Biomedical subjects

Shaun P Brennecke

Publications and source records attributed to Shaun P Brennecke.

16 recordsLinked to original sources

PubMed2006

Homeobox gene ESX1L expression is decreased in human pre-term idiopathic fetal growth restriction.

Fetal growth restriction (FGR) is a clinically significant pregnancy disorder in which the fetus fails to achieve its full growth potential in utero. This study involved idiopathic FGR, which is frequently associated with placental dysfunction. Here, we investigated mRNA levels of the human placental homeobox gene ESX1L in pre-term and term idiopathic FGR pregnancies compared with gestation-matched controls. Real-time PCR quantitation showed ESX1L levels in control placentae decreased between pre-term and term [0.7 +/- 0.20 (27-35 weeks, n = 13) versus 0.2 +/- 0.06 (36-41 weeks, n = 12), t-test, P < 0.005]. ESX1L levels in FGR-affected placentae were significantly lower than in gestation-matched controls, and there was no significant change between pre-term FGR and term FGR [0.32 +/- 0.04 (27-36 weeks, n = 11) versus 0.31 +/- 0.02 (36-41 weeks, n = 14), t-test, P = 0.82]. Multiple linear regression analysis revealed a rapid decline in ESX1L expression in control placentae [0.075-fold of the calibrator for each week of gestation (95% CI = -0.105 to -0.045, P < 0.0005)]. In FGR-affected placentae, ESX1L levels were lower than in gestation-matched controls, and the decline in ESX1L levels with gestation was not significant [0.001-fold of the calibrator for each week of gestation (95% CI = -0.030 to 0.010, P < 0.3]. The linear relationship between ESX1L mRNA levels in FGR-affected placentae and gestation-matched controls during gestation was significantly different (likelihood ratio test for interaction, P = 0.0005). Our findings were consistent with a potential role for the ESX1L gene within the growth control mechanism of the fetus, through its effect on placental function.

Adult↗

PubMed2006

The effect of intrapartum fetal pulse oximetry, in the presence of a nonreassuring fetal heart rate pattern, on operative delivery rates: a multicenter, randomized, controlled trial (the FOREMOST trial).

OBJECTIVE: The objective of the study was to compare operative delivery rates for nonreassuring fetal status between 2 groups of laboring women: those having conventional cardiotocograph monitoring and those having cardiotocograph monitoring plus fetal pulse oximetry. STUDY DESIGN: The intrapartum fetal oximetry prospective, multicenter, randomized, controlled trial (the FOREMOST trial) was conducted in 4 Australian maternity hospitals. The primary outcome was operative birth rates for nonreassuring fetal status. RESULTS: There was a statistically significant 23% relative risk reduction in operative delivery for nonreassuring fetal status in the fetal pulse oximetry + cardiotocograph group (n = 75 of 305, 25%), compared with those in the cardiotocograph-only group (n = 95/295, 32%) (relative risk 0.77, 95% confidence interval 0.599, 0.999, P = .048). There were no significant between-group differences in overall operative births (fetal pulse oximetry + cardiotocograph group 73%, cardiotocograph-only group 71%, relative risk 1.04, 95% confidence interval 0.94, 1.15, P = .478) or neonatal outcomes. CONCLUSION: The use of fetal pulse oximetry to augment fetal well-being assessment during labor resulted in a statistically significant reduction in the operative intervention for nonreassuring fetal status, compared with the use of conventional cardiotocograph monitoring alone. This reduction was achieved with no significant difference in neonatal outcomes.

Adult↗

PubMed2006

Expression of adrenomedullin mRNA is altered with gestation and labour in human placenta and fetal membranes.

The aim of the present study was to investigate whether placental and fetal membrane AdM (adrenomedullin) mRNA expression changes with gestation and human labour, as we have previously found labour-associated changes in AdM content in fetal membranes [Al-Ghafra, Gude, Brennecke and King (2003) Clin. Sci. 105, 419-423]. Placentas and fetal membranes were collected either at term or pre-term from women either in-labour or not-in-labour, and AdM mRNA abundance was measured in tissue extracts by Northern blot analysis. Increases were found in the relative abundance of amniotic tissue AdM mRNA in both in-labour and not-in-labour groups at term compared with those at pre-term, and there were positive correlations with gestational age. Relative abundance of choriodecidual tissue AdM mRNA was also significantly elevated in the not-in-labour groups between pre-term and term tissues, although there was no significant correlation with gestational age. However, placental AdM mRNA expression was neither significantly increased at term (compared with pre-term) nor correlated with gestational age. In addition, there were significant increases in AdM mRNA in amnion and choriodecidua in the in-labour group compared with the not-in-labour group for both pre-term and term gestations. There was no difference in AdM mRNA in placental tissues between labour groups. In conclusion, the present study provides evidence that AdM production by fetal membranes is increased in amniotic and choriodecidual tissues at term, compared with pre-term, and in response to labour.

