Research ArticleInfluence of the Umbilical Cord Insertion Site onthe Optimal Individual Birth Weight AchievementSophie Brouillet,1,2,3,4Ana\s Dufour,1Fabien Prot,1Jean-Jacques Feige,2,3,4Vronique Equy,1Nadia Alfaidy,2,3,4Pierre Gillois,3,5and Pascale Hoffmann1,2,3,41Gynaecology, Obstetric and Reproductive Medicine Department, Grenoble University Hospital, BP 217,38043 Grenoble Cedex, France2Commissariat ` a lEnergie Atomique (CEA), DSV-iRTSV, 38043 Grenoble Cedex, France3Universit e Grenoble-Alpes, 38041 Grenoble, France4Institut National de la Sant e et de la Recherche M edicale U1036 (INSERM U1036), Laboratoire Biologie du Cancer etde lInfection (BCI), Laboratoire BCI-iRTSV, CEA Grenoble, 17 rue des Martyrs, 38054 Grenoble Cedex 9, France5UJF-Grenoble 1, CNRS, TIMC-IMAG UMR 5525, Temas, 38041 Grenoble, FranceCorrespondence should be addressed to Sophie Brouillet; sophie brouillet@yahoo.frReceived 8 February 2014; Revised 27 April 2014; Accepted 30 April 2014; Published 25 May 2014Academic Editor: Andrew HorneCopyright 2014 Sophie Brouillet et al. Tis is anopenaccess article distributed under the Creative Commons AttributionLicense,which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Study Question. To determine whether the umbilical cord insertion site of singleton pregnancies could be linked to the newbornbirth weight at term and its individual growth potential achievement. Material and Methods. A cohort study including 528 recordsof term neonates was performed. Each neonate was assessed for growth adjusted for gestational age according to the infantsgrowth potential using the AUDIPOG module. We considered two categories of umbilical cord insertions: central and peripheral.Intrauterine growth restriction was defned as birth weight below the 10th percentile. Statistical analysis was performed usingChi-square, Students t test, Wilcoxon test, ANOVA, and logistic regression. Results. We observed a total of 343 centrally insertedcords versus 185 peripheral cords. Tere were twice as many smokers in the mothers of the peripheral category compared to thecentrally inserted ones. More importantly, we demonstrated that only 17/343 (5.0%) of infants with central cord insertion weregrowth restricted, compared to 37/185 (20.0%) of the infants born with a peripheral insertion. Neonates with centrally inserted cordwere signifcantly heavier. Conclusion. Te umbilical cord insertion site of singleton pregnancies is associated with the newbornsbirth weight at term and its individual growth potential achievement.1. IntroductionFetal growth is characterized by its genetically predeterminedgrowth potential; however, it is further modulated by mater-nal, fetal, placental, and environmental factors [1, 2]. Hostilecircumstances canthreat theachievement of thegrowthpotential of the fetus throughout pregnancy [2]. Limitationsof fetal growthpotential areknowntoleadtoavarietyof adverse perinatal andadult conditions, rangingfromstillbirth to chronic diseases in adulthood [35]. Adequategrowth of the fetus throughout pregnancy is highly depen-dent on the normal development of the umbilical cord (UC),a structure that connects the growing embryo to its placentaby the third week of gestation [6, 7]. Te UC ensures oxygenandnutrient suppliestothefetusthroughout pregnancy.During the last decades, numerous studies have highlightedthat UC insertion site could be relevant in obstetrics as itsabnormalpositioning has been associated with numerouscomplications of pregnancy, including preterm delivery, lowbirth weight, growth restriction, stillbirth, increased rate ofemergency caesarean section, and low Apgar scores [712].Te UC insertion site can be subdivided into four cat-egories: central, paracentral, marginal/battledore, and vela-mentous/membranous.Te central/paracentralcategory isHindawi Publishing CorporationBioMed Research InternationalVolume 2014, Article ID 341251, 8 pageshttp://dx.doi.org/10.1155/2014/3412512 BioMed Research Internationalconsidered as the normal condition. It is well accepted thatUC insertion is considered aberrant when attached at theedge of the placental disk (marginal/battledore) or when itis inserted into the chorioamniotic membranes (velamen-tous/membranous), which ofen leads to fetal death [8, 1315]. Recent reportssuggestedthat aperipherallyinsertedUCmight alsobeassociatedwithpregnancypathologies[16]. Although noncentral cord insertion is more frequentintwinpregnancies, singletons are alsoconcernedwithan approximate frequency of 7% for marginal and 1% forvelamentous insertion [17].Teetiologyofnoncentral cordinsertionisnotclearand it is probably infuenced by many factors. Tree theorieshave been proposed: frst is the blastocyst polarity theory,which hypothesizes that aberrant insertion site results frommalpositioning of the blastocyst during implantation, withconsequent defective placental diskorientation[18]; thesecond is the abnormal placental development because ofdecreased chorionic vessel branching theory, which positsthat noncentral insertionresultsfromabnormal vasculo-genesisintheplacenta[1921]; andthethirdoneisthetrophotropism/placental migration theory, which proposesthat aberrant insertion develops later on during pregnancywhen the placenta migrates toward sites of optimal perfusion[8]. Because of the early appearance of abnormal cord inser-tion during pregnancy, the latter theory has been excluded[20, 22].Noncentral cord insertion is closely associated