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Biomedical subjects

P W Soothill

Publications and source records attributed to P W Soothill.

At least 19 recordsLinked to original sources
PubMed2006

Detection of cell-free fetal DNA in maternal urine.

OBJECTIVE: To evaluate the presence of cell-free fetal DNA signals in maternal urine as a potential source of material for non-invasive prenatal diagnosis. STUDY DESIGN: Patients referred to the regional fetal medicine unit who underwent prenatal diagnosis by chorionic villus sampling (CVS) were asked to give blood and urine immediately before the procedure. Maternal blood and urine were centrifuged at 10,000 g for 10 min. Plasma (1 mL) and urine (1 mL) supernatant were transferred to a clean tube and centrifuged again. The plasma (0.8 mL) and urine (0.8 mL) supernatant were removed without disturbing the cell pellet and stored at - 80 degrees C. Following DNA extraction, each sample was tested for the presence of Y chromosome associated DYS14 gene using real-time polymerase chain reaction (PCR). The total amount (maternal and fetal) of DNA in each sample was estimated using a quantitative real-time PCR assay. RESULTS: Twenty patients were enrolled in the study. CVS was performed at a median gestational age of 13 weeks (range 11 + 5 - 14 + 1). There were 12 male and 8 female fetuses, as confirmed by karyotype. Y chromosome DNA was not detected in any of the 20 samples of maternal urine, including 12 of the 20 samples in which Y chromosome DNA was detected in maternal plasma (all of whom were subsequently confirmed to be carrying a male fetus). There was considerable variation in the amount of total free DNA detected in maternal urine. CONCLUSIONS: Cell-free fetal DNA either was not present or did not amplify in maternal urine.

Biomarkers↗
PubMed2005

Antenatal interventions for fetomaternal alloimmune thrombocytopenia.

BACKGROUND: Fetomaternal alloimmune thrombocytopenia occurs when the mother produces antibodies against a platelet alloantigen that the fetus has inherited from the father. A consequence of this can be a reduced number of platelets (thrombocytopenia) in the fetus, which can result in bleeding whilst in the womb or shortly after birth. In severe cases this bleeding may lead to long-lasting disability or death. Antenatal management of fetomaternal alloimmune thrombocytopenia centres on preventing severe thrombocytopenia in the fetus. Available management options include administration of intravenous immunoglobulins or corticosteroids to the mother or intrauterine transfusion of antigen compatible platelets to the fetus. All options are costly and need to be assessed in terms of potential risk and benefit to both the mother and an individual fetus. OBJECTIVES: To determine the optimal antenatal treatment of fetomaternal alloimmune thrombocytopenia to prevent fetal and neonatal haemorrhage and death. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register (February 2004), EMBASE (1980 to February 2004) and bibliographies of relevant publications and review articles. SELECTION CRITERIA: Randomised controlled studies comparing any intervention, including corticosteroids with no treatment, or comparing any two interventions. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed eligibility, trial quality and extracted data. MAIN RESULTS: One study met the inclusion criteria (54 pregnant women). This trial compared intravenous immunoglobulins plus corticosteroid (dexamethasone) with intravenous immunoglobulins alone. No significant differences were reported between the treatment and control groups, in any outcome measured: mean platelet count at birth (weighted mean difference (WMD) 14.10 x 10 9/l, 95% confidence interval (CI) -30.26 to 58.46), mean gestational age at birth (WMD -0.50 weeks, 95% CI -2.69 to 1.69), mean rise in platelet count from first to second fetal blood screen (WMD -3.50 x 10 9/l, 95% CI -24.62 to 17.62) and mean rise in platelet count from birth to first fetal blood screen (WMD 24.40 x 10 9/l (95% CI -14.17 to 62.97)). This trial had adequate methodological quality; however the method used to calculate sample size was inappropriate: therefore the power calculation was not sufficient to determine any significance in differences between the treatment groups. AUTHORS' CONCLUSIONS: There are insufficient data from randomised controlled trials to determine the optimal antenatal management of fetomaternal alloimmune thrombocytopenia. Future trials should consider the dose of intravenous immunoglobulins, the timing of initial treatment, monitoring of response to treatment by fetal blood sampling, laboratory measures to define pregnancies with a high risk of intercranial haemorrhage, management of non-responders and long-term follow up of children.

