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Introduction: Preterm prelabor rupture of membranes (PPROM) remains a major complication of fetal laser surgery in the treatment of twin‐to‐twin transfusion syndrome (TTTS). The aim of the study was to determine the impact of cannula size on pregnancy outcomes, with a particular focus on PPROM. Material and methods: The protocol was developed and registered in the PROSPERO database under registration number CRD42022333630. The PubMed, Web of Science, and EMBASE databases were searched electronically on May 18, 2022, and updated on March 2, 2023, utilizing a combination of the relevant MeSH terms, keywords, and word variants for "TTTS" and "laser". Randomized controlled trials, prospective and retrospective cohorts, case–control studies, and case reports/series with more than five participants were considered eligible for inclusion. Studies reporting the cannula diameter and PPROM rate after laser surgery in the treatment of monochorionic pregnancies affected by TTTS between 16‐ and 26 weeks' gestation were included. Data was extracted independently, and when appropriate, a random‐effects meta‐analysis was undertaken to calculate pooled estimates and their confidence intervals. Heterogeneity in the effect estimates of the individual studies was calculated using the I2 statistic. The primary outcome was PPROM rate. Secondary outcomes were survival rate, preterm birth, and incomplete surgery. The quality of the included studies was assessed using a modified quality in prognosis study tool. Results: We included a total of 22 studies, consisting of 3426 patients. Only one study was scored as low quality, seven as moderate quality, and the remaining 14 as high quality. The mean PPROM rate after laser surgery treating TTTS was 22.9%, ranging from 11.6% for 9 French (Fr) to 54.0% for 12 Fr. Subsequent meta‐regression for the clinically relevant PPROM rate before 34 weeks of gestation, showed increased PPROM rates for increased cannula size (p‐value 0.01). Conclusions: This systematic review confirmed PPROM as a frequent complication of fetal laser surgery, with a mean PPROM rate of 22.9%. A larger cannula diameter relates to a significant higher PPROM risk for PPROM before 34 weeks gestation. Hence, the ideal balance between optimal visualization requiring larger port diameters and shorter operation time and more complete procedures that benefit from larger diameters is crucial to reduce iatrogenic PPROM rates. [ABSTRACT FROM AUTHOR]

Uric acid induces radical oxygen species formation, endothelial inflammation, and endothelial dysfunction which contributes to the progression of atherosclerosis. Febuxostat inhibits BCRP- and allopurinol stimulates MRP4-mediated uric acid efflux in human embryonic kidney cells. We hypothesized that endothelial cells express uric acid transporters that regulate intracellular uric acid concentration and that modulation of these transporters by febuxostat and allopurinol contributes to their different impact on cardiovascular mortality. The aim of this study was to explore a potential difference between the effect of febuxostat and allopurinol on uric acid uptake by human umbilical vein endothelial cells. Febuxostat increased intracellular uric acid concentrations compared with control. In contrast, allopurinol did not affect intracellular uric acid concentration. In line with this observation, febuxostat increased mRNA expression of GLUT9 and reduced MRP4 expression, while allopurinol did not affect mRNA expression of these uric acid transporters. These findings provide a possible pathophysiological pathway which could explain the higher cardiovascular mortality for febuxostat compared to allopurinol but should be explored further. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether women with unexplained recurrent pregnancy loss have impaired arterial vascular health compared with controls, and to evaluate whether this is modifiable by exercise. Design: Experimental case–control pilot study. Setting: University medical centre in the Netherlands. Population: Twelve women with unexplained recurrent pregnancy loss, 11 nulliparous women and 19 primiparous women with a history of uncomplicated pregnancies. Methods: In all three groups we measured baseline characteristics, metabolic components and arterial vascular health, and repeated this in women with unexplained recurrent pregnancy loss after 1 month of protocolled and supervised cycle training. Main outcome measures: Differences in arterial vascular health between women with unexplained recurrent pregnancy loss and controls, and the effect of exercise on arterial vascular health in women with unexplained recurrent pregnancy loss. Results: Women with unexplained recurrent pregnancy loss have a significantly increased carotid intima media thickness in comparison with both controls (both P < 0.01), a significantly decreased brachial endothelial dependent flow‐mediated vasodilation in comparison with both controls (nulliparous: P < 0.01; primiparous: P = 0.05) and a significantly decreased femoral endothelial dependent flow‐mediated vasodilation in comparison with primiparous women (P = 0.01). The endothelium independent glyceryl trinitrate response was similar in all groups. With 1 month of exercise, the carotid intima media thickness decreased significantly by 7% (P = 0.05) and the femoral FMD increased significantly by 10% (P = 0.01) in women with unexplained recurrent pregnancy loss. Conclusions: Women with unexplained recurrent pregnancy loss have an impaired vascular health in comparison with controls. This impaired arterial vascular health can be improved by exercise. [ABSTRACT FROM AUTHOR]

