low birth weight ( lbw ) and high birth weight ( hbw ) are both important indicators of suboptimal intrauterine development and have been linked to risk of several chronic diseases later in life . hbw has been associated with childhood and adult obesity   and some cancers , including breast   and prostate cancer , whereas lbw is a consistently identified risk factor for cardiovascular disease ( cvd ) [ 4 , 5 ] and type 2 diabetes ( t2d ) [ 6 , 7 ] . igf - i is a mitogenic and antiapoptotic paracrine growth factor expressed in all fetal organs [ 8 , 9 ] , and is essential in fetal and neonatal growth , differentiation and development [ 1014 ] . several lines of evidence suggest that igf - i levels are associated with birth weight [ 1526 ] ; furthermore higher igf - i levels are associated with higher bw , but not with lower birth weight [ 16 , 17 , 26 ] . in adulthood , elevated concentrations of igf - i are associated with an increased risk of obesity and many cancers , including breast , lung , head and neck , colorectal , pancreas , synovial sarcoma , and prostate cancer [ 2631 ] . although concentrations of circulating igf - i levels vary considerably by race / ethnicity and maternal prepregnancy obesity , few studies included african american women [ 2426 ] , an ethnic group that has an almost 9% higher bmi than european - american women . furthermore , studies examining both maternal obesity , an increasingly common condition , and race / ethnicity are few [ 3335 ] . herein , we examine associations between igf - i levels in relation to body size at birth in a cohort of infants born to obese and non - obese african american and white women . the study protocol was approved by the duke university institutional review board ( irb ) . we also obtained informed written consent from carers or guardians on the behalf of the minors / children participants involved in our study . pregnant women were enrolled as part of the newborn epigenetics study ( nest ) , a prospective study of women and their infants . briefly , pregnant women who were 18 years and older and who planned to give birth at duke university or durham regional hospitals were recruited from durham county , nc prenatal clinics . the 1101 women approached , 940 ( 85% ) consented and were enrolled ; most of the enrolled sample ( 81% ) was successfully followed to delivery ( n = 757 ) . igf - i analyses were performed on the first 251 women and had a gestational age 37 weeks . data from these participants were comparable to participants in whom igf - i was not measured with respect to maternal age , gestational age , race / ethnicity , and maternal prepregnancy bmi . interviewer- or self - administered questionnaires were obtained at the time of enrollment and medical records during pregnancy were abstracted at parturition . data collected using questionnaires included sociodemographic characteristics , reproductive factors , and lifestyle factors such as cigarette smoking and self - reported prepregnancy anthropometric measurements . information on anthropometric measurements during pregnancy , birth outcomes , including birth weight and length , was abstracted from medical records . umbilical cord blood specimens were also collected at birth , as previously described [ 36 , 37 ] . plasma concentrations of igf - i were measured using microplate enzyme - linked immunosorbent assays ( elisa , diagnostic systems laboratories , webster , tx , usa ) according to the manufacture instructions , and triplicate assays per sample were performed . absorbance was read using a microplate reader ( dsl , webster , tx , usa ) . the plasma igf - i concentrations ranged from 3.65  ng / l to 418.36  ng / l , and assay sensitivity was 2.2  ng / ml . infant birth weight was normally distributed and was used as a continuous variable . because both high birth weight ( hbw ) and low birth weight ( lbw ) have been linked to maternal obesity , we also analyzed birth weight as a categorical variable : lbw , < 2500  g , normal birth weight , 25004000  g , and hbw , > 4000  g. we used chi - squared tests to examined distribution of factors that have been previously associated with birth weight > 4000  g and < 2500  g in relation to maternal age ( categorized as 1825 , 2630 , and > 30 years ) ; prepregnancy mothers ' body mass index ( bmi ) ( categorized as < 30 and 30  kg / m ) ; race / ethnicity ( categorized as white , african american , and other ) ; and maternal education ( categorized as less than college , college , and graduate level education ) , maternal smoking , and infant gender . although some of these factors were not statistically significantly associated with bw in this study , we adjusted for maternal age , bmi , race , education , delivery route , gestational age at delivery , maternal smoking during pregnancy , and infant gender , as they are associated with bw and igf - i in the population . the distribution of igf - i levels departed from normality and thus they were categorized into tertiles . we then dichotomized at the top tertile ( 67th percentile ) and compared this tertile ( high igf - i ; > 67th percentile ) to the remainder ( low igf - i ; 67th percentile ) . linear regression models were used to