Implementation of aspirin use during pregnancy in community midwifery-led care in the Netherlands: A pilot survey.

INTRODUCTION: Aspirin nowadays is widely used in pregnancy, but implementation among gynecologists took nearly four decades. For a complete insight in the implementation of aspirin, community midwives are to be involved. Community midwives do not have authority to prescribe aspirin and have to refer to a general practitioner or consultant obstetrician for a prescription. METHODS: The study was an online, national pilot survey about the implementation of aspirin use during pregnancy among independently practicing community midwives consisting of 29 items with five categories: background, advising, prescribing, possible indications, and clinical practice. RESULTS: Forty-seven community midwives completed the survey between April and May 2021. All respondents had experience on advising aspirin use in pregnancy. History of preterm pre-eclampsia or HELLP syndrome was identified as a risk factor for developing utero-placental complications by 97.9% of the community midwives. Moderate risk factors in women with otherwise low-risk pregnancy were identified by >75% of the participants. Practical issues in prescribing aspirin were experienced by one-third of the respondents. Suggestions were made to obtain authority for community midwives to prescribe aspirin and improve collaboration with consultant obstetricians and general practitioners. CONCLUSIONS: Community midwives seem to be adequate in identifying risk factors for developing utero-placental complications in women with otherwise low-risk pregnancy. Practical issues for prescribing aspirin occur often. Obtaining authority for community midwives to prescribe aspirin after education should be considered and consulting a consultant obstetrician should become more accessible to overcome the practical issues. Further educating community midwives and general practitioners might improve implementation rates and perinatal outcomes.

Éléments de données communs pour l'arthrogrypose multiple congénitale: Un cadre international.

OBJECTIF: Afin de faciliter les études multisites et la recherche clinique d'envergure internationale, cette étude a pour but d'identifier des éléments de données communs (EDCs) normalisés et fondés sur un consensus pour l'arthrogrypose multiple congénitale (AMC). MÉTHODE: Une étude à méthodes mixtes comprenant plusieurs groupes de discussion et trois séries d'enquêtes Delphi modifiées pour parvenir à un consensus ont été menées. RÉSULTATS: Dans l'ensemble, 45 experts cliniques ainsi qu'adultes ayant une expérience vécue (dont 12 membres d'un consortium d'AMC) ont participé à cette étude à travers 11 pays en Amérique du Nord, Europe et Australie. Les EDCs comprennent 321 éléments de données et 19 mesures standardisées dans divers domaines, du développement du fœtus à l'âge adulte. Les éléments de données relatifs aux traits phénotypiques de l'AMC ont été cartographiés conformément à l'ontologie du phénotype humain (HPO). Une structure de gouvernance universelle, des protocoles de fonctionnement et des plans de développement durable ont été identifiés comme les principaux facilitateurs considérant que la capacité limitée de partage des données et la nécessité d'une infrastructure informatique fédérée étaient les principaux obstacles. INTERPRÉTATION: Une collecte de données systématiques sur l'AMC à l'aide d'EDCs permettra d'étudier sur les voies étiologiques, décrire le profil épidémiologique, et établir des corrélations génotype­phénotype de manière standardisée. Les EDCs proposés faciliteront les collaborations internationales multidisciplinaires en améliorant à grande échelle les études multicentriques, les possibilités de partage des données, ainsi que le transfert et la diffusion des connaissances.

Elementos de datos comunes para la artrogriposis múltiple congénita: Un marco internacional.

