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Biomedical subjects

P Soothill

Publications and source records attributed to P Soothill.

At least 19 recordsLinked to original sources
PubMed2007

Management of fetal growth restriction.

Fetal growth restriction (FGR) is challenging because of the difficulties in reaching a definitive diagnosis of the cause and planning management. FGR is associated not only with a marked increased risk in perinatal mortality and morbidity but also with long-term outcome risks. Combinations of fetal biometry, amniotic fluid volume, heart rate patterns, arterial and venous Doppler, and biophysical variables allow a comprehensive fetal evaluation of FGR. However, no evidence supports that the use of cardiotocography or the biophysical profile improves perinatal outcome. Therefore, obstetricians aim to identify fetuses with early FGR so delivery can be planned according to gestational age and severity of the condition. The balance of risks and the need for the availability of services mean that the involvement of neonatologists in FGR management is vital. In this review, the focus is on the pathophysiology and management of FGR caused by placental diseases.

Arteries↗
PubMed2006

Pregnancy outcomes in women with or without placental malaria infection.

OBJECTIVE: To assess delivery outcomes in women with placental malaria who presented at public hospitals in Kisumu, a holoendemic region in western Kenya. METHODS: A cross-sectional study using both histology and molecular biology was conducted with 90 consecutive pregnant women who presented at 3 hospitals during a 2-week period. Data collectors completed standardized questionnaires using each patient's hospital record and physical examination results, and registered birth indices such as weight, head circumference, and weight-head ratio. Malaria infection of the placenta was assessed using a molecular biology approach (for genomic differences among parasite species) as well as histology techniques. Of the 5 histologic classes of placental infection, class 1 corresponds to active infection and class 4 to past infection; class 2 and 3 to active chronic infection; and class 5 to uninfected individuals. Plasmodium species typing was determined by polymerase chain reaction amplification of the parasite's genome. RESULTS: In newborns at term, low birth weight was directly associated with classes 2 and 4 of placental infection (P = 0.053 and P = 0.003, respectively), and differences in birth weight remained significant between the 5 classes (P < 0.001) even after adjusting for parity and mother's age. Plasmodium falciparum was the only detected parasite. CONCLUSIONS: In Kisumu, infection with P. falciparum is an important cause of low birth weight and morbidity when it is associated with histologic classes 2 and 4 of placental infection. Moreover, polymerase chain reaction assays should be supported by ministries of health as an ancillary method of collecting data for malaria control during pregnancy and providing a baseline for future interventions.

Adolescent↗
PubMed2005

Prenatal diagnosis of echogenic lung: evolution and outcome.

OBJECTIVES: Despite the feasibility of detecting lung lesions by antenatal ultrasound, there are problems in correlating the prenatal diagnosis with the final histology and in predicting the outcome. In order to better describe these factors, we reviewed the outcome of fetuses that had been diagnosed with echogenic lung in a referral fetal medicine unit. METHODS: We searched the database of a tertiary fetal medicine unit for all cases of fetal echogenic lung seen since 1994 and studied the maternal and neonatal records found. RESULTS: There were 48 cases of echogenic lung diagnosed at a median gestational age of 21 (range, 19-29) weeks, including 43 (90%) cases of congenital cystic adenomatoid malformation (CCAM) and 5 (10%) of pulmonary sequestration (PS). The evolution of the fetal abnormality after diagnosis was: in 22 (45.8%) cases the lesion disappeared; in 17 (35.5%) cases the lesion remained stable and six (12.5%) cases became severe. Three (6%) women underwent termination of pregnancy. The lesions were equally distributed between the two sides of the thorax. Mediastinal shift was associated with a threefold increase in the possibility of clinical deterioration (17% vs. 5%), and the disappearance of the lesion was twice as likely to occur when the lesion was classified as microcystic as when it was macrocystic (67% vs. 36%). Features of hydrops were found in 9 (21%) fetuses and in six (13%) cases progressed and resulted in intrauterine or neonatal death. Sixty-four percent of cases with lesions that disappeared during the pregnancy had an abnormal computed tomography (CT) scan, and the prenatal diagnosis correlated with histology in 36% of these cases. Of the cases in which the lesions remained stable, 70.5% had an abnormal CT scan and the prenatal diagnosis correlated with the histology in 67% of the cases. CONCLUSIONS: Prenatally diagnosed echogenic lung has a good prognosis in the absence of hydrops. The ability to correctly assess echogenic lung lesions and the need for surgery by prenatal ultrasound is limited.

