RESUMO
INTRODUCTION: Following the detection of fetal growth restriction, there is no consensus about the criteria that should trigger delivery in the late preterm period. The consequences of inappropriate early or late delivery are potentially important yet practice varies widely around the world, with abnormal findings from fetal heart rate monitoring invariably leading to delivery. Indices derived from fetal cerebral Doppler examination may guide such decisions although there are few studies in this area. We propose a randomised, controlled trial to establish the optimum method of timing delivery between 32 weeks and 36 weeks 6 days of gestation. We hypothesise that delivery on evidence of cerebral blood flow redistribution reduces a composite of perinatal poor outcome, death and short-term hypoxia-related morbidity, with no worsening of neurodevelopmental outcome at 2 years. METHODS AND ANALYSIS: Women with non-anomalous singleton pregnancies 32+0 to 36+6 weeks of gestation in whom the estimated fetal weight or abdominal circumference is <10th percentile or has decreased by 50 percentiles since 18-32 weeks will be included for observational data collection. Participants will be randomised if cerebral blood flow redistribution is identified, based on umbilical to middle cerebral artery pulsatility index ratio values. Computerised cardiotocography (cCTG) must show normal fetal heart rate short term variation (≥4.5 msec) and absence of decelerations at randomisation. Randomisation will be 1:1 to immediate delivery or delayed delivery (based on cCTG abnormalities or other worsening fetal condition). The primary outcome is poor condition at birth and/or fetal or neonatal death and/or major neonatal morbidity, the secondary non-inferiority outcome is 2-year infant general health and neurodevelopmental outcome based on the Parent Report of Children's Abilities-Revised questionnaire. ETHICS AND DISSEMINATION: The Study Coordination Centre has obtained approval from London-Riverside Research Ethics Committee (REC) and Health Regulatory Authority (HRA). Publication will be in line with NIHR Open Access policy. TRIAL REGISTRATION NUMBER: Main sponsor: Imperial College London, Reference: 19QC5491. Funders: NIHR HTA, Reference: 127 976. Study coordination centre: Imperial College Healthcare NHS Trust, Du Cane Road, London, W12 0HS with Centre for Trials Research, College of Biomedical & Life Sciences, Cardiff University. IRAS Project ID: 266 400. REC reference: 20/LO/0031. ISRCTN registry: 76 016 200.
Assuntos
Nascimento Prematuro , Ultrassonografia Pré-Natal , Cardiotocografia , Criança , Feminino , Retardo do Crescimento Fetal , Peso Fetal , Frequência Cardíaca Fetal/fisiologia , Humanos , Lactente , Recém-Nascido , Gravidez , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Pregnancy termination for fetal abnormality (TFA) may have profound psychological consequences for those involved. Evidence suggests that women's experience of care influences their psychological adjustment to TFA and that they greatly value compassionate healthcare. Caring for women in these circumstances presents challenges for health professionals, which may relate to their understanding of women's experience. This qualitative study examined health professionals' perceptions of women's coping with TFA and assessed to what extent these perceptions are congruent with women's accounts. METHODS: Fifteen semi-structured interviews were carried out with health professionals in three hospitals in England. Data were analysed using thematic analysis and compared with women's accounts of their own coping processes to identify similarities and differences. RESULTS: Health professionals' perceptions of women's coping processes were congruent with women's accounts in identifying the roles of support, acceptance, problem-solving, avoidance, another pregnancy and meaning attribution as key coping strategies. Health professionals regarded coping with TFA as a unique grieving process and were cognisant of women's idiosyncrasies in coping. They also considered their role as information providers as essential in helping women cope with TFA. The findings also indicate that health professionals lacked insight into women's long-term coping processes and the potential for positive growth following TFA, which is consistent with a lack of aftercare following TFA reported by women. CONCLUSIONS: Health professionals' perceptions of women's coping with TFA closely matched women's accounts, suggesting a high level of understanding. However, the lack of insight into women's long-term coping processes has important clinical implications, as research suggests that coping with TFA is a long-term process and that the provision of aftercare is beneficial to women. Together, these findings call for further research into the most appropriate ways to support women post-TFA, with a view to developing a psychological intervention to better support women in the future.