OBJETIVO: Para facilitar los estudios multicéntricos y la investigación clínica internacional, este estudio pretende identificar de forma consensuada los elementos de datos estandarizados para la artrogriposis múltiple congénita (AMC). MÉTODO: Estudio de métodos mixtos de grupos de discusión y tres rondas de encuestas Delphi modificadas para llegar a un consenso utilizando dos escalas de clasificación por niveles. RESULTADOS: En total, 45 expertos clínicos y adultos con experiencia vivida (incluidos 12 miembros de un consorcio de AMC) participaron en este estudio procedentes de 11 países: Norteamérica, Europa y Australia. Los CDEs incluyen 321 elementos de datos y 19 medidas estandarizadas en varios dominios desde el desarrollo fetal hasta la edad adulta. Los elementos de datos relativos a los rasgos fenotípicos del CDEs se mapearon de acuerdo con la Ontología de Fenotipos Humanos. Se identificaron como principales facilitadores la estructura de gobernanza universal, protocolos operados de forma local y los planes de sostenibilidad, mientras que los principales obstáculos observados son la capacidad limitada para compartir datos y la necesidad de una infraestructura informática federada. INTERPRETACIÓN: La recopilación de datos sistemáticos sobre la AMC mediante CDEs permitirá investigar las vías etiológicas, describir el perfil epidemiológico y establecer correlaciones genotipo­fenotipo de forma estandarizada. Los CDEs propuestos facilitarán las colaboraciones multidisciplinares internacionales mejorando los estudios a gran escala y las oportunidades para compartir datos, translación de conocimiento y difusión.

The value of a mobile educative Application additional to Standard counselling on aspirin Adherence in Pregnancy: the ASAP study, a randomised controlled trial.

Objective: To assess the added value of a novel, mobile educative application to standard counselling on aspirin adherence during pregnancy versus standard counselling alone. Methods: Participants were randomly assigned for additional use of a mobile educative application or standard counselling alone. Main outcome measures were adherence to aspirin measured by two validated questionnaires: Simplified Medication Adherence Questionnaire (SMAQ), Believes and Behaviour Questionnaire (BBQ), and patients reported tablet intake >90%. Results: A total of 174 women with an indication for aspirin during pregnancy were included. The questionnaires were filled in by 126 out of the 174 participants (72.4%). Similar results were found in the app group and the standard counselling groups for both validated questionnaires. Tablet intake >90% was seen in 88.7% and 87.5% (p = 0.834) of the app group and standard counselling group respectively. Subgroup analyses demonstrated a negative effect of BMI and a positive effect of educational level on adherence. Conclusions: Our study revealed no added effect of a novel, mobile educative application to standard counselling on aspirin adherence during pregnancy. Tablet intake was equally high in both groups probably explained by our high educated population. Innovation: Future studies should focus on tailored counselling on medication to pregnant women's needs including medication reminders, addressing concerns, adequate health literacy and side effects, offering rewards to further stimulate aspirin adherence in pregnancy with optimal outcome for mother and their neonate.

Common data elements for arthrogryposis multiplex congenita: An international framework.

AIM: To facilitate multisite studies and international clinical research, this study aimed to identify consensus-based, standardized common data elements (CDEs) for arthrogryposis multiplex congenita (AMC). METHOD: A mixed-methods study comprising of several focus group discussions and three rounds of modified Delphi surveys to achieve consensus using two tiered-rating scales were conducted. RESULTS: Overall, 45 clinical experts and adults with lived experience (including 12 members of an AMC consortium) participated in this study from 11 countries in North America, Europe, and Australia. The CDEs include 321 data elements and 19 standardized measures across various domains from fetal development to adulthood. Data elements pertaining to AMC phenotypic traits were mapped according to the Human Phenotype Ontology. A universal governance structure, local operating protocols, and sustainability plans were identified as the main facilitators, whereas limited capacity for data sharing and the need for a federated informatics infrastructure were the main barriers. INTERPRETATION: Collection of systematic data on AMC using CDEs will allow investigations on etiological pathways, describe epidemiological profile, and establish genotype-phenotype correlations in a standardized manner. The proposed CDEs will facilitate international multidisciplinary collaborations by improving large-scale studies and opportunities for data sharing, knowledge translation, and dissemination.

Systemic lupus erythematosus is associated with an increased frequency of spontaneous preterm births: systematic review and meta-analysis.

