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K Spencer

Publications and source records attributed to K Spencer.

At least 19 recordsLinked to original sources
PubMed2007

Overexpression of hippocampal Ca2+/calmodulin-dependent protein kinase II improves spatial memory.

Hippocampal alpha-calcium/calmodulin-dependent protein kinase II (alphaCaMKII) has been implicated in neuronal plasticity and spatial learning. In the present experiment, an adeno-associated virus (AAV) vector was designed to express alphaCaMKII driven by the U6 promotor. Microinfusion of this vector into the rat hippocampus increased alphaCaMKII immunoreactivity by approximately 73% (Western analysis) and improved performance in a water maze task. Locomotor activity and exploratory behavior in an open field task were not altered by the overexpression of alphaCaMKII. These data support a role for alphaCaMKII in spatial or explicit memory storage. The advantages of viral vectors for manipulating target proteins expression compared with genetically modified mouse models are discussed.

Animals↗
PubMed2007

First-trimester maternal serum PP-13, PAPP-A and second-trimester uterine artery Doppler pulsatility index as markers of pre-eclampsia.

OBJECTIVE: To evaluate whether measurement of maternal serum placental protein-13 (PP-13) and pregnancy-associated plasma protein-A (PAPP-A) at 11 + 0 to 13 + 6 weeks of gestation alone or in combination with second-trimester uterine artery pulsitility measured by Doppler velocimetry is useful in predicting those women who will develop pre-eclampsia METHODS: This was a nested case-control study of pre-eclampsia cases with controls matched for gestational age and storage time for the maternal serum. Samples were collected as part of a first-trimester prenatal chromosomal anomaly screening program and were routinely tested for PAPP-A. PP-13 was tested using an enzyme linked immunosorbent assay (ELISA) by an examiner who was blinded to pregnancy outcome. All patients also underwent uterine artery Doppler flow velocimetry to measure the mean pulsatility index (PI) at 22-24 weeks' gestation. RESULTS: There were 446 controls and 44 cases with early pre-eclampsia where delivery was induced prior to 35 weeks. In addition there were a further 44 cases with pre-eclampsia in which delivery was not induced before term. Median PP-13 levels for controls, all cases and early pre-eclampsia cases were 176.9, 121.9 and 111.7 pg/mL, with multiples of the median (MoMs) of 1.00, 0.69 and 0.63, respectively (P < 0.001). PAPP-A MoMs were 1.00, 0.89 (P = 0.076) and 0.89 (P = 0.042) and mean PIs were 1.0, 1.6 (P < 0.001) and 1.7 (P < 0.001) for controls, all cases and early cases, respectively. Receiver-operating characteristics (ROC) curve analysis for either all cases or early cases vs. controls yielded areas under the curve for PP-13, PAPP-A and PI respectively of 0.68 (95% CI, 0.61-0.74; P < 0.001), 0.56 (95% CI, 0.49-0.63; P = 0.076) and 0.79 (95% CI, 0.72-0.87; P < 0.001) for all cases and 0.71 (95% CI, 0.63-0.79; P < 0.001), 0.59 (95% CI, 0.51-0.68; P = 0.076) and 0.86 (95% CI, 0.77-0.94; P < 0.001) for early cases. At a specificity set to 0.80 the sensitivities were 0.50, 0.23 and 0.76 for PP-13, PAPP-A and PI in the early cases and 0.44, 0.24 and 0.73 in all cases. Combining PP-13 and PI using logistic regression analysis yielded an area under the curve of 0.84 (95% CI, 0.78-0.90; P < 0.001) and a sensitivity of 0.74 in all cases, and 0.90 (95% CI, 0.84-0.96; P < 0.001) and a sensitivity of 0.79 for early cases. PAPP-A with PI gave an area under the curve of 0.82 (95% CI, 0.76-0.90; P < 0.001) and a sensitivity of 0.76 in all cases. Combining PAPP-A with PP-13 and PI did not add significantly to the sensitivity. CONCLUSION: First-trimester PP-13 levels may be useful in predicting pre-eclampsia and early pre-eclampsia, and the accuracy of the method increases when coupled with second-trimester Doppler PI measurement. First-trimester PAPP-A provides some prediction for pre-eclamspia when combined with PI but does not add to the prediction of early pre-eclampsia when PP-13 and PI are used together. Further studies are required to establish the real value of PP-13 in first-trimester screening for pre-eclampsia.

Adult↗
PubMed2007

First-trimester combined screening for trisomy 21 in a predominantly Chinese population.

OBJECTIVE: To examine the effectiveness of first-trimester fetal trisomy 21 screening using a combination of maternal age, nuchal translucency thickness (NT) and maternal serum free beta-human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A) levels in a predominantly Chinese population in Hong Kong. METHODS: This was a prospective study over a 1.5-year period of 2990 women who underwent combined screening for trisomy 21 between 11+0 and 13+6 weeks of gestation in a university fetal medicine unit. NT was measured according to the criteria set by The Fetal Medicine Foundation (FMF), maternal serum free beta-hCG and PAPP-A levels were measured, and the risk of trisomy 21 was calculated using The FMF's algorithm. Fetal karyotyping was advised when the risk was 1 : 300 or above. All subjects were followed up for pregnancy and fetal outcome. RESULTS: Of the 2990 women who underwent the screening program, 99% were Chinese. There were 57 twin pregnancies, giving a total of 3047 fetuses. Thirty-one percent of the women were 35 years old or above. One hundred and eighty-five (6.1%) fetuses were screen-positive; this included 14 cases of trisomy 21 and 17 cases of other chromosomal abnormalities. The positive predictive value was 16.7%. Among the 2862 screen-negative fetuses, only 18 (0.6%) cases had an unknown fetal outcome. There were no cases in which trisomy 21 was missed and the infant was liveborn. CONCLUSION: First-trimester combined screening for fetal trisomy 21 is highly effective among Chinese subjects.

