Clinical Study Aorta Structural Alterations in Term...

Hindawi Publishing CorporationBioMed Research InternationalVolume 2013 Article ID 459168 7 pageshttpdxdoiorg1011552013459168

Clinical StudyAorta Structural Alterations in Term NeonatesThe Role of Birth and Maternal Characteristics

Marco Matteo Ciccone1 Pietro Scicchitano1 Christian Salerno2

Michele Gesualdo1 Fara Fornarelli1 Annapaola Zito1 Lucia Filippucci3

Roberta Riccardi1 Francesca Cortese1 Francesca Pini4 Lucia Angrisani4

Antonio Di Mauro4 Federico Schettini4 and Nicola Laforgia4

1 Cardiovascular Disease Section Department of Emergency and Organ Transplantation University of BariPiazza G Cesare 11 70124 Bari Italy

2 Dipartimento di Medicina Traslazionale-Laboratorio Igiene ed Medicina Ambientale University of Piemonte Orientale A AvogadroVia Duomo 6 13100 Vercelli Italy

3 Department of Cardiovascular Disease Rehabilitation USL2 Via Guerra 21 06127 Perugia Italy4Neonatology and Neonatal Intensive Care Section Department of Gynecology Obstetrics and Neonatology University of BariPiazza G Cesare 11 70124 Bari Italy

Correspondence should be addressed to Marco Matteo Ciccone marcomatteocicconeunibait

Received 5 April 2013 Revised 28 June 2013 Accepted 8 July 2013

Academic Editor Egle Bytautiene

Copyright copy 2013 Marco Matteo Ciccone et al This is an open access article distributed under the Creative Commons AttributionLicense which permits unrestricted use distribution and reproduction in any medium provided the original work is properlycited

Aim To evaluate the influence of selected maternal and neonatal characteristics on aorta walls in term appropriately grown-for-gestational age newborns Methods Age parity previous abortions weight height body mass index before and afterdelivery smoking and history of hypertension of diabetes of cardiovascular diseases and of dyslipidemia were all assessed inseventy mothers They delivered 34 males and 36 females healthy term newborns who underwent ultrasound evaluation of theanteroposterior infrarenal abdominal aorta diameter (APAO) biochemical profile (glucose insulin total cholesterol HDL and LDLcholesterol triglycerides fibrinogen and D-dimers homeostasis model assessment [HOMAIR]index) and biometric parametersResults APAO was related to newborn length (119903 = +036 119875 = 0001) head circumference (119903 = +037 119875 = 0001) gestationalage (119903 = +040 119875 = 00005) HOMA index (119903 = +024 119875 = 004) and D-dimers (119903 = +033 119875 = 0004) Smoke influencedAPAO values (odds ratio 180 confidence interval 95 105ndash330) as well as diabetes during pregnancy (119903 = +042 119875 = 00002)Maternal height influenced neonatal APAO (119903 = +047 119875 = 000003) Multiple regression analysis outlined neonatal D-dimers asstill significantly related to neonatal APAO values Conclusions Many maternal and neonatal characteristics could influence aortastructures Neonatal D-dimers are independently related to APAO

1 Introduction

Cardiovascular diseases (CVD) are still the major cause ofdeath in developing countries including China and India [1]Primary prevention programs instrumental evolution phar-macological treatments and lifestyle changes reduce CVDmortality compared to the 1960s data [2] Nevertheless CVDstart since childhood Since 1990s the attention of physiciansmoved on the early stages of life [3] The Cardiovascular Riskin Young Finns [3] was one of the first studies systematically

evaluating the role of different conditions (ie family dietaryhabits and standard of education and diet of mothers) on thefuture cardiovascular risk profile of 3596 children

Dalziel et al [4] demonstrated that adult patients bornmoderately preterm have increased blood pressure andinsulin resistance at 30 years of age Preterm birth rather thanpoor fetal growth seemed to be the major determinant of thisassociation although many epidemiological studies showedthat low birth weight was independently associated withsubsequent cardiovascular disease risk factors and increased

2 BioMed Research International

incidence of cardiovascular disease in adulthood [5 6] Theldquofetal programmingrdquo during critical phases of development inutero could be responsible formetabolic disturbances in adultlife and long-term structural changes of the vascular system[7ndash9]

Neonatal and maternal characteristics could early influ-ence atherosclerosis development Anteroposterior diameterof infrarenal abdominal aorta (APAO) is a reliable and well-established ultrasound parameter to detect early impairmentof vascular structure since childhood [10 11]

The aimof this studywas to evaluate the influence of someselected maternal and neonatal characteristics on aorta walls(evaluated by mean of APAO) in term appropriately grown-for-gestational age (AGA) newborns