OBJECTIVE: Preterm birth is one of the most frequent complications of pregnancy in women with systemic lupus erythematosus. The high indicated preterm birth proportion due to hypertensive disorders of pregnancy and/or fetal growth restriction is well known, and preventive measures and screening for early detection are performed. The risk of spontaneous preterm birth is less well recognized. This study aimed to determine the proportions of spontaneous and indicated preterm birth in pregnancies of women with systemic lupus erythematosus. DATA SOURCES: A systematic literature search using Pubmed, Embase, Web of Science, and Google Scholar was performed in June 2021. STUDY ELIGIBILITY CRITERIA: Studies in pregnant women with systemic lupus erythematosus reporting spontaneous and indicated preterm birth rates were selected. Original research articles published from 1995 to June 2021 were included. METHODS: Quality and risk of bias of the included studies were assessed using the Newcastle-Ottawa quality assessment scale. To estimate the pooled event rates and 95% confidence intervals, meta-analysis of single proportions with a random-effects model was performed. RESULTS: We included 21 articles, containing data of 8157 pregnancies in women with systemic lupus erythematosus. On average, 31% (95% prediction interval, 0.14-0.50) of the pregnancies resulted in preterm birth, including 14% (95% prediction interval, 0.04-0.27) spontaneous and 16% (95% prediction interval, 0.03-0.35) indicated preterm birth. CONCLUSION: In pregnant women with systemic lupus erythematosus, spontaneous and indicated preterm birth proportions are high. This information should be applied in (prepregnancy) counseling and management in pregnancy. The knowledge obtained by this meta-analysis paves the way for further research of associated risk factors and development of interventions to reduce spontaneous preterm birth in systemic lupus erythematosus pregnancies.

Calf circumferences in fetuses and neonates with and without talipes equinovares. A prospective cohort study.

OBJECTIVE: Children and adults with talipes equinovarus (TEV) have smaller calves and shorter feet compared to non-affected controls. Do these changes have a prenatal onset? METHODS: A prospective cohort study (January 2020-July 2021) was conducted with serial ultrasonographic measurements at 20 and 28 weeks gestation and measurements directly and 6 weeks after birth. Calf circumference and width, foot length and length of humerus, ulna, radius, femur, tibia and fibula were measured in TEV and were compared to a control population. Calculated sample size necessitated a minimal population of 10 cases with TEV and 50 controls. RESULTS: Twenty cases with TEV and 62 controls were included. Fetal calf circumference (p < 0.001) and width (p < 0.001) were smaller in the TEV group in comparison to the control group, which persisted after birth. Growth in foot length (p < 0.001) and calf width (p 0.003) declined prenatally over time. The bone lengths and upper leg circumference were not smaller or shorter in TEV compared to controls. CONCLUSION: This prospective cohort study demonstrated the prenatal onset of reduced calf and foot size in fetuses with TEV from 20 weeks and onwards, which persists directly after birth. To investigate whether reduction in circumference initiates TEV or is caused by TEV, further examination is needed.

The effect of low-dose aspirin on platelet function during pregnancy compared to placebo: An explorative study.

OBJECTIVES: To evaluate the effect of aspirin 80 mg compared to placebo on platelet function tests in the second and third trimester of pregnancy. STUDY DESIGN: An explorative study was performed to assess laboratory platelet function in a subpopulation of the APRIL trial: a randomized double-blind trial comparing aspirin 80 mg once daily to placebo for the prevention of recurrent preterm birth. Platelet function was measured between 18 and 22, and between 28 and 32 weeks gestational age with three platelet function tests: VerifyNow®, Chronolog light transmission aggregometry (Chronolog LTA) and serum thromboxane B2 (TxB2). Medication adherence was evaluated by pill counts, self-reported diaries and structured interviews. RESULTS: We included 11 women, six in the aspirin and five in the placebo group. In women receiving aspirin, platelet function was significantly lower compared to women receiving placebo for all three tests: VerifyNow® Aspirin Reaction Units (450.5 vs 648.0, p = 0.017); Chronolog LTA (9.5% vs 94.5%, p = 0.009); serum TxB2 levels (11.9 ng/mL versus 175.9 ng/mL, p = 0.030). For all three tests, platelet function did not differ between the second and third trimester of pregnancy in the aspirin group. In the placebo group, serum TxB2 levels were significantly higher in the third trimester. One non-adherent participant in the aspirin group showed results similar to the placebo group. CONCLUSION: Aspirin 80 mg has a clear inhibitory effect on laboratory platelet function during pregnancy compared to placebo. This effect is similar in the second and third trimester of pregnancy.

