New imaging markers for preconceptional and first-trimester utero-placental vascularization

Introduction: The availability of imaging makers of early placental circulation development is limited. This study aims to develop a reliable and accurate method to assess preconceptional and early first-trimester utero-placental vascular volumes using three-dimensional power Doppler ultrasound (3D PD US) on two different Virtual Reality (VR) systems. Methods: 3D PD US images of the uterine and placental vasculature were obtained in 35 women, either preconceptionally (n=5), or during pregnancy at 7 (n=10), 9 (n=10) or 11 (n=10) weeks of gestation. Preconceptional uterine vascular volume (UVV), and first-trimester placental vascular volume (PVV) and embryonic vascular volume (EVV) were measured by two observers on two VR systems, i.e., a Barco I-Space and VR desktop. Intra- and inter-observer agreement and intersystem agreement were assessed by intra-class correlation coefficients (ICC) and absolute and relative differences. Results: Uterine- , fetal- and placental vascular volume measurements showed good to excellent intra- and inter-observer agreement and inter-system reproducibility with most ICC above 0.80 and relative differences of less than 20% preconceptionally and almost throughout the entire gestational age range. Inter-observer agreement of PVV at 11 weeks gestation was suboptimal (ICC 0.69, relative difference 50.1%). Discussion: Preconceptional and first-trimester 3D PD US utero-placental and fetal vascular volume measurements using VR are feasible and reliable. Longitudinal cohort studies with repeated measurements are needed to further validate these this and assess their value as new imaging markers for placental vascular development and ultimately for the prediction of placenta-related pregnancy complications.This research was funded by the Department of Obstetrics and Gynecology of the Erasmus MC, University Medical Centre, Rotterdam, The Netherlands

Morphologic development of the first-trimester utero-placental vasculature is positively associated with embryonic and fetal growth:the Rotterdam Periconception Cohort

STUDY QUESTION: Is morphologic development of the first-trimester utero-placental vasculature associated with embryonic growth and development, fetal growth, and birth weight percentiles?SUMMARY ANSWER: Using 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. WHAT IS KNOWN ALREADY: First-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. STUDY DESIGN, SIZE, DURATION: This 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 weeks gestational age (GA) at a tertiary referral hospital in The Netherlands between January 2017 and March 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS: We obtained three-dimensional power Doppler volumes of the gestational sac including the embryo and the placenta at 7, 9, and 11 weeks 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). MAIN RESULTS AND THE ROLE OF CHANCE: Increased 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 β = 0.017, 95% CI [0.009; 0.025], bifurcation points β = 0.012, 95% CI [0.006; 0.018], crossing points β = 0.017, 95% CI [0.008; 0.025], vessel points β = 0.01, 95% CI [0.002; 0.008], and total vascular length β = 0.007, 95% CI [0.003; 0.010], and similarly with embryonic volume and Carnegie stage, all P-values ≤ 0.01. Density of vascular branching was negatively associated with estimated fetal weight in the third trimester (endpoints: uPVV β = -94.972, 95% CI [-185.245; -3.698], bifurcation points: uPVV β = -192.601 95% CI [-360.532; -24.670]) and birth weight percentiles (endpoints: uPVV β = -20.727, 95% CI [-32.771; -8.683], bifurcation points: uPVV β -51.097 95% CI [-72.257; -29.937], and crossing points: uPVV β = -48.604 95% CI [-74.246; -22.961])), all P-values &lt; 0.05. After stratification, the associations were observed in natural conceptions specifically.LIMITATION, REASONS FOR CAUTION: Although 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. WIDER IMPLICATIONS OF THE FINDINGS: Our 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. STUDY FUNDING/COMPETING INTEREST(S): This 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. TRIAL REGISTRATION NUMBER: Registered at the Dutch Trial Register (NTR6854).</p

The Edge of Perinatal Viability:Understanding the Dutch Position

Contains fulltext : 231104.pdf (publisher's version ) (Open Access

Intrauterine exposure to mild analgesics during pregnancy and the occurrence of cryptorchidism and hypospadia in the offspring: The Generation R Study

This article is available open access through the publisher’s website. Copyright @ 2012 The Authors.BACKGROUND - Recently, over-the-counter mild analgesic use during pregnancy has been suggested to influence the risk of reproductive disorders in the offspring. We examined the influence of maternal exposure to mild analgesics during pregnancy on the occurrence of cryptorchidism and hypospadia in their offspring. METHODS - Associations between maternal exposure to mild analgesics during pregnancy and cryptorchidism or hypospadia in the offspring were studied in 3184 women participating in a large population-based prospective birth cohort study from early pregnancy onwards in the Netherlands (2002–2006), the Generation R Study. Cryptorchidism and hypospadia were identified during routine screening assessments performed in child health care centres by trained physicians. The use of mild analgesics was assessed in three prenatal questionnaires in pregnancy, resulting in four periods of use, namely, periconception period, first 14 weeks of gestation, 14–22 weeks of gestation and 20–32 weeks of gestation. Logistic regression analyses were used to study the associations between maternal exposure to mild analgesics and cryptorchidism and hypospadia. RESULTS - The cumulative prevalence over 30 months of follow up was 2.1% for cryptorchidism and 0.7% for hypospadia. Use of mild analgesics in the second period of pregnancy (14–22 weeks) increased the risk of congenital cryptorchidism [adjusted odds ratio (OR) 2.12; 95% confidence interval (CI) 1.17–3.83], primarily due to the use of acetaminophen (paracetamol) (adjusted OR 1.89; 95% CI 1.01–3.51). Among mothers of cryptorchid sons, 33.8% reported (23 of 68) the use of mild analgesics during pregnancy, compared with 31.8% (7 of 22) of mothers with a boy with hypospadia and 29.9% (926 of 3094) of mothers with healthy boys. CONCLUSIONS - Our results suggest that intrauterine exposure to mild analgesics, primarily paracetamol, during the period in pregnancy when male sexual differentiation takes place, increases the risk of cryptorchidism.Erasmus University Rotterdam, School of Law and Faculty of Social Sciences, the Municipal Health Service Rotterdam area, Rotterdam, the Rotterdam Homecare Foundation, Rotterdam and the Stichting Trombosedienst & Artsenlaboratorium Rijnmond (STAR), Rotterdam