Assuntos
Aborto Induzido/psicologia , Adaptação Psicológica , Atitude do Pessoal de Saúde , Empatia , Feto/anormalidades , Pessoal de Saúde/psicologia , Adulto , Inglaterra , Feminino , Pesar , Humanos , Masculino , Pessoa de Meia-Idade , Percepção , Cuidado Pós-Natal/psicologia , Gravidez , Pesquisa QualitativaRESUMO
Prostate cancer cells can produce IL-18 binding protein (IL-18BP) in response to interferon-γ (IFN-γ), which may function to neutralize IL-18, an anti-tumor factor formerly known as IFN-γ inducing factor. The consumption of n-3 polyunsaturated fatty acids (PUFAs) has been associated with a lower risk of certain types of cancer including prostate cancer, although the precise mechanisms of this effect are poorly understood. We hypothesized that n-3 PUFAs could modify IL-18BP production by prostate cancer cells by altering IFN-γ receptor-mediated signal transduction. Here, we demonstrate that n-3 PUFA treatment significantly reduced IFN-γ-induced IL-18BP production by DU-145 and PC-3 prostate cancer cells by inhibiting IL-18BP mRNA expression and was associated with a reduction in IFN-γ receptor expression. Furthermore, IFN-γ-induced phosphorylation of Janus kinase 1 (JAK1), signal transducers and activators of transcription 1 (STAT1), extracellular signal-regulated kinases 1/2 (ERK1/2), and P38 were suppressed by n-3 PUFA treatment. By contrast, n-6 PUFA had no effect on IFN-γ receptor expression, but decreased IFN-γ-induced IL-18BP production and IFN-γ stimulation of JAK1, STAT1, ERK1/2, and JNK phosphorylation. These data indicate that both n-3 and n-6 PUFAs may be beneficial in prostate cancer by altering IFN-γ signaling, thus inhibiting IL-18BP production and thereby rendering prostate cancer cells more sensitive to IL-18-mediated immune responses.
Assuntos
Ácidos Graxos Ômega-3/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/biossíntese , Interferon gama/metabolismo , Neoplasias da Próstata/metabolismo , Linhagem Celular Tumoral , Ácidos Graxos Ômega-3/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Interferon gama/farmacologia , Masculino , Neoplasias da Próstata/genética , RNA Mensageiro/genética , Receptores de Interferon/genética , Receptores de Interferon/metabolismo , Transdução de Sinais/efeitos dos fármacos , Receptor de Interferon gamaRESUMO
Whereas structural fetal abnormalities are relatively frequent occurrences, many of these do not impact measurably on future life and/or are amenable to postnatal therapy. A small minority are considered to be potentially lethal or life-limiting. Examples include specific skeletal dysplasias, urinary tract abnormalities - typically those which lead to anhydramnios and pulmonary hypoplasia, some disorders of the central nervous system and trisomies 13 and 18. Without seeking to compile an exhaustive list of such conditions, we discuss the principles and new considerations in relation to antenatal diagnosis and perinatal management of such disorders.
Assuntos
Transtornos Cromossômicos/diagnóstico , Feto/anormalidades , Diagnóstico Pré-Natal/métodos , Feminino , Humanos , Gravidez , Reino UnidoRESUMO
BACKGROUND: Falling consent rates for postmortems, regardless of age of death, have been widely reported in recent years. The aim of this study was to explore parental attitudes to, and decision-making about, a perinatal postmortem after termination for fetal abnormality, late miscarriage, or stillbirth. METHODS: A prospective self-completion questionnaire was given to 35 women and their partners. The participants had experienced second or third trimester pregnancy loss in a single fetal medicine and delivery unit in the United Kingdom and were making decisions about having a postmortem. They were asked to complete a questionnaire about their attitudes to, and expectations of, a perinatal postmortem. RESULTS: Thirty-one questionnaires were received from parents of 17 babies (49% of those asked; 16 from mothers, 15 from fathers). Parents of nine babies (53%) said they would agree to a full postmortem, of three babies to a limited postmortem, and of four babies to an external examination only; one couple were undecided. The most important issues for the parents in this study that related to their decisions about a postmortem centered on the need for information, both for future planning and about what had happened. Moderately important issues related to altruism, which is, improving medical knowledge and helping other parents experiencing similar bereavement. Among the lowest scoring issues were potential barriers, such as concerns about cultural or religious acceptability of a postmortem, funeral delays, and what would happen to the baby's body. CONCLUSIONS: Bereaved parents who participated in this study, where postmortem consent rates were relatively high, thought that their need for knowledge eclipsed assumed barriers when deciding whether or not to have a postmortem for their baby.