Cystic Adenomatoid Malformation of Lung, Congenita↗
PubMed2004

Fetal blood group genotyping from DNA from maternal plasma: an important advance in the management and prevention of haemolytic disease of the fetus and newborn.

The cloning of blood group genes and subsequent identification of the molecular bases of blood group polymorphisms has made it possible to predict blood group phenotypes from DNA with a reasonable degree of accuracy. The major application of this technology, which has now become the standard of care, is the determination of a fetal RHD genotype in women with anti-D, to assess whether the fetus is at risk of haemolytic disease of the fetus and newborn (HDFN). Initially, the procurement of fetal DNA required the invasive procedures of amniocentesis or chorionic villus sampling. Since the discovery of fetal DNA in maternal plasma in 1997, the technology of detecting an RHD gene in this very small quantity of fetal DNA has developed rapidly, so that non-invasive fetal D typing can now be provided as a diagnostic service for D-negative pregnant women with anti-D. Within a few years, it is probable that fetuses of all D-negative pregnant women will be tested for RHD, to establish whether the mother requires antenatal anti-D immunoglobulin prophylaxis.

Blood Group Antigens↗
PubMed2001

[Confirmation of a prenatal diagnosis of trisomy 13 with comparative genomic hybridization (CGH)].

Trisomy 13 was diagnosed with genetic amniocentesis in a fetus of a 50 years old patient. Fetopathologic examination has shown cyclopy, proboscis and semilobar holoprosencephaly of the fetus, which is consistent with Patau syndrome. DNA was extracted from frozen liver tissue. Result of comparative genomic hybridization (CGH) was consistent with trisomy 13. They processed the DNA according Kallioniemi's method with modifications. CGH was developed for cancer genetics in mid 90s and now it is widely used in prenatal diagnosis too. CGH allows global analysis to detect unbalanced chromosome gains and losses in the whole genome in a single experiment without the need for cell culture. Significant results can be expected in those cases where conventional cytogenetics is not able to provide an answer either because postmortem tissue is not appropriate for cytogenetics or because the chromosomal change is sub-microscopical. CGH is a fluorescent in situ hybridization on a healthy target metaphase, with equal amount of competitive hybridization of green labelled digested test DNA and red labelled digested control DNA. Red to green ratio is assessed with the help of an image analyser. Green dominance represents chromosome gain, while red shift chromosome loss. In the paper they present the fetopathologic report of a trisomy 13 fetus and illustrate the method being the first Hungarian obstetric case diagnosed by CGH.

Chromosomes, Human, Pair 13↗
PubMed2001

Analysis of outcome in hydrops fetalis in relation to gestational age at diagnosis, cause and treatment.

OBJECTIVE: To examine fetal outcome in hydrops fetalis in relation to gestational age at diagnosis and following investigation and treatment. METHODS: All cases of hydrops fetalis presenting to the Fetal Medicine Unit during the last seven years, between 1993 and 1999, were identified from the Fetal Medicine Database. During this time 87 of 13,980 patients who attended the Fetal Medicine Unit had hydrops fetalis. The cases were examined for gestational age at presentation according to etiology and fetal survival following investigation and treatment. The fetal survival rates for non-immune cases of hydrops before and after 24 weeks were compared. RESULTS: The cause of hydrops was determined antenatally in 71 of the 87 (82%) cases. Of the 51 cases presenting before 24 weeks' gestation, 23 (45%) were due to chromosomal abnormality. After 24 weeks, fetal tachyarrhythmias and hydrothorax were the most common causes and accounted for 14 (38%) of the 36 cases. Thirty-four cases (39%) of hydrops received intrauterine treatment. The survival rates excluding chromosomal abnormalities in the non-immune cases before and after 24 weeks' gestation were 31% and 48%, respectively, and were not significantly different. CONCLUSIONS: The survival rate in cases of hydrops fetalis may be improved with appropriate prenatal investigation and therapy. The etiology of hydrops is different before and after 24 weeks, and even when cases of chromosomal abnormality are excluded the survival rate is similar before and after 24 weeks.

Female↗
PubMed2001

Prenatal diagnosis of cleft lip and palate.

A prospective study was conducted over a period of 8 years to compare the severity of the cleft lip and palate detected by ultrasound scanning of the foetus with the severity at birth. In the UK all pregnant women undergo a routine perabdominal ultrasound scan at 20 weeks' gestation. There were approximately 250000 scans performed in our catchment area during the study period. A total of 270 children were born with cleft lip and/or palate, of which 130 had cleft lip with or without cleft palate. Out of these, 23 were positively diagnosed by the ultrasound scan. The specificity was 100% and the sensitivity was 17.5%. Only two diagnoses led to termination of the pregnancy.

