Unravelling the fetal origins hypothesis: is there really an inverse association between birthweight and subsequent blood pressure? Glucose tolerance of offspring of mother with gestational diabetes mellitus in a low-risk population. Infant and child growth and fatness and fat distribution in Guatemalan adults. The Pelotas birth cohort study, Rio Grande do Sul, Brazil, 1982-2001. Impaired glucose tolerance and elevated blood pressure in low birth weight, nonobese, young south african adults: early programming of cortisol axis. Fetal origins of hyperphagia, obesity, and hypertension and postnatal amplification by hypercaloric nutrition. Associations between prenatal and postnatal growth and adult body size and composition. Prospective study of protein-energy supplementation early in life and of growth in the subsequent generation in Guatemala. Maternal and child nutritional supplementation are inversely associated with fasting plasma glucose concentration in young Guatemalan adults. Maternal Energy Stores and Diet Composition During Pregnancy Program Adolescent Blood Pressure Nutritional supplementation during the preschool years and physical work capacity in adolescent and young adult Guatemalans. Exposure to a nutrition supplementation intervention in early childhood and risk factors for cardiovascular disease in adulthood: evidence from Guatemala. Effect of a nutrition intervention during early childhood on economic productivity in Guatemalan adults Nutritional supplementation during the preschool years influences body size and composition of Guatemalan adolescents. The Human Capital Study 2002–04: Tracking, data Collection, Coverage, and Attrition Sedentary behavior during postnatal life is determined by the prenatal environment and exacerbated by postnatal hypercaloric nutrition. Prenatal or early postnatal events predict infectious deaths in young adulthood in rural Africa. Long term effect of calcium supplementation during pregnancy on the blood pressure of offspring: follow up of a randomised controlled trial The association between early childhood stunting and weight status in late adolescence Birthweight and blood pressure in five European birth cohort studies: an investigation of confounding factors. Relation of serial changes in childhood body-mass index to impaired glucose tolerance in young adulthood.
BACKGROUND The association between birthweight and subsequent blood pressure levels  has been considered to provide some of the strongest , and most consistent , support for the " fetal origins " hypothesis of adult disease . It had been estimated that a 1 kg higher birthweight is typically associated with a 2 - 4 mm Hg lower systolic blood pressure . METHODS 55 studies that had reported regression coefficients of systolic blood pressure on birthweight ( with 48 further studies that reported only the direction of this association ) , and seven such studies within twin pairs , were identified . Each study was weighted according to the inverse of the variance of the regression coefficient ( ie , " statistical size " ) , and combined using a " fixed effects " approach . FINDINGS Among the 55 studies that reported regression coefficients , there was a clear trend ( p<0.0001 ) towards weaker associations in the larger studies : -1.9 mm Hg/kg in those with less than about 1000 participants ; -1.5 mm Hg/kg with about 1000 - 3000 participants ; and -0.6 mm Hg/kg with more than 3000 participants . By contrast with the inverse associations reported in 52 of these 55 studies , only 25 of the 48 studies that did not report regression coefficients found an inverse association ( p<0.0001 for heterogeneity ) . Almost all of these regression coefficients had been adjusted for current weight ( whereas few were adjusted for potential confounding factors ) , and removal of this adjustment in the larger studies reduced the estimated association to -0.4 mm Hg/kg . For studies within monozygotic twin pairs , the combined estimate was -0.6 mm Hg/kg with adjustment for current weight , and was also reduced without this adjustment . INTERPRETATION Cl aims of a strong inverse association between birthweight and subsequent blood pressure may chiefly reflect the impact of r and om error , selective emphasis of particular results , and inappropriate adjustment for current weight and for confounding factors . These findings suggest that birthweight is of little relevance to blood pressure levels in later life AIMS To describe the prevalence of impaired glucose tolerance and obesity in offspring of mothers whose pregnancies were complicated by gestational diabetes mellitus ( GDM ) in a low-risk population and to investigate the effect on these outcomes of minimal intervention compared with tight control for management of GDM . METHODS Eighty-nine children ( mean age 9.1 years , 93 % Caucasian ) were recruited through a follow-up