Adrenomedullin↗

PubMed2006

The -56T HLA-G promoter polymorphism is not associated with pre-eclampsia/eclampsia in Australian and New Zealand women.

OBJECTIVE: Decreased HLA-G expression has been linked to a number of pregnancy disorders, including preeclampsia, and a genetic basis for HLA-G regulation has yet to be found. The aim of this study was to determine whether a C-to-T base substitution 56 base pairs (bp) upstream from the HLA-G transcription start site is associated with preeclampsia. METHODS: 277 nulliparous women consisting of 113 normotensive, 118 preeclamptic, and 46 eclamptic patients were typed for the -56T polymorphism using restriction fragment length polymorphism and allelic discrimination analysis. RESULTS: -56T allele frequencies for eclamptic, preeclamptic, and normotensive women were 0.053, 0.030, and 0.035, respectively. A chi2 test indicated that there was no significant association with the polymorphism in preeclamptic or eclamptic women with p > 0.05. CONCLUSION: The -56T HLA-G polymorphism is not associated with preeclampsia or eclampsia in our population.

Australia↗

PubMed2006

Women's evaluations of their experience in a multicenter randomized controlled trial of intrapartum fetal pulse oximetry (The FOREMOST Trial).

BACKGROUND: Fetal pulse oximetry improves the assessment of fetal well-being during labor. The objective of this study was to evaluate women's satisfaction with their experience with this additional technology. METHODS: We surveyed women participating in the FOREMOST trial, a randomized controlled trial comparing the addition of fetal pulse oximetry (FPO) to conventional cardiotocograph (CTG) monitoring (intervention group), versus CTG-only (control group), in the presence of nonreassuring fetal status during labor. Our survey evaluated 3 aspects of women's experience: labor, fetal monitoring, and participation in the research. The survey was administered within a few days of giving birth and repeated 3 months later. RESULTS: No differences were found between the intervention and control groups for women's evaluations of their labor, fetal monitoring, research, or overall experiences when surveyed on both occasions. Within each study group, a small but statistically significant decline occurred in women's scores for their experience of labor and overall experience from the initial survey close to the time of giving birth, to 3 months later. The magnitude of differences in responses over time was similar for the both groups. Women were more satisfied after a spontaneous or assisted vaginal birth than after cesarean section. Length of time the research midwife was present had a significant positive effect on women's ratings of their experience several days after giving birth (p = 0.006), but no effect at 3 months. CONCLUSIONS: The addition of fetal pulse oximetry for the assessment of fetal well-being during labor did not affect childbearing women's perceptions of fetal monitoring or their labor. Women evaluated their experience in the research process positively overall. Small changes occurred in women's perception of their satisfaction over time.

Adult↗

PubMed2006

Clinicians' evaluations of fetal oximetry sensor placement in a multicentre randomised trial (the FOREMOST trial).

BACKGROUND: Fetal pulse oximetry (FPO) may improve the assessment of the fetal well-being in labour. Reports of health-care provider's evaluations of new technology are important in the overall evaluation of that technology. AIMS: To determine doctors' and midwives' perceptions of their experience placing FPO sensors. METHODS: We surveyed clinicians (midwives and doctors) following placement of a FPO sensor during the FOREMOST trial (multicentre randomised trial of fetal pulse oximetry). Clinicians rated ease of sensor placement (poor, fair, good and excellent). Potential influences on ease of sensor placement (staff category, prior experience in Birth Suite, prior experience in placing sensors, epidural analgesia, cervical dilatation and fetal station) were examined by ordinal regression. RESULTS: There were 281 surveys returned for the 294 sensor placement attempts (response rate 96%). Sensors were placed by midwives (29%), research midwives (48%), registrars (22%) and obstetricians (1%). The majority of clinicians had 1 or more years' Birth Suite experience, had placed six or more sensors previously, and rated ease of sensor placement as good. Advancing fetal station (P < 0.001) and the presence of epidural analgesia prior to sensor placement (P = 0.029) predicted improved ease of sensor placement. Having a clinician placing a sensor for the first time predicted a lower rating for ease of sensor placement (P = 0.001), compared to having placed one or more sensors previously. CONCLUSIONS: Clinicians with varying levels of Birth Suite experience successfully placed fetal oxygen saturation sensors, with the majority rating ease of sensor placement as good.

