Growth Abnormalities of Fetuses and Infants

155 Pages·2017·11.87 MB·English

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