Programming Early in the Womb

About a new type of gestational diabetes and early programming of subsequent diseases

The publication in the scientific serial PNAS caused quite a stir. Together with scientists from the Netherlands, Germany, and Switzerland, nutritional scientists from the University of Potsdam succeeded in finding a cause of gestational diabetes that had been unknown so far. Berthold Hocher, medical expert and professor of experimental nutritional medicine, examined the mechanisms of insulin resistance caused by a mutation in the kidneys with his research group. In cases of magnesium deficiency, this insulin resistance can cause diabetes mellitus during pregnancy.

 “In cases of gestational diabetes, the risks for the child are not insignificant,” Berthold Hocher explains. “Due to the increased carbohydrate supply through the blood, the foetus gains weight which can lead to problems during childbirth.” At the same time it causes dysmaturity of internal organs. When the maternal supply of sugar stops after birth, it causes hypoglycaemia. The implications might be visible only after many years because the child is at a higher risk of developing diabetes later in life.

For Berthold Hocher this early imprinting of the unborn child during pregnancy has become an important research field. Being a specialist in internal medicine and a nephrologist at the Berlin university hospital Charité, he has very often been consulted when women had health problems during pregnancy. There has always been the question about the influence of a mother’s illness on the development of a child. Are diseases established in the foetus during this early stage of development that manifest themselves in adulthood?

“Foetal programming” is the name of this relatively new field of research, which is gaining in significance. “Twenty years ago one started to understand that there is a connection between pregnancy and later diseases of the offspring,” Hocher says. The British epidemiologist David Barker was the first to put forward this hypothesis. He evaluated statistics which suggested that the mortality rate of newborns was particularly high in the disadvantaged coal-mining regions of England around 1900. About 60 years later there was a high fatality rate from cardiovascular diseases in the same region. Barker assumed that the bad living conditions of pregnant women caused the high infant mortality as well as the cardiovascular diseases later. He found more proof in the records of midwife Ethel Margaret Burnside from 1917. The British Ministry of Defence had commissioned her to give health care advice to young mothers and to look after them because the ministry was concerned about the “children of the country”. Midwives noted weight, food, and growth of the infants meticulously. David Barker was able to use this “database” fifty years later to show the interrelation between low birth weight and the risk of fatal cardiovascular diseases later in life. Another study from the Netherlands shows that high numbers of children born during the “Hunger Winter” of 1944 suffered from type-2 diabetes later in life. Their mothers ingested only 400 to 800 kilocalories per day during their pregnancies.

Meanwhile, nutritional physiologists and medical experts like Berthold Hocher can prove the possible effects of such critical events during the early phase of life on a molecular level, not only for malnutrition but also supernutrition of mothers. Animal experiments suggest that male offspring of pregnant rats on high protein diet suffer from hypertension, whereas female offspring tend to deposit a lot of fat. In the nine months when the human foetus matures, there are short periods during which certain functions of metabolism are established and then remain the same for the whole life. Hocher demands more awareness of, and sensitivity for, such risks in antenatal care. “It is a well-known fact that nicotine is harmful for the unborn child. Nevertheless, a lot of pregnant women smoke,” he remarks and then explains that such negative environmental influences could lead to structural modifications in genes. “Epigenetic modifications of the DNA causing diseases in later life can occur upon environmental stimuli like under-nutrition, over-neutrino or smoking of the pregnant mothers very easily during the early phase of life. Adjustment to the environment happens relatively quickly.” Hocher includes excessive stress of the mother in the critical events that can lead to foetal programming. The placenta usually protects the foetus from the stress hormone cortisol. If the unborn is affected, however, there is an increased risk of suffering from arteriosclerosis as an adult. A high cortisol level in pregnant women also reduces the brain volume of the child. “The related cognitive deficits and language disorders often only become apparent when the child starts to go to school,” Hocher says.

The scientist sees the share of foetal programming in relation to hereditary transmission at 30 per cent. When we understand the processes of early programming in the womb exactly, we have to ask ourselves whether it is possible to “reprogramme” them. “There are first clues but we are still at the very beginning,” Hocher says. “However, it would be a step forward to have routine diabetes check-ups for all pregnant women and to start treatment in time if necessary.” The earlier we take countermeasures, the lower the risk that children are born with an insulin resistance and become diabetics themselves in the course of their lives.

New Type of Gestational Diabetes

Until now, hypomagnesemia during pregnancy was seen as one of the main reasons for hypertension. Now a connection to the development of gestational diabetes has been confirmed for the first time. Pregnant women without previously diagnosed diabetes suddenly exhibit high blood glucose levels. There is a mutation in two to three per cent of all women, which inhibits the transportation of magnesium from the primary urine back to the body in tubules of the kidneys. The considerable loss of magnesium during pregnancy gets even higher. Magnesium is a significant factor contributing to insulin resistance. The risk of developing diabetes increases.

The Scientist

Professor Berthold Hocher, specialist in internal medicine and nephrologist at the university hospital Charité, is now Professor of Experimental Nutritional Medicine (Solvay Personal Chair) at the Institute for Nutritional Science at the Faculty of Science of the University of Potsdam.

Contact

Universität Potsdam

Institut für Ernährungswissenschaften
Arthur-Scheunert-Allee 114–116
14558 Nuthetal OT Bergholz-Rehbrücke

E-Mail: hocheruni-potsdamde

Text: Antje Horn-Conrad, Bearbeitung: Julia Schwaibold

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