study of women previously involved in a r and omized controlled trial of minimal intervention ( control group ) vs. tight glycaemic control ( treatment group ) for GDM . Fasting blood glucose ( FBG ) and 2-h glucose tolerance tests ( 2hGTT ) were performed on offspring and body mass index ( BMI ) calculated . Glucose tolerance and BMI of treatment groups were compared using non-inferiority tests ( non-inferiority margin -15 % ) . RESULTS Of those offspring , 6.9 % ( 5/72 ) had abnormal glucose metabolism [ four children had impaired glucose tolerance ( IGT ) and one had Type 2 diabetes mellitus ( DM ) ( all Caucasian ) ] . Of the four children with IGT , three were male , three had normal BMI , and three had a family history of Type 2 diabetes . Of the 71 offspring who underwent 2hGTT , 25/25 ( 100 % ) of the control offspring and 46/46 ( 100 % ) of the treatment offspring had normal FBG ( FBG < 5.7 mmol/l ) . Twenty-five of 25 ( 100 % ) of control and 42/46 ( 91.3 % ) of the treatment offspring had normal glucose tolerance ( 2hGTT < 7.8 mmol/l ) ( % difference 8.7 , 95 % CI -5.6 , 20.3 ) . BMI < 85th percentile was found in 25/33 ( 75.8 % ) of the treatment group and 44/52 ( 84.6 % ) of the control group ( difference in percentage -8.9 , 95 % CI -27.2 , 7.8 ) . CONCLUSIONS School-age children of mothers with GDM are at risk of IGT and overweight , even if from a low-risk ethnic population . FBG was not adequate for screening this population . Minimal intervention for glycaemic control in GDM pregnancies appears to be as effective as tight control for preventing IGT in childhood but not for preventing obesity To examine whether poor growth in utero or young childhood is associated with adult abdominal fatness in a developing country context , the authors analyzed prospect ively collected data on 372 female and 161 male Guatemalans measured as children between 1969 and 1977 and remeasured as adults in 1988 - 1989 ( men and women ) and 1991 - 1994 ( women only ) . Childhood stunting ( height-for-age z score ) was associated with a lower body mass index and percent body fat in men , while no associations were found in women . In both sexes , however , severely stunted children had significantly greater adult abdominal fatness ( waist : hip ratio ) , once overall fatness and confounders were controlled . The adult waist : hip ratio ( x100 ) was increased by 0.65 ( 95 % confidence interval 0.10 to 1.20 ) in men and 0.29 ( 95 % confidence interval -0.03 to 0.61 ) in women for each height-for-age z score less at age three . Migration to urban centers was significantly associated with an even greater waist : hip ratio in severely stunted females ( p = 0.03 ) . In a sub sample of 137 women , short and thin newborns had significantly greater adult abdominal fatness compared with long and thin or short and fat newborns or children who became stunted postnatally . The adult waist : hip ratio ( x100 ) was increased by 1.58 ( 95 % confidence interval 0.35 to 2.81 ) for each kilogram less birth weight . The authors conclude that , in countries where maternal and child malnutrition exists alongside rapid economic development and urban migration , abdominal obesity and related chronic diseases are likely to increase Given the growing recognition of the importance of the life course approach for the determination of chronic diseases , birth cohort studies are becoming increasingly important . This paper describes the methods used in the 1982 Pelotas ( Brazil ) birth cohort study  , one of the largest and longest studies of this type in developing countries . All 5,914 hospital births occurring in Pelotas in 1982 ( over 99 % of all deliveries ) were studied prospect ively . The main stages of the study took place in 1983 , 1984 , 1986 , 1995 , 1997 , 2000 , and 2001 . More than two thous and variables are available for each subject who participated in all stages of the study . Recent phases of the study included the examination of 2,250 males when presenting for the army recruitment exam in 2000 , the study of a 27 % sample of men and women in 2001 through household visits , and the study of over 400 children born to the cohort women .  