Corrigendum to "Maternal and Perinatal Outcome in Women with Systemic Lupus Erythematosus: A Retrospective Bicenter Cohort Study".

[This corrects the article DOI: 10.1155/2017/8245879.].

Care Pathway for Foetal Joint Contractures, Foetal Akinesia Deformation Sequence, and Arthrogryposis Multiplex Congenita.

INTRODUCTION: The majority of arthrogryposis multiplex congenita (AMC) and lethal forms of AMC such as foetal akinesia deformation sequence (FADS) cases are missed prenatally. We have demonstrated the additional value of foetal motor assessment and evaluation in a multidisciplinary team for the period 2007-2016. An applied care pathway was developed for foetuses presenting with joint contracture(s) in one anatomic region (e.g., talipes equinovarus [TEV]), more than one body part with non-progressive contractures and motility (AMC) and with deterioration over time (FADS). METHODS: The multidisciplinary team of Amsterdam University Medical Centre Expertise Centre FADS and AMC developed the care pathway. Additional tools are provided including a motor assessment by ultrasound examination and a post-mortem assessment form. RESULTS: An eight-step care pathway is presented with a proposed timing for prenatal sonographic examination, genetic examinations, multidisciplinary meetings, prenatal and postnatal counselling of the parents by a specialist also treating after birth, and the follow-up of prenatal and postnatal findings with counselling for future pregnancies. DISCUSSION/CONCLUSION: The scheduled serial structural and motor sonograpahic assessment together with follow-up examinations and genetic analysis should be tailored per prenatal centre per available resources. The multidisciplinary care pathway may pave the way to increase the detection rate and diagnosis of isolated contracture(s), TEV with underlying genetic causes, and the rare phenotypes AMC/FADS and prompt treatment after birth within expertise teams.

Fetal akinesia deformation sequence and massive perivillous fibrin deposition resulting in fetal death in six fetuses from one consanguineous couple, including literature review.

BACKGROUND: Massive perivillous fibrin deposition (MPFD) is associated with adverse pregnancy outcomes and is mainly caused by maternal factors with limited involvement of fetal or genetic causes. We present one consanguineous couple with six fetuses developing Fetal Akinesia Deformation Sequence (FADS) and MPFD, with a possible underlying genetic cause. This prompted a literature review on prevalence of FADS and MPFD. METHODS: Fetal ultrasound examination, motor assessment, genetic testing, postmortem examination, and placenta histology are presented (2009-2019). Literature was reviewed for the association between congenital anomalies and MPFD. RESULTS: All six fetuses developed normally during the first trimester. Thereafter, growth restriction, persistent flexed position, abnormal motility, and contractures in 4/6, consistent with FADS occurred. All placentas showed histologically confirmed MPFD. Genetic analyses in the five available cases showed homozygosity for two variants of unknown significance in two genes, VARS1 (OMIM*192150) and ABCF1 (OMIM*603429). Both parents are heterozygous for these variants. From 63/1999 manuscripts, 403 fetal outcomes were mobilized. In 14/403 fetuses, congenital abnormalities in association with MPFD were seen of which two fetuses with contractures/FADS facial anomalies. CONCLUSION: The low prevalence of fetal contractures/FADS facial anomalies in association with MPFD in the literature review supports the possible fetal or genetic contribution causing FADS and MPFD in our family. This study with literature review supports the finding that fetal, fetoplacental, and/or genetic components may play a role in causing a part of MPFDs.

Evaluation of embryonic posture using four-dimensional ultrasound and virtual reality.

