Growth Abnormalities of Fetuses and Infants PDF
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BioMed Research International Growth Abnormalities of Fetuses and Infants Lead Guest Editor: Erich Cosmi Guest Editors: Enrico Grisan, Vassilios Fanos, Giuseppe Rizzo, Shanthi Sivanandam, and Silvia Visentin Growth Abnormalities of Fetuses and Infants BioMed Research International Growth Abnormalities of Fetuses and Infants Lead Guest Editor: Erich Cosmi Guest Editors: Enrico Grisan, Vassilios Fanos, Giuseppe Rizzo, and Shanthi Sivanandam Copyright©2017Hindawi.Allrightsreserved. Thisisaspecialissuepublishedin“BioMedResearchInternational.”AllarticlesareopenaccessarticlesdistributedundertheCreative CommonsAttributionLicense,whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginal workisproperlycited. Contents GrowthAbnormalitiesofFetusesandInfants ErichCosmi,EnricoGrisan,VassiliosFanos,GiuseppeRizzo,ShanthiSivanandam,andSilviaVisentin Volume2017,ArticleID3191308,4pages DNADamageasaDriverforGrowthDelay:ChromosomeInstabilitySyndromeswithIntrauterine GrowthRetardation BenildeGarcía-deTeresa,MarianaHernández-Gómez,andSaraFrías Volume2017,ArticleID8193892,14pages APsychologicalPerspectiveonPretermChildren:TheInfluenceofContextualFactorsonQualityof FamilyInteractions MichelaGatta,MarinaMiscioscia,LorenzaSvanellini,ChiaraPeraro,andAlessandraSimonelli Volume2017,ArticleID9152627,10pages EchocardiographicTechniquesof DeformationImagingintheEvaluationof MaternalCardiovascular SysteminPatientswith ComplicatedPregnancies SilviaVisentin,ChiaraPalermo,MartinaCamerin,LucianoDaliento, DenisaMuraru,ErichCosmi, andLuigiP.Badano Volume2017,ArticleID4139635,10pages ParacetamolinPatentDuctusArteriosusTreatment:EfficaciousandSafe? FlaminiaBardanzellu,PaolaNeroni,AngelicaDessì,andVassiliosFanos Volume2017,ArticleID1438038,25pages MetabolomicsandCardiology:TowardthePathofPerinatalProgrammingandPersonalizedMedicine RobertaPintus,PierPaoloBassareo,AngelicaDessì,MartinoDeidda,GiuseppeMercuro, andVassiliosFanos Volume2017,ArticleID6970631,8pages ParentalGeneticVariants,MTHFR677C>TandMTRR66A>G,AssociatedDifferentlywithFetal CongenitalHeartDefect Qian-nanGuo,Hong-danWang,Li-zhenTie,TaoLi,HaiXiao,Jian-gangLong,andShi-xiuLiao Volume2017,ArticleID3043476,7pages PostnatalGrowthinaCohortofSardinianIntrauterineGrowth-RestrictedInfants MariaGraziaClemente,GiampieroCapobianco,PaoloMattiaGalasso,FrancescoDessole,GiuseppeVirdis, MariaGraziaSanna,MauroGiorgioOlzai,LinoArgiolas,SalvatoreDessole,andRobertoAntonucci Volume2017,ArticleID9382083,5pages TheRoleofInterleukin-17,Interleukin-23,andTransformingGrowthFactor-𝛽inPregnancy ComplicatedbyPlacentalInsufficiency DorotaDarmochwal-Kolarz,MagdalenaMichalak,BogdanKolarz,MonikaPrzegalinska-Kalamucka, AgnieszkaBojarska-Junak,DariuszSliwa,andJanOleszczuk Volume2017,ArticleID6904325,5pages DoesChemotherapyforGynecologicalMalignanciesduringPregnancyCauseFetalGrowth Restriction? NabilAbdalla,MagdalenaBizoń,RobertPiórkowski,PawełStanirowski,KrzysztofCendrowski,and WłodzimierzSawicki Volume2017,ArticleID7543421,7pages ScientificEvidenceforDifferentOptionsforGDMScreeningandManagement:Controversiesand ReviewoftheLiterature ClaudiaCaissuttiandVincenzoBerghella Volume2017,ArticleID2746471,12pages ApolipoproteinEGenotypeinVeryPretermNeonates withIntrauterineGrowthRestriction: An AnalysisoftheGermanNeonatalNetworkCohort StephenNorda,TanjaK.Rausch,ThorstenOrlikowsky,MatthiasHütten, SörenSchulz,WolfgangGöpel, andUlrichPecks Volume2017,ArticleID2837027,8pages Care-RelatedandMaternalRiskFactorsAssociatedwith theAntenatalNondetectionofIntrauterine GrowthRestriction:ACase-ControlStudyfromBremen,Germany SinjaAlexandraErnst,TilmanBrand,AnnaReeske,JacobSpallek, KnudPetersen,andHajoZeeb