Follow-up rates in the recent stages of the cohort were 78.9 % for the army examination and 69.0 % for the household visits . Ethnographic and oral health studies were conducted in sub- sample s. Some recent results on blood pressure , adolescent pregnancy , and asthma are presented as examples of utilization of the data . Suggestions on lessons learned for other cohort studies are proposed Low birth weight is associated with increased cardiovascular and metabolic disorders in adult life , although the mechanisms of this effect remain uncertain . There is one report of increased morning plasma cortisol levels in an elderly low birth weight cohort , but whether this is primary or secondary to other aspects of the phenotype is unclear . We investigated the association between low birth weight and glucose intolerance , blood pressure , and dyslipidemia in young , nonobese adults from a community undergoing the health transition with a high prevalence of both noncommunicable diseases and low birth weight . Additionally , we investigated whether altered basal and stimulated cortisol levels as a marker of hypothalamic-pituitary-adrenal responsiveness or cortisol metabolism were associated with low birth weight in these young adults . Twenty-year-old , historically disadvantaged , urbanized South Africans ( n = 137 ) with birth weights either below the 10th percentile [ underweight for age ( UFA ) ] or between the 25th and 75th percentiles [ appropriate for gestational age ( AFA ) ] had anthropometry , blood pressure , lipid levels , and glucose tolerance measured . In a subset ( n = 62 ) , 0900 h plasma cortisol concentrations , cortisol responses to 1 microg ACTH , and urinary glucocorticoid metabolites were measured . The mothers of UFA infants were themselves lighter and had a lower body mass index ( P : = 0 . 0016 ) . At age 20 yr , although the UFA group was still smaller and lighter , with a lower body mass index , they had higher fasting plasma glucose levels ( P : = 0.047 ) , and a greater proportion demonstrated glucose intolerance ( 11.9 % vs. 0 % ; P : < 0.01 ) . The UFA group also had higher systolic [ UFA , 126.0 + /- 13.3 ( + /-SD ) ; AFA , 122.0 + /- 11.7 mm Hg ; P : = 0.007 ] and diastolic ( 72.3 + /- 8.4 vs. 69 . 5 + /- 8.7 mm Hg ; P : = 0.02 ) blood pressures , after covarying for current weight and gender . Plasma cortisol levels determined at 0900 h were higher in the UFA group ( 484.9 + /- 166.3 vs. 418.6 + /- 160.6 nmol/L ) and showed a greater plasma cortisol response to low dose ACTH stimulation ( area under the curve for cortisol : UFA , 77,238 + /- 19,511 ; AFA , 66,597 + /- 16,064 nmol/L.min ; P : = 0.04 ) . In conclusion , the link between low birth weight and adult glucose intolerance and blood pressure elevation occurs in young adults in a high risk , disadvantaged population despite a lack of full catch-up growth . Moreover , cortisol axis activation is an early feature in the process linking low birth weight with adult cardiovascular and metabolic disease and is not dependent upon adult obesity or full catch-up growth , at least in this population undergoing the health transition Environmental factors and diet are generally believed to be accelerators of obesity and hypertension , but they are not the underlying cause . Our animal model of obesity and hypertension is based on the observation that impaired fetal growth has long-term clinical consequences that are induced by fetal programming . Using fetal undernutrition throughout pregnancy , we investigated whether the effects of fetal programming on adult obesity and hypertension are mediated by changes in insulin and leptin action and whether increased appetite may be a behavioral trigger of adult disease . Virgin Wistar rats were time mated and r and omly assigned to receive food either ad libitum ( AD group ) or at 30 % of ad libitum intake , or undernutrition ( UN group ) . Offspring from UN mothers were significantly smaller at birth than AD offspring . At weaning , offspring were assigned to one of two diets [ a control diet or a hypercaloric ( 30 % fat ) diet ] . Food intake in offspring from UN mothers was significantly elevated at an early postnatal age . It increased further with advancing age and was amplified by hypercaloric nutrition . UN offspring also showed elevated systolic blood pressure and markedly increased fasting plasma insulin and leptin concentrations . This study is the first to demonstrate that profound adult hyperphagia is a consequence of fetal programming and a key contributing factor in adult pathophysiology . We hypothesize that hyperinsulinism and hyperleptinemia play a key role in the etiology of hyperphagia , obesity , and hypertension as a consequence of altered fetal development BACKGROUND Adult body size and composition ( ABSC ) measures are associated with work capacity and productivity , reproductive performance , and chronic disease risk . Growth failure in early childhood may have important long-term consequences through its influence on ABSC . OBJECTIVE We assessed associations between prenatal and postnatal growth ( 0 - 2 y of age ) and ABSC . DESIGN We included 267 singletons from a prospect i ve study carried out between 1969 and 1977 in 4 ladino Guatemalan villages . We used data from that study and from a follow-up study conducted in 1998 - 1999 ( when the subjects were 21 - 27 y of age ) to determine associations of birth weight , length at 15 d of age , ponderal index , and length at 2 y of age with adult height , weight , fat-free mass ( FFM ) , fat mass , percentage of body