Background Preterm birth is the leading cause of neonatal morbidity and mortality. The recurrence rate of spontaneous preterm birth is high, and additional preventive measures are required. Our objective was to assess the effectiveness of low-dose aspirin compared to placebo in the prevention of preterm birth in women with a previous spontaneous preterm birth. Methods and findings We performed a parallel multicentre, randomised, double-blinded, placebo-controlled trial (the APRIL study). The study was performed in 8 tertiary and 26 secondary care hospitals in the Netherlands. We included women with a singleton pregnancy and a history of spontaneous preterm birth of a singleton between 22 and 37 weeks. Participants were randomly assigned to aspirin 80 mg daily or placebo initiated between 8 and 16 weeks of gestation and continued until 36 weeks or delivery. Randomisation was computer generated, with allocation concealment by using sequentially numbered medication containers. Participants, their healthcare providers, and researchers were blinded for treatment allocation. The primary outcome was preterm birth grade 1, intraventricular hemorrhage > grade 2, necrotising enterocolitis > stage 1, retinopathy of prematurity, culture proven sepsis, or perinatal death). Analyses were performed by intention to treat. From May 31, 2016 to June 13, 2019, 406 women were randomised to aspirin (n = 204) or placebo (n = 202). A total of 387 women (81.1% of white ethnic origin, mean age 32.5 ± SD 3.8) were included in the final analysis: 194 women were allocated to aspirin and 193 to placebo. Preterm birth Conclusions In this study, we observed that low-dose aspirin did not significantly reduce the preterm birth rate in women with a previous spontaneous preterm birth. However, a modest reduction of preterm birth with aspirin cannot be ruled out. Further research is required to determine a possible beneficial effect of low-dose aspirin for women with a previous spontaneous preterm birth. Trial registration Dutch Trial Register (NL5553, NTR5675) https://www.trialregister.nl/trial/5553., Author(s): Anadeijda J. E. M. C. Landman 1,*, Marjon A. de Boer 1, Laura Visser 1, Tobias A. J. Nijman 2, Marieke A. C. Hemels 3, Christiana N. Naaktgeboren 4, [...]

Background Excisional procedures of cervical intraepithelial neoplasia (CIN) may increase the risk of preterm birth. It is unknown whether this increased risk is due to the excision procedure itself, to the underlying CIN, or to secondary risk factors that are associated with both preterm birth and CIN. The aim of this study is to assess the risk of spontaneous preterm birth in women with treated and untreated CIN and examine possible associations by making a distinction between the excised volume of cervical tissue and having cervical disease. Methods and findings This Dutch population-based observational cohort study identified women aged 29 to 41 years with CIN between 2005 and 2015 from the Dutch pathology registry (PALGA) and frequency matched them with a control group without any cervical abnormality based on age at and year of pathology outcome (i.e., CIN or normal cytology) and urbanization ( In total, 29,907, 5,940, and 9,412 pregnancies were included in the control, untreated CIN, and treated CIN group, respectively. The control group showed a 4.8% (1,002/20,969) proportion of spontaneous preterm birth, which increased to 6.9% (271/3,940) in the untreated CIN group, 9.5% (600/6,315) in the treated CIN group, and 15.6% (50/321) in the group with multiple treatments. Women with untreated CIN had a 1.38 times greater odds of preterm birth compared to women without CIN (95% confidence interval (CI) 1.19 to 1.60; P < 0.001). For women with treated CIN, these odds 2.07 times increased compared to the control group (95% CI 1.85 to 2.33; P < 0.001). Treated women had a 1.51 times increased odds of preterm birth compared to women with untreated CIN (95% CI 1.29 to 1.76; P < 0.001). Independent from cervical disease, a volume excised from the cervix of 0.5 to 0.9 cc increased the odds of preterm birth 2.20 times (37/379 versus 1,002/20,969; 95% CI 1.52 to 3.20; P < 0.001). These odds further increased 3.13 times and 5.93 times for women with an excised volume of 4 to 8.9 cc (90/724 versus 1,002/20,969; 95% CI 2.44 to 4.01; P < 0.001) and [greater than or equal to]9 cc (30/139 versus 1,002/20,969; 95% CI 3.86 to 9.13; P < 0.001), respectively. Limitations of the study include the retrospective nature, lack of sufficient information to calculate odds of preterm birth Conclusions In this study, we observed a strong correlation between preterm birth and a volume of [greater than or equal to]0.5 cc excised cervical tissue, regardless of the severity of CIN. Caution should be taken when performing excisional treatment in women of reproductive age as well as prudence in case of multiple biopsies. Fertile women with a history of performing multiple biopsies or excisional treatment for CIN may benefit from close surveillance during pregnancy., Author(s): Diede L. Loopik 1,*, Joris van Drongelen 2, Ruud L. M. Bekkers 3, Quirinus J. M. Voorham 4, Willem J. G. Melchers 5, Leon F. A. G. Massuger 2, [...]