Adult↗

PubMed2006

Homeobox gene HLX1 expression is decreased in idiopathic human fetal growth restriction.

Fetal growth restriction (FGR) is a clinically significant pregnancy disorder in which the fetus fails to achieve its full growth potential in utero. Identifiable causes of FGR account for approximately 30% of cases, but the remainder are idiopathic and are frequently associated with placental malfunction. Previously, we isolated the homeobox gene HLX1 and provided evidence for a regulatory role in normal placental development. Here, we investigated whether placental HLX1 expression levels are changed in placentas from idiopathic FGR pregnancies. Real-time polymerase chain reaction quantitation showed reduced HLX1 mRNA levels with advancing gestation age (preterm control placentas, 27 to 35 weeks, 1.1 +/- 0.3, n = 13, versus term placentas 36 to 41 weeks, 0.74 +/- 0.02, n = 12, P < 0.005). FGR-affected placentas had significantly lower levels of HLX1 expression compared with gestation age-matched controls (0.36 +/- 0.07 versus 1.05 +/- 0.2, n = 25, P < 0.001). Immunoblotting with a rabbit polyclonal HLX1 antibody revealed reduced levels of HLX1 in FGR-affected placentas compared with controls (481.07 +/- 12.3 versus 2766.7 +/- 30.3, n = 10, P < 0.001). Immunohistochemistry showed a qualitative decrease in HLX1 immunoreactivity in FGR-affected term placentas compared with controls. This is the first demonstration that a homeobox transcriptional regulator shows altered expression in an important human placental disorder, suggesting that decreased HLX1 levels contribute to the abnormalities in placental developmental seen in idiopathic FGR.

Adult↗

PubMed2005

5 Beta-dihydroprogesterone and steroid 5 beta-reductase decrease in association with human parturition at term.

The role of progesterone withdrawal in human parturition continues to provoke controversy. One possible mechanism by which functional progesterone withdrawal may be achieved is by a decrease in the circulating concentration of its bioactive metabolites. The progesterone metabolite 5beta-dihydroprogesterone (5betaDHP) has been shown to be a potent tocolytic in vitro. We quantified plasma concentrations of 5betaDHP in association with the onset of spontaneous labour in women at term and steroid 5beta-reductase mRNA expression in placenta, myometrium, chorion and amnion in relation to parturition, using real time RT-PCR. Serial blood samples were obtained from patients late in pregnancy, before term labour, during term labour and within the first 24 h postpartum. Following organic solvent extraction, steroids including 5betaDHP were separated by high-performance liquid chromatography (HPLC) and then quantified by radioimmunoassay (RIA). 5betaDHP concentration decreased two-fold (P = 0.00001, n = 25) from 0.317 +/- 0.039 nmol/ml to 0.178 +/- 0.017 nmol/ml in association with active labour. Tissue 5beta-reductase mRNA-relative abundance was determined in placenta, myometrium, chorion and amnion obtained from labouring and non-labouring women. In placenta and myometrium, relative expression decreased significantly in association with labour, by about two-fold and 10-fold, respectively. These data are consistent with a possible role for 5betaDHP in the onset of spontaneous human labour. Further studies exploring this hitherto unrecognized endocrinological pathway are indicated.

5-alpha-Dihydroprogesterone↗

PubMed2004

Association of the TNF2 allele with eclampsia.

The genetic background predisposing pregnant women to the disorder pre-eclampsia/eclampsia (PE/E) is still unknown. There is compelling evidence to suspect involvement of the immune system in the development of PE/E. The aim of this current study was to investigate whether there is an association between the tumor necrosis factor (TNF)-alpha -307 polymorphism and PE or eclampsia. In this study, 51 cases of eclampsia, 122 cases of PE and 100 normotensive control cases were genotyped for the TNF-alpha -307 polymorphism. We found a significant difference between the TNF2 allele frequencies of eclamptic and normotensive controls (chi(2) = 6.3 and p = 0.025), but not of pre-eclamptic and normotensive controls (chi(2) = 0.5 and p = 1.0). We conclude from this study that the TNF2 allele contributes to the occurrence of eclampsia in our population.

Alleles↗

PubMed2004

Proteomic approaches in endometriosis research.