2 Methods

21 Subjects Seventy mother-newborn pairs admittedrespectively to the Obstetric Section and Neonatology andNeonatal Intensive Care of the Department of GynecologyObstetrics and Neonatology of the University of Bari wereenrolled in the study

The study was approved by the Institutional ReviewBoard of Bari University General Hospital and carried out inaccordance with the principles of the Helsinki Declaration

211 Newborns Characteristics There were 34 males and 36females healthy newborns born at term (after 37 completedweeks of gestation) 38 by vaginal delivery and 32 by C-sectionMean gestational agewas 392plusmn12weeksmean birthweight 32893 plusmn 3412 g (between 10th and 90th percentileas established by gender and gestational age-specific nationalcharts [12] AGA) mean length 495 plusmn 22 cm and headcircumference 340 plusmn 12 cm They all had normal transition(Apgar 51015840 ge 7)Newbornswith any congenitalmalformationswere excluded

After informed consent all newborns had ultrasoundevaluation of the APAO and biochemical profile wasobtained on the blood taken at birth from umbilicalcord Blood samples had been performed early at morning(between 8 00 am and 9 00 am) after an overnight fast onthe same day of the ultrasound

APAO evaluations were done within 24 hours after deliv-ery with the newborn in supine position during a routinedaytime rest period in a warm environment (20-21∘C) Itwas performed by a single operator using a single high-resolution vascular ultrasound Philips 5500 equipped with a3MHz electronic probe To improve the image acquisitionneonates were examined at least 4ndash6 hours after breastfeedingto reduce intestinal bloatingThe electronic probe was placedone centimeter left of the umbilicus Then the best image inlong-axis projection of the abdominal aorta was obtainedThe APAO was defined as the maximal external cross-sectional diameter measurement of the infrarenal abdominalaorta It was calculated as the distance between the nearand the far walls of the abdominal aorta Measurementswere performed 1 cm above and distal to the umbilicus and

expressed in centimeters [10 11] Repeatability and intraob-server variability of all ultrasound scan measurements wereevaluated by means of intraclass correlation coefficient ofgt090 In particular anteroposterior diameter showed goodreproducibility with an intraclass correlation coefficient of092

Biochemical profile included glucose insulin totalcholesterol high-density lipoprotein (HDL) and low-densitylipoprotein (LDL) cholesterol triglycerides fibrinogen andD-dimers determinations Insulin resistance was calculatedby the homeostasis model assessment (HOMAIR) [13 14]

212 Maternal Characteristics For each mother data onage parity previous abortions weight height and bodymass index [weight (kg)][height (m)]2 before and afterdelivery were collected Using a combination of clinicalinterviews and obstetric records information about familiarhistory for hypertensive diabetic cardiovascular diseasesand dyslipidemic conditions were also obtained Motherswere considered as smoker if they smoked at least fivecigarettesday within 3 months before delivery or if theystopped smoking lt1 year before delivery There were noinclusion criteria for the mothers except to have delivered anAGA term newborn 111 mothers and related newborns wereconsecutively enrolled but 70 delivered AGA term newborn

22 Statistical Analysis The continuous variables wereexpressed as mean and standard deviation

Categorical data had been evaluated by means of oddsestimation and CI 95 had been used in order to assess statis-tical significance The Pearsonrsquos linear correlation coefficientwas used to study the relationship between the continuousvariables Multiple regression analysis had been adopted inorder to evaluate the influence of confounding factors onAPAO evaluation A 119875 lt 005 was considered statisticallysignificant

3 Results

Maternal mean age was 32 plusmn 5 years Body mass index beforedelivery was within normal limits (2275plusmn446Kgm2)Therewere 19 smokers (27) Nine (13) had gestational diabetesand 6 (9) and 3 (4) haddyslipidemia 22 (31) had one ormore previous abortions and 5 (7) had 2 or more previouspregnancies Familiarity for hypertension cardiovasculardiseases dyslipidemic conditions and diabetes are shown inTable 1

Neonatal data are shown in Table 2 Mean APAO valuewas 476 plusmn 098 cm

Pearsonrsquos linear regression has been used to assess anyrelationships between APAO values and maternal character-istics (Table 3) Furthermore odds ratio and their relativesconfidential intervals had been calculated for main dichoto-mous maternal variables considered (Table 4) Pearsonrsquos lin-ear regression has been used to assess any relationshipsbetween APAO values and neonatal characteristics (Table 5)

APAO is directly related both to newborn length (119903 =+036 119875 = 0001) and head circumference (119903 = +037

BioMed Research International 3

Table 1 Maternal characteristics

Values ()Total number 70Age (years) 32 plusmn 5

Familiarity for diabetesNone 32 (46)I degree relatives 10 (14)II degree relatives 28 (40)