Volume2017,ArticleID1746146,10pages DomiRNAsPlayaRoleinFetalGrowthRestriction?AFreshLooktoaBusyCorner BenitoChiofalo,AntonioSimoneLaganà,AlbertoVaiarelli,ValentinaLuciaLaRosa,DiegoRossetti, VittorioPalmara,GaetanoValenti,AgneseMariaChiaraRapisarda,RobertaGranese,FabrizioSapia, OnofrioTriolo,andSalvatoreGiovanniVitale Volume2017,ArticleID6073167,8pages First-TrimesterCrown-RumpLengthandEmbryonicVolumeofFetuseswithStructuralCongenital AbnormalitiesMeasuredinVirtualReality:AnObservationalStudy L.Baken,B.Benoit,A.H.J.Koning,P.J.vanderSpek,E.A.P.Steegers,andN.Exalto Volume2017,ArticleID1953076,6pages SuspectedFetalGrowthRestrictionat37Weeks:AComparisonofDopplerandPlacentalPathology WilliamM.Curtin,KarmaineA.Millington,TochiO.Ibekwe,andSerdarH.Ural Volume2017,ArticleID3723879,10pages Hindawi BioMed Research International Volume 2017, Article ID 3191308, 4 pages https://doi.org/10.1155/2017/3191308 Editorial Growth Abnormalities of Fetuses and Infants ErichCosmi,1EnricoGrisan,1VassiliosFanos,2GiuseppeRizzo,3 ShanthiSivanandam,4andSilviaVisentin1 1UniversityofPadua,Padua,Italy 2UniversityofCagliari,Cagliari,Italy 3UniversityofRomeTorVergata,Rome,Italy 4UniversityofMinnesota,Minneapolis,MN,USA CorrespondenceshouldbeaddressedtoErichCosmi;[email protected] Received 27 September 2017; Accepted 27 September 2017; Published 22 November 2017 Copyright©2017ErichCosmietal.ThisisanopenaccessarticledistributedundertheCreativeCommonsAttributionLicense, whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited. The objective of this special issue is to address recent highest rates of infant mortality in the early 20th century research trends and developments about the advancements also had the highest rates of mortality from coronary heart of image processing and vision in healthcare. A substantial diseasedecadeslater.Asthemostcommonlyregisteredcause numberofpapersweresubmitted,andafterathoroughpeer of infant death at the start of 20th century was low birth review process, some of these were selected to be included weight,theseobservationsledtothehypothesisthatlowbirth in this special issue. Growth abnormalities (either growth weightbabieswhosurvivedinfancyandchildhoodmightbe restrictionorlargeforgestationalage)duringperinataland atincreasedriskofcoronaryheartdiseaseinlaterlife.There postnatallifeareahottopicissue,sincetheyareoftenlinked isanincreasedevidenceofthelinkbetweenintrauterineand to alteration of uterine environment caused by placental perinatal alterations and adult diseases. Although the main insufficiency, maternal metabolic syndrome, and in general focus so far has been the timing of delivery and follow-up, under-orovernutritionofthefetus.Thesefetalabnormalities thestudyofthepathophysiologyandofpossiblerecoveryisof account for the leading causes of perinatal morbidity and paramountimportanceandneedsthecontributionsofphysi- mortality.Moreover,underthehypothesisofdevelopmental cians from several fields, biologists, bioinformaticians, and origin of adult diseases, they bear consequences in later engineers. life, programming the infant physiology for a higher risk ofnoncommunicablediseases,cardiovascularadultdiseases, The paper by C. Caissutti and V. Berghella presents andneurodevelopmentdelay.Lowbirthweight,causedeither a comprehensive review about the most important and by preterm birth and/or by intrauterine growth restriction, employed guidelines about screening and management of is recently known to be associated with increased rates of gestationaldiabetes(GDM)thataffectsupto7%ofpregnant cardiovascular disease and noninsulin dependent diabetes womenandisassociatedwithseveralmaternalandperinatal in adult