Antigens, Human Platelet↗
PubMed2005

Comparison of different reference values of fetal blood flow velocity in the middle cerebral artery for predicting fetal anemia.

OBJECTIVES: To compare different normal reference ranges of fetal blood flow velocity in the middle cerebral artery for predicting fetal anemia. METHODS: Eight reference ranges of either middle cerebral artery peak or time-averaged mean velocities were compared using the area under the receiver-operating characteristics (ROC) curve for 113 fetal blood samples from 60 women at risk of fetal red blood cell alloimmunization. RESULTS: The areas under the ROC curves of the different ranges were not significantly different but there were marked differences in sensitivity (range, 7.14-91.78%) and specificity (range, 31.25-96.88%) with the currently used cut-offs. Except for Mari's range, the best theoretical cut-offs, defined as those having the best sensitivity with the best specificity, differed from those in current use, especially when using time-averaged mean velocity. CONCLUSIONS: Any of the previously reported reference ranges perform well in the non-invasive prediction of fetal anemia. However, with the exception of Mari's curve, the currently employed cut-offs for predicting fetal anemia should be changed, some of them markedly, in order to provide reliable support for clinical decisions.

Blood Flow Velocity↗
PubMed2005

Outcome of fetal pleural effusions treated by thoracoamniotic shunting.

OBJECTIVE: Fetal pleural effusions are uncommon, and treatment options for moderate or severe effusions include drainage and thoracoamniotic shunting. However, relatively few records of effusions treated by thoracoamniotic shunting are available in the literature, so our objective was to study the outcome after thoracoamniotic shunting in our unit. METHODS: We searched the database of our tertiary fetal medicine unit for all cases of fetal pleural effusion treated by thoracoamniotic shunting between 1997 and 2003 inclusive, and studied the maternal and neonatal records. RESULTS: Ninety-two cases of fetal pleural effusion were studied, of which 21 had undergone a thoracoamniotic shunt. Sixteen of these 21 fetuses (76%) had associated hydrops, of which seven (44%) survived and, of the five (24%) without associated hydrops, three (60%) survived. There were two procedure-related losses. No shunted cases were associated with abnormal karyotype or proven maternal infection, but it is probable that three cases had been caused by an underlying genetic syndrome. CONCLUSION: The survival of fetuses with severe pleural effusions after thoracoamniotic shunting in this study was 48%.

Amniotic Fluid↗
PubMed2005

Reactivity of T cells from women with antibodies to the human platelet antigen (HPA)-1a to peptides encompassing the HPA-1 polymorphism.

The human platelet antigen-1a (HPA-1a) is the most common alloantigenic target in fetal and neonatal alloimmune thrombocytopenia (NAIT). Treatment currently depends on the outcome in previous pregnancies. HPA-1 specific T cell responses were determined in 14 HPA-1a alloimmunized women during or after pregnancies affected by NAIT. Peripheral blood mononuclear cells were incubated with peptides encompassing the Leu33Pro polymorphism (residues 20-39 and 24-45 in both Leu33 (HPA-1a) and Pro33 (HPA-1b) forms) or control recall antigens in the presence of autologous sera and T cell proliferation was measured by (3)H-thymidine incorporation. Control antenatal and postpartum sera suppressed T cell proliferation and use of such sera was avoided. Most patients (86%) responded to the HPA-1a peptides with 64% also having weaker T cell proliferation to the HPA-1b peptides; 14% had no activity towards any peptide despite responding to control antigens. Administration of IVIG during pregnancy appeared to reduce T cell reactivity to HPA-1 peptides. Postnatal anti-HPA-1a T cell responses from women who had a severe history of NAIT (an intracranial haemorrhage in a previous fetus) were greater than those from women with a mild history. This assay may have the potential to predict disease severity if performed prior to or early in pregnancy.

Antigens, Human Platelet↗
PubMed2003

The effect of metabolic control on fetal nuchal translucency in women with insulin-dependent diabetes: a preliminary study.

