[Paleopsych] WSJ: Grandma's Behavior While Pregnant Affects Her Grandkids' Health

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Grandma's Behavior While Pregnant Affects Her Grandkids' Health
The Wall Street Journal
Sharon Begley
May 13, 2005; Page B1

[Thanks to Louis for this.]

Although life offers no guarantees, parents-to-be can increase their chances of 
having a healthy baby by, among other things, undergoing prenatal testing and 
making sure mom has a healthy pregnancy. But almost 2,500 years after Euripides 
noticed that "the gods visit the sins of the fathers upon the children," 
scientists are discovering that nature can be even crueler than the ancient 
Greek imagined: It can visit the sins of the grandparents on the children.

Such "transgenerational" effects are the latest focus of a growing field called 
fetal programming, or the fetal origins of adult diseases. It examines how 
conditions in the womb shape physiology in a way that makes people more 
vulnerable decades later to cardiovascular disease, diabetes, immune problems 
and other illnesses usually blamed on genetics or lifestyle, not on what 
arrived via the placenta. If a fetus is poorly nourished, for instance, it can 
develop a "thrifty phenotype" that makes it really good at getting the most out 
of every meal. After birth, that lets it thrive if food is scarce, but it's a 
recipe for Type 2 diabetes in a world of doughnuts and fries. Poor fetal 
nutrition can lead to hypertension, too: If it causes the fetus to produce too 
few kidney cells, the adult that the fetus will become won't be able to 
regulate blood pressure well.

Now, in a finding that seems to put our fate even further outside our control, 
researchers are seeing generation-skipping effects.

Last month, scientists reported that a child whose grandmother smoked while 
pregnant with the child's mother may have twice the risk of developing asthma 
as a child whose grandma didn't flood her fetus with carcinogens. Remarkably, 
the risk from grandma's smoking was as great as or greater than from mom's. 
Kids whose mothers smoked while pregnant were 1.5 times as likely to develop 
childhood asthma as children of nonsmoking moms. Kids whose grandmothers smoked 
while pregnant with mom were 2.1 times as likely to develop asthma, scientists 
reported in the journal Chest.

The harmful effects of tobacco, it seems, can reach down two generations even 
when the intervening generation -- mom -- has no reason to suspect her child 
may be at risk.

"Even if the mother didn't smoke, there was an effect on the grandchild," says 
Frank Gilliland of the University of Southern California, Los Angeles, who led 
the study of 908 children. "If smoking has this transgenerational effect, it's 
a lot worse than we realized."

What causes the grandma effect? One suspect is DNA in the fetus's eggs (all the 
eggs a girl will ever have are made before birth). Chemicals in smoke might 
change the on-off pattern of genes in eggs, including genes of the immune 
system, affecting children who develop from those eggs. Men whose mothers 
smoked don't seem to pass on such abnormalities, probably because sperm are 
made after birth.

Animal data hint at other grandma effects. Last week, scientists reported the 
first discovery that obesity and insulin resistance, as in Type 2 diabetes, can 
be visited on the grandkids of female rats that ate a protein-poor diet during 
pregnancy, lactation or both. Again, this occurred even when those rats' 
offspring, the mothers of the affected grandkids, were healthy, Elena Zambrano 
of the Institute of Medical Sciences and Nutrition, Mexico City, and colleagues 
report in the Journal of Physiology.

The findings, says Peter Nathanielsz of the University of Texas Health Sciences 
Center, San Antonio, "stretch the unwanted consequences of poor nutrition 
across generations."

In people, the type of "nutritional insult" to the fetus doesn't seem to 
matter. Too few calories, too little protein, too few other nutrients can all 
lead to diabetes, hypertension and other ills decades later. "That suggests 
that what links diet to adult diseases is something quite fundamental," says 
Simon Langley-Evans of the University of Nottingham, England. The key suspects: 
changes in DNA activity in the fetus or in the balance of hormones reaching it 
via the placenta.

Alarmingly, the list of what can be passed along to the next generation is 
growing. If you are undernourished as a first-trimester fetus, you won't pad 
your hips and thighs with enough fat tissue. If, as a child or adult, you take 
in more calories than you expend, the extras get stored in and around abdominal 
organs rather than on the thighs and hips, says Aryeh Stein of Emory 
University, Atlanta. One result is a body shaped like an apple (which brings a 
higher risk of heart disease). Another is a higher risk of gestational 
diabetes, in which blood glucose levels rise during pregnancy and too much 
glucose reaches the fetus. Babies born to moms with gestational diabetes have a 
higher risk of Type 2 diabetes.

When undernourished fetuses grow into adolescents, they don't respond as well 
to vaccines as babies who had a healthy gestation, scientists led by Thomas 
McCune of Northwestern University, Evanston, Ill., find. One reason may be that 
the third trimester is a critical time for development of the thymus, which 
produces the immune system's T cells. When immune-compromised girls become 
pregnant, they have less chance of having a healthy pregnancy and a healthy 
baby. Score another for the grandma effect.

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