life. The “developmental origins of adult disease” morbidities. It is well known that GDM represents over hypothesis, often called “the Barker hypothesis,” proposes time a risk factor of type 2 diabetes, for both the mother thatthesediseasesoriginatethroughadaptationsofthefetus andthefetus.Nowadays,therearemanyunsolvedquestions whenitisundernourished.Theseadaptationsmaybecardio- concerningtheindicationsofscreening,thetimingandtype vascular,metabolic,orendocrineandtheymaypermanently of screening, the criteria for diagnosis, and the population change the structure and function of the body, increasing toscreen.Thecorrectidentificationofuniversallyapproved coronaryheartdiseaseriskfactors,suchashypertension,type and shared recommendations should improve the GDM 2 diabetes mellitus,insulinresistance, andhyperlipidaemia. pregnancyoutcomes(gestationalhypertension,prematurity, This hypothesis originally involved from observation by cesarean deliveries, number of large for gestational age and Barker and colleagues that the regions in England with the smallforgestationalagefetuses,and1-minuteApgarscores 2 BioMedResearchInternational <7), improving the health care and maintaining a cost- IUGR in our series showed significant postnatal catch-up effectivebenefit. growth essentially during the first 12 months of life. The The paper by B. Chiofalo et al. takes into account modern research describes a new personalized medicine the role of microRNAs (miRNAs) of the placenta in the approachthroughtheNewbornIndividualizedDevelopmen- intrauterinegrowthrestriction(IUGR)disease.IUGRcould tal Care and Assessment Program (NIDCAP), conducted beconsideredasaplacentationdisorder,derivedfromadys- on preterm infantsborn with severe IUGR by a multidisci- regulation in trophoblast invasion with characteristic tissue plinary research working group. It seems to be effective in morphologythatleadstouteroplacentalinsufficiency.More amelioratingtheneurobehavior,electrophysiology,andbrain than1880miRNAshavebeenreportedinhumansandmost structureoutcomes.Animprovedknowledgeofthecausesof of them are expressed in placenta. They seem to modulate IUGR will help to develop measures for its prevention and celldevelopment,differentiation,andproliferation,celltype- individualizedtreatment. specificfunction,andepigeneticprocesses.Inseveralcases, The paper of Q. Guo et al. takes into account the con- miRNA is significantly different between physiology and genital heart defect (CHD), one of the most commonbirth pathologicalconditions.Anabnormalupregulatedplacental defectsintheworld.Aroundtheworld,periconceptionalfolic expression regulating some angiogenic regulatory pathways acidintakeinfemalesisthoughttoreducetheriskofCHD seems to increase vascular resistances, also in growth- in the newborn. The methylenetetrahydrofolate reductase restricted human pregnancies. Despite the fact that several (MTHFR)andmethioninesynthasereductase(MTRR)genes authors have demonstrated a relatively easy and feasible are two of the most important candidate genes for fetal detection of some miRNAs in maternal whole peripheral CHD.However,thecorrelationsbetweenthetwogenesand blood, costs of these tests should be reduced in order to fetal CHD were inconsistent in various reports. This study increasecohortsandhavestrongerevidence.Alargecohort is aimed to evaluate the parental effects of the two genes and an adequate statistical power could identify a panel of on fetal CHD via three genetic polymorphisms, MTHFR biomarkersonmaternalperipheralbloodforearlydiagnosis 677C>T (rs1801133), MTHFR 1298 A>C (rs1801131), and ofIUGR. MTRR 66A>G (rs1801394). Parents with pregnancy history The paper of W. M. Curtin et al. analyzes