examine the extent to which igf - i levels differed by birth weight , as described in . all statistical analyses were conducted in sas v9.2 ( sas institute inc . , cary , nc , usa ) . approximately 4% of the 251 newborns were born < 2500  g and ~8% were born > 4000  g. mean gestational age at delivery was 39 weeks ( sd = 1.14 ) . most low birth weight infants ( < 2500  g ) were born to african americans ( 89% ) , cigarette smokers ( before and during pregnancy , 80% ) , and those with a lower educational achievement ( 67% ) ; however the differences were not statistically significant . lbw were however comparable to infants born 25004000  g with respect to maternal age . hbw infants were comparable to those born 25004000  g with respect to education and maternal smoking , although they were more frequently born to white women and those with a bmi 30 before pregnancy . no statistically significant differences in igf - i levels were found between birth weight < 2500  g infants and birth weight > 4000  g infants ; however birth weight < 2500  g infants were born two weeks earlier than infants born 25004000  g and birth weight > 4000  g infants ( p = 0.006 ) ( table 1 ) . birth weight ranged between 2000 and 5160  g ( mean = 3315  g , sd = 486 ) . infants with higher levels of igf - i ( > 3rd tertile ) were born slightly heavier than infants with lower igf - i concentrations ( 3rd tertile ) , although the differences were not statistically significant . infants with higher igf - i levels were comparable to those with lower levels with respect to maternal age ( p = 0.65 ) , race ( p = 0.83 ) , maternal education ( p = 0.38 ) , maternal smoking ( p = 0.63 ) , obesity ( p = 0.28 ) , and gestational age ( p = 0.91 ) ( table 2 ) , although they may differ by delivery route ( p = 0.14 ) . table 3 shows coefficient estimates (  's ) and their standard errors ( ses ) for five multivariate linear regression models of birth weight on igf - i levels , in which igf - i 67th percentile concentrations or 3rd tertile served as referents ; one for all participants , one restricted to african americans , one restricted to whites , one restricted to maternal bmi < 30 , and one restricted to maternal bmi 30 . the first model shows that after adjusting for infant gender , race , gestational age at delivery , delivery route , maternal bmi and smoking during pregnancy , infants in the upper tertile of igf - i were larger at birth (  = 230.46 , se = 58.0 , p = 0.0001 ) , corresponding to 130  g increased birth weight in infants born to those with high igf - i levels ( table 3 ) . we also found that this association was slightly higher in african american infants ( p = 0.002 ) compared to white infants ( p = 0.02 ) . however , the cross - product term for race and igf - i was not significant ( p = 0.5 ) . since the prevalence of bmi 30 in african american women in our study is higher ( 67% ) compared to whites ( 24% ) ( p < 0.0001 ) , we examined the role of maternal bmi on the relationship between igf - i levels and birth weight . the pair of models restricted by bmi revealed that the association of igf - i levels and infant size was limited to women with a bmi 30 (  = 617.78 , se = 134.68 , p < 0.0001 ) . we found a strong positive association in infants born to obese women ; the cross - product term for maternal bmi and igf - i was p = 0.0004 . our key finding was a positive association among term infants with elevated igf - i levels and an increased risk of higher birth weight . high birth weight and high igf - i levels  a potent mitogen  have been linked to cvd , t2d , and some cancers [ 27 ] . importantly , our data also demonstrate that , after accounting for maternal obesity before pregnancy , the influence of ethnicity / race on the association between igf - i and birth weight ( an important risk factor for common chronic diseases ) is dramatically diminished .   the extent to which the positive association between igf - i at birth and early postnatal growth that is maintained during life course to adulthood is still unclear , although a few studies report that elevated igf - i levels measured at birth are associated with age 4 - 5 year obesity [ 38 , 39 ] . igf - i levels found in this study ( median = 36  ng / l , icr 17  ng / l66  ng / l ) are slightly lower than those reported in previous studies ; however our findings that higher igf - i levels at birth are associated with increased birth weight are consistent with those of others , and with reports which found positive associations between both placental   and cord plasma igf - i concentrations and lower birth weight infants , compared with igf - i concentrations in normal birth weight infants [ 19 , 4144 ] . and deiber et al . , who found low birth weight associated with higher igf - i in populations of infants born to white women . divergent findings may be due , in part , to lower incidence of maternal obesity among european women ; the strongest association between igf - i and birth weight was found in infants born to obese women . it is speculated that such differences may involve the igf axis through igf - i and growth hormone ( gh ) signaling , which differ by obesity [ 21 , 23 , 47 ] . these race / ethnic