as the prevalence of obesity in children and adolescents has escalated worldwide , signs of the metabolic syndrome ( mets ) are increasingly observed in the pediatric age range .
mets refers to a cluster of abnormal physical examination and laboratory findings , including high waist circumference , serum triglyceride , serum glucose , and blood pressure , and low - serum hdl - cholesterol .
these findings synergistically relate to risk for developing type 2 diabetes and cardiovascular diseases ( cvds ) , including coronary artery disease and stroke [ 24 ] . in a study of a representative sample of us 12- to 19-year - old , 8.6% met criteria for mets ; hispanic youth had a higher prevalence ( 11.2% ) than white ( 8.9% ) or black adolescents ( 4.0% ) .
children who meet the criteria are at increased risk for cvd in adulthood . focusing on the mets during the pediatric period is expected to lead to early - prevention strategies for diabetes and cvd .   a large body of evidence suggests that metabolic programming can occur early in life [ 68 ] .
early - life risk factors include low birth weight and rapid postnatal weight gain . breastfeeding including duration and dose appears to offer protection for obesity , type 2 diabetes , the mets , and cvd [ 912 ] .
in fact , the time immediately before and after birth may be a sensitive period related to metabolic and cardiovascular risk .
rapid post - natal weight gain is associated with increased risk for obesity , type 2 diabetes and hypertension in young adulthood [ 1318 ] .
infant weight gain , especially in the first 3 months , may be more important than birth weight as a predictor of later health outcomes .
adolescent mets has previously been found to be associated with infancy growth in the setting of a developed country .  
much of the work on fetal origins of disease has been done in developed countries beginning with barker 's work in england .
research in low- to middle - income countries is needed to further delineate the roles of biology and environment related to early - life risk for cardiovascular disease and related conditions .
our cohort of low- to middle - income chilean adolescents , studied since infancy , provides a special opportunity to address these research questions , especially because the participants were born during a period of rapid nutritional and economic transition in chile .
this transition was characterized by economic progress that led to increased consumption of calories , fat , animal protein , and processed foods , and increased mortality from noncommunicable chronic diseases .
the aims of this study were to examine the association between infant weight gain from birth to 3 months and risk for the mets in mid - adolescence , accounting for the extent of exclusive breastfeeding in infancy and covariates known to be associated with infant growth and the mets , gender , birth weight , and socioeconomic status ( ses ) .
this is an observational cohort study involving adolescents who were enrolled as infants in a randomized controlled trial of iron supplementation to prevent iron deficiency anemia .
infants were enrolled from 19911996 in santiago , chile ; 1657 infants completed the preventive trial at 1 year .
the inclusion criteria for the preventive trial were infant birth weight of 3  kg or more , with no birth complications , major congenital abnormalities , or prior iron therapy . due to a highly successful national breastfeeding campaign , all but 8 infants in the cohort were initially breastfed .
infants were randomly assigned to low or high iron supplementation , or usual nutrition ( no added iron ) .
a more detailed description of randomization techniques , sampling , and entrance and exclusion criteria is published elsewhere .
the participants have been involved in follow - up studies at 5 , 10 , and 16 years . at 16 years , the participants from the longitudinal cohort were invited to enroll in a study of adolescent obesity and cardiovascular risk .
we report on the first 384 studied from a randomly selected sample of the original cohort evaluated at 16 years between may 2009 and january 2011 .
complete data from the infancy and adolescent waves were available for 357 of the 384 adolescents .
infancy variables ( birth weight , weight at 3 months , and gestational age ) did not differ between the 357 studied and the original 1657 infant participants .
our analytic sample was more likely to receive bottle supplementation before 90 days , compared to the larger cohort ( 52% versus 45% , p < 0.05 ) .
the longitudinal study has been approved by the institutional review boards of the university of michigan , ann arbor usa ; institute of nutrition and food technology , university of chile , santiago , chile for each wave of study ; by the university of california , san diego , for the 16-year study of obesity and cardiovascular risk .
we included the following infancy measures : gender , weight measured at birth and at 3 months , and date of the first supplemental bottle .
mother 's prepregnancy bmi was calculated from measured height and self - report of prepregnancy weight .
data on pre - pregnancy weight was not collected for the infancy study . during the 10-year wave of data collection ,
mothers reported their pre - pregnancy weight ; it was highly correlated with their actual weight 10 years later .  
adolescents were assessed between 16 and 17 years during the fourth wave of the longitudinal research study ( infancy , 5 years , 10 years , and 16 - 17 years ) .
