Firstborn children have a higher risk of developing allergies and even asthma, new research says.

The findings, to be presented Wednesday at the American Thoracic Society's 2008 International Conference in Toronto, indicate that a firstborn child faces different conditions in the womb than his or her subsequent siblings.

The researchers, led by Dr. Wilfried Karmaus of the University of South Carolina, studied more than 1,200 newborns from the Isle of Wight in the United Kingdom. The team analyzed whether the immune system's genetic markers, which are determined at birth, would develop differently in firstborn children.

They were specifically interested if being firstborn influenced the development of a DNA variation of the IL-13 gene, which is associated with the development of allergies.

Researchers first measured the babies' cord blood for IgE, a marker for allergy development, and then gave the children the common allergy skin-prick test at ages four and 10.

They found that in firstborns, the IL-13 gene variant was linked to a higher risk of having more IgE in umbilical cord blood. As well, the children with increased IgE in the cord blood had a greater likelihood of having a positive skin prick test for allergies both at ages four and 10.

The findings were not duplicated in children who were not firstborn.

The researchers said that their conclusions are proof that genetic development occurs differently in firstborn kids, with health effects that last for many years.

Karmaus told CTV.ca that during a mother's first pregnancy, she is fighting a foreign body, the baby, in her womb. Her body will produce antigens, or an immune response to this foreign body. That immune response could lead to the IL-13 gene being expressed in her and her baby.

The researchers point out that birth rates are in decline worldwide while allergy and asthma rates are on the rise. This means that there are more firstborns and fewer subsequent babies.

But Karmaus hopes that if scientists can identify the factors that affect immune-system development in utero, then new treatments to alter fetal development could be developed.

"The idea is how can we simulate the first pregnancy to be as if it were the second or other pregnancies," study author Karmaus told CTV.ca.

"That's the idea in the long run."


Abstract:

W. Karmaus, M.D., M.P.H., S.H. Arshad, D.M., I.U. Ogbuanu, M.B.B.S., M. Huebner, Ph.D., S. Matthews, R.G.M., S. Ewart, Ph.D., East Lansing, MI, Columbia, SC, Isle of Wight, England

RATIONALE: Evidence indicates that firstborns have an increased susceptibility to atopy and asthma. However, there is dispute on whether this effect has pre- or postnatal origin (prenatal programming vs. hygiene hypothesis). Prenatal programming would be supported if birth order modifies associations of genetic polymorphisms with atopic markers. We chose to test a possible effect modification for the nonsynonymous SNP rs20541of the IL13, which has been shown to be associated with allergy (common allele G and minor allele A). As outcome, we chose objective immune markers.

METHODS: Immune markers were determined at birth (cord serum IgE, CS-IgE, n=1,319), at age 4 (skin prick tests, SPT4, n=981), and at age 10 (SPT10 and IgE10, n=1,036 and n=953, respectively) in the Isle of Wight birth cohort. Genotypes were determined on DNA isolated from whole-blood of an unselected sample of children at age 10 (n=923). Birth order (parity) was ascertained for 1,212 newborns. Data were analyzed using logistic and linear regression.

RESULTS: Among children with rs20541 GA-genotype (n=260), first-born status significantly increased the odds ratio for having elevated CS-IgE (odds ratio [OR]=1.88), and for SPT 4 and SPT10 (OR=1.67 and 2.07, respectively). This gene x birth order interaction also resulted in a significantly higher geometric mean of serum IgE10 (78.5 vs. 66.5 IkU). There was no effect of rs20541 on immune markers in children with birth order of two and more.

CONCLUSIONS: Our findings of a birth order x gene interaction support the prenatal programming hypothesis, since the intrauterine environment of firstborns is likely to prime the impact of the IL13 gene on immune responses in children.