fat , and waist-to-hip ratio . Multivariate linear regression analyses with mixed models were carried out to account for sibling clustering . Two-stage least-squares analyses were used to separate specific effects of prenatal and postnatal growth . RESULTS Birth weight , length at 15 d of age , and length at 2 y of age were positively associated with height , weight , and FFM in both sexes ( P < 0.05 ) . Prenatal growth and postnatal growth were equally important determinants of height , weight , and FFM . Weak positive associations of postnatal growth with adult fat mass and percentage of body fat were found in both sexes , whereas similar associations for prenatal growth were found in women only . Growth in early childhood was not related to waist-to-hip ratio . CONCLUSIONS Growth retardation in early childhood was associated with shortness and less FFM in adulthood . Preventing growth failure in utero and preventing growth failure during the first 2 y of life are equally important for ABSC BACKGROUND The secular increase in height is assumed to result from long-term improvements in nutritional intakes and reductions in infectious disease burdens . Nutritional supplementation in early life reduces stunting in chronically undernourished population s. It is unknown whether these improvements can be transmitted to subsequent generations . OBJECTIVE Our objective was to estimate the intergenerational effect on offspring length of improved nutrition in the mother 's childhood . DESIGN We studied 263 children born in 1996 - 1999 to 231 women who had received nutritional supplementation , ie , atole ( high-protein , moderate-energy drink ) or fresco ( nonprotein , low-energy drink ) , prenatally and up to age 7 y as part of a community trial in Guatemala between 1969 and 1977 . Child length was measured at different times to age 36 mo . RESULTS Children born to women who received the enhanced supplement were taller ( age-adjusted difference : 0.80 cm ; 95 % CI : 0.16 , 1.44 cm ) than were children whose mothers received the low-energy supplement . This increment was independent of the children 's birth weight or socioeconomic status but was substantially attenuated and no longer significant after adjustment for maternal height ( adjusted difference : 0.43 cm ; 95 % CI : -0.10 , 0.96 cm ; P > 0.10 ) . The effect of maternal nutritional supplementation  was more pronounced in boys than in girls ( P for interaction < 0.10 ) and in children born to women who received supplements at ages 3 - 7 y than in children born to women who received supplements at ages 0 - 3 y ( P for interaction < 0.01 ) . CONCLUSION Nutritional supplementation in childhood has positive effects on both the supplemented persons and on the subsequent generation Cardiovascular disease and diabetes may be programmed early in life by abnormal development associated with undernutrition . We investigated whether maternal nutritional status ( MNS ; height , pregnancy weight gain , nonpregnant BMI , and prenatal supplementation )  or childhood nutritional status ( CNS ; birth weight , length , ponderal index , height-for-age Z-score at 24 mo , and supplementation from 0 to 24 mo ) were related to fasting plasma glucose levels in rural-born Guatemalan adults . We studied 209 men and 220 women ( mean age 24.4 y ) who were involved in a r and omized trial of nutritional supplementation of their mothers during pregnancy and during their early childhoods , conducted from 1969 to 1977 . In 2 villages , residents were offered Atole ( 3.8 MJ and 64 g protein/L ) ; 2 other villages were offered Fresco ( 1.4 MJ/L , no protein ) . No associations were observed between anthropometric measures of MNS or CNS and fasting plasma glucose levels . In subgroup analyses , inverse associations ( all P < 0.15 ) with birth size were found among women born to fatter mothers , women with low supplement intake , men born to short mothers , and men more severely stunted at 24 mo . Prenatal supplementation was inversely associated with fasting plasma glucose among women [ -0.40 + /- 0.17 mmol/(L. MJ . d ) , P = 0.02 ] . Among men , postnatal intake of supplementation of 0.10 to 0.20 MJ/d was associated with up to a 0.56 mmol/L reduction in fasting plasma glucose ( P = 0.03 ) , but intake in excess of 0.20 MJ/d provided no added benefit . Among women , the benefit of postnatal supplementation was restricted to those born thin ( test for interaction P = 0.10 ) . Improving the nutritional status of undernourished women and children may have positive long-term consequences Background —Fetal undernutrition is hypothesized to program blood pressure ( BP ) later in life . Human epidemiological studies that use birth weight as a proxy for fetal malnutrition fail to identify specific aspects of maternal nutrition responsible for programming . Methods and Results —We examined how maternal