height ( cm ) , weight ( kg ) , waist and hip circumference ( cm ) , and blood pressure ( mm hg ) were measured by a physician - investigator at the nutrition research center .
standardized procedures   were used to measure weight to the closest 0.1  kg , using a seca scale , and height to the closest 0.1  cm , using a holtain stadiometer .
measurements were taken twice , with a third measurement if the difference between the first two exceeded 0.3  kg for weight and 0.5  cm for height .
serum glucose concentration ( mg / dl ) , triglycerides ( mg / dl ) , and cholesterol ( mg / dl ) levels were determined using an enzymatic - colorimetric test ( qca s.a . , amposta , spain ) . using a standardized questionnaire , parents reported family history of type 2 diabetes , hypertension , dyslipidemia , and heart attack before the age of 60 , in first - degree relatives .  
infant weight gain in the first 3 months was calculated as weight gain velocity over the first 3 months ( 91.3 days ) : ( weight [ kg ] at 3-month birth weight [ kg])/(age at 3-month measurement  91.3 days ) . extent of breastfeeding was assessed as a dichotomous variable representing breastfeeding without bottle supplementation for less than 90 days , compared to 90 days or more .
maternal education was assessed as a continuous measure ( median for sample = 10 years ) .
we constructed a metabolic syndrome risk z - score according to the work of brage and colleagues .
the following variables were converted to z - scores : the reciprocal of the hdl value , the mean of the systolic and diastolic blood pressure measurements , waist circumference , fasting serum triglyceride , and glucose .
we obtained a continuous , normally distributed metabolic risk z - score by averaging these 5 values .  
for descriptive statistics , continuous variables were expressed as median and interquartile ranges and categorical variables as frequencies .
we evaluated cardio / metabolic risk factors and overall prevalence of the mets according to international diabetes federation definition : waist circumference 94  cm for boys and 80  cm for girls , plus any two of the following four factors : triglycerides 1.7 
mmol / l , hdl - cholesterol < 40  mg / dl in males and < 50  mg / dl in females , systolic bp 130 or diastolic bp 85  mm hg , fasting plasma glucose 100  mg / dl .
we used spss for windows version 18.0 ( chicago , il , usa ) , a p value of < 0.05 denoted statistical significance .
multiple linear regression models were used to determine the relationship between change in weight ( kg ) in the first 3 months and metabolic syndrome risk z - score , adjusting for extent of breastfeeding and the following covariates : birth weight , gender , ses , age , mother 's age at birth of infant , mother 's pre - pregnancy bmi , and family history of type 2 diabetes , dyslipidemia , and heart attack .
we tested the full model and then , using backward elimination , removed each variable that was not significantly related to the outcome in the model based on a significant p value of < 0.05 . as the sample came from an iron - deficient anemia prevention trial , we tested whether iron - deficient anemia during the first year of life or iron supplementation were significant covariates in our models .
neither variable showed significant relationship in the models and were thus removed from the final models .
participants had been born at 40 weeks of gestation weighing 3.5  kg , on average , and 48% were exclusively breastfed for 90 days .
the median bmi percentile was 68.7 with 15.2% in the obese range and 10.4% met criteria for mets .  
table 1 describes infant and family background characteristics by gender of the 357 participants in infancy and adolescence .
males had higher birth length , weight at three months , and higher weight gain between birth and 3 months compared to females .
males also had significantly lower hdl cholesterol and higher blood pressure values ( systolic and diastolic ) , glucose and mets risk z - scores than females .
there were no significant differences between males and females in gestational age , birth weight , maternal education , exclusive breastfeeding for 90 days , and prevalence of the mets .  
the multiple variable linear regression models ( full and final ) are shown in table 2 .
the final model revealed that weight gain over the first three months was associated with an increased mets risk score at 16 - 17 years , taking into account extent of breastfeeding and gender ( b = 0.16 , 95%  ci = 0.04 , 0.27 , p < 0.05 ) .
introduction of the first bottle at 90 days or after was related to a lower mets risk score in adolescence ( b = 0.16 , 95%  ci = 0.29 , 0.04 , p < 0.05 ) , taking into account other covariates .
additionally , being male was associated with an increased mets risk score in the model ( b = 0.24 , 95%  ci = 0.11 , 0.37 , p < 0.05 ) .
