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1.
Acta Obstet Gynecol Scand ; 99(7): 865-874, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31943128

RESUMO

INTRODUCTION: Late-gestation adverse pregnancy outcome is associated with reduced placental villous vascularity but rarely with a frankly abnormal umbilical artery Doppler waveform. The clinical utility of umbilical artery Doppler velocimetry in late gestation is limited by poor understanding of what aspect(s) of placental structure and function the impedance reflects. We hypothesized that placental arterial circulation impedance reflects placental vascularity and arterial function. MATERIAL AND METHODS: This was a secondary analysis of data from the FEMINA2 study, a study of pregnancy outcome after reduced fetal movement. Forty-three pregnancies that delivered within 7 days of ultrasound assessment were examined. Impedance was quantified by pulsatility index (PI) from umbilical, chorionic plate arteries, and intra-placental arteries. Site-specific PI was compared with villous vascularity (CD31 immunostaining) and placental arterial function (wire myography) by regression analysis (P < .01) where factor analysis suggested potential co-variance (Eigen value > 2). RESULTS: Pulsatility index decreased with proximity to the placental microvasculature (P < .0001). Intra-placental artery PI correlated significantly with vessel number (R2  = 0.40, P = .0007). No significant relations between umbilical or chorionic plate artery PI and villous vascularity were found (P ≥ .11 and P ≥ .042). No significant co-variance was suggested between PI at any Doppler sampling site and ex vivo placental arterial function indices. Measurement reliability (intraclass correlation coefficient) was highest in the umbilical artery (PI 0.75 and 0.50 for intra- and interoperator reliability, respectively) and lowest in the intra-placental arteries (PI 0.55 and 0.41, respectively). Systematic bias in umbilical artery PI was observed between observers, but not at other Doppler sampling sites. CONCLUSIONS: More vascular placentas ex vivo are associated with reduced intra-placental artery Doppler impedance in utero. Although umbilical (but not intra-placental) artery Doppler PI is associated with adverse outcome after reduced fetal movement, this predictive ability does not appear to be through assessment of placental vascularity or chorionic plate arterial function. The inferior reliability of intra-placental artery Doppler, although similar to previously published reliability of umbilical artery Doppler, impairs its ability to detect subtle differences in placental vascularity, and must be significantly improved before it could be considered a clinically useful test.

3.
PLoS One ; 13(11): e0206533, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30395584

RESUMO

OBJECTIVE: To assess the value of in utero placental assessment in predicting adverse pregnancy outcome after reported reduced fetal movements (RFM). METHOD: A non-interventional prospective cohort study of women (N = 300) with subjective RFM at ≥28 weeks' gestation in singleton non-anomalous pregnancies at a UK tertiary maternity hospital. Clinical, sonographic (fetal weight, placental size and maternal, fetal and placental arterial Doppler) and biochemical (maternal serum hCG, hPL, progesterone, PlGF and sFlt-1) assessment was conducted. Multiple logistic regression identified combinations of measurements (models) most predictive of adverse pregnancy outcome (perinatal mortality, birth weight <10th centile, five minute Apgar score <7, umbilical arterial pH <7.1 or base excess <-10, neonatal intensive care admission). Models were compared by test performance characteristics (ROC curve, sensitivity, specificity, positive/negative predictive value, positive/negative likelihood ratios) against baseline care (estimated fetal weight centile, amniotic fluid index and gestation at presentation). RESULTS: 61 (20.6%) pregnancies ended in adverse outcome. Models incorporating PlGF/sFlt-1 ratio and umbilical artery free loop Doppler impedance demonstrated modest improvement in ROC area for adverse outcome (baseline care 0.69 vs. proposed models 0.73-0.76, p<0.05). However, there was little improvement in other test characteristics (baseline vs. best proposed model: sensitivity 21.7% [95% confidence interval 13.1-33.6] vs. 35.8%% [24.4-49.3], specificity 96.6% [93.4-98.3] vs. 94.7% [90.7-97.0], PPV 61.9% [40.9-79.3] vs. 63.3% [45.5-78.1], NPV 82.8% [77.9-86.8] vs. 85.2% [80.0-89.2], positive LR 6.3 [2.8-14.6] vs. 6.7 [3.4-3.3], negative LR 0.81 [0.71-0.93] vs. 0.68 [0.55-0.83]) and wide confidence intervals. Negative post-test probability remained high (16.7% vs. 14.0%). CONCLUSION: Antenatal placental assessment may improve identification of RFM pregnancies at highest risk of adverse pregnancy outcome but further work is required to understand and refine currently available outcome definitions and diagnostic techniques to improve clinical utility.


