Maternal hypertensive disorders in pregnancy and early childhood cardiometabolic risk factors:The Generation R Study

The objective of this study was to determine the associations between hypertensive disorders of pregnancy and early childhood cardiometabolic risk factors in the offspring. Therefore, 7794 women from the Generation Rotterdam Study were included, an ongoing population-based prospective birth cohort. Women with a hypertensive disorder of pregnancy were classified as such when they were affected by pregnancy induced hypertension, pre-eclampsia or the haemolysis, elevated liver enzymes and low platelet count (HELLP) syndrome during pregnancy. Early childhood cardiometabolic risk factors were defined as the body mass index at the age of 2, 6, 12, 36 months and 6 years. Additionally, it included systolic blood pressure, diastolic blood pressure, total fat mass, cholesterol, triglycerides, insulin and clustering of cardiometabolic risk factors at 6 years of age. Sex-specific differences in the associations between hypertensive disorders and early childhood cardiometabolic risk factors were investigated. Maternal hypertensive disorders of pregnancy were inversely associated with childhood body mass index at 12 months (confounder model: -0.15 SD, 95% CI -0.27; -0.03) and childhood triglyceride at 6 years of age (confounder model: -0.28 SD, 95% CI -0.45; -0.10). For the association with triglycerides, this was only present in girls. Maternal hypertensive disorders of pregnancy were not associated with childhood body mass index at 2, 6 and 36 months. No associations were observed between maternal hypertensive disorders of pregnancy and systolic blood pressure, diastolic blood pressure, body mass index, fat mass index and cholesterol levels at 6 years of age. Our findings do not support an independent and consistent association between maternal hypertensive disorders of pregnancy and early childhood cardiometabolic risk factors in their offspring. However, this does not rule out possible longer term effects of maternal hypertensive disorders of pregnancy on offspring cardiometabolic health

Preventing cardiovascular disease after hypertensive disorders of pregnancy: Searching for the how and when

Background: Women with a history of a hypertensive disorder during pregnancy (HDP) have an increased risk of cardiovascular events. Guidelines recommend assessment of cardiovascular risk factors in these women later in life, but provide limited advice on how this follow-up should be organized. Design: Systematic review and meta-regression analysis. Methods: The aim of our study was to provide an overview of existing knowledge on the changes over time in three major modifiable components of cardiovascular risk assessment after HDP: blood pressure, glucose homeostasis and lipid levels. Data from 44 studies and up to 6904 women with a history of a HDP were compared with risk factor levels reported for women of corresponding age in the National Health And Nutrition Examination Survey, Estudio Epidemiólogico de la Insuficiencia Renal en España and Hong Kong cohorts (N = 27,803). Results: Compared with the reference cohort, women with a HDP presented with higher mean blood pressure. Hypertension was present in a higher rate among women with a previous HDP from 15 years postpartum onwards. At 15 years postpartum (±age 45), one in five women with a history of a HDP suffer from hypertension. No differences in glucose homeostasis parameters or lipid levels were observed. Conclusions: Based on our analysis, it is not possible to point out a time point to commence screening for cardiovascular risk factors in women after a HDP. We recommend redirection of future research towards the development of a stepwise approach identifying the women with the highest cardiovascular risk

Increased plasma CD14 levels 1 year postpartum in women with pre-eclampsia during pregnancy: a case–control plasma proteomics study

Epidemiological data suggest that pre-eclampsia (PE) is associated with an increased risk of post-delivery metabolic dysregulation. The aim of the present case–control observational study was to examine the global plasma proteomic profile 1 year postpartum in women who developed PE during pregnancy (n = 5) compared to controls (n = 5), in order to identify a novel predictive marker linking PE with long-term metabolic imbalance. Key findings were verified with enzyme-linked immunosorbent assay (ELISA) in a separate cohort (n = 17 women with PE and n = 43 controls). One hundred and seventy-two proteins were differentially expressed in the PE vs. control groups. Gene ontology analysis showed that Inflammatory|Immune responses, Blood coagulation and Metabolism were significantly enriched terms. CD14, mapping to the inflammatory response protein network, was selected for verification based on bibliographic evidence. ELISA measurements showed CD14 to be significantly increased 1 year postpartum in women with PE during pregnancy compared to controls [PE group (median ± SD): 296.5 ± 113.6; control group (median ± SD): 128.9 ± 98.5; Mann–Whitney U test p = 0.0078]. Overall, the identified proteins could provide insight into the long-term disease risk among women with PE during pregnancy and highlight the need for their postpartum monitoring. CD14 could be examined in larger cohorts as a predictive marker of insulin resistance and type II diabetes mellitus among women with PE

The Value of Early Tumor Size Response to Chemotherapy in Pediatric Rhabdomyosarcoma

Rhabdomyosarcoma is the most common soft tissue sarcoma in childhood. Results of clinical trials, with three-year event-free and overall survival as primary outcomes, often take 7 to 10 years. Identification of an early surrogate biomarker, predictive for survival, is therefore crucial. We conducted a systematic review to define the prognostic value of early tumor size response in children with IRSG group III rhabdomyosarcoma. The search included MEDLINE/EMBASE from inception to 18 November 2020. In total, six studies were included, describing 2010 patients, and assessed by the Quality in Prognosis Studies (QUIPS) instrument. Four studies found no prognostic value for tumor size response, whereas two studies reported a prognostic effect. In these two studies, the survival rate of patients with progressive disease was not separately analyzed from patients with stable disease, potentially explaining the difference in study outcome. In conclusion, our findings support that early progression of disease is associated with poorer survival, justifying adaptation of therapy. However, in patients with non-progressive disease, there is no evidence that the degree of response is a prognostic marker for survival. Because the vast majority of patients do not have progressive disease, early tumor size response should be reconsidered for assessment of treatment efficacy. Therefore, at present, early surrogate biomarkers for survival are still lacking