To date, the quest to develop a noninvasive diagnostic test for endometriosis has mostly concentrated on the levels of cytokines and growth factors that are involved in inflammation, angioneogenesis and tissue remodeling, present in serum, peritoneal fluid, endometrium and endometriotic lesions. As this has not yet translated into the development of such a diagnostic test, proteomic techniques are now being employed to identify proteins that are potential biomarkers for the disease. As proteomics allows the comprehensive analysis of complex fluid and tissue samples with good sensitivity and resolution, it has promise in delivering markers associated with endometriosis. Once identified, the challenge will be in translating these markers into a clinically useful test for endometriosis, as the pathophysiology of this disease is unknown and likely to be complex and multifactorial. Also, with variation between individuals and the influences of steroid hormones during the menstrual cycle, it could be difficult to validate findings relating to a single protein or small groups of proteins differentially expressed in the disease state. Proteomic profiling, using mass spectrometry in combination with sophisticated bioinformatics software to identify protein patterns, may be where a significant clinical diagnostic contribution can be made.

Endometriosis↗

PubMed2004

Patient satisfaction with the SpaceLabs 90207 ambulatory blood pressure monitor in pregnancy.

OBJECTIVE: The objective of this study was to evaluate the acceptability of the SpaceLabs 90207 ambulatory blood pressure monitor among pregnant women. METHODS: Patients participating in research projects involving ambulatory blood pressure monitoring (ABPM) in pregnancy (N = 110) were asked to complete a questionnaire relating to patient satisfaction on completion of the monitoring period. The first part of the questionnaire involved rating on a visual Likert scale (0-10) whether they found the monitor heavy, noisy, cumbersome, disturbing, or embarrassing to wear. The second part of the questionnaire addressed whether cuff inflation caused significant sleep disturbance or physical discomfort. OUTCOME MEASURES: The mean (SD) and range of the Likert scores are reported. The number of patients reporting sleep disturbance or physical discomfort was calculated. Logistic regression was used to examine which factors were significant predictors of discontinuing monitoring. RESULTS: The mean (SD) responses measured by the Liken scores were: finding the monitor heavy 3.2 (2.3); comfortable 4.8 (2.3); straightforward to use 8.8 (1.8); cumbersome 3.8 (2.3); disturbing 4.5 (2.7); noisy 1.6 (2.2); and embarrassing to wear 1.7 (2.1). Difficulty initiating sleep was reported by 28.8% of patients, and a further 56.3% reported difficulty maintaining sleep due to the monitor. Sleep disturbance was found to be the strongest predictor [r = 0.52; OR 1.68 (1.23, 2.27), p = 0.0009] for the 15% of patients discontinuing the monitoring. CONCLUSIONS: While pregnant women tolerate the noise, weight, inconvenience, and disturbance associated with ambulatory blood pressure monitoring (ABPM) well, sleep disturbance is a major cause of dissatisfaction and noncompliance. Future studies should evaluate critically the number of nocturnal blood pressure assessments required, and should allow for a withdrawal rate of approximately 15% when performing sample size calculations for ABPM studies in pregnancy.

Blood Pressure Monitoring, Ambulatory↗

PubMed2004

Cervical surveillance as an alternative to elective cervical cerclage for pregnancy management of suspected cervical incompetence.

OBJECTIVE: The aim of the present study was to compare the outcome of pregnancies among patients with suspected cervical incompetence treated either by elective cervical cerclage or an alternative management program involving cervical surveillance. DESIGN, SETTING AND METHODS: A prospective cohort study was performed in two groups of patients at risk of cervical incompetence with singleton gestations attending the Royal Women's Hospital, Melbourne, Australia, from 1996 to 2000. The first group was managed by their obstetric carers with an elective cerclage, while the second group was managed conservatively as part of a cervical surveillance program offered to patients attending the Department of Perinatal Medicine for pregnancy care. This program consists of weekly visits from 16 weeks' gestation and involves alternating transvaginal ultrasound assessment of cervical morphometry with cervico-vaginal bacteriology and fetal fibronectin swabs. Empiric insertion of a cerclage is undertaken when there is evidence of significant cervical shortening (cervical canal <2.5 cm in length at </=24 weeks). RESULTS: A total of 135 patients were identified for the study. Ninety-seven patients had an elective cervical cerclage inserted. Thirty-eight patients were followed through the cervical surveillance program. Twelve (32%) of the surveillance patients had a cerclage inserted at a mean gestational age of 20.6 weeks. There were no statistically significant differences between the groups in terms of maternal demographics or risk assessment scoring. One out of 38 (2.6%) patients of the surveillance group and 18/97 (18.6%) of the elective cerclage group delivered before 30 weeks' gestation (P = 0.034). CONCLUSIONS: Our study suggests that by only inserting a cerclage when indicated on the basis of ultrasound assessment of cervical morphometry, the number of cerclages required can be reduced while the perinatal outcome is significantly improved.