AIM: To assess the possibility of embryonic posture evaluation (=feasibility, reproducibility, variation) at rest at 9 weeks' (+0-6 days) gestational age (GA) using four-dimensional ultrasound and virtual reality (VR) techniques. Moreover, it is hypothesized that embryonic posture shows variation at the same time point in an uneventful pregnancy. METHODS: In this explorative prospective cohort study, 23 pregnant women were recruited from the Rotterdam periconceptional cohort. A transvaginal four-dimensional ultrasound examination of 30 min per pregnancy was performed between 9 and 10 weeks' GA. The acquired datasets were offline evaluated longitudinally (i.e. per frame) using VR techniques. RESULTS: The ultrasound data of 16 (70%) out of 23 pregnancies were eligible for evaluation. At rest the analysis of the embryonic posture was feasible and showed a strong (>80%) intraobserver and interobserver reproducibility for most body parts. The majority of the body parts were in similar anatomic positions at rest. However, variations in anatomic positions (e.g. 6% rotated head, 9% laterally bent spine), within and between embryos, were seen at 9 weeks' GA. CONCLUSION: In this unique study, we showed for the first time that embryonic posture measurements at rest can be performed in a reliable way using state-of-the-art four-dimensional ultrasound and VR techniques. Already early in prenatal life there are differences regarding posture within and between embryos.

Patients' perspective on aspirin during pregnancy: a survey.

OBJECTIVE: To elucidate patients' knowledge and counseling perspective on aspirin reducing the risk of hypertensive disorders of pregnancy (HDP). METHODS: A quantitative survey was performed including women who are members of the patient orgasnization Dutch HELLP Foundation due to a history of HDP. RESULTS: Awareness of the risk-reducing effect of aspirin on HDP was present in 51.9% of the 189 women. The majority was informed by their gynecologist (89.8%) and preferred to be informed by a gynecologist (79.4%), at the postpartum checkup (42.3%) or in the consecutive pregnancy (30.7%), both orally and written (62.4%). CONCLUSION: Half of the women with a history of HDP were aware of the risk-reducing effect of aspirin in a consecutive pregnancy.

The relationship of a Prothrombin G20210A mutation or a factor V Leiden mutation and on-aspirin platelet (re-)activity.

INTRODUCTION: The interplay between platelets and pro-thrombotic factors may have been under-investigated in the identification of aspirin users at high risk for cardiovascular event reoccurrences. There is growing evidence that a Prothrombin G20210A (FII) or a Factor V Leiden (FVL) mutation might increase platelet activity. Subsequently, this study assessed on-aspirin platelet (re-)activity in non-pregnant participants with a FII - or a FVL mutation in comparison with non-pregnant data derived from controls. METHODS: This study was conducted with data derived from the follow-up FRUIT-RCT. This is a unique cohort namely, participants without a history of cardiovascular disease or thrombotic events, but who are a carrier of a pro-thrombotic mutation. All participants were instructed to ingest aspirin once daily for 10 days. Platelet (re-)activity was measured by the PFA Closure Time (PFA-CT), the VerifyNow (VN-ARU), and serum Thromboxane B2 (sTxB2) levels. RESULTS: In total, eight participants with a FII-, 15 with a FVL mutation, and 21 controls were included. The FII mutation carriers demonstrated significantly higher on-aspirin platelet (re)-activity (PFA-CT, -92 sec.; VN-ARU, +37 ARU) vs. controls. The FVL carriers demonstrated similar on-aspirin platelet (re-)activity vs. controls. The sTxB 2 levels were similar in either of the carrier groups vs. controls. CONCLUSION: We feel these data are suggestive of increased on-aspirin platelet (re-)activity, as measured by the PFA-200 and the VerifyNow, in non-pregnant carriers of a FII-mutation, but not in carriers of FVL-mutation. Interestingly, this increased on-aspirin platelet (re-)activity is present in spite of low sTxB2 levels.

Resistance of aspirin during and after pregnancy: A longitudinal cohort study.