Assuntos
Movimento Fetal/fisiologia , Placenta/diagnóstico por imagem , Resultado da Gravidez , Adulto , Índice de Apgar , Estudos de Coortes , Cordocentese , Feminino , Humanos , Concentração de Íons de Hidrogênio , Recém-Nascido de Baixo Peso , Recém-Nascido , Terapia Intensiva Neonatal , Modelos Logísticos , Estudos Longitudinais , Modelos Biológicos , Morte Perinatal , Placenta/irrigação sanguínea , Valor Preditivo dos Testes , Gravidez , Estudos Prospectivos , Natimorto , Ultrassonografia Pré-Natal
4.
Paediatr Perinat Epidemiol ; 32(5): 474-481, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30300448

RESUMO

BACKGROUND: The UK Medical Certificate of Stillbirth (MCS) records information relevant to the cause of stillbirth of infants ≥24 weeks' gestation. A cross-sectional audit demonstrated widespread inaccuracies in MCS completion in 2009 in North West England. A repeat study was conducted to assess whether practice had improved following introduction of a regional care pathway. METHODS: 266 MCS issued in 14 North West England obstetric units during 2015 were studied retrospectively. Cause of death was assigned following review of information available at the time of MCS completion. This was compared to that documented on the MCS, and to data from 2009. RESULTS: Twenty-three certificates were excluded (20 inadequate data, 3 late miscarriages). 118/243 (49%) MCS contained major errors. Agreement between the MCS and adjudicated cause of stillbirth was fair (Kappa 0.31; 95% CI 0.24, 0.38) and unchanged from 2009 (0.29). In 2015, excluding 34 terminations of pregnancy, the proportion of MCSs documenting "unexplained" stillbirths (113/211; 54%) was reduced compared to 2009 (158/213; 74%); causality could be assigned after case note review in 78% cases. Recognition of fetal growth restriction (FGR) as a cause of stillbirth improved (2015: 30/211; 14% vs 2009: 1/213; 0.5%), although 71% cases were missed. 47% MCSs following termination of pregnancy documented an iatrogenic primary cause of death. CONCLUSIONS: Completion of MCSs remains inaccurate, particularly in recognition of FGR as a cause of stillbirth. Detailed case note review before issuing the MCS could dramatically improve the usefulness of included information; evaluation of practitioner education programmes/internal feedback systems are recommended.


Assuntos
Causas de Morte , Fidelidade a Diretrizes/estatística & dados numéricos , Auditoria Médica , Registros Médicos/normas , Natimorto , Estudos Transversais , Inglaterra , Idade Gestacional , Humanos , Recém-Nascido , Guias de Prática Clínica como Assunto , Reprodutibilidade dos Testes
5.
Acta Obstet Gynecol Scand ; 97(12): 1515-1523, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30132798

RESUMO

INTRODUCTION: Continuous fetal monitoring is used to objectively record the fetal heart rate and fetal activity over an extended period of time; however, its feasibility and acceptability to women is currently unknown. The study addressed the hypothesis that continuous fetal monitoring is feasible and acceptable to pregnant women. MATERIAL AND METHODS: Pregnant participants (n = 22) were monitored using a continuous fetal electrocardiography device, the Monica AN24. Signal quality, duration of recording and cardiotocography findings were correlated with maternal and fetal factors. Participants' change in anxiety before and after monitoring was assessed using validated questionnaires. Participants' experiences were explored through a questionnaire (n = 20) and semi-structured interview (n = 13). RESULTS: Recordings were successfully obtained in 19 of the 22 participants (86.3%). The mean recording quality of fetal heart rate was 69.0% (range 17.4%-99.4%) and maternal heart rate was 99.0% (90.9%-100.0%). Recording quality was positively correlated with gestational age (P = 0.05) and negatively correlated with uterine activity and maternal movement (P < 0.001). Overall, participants were satisfied with their experience of continuous fetal monitoring; 30% considered it preferable to intermittent monitoring. Continuous fetal monitoring did not significantly increase maternal anxiety, with a trend towards a reduction in Pregnancy Specific Anxiety score (P = 0.07). Qualitative analysis grouped women's responses into three themes: (a) reassurance and anxiety, (b) the physical device and (c) future developments in continuous fetal monitoring. CONCLUSIONS: Continuous fetal monitoring is a feasible and acceptable form of monitoring to pregnant women although further practical improvements could be incorporated. Further research is required to assess the ability of continuous fetal monitoring to detect fetal compromise.