with earlyimpaireddevelopmentandfunctionoftheplacenta, sug-gesting genetic and/or environmental associated mechanisms[6, 23]. Fetal growth is dependent on oxygen and nutrient-transfer capacity of the placenta, which is highly associatedwith the vascular network development within the chorionicvilli. Abnormal umbilical cord insertion is associated withsmaller placenta [23] and lower placental vessel density [24].Teplacental insufciencyaccompanyingabnormal cordinsertionmayincreasethesusceptibilitytoperinatal riskofenassociatedwiththeseconditions[25, 26]. Wethushypothesize that optimal placentation will result in a centralinsertionof theumbilical cordwhichinturnallows anoptimal growth of the fetus throughout gestation. Terefore,the aim of the present study was to examine if the site ofumbilical cordinsertionwithintheplacentaof singletonpregnancies could be correlated to the newborn birth weightat term and to its individual growth potential achievement.2. Material and MethodsAcohort study, including 603 consecutive singletondeliveriesafer 36 weeks of gestation (WG), from August 1, 2006, toDecember 31, 2006, was performed at the Grenoble Univer-sity Hospital, Maternity Clinic. Neonates with malformations(36/75)andincompletefles(39/75)wereexcluded( =75, 12.4%). Atotal of 528fleswereevaluated(Figure 1).Te data were then collected from the computerized fles.Te maternal data collected included ethnicity (Caucasian,North African, African, or Asian), age, prepregnancy bodymass index (BMI), tobacco use, spontaneous frst trimesterpregnancy loss records, uterine anomalies such as myomas,andprepregnancyhealthstatus infuencingfetal growth(i.e., hypertension, autoimmunediseases, cardiomyopathy,diabetes,renalimpairment,parity,and pregnancy pathol-ogy, suchasgestational diabetes, preeclampsia/eclampsia,anaemia, andobstetriccholestasis). Teselectedneonatalitemswereasfollows: gestational ageat birth(indays),babys gender, size, andweight, andcordinsertionsite.Two categories were used: central insertion and peripheralinsertion (paracentral, battledore, and velamentous). CentralUCwas defnedasUCinsertionnearthecenterof theplacenta (i.e., less than 3 cm from the center). ParacentralUCwasdefnedasinsertionof theUCmorethan3 cmfromthe center andmore than2 cmfromthe nearestmargin. Marginal UC insertion was defned within 2 cm ofthediscsedge, whereasvelamentousinsertionrepresentsanUCinsertiondirectlyintothemembranes. Eachnewborn was individually assessed for growth and adjusted toits gestational age according to the infants growth potential.Tis was performed based on AUDIPOG online fetal growthassessment module(AUDIPOGAssociationof Users ofComputerizedMedical RecordsinPaediatrics, Obstetricsand Gynaecologyhttp://www.audipog.net/) [27, 28]. TisFrench module takes into account maternalage,prepreg-nancy BMI, birthrank, newborngender, gestational age, birthweight, and length to predict the individual infants geneticgrowth potential [2730]. From a sample of 43,654 infantsfrom the AUDIPOG database,two statistical models gaveindividualized limits of birth weight and birth length belowwhich, afer adjustment for its individual growth potential,anewbornmustbeconsideredasFGRinweightand/orin length. Tis new approach has been validated in severalpublications [2730] andallows classifying some newborns asconstitutionally small due to their lowgrowth potential andidentifying newborns with fetal growth restriction (FGR). Inthis study, we used the individualized limits of birth weightto identify newborns with FGR. Once the infants estimatedpersonal percentile is calculated with AUDIPOGcurves, eachneonate is classifed under three categories: growth restricted(less than the 10th percentile, with severe growth restrictionbelowthe3rdpercentile), appropriateforgestational age(from the 10th percentile to the 90th percentile), or large forgestational age (over the 90th percentile).Variables were described as mean and standard deviationfor continue quantitative data, number and proportion forqualitativedata, andmedianandinterquartilerangefordiscrete quantitative data. Te normality was checked withhistogramof the sample data, also with skewness and kurtosisstandardized moments (age and size) and with the ShapiroWilk normality test (birth weight).Te nonnormal initialdistribution (BMI and weight) was transformed with a logfunction. Te analyses with nonnormal distribution (parity)were switched to nonparametric test, as Wilcoxon test. Stu-dents -test was appropriate for categorical and continuousdata. Chi-square test was appropriate for categorical data. Weperformed multivariate ANOVA (umbilical cord insertionsite and tobacco) and logistic regression modeling for fetalgrowth restriction explained by tobacco and umbilical cordinsertion site in the model, both of themwith interaction. TeOR and 95 IC for each factor were performed.BioMed Research International 3603 consecutive singleton deliveriesafer 36 weeks of gestation528 singleton deliveries343 (60%) central umbilical cords75 not includedfor exclusion criteria(36/75 for neonates malformations/39/75 for missing data)185 (40%) outlying umbilical cords37/185 (20.0%) growth restriction137/185 (74.0%) appropriate growth11/185 (6%) overgrowth17/343 (5.0%) growth restriction300/343 (87.4%) appropriate growth26/343 (7.6%) overgrowth(with 136 (73%) paracentral, 44 (24%) battledore insertion, and 5 (3%) velamentous insertion)Figure 1: Flowchart of the study group.A value