Периоды апробации метода прогноза интегральной метанообильности шахты

Розроблені аналітичній та натурній методи урахування метанового потенціалу вугільних шахт, апробація яких в умовах діючих об’єктів вдовж 5 термінів (1967 – 2009 рр.) показала високу надійність метода прогнозу інтегральної метанообільності шахт ІМА (~9 тис. порівнянь). На базі цього методу пропонується розробить державний нормативний документ для урахування метанового потенціалу вугільних шахт та реалізувати науково-технічні проекти авторів, які включені в програму науково-технічного розвитку Донецької області до 2020 р.Analytic and nature methods of calculation of methane potential of the collieries which check in the conditions of operating objects during 5 periods (1967 – 2009 years) has shown high reliability concerning of the method integrated methane of abundance of object IMA (~9 000 results) are developed. On the basis of this method it is offered to develop the state standard document for calculation of methane potential of collieries and to realize author’s projects to be conclusion to the science-technical program of development of Donetsk region to 2020 year

Epidemiology and (Patho)physiology of folic acid supplement use in obese women before and during pregnancy

Preconception folic acid supplement use is a well-known method of primary prevention of neural tube defects (NTDs). Obese women are at a higher risk for having a child with a NTD. As different international recommendations on folic acid supplement use for obese women before and during pregnancy exist, this narrative review provides an overview of epidemiology of folate deficiency in obese (pre)pregnant women, elaborates on potential mechanisms underlying folate deficiency, and discusses considerations for the usage of higher doses of folic acid supplements. Women with obesity more often suffer from an absolute folate deficiency, as they are less compliant to periconceptional folic acid supplement use recommendations. In addition, their dietary folate intake is limited due to an unbalanced diet (relative malnutrition). The association of obesity and NTDs also seems to be independent of folate intake, with studies suggesting an increased need of folate (relative deficiency) due to derangements involved in other pathways. The relative folate deficiency, as a result of an increased metabolic need for folate in obese women, can be due to: (1) low-grade chronic inflammation (2) insulin resistance, (3) inositol, and (4) dysbiotic gut microbiome, which plays a role in folate production and uptake. In all these pathways, the folate-dependent one-carbon metabolism is involved. In conclusion, scientific evidence of the involvement of several folate-related pathways implies to increase the recommended folic acid supplementation in obese women. However, the physiological uptake of synthetic folic acid is limited and side-effects of unmetabolized folic acid in mothers and offspring, in particular variations in epigenetic (re)programming with long-term health effects, cannot be excluded. Therefore, we emphasize on the urgent need for further research and preconception personalized counseling on folate status

Continuous glucose monitoring metrics and pregnancy outcomes in insulin-treated diabetes : A post-hoc analysis of the GlucoMOMS trial

Funding Information: BWM is supported by a NHMRC investigatorgrant (GNT1176437) and BWM reports consultancy, travel support and research funding from Merck. All other authors declare no conflict of interest. The GlucoMOMS trial was funded by ZonMw, the Dutch Organisation for Health Research and Development, project number 80‐82310‐97‐11157. Continuous Glucose Monitors were purchased at a discount price at Medtronic®, Heerlen, The Netherlands. Neither ZonMw nor Medtronic had a role in study design, data collection, data analysis, data interpretation, or writing of the reports of either the original study or the current post hoc analysis. 10 Publisher Copyright: © 2023 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.Peer reviewedPublisher PD

Indeterminate Pulmonary Nodules at Diagnosis in Rhabdomyosarcoma: Are They Clinically Significant? A Report From the European Paediatric Soft Tissue Sarcoma Study Group

PURPOSE: To evaluate the clinical significance of indeterminate pulmonary nodules at diagnosis (defined as ≤ 4 pulmonary nodules < 5 mm or 1 nodule measuring ≥ 5 and < 10 mm) in patients with pediatric rhabdomyosarcoma (RMS). PATIENTS AND METHODS: We selected patients with supposed nonmetastatic RMS treated in large pediatric oncology centers in the United Kingdom, France, Italy, and the Netherlands, who were enrolled in the European Soft Tissue Sarcoma Study Group (E pSSG) RMS 2005 study. Patients included in the current study received a diagnosis between September 2005 and December 2013, and had chest computed tomography scans available for review that were done at time of diagnosis. Local radiologists were asked to review the chest computed tomography scans for the presence of pulmonary nodules and to record their findings on a standardized case report form. In the E pSSG RMS 2005 Study, patients with indeterminate pulmonary nodules were treated identically to patients without pulmonary nodules, enabling us to compare event-free survival and overall survival between groups by log-rank test. RESULTS: In total, 316 patients were included; 67 patients (21.2%) had indeterminate pulmonary nodules on imaging and 249 patients (78.8%) had no pulmonary nodules evident at diagnosis. Median follow-up for survivors (n = 258) was 75.1 months; respective 5-year event-free survival and overall survival rates (95% CI) were 77.0% (64.8% to 85.5%) and 82.0% (69.7% to 89.6%) for patients with indeterminate nodules and 73.2% (67.1% to 78.3%) and 80.8% (75.1% to 85.3%) for patients without nodules at diagnosis ( P = .68 and .76, respectively). CONCLUSION: Our study demonstrated that indeterminate pulmonary nodules at diagnosis do not affect outcome in patients with otherwise localized RMS. There is no need to biopsy or upstage patients with RMS who have indeterminate pulmonary nodules at diagnosis