De psychometrische eigenschappen van de ReproQuestionnaire

__Abstract__ De organisatie van de geboortezorg is in beweging. Er zijn nieuwe samenwerkingsvormen, er zijn nieuwe risicobenaderingen, nieuwe verdelingen van taken en andere settings van bevallingszorg. Sommige disciplines zoals de huisarts hebben een steeds kleinere rol, andere zoals de klinisch-verloskundigen een steeds grotere. Er is geen masterplan van verandering, en er heerst op onderdelen verscheidenheid van opvatting over de wenselijke richting. Al deze veranderingen zijn - naar men stelt - gericht op het verbeteren van de kwaliteit van zorg. Hiermee wordt niet alleen het terugdringen van de perinatale sterfte (‘baby-sterfte’) beoogd, maar ook het verbeteren van de onderlinge samenwerking, met name, tussen eerstelijns verloskundigen en gynaecologen, en het realiseren van zorg die de zwangere als cliënt centraal stelt. Er is weinig informatie bekend over de huidige proceskwaliteit van de Nederlandse geboortezorg, mede door het ontbreken van daartoe geëigende lijnoverstijgende instrumenten. Kwaliteitsindicatoren zijn momenteel primair harde uitkomstindicatoren ontleend aan informatie uit zorgregistraties zoals de PRN. Deze geven wel een beeld van de medische uitkomsten, van sommige procedures, en van de belangrijkste bevallingsinterventies, maar niet van de cliëntervaringen met de zorgverlening, en ook niet van de subjectief ervaren uitkomst van c.q. bij moeder en kind. Proceskwaliteit kan men benaderen vanuit de professional bijvoorbeeld aan de hand van richtlijnen of het realiseren van procesdoelen zoals bij risicoselectie, maar dat is een ander perspectief dan de proceskwaliteit vanuit het cliëntperspectief. Ongeacht de vraag wie de zorg verleende, en los van de vraag of alle richtlijnen in acht werden genomen, is namelijk van belang of de cliënte in haar eigen ogen respect en bejegening ontving, of de communicatie in orde was, en of faciliteiten voldeden. Een en ander vraagt zorgvuldig ontwerp van vragenlijsten omdat alle betrokken professionals zeggen vanuit het cliëntperspectief te werken. Vaak, zo is ons gebleken, doelen professionals dan op het volgen van gedragsregels en richtlijnen zoals de beroepsorganisaties die aan hun leden voorschrijven. Het cliëntperspectief doet niets af aan dit professioneel perspectief, en een eindoordeel over de zorg kan ook niet zonder harde uitkomsten en procedure kwaliteit worden geveld, maar het cliëntperspectief vraagt niettemin een ander type vragen

New imaging markers for preconceptional and first-trimester utero-placental vascularization

INTRODUCTION: The availability of imaging makers of early placental circulation development is limited. This study aims to develop a feasible and reliable method to assess preconceptional and early first-trimester utero-placental vascular volumes using three-dimensional power Doppler (3D PD) ultrasound on two different Virtual Reality (VR) systems. METHODS: 3D PD ultrasound images of the uterine and placental vasculature were obtained in 35 women, either preconceptionally (n = 5), or during pregnancy at 7 (n = 10), 9 (n = 10) or 11 (n = 10) weeks of gestation. Preconceptional uterine vascular volume (UVV), first-trimester placental vascular volume (PVV) and embryonic vascular volume (EVV) were measured by two observers on two VR systems, i.e., a Barco I-Space and VR desktop. Intra- and inter-observer agreement and intersystem agreement were assessed by intra-class correlation coefficients (ICC) and absolute and relative differences. RESULTS: Uterine-, embryonic- and placental vascular volume measurements showed good to excellent intra- and inter-observer agreement and inter-system reproducibility with most ICC above 0.80 and relative differences of less than 20% preconceptionally and almost throughout the entire gestational age range. Inter-observer agreement of PVV at 11 weeks gestation was suboptimal (ICC 0.69, relative difference 50.1%). DISCUSSION: Preconceptional and first-trimester 3D PD ultrasound utero-placental and embryonic vascular volume measurements using VR are feasible and reliable. Longitudinal cohort studies with repeated measurements are needed to further validate this and assess their value as new imaging markers for placental vascular development and ultimately for the prediction of placenta-related pregnancy complications