OBJECTIVES: The objective of this study is to investigate possible changes in aspirin resistance during and after pregnancy over time. STUDY DESIGN: A longitudinal cohort study in obstetric high risk women with an indication for aspirin usage during pregnancy to prevent placenta mediated pregnancy complications. MAIN OUTCOME MEASURES: Aspirin resistance measured in the first, second and third trimester of pregnancy and at least three months postpartum by four complementary test: PFA-200, VerifyNow®, Chronolog light transmission aggregometry (Chronolog LTA) and serum thromboxane B2 (TxB2) level measurements. Correlation between the devices was investigated. RESULTS: In total, 23 pregnant women participated in the present study. Aspirin resistance according to the PFA-200, VerifyNow®, Chronolog LTA and serum TxB2, was 30.4%, 17.4%, 26.1% and 23.8% respectively. Resistance by any device was 69.6%. Aspirin resistance measured by the VerifyNow®, Chronolog LTA, serum TxB2 and aspirin resistance by any device during pregnancy was demonstrated more frequently than aspirin resistance after pregnancy. Correlation between the different devices was weak. CONCLUSION: Aspirin resistance was found in a considerable part of the participants. Considerable variation between participants, within participants over time and between the different devices was found. Prevalence of aspirin resistance during pregnancy differs from after pregnancy. More research on aspirin resistance and clinical obstetric outcome is needed.

Peptide hormone ELABELA enhances extravillous trophoblast differentiation, but placenta is not the major source of circulating ELABELA in pregnancy.

Preeclampsia is a frequent gestational hypertensive disorder with equivocal pathophysiology. Knockout of peptide hormone ELABELA (ELA) has been shown to cause preeclampsia-like symptoms in mice. However, the role of ELA in human placentation and whether ELA is involved in the development of preeclampsia in humans is not yet known. In this study, we show that exogenous administration of ELA peptide is able to increase invasiveness of extravillous trophoblasts in vitro, is able to change outgrowth morphology and reduce trophoblast proliferation ex vivo, and that these effects are, at least in part, independent of signaling through the Apelin Receptor (APLNR). Moreover, we show that circulating levels of ELA are highly variable between women, correlate with BMI, but are significantly reduced in first trimester plasma of women with a healthy BMI later developing preeclampsia. We conclude that the large variability and BMI dependence of ELA levels in circulation make this peptide an unlikely candidate to function as a first trimester preeclampsia screening biomarker, while in the future administering ELA or a derivative might be considered as a potential preeclampsia treatment option as ELA is able to drive extravillous trophoblast differentiation.

The risk of cesarean delivery after labor induction among women with prior pregnancy complications: a subgroup analysis of the AFFIRM study.

BACKGROUND: To determine the risk of cesarean delivery after labor induction among patients with prior placenta-mediated pregnancy complications (pre-eclampsia, late pregnancy loss, placental abruption or intrauterine growth restriction). METHODS: The AFFIRM database includes patient level data from 9 randomized controlled trials that evaluated the role of LMWH versus no LMWH during pregnancy to prevent recurrent placenta-mediated pregnancy complications. The primary outcome of this sub-study was the proportion of women who had an unplanned cesarean delivery after induction of labor compared to after spontaneous labor. RESULTS: There were 512 patients from 7 randomized trials included in our sub-study. There was no difference in the risk of cesarean delivery between women with labor induction (21/148, 14.2%) and spontaneous labor (79/364, 21.7%) (odds ratio (OR) 0.60, 95% CI, 0.35-1.01; p = 0.052). Among 274 women who used LMWH prophylaxis during pregnancy, the risk of cesarean delivery was lower among those that underwent labor induction (9.8%) compared to spontaneous labor (22.4%) (OR 0.38, 95% CI, 0.17-0.84; p = 0.01). CONCLUSIONS: The risk of cesarean delivery is not increased after labor induction among a higher risk patient population with prior pregnancy complications. Our results suggest that women who receive LMWH during pregnancy might benefit from labor induction.