HELLP babies link a novel lincRNA to the trophoblast cell cycle

The HELLP syndrome is a pregnancy-associated disease inducing hemolysis, elevated liver enzymes, and low platelets in the mother. Although the HELLP symptoms occur in the third trimester in the mother, the origin of the disease can be found in the first trimester fetal placenta. A locus for the HELLP syndrome is present on chromosome 12q23 near PAH. Here, by multipoint nonparametric linkage, pedigree structure allele sharing, and haplotype association analysis of affected sisters and cousins, we demonstrate that the HELLP locus is in an intergenic region on 12q23.2 between PMCH and IGF1. We identified a novel long intergenic noncoding RNA (lincRNA) transcript of 205,012 bases with (peri)nuclear expression in the extravillous trophoblast using strand-specific RT-PCR complemented with RACE and FISH. siRNA-mediated knockdown followed by RNA-sequencing, revealed that the HELLP lincRNA activated a large set of genes that are involved in the cell cycle. Furthermore, blocking potential mutation sites identified in HELLP families decreased the invasion capacity of extravillous trophoblasts. This is the first large noncoding gene to be linked to a Mendelian disorder with autosomal-recessive inheritance

Hyperemesis gravidarum severity, enteral tube feeding and cardiometabolic markers in offspring cord blood

Publisher Copyright: © The Authors 2022.Peer reviewedPublisher PD

Evaluation of low-dose aspirin in the prevention of recurrent spontaneous preterm labour (the APRIL study) : A multicentre, randomised, double-blinded, placebo-controlled trial

Funding: MdB, LV, TN, BM, MO and CdG received funding from ZonMw, The Dutch Organisation for Health Research and Development (grant number 836041006). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Thyroid-stimulating hormone and free thyroxine fail to predict the severity and clinical course of hyperemesis gravidarum : A prospective cohort study

Funding information: This prospective cohort study was supported by a research grant from North West Hospital Group, Alkmaar, the Netherlands (Grant number: 2013T085) and by a research grant from the Amsterdam Reproduction and Development (AR&D) Research Institute, Amsterdam UMC, the Netherlands (Project number: 23346). ACKNOWLEDGMENTS We thank Dr. J.P. Bestwick (employed at Queen Mary University of London, London, UK) and Professor Dr. J.H. Lazarus (employed at Cardiff School of Medicine, Cardiff, UK) for providing TSH medians from their study in the UK. Dr. J.P. Bestwick and Professor Dr. Lazarus have nothing to disclose.Peer reviewedPublisher PD

Effectiveness of a multidisciplinary care program on recovery and return to work of patients after gynaecological surgery; design of a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Return to work after gynaecological surgery takes much longer than expected, irrespective of the level of invasiveness. In order to empower patients in recovery and return to work, a multidisciplinary care program consisting of an e-health intervention and integrated care management including participatory workplace intervention was developed.</p> <p>Methods/Design</p> <p>We designed a randomized controlled trial to assess the effect of the multidisciplinary care program on full sustainable return to work in patients after gynaecological surgery, compared to usual clinical care. Two hundred twelve women (18-65 years old) undergoing hysterectomy and/or laparoscopic adnexal surgery on benign indication in one of the 7 participating (university) hospitals in the Netherlands are expected to take part in this study at baseline. The primary outcome measure is sick leave duration until full sustainable return to work and is measured by a monthly calendar of sickness absence during 26 weeks after surgery. Secondary outcome measures are the effect of the care program on general recovery, quality of life, pain intensity and complications, and are assessed using questionnaires at baseline, 2, 6, 12 and 26 weeks after surgery.</p> <p>Discussion</p> <p>The discrepancy between expected physical recovery and actual return to work after gynaecological surgery contributes to the relevance of this study. There is strong evidence that long periods of sick leave can result in work disability, poorer general health and increased risk of mental health problems. We expect that this multidisciplinary care program will improve peri-operative care, contribute to a faster return to work of patients after gynaecological surgery and, as a consequence, will reduce societal costs considerably.</p> <p>Trial registration</p> <p>Netherlands Trial Register (NTR): <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2087">NTR2087</a></p

Mifepristone followed by home administration of buccal misoprostol for medical abortion up to 70 days of amenorrhoea in a general practice in Curacao

Objective To evaluate the efficacy and safety of home administration of buccal misoprostol after mifepristone for medical abortion up to 70 days' gestation in a general practice in Curacao, where induced abortion is severely restricted by law. Methods In a prospective study 330 women received 200 mg mifepristone and were instructed to take four tablets (800 mg) of misoprostol via the buccal route 24-36 h later, at home. One week later, follow-up took place. Results The outcome could be evaluated in 307 of the 330 women. The efficacy of the mifepristone-buccal misoprostol procedure was 97.7% (300/307). In seven women vacuum aspirations for continuing pregnancy or incomplete abortion following treatment were required. Success rates at 64-70 days' gestation were the same as for gestations of less than 64 days duration. The main adverse effects were nausea and diarrhoea. Conclusion Home administration of buccal misoprostol 24-36 h after mifepristone is a safe and effective method of medical abortion up to 70 days. It could be applied in a general practice in Curacao, where induced abortion is legally restricted

Dutch GPs'views on prescribing mifepristone and misoprostol: a mixed-methods study

Background The World Health Organization has indicated that GPs can safely and effectively provide mifepristone and misoprostol for medical termination of pregnancy (TOP). Dutch GPs are allowed to treat miscarriages with mifepristone and misoprostol, but few do so. Current Dutch abortion law prohibits GPs from prescribing these medications for medical TOP. Medical TOP is limited to the specialised settings of abortion clinics and hospitals. Recently, the House of Representatives debated shifting abortion to the domain of primary care, following the example of France and the Republic of Ireland. This would improve access to sexual and reproductive health care, and increase choices for women. Nevertheless, little is known about GPs' willingness to provide medical TOP and miscarriage management. Aim To gain insight into Dutch GPs' willingness to prescribe mifepristone and misoprostol for medical TOP and miscarriages, as well as the anticipated barriers. Design and setting Mixed-methods study among Dutch GPs. Method A questionnaire provided quantitative data that were analysed using descriptive methods. Thematic analyses were performed on qualitative data collected through in-depth interviews. Results The questionnaire was sent to 575 GPs; the response rate was 22.1% (n = 127). Of the responders, 84.3% (n = 107) were willing to prescribe mifepristone and misoprostol, with 58.3% (n = 74) willing to provide this medication for both medical TOP and miscarriage management. A total of 57.5% (n = 73) of participants indicated a need for training. The main barriers influencing participants' willingness to provide medical TOP and miscarriage management were lack of experience, lack of knowledge, time constraints, and a restrictive abortion law. Conclusion Over 80.0% of responders were willing to prescribe mifepristone and misoprostol for medical TOP or miscarriages. Training, (online) education, and a revision of the abortion law are recommended