OBJECTIVE: Diabetes could potentially alter fetal nuchal translucency (NT) measurements mainly by increasing microvascular permeability. The aim of this study was to test this hypothesis. METHODS: Sixty-five women with pre-pregnancy insulin-dependent diabetes mellitus undergoing NT screening were evaluated. The main outcome measure was the NT measurement, expressed as both absolute measurements and delta values (number of standard deviations by which the observed value differed from the normal mean for the same gestation). The relationships between NT and years of diabetes, insulin dose, glycosylated hemoglobin, and glycemic capillary profiles ('tight' glycemic control) were studied. RESULTS: There was no significant correlation between NT and any of the studied parameters. There were no differences in NT according to the result of either glycosylated hemoglobin or 'tight' control. CONCLUSIONS: Metabolic control does not affect the result of ultrasound-determined fetal NT measurement which, when available, seems to be the best option for screening for Down syndrome in women with diabetes mellitus.

Adult↗
PubMed2003

Fetal sex determination from maternal blood at 6 weeks of gestation when at risk for 21-hydroxylase deficiency.

BACKGROUND: 21-hydroxylase deficiency can lead to masculinization of female fetuses. Corticosteroid therapy may reduce these effects. When the fetus is male, this approach means that unnecessary treatment, with theoretic side effects, is given until the result of chorionic villus sampling (CVS), a procedure with known risks, is available. CASE: A woman was referred for prenatal assessment at 6 weeks' gestation because her first daughter had been born virilized from 21-hydroxylase deficiency. A real-time polymerase chain reaction assay was performed on maternal blood to detect the fetal Y chromosome-associated SRY gene. A positive signal for the SRY gene was observed. The assay was repeated a few days later, and the result was again consistent with a male fetus. CONCLUSION: Analysis of cell-free fetal deoxyribonucleic acid in maternal plasma for fetal sex determination might reduce the need for corticosteroid administration and CVS in women with fetuses at risk for 21-hydroxylase deficiency.

Adrenal Hyperplasia, Congenital↗
PubMed2002

Prediction of fetal D status from maternal plasma: introduction of a new noninvasive fetal RHD genotyping service.

BACKGROUND: Invasive procedures to obtain fetal DNA for prenatal blood grouping present a risk to the fetus. During pregnancy, cell-free fetal DNA is present in maternal blood. The detection of RHD sequences in maternal plasma has been used to predict fetal D status, based on the assumption that RHD is absent in D- genomes. STUDY DESIGN AND METHODS: Real-time PCR assays were designed to distinguish RHD from RHDpsi (possessed by the majority of D- black Africans). Plasma-derived DNA from 137 D- women was subjected to real-time PCR to detect fetal RHD and Y chromosome-associated SRY sequences. The accuracy of RHD genotyping from maternal plasma was investigated by comparing results with those obtained by conventional RHD genotyping from fetal tissue or serologic tests on the infant's RBCs. The quantity of fetal DNA in maternal plasma was investigated in 94 pregnancies. RESULTS: Fetal D status was predicted with 100-percent accuracy from maternal plasma. The number of copies of fetal DNA in maternal plasma was found to increase with gestation. CONCLUSION: Combination of the sensitivity of real-time PCR with an improved RHD typing assay to distinguish RHD from RHDpsi enables highly accurate prediction of fetal D status from maternal plasma. This has resulted in the implementation of a clinical noninvasive fetal RHD genotyping service.

DNA↗
PubMed2002

Application of a novel human cervical mucin-based assay demonstrates the absence of increased mucinase activity in bacterial vaginosis.

Enzymes produced in bacterial vaginosis (BV) have been proposed as possible mediators of pre-term birth. Most studies have concentrated on mid-trimester measurements of enzyme activity, and utilize synthetic substrates to measure enzyme activity, which may not accurately represent mucinase activity in vivo. We have developed a novel ELISA mucinase assay using biotinylated human cervical mucin as a substrate. The assay is rapid, sensitive and can be used to screen large numbers of samples. The new assay has been used to assess vaginal mucinase activities in 92 women <14 weeks gestational age with and without BV. No differences in mucinase activity were detected between normal and BV groups while significant elevation of sialidase and other glycosidases was confirmed as reported before. This study shows that significant mucinase activity is a normal event in the mucus barrier, but does not reflect changes identified for individual enzyme activities associated with BV.

