm birth to an individual mother. They used a database of 1.5 million births in Missouri between 1978 and 1997 that included all births to a given mother and a number of risk factors.

Their analysis suggested that mothers who had already had a preterm birth had two to three times greater risk of having a preterm birth in a subsequent pregnancy than women who had a term birth in a first pregnancy.

An interesting finding from the study was that when mothers had a recurrent preterm birth, it was usually within the same week of gestation as the first preterm birth.

“If you thought there was a random environmental influence, you wouldn’t expect it to cause the timing to repeat across pregnancies,” Muglia says.

The investigators also have examined birth timing in twins – births to identical twin sisters compared to non-identical twin or non-twin sisters. Twin studies allow the team to model genetic factors, shared environmental factors and unique environmental factors.

“We can show that there’s no way to generate the patterns that are observed unless there is a significant genetic component to maternal birth timing.”

To probe the genetic contribution of the fetus, Muglia’s group performed a similar twins versus siblings study focused on the fathers.

They found no evidence for a strong paternal genetic contribution to birth timing, which suggests there may not be a strong fetal contribution, though the studies didn’t rule out genes from the mother that might be expressed by the fetus, Muglia notes.

These and other studies have supported the notion that maternal genes (expressed either in the mother or in the fetus) are key determinants for preterm birth. Muglia estimates that 30 percent to 40 percent of the variation in birth timing is due to genetic factors.

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