Cleft Lip↗
PubMed2001

The role of comparative genomic hybridisation in prenatal diagnosis.

The aims of this study were to assess the feasibility of using comparative genomic hybridisation instead of conventional cytogenetics in prenatal diagnosis and to determine the size of DNA loss that can be detected. Using comparative genomic hybridisation, six cases with standard aneuploidies were diagnosed correctly. This technique clearly identified a partial duplication of the long arm of chromosome 1 but was not capable of detecting the associated inversion. A small interstitial deletion on short arm of chromosome 10 also was detected precisely. Although the current comparative genomic hybridisation resolution is similar to the sensitivity of the highest resolution G banding, the latter is not a routine strategy in prenatal diagnosis. Comparative genomic hybridisation can allow full chromosome assessment equal to the highest resolution cytogenetic studies without the need for cell culture.

Cytogenetic Analysis↗
PubMed1999

Selective cleaning of the cell debris in human chromosome preparations studied by scanning force microscopy.

The chromosome structure is one of most challenging biological structures to be discovered. Most evidence about the structure comes from optical microscopy. Scanning force microscopy (SFM) can achieve molecular resolution and allows imaging in liquids. However, little information about the chromosome structure has been revealed by SFM. In this work, a mild enzymatic treatment is applied to the chromosomes to remove selectively the RNA and proteins coming from the cell. The resulting SFM images indicate that a protein film with embedded RNA molecules covers chromosomes in standard cytogenetic preparations. The thickness of the protein layer is 15-35 nm and the RNA adheres preferentially to the chromosome surface. The cell material film results in a quite smooth chromosome surface without evidence of any structural detail. After treatment, the chromosome was cleaned from cell residues and individual chromatin fibers at the surface were resolved. Furthermore, insights about the higher order structure of the chromosome can be inferred.

Chromatin↗
PubMed1999

An immunohistochemical study of type I insulin-like growth factor receptors in the placentae of pregnancies with appropriately grown or growth restricted fetuses.

Insulin-like growth factors (IGFs) and their receptors in the fetus are essential for growth and postnatal survival but the role of maternal IGFs is less well understood. Animal and in vitro evidence suggests that maternal IGF-I may have important effects on placental function. Recent work in humans suggests that although there is no relationship between maternal serum IGF-I and normal fetal growth, levels are low in pregnancies complicated by fetal growth restriction due to placental dysfunction. A prospective and observational study was undertaken of the distribution and concentration of placental type I IGF receptors (IGF-IR) in women with small for gestational age (n=26) or appropriately grown (n=14) fetuses. Women were scanned biweekly from 24 weeks to delivery and cases (birthweight <5th centile) were assigned to two groups: 'fetal growth restriction' (FGR; umbilical artery pulsatility index [UAPI] > +2 s.d.; n=16) and 'normal small for gestational age' (SGA; normal UAPI, growth velocity and amniotic fluid; n=10). Immunohistochemistry of the IGF-IR was performed on formol saline-fixed placental biopsies obtained at delivery. In control pregnancies IGF-IR were present in villous endothelium and stroma, trophoblast and decidua and their distribution and density were unchanged in both SGA and FGR pregnancies. We hypothesize that a therapeutic elevation of maternal IGF-I in FGR pregnancy might lead to enhanced placental function and so fetal growth. Our findings of normal localization and density of placental IGF-IR in FGR encourage us to extend our work to look at the effects of maternal IGF-I on the transport of glucose and amino acids.

Chorionic Villi↗
PubMed1998

Prognosis following prenatal diagnosis of heart malformations.

Our objective was to document the prognosis of cases with fetal heart malformations (FHM). Forty-two fetuses assessed both in a regional fetal medicine and paediatric cardiology unit were classified prenatally into isolated FHM or those associated with extra-cardiac structural or karyotypic anomalies (ECA) and this classification was not changed subsequently (analogous to an intention to treat analysis). The end points studied included chromosomal abnormality, pregnancy outcome and follow-up at one year of age. FHM were isolated in 16 (38%) and associated with ECA in 26 (62%) of cases. The karyotypic abnormality rate was 8/42 (19%) overall and 8/26 (31%) in ECA cases. The pregnancy outcome included termination of pregnancy in 19 (45%), intrauterine death of two (5%) and live birth in 21 (50%). 12/16 (75%) of isolated FHM cases were live born compared with 9/26 (35%) of ECA cases (P < 0.03). Of the isolated FHM live born babies, 8/12 (67%) were alive at the end of the first year and seven of these were growing normally and did not require cardiac medication. However, a considerable proportion of their first year was spent in hospital (median 8%, interquartile range 5-10). Only one of nine ECA live born cases was alive but with poor growth and dependence on cardiac drugs at one year. These data confirm previous findings in prenatal diagnosis series that the prognosis for FHM is worse than that reported in studies of congenital heart disease at birth and is strongly dependent upon the presence of ECA. In their absence, outcome is better than previously published. Counselling must take place only after full fetal medicine assessment and should be based upon prenatal data.