Familiarity for cardiovascular diseasesNone 39 (56)I degree relatives 19 (27)II degree relatives 12 (17)

Familiarity for hypertensionNone 35 (50)I degree relatives 27 (39)II degree relatives 8 (11)

Familiarity for dyslipidemiaNone 47 (67)I degree relatives 17 (24)II degree relatives 6 (9)

Previous abortions 22 (31)No of pregnancy gt2 5 (7)Smoking 19 (27)Hypertension 6 (9)Diabetes 9 (13)Dyslipidemia 3 (4)BMI before pregnancy (Kgm2) 2275 plusmn 446

Weight before pregnancy (Kg) 6093 plusmn 1172

Weight after pregnancy (Kg) 7300 plusmn 1179

Height before pregnancy (cm) 16381 plusmn 658

Values are expressed as numbers and related percentages BMI body massindex

119875 = 0001) at birth but not to birth weight (Table 5) andit is also strongly related to gestational age (119903 = +040119875 = 00005)

Interestingly APAO is positively related to HOMA index(119903 = +024 119875 = 004) that is an early marker ofatherosclerosis (Table 5) while no correlation betweenAPAOand insulin (119903 = +022119875 = 0056) was foundNo correlationshave been found between lipids blood levels and coagulationparameters (fibrinogen and prothrombin time-internationalnormalized ratio [PT-INR]) withAPAOvalues butD-dimers(119903 = +033 119875 = 0004) (Figure 1)

Important data come from the analysis of correlationsbetween maternal characteristics and APAO Smoking habitis a strong predictor of greater APAO values [Odds Ratio(OR) 180 (CI 95 105ndash330)] thus smoking could alreadyexert a deleterious effect on the cardiovascular system ofnewborns Even dyslipidemia familiarity seems to be slightlyrelated to APAO increase [OR 118 (CI 95 070ndash192)]The same effect resulted for diabetes during pregnancy (119903 =+042 119875 = 00002)

Table 2 Neonatal characteristics

Values ()Total number 70Male gender 34 (49)Gestational age (weeks) 392 plusmn 12Weight at delivery (gr) 32893 plusmn 3412Length at delivery (cm) 495 plusmn 22Head circumference (cm) 340 plusmn 12APAO (cm) 476 plusmn 098D-dimers (120583gmL) 3325 plusmn 6485PT-INR 16 plusmn 07Fibrinogen (mgdL) 2109 plusmn 495APGAR 51015840 97 plusmn 11Glycemia (mgdL) 489 plusmn 252Insulin (120583UImL) 38 plusmn 14HOMA index 059 plusmn 098Total cholesterol (mgdL) 739 plusmn 272LDL-cholesterol (mgdL) 293 plusmn 140HDL-cholesterol (mgdL) 306 plusmn 126Triglycerides (mgdL) 709 plusmn 455Spontaneous delivery 38 (54)Caesarean delivery 32 (46)Values are expressed as numbers and percent APAO anteroposteriorabdominal aorta diameter APGAR 51015840 American Pediatric Gross Assess-ment Record at 5 minutes HDL high-density lipoprotein HOMA homeo-static model assessment LDL low-density lipoproteins PT-INR prothrom-bin time-international normalized ratio

Table 3 Linear correlation analysis between neonatal antero-posterior abdominal aorta diameter (APAO) and main maternalvariables considered

Maternal variables Correlation coefficient (119903) 119875 valueMean age +022 006Total amount of pregnancy 019Eclampsia 098Hypertension 097Diabetes +042 00002Dyslipidaemia 098BMI before pregnancy 045BMI after delivery 021Height +047 000003Weight before delivery 016Weight after delivery +024 004APAO anteroposterior abdominal aorta diameter BMI body mass indexCVD cardiovascular diseases

Maternal height influences neonatal APAO (119903 = +047119875 = 000003) while BMI before delivery andor weight beforedelivery do not

Because of multiple associations between maternal andneonatal characteristics with neonatal APAO we performeda multivariate regression (Table 6) Only neonatal D-dimerswere still significantly related to neonatal APAO values


Table 4 Odds ratio evaluations between neonatal antero-posteriorabdominal aorta diameter (APAO) andmain dichotomousmaternalvariables considered

Findings Odds ratio 95 CISmoke 180 105ndash330CVD familiarity 078 047ndash129Diabetes familiarity 059 035ndash101Dyslipidaemia familiarity 118 070ndash192Hypertension familiarity 082 050ndash135CI confidential interval CVD cardiovascular disease

Table 5 Linear correlation analysis between neonatal antero-posterior abdominal aorta diameter (APAO) and main neonatalvariables considered

