91av

HORMONAL changes in women over successive pregnancies could partly explain
why firstborns are more likely to develop allergies than their younger brothers
and sisters.

Wilfried Karmaus of Michigan State University in East Lansing and his
colleagues have found that firstborn babies have higher levels of a key immune
protein associated with allergies.

Epidemiologist David Strachan, now at St George’s Hospital Medical School in
London, was the first to notice that the bigger a family is, the less likely its
youngest members are to have allergies such as asthma, hay fever and eczema.
Other studies have confirmed this. “I don’t think there’s any doubt that there’s
some sort of a relationship,” he says.

In 1989, to explain the sibling effect, Strachan proposed the hygiene
hypothesis—the idea that children’s immune systems go haywire if they
aren’t exposed to enough challenges early on
(91av, 18 July1998, p 26).
Being surrounded by grubby, snuffling older siblings makes a child
less likely to get allergies, he reasoned.

But the latest study suggests that the advantage may arise earlier—in
the womb. If so, the vaccines some are trying to develop to mimic a dirty
environment might not be the complete answer.

To check for prenatal effects, Karmaus’s team focused on a key immune system
protein called immunoglobulin E (IgE). Other studies have shown that children
born with high levels of IgE in their umbilical-cord blood have an increased
risk of developing allergies. “The question was, can this be related to birth
order?” says Karmaus.

Looking at 981 children born between 1989 and 1990 on the Isle of Wight,
Karmaus’s team found that 16.5 per cent of firstborns had IgE levels of higher
than 0.5 kilounits per litre. Such levels were found in only 12.8 per cent of
children with one older sibling and in just 8 per cent of children with two or
more older siblings.

This suggests something within pregnancy contributes to the sibling effect,
says Karmaus—an idea backed by recent studies showing high cord IgE is
linked to raised levels of an endocrine disrupter called organochlorine in the
placenta—and that levels of this chemical in breast milk are lower after
later births.

Anne Wright, an asthma epidemiologist at the University of Arizona in Tucson,
finds this reasoning persuasive. “The relationship between birth order and cord
blood IgE cannot possibly be attributed to infections by being around other
children,” she says.

However, the study also showed that while 37.5 per cent of the firstborns
with high IgE levels at birth were sensitive to a skin prick allergy test, only
23.5 per cent of the children who had similarly high levels of IgE in their cord
blood but more than one sibling had an allergic reaction. This suggests Karmaus
has discovered an additional reason for the sibling effect, rather than the
hygiene hypothesis being wrong, Wright says.