the corre- of fetal CHD were divided into two subgroups in base on lation between Doppler abnormalities in fetuses with sus- ventricular septal defect (VSD) and non-VSD groups. In pected IUGR delivered at 37 weeks’ gestation and placental either maternal or paternal group, the MTHFR 677C>T histopathologicallesions,inordertoremovetheconfounding polymorphismwasindependentlyrelatedtofetalnon-VSD, factorthatgestationalagehasoninterpretationofplacental whiletheMTRR66A>Gpolymorphismwasindependently disease.ThecorrectdefinitionofIUGRnowadaysisobjectof relatedtofetalVSD.Thefindingsofthisstudycouldhelpto discussion.Upto70%offetuseswithsuspectedIUGRmaybe explainwhytherelationshipbetweenthetwopolymorphisms constitutionallysmallnormalinfantsandtheremainderwill (MTHFR 677C>T and MTRR 66A>G) and CHD varied beclassifiedasIUGRpresumablysecondarytoapathologic among different studies due to different proportion of VSD placentalprocess.InIUGRatlatergestationalages,abnormal andnon-VSDsubjectsincludedinthosedifferentpopulation umbilical artery Doppler patterns are less frequent; the studies. placentalpathologyissubtlerandthelesionscanoverlapwith The paper of D. Darmochwal-Kolarz et al. investi- normalpregnancies.Thisaspectcoulddistinguishthe“true” gates the role of Interleukin-17 (IL-17), Interleukin-23 (IL- or “pathologic” IUGR fetuses. In their study the authors 23), and transforming growth factor 𝛽 (TGF 𝛽) in preg- showanassociationbetweenabnormalDopplerpatternsand nancy complicated by placental insufficiency, fetal growth thepresenceofplacentalpathologyinsingletonpregnancies restriction, and preeclampsia. In recent years, in order to delivered at 37 weeks’ gestation for suspected IUGR. In clarify the immunological mechanisms responsible for the particular, an abnormal MCA Doppler had the strongest proper implantation process, the interest has moved on the associationandunderscoresthelimitationofumbilicalartery Th1/Th2/Th17paradigm.Interleukin-17(IL-17)isacytokine Doppler alone in IUGR at later gestational ages. Further with potent proinflammatory properties and has a proven investigation and tools for separating the constitutionally role in the development of inflammatory processes. More- smallnormalfetusfromtheIUGRfetusareneeded. over, Interleukin-23, which is produced, among others, by The paper of M. G. Clemente et al. describes an obser- macrophagesanddendriticcells,isanimportantcomponent vational retrospective study about the postnatal growth in oftheinflammatoryresponse.Finally,transforminggrowth a cohort of IUGR infants. The fetal programming theory factor 𝛽 (TGF 𝛽) released, among others, by macrophages, postulates that the conditionof IUGR is associated with an neutrophils, platelets, and lymphocytes, acts primarily to increasedriskofcardiovasculareventsinadultlife,asstroke, reducethereleaseofproinflammatorycytokines.Inaddition, type II diabetes, metabolic syndrome, and neurocognitive TGF 𝛽 is involved in the processes of angiogenesis, wound impairment. At birth, significant differences were found healing,andrepairprocesses,aswellasregulationoftheentry between IUGR and controls neonates with regard to all ofcellsontotheapoptoticpathway.Inthegroupofpatients theauxologicalparameters(weight,headcircumference,and with placental insufficiency, the maternal sera levels of IL- length). During the 1st year, 8 of 12 (70%) IUGR infants 17positivelycorrelatedwithmaternalsystolicbloodpressure exhibited a significant catch-up growth in the 3 anthropo- and the concentrations of TGF 𝛽 were significantly lower, metric parameters and a regular growth until the 3rd year whileIL-23wascomparablewithrespecttocontrolgroup.It of follow-up. The majority but not all