Adolescent↗
PubMed2002

Middle cerebral artery Doppler for the prediction of fetal anaemia in cases without hydrops: a practical approach.

The aim of this study was to assess the value of the middle cerebral artery (MCA) Doppler time-averaged mean velocity (TAMV) for the prediction of fetal anaemia in at-risk cases without ultrasound evidence of hydrops. The study included 35 pregnant women with non-hydropic fetuses and with known red cell antibodies, referred either because of a rapid increase in antibody levels or because of a previous history of a severely anaemic fetus or neonate. After full ultrasound examination of the fetus, MCA Doppler TAMV was measured and, if severe anaemia was suspected, fetal blood sampling by cordocentesis was performed with blood ready for intrauterine transfusion if necessary. Of the 35 fetuses, 28 were anaemic and 7 had a haemoglobin (Hb) value within the normal range. There was a strong negative correlation between the MCA Doppler TAMV and the Hb values (correlation coefficient r=-0.65, p<0.0001). The mean MCA Doppler TAMV (z score) for fetuses with normal Hb was 1.55+/-1.68, while that for the anaemic fetuses was 4.06+/-1.38, (p<0.001). The sensitivity of the increased MCA Doppler TAMV to predict fetal anaemia in these cases was 96.4% and the specificity was 71.4%. These data confirm that MCA Doppler TAMV is significantly correlated to fetal Hb. This non-invasive investigation can be reliable in predicting anaemia in cases in which the need to sample fetal blood is not certain, therefore delaying invasive testing until treatment is likely to be required.

Adolescent↗
PubMed2001

Outcome of fetal talipes following in utero sonographic diagnosis.

OBJECTIVES: To examine the association between fetal talipes and other defects, and outcome in relation to postnatal surgery. METHODS: All cases of talipes presenting to the fetal medicine unit between 1993 and 1998 and cases of isolated talipes presenting to the ultrasound department between 1991 and 1998 were examined. The infants were followed-up to determine the number of cases that had structural or positional talipes and the number of cases requiring surgery. RESULTS: There were 76 cases, 59 of which attended the fetal medicine unit and 17 the ultrasound department. Postnatal follow-up details were available in 31 of the 40 live births. There were three neonates with unilateral talipes at birth who were thought to have bilateral talipes on prenatal ultrasound and one neonate had bilateral talipes at birth who had been thought to have unilateral talipes prenatally. In two (6.4%) neonates in whom talipes was not confirmed at birth the abnormality was diagnosed prenatally. Of the 29 neonates with confirmed talipes at birth, the defect was structural in 26 (90%) cases and positional in three. Surgery was necessary in 21 (72%) of the 29 cases and 18 (86%) of those undergoing surgery required only one operation. When live births with associated anomalies were excluded, there were 24 cases with confirmed isolated talipes and 18 (75%) required surgery. CONCLUSIONS: This study provides long-term outcome data which can be used to complement current prenatal counseling and shows that in cases of fetal talipes diagnosed prenatally, 90% have a structural rather than a positional deformity. For isolated talipes three quarters of children will require surgery and in the majority of cases only one operation on the foot is necessary. Parents should be made aware of the small possibility of a false-positive diagnosis and discrepancy between the ultrasound and postnatal diagnoses of laterality.

Abnormalities, Multiple↗
PubMed2001

Vesicocentesis at 10-14 weeks of gestation for treatment of fetal megacystis.

This report of four cases shows that fetal vesicocentesis at 10-14 weeks of gestation is a useful treatment option in some cases with megacystis. Although megacystis at this gestation has been reported, there are few studies examining the role of early vesicocentesis. The natural history of the condition and outcome following treatment is reviewed with reference to the literature.

Adolescent↗
PubMed2001

Fetal protein loss in gastroschisis as an explanation of associated morbidity.