similarities exist despite igf - i concentrations being generally lower in african american than in white neonates born with normal weight , as shown in male   and in female newborns , and in studies performed in adults . our findings that elevated igf - i levels are associated with increased birth weight in infants born to obese mothers , are consistent with at least three other studies comprising european , maori , south asian , and pacific islands ' cohorts [ 33 , 47 , 48 ] , supporting the hypothesis that igf - i and insulin resistance perhaps driven by genetic factors may play a role in fetal growth . igf - i levels in pregnant women have been positively correlated with maternal body weight [ 33 , 49 ] . maternal insulin sensitivity has been proposed as an important endogenous environmental factor in fetal size . maternal hyperglycemia , a correlate of obesity , even considered in the normal range , may affect fetal weight . together , these findings suggest that the igf axis may play a key role in fetal overgrowth and maternal obesity may be an important driver in placental igf - axis concentrations , and thus increasing the risk for higher birth weight and infant obesity in childhood . the main limitation of this study was relatively small sample size for analyses restricted to maternal bmi ( bmi < 30 versus bmi  30 ) ; however , findings are consistent with the expected role of igf - i , and igf - i values themselves ( range , median , and skewness of igf - i levels ) and the magnitude of the positive associations with higher birth weight and growth are similar to previous reports [ 25 , 26 ] . also , we relied on a single measure of igf - i levels at delivery ; however it was not feasible to obtain igf - i levels before birth in these infants . however , at least postnatally , interindividual variation seems stable and most studies relating cord blood igf - i protein concentrations and birth weight reported single measurements at birth [ 18 , 52 ] , and findings are similar . consideration should also be given to the fact that infant 's race / ethnicity is the self - reported mother 's race / ethnicity and the study is predominantly african americans and whites . another limitation was that we did not measure other components of the igf axis , including growth hormone , insulin , igf binding proteins ( igfbp1 - 5 ) , and receptors ' ( igf-1r and 2r ) concentrations in the newborns , to further establish the potential implication of other components of the igf system in fetal growth . however the assay used measured total cord blood igf - i in circulation . despite these limitations , our findings support the hypothesis that elevated igf - i is an important growth factor in early development that has been linked to a number of common chronic diseases , regardless of race / ethnicity .   in summary , we found that elevated igf - i levels in newborns increase the risk of higher birth weight in african american and white infants . our findings also suggest that maternal bmi 30 may modify positive associations between igf - i and higher birth weight , supporting the idea that maternal obesity may be key in increasing the risk of higher birth weight in the newborns , an important risk factor for several chronic diseases , including cancer . these findings suggest that the potential utility of igf - i levels as a marker of future obesity in the offspring is limited to those born to obese women . as the prevalence of maternal obesity continues to increase , larger multiethnic studies with followup at shorter intervals that allow for maternal obesity - specific analyses are required to further elucidate the nature of the positive association between igf - i levels and higher birth weight .
at birth , elevated igf - i levels have been linked to birth weight extremes ; high birth weight and low birth weight are risk factors for adult - onset chronic diseases including obesity , cardiovascular disease , and type 2 diabetes . 
 we examined associations between plasma igf - i levels and birth weight among infants born to african american and white obese and nonobese women . 
 prepregnancy weight and height were assessed among 251 pregnant women and anthropometric measurements of full term infants ( 37 weeks of gestation ) were taken at birth . circulating igf - i was measured by elisa in umbilical cord blood plasma . 
 linear regression models were utilized to examine associations between birth weight and high igf - i , using the bottom two tertiles as referents . compared with infants with lower igf - i levels ( 3rd tertile ) , 
 those with higher igf - i levels ( > 3rd tertile ) were 130  g heavier at birth , ( -coefficient = 230 , se = 58.0 , p = 0.0001 ) , after adjusting for gender , race / ethnicity , gestational age , delivery route , maternal bmi and smoking . 
 stratified analyses suggested that these associations are more pronounced in infants born to african american women and women with bmi 30  kg / m2 ; the cross product term for igf - i and maternal bmi was statistically significant ( p  0.0004 ) . 
 our findings suggest that the association between igf - i levels and birth weight depends more on maternal obesity than african american race / ethnicity .