there is a body of evidence suggesting that type 2 diabetes is programmed in utero [ 1 , 2 ] . fetal programming is the process through which fetal malnutrition leads to lifelong changes in the body organs and systems in ways that might cause disease in later life . there is some evidence that obesity , a major risk factor for type 2 diabetes , is also programmed in utero . maternal hyperglycemia is associated with obesity in the next generation [ 4 , 5 ] . women who were in utero during the dutch famine tended to be overweight as adults as a consequence of early programming . fetal nutrition depends on the placenta ability to transport nutrients to the fetus from its mother . small babies generally have small placentas , but , in some circumstances , an undernourished fetus can expand its placental surface to extract more nutrients from the mother . this phenomenon is well known to sheep farmers who induce placental expansion by undernourishing ewes in midgestation . when the ewes are returned to good pasture the expanded placenta results in a larger fatter lamb than they otherwise would be . there are findings suggesting that placental expansion occurs in humans through extension of the placental surface along its minor axis . interestingly , in sheep placental expansion can only occur if the ewe was well nourished up to the time of mating . maternal body size , especially height , can be used as a marker of her life time nutrition . short maternal stature is a product of poor fetal and childhood nutrition , or recurrent exposure to infections , and genetic factors . the peroxisome - proliferator - activated receptor 2 ( ppar2 ) gene encodes a nuclear hormone receptor that mediates adipocyte differentiation and regulates glucose and lipid metabolism [ 1417 ] . variants of the ppar2 have repeatedly been linked to overweight , insulin resistance , and type 2 diabetes . furthermore , ppar is known to play an important role in controlling placental vascular proliferation , trophoblast differentiation , and invasion [ 18 , 19 ] . we have previously shown that the association between expansion of the placental surface with later hypertension is dependent upon maternal height . we now speculate that the long - term costs could also include overweight and obesity in later life . we therefore examined the long - term effects of placental expansions on overweight and body composition taking maternal height and genetic factors , the ppar2 gene , into account . we examined this in the helsinki birth cohort study ( hbcs ) , which comprises people born in 193444 for whom the size of the placental surface was measured at birth . the study cohort consists of 8760 men and women who were born between 1934 and 1944 in helsinki university central hospital and who visited child welfare clinics in the city . details of the birth records and child welfare clinic records have been described [ 20 , 21 ] . the weight and length of the baby at birth were recorded , and we calculated the ponderal index ( birth weight / length ) . the records also included the weight of the placenta , together with the maximal so - called diameter  of the surface and a lesser  diameter  bisecting it at right angles . the diameters were measured because it was recognized that the placental surface is more oval than circular and the two diameters were used to describe this . assuming an elliptical surface , we estimated the surface area of the placenta as maximal  lesser diameter /4 . we used random number tables to select a sample of people within the cohort who were still living in finland . in order to achieve a sample size in excess of 2000 people we selected 2902 subjects and invited them to a clinic the ethics committee at the national public health institute , finland , approved the study . at the clinic height and weight body mass index ( bmi ) was calculated as weight ( kg ) divided by height ( m ) . estimates of total lean and fat mass were measured by bioelectrical impedance analysis using the inbody 3.0 eight - polar tactile electrode system , biospace co. , ltd , seoul , republic of korea , as described . we analysed overweight using multiple logistic regression and percent body fat and lean body mass using multiple linear regression . table 1 shows the measurements of birth and placental size and current body size , together with the frequency of the pro12pro genotype . table 2 shows the odds ratios and regression coefficients for three outcomes , overweight ( bmi  25  kg / m ) , body fat percentage , and lean body mass , according to birth weight , ponderal index ( birth weight / length ) , and placental size . the odds ratios and regression coefficients represent the change in each outcome that is associated with a 1  sd increase in birth size or placental size . overweight was predicted by high birth weight and high ponderal index , while percent body fat was predicted by high ponderal index . neither overweight nor percent body fat was predicted by measurements of placental size . as in previous analyses we divided the subjects around the mother 's median height ( 160  cm ) ( table 3 ) . in both maternal height groups lean body mass was predicted by all measurements of body and placental size . among people whose mothers were tall a long lesser placental diameter predicted both overweight and percent body fat . there was a statistically significant interaction between the effects of mother 's height and the lesser diameter on percent body fat ( p for interaction = 0.02 ) . among people whose mothers were short , no measurements of placental size predicted