we examined weight gain in the first 3 months of life and timing of bottle supplementation related to mets risk at 16 years . in both sexes , adolescents who had more rapid weight gain during the first 3 months of infancy had higher adolescent mets risk scores compared to those who gained less weight in early infancy .
the association of weight gain with mets risk is consistent with findings from a study addressing the same question , in a scandinavian country .
infancy weight gain has previously been associated with later obesity in childhood and adulthood [ 15 , 18 , 25 , 26 ] . in addition , especially for low - birth - weight infants , more rapid early weight gain , sometimes called catch - up growth , has been related to higher risk of developing type 2 diabetes and/or cardiovascular disease .
contrary to our findings , a finnish study found that infants who had low weight gain in the first 6 months had higher risk for development of glucose intolerance , an effect that was greater for those with low birth weight . since our cohort excluded infants with birth weights below 3  kg , it is clear that the association we find between infant weight gain and adolescent mets risk is independent of low birth weight
furthermore , this association did not depend on family history of conditions related to the mets such as type 2 diabetes , dyslipidemia , or myocardial infarction .
there is accumulating evidence that breastfeeding offers some protection related to the development of obesity , and that the effect may be  dose - dependent  [ 28 , 29 ] .
because breastfed infants gain weight more slowly over the first year compared to formula - fed infants [ 30 , 31 ] , infant weight gain may pertain to the mechanism that decreases obesity risk in those who were breastfed .
having been breastfed has also been associated with lower risk for hypercholesterolemia , hypertension , diabetes , glucose intolerance , and insulin resistance [ 912 ] . to our knowledge
, no other study has shown an association between breastfeeding and mets risk in adolescence .
importantly , the significant effects of weight gain and breastfeeding were independent , suggesting that the effect of breastfeeding on mets risk was not mediated by early infancy weight gain .
we do not know why males had higher mets risk scores compared to females , but they had marginally significant higher birth weights and gained more weight in the first 3 months . nonetheless , the effect of gender on mets was independent of birth weight and infancy weight gain .
this finding is consistent with higher prevalence rates of mets in men compared to women in chile . in us
adolescents , males are also more likely to have clustering of metabolic syndrome risk factors compared to girls .
however , in the scandinavian study of infant weight gain and the mets , male gender was not related to higher mets risk , even though boys were similarly heavier at birth and gained more in infancy than girls .
the cohort was enrolled from a low- to middle - income community in santiago , chile , during a period of economic and nutritional transition .
the setting and the fact that children with birth weights under 3  kg were not included limits generalizability .
the context of economic growth , high rates of breastfeeding , and nutritional support for infants allowed us to assess a sample where malnutrition was not a confounding factor .
the longitudinal study took place at a nutrition research center allowing for detailed anthropometric measurement during infancy and the adolescent wave of data collection .
other strengths of the study include prospective data collection including monthly anthropometry in infancy and breastfeeding data collected from 4 to 12 months .
in addition , the adolescent data collection included family history of diabetes , hypertension , elevated cholesterol , and heart attack .
in conclusion , this study adds to the current knowledge about early infant growth and breastfeeding and their long - term health effects .
higher infant weight gain was associated with increased mets risk , whereas longer duration of exclusive breastfeeding was protective in healthy adolescents living in a rapidly developing country . considering the increasing prevalence of the mets in younger age groups and associations between the mets and later disease ,
 
 background . 
 prevalence of the metabolic syndrome is increasing in pediatric age groups worldwide . meeting the criteria for the metabolic syndrome 
 puts children at risk for later cardiovascular and metabolic disease . methods . using linear regression , we examined the association between infant weight gain from birth to 3 months and risk for the metabolic syndrome among 16- to 17-year - old chilean adolescents ( n = 357 ) , accounting for the extent of breastfeeding in infancy and known covariates including gender , birth weight , and socioeconomic status . results . 
 participants were approximately half male ( 51% ) , born at 40 weeks of gestation weighing 3.5  kg , and 48% were exclusively breastfed for 90 days . 
 factors independently associated with increased risk of metabolic syndrome in adolescence were faster weight gain in the first 3 months of life ( b = 0.16 , p < 0.05 ) and male gender ( b = 0.24 , p < 0.05 ) . breastfeeding as the sole source of milk for 90 days was associated with significantly decreased risk of metabolic syndrome ( b = 0.16 ) . conclusion . 
 this study adds to current knowledge about early infant growth and breastfeeding and their long - term health effects . 
1. Introduction
2. Methods
3. Results
4. Discussion
5. Conclusion