Assuntos
Atitude Frente a Saúde , Autopsia , Luto , Tomada de Decisões , Pais/psicologia , Aborto Espontâneo , Adulto , Anormalidades Congênitas , Feminino , Humanos , Lactente , Masculino , Gravidez , Estudos Prospectivos , Natimorto , Inquéritos e Questionários , Reino UnidoRESUMO
OBJECTIVE: To study parental attitudes to participating in questionnaire research about perinatal postmortem immediately after late miscarriage, stillbirth and termination for fetal abnormality. DESIGN: Prospective self-completion questionnaire. SETTING: UK fetal medicine and delivery unit. PATIENTS: 35 women and their partners after second or third trimester pregnancy loss, making decisions about having a postmortem. METHODS: Participants were asked to complete a questionnaire about postmortem decision-making which included questions about their attitudes to taking part in research. Prior to giving full approval for the study, the Research Ethics Committee (REC) requested feedback after 10 questionnaires had been returned. RESULTS: Responses from the first 10 participants were positive about the research and the REC allowed the study to continue. 31 questionnaires were received from parents of 17 babies (49% of those asked; 16 from mothers, 15 from fathers). Of the 22 participants who answered a question about the impact of participating in this research, 73% stated that completing the questionnaire had helped them feel better about the decision whether or not to consent to postmortem and none reported any adverse effect of completing the questionnaire. Additional comments made by 19 participants supported this finding. CONCLUSION: Research into this sensitive area of perinatal medicine where there is a poor outcome is possible and is indeed well received by many parents. RECs should not automatically take a negative stance towards studies of this type.
Assuntos
Aborto Espontâneo/psicologia , Atitude Frente a Morte , Morte Fetal , Pais/psicologia , Natimorto/psicologia , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gravidez , Sujeitos da Pesquisa/psicologia , Inquéritos e Questionários , Adulto JovemRESUMO
The aim of this study was to determine whether women induced for obstetric cholestasis (OC) have increased rates of operative delivery compared with women without OC who are induced. This retrospective case-control study included 64 women with OC (singleton pregnancies), who had labour induced compared with two control groups (matched for parity and gestational week at delivery). The majority of women were induced at 37 weeks. We found no significant increase in the rate of operative or assisted delivery in OC cases compared with either control group. Women with OC who are induced between 36 and 40 weeks gestation do not have increased rates of assisted or operative delivery compared with induced controls.
RESUMO
Assessment of fetal growth and wellbeing is one of the major purposes of antenatal care. Some fetuses have smaller than expected growth in utero and while some of these fetuses are constitutionally small, others have failed to meet their growth potential, that is they are growth restricted. While severe growth restriction is uncommon, the consequences of it being undetected may include perinatal death or severe morbidity. It is, therefore, important to have strategies in place to detect the fetus at risk of growth restriction. These would include an assessment of 'prior risk' from maternal history and examination combined with the results of biochemical and ultrasound investigations, the most promising of which are uterine artery Doppler and biochemistry. We discuss some of the factors to consider when stratifying the obstetric population into degrees of likelihood for growth restriction, and discuss aspects of the management and outcome of pregnancies complicated by growth restriction.
Assuntos
Retardo do Crescimento Fetal/diagnóstico , Ultrassonografia Pré-Natal/métodos , Biomarcadores , Feminino , Monitorização Fetal , Humanos , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional/fisiologia , Valor Preditivo dos Testes , Gravidez , Segundo Trimestre da Gravidez/sangue , Prognóstico , Medição de Risco , Ultrassonografia DopplerRESUMO
OBJECTIVE: To determine the early outcome and the incidence of associated structural anomalies in pregnancies complicated by severe fetal ventriculomegaly (VM). METHODS: A review of cases of severe fetal VM (posterior horn of lateral ventricle > 15 mm at referral or during prenatal follow-up) referred to a fetal medicine centre in Eastern England over 4 years from 2001 was made. Results of specialist prenatal investigations including ultrasound (US), karyotype, antiplatelet antibodies and congenital infection screen were noted. Neonatal clinical and cranial US findings, autopsy findings and neurodevelopmental follow-up at 4 months were obtained. RESULTS: Twenty cases of severe VM were identified, including 3 with spina bifida. Median gestation at diagnosis was 28 weeks (range 16-36 weeks). Twelve cases had additional intra-cranial abnormalities and two had abnormalities outside the central nervous system. One case was complicated by toxoplasmosis. There was one case of trisomy 21. Ten pregnancies were terminated. Ten babies were live born, all of whom had VM confirmed, and two of these babies died within 4 months. Of the remaining eight, seven have abnormal neurodevelopment. CONCLUSIONS: Severe VM is often diagnosed after the threshold of viability. Termination of pregnancy was requested in about half the cases owing to the risk of long-term neurodisability, and in all cases diagnosed before 24 weeks. In those live born, there was abnormal outcome in all but one.
