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1.
J Hepatol ; 74(5): 1087-1096, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33276032

RESUMO

BACKGROUND & AIMS: Intrahepatic cholestasis of pregnancy (ICP) is associated with an increased risk of stillbirth. This study aimed to assess the relationship between bile acid concentrations and fetal cardiac dysfunction in patients with ICP who were or were not treated with ursodeoxycholic acid (UDCA). METHODS: Bile acid profiles and NT-proBNP, a marker of ventricular dysfunction, were assayed in umbilical venous serum from 15 controls and 76 ICP cases (36 untreated, 40 UDCA-treated). Fetal electrocardiogram traces were obtained from 43 controls and 48 ICP cases (26 untreated, 22 UDCA-treated). PR interval length and heart rate variability (HRV) parameters were measured in 2 behavioral states (quiet and active sleep). RESULTS: In untreated ICP, fetal total serum bile acid (TSBA) concentrations (r = 0.49, p = 0.019), hydrophobicity index (r = 0.20, p = 0.039), glycocholate concentrations (r = 0.56, p = 0.007) and taurocholate concentrations (r = 0.44, p = 0.039) positively correlated with fetal NT-proBNP. Maternal TSBA (r = 0.40, p = 0.026) and alanine aminotransferase (r = 0.40, p = 0.046) also positively correlated with fetal NT-proBNP. There were no significant correlations between maternal or fetal serum bile acid concentrations and fetal HRV parameters or NT-proBNP concentrations in the UDCA-treated cohort. Fetal PR interval length positively correlated with maternal TSBA in untreated (r = 0.46, p = 0.027) and UDCA-treated ICP (r = 0.54, p = 0.026). Measures of HRV in active sleep and quiet sleep were significantly higher in untreated ICP cases than controls. HRV values in UDCA-treated cases did not differ from controls. CONCLUSIONS: Elevated fetal and maternal serum bile acid concentrations in untreated ICP are associated with an abnormal fetal cardiac phenotype characterized by increased NT-proBNP concentration, PR interval length and HRV. UDCA treatment partially attenuates this phenotype. LAY SUMMARY: The risk of stillbirth in intrahepatic cholestasis of pregnancy (ICP) is linked to the level of bile acids in the mother which are thought to disrupt the baby's heart rhythm. We found that babies of women with untreated ICP have abnormally functioning hearts compared to those without ICP, and the degree of abnormality is closely linked to the level of harmful bile acids in the mother and baby's blood. Babies of women with ICP who received treatment with the drug UDCA do not have the same level of abnormality in their hearts, suggesting that UDCA could be a beneficial treatment in some ICP cases, although further clinical trials are needed to confirm this.


Assuntos
Alanina Transaminase/sangue , Ácidos e Sais Biliares/sangue , Colestase Intra-Hepática , Coração Fetal/fisiopatologia , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Complicações na Gravidez , Ácido Ursodesoxicólico/uso terapêutico , Disfunção Ventricular , Adulto , Biomarcadores/sangue , Colagogos e Coleréticos/uso terapêutico , Colestase Intra-Hepática/sangue , Colestase Intra-Hepática/diagnóstico , Colestase Intra-Hepática/tratamento farmacológico , Correlação de Dados , Eletrocardiografia/métodos , Feminino , Sangue Fetal , Humanos , Gravidez , Complicações na Gravidez/sangue , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/tratamento farmacológico , Medição de Risco , Natimorto/epidemiologia , Resultado do Tratamento , Disfunção Ventricular/sangue , Disfunção Ventricular/diagnóstico , Disfunção Ventricular/tratamento farmacológico
2.
BMJ Open Qual ; 7(2): e000070, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29682617

RESUMO

Local anaesthetic (LA) agents are widely used in maternity care. Although relatively safe, their use does carry risks, the most serious of which is systemic toxicity (LAST). LAST poses a major threat to maternal and neonatal safety due to the frequency of LA administration in maternity care and the under-recognition of toxicity in such settings, which has been reported globally. Our aim was to prevent LAST occurrence in a District General Hospital (DGH) maternity unit by improving staff awareness through the implementation of a tailored educational programme. We used a standardised 14-point questionnaire to evaluate LAST awareness among staff of all disciplines. Domains of interest were LA maximum safe doses, LAST recognition, immediate management and use of antidote. Following baseline assessment, we implemented an educational programme in three stages. Each featured a distinct tool: video presentation, poster and lanyard card. Awareness was reassessed between stages using the same questionnaire. We identified poor baseline awareness across all non-anaesthetic disciplines. Average questionnaire score improved from 3.9/14 (n=23) to 8.1/14 (n=30) during the project period, an increase of 109.3%. Scores improved in all professional groups and a change in workplace culture has been reported. Using a tailored interprofessional educational intervention, we generated an increase in awareness and maintained this over a 4-month period. Improved knowledge and a shift in clinical attitudes towards shared responsibility will reduce avoidable peripartum risk associated with LAST at this DGH. Although the tools used were specific to LAST in this setting, they could be easily adapted for NHS maternity services elsewhere and indeed other areas of care.

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