{
    "abstract": "Is morphologic development of the first-trimester utero-placental vasculature associated with embryonic growth and development, fetal growth, and birth weight percentiles?\nUsing the utero-placental vascular skeleton (uPVS) as a new imaging marker, this study reveals morphologic development of the first-trimester utero-placental vasculature is positively associated with embryonic growth and development, fetal growth, and birth weight percentiles.\nFirst-trimester development of the utero-placental vasculature is associated with placental function, which subsequently impacts embryonic and fetal ability to reach their full growth potential. The attribution of morphologic variations in the utero-placental vascular development, including the vascular structure and branching density, on prenatal growth remains unknown.\nThis study was conducted in the VIRTUAL Placental study, a subcohort of 214 ongoing pregnancies, embedded in the prospective observational Rotterdam Periconception Cohort (Predict study). Women were included before 10\u2009weeks gestational age (GA) at a tertiary referral hospital in The Netherlands between January 2017 and March 2018.\nWe obtained three-dimensional power Doppler volumes of the gestational sac including the embryo and the placenta at 7, 9, and 11\u2009weeks of gestation. Virtual Reality-based segmentation and a recently developed skeletonization algorithm were applied to the power Doppler volumes to generate the uPVS and to measure utero-placental vascular volume (uPVV). Absolute vascular morphology was quantified by assigning a morphologic characteristic to each voxel in the uPVS (i.e. end-, bifurcation-crossing-, or vessel point). Additionally, total vascular length (mm) was calculated. The ratios of the uPVS characteristics to the uPVV were calculated to determine the density of vascular branching. Embryonic growth was estimated by crown-rump length and embryonic volume. Embryonic development was estimated by Carnegie stages. Fetal growth was measured by estimated fetal weight in the second and third trimester and birth weight percentiles. Linear mixed models were used to estimate trajectories of longitudinal measurements. Linear regression analysis with adjustments for confounders was used to evaluate associations between trajectories of the uPVS and prenatal growth. Groups were stratified for conception method (natural/IVF-ICSI conceptions), fetal sex (male/female), and the occurrence of placenta-related complications (yes/no).\nIncreased absolute vascular morphologic development, estimated by positive random intercepts of the uPVS characteristics, is associated with increased embryonic growth, reflected by crown-rump length (endpoints \u03b2\u2009=\u20090.017, 95% CI [0.009; 0.025], bifurcation points \u03b2\u2009=\u20090.012, 95% CI [0.006; 0.018], crossing points \u03b2\u2009=\u20090.017, 95% CI [0.008; 0.025], vessel points \u03b2\u2009=\u20090.01, 95% CI [0.002; 0.008], and total vascular length \u03b2\u2009=\u20090.007, 95% CI [0.003; 0.010], and similarly with embryonic volume and Carnegie stage, all P-values\u2009\u2264\u20090.01. Density of vascular branching was negatively associated with estimated fetal weight in the third trimester (endpoints: uPVV \u03b2 = -94.972, 95% CI [-185.245; -3.698], bifurcation points: uPVV \u03b2 = -192.601 95% CI [-360.532; -24.670]) and birth weight percentiles (endpoints: uPVV \u03b2 = -20.727, 95% CI [-32.771; -8.683], bifurcation points: uPVV \u03b2 -51.097 95% CI [-72.257; -29.937], and crossing points: uPVV \u03b2 = -48.604 95% CI [-74.246; -22.961])), all P-values\u2009<\u20090.05. After stratification, the associations were observed in natural conceptions specifically.\nAlthough the results of this prospective observational study clearly demonstrate associations between first-trimester utero-placental vascular morphologic development and prenatal growth, further research is required before we can draw firm conclusions about a causal relationship.\nOur findings support the hypothesis that morphologic variations in utero-placental vascular development play a role in the vascular mechanisms involved in embryonic and fetal growth and development. Application of the uPVS could benefit our understanding of the pathophysiology underlying placenta-related complications. Future research should focus on the clinical applicability of the uPVS as an imaging marker for the early detection of fetal growth restriction.\nThis research was funded by the Department of Obstetrics and Gynecology of the Erasmus MC, University Medical Centre, Rotterdam, The Netherlands. There are no conflicts of interest.\nRegistered at the Dutch Trial Register (NTR6854).",
    "authors": [
        {
            "affiliation": "Department of Obstetrics and Gynecology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.",
            "firstname": "E S",
            "initials": "ES",
            "lastname": "De Vos"
        },
        {
            "affiliation": "Department of Obstetrics and Gynecology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.",
            "firstname": "A G M G J",
            "initials": "AGMGJ",
            "lastname": "Mulders"
        },
        {
            "affiliation": "Department of Pathology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.",
            "firstname": "A H J",
            "initials": "AHJ",
            "lastname": "Koning"
        },
        {
            "affiliation": "Department of Obstetrics and Gynecology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.\nDepartment of Biostatistics, Erasmus MC University Medical Center, Rotterdam, The Netherlands.",
            "firstname": "S P",
            "initials": "SP",
            "lastname": "Willemsen"
        },
        {
            "affiliation": "Department of Obstetrics and Gynecology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.",
            "firstname": "M",
            "initials": "M",
            "lastname": "Rousian"
        },
        {
            "affiliation": "Department of Obstetrics and Gynecology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.",
            "firstname": "B B",
            "initials": "BB",
            "lastname": "Van Rijn"
        },
        {
            "affiliation": "Department of Obstetrics and Gynecology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.",
            "firstname": "E A P",
            "initials": "EAP",
            "lastname": "Steegers"
        },
        {
            "affiliation": "Department of Obstetrics and Gynecology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.",
            "firstname": "R P M",
            "initials": "RPM",
            "lastname": "Steegers-Theunissen"
        }
    ],
    "conclusions": null,
    "copyrights": "\u00a9 The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.",
    "doi": "10.1093/humrep/deae056",
    "journal": "Human reproduction (Oxford, England)",
    "keywords": [
        "3D",
        "early pregnancy",
        "fetal growth restriction",
        "placenta",
        "power Doppler",
        "prenatal growth",
        "spiral artery",
        "ultrasound",
        "vascular morphology",
        "virtual reality"
    ],
    "methods": null,
    "publication_date": "2024-03-20",
    "pubmed_id": "38503486\n28613398\n25152565\n29221766\n20123792\n26179828\n21094932\n15350246\n29422210\n19375795\n33099621\n35378370\n20004469\n19948659\n23219036\n31730305\n36125007\n32107757\n19844898\n26909664\n3881966\n25287859\n27255904\n34167152\n29701150\n24458585\n29955830\n12507895\n11106583\n25145956\n12620937\n35846290\n15752534\n30792696\n34203717\n20185898\n29277277\n33823358\n24798392\n27071962\n29409677\n34097026\n31485310\n29622278\n29959621\n23959022\n26224071\n30137229\n32421528\n24339044\n18296447\n29779863\n27510415\n27685026\n32319609",
    "results": null,
    "title": "Morphologic development of the first-trimester utero-placental vasculature is positively associated with embryonic and fetal growth: the Rotterdam Periconception Cohort.",
    "xml": "<Element 'PubmedArticle' at 0x788502d46f70>"
}