Female↗
PubMed1998

Antenatal invasive therapy.

The value of fetal therapy relates to the balance of benefit versus risk taking into account alternatives such as post-natal therapy. Since this balance is also determined by the natural history and prognosis of a given condition, the fact that any condition diagnosed pre-natally has a worse prognosis than the same condition diagnosed post-natally will be described. On this basis we classify the interventions into those that are clearly of benefit in the right cases, those that are possible now but are still being assessed and other experimental ideas.

Female↗
PubMed1998

The ability of the chemiluminescence test to predict clinical outcome and the necessity for amniocenteses in pregnancies at risk of haemolytic disease of the newborn.

The chemiluminescence test measures the ability of anti-D to sensitise red cells for recognition by monocytes. It predicts clinical outcome in haemolytic disease of the newborn with greater precision than quantification of anti-D levels by AutoAnalyzer. However, whether or not the chemiluminescence test can, or should, affect clinical management is not clear. Of 56 alloimmunised women referred to a single fetal medicine unit, 30 underwent a total 63 amniocenteses to establish the extent of fetal haemolysis. Overall, chemiluminescence test results were a better predictor of amniocenteses with elevated bilirubin levels than the AutoAnalyzer (P < 0.01). Chemiluminescence results > 30% were always associated with elevated bilirubin levels. The chemiluminescence test might be used to prompt the direct evaluation of fetal haemolysis in patients with borderline levels of anti-D (5-15 IU/mL). However, the ability of the test to predict amniocenteses with normal bilirubin levels was less clear.

Amniocentesis↗
PubMed1997

Fetal and maternal plasma insulin-like growth factors and binding proteins in pregnancies with appropriate or retarded fetal growth.

A prospective observational study of 104 women was performed to study whether the insulin-like growth factor (IGF) system in pregnancy before labour is associated with reduced fetal growth. Fetal blood was obtained by cordocentesis for prenatal diagnosis or at elective caesarean delivery and a maternal sample was also obtained, IGF-1 and IGF-2 and their binding proteins -1 and -3 were measured by RIA. The 35 case were smaller than -2S.D.s by ultrasound abdominal circumference and birthweight and were subdivided into fetal growth retardation (FGR, n = 20) and small for gestational age (SGA, n = 15) by Doppler velocimetry and neonatal outcome. Controls (n = 69) were normally grown. Control maternal IGF-1 (r = 0.65, P < 0.0001) and IGFBP-3 (r = 0.46, P = 0.001) increased with advancing gestational age. In FGR cases, maternal IGF-1 was low (P = 0.0001) and IGFBP-1 was high (P = 0.03) and maternal IGF-2 was low in SGA (P = 0.005). In the SGA fetus, IGF-2 was low (P = 0.0009) and IGFBP-3 (P = 0.02) was high. In FGR, IGFBP-1 (P < 0.0001) and IGFBP-3 (P = 0.002) were both elevated. These data do not support the hypothesis that fetal IGF-1 deficiency is a common cause of FGR. Elevated binding proteins may lead to a relative deficiency of free IGF but changes in binding proteins may be secondary to metabolic changes. In FGR, maternal IGF-1 was low with high binding proteins, so this system may be important in controlling placental transfer.

Embryonic and Fetal Development↗
PubMed1996

Fetal medicine in an unselected pregnant population.

To determine the proportion of an unselected pregnant population referred to a Fetal Medicine Unit, we undertook an observational time-limited cohort study. Of 530 pregnant women booked for delivery at our hospital and with a local postcode in the local District Health Authority, 81 (15.3%) were referred to the Fetal Medicine Unit at least once. The average number of fetal medicine visits was 1.5, a rate of 22 per 100 pregnancies. The indications for referral were assessed as appropriate for all but 2 cases. In 3 cases (0.6%), major genetic diseases were prevented by termination of pregnancy.

Adult↗