Assuntos
Anormalidades Múltiplas/epidemiologia , Ventrículos Cerebrais/anormalidades , Doenças Fetais/epidemiologia , Malformações do Sistema Nervoso/epidemiologia , Resultado da Gravidez , Anormalidades Múltiplas/diagnóstico por imagem , Anormalidades Múltiplas/patologia , Aborto Eugênico , Adulto , Agenesia do Corpo Caloso , Ventrículos Cerebrais/diagnóstico por imagem , Corpo Caloso/diagnóstico por imagem , Feminino , Doenças Fetais/diagnóstico por imagem , Doenças Fetais/patologia , Seguimentos , Idade Gestacional , Humanos , Recém-Nascido , Malformações do Sistema Nervoso/diagnóstico por imagem , Malformações do Sistema Nervoso/patologia , Gravidez , Prognóstico , Ultrassonografia Pré-Natal , Reino Unido/epidemiologiaRESUMO
OBJECTIVES: To determine detection and false-positive rates for trisomy 21 using two-stage combined nuchal translucency (NT) and triple testing, whilst disclosing abnormal nuchal measurements at the scan. METHODS: A prospective audit in a UK women's hospital, of 3188 women with singleton pregnancies, requesting screening for trisomy 21. Median age was 37 years (range 19-46). Women were offered NT screening at 11 to 14 weeks. Those with NT > or =3 mm were offered chorionic villus sampling. Those declining CVS, and those with NT <3 mm, were offered early triple tests. Women with a term combined risk of trisomy 21 > or = 1:250, based on age, NT, and triple test results were offered amniocentesis. RESULTS: Using a 3-mm NT 'cut-off' identified 16/25 cases of trisomy 21 (64%; 95% CI 38.8, 78.9). Of 2725 women who had a combined nuchal plus triple test assessment, 79 (2.6%) had a > or = 1:250 term risk of trisomy 21. Forty (1.3%) had amniocentesis identifying 6/9 remaining cases (67%:95% CI:27.9, 92.5). Overall, the detection rate was 88% (95% CI:68.8, 97.5) for a 4.8% FPR. For the screened population, to achieve an 88% detection rate using the triple test alone, the predicted FPR would be 20%. Conversely, for an FPR of 4.8% using the triple test alone, the detection rate would be only 60%. CONCLUSION: In a high-risk group, the combination of NT with triple test offers detection of trisomy 21 at least equivalent to either test, while allowing disclosure of an abnormal NT at the scan and reducing the FPR. Importantly, the FPR is less than 5%, considerably lower than expected for triple test alone for this population.
Assuntos
Síndrome de Down/diagnóstico , Auditoria Médica , Medição da Translucência Nucal , Diagnóstico Pré-Natal/métodos , Adulto , Amniocentese , Gonadotropina Coriônica/sangue , Amostra da Vilosidade Coriônica , Síndrome de Down/diagnóstico por imagem , Estriol/sangue , Reações Falso-Positivas , Feminino , Idade Gestacional , Humanos , Pessoa de Meia-Idade , Gravidez , Diagnóstico Pré-Natal/estatística & dados numéricos , Estudos Prospectivos , Fatores de Risco , alfa-Fetoproteínas/análiseRESUMO
AIMS AND METHODS: To determine obstetrical and neonatal outcomes in referrals of apparently isolated mild ventriculomegaly following routine ultrasound scan, over the period 2001-2003. Specialist ultrasound and other investigations were performed. Neonatal examination and postnatal ultrasound findings were collected and local neurodevelopmental follow-up was obtained. RESULTS: 30 cases of suspected isolated mild ventriculomegaly (posterior horn of lateral ventricle 10-15 mm at diagnosis) were identified. There were two abnormal karyotypes, no abnormal TORCH screens, and only one false-positive alloimmune thrombocytopenia screen. In 21 cases, isolated ventriculomegaly was confirmed following specialist investigation. In 11 of 21 cases, ventriculomegaly resolved during antenatal follow-up, and in one case it progressed. Six of 21 had ventriculomegaly confirmed on postnatal ultrasound and lissencephaly was diagnosed in one following postnatal MRI. Of the 11 infants with antenatal resolution of ventriculomegaly, 2 have delayed development. The infant with progressive ventriculomegaly has severe developmental problems.