Even moderate diet during pregnancy can impair development, researchers say


In a study investigating developmental programming, or how the development of the fetus in the womb affects that individual’s lifetime health, researchers have found new evidence emphasizing the critical need for expectant mothers to get adequate nutrition. The study shows that even moderate maternal nutrient restriction can impair kidney development in the fetus, a problem that has been associated with hypertension in adulthood.

The collaborative project between scientists at the Center for Pregnancy and Newborn Research at the Health Science Center and Southwest Foundation for Biomedical Research (SFBR) and its Southwest National Primate Research Center showed that when pregnant baboons received only 70 percent of their normal caloric intake – roughly the equivalent of someone going on a slimming diet – their fetuses experienced stunted renal growth. Their kidneys’ filtering units, called tubules, were shorter and straighter than those of fetuses whose mothers were allowed to eat as much as they wanted during pregnancy.

“This is very important, because the kidneys are the body’s clearinghouse,” said Peter Nathanielsz, M.D., Ph.D., director of the Pregnancy and Newborn Research Center at the Health Science Center and an adjunct faculty member at SFBR. “The kidneys are constantly filtering impurities from the blood. But with shorter tubules, this filtering process is also shortened, and the kidneys aren’t able to do their job adequately.”

Dr. Nathanielsz explained that this can lead to high blood pressure as part of the body’s natural defense. When the body detects that its blood is not being properly filtered, it raises its blood pressure to pump more blood through the kidneys and boost the filtering process. “But if your kidneys are already damaged, they’re not going to be able to succeed [in adequately filtering the blood,] and over time, this increased stress on the kidneys will damage them even further,” Dr. Nathanielsz said.

That is why, in a paper published in the April issue of the Journal of Physiology, the research team concluded, “The negative impact of poor maternal nutrition on the fetal kidney … may have important implications for postnatal renal function, thereby contributing to the observed increased predisposition to hypertension and renal disease in the offspring of nutrient-restricted mothers.”

The reason for the effect – how genes are at play

In addition to finding evidence of restricted renal development in the fetuses of moderately undernourished baboon mothers – the first evidence of its kind in a nonhuman primate, verifying findings from other studies with rats and guinea pigs – the research team also uncovered the mechanism by which this occurs.

As the first group ever to apply the use of powerful gene arrays called “gene chips” to a study on developmental programming in primates, scientists looked at the expression of genes across the entire genome of baboons in the study. What they found was that the cells in the kidneys of the fetuses whose mothers were moderately undernourished during pregnancy were expressing, or using, different sets of genes than the fetuses whose mothers consumed their full diet.

“Different sets of genes were active [and different sets of genes were] inactive in the two groups of baboons whose mothers ate all they wanted and those whose mothers were nutrient deficient, and we found these genetic differences to be consistent with the structural changes seen in the fetal kidneys,” said Laura Cox, Ph.D., of SFBR, the molecular geneticist on the study and lead author on the team’s recent publication in the Journal of Physiology. “This helps us understand the physiological mechanism behind the stunted renal growth in the nutrient-restricted group.”

Implications in the United States

Dr. Cox says that besides being a first of their kind, the study results are somewhat surprising considering the moderate nature of the maternal nutrient restriction. “Since we only restricted caloric intake by 30 percent, many people [in the scientific community] didn’t think we would see much impact on the developing fetus,” she said.

Explaining why the group chose this moderate level of nutrient restriction, Nathanielsz said, “We wanted to see the impact of a diet that might be experienced by women in the Western world. It’s realistic that women in the lower socio-economic area of society might consume 30 percent fewer calories than recommended. This also might be the case with women of any economic status who diet during pregnancy to avoid gaining unwanted pounds.”

The larger questions about lifetime health

Dr. Cox explained that this particular study on the effect of maternal nutrition on the fetal kidney, funded by the National Institute of Child Health and Human Development, is really part of a much larger investigation.

“The overarching question is, ‘Does maternal nutrition impact the health of the offspring? By restricting the diet of the mother, are you setting an individual up for a higher risk of atherosclerosis, diabetes, hypertension and obesity?’” she asked. “That’s the global question. By looking at the kidney in particular, we’re focusing more specifically at the issue of hypertension, but it’s still part of the bigger question about post-natal health.”

The same study also is looking at the impact of maternal nutrition on other areas of fetal development. In the same issue of the Journal of Physiology, the research team published a second paper on the role of genes in the development of the liver. Further investigations will be conducted to see how maternal nutrient restriction impacts those genes, as well as the structural development of the liver.

To further examine how moderate maternal nutrient restriction affects baboons’ lifetime health – and ultimately, people’s health – the group received a new grant in December 2005 from the National Center for Research Resources. With this funding, the research team will follow infant baboons through their first four years of life to monitor their health after birth. For example, they will look to see if the impaired kidney development in the nutrient-restricted group does in fact increase susceptibility to renal disease and hypertension.

“Other studies have shown this to be true in rats and guinea pigs, so now we want to look at the similarities and difference in the long-term impact on baboon health,” Dr. Nathanielsz said. “It’s important to do this investigation in animals most similar to humans in genetics and physiology if we want to know more about the implications for human health, and the Southwest National Primate Research Center at SFBR is the best place in the world to do this research.”

In addition to Drs. Nathanielsz and Cox, other researchers involved in these studies include Drs. Robert Shade and Gene Hubbard of SFBR; Drs. Mark Nijland and Jeffrey Gilbert of the Center for Pregnancy and Newborn Research at the Health Science Center; and Drs. Tom McDonald and Natalia Schlabritz-Loutsevitch, who serve at both institutions.

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