Neonatal variables Correlation coefficient (119903) 119875 valueGestational age +040 00005Weight 077Length +036 0001Head circumference +037 0001PT-INR 017Fibrinogen 024D-dimers +033 0004APGAR 51015840 012Glycemia 018Insulin +022 0056HOMA index +024 004HDL-cholesterol 035LDL-cholesterol 056Total-cholesterol 052Triglycerides 056APAO anteroposterior abdominal aorta diameter APGAR 51015840 AmericanPediatric Gross Assessment Record at 5minutes HDL high-density lipopro-tein HOMA homeostatic model assessment LDL low-density lipoproteinsPT-INR prothrombin time-international normalized ratio

4 Discussion

In the last two decades the scientific international com-munity investigated the early phases of life as the momentfrom which atherosclerosis process could be outlined andmaybe forced to reduce its development [3 6] The effortsto discover early markers of atherosclerosis since childhoodlead to a new era of noninvasive technologies able to findthe first moments of such a disabling process such asechocardiographic-Doppler evaluations [15] carotid intima-media thickness flow-mediated vasodilatation and APAO[10 11 16] Our study aim was to evaluate the influenceof maternal and neonatal characteristics on APAO in orderto evaluate possible early factors of abdominal aorta wallsalterations that is the beginning of atherosclerotic diseaseAPAO is an indicator of an earlier vascular remodeling anda high aortic stiffness and it is therefore associated witha widespread vascular disease It can be used to monitorpatients at risk even children [10 11] At the best of ourknowledge few studies have evaluated APAO in newborns

0500

100015002000250030003500400045005000

APAO (cm)30 35 40 45 50 55 60 65 70

minus500

minus1000

D-d

imer

s (120583

gm

L)

r = +033 P = 0004

Figure 1 Linear regression analysis comparing anteroposteriorabdominal aorta diameter and newborns D-dimers levels

Shankaran et al [17] demonstrated a tight relationshipbetween some maternal (smoke habits during pregnancyalcohol intake drug-addiction etc) and neonatal (birthweight gender etc) characteristics with the cardiovascularrisk profile evaluated at a 6-years followupTheywere all termnewborns but the study showed the increase of blood pres-sure at 6 years of age only in those with intrauterine growthrestriction (IUGR)Our study included onlyAGA infants anddifferent maternal and neonatal characteristics because it isalready known that preterm delivery andor IUGR are bothfactors able to increase the future cardiovascular risk [18 19]

Some authors [20 21] pointed out that maternal weight isa predictive factor for coronary heart diseases in adulthoodand Poston [22] showed that gestational weight gain couldinfluence long-term health of the neonate Our study didnot demonstrate a relationship between APAO and maternalweight and body mass index before delivery We furthershowed a relationship between APAO and maternal height

Our finding of a relationship betweenneonatal APAOandmaternal smoking habits suggests that maternal smoking cancause an increased cardiovascular risk already since birth[23ndash25] Anna-Karin et al [23] have found that maternalsmoking is related to reduced descending aorta diameterin preterm newborns Nevertheless Anna-Karin et al con-sidered preterm newborns who had different physiologicalconditions than termneonates Furthermore their regressionanalysis did not consider all the confounding factors able toinfluence the predictability of the results except gender andsmoking Differently from Anna-Karin et al we have onlyevaluated term newborns by considering all the parameterable to influence the relationship At a linear analysis smok-ing increased abdominal aorta intima-media thickness [24]probably through endocrine modifications involving seruminsulin-like growth factor-I (IGF-I) and insulin-like growthfactor binding protein-3 (IGFBP-3) levels and actions [23]or by inducing a long-lasting ldquoreprogrammingrdquo of the bloodpressure control mechanisms [25] but the evaluation wasnot confirmed after adjustment for confounding variablesNevertheless as the hypothesis of Anna-Karin et al about


Table 6 Multivariate correlation analysis between neonatal antero-posterior abdominal aorta diameter (APAO) and main maternal andneonatal variables considered

Coefficient Standard error 119875 valueModel 1

Maternal variablesMaternal age minus0006 0023 0808187BMI-after 0018 0029 0538889Height 0031 0020 0119716Smoke 0337 0283 0239169CVD familiarity 0022 0180 0901925Diabetes familiarity minus0169 0150 0264693Dyslipidaemia familiarity 0051 0212 0810230Hypertension familiarity minus0051 0205 0803890Eclampsia minus0019 0531 0970903Total pregnancies minus0188 0157 0237714Type of delivery (spontaneouscaesarean) minus0218 0220 0324930

Model 2Neonatal variables

Gestational age 0053 0117 0651170Length minus0029 0059 0632319Weight 0000 0000 0553384Head circumference minus0051 0111 0649230PT-INR 0105 0174 0548517D-dimers 0001 0000 0010114Fibrinogen minus0001 0003 0827094Total cholesterol minus0049 0055 0375519HDL-cholesterol 0029 0055 0594972LDL-cholesterol 0055 0058 0347597Triglycerides 0009 0012 0441564Glycemia minus0004 0007 0518465Insulin minus0048 0090 0593545HOMA index 0153 0498 0759908

