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

Towards segmentation and spatial alignment of the human embryonic brain using deep learning for atlas-based registration

We propose an unsupervised deep learning method for atlas based registration to achieve segmentation and spatial alignment of the embryonic brain in a single framework. Our approach consists of two sequential networks with a specifically designed loss function to address the challenges in 3D first trimester ultrasound. The first part learns the affine transformation and the second part learns the voxelwise nonrigid deformation between the target image and the atlas. We trained this network end-to-end and validated it against a ground truth on synthetic datasets designed to resemble the challenges present in 3D first trimester ultrasound. The method was tested on a dataset of human embryonic ultrasound volumes acquired at 9 weeks gestational age, which showed alignment of the brain in some cases and gave insight in open challenges for the proposed method. We conclude that our method is a promising approach towards fully automated spatial alignment and segmentation of embryonic brains in 3D ultrasound

A common genetic variant at 15q25 modifies the associations of maternal smoking during pregnancy with fetal growth: The generation r study

Objective: Maternal smoking during pregnancy is associated with fetal growth retardation. We examined whether a common genetic variant at chromosome 15q25 (rs1051730), which is known to be involved in nicotine metabolism, modifies the associations of maternal smoking with fetal growth characteristics. Methods: This study was performed in 3,563 European mothers participating in a population-based prospective cohort study from early pregnancy onwards. Smoking was assessed by postal questionnaires and fetal growth characteristics were measured by ultrasound examinations in each trimester of pregnancy. Results: Among mothers who did not smoke during pregnancy (82.9%), maternal rs1051730 was not consistently associated with any fetal growth characteristic. Among mothers who continued smoking during pregnancy (17.1%), maternal rs1051730 was not associated with head circumference. The T-allele of maternal rs1051730 was associated with a smaller second and third trimester fetal femur length [differences -0.23 mm (95%CI -0.45 to -0.00) and -0.41 mm (95%CI -0.69 to -0.13), respectively] and a smaller birth length [difference -2.61 mm (95%CI -5.32 to 0.11)]. The maternal T-allele of rs1051730 was associated with a lower third trimester estimated fetal weight [difference -33 grams (95%CI -55 to -10)], and tended to be associated with birth weight [difference -38 grams (95%CI -89 to 13)]. This association persisted after adjustment for smoking quantity. Conclusions: Our results suggest that maternal rs1051730 genotype modifies the associations of maternal smoking during pregnancy with impaired fetal growth in length and weight. These results should be considered as hypothesis generating and indicate the need for large-scale genome wide association studies focusing on gene - fetal smoke exposure interactions

The Association of Neighborhood Social Capital and Ethnic (Minority) Density with Pregnancy Outcomes in the Netherlands

Background: Perinatal morbidity rates are relatively high in the Netherlands, and significant inequalities in perinatal morbidity and mortality can be found across neighborhoods. In socioeconomically deprived areas, ‘Western’ women are particularly at risk for adverse birth outcomes. Almost all studies to date have explained the disparities in terms of individual determinants of birth outcomes. This study examines the influence of neighborhood contextual characteristics on birth weight (adjusted for gestational age) and preterm birth. We focused on the influence of neighborhood social capital – measured as informal socializing and social connections between neighbors – as well as ethnic (minority) density. Methods: Data on birth weight and prematurity were obtained from the Perinatal Registration Netherlands 2000–2008 dataset, containing 97% of all pregnancies. Neighborhood-level measurements were obtained from three different sources, comprising both survey and registration data. We included 3.422 neighborhoods and 1.527.565 pregnancies for the birth weight analysis and 1.549.285 pregnancies for the premature birth analysis. Linear and logistic multilevel regression was performed to assess the associations of individual and neighborhood level variables with birth weight and preterm birth. Results: We found modest but significant neighborhood effects on birth weight and preterm births. The effect of ethnic (minority) density was stronger than that of neighborhood social capital. Moreover, ethnic (minority) density was associated with higher birth weight for infants of non-Western ethnic minority women compared to Western women (15 grams; 95% CI: 12,4/17,5) as well as reduced risk for prematurity (OR 0.97; CI 0,95/0,99). Conclusions: Our results indicate that neighborhood contexts are associated with birth weight and preterm birth in the Netherlands. Moreover, ethnic (minority) density seems to be a protective factor for non-Western ethnic minority women, but not for Western women. This helps explain the increased risk of Western women in deprived neighborhoods for adverse birth outcomes found in previous studies

