Higher body mass index (BMI) is associated with osteoarthritis (OA) in both weight-bearing and non-weight-bearing joints, suggesting a link between OA and poor metabolic health beyond mechanical... Show moreHigher body mass index (BMI) is associated with osteoarthritis (OA) in both weight-bearing and non-weight-bearing joints, suggesting a link between OA and poor metabolic health beyond mechanical loading. This risk may be influenced by systemic factors accompanying BMI. Fluctuations in concentrations of metabolites may mark or even contribute to development of OA. This study explores the association of metabolites with radiographic knee/hip OA prevalence and progression. A H-1-NMR-metabolomics assay was performed on plasma samples of 1564 cases for prevalent OA and 2,125 controls collected from the Rotterdam Study, CHECK, GARP/NORREF and LUMC-arthroplasty cohorts. OA prevalence and 5 to 10 year progression was assessed by means of Kellgren-Lawrence (KL) score and the OARSI-atlas. End-stage knee/hip OA (TJA) was defined as indication for arthroplasty surgery. Controls did not have OA at baseline or follow-up. Principal component analysis of 227 metabolites demonstrated 23 factors, of which 19 remained interpretable after quality-control. Associations of factor scores with OA definitions were investigated with logistic regression. Fatty acids chain length (FALen), which was included in two factors which associated with TJA, was individually associated with both overall OA as well as TJA. Increased Fatty Acid chain Length is associated with OA. Show less
Pool, R.; Hagenbeek, F.A.; Hendriks, A.M.; Dongen, J. van; Willemsen, G.; Geus, E. de; ... ; Duijn, C.M. van 2020
Metabolites are small molecules involved in cellular metabolism where they act as reaction substrates or products. The term 'metabolomics' refers to the comprehensive study of these molecules. The... Show moreMetabolites are small molecules involved in cellular metabolism where they act as reaction substrates or products. The term 'metabolomics' refers to the comprehensive study of these molecules. The concentrations of metabolites in biological tissues are under genetic control, but this is limited by environmental factors such as diet. In adult mono- and dizygotic twin pairs, we estimated the contribution of genetic and shared environmental influences on metabolite levels by structural equation modeling and tested whether the familial resemblance for metabolite levels is mainly explained by genetic or by environmental factors that are shared by family members. Metabolites were measured across three platforms: two based on proton nuclear magnetic resonance techniques and one employing mass spectrometry. These three platforms comprised 237 single metabolic traits of several chemical classes. For the three platforms, metabolites were assessed in 1407, 1037 and 1116 twin pairs, respectively. We carried out power calculations to establish what percentage of shared environmental variance could be detected given these sample sizes. Our study did not find evidence for a systematic contribution of shared environment, defined as the influence of growing up together in the same household, on metabolites assessed in adulthood. Significant heritability was observed for nearly all 237 metabolites; significant contribution of the shared environment was limited to 6 metabolites. The top quartile of the heritability distribution was populated by 5 of the 11 investigated chemical classes. In this quartile, metabolites of the class lipoprotein were significantly overrepresented, whereas metabolites of classes glycerophospholipids and glycerolipids were significantly underrepresented. Show less
Pool, R.; Hagenbeek, F.A.; Hendriks, A.M.; Dongen, J. van; Willemsen, G.; Geus, E. de; ... ; BBMRI Metabol Consortium 2020
Metabolites are small molecules involved in cellular metabolism where they act as reaction substrates or products. The term 'metabolomics' refers to the comprehensive study of these molecules. The... Show moreMetabolites are small molecules involved in cellular metabolism where they act as reaction substrates or products. The term 'metabolomics' refers to the comprehensive study of these molecules. The concentrations of metabolites in biological tissues are under genetic control, but this is limited by environmental factors such as diet. In adult mono- and dizygotic twin pairs, we estimated the contribution of genetic and shared environmental influences on metabolite levels by structural equation modeling and tested whether the familial resemblance for metabolite levels is mainly explained by genetic or by environmental factors that are shared by family members. Metabolites were measured across three platforms: two based on proton nuclear magnetic resonance techniques and one employing mass spectrometry. These three platforms comprised 237 single metabolic traits of several chemical classes. For the three platforms, metabolites were assessed in 1407, 1037 and 1116 twin pairs, respectively. We carried out power calculations to establish what percentage of shared environmental variance could be detected given these sample sizes. Our study did not find evidence for a systematic contribution of shared environment, defined as the influence of growing up together in the same household, on metabolites assessed in adulthood. Significant heritability was observed for nearly all 237 metabolites; significant contribution of the shared environment was limited to 6 metabolites. The top quartile of the heritability distribution was populated by 5 of the 11 investigated chemical classes. In this quartile, metabolites of the class lipoprotein were significantly overrepresented, whereas metabolites of classes glycerophospholipids and glycerolipids were significantly underrepresented. Show less