APAO anteroposterior abdominal aorta diameter BMI bodymass index CVD cardiovascular diseases HDL high-density lipoprotein HOMA homeostaticmodel assessment LDL low-density lipoproteins PT-INR prothrombin time-international normalized ratio

a reduced flow in placental circulation due to smoke couldhave influenced the reduced diameter found at abdominalaortic level the same vascular alterations induced by smokecould enlarge the aortic diameter For this reason furtherstudies are needed in order to make such a matter clearer

The relationship between APAO and coagulation param-eters shows a statistically significant relationship betweenabdominal aorta diameter and D-dimers the end productof stabilized fibrin degradation whose values are higherin newborns compared to children and adults D-dimersderive from the fibrin degradation through fibrinolysis pro-cess activation It is encountered among those haemostatictests able to improve the detection of coagulation processactivation Giannitsis et al [26] already demonstrated therelationship between haemostatic factors and coronary arterydiseases Krupinski et al [27] found an increased value ofD-dimers in patients undergoing carotid endarterectomyunstable plaques in fact seemed to show a higher fibrinintraplaque turnover able to induce an augmentation of D-dimers products thus making D-dimers a surrogate marker

of plaque instability Clinical data recently indicated anassociation between elevated levels of D-dimers and therisk of subsequent clinical manifestations of cardiovasculardisease [28] The relationship between APAO and D-dimersin neonates is similar to the data from Empana et al [28] inadults and it has been confirmed by multivariate regressionanalysis Thus D-dimers could really become a markerof vessels walls instability and modification of their innermorphological structure since first days of life At the bestof our knowledge no study have showed these results butfurther studies are needed

Furthermore our data outlined a direct relationshipbetween other neonatal parameters and APAO

In particular gestational age (119903 = +040 119875 = 00005)length (119903 = +036 119875 = 0001) head circumference (119903 =+037 119875 = 0001) and HOMA index (119903 = +024 119875 = 0004)are all related to APAO

Late gestational age is related to increased cardiovascu-lar risk [29] Our data seem to corroborate the literaturefindings late gestational age is associated with increased


cardiovascular risk Nevertheless biometrics in newbornsrsquodevelopment is an important factor linked to cardiovascularrisk Touwslager et al [30] demonstrated that birth weightlength and head circumference of the infants were associatedwith impaired endothelial vasodilatation that is an earlymarker of atherosclerosis Our findings seem to completethose of Touwslager et al we demonstrated that birthweight length and head circumference were all related tomorphological alterations of the newbornsrsquo vasculature Thismeans that such neonatal parameters when altered could beconsidered as expression of morphological and functionalearly alterations of cardiovascular system thus they reallyincrease cardiovascular risk profile of each individual

In contrast with other studies [30 31] we have not foundthat birth weight influences APAO

APAO in our study population (term AGA newborns)is related to HOMAIR-index similarly to what Simental-Mendıa et al [32] have demonstrated in small-for-gestationalage (SGA) and large-for-gestational age (LGA) HOMAIRindex is a fundamental parameter calculated in order toevaluate onersquos insulin resistance condition According toGesteiro et al data [33] our newborns showed normal valuesof HOMAIR index in agreement with their age Insulin resis-tance is already known to damage vesselswalls by acceleratingatherosclerotic process Iannuzzi et al [34] demonstratedan increased aortic stiffness related to HOMAIR valuesNevertheless these data involved obese children while nodata concerned newborns At the best of our knowledge thisis the first study showing a direct relationship between insulinresistance increase and damages to aortic walls since thefirst moments of individualsrsquo life This means that physiciansshould better control pancreatic function of newborns inorder to prevent further damages to cardiovascular system

5 Conclusions

Despite the small sample size we obtained a preliminaryevaluation of the relationship betweenmaternal and neonatalcharacteristics and the cardiovascular system of the newbornevaluated as APAO an excellent noninvasive and repro-ducible tool able to evaluate the cardiovascular risk profile innewborns Further researches are needed in order to improveour findings

Conflict of Interests

The authors declare that there is no conflict of interests

References

[1] D S Celermajer C K Chow E Marijon N M Ansteyand K S Woo ldquoCardiovascular disease in the developingworld prevalences patterns and the potential of early diseasedetectionrdquo Journal of the American College of Cardiology vol60 pp 1207ndash1216 2012

[2] M OrsquoFlaherty I Buchan and S Capewell ldquoContributions oftreatment and lifestyle to declining CVD mortality why haveCVDmortality rates declined so much since the 1960srdquoHeartvol 99 pp 159ndash162 2013