infants born with seemspossiblethattheincreasedconcentrationsofIL-17and BioMedResearchInternational 3 the deficiency of TGF 𝛽 in pregnancy complicated by fetal subsequentalteredenergymetabolismincardiacdiseases,in growth restriction and preeclampsia can be responsible for particular in case of heart failure. Moreover, every adverse theactivationofinflammatoryresponse. eventthatmayoccurduringpregnancy“shapes”thehealth The paper of L. Baken et al. discusses the introduction status of the fetus and its development and could affect its of three-dimensional (3D) ultrasound in the evaluation of life course, also with cardiovascular problems. Congenital the crown-rump length (CRL), in particular whether the malformations, gut colonization by microbiota, individual embryonicvolume(EV),measuredbyaVirtualReality(VR) geneticarrangement,anditsinterplaywithbothbehavioral system,isabetterparametertodeterminegrowthrestriction and risk factors, such as drugs assumption, can influence infetuseswithstructuralcongenitalabnormalities,diagnosed the occurrence of heart diseases. During the last decade, inthefirsttrimesterofpregnancy.Itisknowthattherelative animal and human studies have applied metabolomics to incrementoftheEVismuchlargerthantheincrementofthe cardiovascularresearch,usingbothtargetedanduntargeted CRL during the same period. Moreover, if a too small CRL approaches;assuch,metabolicfingerprintshavebeenidenti- is a clinical predictor for miscarriage, chromosomal abnor- fiedforseveralcardiovascularriskfactorsanddiseases.These malities(especiallytrisomy18),andfetalgrowthrestrictionin techniques could be applied to heart tissue and biofluids, thesecondandthirdtrimesterofpregnancy,severalauthors suchasblood,saliva,andurine,withaminimumcompliance underlined that EV was not only smaller in trisomy 18 neededfromthepatient,sincetheircollectionisnotinvasive. pregnanciesbutalsointrisomy21andtrisomy13pregnancies. Metabolomics,foritspeculiarities,seemstobesopromising In this study, measured CRL and EV were converted to thatseveralindustriesaretryingtosetupkitstoimmediately 𝑧-scores and to percentages of the expected mean, using assessthemetabolitesvariationsinordertoprovideafaster published reference curves of euploid fetuses. The EV was diagnosis and the best treatment specific for that patient, smaller than expected for gestational age in fetuses with offering a further step toward the path of the development structural congenital abnormalities, whereas CRL was not. ofatailoredmedicine. BymeasuringEV,first-trimestergrowthrestrictionbecomes The paper of N. Abdalla et al. describes complete up- moreevidentandmightenableanearlierdetectionofcases to-date findings from the literature regarding the impact atriskforacongenitalabnormality. of chemotherapy on fetal growth. Cancer and pregnancy ThepaperofF.Bardanzelluetal.presentsacomprehen- rarely coincide. Gynecological cancers are among the most sivereviewofparacetamolefficacyinDuctusArteriosus(DA) common malignancies to occur during pregnancy, and closureinpreterminfants,inwhichthefailureordelayofits chemotherapywithorwithoutsurgeryistheprimarytreat- spontaneousclosureresultsintheconditionofPatentDuctus mentoption.Themainconcernofadministeringchemother- Arteriosus (PDA). A prolonged situation of PDA can be apyduringpregnancyiscongenitalmalformation,althoughit associatedwithseveralshort-andlong-termcomplications. canbeavoidedbydelayingtreatmentuntilafterorganogene- Despite years of researches and clinical experience on PDA sis.Thedose,frequency,choiceofchemotherapeuticagents, management,unresolvedquestionsaboutthetreatmentand timeoftreatmentcommencement,andmethodofadminis- heterogeneity of clinical practices still