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Long-term cardiovascular outcome following fetal anaemia and intrauterine transfusion: a cohort study.

ABSTRACT: To compare long-term cardiovascular outcomes in survivors of fetal anaemia and intrauterine transfusion with those of non-anaemic siblings.Retrospective cohort study.Auckland, New Zealand.Adults who received intrauterine transfusion for anaemia due to rhesus disease (exposed) and their unexposed sibling(s).Fetal anaemia requiring intrauterine transfusion.Anthropometry, blood pressure, lipids, heart rate variability and cardiac MRI, including myocardial perfusion.Exposed participants (n=95) were younger than unexposed (n=92, mean±SD 33.7±9.3 vs 40.1±10.9?years) and born at earlier gestation (34.3±1.7 vs 39.5±2.1?weeks). Exposed participants had smaller left ventricular volumes (end-diastolic volume/body surface area, difference between adjusted means -6.1, 95% CI -9.7 to -2.4?mL/m2), increased relative left ventricular wall thickness (difference between adjusted means 0.007, 95% CI 0.001 to 0.012?mm.m2/mL) and decreased myocardial perfusion at rest (ratio of geometric means 0.86, 95% CI 0.80 to 0.94). Exposed participants also had increased low frequency-to-high frequency ratio on assessment of heart rate variability (ratio of geometric means 1.53, 95% CI 1.04 to 2.25) and reduced high-density lipoprotein concentration (difference between adjusted means -0.12, 95% CI -0.24 to 0.00?mmol/L).This study provides the first evidence in humans that cardiovascular development is altered following exposure to fetal anaemia and intrauterine transfusion, with persistence of these changes into adulthood potentially indicating increased risk of cardiovascular disease. These findings are relevant to the long-term health of intrauterine transfusion recipients, and may potentially also have implications for adults born preterm who were exposed to anaemia at a similar postconceptual age.

SUBMITTER: Wallace AH

PROVIDER: S-EPMC5297634 | biostudies-other | 2017 Jan

REPOSITORIES: biostudies-other

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Long-term cardiovascular outcome following fetal anaemia and intrauterine transfusion: a cohort study.

Wallace Alexandra H AH Dalziel Stuart R SR Cowan Brett R BR Young Alistair A AA Thornburg Kent L KL Harding Jane E JE

Archives of disease in childhood 20160923 1

<h4>Objective</h4>To compare long-term cardiovascular outcomes in survivors of fetal anaemia and intrauterine transfusion with those of non-anaemic siblings.<h4>Design</h4>Retrospective cohort study.<h4>Setting</h4>Auckland, New Zealand.<h4>Participants</h4>Adults who received intrauterine transfusion for anaemia due to rhesus disease (exposed) and their unexposed sibling(s).<h4>Exposure</h4>Fetal anaemia requiring intrauterine transfusion.<h4>Main outcome measures</h4>Anthropometry, blood press ...[more]

PMID: 27664264

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Project description:IntroductionWe aimed to evaluate the neuroimaging findings and long-term neurodevelopmental outcomes of fetuses and children following intrauterine blood transfusion (IUT) for parvo B19 infection-induced anemia compared to those with RBC alloimmunization.MethodsWe conducted a retrospective cohort study including women who underwent an IUT due to fetal anemia between 2006 and 2019 in a tertiary, university-affiliated medical center. The cohort was divided into two groups: a study group - fetuses affected by congenital parvo B19 infection; and a control group - fetuses affected by RBC alloimmunization. Retrospective data such as antenatal sonographic evaluations, fetal brain MRI results, and short-term fetal and neonatal outcomes were collected. All children underwent a neurodevelopmental evaluation after birth using a Vineland questionnaire. Primary outcome was defined as the presence or absence of neurodevelopmental delay. Secondary outcome was defined as the presence of abnormal fetal neuroimaging findings such as cerebellar hypoplasia, polymicrogyria, intracranial hemorrhage, or severe ventriculomegaly.ResultsOverall, 71 fetuses requiring at least one IUT were included in the study. Of these, 18 were affected by parvo B19 infection and 53 by RBC alloimmunization with various associated antibodies. Fetuses in the parvo B19 group presented at an earlier gestational age (22.91 ± 3.36 weeks vs. 27.37 ± 4.67 weeks, p = 0.002) and were more affected by hydrops (93.33% vs. 16.98%, p < 0.001). Three fetuses out of the 18 (16.67%) fetuses in the parvo B19 group died in utero following the IUT. Abnormal neuroimaging findings were detected in 4/15 (26.7%) of the parvo B19 survivors versus 2/53 (3.8%) of fetuses affected by RBC alloimmunization (p = 0.005). There was no difference in long-term neurodevelopmental delay rates between the children in the study and control groups, as assessed at the average age of 3.65 and 6.53 years, accordingly.ConclusionFetal anemia due to parvo B19, treated with IUT, might be associated with increased rates of abnormal neurosonographic findings. The correlation between those findings and long-term adverse neurodevelopmental outcomes requires further investigation.