[3] J Viikari H K Akerblom L Rasanen M Kalavainen and OPietarinen ldquoCardiovascular risk in young Finns experiencesfrom the Finnish multicentre study regarding the prevention ofcoronary heart diseaserdquo Acta Paediatrica Scandinavica Supple-ment vol 79 no 365 pp 13ndash19 1990

[4] S R Dalziel V Parag A Rodgers and J E Harding ldquoCar-diovascular risk factors at age 30 following pre-term birthrdquoInternational Journal of Epidemiology vol 36 no 4 pp 907ndash915 2007

[5] S P Efstathiou I I Skeva E Zorbala E Georgiou and TD Mountokalakis ldquoMetabolic syndrome in adolescence can itbe predicted from natal and parental profile the prediction ofmetabolic syndrome in adolescence (PREMA) studyrdquo Circula-tion vol 125 no 7 pp 902ndash910 2012

[6] M G Frontini S R Srinivasan J Xu and G S BerensonldquoLowbirthweight and longitudinal trends of cardiovascular riskfactor variables from childhood to adolescence the bogalusaheart studyrdquo BMC Pediatrics vol 4 article 22 2004

[7] R E Fisher M Steele and N A Karrow ldquoFetal programmingof the neuroendocrine-immune system and metabolic diseaserdquoJournal of Pregnancy vol 2012 Article ID 792934 10 pages2012

[8] N Koleganova K Benz G Piecha E Ritz and K AmannldquoRenal cardiovascular and metabolic effects of fetal program-mingrdquo Nephrology Dialysis Transplantation vol 27 pp 3003ndash3007 2012

[9] J R Ingelfinger and A M Nuyt ldquoImpact of fetal programmingbirth weight and infant feeding on later hypertensionrdquo Journalof Clinical Hypertension vol 14 pp 365ndash371 2012

[10] M M Ciccone V Miniello R Marchioli et al ldquoMorphologicaland functional vascular changes induced by childhood obesityrdquoEuropean Journal of Cardiovascular Prevention and Rehabilita-tion vol 18 no 6 pp 831ndash835 2011

[11] M M Ciccone S Favale A Bhuva et al ldquoAnteroposteriordiameter of the infrarenal abdominal aorta is higher in womenwith polycystic ovary syndromerdquo Vascular Health and RiskManagement vol 5 pp 561ndash566 2009

[12] E Bertino E Spada L Occhi et al ldquoNeonatal anthropomet-ric charts the Italian neonatal study compared with otherEuropean studiesrdquo Journal of Pediatric Gastroenterology andNutrition vol 51 no 3 pp 353ndash361 2010

[13] E Bonora G Targher M Alberiche et al ldquoHomeostasis modelassessment closely mirrors the glucose clamp technique in theassessment of insulin sensitivity studies in subjects with variousdegrees of glucose tolerance and insulin sensitivityrdquo DiabetesCare vol 23 no 1 pp 57ndash63 2000

[14] E Gesteiro S Bastida and F-J Sanchez Muniz ldquoEffects ofmaternal glucose tolerance pregnancy diet quality and neonatalinsulinemia upon insulin resistancesensitivity biomarkers innormoweight neonatesrdquo Nutricion Hospitalaria vol 26 no 6pp 1447ndash1455 2011

[15] M M Ciccone P Scicchitano A Zito et al ldquoDifferentfunctional cardiac characteristics observed in termpretermneonates by echocardiography and tissue doppler imagingrdquoEarly Human Development vol 87 no 8 pp 555ndash558 2011

[16] G Mercuro P P Bassareo G Flore et al ldquoPrematurity and lowweight at birth as new conditions predisposing to an increasedcardiovascular riskrdquo European Journal of Preventive Cardiologyvol 20 pp 357ndash367 2013

[17] S Shankaran A Das C R Bauer et al ldquoFetal origin ofchildhood disease intrauterine growth restriction in term


infants and risk for hypertension at 6 years of agerdquo Archives ofPediatrics and Adolescent Medicine vol 160 no 9 pp 977ndash9812006

[18] D LeyH Stale andKMarsal ldquoAortic vessel wall characteristicsand blood pressure in children with intrauterine growth retar-dation and abnormal foetal aortic blood flowrdquoActa PaediatricaInternational Journal of Paediatrics vol 86 no 3 pp 299ndash3051997

[19] N Evans J Hutchinson J M Simpson D Donoghue B Dar-low andD Henderson-Smart ldquoPrenatal predictors of mortalityin very preterm infants cared for in the Australian and NewZealand Neonatal Networkrdquo Archives of Disease in Childhoodvol 92 no 1 pp F34ndashF40 2007