Assuntos
Cardiotocografia/métodos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Adolescente , Adulto , Ansiedade/diagnóstico , Ansiedade/epidemiologia , Ansiedade/etiologia , Cardiotocografia/psicologia , Estudos de Viabilidade , Feminino , Frequência Cardíaca Fetal , Humanos , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Gravidez , Pesquisa Qualitativa , Fatores de Tempo , Adulto Jovem
6.
FASEB J ; 32(10): 5436-5446, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29723064

RESUMO

Cell free hemoglobin impairs vascular function and blood flow in adult cardiovascular disease. In this study, we investigated the hypothesis that free fetal hemoglobin (fHbF) compromises vascular integrity and function in the fetoplacental circulation, contributing to the increased vascular resistance associated with fetal growth restriction (FGR). Women with normal and FGR pregnancies were recruited and their placentas collected freshly postpartum. FGR fetal capillaries showed evidence of erythrocyte vascular packing and extravasation. Fetal cord blood fHbF levels were higher in FGR than in normal pregnancies ( P < 0.05) and the elevation of fHbF in relation to heme oxygenase-1 suggests a failure of expected catabolic compensation, which occurs in adults. During ex vivo placental perfusion, pathophysiological fHbF concentrations significantly increased fetal-side microcirculatory resistance ( P < 0.05). fHbF sequestered NO in acute and chronic exposure models ( P < 0.001), and fHbF-primed placental endothelial cells developed a proinflammatory phenotype, demonstrated by activation of NF-κB pathway, generation of IL-1α and TNF-α (both P < 0.05), uncontrolled angiogenesis, and disruption of endothelial cell flow alignment. Elevated fHbF contributes to increased fetoplacental vascular resistance and impaired endothelial protection. This unrecognized mechanism for fetal compromise offers a novel insight into FGR as well as a potential explanation for associated poor fetal outcomes such as fetal demise and stillbirth.-Brook, A., Hoaksey, A., Gurung, R., Yoong, E. E. C., Sneyd, R., Baynes, G. C., Bischof, H., Jones, S., Higgins, L. E., Jones, C., Greenwood, S. L., Jones, R. L., Gram, M., Lang, I., Desoye, G., Myers, J., Schneider, H., Hansson, S. R., Crocker, I. P., Brownbill, P. Cell free hemoglobin in the fetoplacental circulation: a novel cause of fetal growth restriction?


Assuntos
Células Endoteliais/metabolismo , Retardo do Crescimento Fetal/sangue , Hemoglobina Fetal/metabolismo , Placenta , Circulação Placentária , Resistência Vascular , Adulto , Células Endoteliais/patologia , Feminino , Retardo do Crescimento Fetal/fisiopatologia , Heme Oxigenase-1/sangue , Humanos , Placenta/irrigação sanguínea , Placenta/metabolismo , Placenta/patologia , Placenta/fisiopatologia , Gravidez
7.
J Ultrasound Med ; 36(7): 1415-1429, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28339117

RESUMO

OBJECTIVES: To assess intraexaminer and interexaminer reliability of 3-dimensional fetal sonographic measurements. METHODS: Three-dimensional fetal organ volumes (head, kidney, total thigh volume, and fractional thigh volume) were acquired during the second and third trimesters, with the addition of placental volume in the second trimester, by 2 different experienced, blinded sonographers. Fifty-eight fetuses were examined from 21 to 39 weeks' gestation. Intraexaminer and Interexaminer reliability was assessed with Bland-Altman plots, and their 95% limits of agreement and intraclass correlation coefficients. RESULTS: The most significant interexaminer error was observed in the second-trimester kidney volume (95% limits of agreement, ± 110%), and the best agreement was for the third-trimester fractional thigh volume (95% limits of agreement, ± 25%) and second-trimester head volume (95% limits of agreement, -7%-25%). Second- and third-trimester intraclass correlation coefficient results were all greater than 0.75, apart from second-trimester kidney volume intraexaminer (0.374) and interexaminer (0.061) measurements, second-trimester placenta interexaminer measurements (0.390), and third-trimester kidney interexaminer measurements (0.647). CONCLUSIONS: Three-dimensional fetal sonographic volumes of the head, kidney, total thigh, and placenta have limited reproducibility, and improvements in measurement techniques are needed before they can be used routinely to assess fetal growth. The 3-dimensional fractional thigh volume can be reliably obtained in the late third trimester.