nutrition during pregnancy and infant birth weight relate to systolic and diastolic BP ( SBP and DBP ) in 2026 Filipino adolescents . Data were collected prospect ively during the Cebu ( Philippines ) Longitudinal Health and Nutrition Survey . Women were assessed at ≈30 weeks gestation , and children were followed from birth through adolescence . Regression models were used to examine how the mothers ’ total energy intake , percentage of energy from protein and fat , triceps skinfold thickness during pregnancy , and infant birth weight relate to adolescent BP , controlling for current age , height , and body mass index and other potential confounders . Maternal triceps skinfold thickness was significantly inversely related to SBP among boys and to DBP in boys and girls . Maternal nutrition variables attenuated but did not eliminate an inverse birth weight – SBP relationship in boys . SBP was significantly inversely related to the mothers ’ percent of dietary energy from protein in boys . Among girls , SBP and DBP were inversely related to the mothers ’ percentage of calories from fat . There was no evidence of confounding of these relationships by current diet , maturation status , physical activity , or socioeconomic status . Conclusions —Maternal diet composition and energy stores in the form of subcutaneous fat have long-term effects on offspring BP in adolescence A follow-up study ( 1988 - 89 ) was carried out in 364 rural Guatemalans , 11 - 27 y of age , who earlier had participated in a nutritional supplementation experiment . Among its objectives was the assessment of the long-term effects of the nutrition intervention on physical work capacity .  Subjects and their mothers from two villages had available a high-energy , high-protein supplement ( Atole : 163 kcal/682 kJ and 6.4 g protein per serving or 180 mL ) , whereas in two other villages a low-energy , no-protein supplement ( Fresco : 59 kcal/247 kJ per 180 mL ) was provided . Consumption was ad libitum . Maximum oxygen consumption ( VO2max ) at follow-up was significantly greater in Atole compared with Fresco subjects of both sexes . In subjects 14 - 19 y , exposed to supplementation throughout gestation and the first 3 y of life , Atole males had a significantly higher VO2max ( 2.62 L/min ) than Fresco males ( 2.24 L/min ) , the differences remaining significant even after controlling for body weight and fat-free mass ; also , there was a significant positive relationship between amount of supplement consumed and VO2max . The supplementation effect in females of similar age was not statistically significant . It is concluded that early nutritional improvements can have long-lasting effects on physical performance To study the role of nutrition in the association of birth size and childhood growth with development of cardiovascular disease , the authors in 2002 - 2004 surveyed 665 men and 790 women aged 25 - 42 years who had been exposed as children to a community-r and omized nutrition supplementation intervention in four villages in eastern Guatemala . Exposure was associated with a lower fasting glucose level ( 7.0 mg/dl , 95 % confidence interval ( CI ) : 0.5 , 13.5 ) for exposure at ages 36 - 72 months ; lower systolic blood pressure ( 3.0 mmHg , 95 % CI : 0.4 , 5.6 ) for exposure at ages 24 - 60 months ; and a lower triglyceride level ( sex-adjusted ; 22.2 mg/dl , 95 % CI : 0.4 , 44.1 ) and higher high density lipoprotein cholesterol level ( males only ; 4.7 mg/dl , 95 % CI : 1.5 , 7.9 ) for exposure prior to age 36 months . Improved nutrition at any age prior to 7 years was not associated with diastolic blood pressure , total or low density lipoprotein cholesterol level , or prevalence of the metabolic syndrome .  Interventions design ed to address nutrient deficiencies and ameliorate stunting that are targeted at pregnant women and young children are unlikely to increase cardiovascular disease risk later in life and may instead lower the risk BACKGROUND Substantial , but indirect , evidence suggests that improving nutrition in early childhood in developing countries is a long-term economic investment . We investigated the direct effect of a nutrition intervention in early childhood on adult economic productivity . METHODS We obtained economic data from 1424 Guatemalan individuals ( aged 25 - 42 years ) between 2002 and 2004 . They accounted for 60 % of the 2392 children ( aged 0 - 7 years ) who had been enrolled in a nutrition intervention study during 1969 - 77 . In this initial study , two villages were r and omly assigned a nutritious supplement ( atole ) for all children and two villages a less nutritious one ( fresco ) . We estimated annual income , hours worked , and average hourly wages from all economic activities . We used linear regression models , adjusting for potentially confounding factors , to assess the relation between economic