At least some of the biological risk for childhood asthma and allergies traces back to the womb, new research suggests.

Both the order of birth and even the way a baby is delivered have a significant impact on the long-term strength of a child's allergic defenses, scientists say.

The findings were presented during the American Thoracic Society's International Conference in Toronto.

At the meeting, one team of scientists said it had evidence indicating that when a specific genetic marker linked to the development of allergies and asthma is present among a firstborn child, it appears to raise the risk for allergic conditions as far as ten years down the road. However, when the exact same marker is present in a family's second or third child, the gene seems to have exactly the opposite effect—actually lowering such risk.

"This is the first time it has been demonstrated that birth order can affect the behavior of genes related to asthma and allergies, and that birth order can therefore affect the risk for developing one or the other," said study author Wilfried Karmaus, MD, a professor in the department of epidemiology and biostatistics at the University of South Carolina in Columbia.

Ona second front, another team of researchers suggested that regulatory cells associated with proper immune function might be impaired in babies delivered by cesarean section.

"We found a dysfunctional cellular response in the normally protective immune system among C-section babies," observed Ngoc Ly, MD, an assistant professor of pediatrics at the University of California at San Francisco. "And although more work needs to be done to follow how long this response might endure, we think this disrupted immune pathway may influence the development of asthma later on."

Birth Order Study

To explore the relationship between birth order and asthma/allergy risk, Dr. Karmaus and his team tracked more than 1,200 newborns from Great Britain's Isle of Wight.

After recording birth orders, the researchers tested each newborn's allergic status by examining indicators present in umbilical cord blood. They also conducted standard skin prick allergy tests at age 4 and age 10.

The authors found that among firstborn children, the presence of a particular gene strain—known as the IL-13 gene variant—was associated with a higher risk for having an "allergic response." This link continued to persist a decade later.

By contrast, among second or later-born children, no such association between IL-13 and higher risk was found. In fact, the role of IL-13 seemed to switch over to that of a risk protector.


"The fetus is, in effect, a foreign body," noted Dr. Karmaus. "And a foreign body can be exposed to a lot of immune arousal or not, depending. So we think that something during pregnancy-it's probably the immune system of the mother-stimulates the IL-13 gene to act differently, depending on birth order. We haven't shown how this works yet, but that's the idea."


Dr. Karmaus suggested that the finding could theoretically lead to the crafting of interventions-perhaps therapeutic, perhaps simply lifestyle changes-which could reduce the allergic response risk for firstborns.

Cesarean Section Study

Meanwhile, Dr. Ly and her colleagues explored similar risks associated with cesarean sections by analyzing the cellular immune regulatory activity present in the form of so-called treg cells) in the umbilical cord blood of 50 babies born by cesarean and 68 babies delivered vaginally. All the babies had at least one parent with allergies and/or asthma.

The authors found that among C-section babies, treg cells were more likely to fail to operate properly, raising the risk for the early onset of immune system disruption. This, in turn, may increase the likelihood that a child could grow up to develop an allergy or asthma.


Dr. Ly and her team said that the suggestion that the manner of delivery could actually influence immune system development, and ultimately asthma/allergy risk, could be due to the fact that vaginal labor provides beneficial exposure to birth canal microbes that simply aren't available to a C-section baby.


"But still I think it's important to reiterate that while this is interesting research, it is a small study and the first of its kind," noted Dr. Ly. "So there is much more follow-up work that needs to be done to see if these newborns in fact start developing symptoms of asthma or allergies as they grow."

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