The evidence on the effects of poor fetal growth on The evidence on the effects of poor fetal growth on the development of obesity in adult life gives a mixed picture. Size at birth seems to be associated with the distribution of body fat rather than with total body mass. For example, people who were light as babies were found to have more truncal fat independent of overall fatness. 1 On the other hand, people who had high birthweight were found to be somewhat more obese as adults than those

more »

... h low birthweight. 2,3 In their paper on the effect of maternal smoking on adult obesity, published in this issue of the International Journal of Epidemiology, Power and co-workers point out that size at birth only indirectly reflects the severity and timing of adverse environmental events during gestation. 4 For this reason, they suggest that 'other models (than studies relying on birthweight as a proxy for fetal growth) are needed to elucidate the role of fetal growth in the development of obesity'. But, can we gain more insight into the fetal origins of adult obesity by studying the body composition of people whose mothers smoked during pregnancy? Fetal growth is thought to be controlled by environmental influences-through their effects on the mother's body-rather than through genetic make-up. For example, it was found that the birthweight of the mother, but not that of the father, was associated with fetal growth. 5 The supply of nutrients and oxygen is considered to be the determinant of fetal growth, 6 and in turn the nutritional supply depends on many factors, such as the mother's body composition, her lifelong nutritional status, food intake during pregnancy, and the transport capacity of the placenta. It is unclear how these factors are affected by maternal smoking. Power and co-workers show that there is an increased risk of obesity at age 33 in men and women whose mothers smoked in the second half of gestation. They also found that babies of mothers who smoked were 160 g lighter at birth than babies of non-smokers, which is in agreement with a large number of studies that show that smoking during pregnancy produces on average a reduction in birthweight between 150 and 300 g. The association between maternal smoking and obesity, however, was not affected by adjustment for birthweight, which suggests that smoking influences adult obesity independently of its effect on fetal growth. Consequently, an adverse fetal environment-in this case maternal smoking-may contribute to the development of obesity later in life without affecting size at birth. A similar conclusion was drawn from the results of the Dutch famine studies. The Dutch famine was a sudden period of severe food shortage that occurred in the western part of the Netherlands between November 1944 and May 1945. Studies of people who were born around this period demonstrate that exposure to maternal starvation in early gestation is associated with obesity in adult life independent of its effect on fetal growth. It was found in 300 000 Dutch conscripts that the rate of obesity (body weight for height ജ120% of a population standard) was higher among men exposed to the Dutch famine in the first half of gestation (2.8%), and lower among men exposed in the last trimester of gestation or the immediate postnatal period (0.8%), compared to non-exposed men (1.8%). 7 A more recent study of the effects of the Dutch famine in 741 people for whom detailed birth records were available showed again that exposure in early gestation increased body weight, body mass index and waist circumference at age 50, although only in women and not in men, whereas body size at birth was not affected. 8 In other words, the observed association between exposure to famine in early gestation and obesity later in life was independent of body size at birth. Potential mechanisms underlying the development of obesity are sometimes bluntly grouped into two categories. The first refers to hypothalamic dysfunction and the second to abnormalities at the level of the fat cell. The Dutch famine studies suggest that there are effects of maternal exposure to famine on the distribution of body fat in women but not in men. A series of studies in rats, performed in response to the study in the Dutch conscripts, also found differences in effects of maternal starvation between male and female offspring, 9 and larger retroperitoneal and parametrial fat pads rather than increases in total bodyweight. 10 All these findings support the idea that the increased levels of obesity in offspring of mothers who were starved in early gestation were due to permanently altered central regulatory mechanisms of energy intake and expenditure rather than to abnormalities of the adipocytes. One of the most important insights provided by the large body of evidence on the fetal origins hypothesis, generated by epidemiological studies as well as laboratory experiments, is that the effects of an adverse fetal environment depend on its nature, severity and timing. It is therefore unlikely that there is one simple explanation for the finding that children of mothers who smoke during pregnancy have an elevated risk of obesity. Therefore, we need to know more about how smoking affects fetal development. In this respect, the most important finding in the paper by Power and co-workers seems to be that people whose mothers smoke during gestation have a lower birthweight and, independently of birthweight, a higher body mass index in adult life. It may be the adaptations of the fetus to maintain its growth rather than the direct effects of maternal