overweight or percent body fat . allele overweight was predicted by a large maximal diameter but there were no other associations between placental size and either overweight or percent body fat . among people with the pro12pro genotype large placental area and a long lesser diameter predicted both overweight and percent body fat ( table 4 ) . there were statistically significant interactions between the genotypes and the effects of placental area and the lesser diameter on overweight and percent body fat ( p for interaction = 0.004 and 0.05 for area and 0.03 and 0.09 for the lesser diameter , resp . ) . in people with the pro12pro genotype a long maximal diameter predicted overweight but not percent body fat . in a simultaneous regression with the lesser diameter in the whole study sample placental size was not associated with either overweight or a high percent of body fat . we found , however , that an expanded placental surface and a long lesser diameter predicted overweight and high percent of body fat in a subset of men and women whose mothers were tall and who carried the pro12pro genotype of the ppar2 gene . higher birth weight was associated with an increased risk of having a bmi greater than 25  kg / m and with a greater lean body mass . this has been shown before and suggests that birth weight influences adult body mass index through its effect on lean body mass [ 22 , 24 ] . our findings suggest that lean body mass is related to the volume of placental tissue , reflected in its weight , while fat mass is related to placental surface area . we have previously shown that an enlarged placental surface is associated with later hypertension , but this association was confined to people whose mothers were tall . we interpreted this as evidence that compensatory placental expansion in humans is similar to compensatory expansion in sheep , in that it can only occur in women who were well nourished before they conceived . we have shown that people who had an enlarged placental surface and later hypertension had above - average birthweight . this is consistent with sheep farming practices in which placental expansion is induced by undernourishing ewes [ 10 , 12 ] . the association between a large placental surface and later hypertension depended on a large lesser diameter rather than a large maximal diameter . our findings for overweight and percentage body fat are similar in that they are only predicted by large lesser diameter . this is a further evidence that tissue along the minor axis of the placental surface is qualitatively different to tissue along the major axis . we suggest that placental expansion increases the nutrient supply to the fetus , but this supply is unbalanced . we have previously proposed that compensatory placental expansion increases glucose transfer to the fetus , but this may not be matched by transfer of other nutrients , including proteins [ 26 , 27 ] . placental enlargement could affect the fetus in the same way as high circulating maternal glucose concentrations , initiating biochemical changes that ultimately lead to obesity . our findings suggest that this only occurs in people who are homozygotes for the pro12 allele of the ppar2 gene . we have previously discussed limitations of the helsinki birth cohort study [ 20 , 21 ] . the data are restricted to subjects who were born in helsinki university central hospital and attended voluntary child welfare clinics , did not emigrate , and were still alive and willing to participate in the year 2003 . however , we believe that our results , based on internal comparisons within the cohort , are unlikely to differ between those who attended and those who did not . we have no information about what aspect of maternal malnutrition stimulated compensatory placental growth . in finland , as in other northern european countries , the long winters brought shortages of fruit and vegetables . in addition , there were widespread food shortages around the time of the second world war , when our cohort was born . we have found that a large placental surface area is associated with a high body fat percentage and an increased risk of being overweight in adult life . we suggest that the enlarged surface is the result of expansion of the placental surface to compensate for fetal malnutrition in midgestation . the association between the placental surface area and adiposity was only found in people with the pro12pro genotype of the ppar2 gene . we suggest that there is an interplay between nutritional factors and genes at the placental level , which is affecting the later risk for obesity .
obesity is programmed in utero and small babies generally have small placentas . in some circumstances , an undernourished fetus can expand its placental surface to extract more nutrients . 
 we hypothesize that this results in an imbalanced nutrient supply to the fetus leading to obesity . to determine whether placental size determines overweight and body composition , we studied 2003 subjects in adult life . associations between placental surface area and indices of overweight were restricted to people who carried the pro12pro genotype of the ppar2 gene . 
 for every 1 sd increase in placental surface area , the odds ratio for overweight was 1.37 ( 95% ci 1.10 to 1.71 ; p = 0.005 ) . 
 expansion of the placental surface in compensation for fetal undernutrition increases the risk of overweight and a higher body fat percentage in people carrying the pro12pro genotype . 
 we suggest that similar underlying multifactorial mechanisms affect the development of obesity in general .