variables and exposure to atole or fresco at specific ages between birth and 7 years . FINDINGS Exposure to atole before , but not after , age 3 years was associated with higher hourly wages , but only for men . For exposure to atole from 0 to 2 years , the increase was US$ 0.67 per hour ( 95 % CI 0.16 - 1.17 ) , which meant a 46 % increase in average wages . There was a non-significant tendency for hours worked to be reduced and for annual incomes to be greater for those exposed to atole from 0 to 2 years . INTERPRETATION Improving nutrition in early childhood led to substantial increases in wage rates for men , which suggests that investments in early childhood nutrition can be long-term drivers of economic growth Effects of supplementary feeding during early childhood on body size and composition at adolescence are examined in a population with marked growth failure in the first 3 y of life . The data came from a supplementation trial conducted in rural Guatemala from 1969 to 1977 and a 1988 - 89 follow-up study of the same subjects at adolescence . Two pairs of villages participated in the trial . One village from each pair received a high protein-energy supplement ( Atole ) , which significantly improved dietary intakes , whereas the other village of the pair received a low-energy , no-protein supplement ( Fresco ) , which did not impact appreciably on dietary intakes .  Children from Atole villages  grew better during the preschool period than children from  Fresco villages . At adolescence , subjects from Atole villages were taller , weighed more and had greater fat-free masses than subjects from Fresco villages . Differences in height at adolescence were slightly reduced in magnitude relative to differences at 3 y of age . However , differences in weight were increased in adolescence relative to 3 y of age Between 2002 and 2004 , the Institute of Nutrition of Central America and Panama ( INCAP ) , in collaboration with Emory University , the International Food Policy Research Institute ( IFPRI ) , and the University of Pennsylvania , re-surveyed young Guatemalan adults who had , as children , been participants in a nutrition supplementation trial conducted by INCAP between 1969 and 1977 . This “ Human Capital Study 2002–04 ” complements and extends data obtained in previous studies by collecting new information on measures of physical health and well-being , schooling and cognitive ability , wealth , consumption and economic productivity , and marriage and fertility histories . This paper describes the study domains and data collection procedures . Among 2,393 members of the original sample , 1,856 ( 77 % ) were targets for enrollment . Response rates varied by gender , current place of residence , and domain of data collection , with 80 % of males and 89 % of females completing at least one data collection instrument . Attrition was not r and om and appears to be associated with a number of initial characteristics of individuals and their households that should be controlled for in future analyses . We conclude that data collection was successful and data quality is high , facilitating the successful undertaking of our planned investigation of important study hypotheses The discovery of a link between in utero experience and later metabolic and cardiovascular disease is one of the most important advances in epidemiology research of recent years . There is now increasing evidence that alterations in the fetal environment have long-term consequences on metabolic and endocrine pathophysiology in adult life . This process has been termed " fetal programming , " and we have shown that undernutrition of the mother during gestation leads to obesity , hypertension , hyperphagia , hyperinsulinemia , and hyperleptinemia in offspring . Using this model of maternal undernutrition throughout pregnancy , we investigated whether prenatal influences may lead to alterations in postnatal locomotor behavior , independent of postnatal nutrition . Virgin Wistar rats were time mated and r and omly assigned to receive food either ad libitum ( ad libitum group ) or at 30 % of ad libitum intake ( undernourished group ) . Offspring from UN mothers were significantly smaller at birth than AD offspring . At weaning , offspring were assigned to one of two diets [ control or hypercaloric ( 30 % fat ) ] . At ages of 35 days , 145 days , and 420 days , voluntary locomotor activity was assessed . At all ages studied , offspring from undernourished mothers were significantly less active than offspring born of normal birth weight for all parameters measured , independent of postnatal nutrition . Sedentary behavior in programmed offspring was exacerbated by postnatal hypercaloric nutrition . This work is the first to clearly separate prenatal from postnatal effects and shows that lifestyle choices themselves may have a prenatal origin . We have shown that predispositions to obesity , altered eating behavior , and sedentary activity are linked and occur independently of postnatal hypercaloric nutrition . Moreover , the prenatal influence may be permanent as offspring of undernourished mothers were still significantly less active compared with normal offspring at an advanced adult age , even in the presence of a healthy diet throughout postnatal life BACKGROUND Research over the past decade has suggested that prenatal and early postnatal nutrition influence the risk of developing chronic degenerative diseases up to 60 years later . We now present evidence that risk of death from infectious diseases in young adulthood is similarly programmed by early life events . METHODS In three rural Gambian villages , affected by a marked annual seasonality in diet and disease , we have kept detailed demographic , anthropometric and health records since 1949 . Fate was known with certainty for 3,162 individuals ( 2,059 alive/1,103 dead , most dying in childhood ) . For this case-control analysis of antecedent predictors of premature mortality , all adult deaths ( n = 61 ) were paired with  two r and omly selected controls matched for sex and year of birth . RESULTS Mean age at death was 25 ( SD : 8) years . Adult death was associated with a profound bias in month of birth with 49 cases born in the nutritionally-debilitating hungry season ( Jul-Dec ) versus 12 in the harvest season ( Jan-Jun ) . Relative to harvest season the hazard ratio for early death in hungry-season births rose from 3.7 ( for deaths > 14.5 years , P = 0.000013 ) to 10.3 ( for deaths > 25 years , P = 0.00002 ) . Anthropometric and haematological status at 18 months of age was identical in cases and controls , indicating an earlier origin to the defect . Most deaths for which cause was known had a definite or possible infectious aetiology ; none were from degenerative diseases of affluence . CONCLUSIONS Early life exposures , correlated with season of birth , strongly influence susceptibility to fatal infections in young adulthood . The evidence suggests that nutritionally-mediated intrauterine growth retardation may permanently impair the development of immune function Abstract Objective : To explore the long term effect of calcium supplementation during pregnancy on the offspring 's blood pressure during childhood . Design : Follow up of a population enrolled in a double blind , r and omised , placebo controlled trial . Setting : Perinatal research unit , World Health Organisation 's collaborative research centre . Subjects : 591 children at a mean age of 7 years whose mothers were r and omly assigned during pregnancy to receive 2 g/day of elemental calcium ( n=298 ) or placebo ( n=293 ) . Main outcome measures : Mean blood pressure and rate of high blood pressure of children . Results : Overall , systolic blood pressure was lower in the calcium group ( mean difference -1.4 mm Hg ; 95 % confidence interval -3.2 to 0.5 ) than in the placebo group . The effect was found predominantly among children whose body mass index at assessment was above the median for this population ( mean difference in systolic blood pressure -5.8 mm Hg ( -9.8 mm Hg to -1.7 mm Hg ) for children with an index > 17.5 and -3.2 mm Hg ( -6.3 mm Hg to -0.1 mm Hg ) for those with an index of > 15.7 to 17.5 ) . The risk of high systolic blood pressure was also lower in the calcium group than in the placebo group ( relative risk 0.59 ; 0.39 to 0.90 ) and particularly among children in the highest fourth of body mass index ( 0.43 ; 0.26 to 0.71 ) . Conclusion : Calcium supplementation during pregnancy is associated with lower systolic blood pressure in the offspring , particularly among overweight children . Key messages Impaired fetal and maternal nutrition seem to be associated with childhood blood pressure , but most of the evidence comes from uncontrolled studies Systolic blood pressure of children aged between 5 and 9 years was lower when mothers took calcium rather than placebo during pregnancy The effect is found predominantly among children with a body mass index above the median for this population Fetal life seems to be a period for programming blood pressure ; the magnitude of the effect observed has health implication s among overweight Background : Cross-sectional studies have shown associations between stunting and overweight ; however , there are few prospect i ve studies of stunted children . Objectives : To determine whether stunting before age 2 years is associated with overweight and central adiposity at 17–18 years and whether growth in height among stunted children predicts body mass index ( BMI ) in late adolescence . Design : Prospect i ve cohort study . Participants : One-hundred and three participants stunted by age 2 years and 64 non-stunted participants ( 78 % of participants enrolled in