As reported by The Hartford Courant, June 20, 2006.

A Mother's Protection

By William Hathaway

This gift won't turn up on anyone's baby shower list, but one thing an expectant mom can do for her baby is to get sick.

That's not to suggest that a pregnant woman should deliberately get sick, but if she does become ill, she can pass antibodies on to her baby, who will be born with at least temporary immunological protection against the infectious agents. If the fetus does not develop a potentially dangerous infection, the newborn will have received a sort of vaccination within the womb without suffering any ill effects.

There does appear to be at least one curious exception to this rule, scientists from University of Connecticut and Case Western Reserve University in Cleveland have found.

A pregnant mother infected by the parasite that causes lymphatic filariasis early in her term is more likely, not less likely, to deliver a baby who will get sick later in life. Apparently, her child's immune system does not recognize the mosquito-borne parasite as a threat and will tolerate its presence, says T.V. Rajan, a professor of immunology and pathology at the UConn Health Center.

That means the child does not mount a defense against the thread-like worm that causes the disfiguring swelling and hardening of the skin known as elephantiasis, which afflicts tens of millions of people in the developing world. The medical oddity is that for the child to come down with the disease, the mother must be infected during her pregnancy.

"There is a huge difference in health outcomes, not because of your genetics but because of the environment in your mother's womb," says Rajan, who has studied the phenomenon in mice.

The observation of such researchers as Rajan, UConn doctoral student Manish Ramesh and Christopher King, professor of geographic medicine at Case Western Reserve, might be more than a biological footnote, they say.

Understanding how a fetus becomes tolerant of pathogens could be a key in developing effective malaria vaccines, says Jim Kazura, professor of international health at Case Western.

Rajan and Ramesh speculate it also might help explain why children in the Third World are less prone to asthma than their peers in more developed countries.

The phenomenon of immunological tolerance was not even on Rajan's radar screen in 1991, when be began to use mice to study lymphatic filariasis, a disease that ravages poor areas of his native India. Rajan was puzzled why his mice managed to rid themselves of the parasites and never became chronically ill, while tens of millions of people in hard-hit areas of the world came down with the disfiguring disease. He also wondered about a study of American soldiers in World War II who became infected but, like his mice, did not develop the chronic form of the disease, with the grotesque swelling of limbs.

Mothers, it turned out, were the answer.

When researchers at Case Western tested 159 newborns and mothers in Kenya, they found babies whose mothers were infected during gestation were 14 times more likely to become infected than babies whose mothers were not infected.

Kazura says Case Western researchers are also studying whether a mother's infectious status could influence whether her children are more susceptible to malaria as well. The question is particularly crucial as new malarial vaccines are tested, he says. For instance, if a vaccine is tested on children whose mothers were not exposed to malarial parasites during pregnancy, then it may provoke a robust immune response to the foreign invader. However, if a woman was actively infected during pregnancy, her baby's immune system might become tolerant to the invader and not react as strongly, he says.

The dramatic increase in the number of allergy and asthma cases in the developed world has puzzled researchers. Rajan and Ramesh theorize that prenatal tolerance to pathogens may help explain the phenomenon.

If a mother is exposed to allergens during pregnancy, the baby's developing immune system will perceive them, properly, as harmless.

"The baby will say, `This is OK; I am getting this from my mom, it is not bad for me,'"Rajan explains.

However, if the mother lives in a hyper-clean environment, then the baby's immune system will respond as if the allergens are a threat, triggering an immune response that causes the symptoms of allergies and asthma.

"Everyone, myself included, used to believe that this training of the immune system occurred after we are born," Rajan says. "What the Case Western Reserve group and I are saying is that the training may actually begin when you are still in your mother's womb."