Prenatal growth has a major impact on health throughout the life course. The association between a small birth size and cardiovascular disease has been shown in more than 100 demographic studies. In this context "small body size at birth" generally refers to slow fetal growth of a full-term baby; the possible long-term effects of premature birth are still poorly known. The impact of confounding factors such as social class and lifestyle has had little influence on the association. Early growth does not only predict cardiovascular disease but seems to be associated with a wide variety of health-related outcomes.
Why and how does the human organism remember the fetal environment?
Findings based on animal studies have lead to the concept of programming: a malnourished fetus "programs" e.g. its hormone system or the size of its organs for the whole life course in order to enable the individual to function on minimal nutrition. From the evolutionary point of view this is an advantageous feature. If the prognosis fails, these adaptive responses can lead to increased disease risk. Not only malnutrition but several other factors (e.g. stress, infections) acting during the prenatal period can cause programming-like effects.
What does the birth size in fact tell us?
In demographic studies the weight at birth is generally used to measure prenatal living conditions. However the weight at birth is a crude measurement. On the other hand weight, is a well-defined, unambiguous number, which has been measured in many countries for a long period of time for new born babies. However, birth weight depends on the length of gestation. A baby girl who weighs 2.5 kg and is born in the 34th week of gestation (6 weeks before term) is of about average weight, but a full term baby of the same weight is very small. When duration of pregnancy is reliably known, the birth weight is stated in relation to the mean weight for that duration of gestation, expressing the difference in units of the standard deviation (Standard deviation, SD, means "the average deviation from the mean value"). The adjusted weight for the above mentioned baby girl, if born in the 34th week of pregnancy, would be +0.2 SD, whereas if born at full term it would be -2.3 SD.
Even this birth weight does not tell us very much. A baby with a birth weight of -2.3 SD could have suffered from severe growth retardation because of placental insufficiency or its small size could just indicate a healthy baby with a genetic predisposition towards a small birth weight. Furthermore birth weight does not tell us about body composition, i.e. the distribution of fat and muscle tissue. In other words individual health predictions should not be made based upon birth size.
How can the relation between fetal growth and diseases in adulthood be investigated?
Demographic studies often study a randomly selected subgroup of some specific part of the population. These studies often need hundreds or thousands of people, about whose earlier life something is known - for example their birth weights.
In a clinical demographic study voluntary participants are invited to a physical examination, the results of which are compared with birth weight and other early life characteristics. In Finland and some other countries, for example the other Nordic countries, there are public health care registers which enable register studies - it is possible to investigate for instance if small-borns have more often been hospitalized for hypertension, diabetes or other common chronic disease.
The most reliable data comes from prospective demographic studies where the same group of people are studied from birth - on the other hand this kind of study can take a generation to complete. Demographic studies can investigate a particular disease, for instance coronary artery disease. For more detailed information one can examine factors that increase the risk for or protect from a disease - in the case of coronary artery disease, for instance lipid- and glucose-metabolism, blood pressure regulation and the function of different hormonal systems. The investigation is not necessarily focused only on diseases. It is likely that factors that affect early growth can contribute to the normal variations existing between individuals.
In disease-focused research one can compare the birth weight and other early data for some patients with the disease to the corresponding data for the whole population. This kind of approach is particularly suited for investigating rare diseases. Demographic studies seldom prove causal relationships. This kind of information can be obtained from animal research. An often mentioned example is a cortisol-like hormone given to pregnant rats: mother rats given the hormone give birth to small- sized baby rats that develop hypertension as adults. Similar animal studies have shown a large number of other possible mechanisms, through which early growth can influence health in adulthood.
Are some groups at an exceptionally high risk?
We do not know yet. The demographic studies have mostly been performed within the whole population, consequently the number of persons who have suffered severe growth disorder is small. Still, it has been shown that those who have suffered from fetal growth disorders have changes already as young adults when it comes to blood pressure, glucose tolerance, cholesterol, vascular elasticity, body fat mass - all known risk factors and pre-stages of cardiovascular diseases. Very small premature babies live their first months of life under conditions that are very different from those in the womb, and often grow very slowly during this period. Very little is however known about the health of small prematures as adults, because the oldest small prematures who have survived thanks to modern intensive care are still young adults. Considering the risks of such special groups it has to be remembered that although the risk for some diseases may be clearly higher, the same mechanisms might protect from other diseases. For example those born as very small prematures are known to have less allergic diseases, at least in childhood.
Can an increased risk be decreased?
Most likely it can. For instance the risk of cardiovascular disease can be reduced by normal healthy life style - weight control, physical exercise and diet.
The HBCS-study has also shown that regular exercise has a strong and exceptionally protective effect against type 2 diabetes among those born small. It is also possible that the investigation of the long-term effects of fetal growth will give us new knowledge about the mechanisms behind many common diseases, and that this new knowledge can be used to develop new methods for preventing diseases.