OBJECTIVE: Our purpose was to examine whether protein deficiency in utero develops in fetuses with gastroschisis. STUDY DESIGN: Twelve infants with prenatally diagnosed gastroschisis were compared with 29 control infants without gastroschisis and 2 infants with exomphalos who were delivered between 35 and 42 weeks of gestation. The groups were compared for birth weight, cord serum total protein and amniotic fluid total protein, and alpha-fetoprotein concentrations. The amniotic fluid samples were collected when the amniotic membranes were ruptured either during cesarean delivery or at artificial rupture of the membranes, and umbilical cord blood was obtained after delivery. RESULTS: In the 10 cases of gastroschisis in which cord serum total protein was measured, the median concentration was 51 g/L (range, 43-61 g/L) and was significantly lower than the median level of 62 g/L (range, 47-78 g/L) in the control group (P <.001). In the 8 cases of gastroschisis in which amniotic fluid total protein and alpha-fetoprotein concentrations were measured, the respective median levels were 5.1 g/L (range, 4.3-18.4 g/L) and 5.0 g/L (range, 2.4-13.2 g/L), which were significantly higher than the median levels of 2.0 g/L (range, 0.5-5.4 g/L) and 0.8 g/L (range, 0.5-1.7 g/L) in the control group (P <.0001). The ratio of amniotic fluid to cord serum total protein was significantly higher than that in the cases of exomphalos and in the control group (P <.001). The median birth weight in the neonates with gastroschisis was 2400 g (range, 1192-3155 g) and was significantly lower than the median value of 3535 g (range, 2520-4680 g) in the control group (P <.0001). CONCLUSIONS: Fetuses with gastroschisis have protein loss that could partly explain associated morbidity. However, whether this is a major contributor to poor fetal outcome remains to be shown.

Amniotic Fluid↗
PubMed2001

Noninvasive diagnosis of anemia in hydrops fetalis with the use of middle cerebral artery Doppler velocity.

OBJECTIVE: The purpose of this study was to assess the value of the middle cerebral artery time-averaged mean velocity for the detection of anemia as the cause of fetal hydrops. STUDY DESIGN: We examined 17 pregnant women with fetuses with hydrops (with ascites as the main component of hydrops) and who were considered at risk for anemia because there was no obvious explanation for the hydrops on the initial scan. Assessment included the measurement of the middle cerebral artery time-averaged mean velocity by color flow Doppler scan, followed by fetal blood sampling for investigations that included fetal hemoglobin. We investigated the correlation between increased middle cerebral artery time-averaged mean velocity (>2 SDs for gestational age) and fetal anemia (<2 SDs for gestational age). RESULTS: Eleven fetuses had anemia; 3 of the fetuses had red cell antibodies, and 6 of the fetuses had normal hemoglobin. There was a strong negative correlation between the middle cerebral artery time-averaged mean velocity and the hemoglobin values (r = -.9; P <.0001). The mean (z score) of middle cerebral artery time-averaged mean velocity for fetuses with normal hemoglobin was 1.1 +/- 0.81 and for the fetuses with anemia was 4.71 +/- 2.16 (P <.001). The sensitivity for the increased middle cerebral artery time-averaged mean velocity to predict fetal anemia was 91%, and the specificity was 100%. CONCLUSION: The middle cerebral artery time-averaged mean velocity is significantly increased in cases of hydrops caused by anemia, including cases other than red-cell alloimmunization. These findings can be useful for counseling and treatment and allow the investigation of the cause of hydrops without awaiting blood for intrauterine transfusion in patients who are very unlikely to be anemic and often avoids 2 procedures in those patients who require transfusion. Larger studies are required to further confirm these findings.

Adolescent↗
PubMed2001

Mucinases and sialidases: their role in the pathogenesis of sexually transmitted infections in the female genital tract.

BACKGROUND: Mucinases and sialidases contribute to the process of invasion and colonisation in many conditions and infections of the female reproductive tract by degrading the protective cervical mucus. The role of hydrolytic enzymes in the pathogenesis of sexually transmitted diseases and their effect on cervical mucus are discussed in this review. METHODS: Articles were searched for using the keywords "sialidase," "mucinase," "protease," and "sexually transmitted infections." As well as review and other articles held by our group, searches were conducted using PubMed, Grateful Med, and the University of Bath search engine, BIDS. RESULTS: Numerous publications were found describing the production of hydrolytic enzymes in sexually transmitted diseases. Because the number of publications exceeded the restrictions imposed on the size of the review, the authors selected and discussed those which they considered of the most relevance to sexually transmitted infections.

Cervix Mucus↗