[20] T Forsen J G Eriksson J Tuomilehto K Teramo C Osmondand D J P Barker ldquoMotherrsquos weight in pregnancy and coronaryheart disease in a cohort of Finnish men follow up studyrdquoBritish Medical Journal vol 315 no 7112 pp 837ndash840 1997

[21] M R Skilton ldquoIntrauterine risk factors for precociousatherosclerosisrdquo Pediatrics vol 121 no 3 pp 570ndash574 2008

[22] L Poston ldquoGestational weight gain influences on the long-termhealth of the childrdquo Current Opinion in Clinical Nutrition ampMetabolic Care vol 15 pp 252ndash257 2012

[23] E B Anna-Karin J JohanBengtsson Z Nagy H De Keyzerand M Norman ldquoPreterm birth and maternal smoking inpregnancy are strong risk factors for aortic narrowing in ado-lescencerdquo Acta Paediatrica International Journal of Paediatricsvol 97 no 8 pp 1080ndash1085 2008

[24] T Gunes E Koklu A Yikilmaz et al ldquoInfluence of maternalsmoking on neonatal aortic intima-media thickness serumIGF-I and IGFBP-3 levelsrdquo European Journal of Pediatrics vol166 no 10 pp 1039ndash1044 2007

[25] G Cohen H Jeffery H Lagercrantz and M Katz-SalamonldquoLong-term reprogramming of cardiovascular function ininfants of active smokersrdquoHypertension vol 55 no 3 pp 722ndash728 2010

[26] E Giannitsis H J Siemens R Mitusch et al ldquoProthrombinfragments F1+2 thrombin-antithrombin III complexes fibrinmonomers and fibrinogen in patients with coronary atheroscle-rosisrdquo International Journal of Cardiology vol 68 no 3 pp 269ndash274 1999

[27] J Krupinski E Catena M Miguel et al ldquoD-dimer localexpression is increased in symptomatic patients undergoingcarotid endarterectomyrdquo International Journal of Cardiologyvol 116 no 2 pp 174ndash179 2007

[28] J-P Empana F Canoui-Poitrine G Luc et al ldquoContribution ofnovel biomarkers to incident stable angina and acute coronarysyndrome the PRIME Studyrdquo European Heart Journal vol 29no 16 pp 1966ndash1974 2008

[29] MAltmanAK Edstedt BonamyAKWikstrom and SCnat-tingius ldquoCause-specific infant mortality in a population-basedSwedish study of term and post-term births the contribution ofgestational age and birth weightrdquo BMJ Open vol 2 no 4 2012

[30] R N H Touwslager A J H M Houben M Gielen et alldquoEndothelial vasodilatation in newborns is related to body sizeand maternal hypertensionrdquo Journal of Hypertension vol 30no 1 pp 124ndash131 2012

[31] J Eriksson T Forsen J Tuomilehto C Osmond andD BarkerldquoSize at birth childhood growth and obesity in adult liferdquoInternational Journal of Obesity vol 25 no 5 pp 735ndash740 2001

[32] L E Simental-Mendıa A Castaneda-Chacon M Rodrıguez-Moran and F Guerrero-Romero ldquoBirth-weight insulin levels

and HOMA-IR in newborns at termrdquo BMC Pediatr vol 12article 94 2012

[33] E Gesteiro S Bastida and F J Sanchez-Muniz ldquoInsulinresistance markers in term normoweight neonates the Meridacohortrdquo European Journal of Pediatrics vol 168 no 3 pp 281ndash288 2009

[34] A Iannuzzi M R Licenziati C Acampora et al ldquoPreclinicalchanges in the mechanical properties of abdominal aorta inobese childrenrdquoMetabolism vol 53 no 9 pp 1243ndash1246 2004

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Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom


incidence of cardiovascular disease in adulthood [5 6] Theldquofetal programmingrdquo during critical phases of development inutero could be responsible formetabolic disturbances in adultlife and long-term structural changes of the vascular system[7ndash9]

Neonatal and maternal characteristics could early influ-ence atherosclerosis development Anteroposterior diameterof infrarenal abdominal aorta (APAO) is a reliable and well-established ultrasound parameter to detect early impairmentof vascular structure since childhood [10 11]

The aimof this studywas to evaluate the influence of someselected maternal and neonatal characteristics on aorta walls(evaluated by mean of APAO) in term appropriately grown-for-gestational age (AGA) newborns

2 Methods

21 Subjects Seventy mother-newborn pairs admittedrespectively to the Obstetric Section and Neonatology andNeonatal Intensive Care of the Department of GynecologyObstetrics and Neonatology of the University of Bari wereenrolled in the study

The study was approved by the Institutional ReviewBoard of Bari University General Hospital and carried out inaccordance with the principles of the Helsinki Declaration

