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Where we come from determines how we fare – the fetal origins of adult disease

We may be permanently programmed by our response to adverse environments during pre-natal life. storyvillegirl/Flickr

Non-communicable diseases – William Ledger discusses the impact of fetal health on the development of NCDs.

We like to think that we are, to a greater or lesser extent, the masters of our own destiny. We suppose that the way in which we live, our diet, exercise level, smoking and drinking habits, determine our level of health and our life expectancy.

There is, of course, some truth in this, but studies over many years have shown one of the major determinant of health as an adult is nutrition and growth before birth.

Barker hypothesis

The so-called “developmental origins of adult disease” hypothesis was famously propounded by David Barker and his colleagues working in United Kingdom in the 1970s and 1980s.

It suggests poor nutrition leading to impaired fetal growth results in an increased risk of many adult diseases including diabetes, heart disease and high blood pressure.

Barker’s work was based on meticulously kept records from labour wards at the Jessop Hospital for Women in Sheffield and from other units in Hertfordshire and Lancashire.

He linked records of birth weight and measurements of head and abdominal circumference of newborn babies to the health and life expectancy of adults. Babies with the lowest birthweight were found to have the highest levels of heart disease in later life.

These findings have been replicated many times, and apply equally to men and women as well as across different racial groups.

Children born in Helsinki between 1934 and 1944 who developed heart disease, diabetes and high blood pressure as adults, for instance, were generally short and thin at birth, had poor growth in the first year of life but accelerated growth as older children.

Genetic changes?

There are many theories concerning the mechanism by which poor growth in utero may lead to ill health in later life.

The most popular is the “thrifty phenotype” hypothesis that suggests diabetes (and subsequently other disorders) in adults may result from the persistence of a glucose-conserving adaptation to starvation within the womb.

The fetus becomes permanently programmed by its response to the adverse environment during pre-natal life, creating changes in metabolism that cause problems when they persist into adulthood. Hence small, thin newborns become obese and develop type 2 diabetes in later life.

More information has been provided by observations of the effects of malnutrition on the health of children and adults born after their mothers experienced starvation.

The Dutch hunger winter of 1944–5, for instance, involved a five-month period of extreme starvation.

Female babies whose mothers were starved during the first three months of pregnancy were of normal weight at birth but, intriguingly, 50 years later had altered patterns of growth factor genes such as IGF-2, and had children who were themselves smaller in the next generation.

Evidence of this type suggests an imprinted intergenerational effect of an adverse environment during pregnancy.

Other possible causes

Both lack of macronutrients and certain micronutrients have been implicated as being significant in leading to later chronic disorders.

A balanced diet during pregnancy can ward of the development of non-communicable diseases. CDC/James Gathany

Low intake of protein and carbohydrates in pregnancy has been associated with reduced birthweight and later high blood pressure.

And increased intake of fruit and vegetables in a study from India was associated with increased birth weight and improved glucose tolerance in the offspring.

In an Australian study, a third of the mothers who had significantly small gestational age babies had previously been diagnosed with an eating disorder.

Even women who had apparently responded to treatment for their eating disorder still had a higher than expected incidence of low birthweight babies and preterm birth.

The other side

Overnutrition during fetal life can also be deleterious, and is probably a greater problem in the Western world in the 21st century.

Infants of diabetic mothers are over-exposed to glucose and fatty acids in utero and have higher risk of having high birthweight and of developing type 2 diabetes in later life.

High birthweight female babies may develop problems of polycystic ovary syndrome and are more likely to develop certain cancers as adults.

There are many studies showing how fundamental homeostatic mechanisms regulating features, such as blood pressure and body size in the adult, can be programmed during fetal life by an adverse nutritional environment.

But there’s also debate concerning the stage of pregnancy at which this programming occurs.

The Dutch starvation study indicates maternal malnutrition can have a significant influence on the later development of the child in the first trimester.

Studies of offspring from IVF pregnancies suggest that some aspects of programming for post-natal life may be initiated as early as the first few days of embryonic life.

It seems reasonable to suppose that the longer the adverse influences, the greater the risk of later problems although this has not been proven.

Preterm birth may also be a contributor to the overall adverse effects of an unhealthy start to life, and often occurs either naturally or due to illness during pregnancies.

But shorter gestational age also creates a possible confounding factor in the link between nutrition in utero and adult disease.

Seeking solutions

If we accept that malnutrition in utero may have consequences in later life, then what can be done about it?

Ultrasound scanning can be used in pregnancy to identify those babies who are not growing as expected, but this assessment can only be made reliably at a fairly late stage of pregnancy.

This may be too late for effective intervention.

Preliminary studies on rodents have shown that optimization of post-natal nutrition may correct for the effects of undernutrition during pregnancy and, if extrapolated to human pregnancy, may lead to new approaches to reprogramming this lifelong system.

While the Barker hypothesis has gained widespread acceptance, medical science is still at a loss to know what to do about it, other than recommending better nutrition and lifestyle change to mothers and mothers to be.

What we can say with certainty is that a healthy mother makes for not just a healthy baby but good maternal health means a life, at least in part, protected from non-communicable diseases.

This is the ninth part of our non-communicable diseases series. To read the other instalments, follow the links here:

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