Hagenbeek, F.A.; Pool, R.; Dongen, J. van; Draisma, H.M.; Hottenga, J.J.; Willemsen, G.; ... ; Abdel Abdellaoui 2020
Correction to: Nature Communicationshttps://doi.org/10.1038/s41467-019-13770-6, published online 7 January 2020.The original version of the Supplementary Information associated with this Article... Show moreCorrection to: Nature Communicationshttps://doi.org/10.1038/s41467-019-13770-6, published online 7 January 2020.The original version of the Supplementary Information associated with this Article included an incorrect Supplementary Data 1 file, in which additional delimiters were included in the first column for a number of rows, resulting in column shifts for some of these rows. The HTML has been updated to include a corrected version of Supplementary Data 1; the original incorrect version of Supplementary Data 1 can be found as Supplementary Information associated with this Correction. Show less
Hagenbeek, F.A.; Pool, R.; Dongen, J. van; Draisma, H.H.M.; Hottenga, J.J.; Willemsen, G.; ... ; BBMRI Metabolomics Consortium 2020
Metabolomics examines the small molecules involved in cellular metabolism. Approximately 50% of total phenotypic differences in metabolite levels is due to genetic variance, but heritability... Show moreMetabolomics examines the small molecules involved in cellular metabolism. Approximately 50% of total phenotypic differences in metabolite levels is due to genetic variance, but heritability estimates differ across metabolite classes. We perform a review of all genome-wide association and (exome-) sequencing studies published between November 2008 and October 2018, and identify > 800 class-specific metabolite loci associated with metabolite levels. In a twin-family cohort (N = 5117), these metabolite loci are leveraged to simultaneously estimate total heritability (h(total)(2)), and the proportion of heritability captured by known metabolite loci (h(Metabolite-hits)(2)) for 309 lipids and 52 organic acids. Our study reveals significant differences in h(Metabolite-hits)(2) among different classes of lipids and organic acids. Furthermore, phosphatidylcholines with a high degree of unsaturation have higher h(Metabolite-hits)(2) estimates than phosphatidylcholines with low degrees of unsaturation. This study highlights the importance of common genetic variants for metabolite levels, and elucidates the genetic architecture of metabolite classes. Show less
Ramler, P.I.; Henriquez, D.D.C.A.; Akker, T. van den; Caram-Deelder, C.; Groenwold, R.H.H.; Bloemenkamp, K.W.M.; ... ; TeMpOH-1 Study Grp 2019
IMPORTANCE Early plasma transfusion for women with severe postpartum hemorrhage (PPH) is recommended to prevent coagulopathy. However, there is no comparative, quantitative evidence on the... Show moreIMPORTANCE Early plasma transfusion for women with severe postpartum hemorrhage (PPH) is recommended to prevent coagulopathy. However, there is no comparative, quantitative evidence on the association of early plasma transfusion with maternal outcomes.OBJECTIVE To compare the incidence of adverse maternal outcomes among women who received plasma during the first 60 minutes of persistent PPH vs women who did not receive plasma for similarly severe persistent PPH.DESIGN, SETTING, AND PARTICIPANTS This multicenter cohort study used a consecutive sample of women with persistent PPH, defined as PPH refractory to first-line measures to control bleeding, between January 1, 2011, and January 1, 2013. Time-dependent propensity score matching was used to select women who received plasma during the first 60 minutes of persistent PPH and match each of them with a woman who had shown the same severity and received the same treatment of PPH but who had not received plasma at the moment of matching. Transfusions were not guided by coagulation tests. Statistical analysis was performed from June 2018 to June 2019.EXPOSURES Transfusion of plasma during the first 60 minutes of persistent PPH vs no or later plasma transfusion.MAIN OUTCOMES AND MEASURES Incidence of adverse maternal outcomes, defined as a composite of death, hysterectomy, or arterial embolization.RESULTS This study included 1216 women (mean [SD] age, 31.6 [5.0] years) with persistent PPH, of whom 932 (76.6%) delivered vaginally and 780 (64.1%) had PPH caused by uterine atony. Seven women (0.6%) died because of PPH, 62 women (5.1%) had a hysterectomy, and 159 women (13.1%) had arterial embolizations. Among women who received plasma during the first 60 minutes of persistent PPH, 114 women could be matched with a comparable woman who had not received plasma at the moment of matching. The incidence of adverse maternal outcomes was similar between the women, with adverse outcomes recorded in 24 women (21.2%) who received early plasma transfusion and 23 women (19.9%) who did not receive early plasma transfusion (odds ratio, 1.09; 95% CI, 0.57-2.09). Results of sensitivity analyses were comparable to the primary results.CONCLUSIONS AND RELEVANCE In this cohort study, initiation of plasma transfusion during the first 60 minutes of persistent PPH was not associated with adverse maternal outcomes compared with no or later plasma transfusion, independent of severity of PPH. Show less