childhood ) . Participants were measured in early childhood and at ages 7 , 11 and 17 years . Results : Stunted subjects remained shorter and had lower BMI s , smaller skinfolds and circumferences than non-stunted subjects . Overweight ( BMI ⩾25 m2 ) was not significantly different among stunted and non-stunted male subjects ( 5.2 and 12.5 % ) but non-stunted female subjects were more likely to be overweight than those who experienced early childhood stunting ( 11.1 and 34.4 % , P=0.013 ) . Central ization of fat ( waist to hip ratio ( WHR ) , subscapular/triceps skinfold ratio ( SSF/TSF ) ) did not differ between stunted and non-stunted groups ( mean WHR 0.77 and mean SSF/TSF 1.18 in both groups ) . Stunted subjects with greater increases in height-for-age for the intervals 3–7 and 7–11 years had higher BMI at age 17 years ( P=0.04 and P=0.001 , respectively ) . Conclusion : Participants stunted by age 2 years were less likely to be overweight than those who were never stunted . This suggests that cross-sectional studies of the association between stunting and overweight may be misleading . Among stunted children , greater linear growth during mid- to late childhood was associated with greater BMI at age 17 years BACKGROUND It has been suggested that the association between birthweight and blood pressure has been overstated as a result of publication bias and , within studies , a lack of adjustment for potentially important maternal and socioeconomic confounding factors and ' overadjustment ' for current body size . This study investigates the impact of potential confounding variables on the birthweight-blood pressure association in birth cohort studies from different time periods and geographical locations in Europe . METHODS Data from five European birth cohort studies ( from Finl and , the UK , and the Faroe Isl and s ) taking part in the European Birth-Lifecourse- Studies ( EURO-BLCS ) project were analysed . Birthweight was measured at birth in all cohorts and confounding variable information was collected prospect ively at subsequent follow-ups in all cohorts . Regression models were used to assess the unadjusted association between birthweight and blood pressure and then to assess the impact of potential maternal and socioeconomic confounding variables and adjustment for later body size . Analyses were carried out in the same way across all five cohorts . RESULTS Birthweight was consistently negatively associated with systolic blood pressure ( SBP ) across all cohorts . Gestational age and possibly maternal pre-pregnancy weight , but not socioeconomic status , may be important confounding factors of the relationship between birthweight and SBP . The size of the birthweight-SBP association in adulthood may be larger than in childhood before adjustment for current body size , although a cohort effect can not be ruled out . CONCLUSION This study highlights the value of future cross-cohort comparisons in the investigation of the foetal origins of adult disease BACKGROUND The risk of type 2 diabetes mellitus is increased in people who have low birth weights and who subsequently become obese as adults . Whether their obesity originates in childhood and , if so , at what age are unknown . Underst and ing the origin of obesity may be especially important in developing countries , where type 2 diabetes is rapidly increasing yet public health messages still focus on reducing childhood " undernutrition . " METHODS We evaluated  glucose tolerance and plasma insulin concentrations  in 1492 men and women 26 to 32 years of age who had been measured at birth and at intervals of three to six months throughout infancy , childhood , and adolescence in a prospect i ve , population -based study . RESULTS The prevalence of impaired glucose tolerance was 10.8 percent , and that of diabetes was 4.4 percent . Subjects with impaired glucose tolerance or diabetes typically had a low body-mass index up to the age of two years , followed by an early adiposity rebound ( the age after infancy when body mass starts to rise ) and an accelerated increase in body-mass index until adulthood . However , despite an increase in body-mass index between the ages of 2 and 12 years , none of these subjects were obese at the age of 12 years . The odds ratio for disease associated with an increase in the body-mass index of 1 SD from 2 to 12 years of age was 1.36 ( 95 percent confidence interval , 1.18 to 1.57 ; P<0.001 ) . CONCLUSIONS There is an association between thinness in infancy and the presence of impaired glucose tolerance or diabetes in young adulthood . Crossing into higher categories of body-mass index after the age of two years is also associated with these disorders
In this paper we review the associations between  maternal and child undernutrition with human capital and risk of adult diseases in low-income and middle-income countries .