211 Newborns Characteristics There were 34 males and 36females healthy newborns born at term (after 37 completedweeks of gestation) 38 by vaginal delivery and 32 by C-sectionMean gestational agewas 392plusmn12weeksmean birthweight 32893 plusmn 3412 g (between 10th and 90th percentileas established by gender and gestational age-specific nationalcharts [12] AGA) mean length 495 plusmn 22 cm and headcircumference 340 plusmn 12 cm They all had normal transition(Apgar 51015840 ge 7)Newbornswith any congenitalmalformationswere excluded

After informed consent all newborns had ultrasoundevaluation of the APAO and biochemical profile wasobtained on the blood taken at birth from umbilicalcord Blood samples had been performed early at morning(between 8 00 am and 9 00 am) after an overnight fast onthe same day of the ultrasound

APAO evaluations were done within 24 hours after deliv-ery with the newborn in supine position during a routinedaytime rest period in a warm environment (20-21∘C) Itwas performed by a single operator using a single high-resolution vascular ultrasound Philips 5500 equipped with a3MHz electronic probe To improve the image acquisitionneonates were examined at least 4ndash6 hours after breastfeedingto reduce intestinal bloatingThe electronic probe was placedone centimeter left of the umbilicus Then the best image inlong-axis projection of the abdominal aorta was obtainedThe APAO was defined as the maximal external cross-sectional diameter measurement of the infrarenal abdominalaorta It was calculated as the distance between the nearand the far walls of the abdominal aorta Measurementswere performed 1 cm above and distal to the umbilicus and

expressed in centimeters [10 11] Repeatability and intraob-server variability of all ultrasound scan measurements wereevaluated by means of intraclass correlation coefficient ofgt090 In particular anteroposterior diameter showed goodreproducibility with an intraclass correlation coefficient of092

Biochemical profile included glucose insulin totalcholesterol high-density lipoprotein (HDL) and low-densitylipoprotein (LDL) cholesterol triglycerides fibrinogen andD-dimers determinations Insulin resistance was calculatedby the homeostasis model assessment (HOMAIR) [13 14]

212 Maternal Characteristics For each mother data onage parity previous abortions weight height and bodymass index [weight (kg)][height (m)]2 before and afterdelivery were collected Using a combination of clinicalinterviews and obstetric records information about familiarhistory for hypertensive diabetic cardiovascular diseasesand dyslipidemic conditions were also obtained Motherswere considered as smoker if they smoked at least fivecigarettesday within 3 months before delivery or if theystopped smoking lt1 year before delivery There were noinclusion criteria for the mothers except to have delivered anAGA term newborn 111 mothers and related newborns wereconsecutively enrolled but 70 delivered AGA term newborn

22 Statistical Analysis The continuous variables wereexpressed as mean and standard deviation

Categorical data had been evaluated by means of oddsestimation and CI 95 had been used in order to assess statis-tical significance The Pearsonrsquos linear correlation coefficientwas used to study the relationship between the continuousvariables Multiple regression analysis had been adopted inorder to evaluate the influence of confounding factors onAPAO evaluation A 119875 lt 005 was considered statisticallysignificant

3 Results

Maternal mean age was 32 plusmn 5 years Body mass index beforedelivery was within normal limits (2275plusmn446Kgm2)Therewere 19 smokers (27) Nine (13) had gestational diabetesand 6 (9) and 3 (4) haddyslipidemia 22 (31) had one ormore previous abortions and 5 (7) had 2 or more previouspregnancies Familiarity for hypertension cardiovasculardiseases dyslipidemic conditions and diabetes are shown inTable 1

Neonatal data are shown in Table 2 Mean APAO valuewas 476 plusmn 098 cm

Pearsonrsquos linear regression has been used to assess anyrelationships between APAO values and maternal character-istics (Table 3) Furthermore odds ratio and their relativesconfidential intervals had been calculated for main dichoto-mous maternal variables considered (Table 4) Pearsonrsquos lin-ear regression has been used to assess any relationshipsbetween APAO values and neonatal characteristics (Table 5)

APAO is directly related both to newborn length (119903 =+036 119875 = 0001) and head circumference (119903 = +037



























4 Discussion


0500

100015002000250030003500400045005000

APAO (cm)30 35 40 45 50 55 60 65 70

minus500

minus1000

D-d

imer

s (120583

gm

L)

r = +033 P = 0004






















5 Conclusions




References











































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of










































4 Discussion


0500

100015002000250030003500400045005000

APAO (cm)30 35 40 45 50 55 60 65 70

minus500

minus1000

D-d

imer

s (120583

gm

L)

r = +033 P = 0004






















5 Conclusions




References











































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

































5 Conclusions




References











































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of









































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
















Clinical Study Aorta Structural Alterations in Term...

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