Project description:Preoperative anemia is a well-established risk factor for short-term mortality in patients undergoing noncardiac surgery, but appropriate thresholds for transfusion remain uncertain. The objective of this study was to determine long-term outcomes associated with anemia, hemorrhage, and red blood cell transfusion in patients undergoing noncardiac surgery.We performed a long-term follow-up study of consecutive subjects undergoing hip, knee, and spine surgery between November 1, 2008 and December 31, 2009. Clinical data were obtained from administrative and laboratory databases, and retrospective record review. Preoperative anemia was defined as baseline hemoglobin < 13 g/dL for men and < 12 g/dL for women. Hemorrhage was defined by International Classification of Diseases, Ninth Revision coding. Data on long-term survival were collected from the Social Security Death Index database. Logistic regression models were used to identify factors associated with long-term mortality.There were 3050 subjects who underwent orthopedic surgery. Preoperative anemia was present in 17.6% (537) of subjects, hemorrhage occurred in 33 (1%), and 766 (25%) received at least one red blood cell transfusion. Over 9015 patient-years of follow-up, 111 deaths occurred. Anemia (hazard ratio [HR] 3.91; confidence interval [CI], 2.49-6.15) and hemorrhage (HR 5.28; 95% CI, 2.20-12.67) were independently associated with long-term mortality after multivariable adjustment. Red blood cell transfusion during the surgical hospitalization was associated with long-term mortality (HR 3.96; 95% CI, 2.47-6.34), which was attenuated by severity of anemia (no anemia [HR 4.39], mild anemia [HR 2.27], and moderate/severe anemia [HR 0.81]; P for trend .0015).Preoperative anemia, perioperative bleeding, and red blood cell transfusion are associated with increased mortality at long-term follow-up after noncardiac surgery. Strategies to minimize anemia and bleeding should be considered for all patients, and restrictive transfusion strategies may be advisable. Further investigation into mechanisms of these adverse events is warranted.

Project description:Intrauterine fetal death or stillbirth occurs in approximately 1 out of every 160 pregnancies and accounts for 50% of all perinatal deaths. Postmortem evaluation fails to elucidate an underlying cause in many cases. Long QT syndrome (LQTS) may contribute to this problem.To determine the spectrum and prevalence of mutations in the 3 most common LQTS susceptible genes (KCNQ1, KCNH2, and SCN5A) for a cohort of unexplained cases.In this case series, retrospective postmortem genetic testing was conducted on a convenience sample of 91 unexplained intrauterine fetal deaths (mean [SD] estimated gestational age at fetal death, 26.3 [8.7] weeks) that were collected from 2006-2012 by the Mayo Clinic, Rochester, Minnesota, or the Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. More than 1300 ostensibly healthy individuals served as controls. In addition, publicly available exome databases were assessed for the general population frequency of identified genetic variants.Comprehensive mutational analyses of KCNQ1 (KV7.1, LQTS type 1), KCNH2 (HERG/KV11.1, LQTS type 2), and SCN5A (NaV1.5, LQTS type 3) were performed using denaturing high-performance liquid chromatography and direct DNA sequencing on genomic DNA extracted from decedent tissue. Functional analyses of novel mutations were performed using heterologous expression and patch-clamp recording.The 3 putative LQTS susceptibility missense mutations (KCNQ1, p.A283T; KCNQ1, p.R397W; and KCNH2 [1b], p.R25W), with a heterozygous frequency of less than 0.05% in more than 10 000 publicly available exomes and absent in more than 1000 ethnically similar control patients, were discovered in 3 intrauterine fetal deaths (3.3% [95% CI, 0.68%-9.3%]). Both KV7.1-A283T (16-week male) and KV7.1-R397W (16-week female) mutations were associated with marked KV7.1 loss-of-function consistent with in utero LQTS type 1, whereas the HERG1b-R25W mutation (33.2-week male) exhibited a loss of function consistent with in utero LQTS type 2. In addition, 5 intrauterine fetal deaths hosted SCN5A rare nonsynonymous genetic variants (p.T220I, p.R1193Q, involving 2 cases, and p.P2006A, involving 2 cases) that conferred in vitro electrophysiological characteristics consistent with potentially proarrhythmic phenotypes.In this molecular genetic evaluation of 91 cases of intrauterine fetal death, missense mutations associated with LQTS susceptibility were discovered in 3 cases (3.3%) and overall, genetic variants leading to dysfunctional LQTS-associated ion channels in vitro were discovered in 8 cases (8.8%). These preliminary findings may provide insights into mechanisms of some cases of stillbirth.

Dataset Information

Long-term cardiovascular outcome following fetal anaemia and intrauterine transfusion: a cohort study.

Publications

Long-term cardiovascular outcome following fetal anaemia and intrauterine transfusion: a cohort study.

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