remain, in particular trationcanbeadjustedtoobtainthebestmaternaltreatment regarding timing and modality of intervention. Nowadays, outcomeswhilesimultaneouslyminimizingfetaltoxicity.Use the most reasonable strategy seems to be reserving the of chemotherapy after the first trimester, while seemingly treatment only to hemodynamically significant PDA. The safe, can cause fetal growth restriction. However, the exact first-linetherapyismedical,andibuprofen,relatedtoseveral effect of chemotherapy on such fetal growth restriction has sideeffectsespeciallyintermsofnephrotoxicity,isthedrug notbeenfullyestablished;informationisscarceowingtothe of choice. Administration of oral or intravenous paraceta- rarity of malignancy occurring during pregnancy, the lack mol (acetaminophen) recently gained attention, appearing of uniform treatment protocols, different terminologies for effectiveastraditionalnonsteroidalanti-inflammatorydrugs definingcertainfetalgrowthabnormalities,theinfluenceof (NSAIDs) in PDA closure, with lower toxicity. The results mothers’ preferred options, and ethical issues. Fetal growth ofthestudiesanalyzedinthisreviewmostlysupportparac- abnormalitiesarerecognizedsequelaeofchemotherapy,and etamol efficacy in ductal closure, with inconstant low and the possibility of fetal growth abnormalities as well as the transient elevation of liver enzymes as reported side effect. othersideeffectsofdifferentchemotherapeuticagentsshould More studies are needed to confirm if this therapy shows a bediscussedwiththepatients. realsafetyprofileandtoevaluateitslong-termoutcomes. Thetypeofmalignancyanditsstage,theuseofsurgery ThepaperofR.Pintusetal.discussesthemostrecentlit- and/orradiotherapy,thestageofpregnancy,theprobability eratureaboutthemetabolomictechnologyanditsapplication ofsideeffectsduringtreatment,andthepatient’sownwishes inthecardiologicfield,inordertounderstandthemetabolic influence the final decision regarding treatment. Moreover, shifts that occur even before the manifestation of heart ethical concerns cannot be ignored. Each patient should diseases and to find possible early predictive biomarkers. ultimately be managed individually with the guidance of a Cardiac pathologiesare a criticalhealthissue affectingmil- multidisciplinaryteam. lionsofpeopleworldwide,withaconstantmortalityratein The paper of S. A. Ernst et al. investigates what care- particularintheelderly,adifficultprognosis,andaworsening related and maternal risk factors could influence the ante- in quality of life of affected people. The pathophysiology of natal nondetection of IUGR during pregnancy and exam- heartpathologiesiscomplex.Recentfindingspointedouta ine if there are specific groups with a higher chance of possible pivotal role of mitochondrial dysfunction and the nondetected suboptimal fetal growth. Approximately 3% to 4 BioMedResearchInternational 8% of all infants born in developed countries have been of life. Few studies have stressed the assessment of mother- identifiedasgrowthrestricted.IUGRisaprenatalcondition father-child interaction in families with preterm children, associated with a higher risk for perinatal morbidity and generating contradictory results. The authors recruited 78 mortality, increasing the stillbirth rate fourfold compared families, 39 families with preterm children, and 39 families topregnancieswithnormallygrownfetuses;antenatalnon- with full-term children. Results show that families with detection further increases the rate by a factor of 2. An pretermchildrendisplayalowqualityofmother-father-child early antenatal detection, choosing the optimal time and interactions. After six months, family interactions result is method of delivery, and