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

Artificial intelligence for automated detection of congenital brain anomalies in the first trimester:the Rotterdam Periconception Cohort

Here, we showed the first steps towards automatic detection of brain anomalies in first trimester pregnancies using 3D ultrasound images. The next step is to evaluate if the abnormal features correspond with the brain anomalies. In the future, we will extend this algorithm towards a broader age range and towards all anatomical structures to enable automated congenital anomaly screening during the first trimester

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

Maternal lifestyle risk factors and human embryonic morphologic development:the Generation R Next study

Inadequate folic acid supplement use is associated with decelerated embryonic development. This emphasises the importance of preconceptional counselling on healthy lifestyle choices to create an optimal environment for the developing embryo

Dutch trends in the use of potentially harmful medication during pregnancy

Aims: Recent population-based data on drug utilization around pregnancy are lacking. This study aims to examine the prevalence of drug exposure in the Netherlands during the preconception, pregnancy and postpartum periods, with special emphasis on trends of potentially harmful medication over the years. Methods: A population-based study was conducted using records from the PHARMO Perinatal Research Network. From 1999 to 2017, the proportion of pregnancies during which women used any medication or potentially harmful medication was assessed, overall and stratified by timing of exposure relative to pregnancy and by the year of delivery. Results: Overall, 357 226 (73%) and 166 484 (34%) of 487 122 selected pregnancies were exposed to any and potentially harmful medication, respectively. Among these 487 122 pregnancies, preconception prevalence for use of potentially harmful medication was 43%, 24% during the first trimester, 19% during the second, 16% during the third, and 45% postpartum. A declining trend was observed for exposure to any medication, from 84% in 1999 to 68% in 2017. No clear changes were observed over time for the proportion of pregnancies exposed to potentially harmful medication. Conclusions: Our study shows that the use of potentially harmful medication was high over the last two decades. Although there was a declining trend over the years in overall medication use, during a steady one-third of pregnancies, women used potentially harmful medication. Our findings highlight the need for an increased sense of urgency among both healthcare providers and women of reproductive age regarding potential risks associated with pharmacological treatment during pregnancy

The impact of maternal lifestyle factors on periconception outcomes: a systematic review of observational studies

The main risk factors for important reproductive health issues such as subfertility and perinatal mortality largely originate in the periconception period. To evaluate associations between modifiable maternal lifestyle factors and periconception outcomes, a systematic search was conducted for relevant studies published from 1990 to February 2017 on Embase, Medline, Web of Science, Cochrane database, PubMed and Google Scholar. The initial search identified 6166 articles, of which 49 studies were eligible for inclusion. Fecundity (the capacity to have a live birth) showed significant inverse associations with smoking, alcohol use and poor diet. Studies regarding time to pregnancy showed a decline in fecundity ratios (the monthly conception rate among exposed relative to unexposed couples) with increasing body mass index (BMI). Furthermore, risk of first-trimester miscarriage was found to be increased in smokers, alcohol and caffeine consumers, and with increasing BMI. Vitamin supplement use showed a decrease in this risk. This review demonstrates that maternal modifiable lifestyle factors affect periconception outcomes. If couples planning a pregnancy are more aware and supported to adopt healthy lifestyles during the periconceptional ‘window of opportunity’, short-term reproductive health as well as health in later life and even of future generations can be further improved

Perinatale gezondheid in Rotterdam; nulmeting periode 2000-2007

Inleiding Rotterdam heeft binnen Nederland een relatief hoog perinataal sterftecijfer. Onder perinatale sterfte verstaan we sterfte vanaf 22 weken zwangerschapsduur tot en met de eerste 7 dagen na de geboorte. Dit bleek reeds in 2008 toen De Graaf et al. beschreven dat vrouwen in de vier grote steden een sterk verhoogde kans hebben op perinatale sterfte en daarmee samenhangende perinatale ziekte. De belangrijkste vier perinatale ziekten, die vaak voorlopers zijn van perinatale sterfte, zijn aangeboren afwijkingen, vroeggeboorte, laag geboortegewicht gelet op de zwangerschapsduur, en een lage Apgar score (een slechte start bij de geboorte). In vervolg op de bevindingen voor Rotterdam is in 2008 het Aanvalsplan Perinatale Sterfte Rotterdam van start gegaan. Dit is een meerjarig programma waarin de Gemeente Rotterdam in samenwerking met het Erasmus MC en de GGD Rotterdam Rijnmond tot doel heeft de perinatale sterfte en perinatale ziekte binnen Rotterdam te verminderen. Een eerste stap hierbij is het nauwkeurig in kaart brengen van perinatale ziekten en sterfte, en de factoren die mogelijk hiervoor verantwoordelijk zijn. Deze factoren kunnen gebonden zijn aan zwangeren zelf, met hun omgeving te maken hebben of met de zorg te maken hebben

Planned home compared with planned hospital births: Mode of delivery and Perinatal mortality rates, an observational study

Background: To compare the mode of delivery between planned home versus planned hospital births and to determine if differences in intervention rates could be interpreted a