Objective Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is associated with life-threatening bleeding. This systematic review of postnatal management of FNAIT examined transfusion of human... Show moreObjective Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is associated with life-threatening bleeding. This systematic review of postnatal management of FNAIT examined transfusion of human platelet antigen (HPA) selected or unselected platelets, and/or IVIg on platelet increments, hemorrhage and mortality.Study design MEDLINE, EMBASE and Cochrane searches were conducted until 11 May 2018.Result Of 754 neonates, 382 received platelet transfusions (51%). HPA-selected platelets resulted in higher platelet increments and longer response times than HPA-unselected platelets. However, unselected platelets generally led to sufficient platelet increments to 30 x 10(9)/L, a level above which intracranial hemorrhage or other life-threatening bleeding rarely occurred. Platelet increments were not improved with the addition of IVIg to platelet transfusion.Conclusion Overall, HPA-selected platelet transfusions were more effective than HPA-unselected platelets but unselected platelets were often effective enough to achieve clinical goals. Available studies do not clearly demonstrate a benefit for addition of IVIg to platelet transfusion. Show less
Kjaer, M.; Bertrand, G.; Bakchoul, T.; Massey, E.; Baker, J.M.; Lieberman, L.; ... ; Int Collaboration Transfusion Med 2019
Background and Objectives In Caucasians, fetal/neonatal alloimmune thrombocytopenia (FNAIT) is most commonly due to maternal HPA-1a antibodies. HPA-1a typing followed by screening for anti-HPA-1a... Show moreBackground and Objectives In Caucasians, fetal/neonatal alloimmune thrombocytopenia (FNAIT) is most commonly due to maternal HPA-1a antibodies. HPA-1a typing followed by screening for anti-HPA-1a antibodies in HPA-1bb women may identify first pregnancies at risk. Our goal was to review results from previous published studies to examine whether the maternal antibody level to HPA-1a could be used to identify high-risk pregnancies. Materials and Methods The studies included were categorized by recruitment strategies: screening of unselected pregnancies or samples analyzed from known or suspected FNAIT patients. Results Three prospective studies reported results from screening programmes, and 10 retrospective studies focused on suspected cases of FNAIT. In 8 studies samples for antibody measurement, performed by the monoclonal antibody immobilization of platelet antigen (MAIPA) assay, and samples for determining fetal/neonatal platelet count were collected simultaneously. In these 8 studies, the maternal antibody level correlated with the risk of severe thrombocytopenia. The prospective studies reported high negative predictive values (88-95%), which would allow for the use of maternal anti-HPA-1a antibody level as a predictive tool in a screening setting, in order to identify cases at low risk for FNAIT. However, due to low positive predictive values reported in prospective as well as retrospective studies (54-97%), the maternal antibody level is less suited for the final diagnosis and for guiding antenatal treatment. Conclusion HPA-1a antibody level has the potential to predict the severity of FNAIT. Show less
Ramler, P.I.; Henriquez, D.D.C.A.; Akker, T. van den; Caram-Deelder, C.; Groenwold, R.H.H.; Bloemenkamp, K.W.M.; ... ; TeMpOH-1 Study Grp 2019
Introduction: To compare the outcomes of women who were initially managed by intrauterine balloon tamponade or uterine artery embolization because of persistent postpartum hemorrhage demanding an... Show moreIntroduction: To compare the outcomes of women who were initially managed by intrauterine balloon tamponade or uterine artery embolization because of persistent postpartum hemorrhage demanding an immediate intervention to control bleeding.Material and Methods: Propensity score-matched cohort study including women who had intrauterine balloon tamponade or uterine artery embolization as initial management strategy to control persistent postpartum hemorrhage, that is, refractory to first-line therapy combined with at least one uterotonic agent. The primary outcome measure was a composite of peripartum hysterectomy and/or maternal mortality. Secondary outcomes measures were total volume of blood loss and total number of packed red blood cells transfused.Results: Our 1:1 propensity score-matched cohort comprised of 50 women who had intrauterine balloon tamponade and 50 women who underwent uterine artery embolization at a blood loss between 1000 and 7000 mL. There was no statistically significant difference in the hysterectomy risk between the two groups (n = 6 in each group, odds ratio [OR] 1.00, 95% confidence interval [CI] .30-3.34), in total volume of blood loss (median 4500 mL, interquartile range [IQR] 3600-5400) for balloon vs 4000 mL (IQR 3250-5000) for embolization, P = 0.382) or in total units of packed red blood cells transfused (median 7 (IQR 5-10) for balloon vs 6 [IQR 4-9] for embolization, P = 0.319). Fifteen women (30%) who were initially managed by an intrauterine balloon still underwent uterine artery embolization, of whom one had an embolization-related thrombo-embolic event. Maternal mortality occurred in neither of the intervention groups.Conclusions: No difference in the risk of peripartum hysterectomy and/or maternal death was observed between women who had intrauterine balloon tamponade and women who underwent uterine artery embolization as an initial management for persistent postpartum hemorrhage. Although this study was underpowered to demonstrate equivalence, our study design provides a framework for future research in which intrauterine balloon tamponade may prove to be a suitable intervention of first choice in the management of persistent postpartum hemorrhage. Show less
Voorn, V.M.A.; Bodegom-Vos, L. van; So-Osman, C. 2018
Voorn, V.M.A.; Marang-van de Mheen, P.J.; Hout, A. van der; Hofstede, S.N.; So-Osman, C.; Akker-van Marle, M.E. van den; ... ; Bodegom-Vos, L. van 2017
