The human umbilical cord (hUC) is the lifeline that connects the fetus to the mother. Hypercoiling of the hUC is associated with pre- and perinatal morbidity and mortality. We investigated the... Show moreThe human umbilical cord (hUC) is the lifeline that connects the fetus to the mother. Hypercoiling of the hUC is associated with pre- and perinatal morbidity and mortality. We investigated the origin of hUC hypercoiling using state-of-the-art imaging and omics approaches. Macroscopic inspection of the hUC revealed the helices to originate from the arteries rather than other components of the hUC. Digital reconstruction of the hUC arteries showed the dynamic alignment of two layers of muscle fibers in the tunica media aligning in opposing directions. We observed that genetically identical twins can be discordant for hUC coiling, excluding genetic, many environmental, and parental origins of hUC coiling. Comparing the transcriptomic and DNA methylation profile of the hUC arteries of four twin pairs with discordant cord coiling, we detected 28 differentially expressed genes, but no differentially methylated CpGs. These genes play a role in vascular development, cell–cell interaction, and axis formation and may account for the increased number of hUC helices. When combined, our results provide a novel framework to understand the origin of hUC helices in fetal development. Show less
Cardiac involvement is the main cause of death in Becker muscular dystrophy (BMD). Identification of left ventricular (LV) function is crucial, but standard echocardiographic measurements such as... Show moreCardiac involvement is the main cause of death in Becker muscular dystrophy (BMD). Identification of left ventricular (LV) function is crucial, but standard echocardiographic measurements such as LV ejection fraction (LVEF) might not be sensitive enough to detect early myocardial dysfunction. We explored the value of LV global longitudinal strain (GLS) as a more accurate echocardiographic parameter to detect and monitor LV dysfunction in BMD. Furthermore, we studied possible factors associated with LV dysfunction and progression. A total of 40 patients with BMD (age 39.0 +/- 13.2 years) and 21 matched controls were included. Clinical variables, pulmonary tests, serum biomarkers, and echocardiograms were collected at baseline and after 2 years. LV systolic function was assessed by LVEF and LV GLS; a significant progression in LV dysfunction was defined as an absolute LV GLS deterioration >= 15%. Responsiveness to cardiac disease progression was determined using standardized response means. Patients showed impaired LVEF and LV GLS compared with controls (p <0.001). Of interest, 31 patients (77.5%) showed impaired LV GLS (defined as greater than -18%), whereas only 24 patients (60%) had reduced LVEF. LV GLS and LVEF correlated with troponin I (r = 0.553 and -0.523) and N-terminal pro-b-type natriuretic peptide (r = 0.506 and -0.585), but not with skeletal muscle or pulmonary function. At follow-up (2.0 +/- 0.5 years, n = 29), LV GLS worsened significantly (-1.3 +/- 0.8%, p = 0.002, standardized response mean = 0.70, annually = 0.60%), whereas LVEF remained stable. No risk factors for LV dysfunction progression were identified. In BMD, LV GLS is frequently impaired and shows deterioration over time compared with LVEF. LV GLS could be used as a more sensitive parameter to identify and monitor LV dysfunction. (c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license Show less
Brouwer, E.; Knol, R.; Kroushev, A.; Akker, T. van den; Hooper, S.B.; Roest, A.A.; Pas, A.B. te 2021
Real-time echocardiographic monitoring of blood flow in the ductus venosus and hepatic vein was undertaken during perinatal transition with intact umbilical cord of term born infants. Antegrade... Show moreReal-time echocardiographic monitoring of blood flow in the ductus venosus and hepatic vein was undertaken during perinatal transition with intact umbilical cord of term born infants. Antegrade flow increased during inspiration, preferentially directing blood flow from the ductus venosus into the right atrium.Objective To investigate the effect of spontaneous breathing on venous return in term infants during delayed cord clamping at birth. Methods Echocardiographic ultrasound recordings were obtained directly after birth in healthy term-born infants. A subcostal view was used to obtain an optimal view of the inferior vena cava (IVC) entering the right atrium, including both the ductus venosus (DV) and the hepatic vein (HV). Colour Doppler was used to assess flow direction and flow velocity. Recordings continued until the umbilical cord was clamped and were stored in digital format for offline analyses. Results Ultrasound recordings were obtained in 15 infants, with a median (IQR) gestational age of 39.6 (39.0-40.9) weeks and a birth weight of 3560 (3195-4205) g. Flow was observed to be antegrade in the DV and HV in 98% and 82% of inspirations, respectively, with flow velocity increasing in 74% of inspirations. Retrograde flow in the DV was observed sporadically and only occurred during expiration. Collapse of the IVC occurred during 58% of inspirations and all occurred caudal to the DV inlet (100%). Conclusion Spontaneous breathing was associated with collapse of the IVC and increased antegrade DV and HV flow velocity during inspiration. Therefore, inspiration appears to preferentially direct blood flow from the DV into the right atrium. This indicates that inspiration could be a factor driving placental transfusion in infants. Show less