treatment where appropriate could generally stable, except for some Lausanne Trilogue Play- minimize the risks significantly. However, low antenatal scales,reflectingahardadjustmentofparentingstyletothe detection rates of suboptimal fetal growth through routine evolutionofthechild.TheLausanneTriloguePlayisasemi- fetalultrasonographyhavebeenreported.InfactIUGRhas standardized observation situation designed to assess the been reported to be antenatally detected only in one-third quality of family interactions. The administration involved (25% to 32%) of pregnancies with suboptimal fetal growth. themother-father-childtriadinvitedtocooperateandwork Moreover,theauthorsidentifiedthreefactorsthatinfluenced together in order to conduct an activity. In families with IUGRdetection:ahigherseverityofthegrowthrestriction, pretermchildren,theparentingstressseemedtobecorrelated maternal complications/diseases during pregnancy, and a withthequalityofmother-father-childinteractions. Doppler examination. The authors did not find statistically significantdifferencesregardingparentalsocioeconomicsta- Acknowledgments tus and maternal migration background. Future in-depth studieswithlargerstudypopulationsshouldfurtherexamine Wewouldliketothankalltheauthorswhocontributedtothis factorsthatcouldincreaseantenataldetectionratesforIUGR. specialissue.Thispublicationwouldnotbepossiblewithout ThepaperofS.Nordaetal.discussestheroleofneonatal theparticipationofourexpertreviewers,whoprovidedvital ApoEe4haplotypeonIUGRanditscontributiononimpaired constructive feedback and criticism throughout the review fetal growth and the possible link of IUGR with cardiovas- process. cular and metabolic diseases later in life. Apolipoprotein E (ApoE)isanimportantcirculatingserumproteininvolvedin ErichCosmi transportinglipidsandcholesterolandregulatinglipidlevels. EnricoGrisan Its regulatory functions have been attributed to many bio- VassiliosFanos physiologicalprocessesincludingneuronalgrowthandmod- GiuseppeRizzo ulationofoxidantandinflammatoryprocesses.Cordbloodof ShanthiSivanandam IUGRneonatesdisplayslipidchangestowardsatherosclerotic SilviaVisentin profiles. IUGR born babies were found to have lower con- centrationsofhigh-densitylipoproteincholesterol(HDL-C), knownforhavingananti-inflammatoryeffectandprotective propertiesagainstthedevelopmentofatherosclerosis,while triglycerides and oxidized low-density lipoprotein (oxLDL) levelswereelevatedinsamplesofumbilicalbloodcompared toadequateweightnewborns.Thisdisruptedcholesteroland triglyceridehandlingplaysaroleincausingsuboptimalfetal developmentandexposesthenewborntoanatherosclerotic environmentearly,consequentiallygivingraisetoirreversible damage to vessels. The association of ApoE e4 with the development of dyslipidemia and cardiovascular disease is known. In newborns, carrying the ApoE e2 allele has been associated with lower fetal cord blood LDL-C levels and higher levels of HDL-C suggesting a beneficial effect of this genotype on blood lipid configuration, modulating the fetal growth and the severity of IUGR. In this cohort, 4885 preterm infants were analyzed. Neonates were categorized into subgroups of <3rd, 3rd–10th, and >10th birth weight percentile. The identification of the ApoE genotype was carried out. No association was found between genotype andbirthweightpercentilesineachofthesubgroups.ApoE genotypeandlowbirthweightdepicttwodistinctriskfactors forcardiovasculardiseasewithoutbeingdirectlyassociated. The paper of M. Gatta et al. describes that prematurity has a critical influence on interactive, communicative, and expressivechildbehaviour,particularlyduringthefirstyears
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