Adult↗

PubMed2004

Factors identified during the neonatal period associated with risk of cerebral palsy.

OBJECTIVE: To identify factors during the neonatal period that are associated with the subsequent development of cerebral palsy (CP). DESIGN: Case-control study. SETTING: Ten hospitals in Victoria, Australia. SAMPLE: Cases were babies with moderate or severe CP identified from the Victorian Cerebral Palsy Register. Controls were matched with cases for year of birth, plurality, sex, birthweight, gestation and hospital of birth. METHODS: A range of neonatal variables was compared between cases and controls, initially in a univariate analysis and subsequently in a logistic regression. The analysis was matched where possible. Where missing data prevented a matched analysis, an adjusted unmatched analysis was performed. MAIN OUTCOME MEASURES: Those neonatal factors making an independent contribution to the risk of CP in both term and preterm infants. RESULTS: Among babies born at term, 73% of cases and 2% of controls were identified by at least one of the following factors: seizures, congenital abnormalities of the brain and elsewhere, 'other lesions', abnormal muscle tone and meconium aspiration. Among babies born preterm, 68% of cases and 26% of controls were identified by the following factors: seizures, intraventricular haemorrhage, periventricular leukomalacia, 'other lesions' and abnormal muscle tone. CONCLUSIONS: The neonatal factors which best identify neonates who will subsequently develop CP are different for term and preterm babies. Babies born at term are identified more efficiently than those born preterm. Among term babies especially, some of these factors are clearly of a long-standing nature and are not associated with delivery.

Apgar Score↗

PubMed2003

Effect of fetal macrosomia on human placental glucose transport and utilization in insulin-treated gestational diabetes.

The aim of this study was to compare glucose transport and utilization in human placentae from pregnancies affected by insulin-treated GDM with and without macrosomia, and from non-diabetic control pregnancies. Placental lobules were perfused for 4 h. Maternal D-glucose concentration was 4, 8, 16, or 24 mM while the fetal D-glucose was maintained at 3mM. 14C-D-glucose and 3H-L-glucose were infused into the maternal circulation. Radioactivity, D-glucose and L-lactate levels were measured in the fetal and maternal effluent perfusates. Glucose uptake from the maternal perfusate, and transfer to the fetal effluent were not significantly different between groups. Insulin-treated GDM group without macrosomia had reduced glucose utilization compared to the control group while the insulin-treated GDM group with macrosomia did not. Lactate release into the fetal effluent was significantly reduced in both insulin-treated GDM groups compared to the control group. In conclusion, placental glucose utilization is different between insulin-treated GDM placentae with and without fetal macrosomia.

Adult↗

PubMed2002

Update on intrapartum fetal pulse oximetry.

This article examines the current status of fetal pulse oximetry (FPO) as a means of intrapartum assessment of fetal wellbeing. FPO has been developed to a stage where it is a safe and accurate indicator of intrapartum fetal oxygenation. In general, sliding the FPO sensor along the examiner's fingers and through the cervix, to lie alongside the fetal cheek or temple is easy The recent publication of a randomised controlled trial (RCT) of FPO versus conventional intrapartum monitoring has validated its use to reduce caesarean section rates for nonreassuring fetal status. An Australian multicentre RCT is currently underway. Maternal satisfaction rates with FPO are high. FPO may be used during labour when the electronic fetal heart rate trace is nonreassuring or when conventional monitoring is unreliable, such as with fetal arrhythmias. If the fetal oxygen saturation (FSpO2) values are < 30%, prompt obstetric intervention is indicated, such as fetal scalp blood sampling or delivery FSpO2 monitoring should not form the sole basis of intrapartum fetal welfare assessment. Rather, the whole clinical picture should be considered.

Female↗

PubMed2002

Thrombomodulin Ala455Val dimorphism is not associated with pre-eclampsia in Australian and New Zealand women.

Thrombomodulin plays an important role in thromboresistance. A common mutation of the gene at amino acid 455 producing valine instead of alanine has been implicated as being a risk factor in myocardial infarction and chronic heart disease. However, its link with pre-eclampsia remains controversial. This report explores the Ala455Val point mutation in 280 women as a predictor of pre-eclampsia with the conclusion that in this regard, the dimorphism is essentially neutral.

Alleles↗