Assuntos
Peso Fetal/fisiologia , Feto/diagnóstico por imagem , Feto/fisiologia , Imageamento Tridimensional/métodos , Segundo Trimestre da Gravidez , Terceiro Trimestre da Gravidez , Ultrassonografia Pré-Natal/métodos , Feminino , Humanos , Masculino , Variações Dependentes do Observador , Tamanho do Órgão , Gravidez , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
8.
J Matern Fetal Neonatal Med ; 29(13): 2145-50, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26364651

RESUMO

OBJECTIVE: A reduction in fetal movements has been proposed to identify pregnancies at risk of stillbirth. The utility of this approach is limited by variability in maternal perception of fetal movements. We aimed to determine the proportion of fetal movements observed by ultrasound that were maternally perceived and identify factors that affected maternal perception. METHOD: During 30-min recordings, women (n = 21) depressed a trigger upon perception of a fetal movement, while an ultrasound operator recorded observed movements according to the fetal parts involved. RESULTS: Women perceived between 2.4% and 81.0% (median 44.8%) of movements observed on scan. Synchronous movement of the fetal trunk and limbs was more likely to be recognized than either part in isolation (60.5% versus 37.5% and 30%, respectively). The ultrasound operator judged the fetus to be moving for a significantly greater proportion of the time than mothers (median 1.5% of total recording time versus 0.7%). There was no significant relationship between the ability to perceive fetal activity and placental site, parity, amniotic fluid index or maternal body mass index. CONCLUSION: Variations in maternal perception of fetal movements may affect detection of a clinically significant reduction in fetal movements for some women.


Assuntos
Monitorização Fetal , Movimento Fetal/fisiologia , Mães/psicologia , Percepção , Terceiro Trimestre da Gravidez , Adulto , Índice de Massa Corporal , Feminino , Monitorização Fetal/métodos , Feto/fisiologia , Humanos , Recém-Nascido , Obesidade/diagnóstico , Obesidade/psicologia , Paridade , Gravidez , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/psicologia , Ultrassonografia Pré-Natal , Adulto Jovem
9.
PLoS One ; 10(6): e0129117, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26120838

RESUMO

OBJECTIVE: Currently, no investigations reliably identify placental dysfunction in late pregnancy. To facilitate the development of such investigations we aimed to identify placental features that differ between normal and adverse outcome in late pregnancy in a group of pregnancies with reduced fetal movement. METHODS: Following third trimester presentation with reduced fetal movement (N = 100), placental structure ex vivo was measured. Placental function was then assessed in terms of (i) chorionic plate artery agonist responses and length-tension characteristics using wire myography and (ii) production and release of placentally derived hormones (by quantitative polymerase chain reaction and enzyme linked immunosorbant assay of villous tissue and explant conditioned culture medium). RESULTS: Placentas from pregnancies ending in adverse outcome (N = 23) were ~25% smaller in weight, volume, length, width and disc area (all p<0.0001) compared with those from normal outcome pregnancies. Villous and trophoblast areas were unchanged, but villous vascularity was reduced (median (interquartile range): adverse outcome 10 (10-12) vessels/mm2 vs. normal outcome 13 (12-15), p = 0.002). Adverse outcome pregnancy placental arteries were relatively insensitive to nitric oxide donated by sodium nitroprusside compared to normal outcome pregnancy placental arteries (50% Effective Concentration 30 (19-50) nM vs. 12 (6-24), p = 0.02). Adverse outcome pregnancy placental tissue contained less human chorionic gonadotrophin (20 (11-50) vs. 55 (24-102) mIU/mg, p = 0.007) and human placental lactogen (11 (6-14) vs. 27 (9-50) mg/mg, p = 0.006) and released more soluble fms-like tyrosine kinase-1 (21 (13-29) vs. 5 (2-15) ng/mg, p = 0.01) compared with normal outcome pregnancy placental tissue. CONCLUSION: These data provide a description of the placental phenotype of adverse outcome in late pregnancy. Antenatal tests that accurately reflect elements of this phenotype may improve its prediction.


Assuntos
Placenta/patologia , Resultado da Gravidez , Terceiro Trimestre da Gravidez/fisiologia , Adulto , Sistema Endócrino/patologia , Sistema Endócrino/fisiopatologia , Feminino , Retardo do Crescimento Fetal/patologia , Movimento Fetal , Humanos , Placenta/irrigação sanguínea , Placenta/fisiopatologia , Gravidez , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Natimorto
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