fifty fetuses initially met our inclusion criteria for the study , but only data on 44 subjects ( n=23 iugr , n=21 aga ) were included in our final statistical analysis . six subjects were excluded ( two iugr and four aga ) because they did not provide urine samples . the median estimated fetal weight ( efw ) at the time of the initial aimt measurement was 1750  g ( < 5th percentile ) in the iugr group , and 2200  g ( 50th percentile ) in the aga group . the median maternal age at the time of delivery was 30.5 years in the iugr group and 31.2 years in the aga group . nine ( 39% ) women in the iugr group had a vaginal delivery , while 14 ( 61% ) underwent cesarean section . in the aga group , there were 14 ( 77% ) vaginal deliveries and 7 ( 33% ) cesarean sections . the median birth weight of the 23 children born iugr was 1850  g ( < 5th percentile ) at a median gestational age of 33 weeks . neonates that were aga had a median gestational duration of 38 weeks , with a median birth weight of 2975  g ( 50th percentile ) . the median fetal aimt was significantly different between iugr and aga fetuses ( iugr 2.0  mm vs aga 1.05  mm ; p<0.001 ) . at the 18-month follow - up evaluation , there was no statistically significant difference in median weight in the iugr and aga groups ( 12.3 vs 12.5  kg , p=0.23 ) . the aimt , however , remained significantly larger among infants in the iugr group compared with those in the aga group ( 2.1 vs 1.05  mm ; p<0.001 ) . iugr infants had a higher systolic blood pressure ( sbp ) compared with aga infants ( p<0.001 ) . l ; p=0.001 ) and the albumin / creatinine ratio ( a / cr ) ( 26 vs 14.6  mg / l ; p=0.001 ) ( figure 1 ) were higher in the iugr infants compared with aga infants . univariate analysis defined the following variables as being related to aimt in fetuses : iugr ( p<0.001 ) and estimated fetal weight ( p<0.001 ) , and the following in infants : iugr ( p<0.001 ) , microalbuminuria ( p<0.001 ) , systolic blood pressure ( p<0.001 ) , and albumin / creatinine ratio ( p<0.001 ) ( table 2 ) . in addition , a positive association was observed between the prenatal aimt values and 18-month postnatal aimt ( regression coefficient 0.86 , standard error 0.24 ; p=0.001 and regression coefficient 0.46 , standard error 0.22 ; p=0.04 , respectively ) within the children born with iugr , a phenomenon not observed among aga children . among iugr infants , sbp was also positively associated with the post - natal aimt ( regression coefficient 0.02 , standard error 0.009 ; p=0.04 ) ( table 3 ) . the present study highlights that aortic wall thickness and microalbuminuria are significantly higher in iugr compared with aga infants at a mean age of 18 months . although the exact mechanisms that underlie these associations remain unclear , these data , indicating early glomerular damage , extend the findings of our previous study on the natural course of aimt among iugr fetuses and other studies in intrauterine fetal growth - restricted children , adolescents , and young adults at risk for premature cardiovascular and kidney diseases . aortic intima  media thickening is the best currently available non - invasive marker of preclinical atherosclerosis . evidence from non - invasive ultrasound studies of the neonatal aorta , combined with fetal and early childhood postmortem studies , indicates that impaired fetal growth , in utero exposure to maternal hypercholesterolemia , and diabetic macrosomia might all be important risk factors for vascular changes consistent with the earliest physical signs of atherosclerosis . these changes first develop in the intima of the aorta by both native and oxidized ldl and macrophage infiltration . , the decreased glomerular filtration surface leads to glomerular hypertension and hypertrophy , which causes systemic hypertension and glomerular damage , and ultimately results in glomerulosclerosis and albuminuria later in life . however , whether fetal intima  media thickening and early endothelial dysfunction among iugr infants are significant contributors to later atherosclerosis and glomerulosclerosis is not yet known . it is now possible to measure aortic wall thickness accurately and reproducibly in vivo during fetal and postnatal life with external ultrasonography . ultrasound - based measurement of aimt in iugr children was found to be a sensitive marker of hypertension in young iugr children and of atherosclerosis risk in adult life , supporting the epidemiological link between impaired fetal growth and later cardiovascular disease . in addition , singh and hoy described an association between low birth weight , kidney size , and albuminuria in aboriginal subjects between 4 to 72 years of age . recently , keijzer - veen 's prospective follow - up study showed an association between the severity of iugr and renal function in young adults born very prematurely . on average , their low birth weight subjects had lower glomerular filtration rates ( gfrs ) , higher serum creatinine concentrations , and higher microalbumin secretion at the age of 19 years . more recently , puddu et al . reported high levels of microalbuminuria in a group of very low birth weight infants . microalbuminuria is one of the first symptoms of developing renal disease and precedes a decrease in gfr . the higher risk of aortic intima  media thickening and microalbuminuria may have clinical implications for iugr infants at 18 months of age . early endothelial dysfunction and intima  media thickening could be significant contributors to premature stiffening of the arterial tree , which ultimately might predispose these individuals to systemic hypertension and increased cardiovascular risk . our results are in agreement with previous studies that correlate low birth weight with endothelial damage that may influence arterial function and the overall incidence of cardiovascular events . unlike these studies , which focused on aortic wall thickness in term iugr infants and in high - risk children and young adults , we evaluated the natural course of this marker of endothelial dysfunction in fetuses with iugr and severe doppler abnormalities , both in utero and at 18 months of age . these results suggest that , in addition to other pathogenic mechanisms , higher arterial thickness is already present