Mother's Health Before Conception May Influence Child's Disease Risk

July 22, 2009— -- A mother's health and diet just before conception and during the first few days of fetal development could have an impact on a child's health in the long run, researchers say.

New evidence on this crucial window of time -- much of it from animal studies -- was presented at this year's meeting of the Society for the Study of Reproduction in Pittsburgh.

Researchers found that the effects of nutrition, such as a high-fat diet and vitamin B and folate deficiencies, as well as diseases such as diabetes, during this time could trigger epigenetic changes that manifest in offspring as obesity, insulin resistance, and cardiovascular disease.

"All of our work suggests there should be a three- to four-month preconception period that's included in good maternal health," said Dr. Kelle Moley of Washington University School of Medicine in St. Louis, who presented one of the studies.

"Early dietary changes or early nutritional changes in the mom can effect epigenetic modifications," she said. "These are persistent in offspring and can be passed down across generations."

The researchers said that they became interested in this period of time after finding evidence of higher rates of genetic imprinting disorders in babies conceived via in-vitro fertilization.

"This opened the door to ideas that changes early in development could have long-term effects," Moley said.

"An unfertilized egg and early embryos are very sensitive to their environments," said Kevin Sinclair of the University of Nottingham in England, also an author of one of the studies.

Moley has been studying how diabetes affects production of a mother's egg cells, potentially leading to mitochondrial metabolic dysfunction -- and hence, birth defects.

"We've been tackling the question of why, even though we control blood sugar during pregnancy, we still have three- to four-fold greater numbers of birth defects than control patients," she said.

Sinclair's work focused on the effects of vitamin deficiency during the time leading up to conception. He looked at sheep that were fed a normal diet or a diet deficient in vitamin B12 and folate.

The offspring of those on the vitamin-deficient diet were more likely to become obese, experience insulin resistance, and have high blood pressure.

The effects were most pronounced in male offspring, Sinclair said, and he saw similar results in a mouse model.

A third study by Tom Fleming of the University of Southampton in England looked at the effects of a low-protein diet just prior to conception and during the early days of fetal development in mice.

Throughout the rest of their pregnancy, the animals were fed a normal diet.

The researchers found that this caused cardiovascular problems, particularly hypertension and arterial disease, as well as other metabolic disorders in the offspring.

Again, there was evidence of stronger effects in male mice.

Fleming said what's happening during this short window of time is that the tiny ball of cells that is the fetus is "sensing" its maternal nutritional environment.

If nutrients are scarce, the embryo will make decisions about how best to get nutrients from its mother, potentially overcompensating.

In a fourth study, researchers have been attempting to get even closer to a human model by looking at primates. Dr. Kjersti Aagaard-Tillery of Baylor College in Houston, Texas, and colleagues studied macaques given a 35 percent high-fat diet.

Some of the animals became obese as a result of the diet, while others did not. But of those who became pregnant, all gave birth to offspring that developed non-alcoholic fatty liver disease and high levels of fats known as triglycerides in the blood.

Moms, Dads Should Watch Diet While Trying to Conceive

"It is clear that changes to diet, glucose levels in the mother, and vitamin intake, prior to ovulation and conception can have long-term effects on fetal growth and adolescent and adult disease," Moley said.

However, she cautioned women to restrain their worry, because the researchers aren't certain of the timing surrounding these events.

"[Egg cells] are constantly being turned over," she said. "The key is to maintain adequate metabolic control for about three months prior to attempts at conception."

Shuk-mei Ho of the University of Cincinnati, who also presented data on the subject, said that similar effects in fathers should be noted as well.

"The contribution of paternal influences is very important," Ho said.