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

Sublingual sufentanil for postoperative pain relief: First clinical experiences

Background: The sublingual sufentanil tablet system (SSTS) is a novel hand-held patientcontrolled analgesia device developed for treatment of moderate-to-severe postoperative pain. Here we present the first results of its clinical use. Methods: Adult patients undergoing major surgery in five hospitals in the Netherlands received the SSTS for postoperative pain relief as part of multimodal pain management that further included paracetamol and a nonsteroidal anti-inflammatory drug (NSAID). The following variables were collected: postoperative pain scores using the 11-point numerical rating score (NRS) at rest, number of tablets used, occurrence of nausea, and patient satisfaction scores. Results: We included 280 patients in the study; the majority underwent laparoscopic abdominal (49%) or orthopedic (knee replacement) surgery (34%). The median NRS was 3.5 (interquartile range 2.3–4.0) on the day of surgery, 3.3 (2.3–4.0) on the first postoperative day, and 2.8 (2.0–4.0) on the second postoperative day; pain scores did not differ between surgery types. Mean number of tablets used was 19 (range 0–86). Nausea occurred in 34% of patients, more often in women (45% vs 19%). Overall satisfaction was high in 73% of patients. Satisfaction was correlated with pain relief (p < 0.001) and inversely correlated with occurrence of nausea (p=0.01). Discussion: In this data set obtained under real-life conditions we show that the SSTS effectively managed postoperative pain in abdominal and orthopedic surgeries. Future studies should determine patient populations that benefit most from the SSTS, assess the added values versus intravenous patient-controlled analgesia, and determine the pharmacoeconomics of the system

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

Risk factors and outcomes associated with first-trimester fetal growth restriction

Context: Adverse environmental exposures lead to developmental adaptations in fetal life. The influences of maternal physical characteristics and lifestyle habits on first-trimester fetal adaptations and the postnatal consequences are not known. Objective: To determine the risk factors and outcomes associated with firsttrimester growth restriction. Design, Setting, and Participants: Prospective evaluation of the associations of maternal physical characteristics and lifestyle habits with first-trimester fetal crown to rump length in 1631 mothers with a known and reliable first day of their last menstrual period and a regular menstrual cycle. Subsequently, we assessed the associations of first-trimester fetal growth restriction with the risks of adverse birth outcomes and postnatal growth acceleration until the age of 2 years. The study was based in Rotterdam, the Netherlands. Mothers were enrolled between 2001 and 2005. Main Outcome Measures: First-trimester fetal growth was measured as fetal crown to rump length by ultrasound between the gestational age of 10 weeks 0 days and 13 weeks 6 days. Main birth outcomes were preterm birth (gestational age <37 weeks), low birth weight (<2500 g), and small size for gestational age (lowest fifth birth centile). Postnatal growth was measured until the age of 2 years. Results In the multivariate analysis, maternal age was positively associated with firsttrimester fetal crown to rump length (difference per maternal year of age, 0.79 mm; 95% confidence interval [CI], 0.41 to 1.18 per standard deviation score increase). Higher diastolic blood pressure and higher hematocrit levels were associated with a shorter crown to rump length (differences, -0.40 mm; 95% CI, -0.74 to -0.06 and -0.52 mm; 95% CI, -0.90 to -0.14 per standard deviation increase, respectively). Compared with mothers who were nonsmokers and optimal users of folic acid supplements, those who both smoked and did not use folic acid supplements had shorter fetal crown to rump lengths (difference, -3.84 mm; 95% CI, -5.71 to -1.98). Compared with normal first-trimester fetal growth, first-trimester growth restriction was associated with increased risks of preterm birth (4.0% vs 7.2%; adjusted odds ratio [OR], 2.12; 95% CI, 1.24 to 3.61), low birth weight (3.5% vs 7.5%; adjusted OR, 2.42; 95% CI, 1.41 to 4.16), and small size for gestational age at birth (4.0% vs 10.6%; adjusted OR, 2.64; 95% CI, 1.64 to 4.25). Each standard deviation decrease in firsttrimester fetal crown to rump length was associated with a postnatal growth acceleration until the age of 2 years (standard deviation score increase, 0.139 per 2 years; 95% CI, 0.097 to 0.181). Conclusions Maternal physical characteristics and lifestyle habits were independently associated with early fetal growth. First-trimester fetal growth restriction was associated with an increased risk of adverse birth outcomes and growth acceleration in early childhood

Associations of maternal and paternal blood pressure patterns and hypertensive disorders during pregnancy with childhood blood pressure

Background-Hypertensive disorders in pregnancy may affect the cardiovascular risk of offspring. We examined the associations of maternal blood pressure throughout pregnancy and hypertensive disorders in pregnancy with childhood blood pressure of offspring. Specific focus was on the comparison with paternal blood pressure effects, the identification of critical periods, and the role of birth outcomes and childhood body mass index in the observed associations. Methods and Results-This study was embedded in a population-based prospective cohort study among 5310 mothers and fathers and their children. We measured maternal blood pressure in each trimester of pregnancy and paternal blood pressure once. Information about hypertensive disorders in pregnancy was obtained from medical records. We measured childhood blood pressure at the median age of 6.0 years (95% range 5.7-8.0 years). Both maternal and paternal blood pressure were positively associated with childhood blood pressure (all P < 0.05), with similar effect estimates. Conditional regression analyses showed that early, mid-, and late-pregnancy maternal blood pressure levels were all independent and positively associated with childhood blood pressure, with the strongest effect estimates for early pregnancy. Compared with children of mothers without hypertensive disorders in pregnancy, children of mothers with hypertensive disorders in pregnancy had higher diastolic blood pressure by a standard deviation score of 0.13 (95% CI 0.05-0.21). The observed associations were not materially affected by birth outcomes and childhood body mass index. Conclusions-Both maternal and paternal blood pressure affects childhood blood pressure, independent of fetal and childhood growth measures, with the strongest effect of maternal blood pressure in early pregnancy