Toemen, L.; Santos, S.; Roest, A.A.; Jelic, G.; Lugt, A. van der; Felix, J.F.; ... ; Jaddoe, V.W.V. 2020
BACKGROUND: Adiposity is associated with larger left ventricular mass in children and adults. The role of body fat distribution in these associations is not clear. We examined the associations of... Show moreBACKGROUND: Adiposity is associated with larger left ventricular mass in children and adults. The role of body fat distribution in these associations is not clear. We examined the associations of body fat distribution and overweight with cardiac measures obtained by cardiac magnetic resonance imaging in school--age children.METHODS AND RESULTS: In a population--based cohort study including 2836 children, 10 years of age, we used anthropometric measures, dual--energy X--ray absorptiometry, and magnetic resonance imaging to collect information on body mass index, lean mass index, fat mass index, and abdominal visceral adipose tissue index. Indexes were standardized by height. Cardiac measures included right and left ventricular end--diastolic volume, left ventricular mass, and mass--to--volume ratio as a marker for concentricity. All body fat measures were positively associated with right and left ventricular end--diastolic volumes and left ventricular mass, with the strongest associations for lean mass index (all P<0.05). Obese children had a 1.12 standard deviation score (95% CI, 0.94-1.30) larger left ventricular mass and a 0.35 standard deviation score (95% CI, 0.14- 0.57) higher left ventricular mass--to--volume ratio than normal weight children. Conditional on body mass index, higher lean mass index was associated with higher right and left ventricular end--diastolic volume and left ventricular mass, whereas higher fat mass measures were inversely associated with these cardiac measures (all P<0.05).CONCLUSIONS: Higher childhood body mass index is associated with a larger right and left ventricular size. This association is influenced by higher lean mass. In childhood, lean mass may be a stronger determinant of heart growth than fat mass. Fat mass may influence cardiac structures at older ages. Show less
Background Umbilical venous catheters (UVCs) are associated with thrombus formation. Most studies on thrombosis in infants with UVCs focus on only one part of the route, and none assessed a control... Show moreBackground Umbilical venous catheters (UVCs) are associated with thrombus formation. Most studies on thrombosis in infants with UVCs focus on only one part of the route, and none assessed a control group of infants without UVCs.Objective To determine the incidence and location of thrombi in infants after umbilical catheterisation and compare this with a control group of infants without umbilical catheters.Design Prospective observational study with serial ultrasonography of the UVC route from the umbilico-portal confluence to the heart. Ultrasonography was performed until day 14 after catheterisation in cases and day 14 after birth in controls.Results Thrombi in the UVC route were detected in 75% (30/40) of infants with UVCs in the study group, whereas no thrombi were detected in the control group of infants without UVCs (0/20) (p<0.001). Six thrombi (20%) were located in the right atrium. Most of these were also partly present in the ductus venosus. Six thrombi (20%) were located in the ductus venosus only, and in 12 infants (40%), the thrombus was at least partly located in the umbilico-portal confluence. Thrombi persisted after UVC removal in 25/30 cases. Two infants with thrombotic events were treated with low-molecular-weight heparin and resolution was found. In the other 23 infants managed expectantly, 2 died due to necrotising enterocolitis, 1 was lost to follow-up and in 20 spontaneous regression was seen.Conclusions Thrombotic events occur frequently in infants after umbilical catheterisation. Most thrombi were asymptomatic and regressed spontaneously with expectant management. Routine screening for thrombi in UVCs is therefore not advised. Show less
Toemen, L.; Gaillard, R.; Roest, A.A.; Geest, R.J.; Steegers, E.A.P.; Lugt, A. van der; ... ; Jaddoe, V.W.V. 2020