in iugr fetuses during intrauterine life and this , together with factors such as impaired nephrogenesis and glomerulosclerosis , could have a role in programming adult disease , as previously suggested . there are limitations to our study that must be considered in the interpretation of these results . first of all , the markedly greater range in ultrasound aimt measurements and the wide pattern of doppler abnormalities of iugr fetuses limited the possibility of making comparisons with other studies , performed with different equipment ( 712  mhz probe ) , in both term growth - restricted neonates and in high - risk children and young adults . third , we are unable to establish whether renal function will decrease more rapidly with age compared with aortic wall thickening . it is also not known whether screening for microalbuminuria and aimt will help to prevent the loss of renal function , atherosclerosis , and hypertension at an early stage . in conclusion , these findings indicate that iugr children have a higher risk of both aortic wall thickening and glomerular proteinuria , which may contribute to cardiovascular and renal disease in later life . follow - up studies are needed to confirm the prognostic role of these markers of atherosclerosis and renal disease . subjects were recruited from the obstetrics and gynaecology clinics at the university hospital of padua ( italy ) between january 2006 and august 2008 . written informed consent was obtained from each woman before enrolment and the project was approved by the university hospital committee for research on human subjects . data concerning women and their pregnancies were recorded according to the routine practice of the department of obstetrics and gynaecology . inclusion criteria at admission were single pregnancy , gestational age determined from known last maternal menstrual period and/or ultrasound dating before 20 weeks of gestation , and women originating from the veneto region ( italy ) . exclusion criteria were twin pregnancy , major congenital anomalies , pregnancies complicated by maternal history of cardiovascular disease or endocrine disorders such as diabetes , hypercholesterolemia , pre - eclampsia , thyroid or adrenal problems , and clinical chorioamnionitis . women who received alcohol , nicotine , or medications such as ritodrine and corticosteroids ( except for fetal lung maturation ) were excluded . fetuses were classified as iugr if the estimated fetal weight ( efw ) was < 10th percentile and the umbilical artery pulsatility index ( pi ) > 2 standard deviations ( s.d . ) above the mean , and aga if the efw was between 10th and 90th percentiles . enrolled iugr and aga fetus , efw and antenatal testing were available , despite no indications or guidelines recommending the use of doppler ultrasonography in uncomplicated pregnancies . fetal aimt was measured in each iugr and aga subject at a median gestational age of 32 weeks ( interquartile range ( iqr ) 3034 weeks ) by high - resolution ultrasound scan ( antares , siemens medical solutions , mountain view , ca ) using a 3.55  mhz linear array transducer , as previously reported . fetal examination required no more than 20  min , with about 40  min required for the children . a single , skilled practitioner performed all ultrasound studies , in both fetuses and children , using the same equipment , unaware of their clinical course and outcomes . the follow - up examination was performed at a median corrected postnatal age of 18 months ( iqr 1521 months ) and included aimt , growth parameters , blood pressure , and a urine sample . blood pressure measurements were performed using a standard doppler sphygmomanometer ( philip medical system monitor , agilent , m3046a model , m4 , boebingen , germany ) using a cuff size appropriate for the subject 's right arm circumference . three independent measurements for each child were taken and the arithmetic mean was used for the study , as recommended by the current guidelines . urine microalbumin was assayed using an immunonephelometric method ( bnii , siemens medical solutions ) . urine creatinine was tested by a colorimetric jaff method ( roche diagnostics , monza , italy ) . differences between groups were tested using the fisher 's exact test for categorical variables and the mann as previously reported , intra - observer and inter - observer aimt correlation coefficients were 0.876 and 0.856 , respectively . multivariate analysis by median regression was performed to identify the independent effect of iugr / aga on fetal and infant aimt after controlling for potential confounders ( sex , gestational and corrected postnatal age , estimated fetal weight , body weight , systolic and diastolic blood pressure , microalbuminuria , and a / cr ) . statistical analysis was performed using the spss 17 software package ( spss , chicago , il ) and r 2.5 statistical language .
low birth weight , caused either by preterm birth or by intrauterine growth restriction , has recently been associated with increased rates of adult renal and cardiovascular disease . since aortic intima 
 media thickening is a noninvasive marker of preclinical vascular disease , we compared abdominal aortic intima  media thickness among intrauterine growth restricted and equivalent gestational age fetuses in utero and at 18 months of age . 
 the relationship between intrauterine growth restriction , fetal aortic thickening , and glomerular function during infancy was measured by enrolling 44 mothers with single - fetus pregnancies at 32 weeks gestation : 23 growth restricted and 21 of appropriate gestational age as controls . abdominal aortic intima  media thickness was measured by ultrasound at enrollment and again at 18 months of age . 
 fetuses with intrauterine growth restriction had significantly higher abdominal aortic intima 
 media thickness compared with age controls when measured both in utero and at 18 months . at 18 months , the median urinary microalbumin and median albumin  creatinine ratio were significantly higher in those infants who experienced intrauterine growth restriction compared to the controls . 
 our results show that intrauterine growth restriction is associated with persistent aortic wall thickening and significantly higher microalbuminuria during infancy .