Adult↗
PubMed2006

Prediction of pre-eclampsia by uterine artery Doppler ultrasonography and maternal serum pregnancy-associated plasma protein-A, free beta-human chorionic gonadotropin, activin A and inhibin A at 22 + 0 to 24 + 6 weeks' gestation.

OBJECTIVE: To investigate the potential value of combining uterine artery Doppler ultrasonography with the measurement of maternal serum pregnancy-associated plasma protein-A (PAPP-A), free beta-human chorionic gonadotropin (beta-hCG), activin A and inhibin A at 22 + 0 to 24 + 6 weeks' gestation, in the prediction of pregnancies that subsequently develop pre-eclampsia. METHODS: The maternal serum PAPP-A, free beta-hCG, activin A and inhibin A concentrations at 22 + 0 to 24 + 6 weeks' gestation were measured in samples obtained from women with singleton pregnancies who participated in a screening study for pre-eclampsia by transvaginal color flow Doppler measurement of the uterine artery pulsatility index (PI). A search was made of the database to identify those who subsequently developed pre-eclampsia (n = 24) and a group of controls with normal outcome (n = 144). Regression analysis was performed to establish any relationship between the biochemical markers themselves and between the biochemical markers and uterine artery mean PI. A multivariate Gaussian model combining various biochemical markers with uterine artery mean PI was developed using standard statistical modeling techniques and the performance of such models in discriminating cases with pre-eclampsia was evaluated by receiver-operating characteristics curve (ROC) analysis. RESULTS: In the pre-eclampsia group, compared to the controls, the uterine artery mean PI and the maternal serum levels of PAPP-A, free beta-hCG, activin A and inhibin A were significantly increased. The predicted detection rates of pre-eclampsia, for a false positive rate of 5%, was 50% by uterine artery mean PI, 5% by PAPP-A, 10% by free beta-hCG, 35% by inhibin A and 44% by activin A. Screening by a combination of uterine artery mean PI and maternal serum activin A and inhibin A could detect 75% and 92% of patients who subsequently developed pre-eclampsia, for false positive rates of 5% and 10%, respectively. CONCLUSION: Screening for pre-eclampsia by uterine artery PI at 22 + 0 to 24 + 6 weeks' gestation can be improved by measurement of activin A and inhibin A levels.

Activins↗
PubMed2006

Screening for trisomy 21 by fetal tricuspid regurgitation, nuchal translucency and maternal serum free beta-hCG and PAPP-A at 11 + 0 to 13 + 6 weeks.

OBJECTIVE: To examine whether in pregnancies with fetal trisomy 21 the level of maternal serum free beta-human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A) at 11 + 0 to 13 + 6 weeks' gestation is independent of the presence or absence of tricuspid regurgitation and to estimate the performance of a screening test that combines tricuspid regurgitation with fetal nuchal translucency (NT) thickness and serum free beta-hCG and PAPP-A. METHODS: The study population comprised 77 trisomy 21 and 232 chromosomally normal fetuses from singleton pregnancies at 11 + 0 to 13 + 6 weeks of gestation. In all cases the fetal karyotype was determined by chorionic villus sampling (CVS), which was carried out at the request of the parents after first-trimester screening for trisomy 21 by fetal NT and maternal serum free beta-hCG and PAPP-A. Immediately before chorionic villus sampling, fetal echocardiography was performed and the presence or absence of tricuspid regurgitation was determined by pulsed wave Doppler ultrasonography. The distribution of fetal NT, maternal serum free beta-hCG and PAPP-A in trisomy 21 fetuses with absent and present tricuspid regurgitation was examined. We examined two screening strategies: first, integrated first-trimester screening in all patients and second, first-stage screening of all patients using fetal NT and maternal serum free beta-hCG and PAPP-A followed by second-stage assessment of tricuspid regurgitation only in those with an intermediate risk of 1 in 101 to 1 in 1000 after the first stage. RESULTS: Tricuspid regurgitation was observed in 57 (74.0%) of the trisomy 21 fetuses and in 16 (6.9%) of the chromosomally normal fetuses. There were no significant differences in median maternal age, median gestational age, free beta-hCG multiples of the median (MoM) and PAPP-A MoM in trisomy 21 fetuses with and without tricuspid regurgitation. The modeled detection rates of trisomy 21 for fixed false positive rates of 1%, 2% and 5% in screening by maternal age, fetal NT thickness and maternal serum free beta-hCG and PAPP-A and assessment of tricuspid flow in all cases were 87%, 90% and 95%. In the two-stage approach, the estimated detection rate was 91% and the false positive rate was 2.6%. CONCLUSIONS: There is no relationship between tricuspid regurgitation and the levels of maternal serum free beta-hCG and PAPP-A in cases with trisomy 21. An integrated sonographic and biochemical test at 11 + 0 to 13 + 6 weeks can potentially identify about 90% of trisomy 21 fetuses for a false-positive rate of 2-3%.

Adult↗
PubMed2006

First-trimester ultrasound and biochemical markers of aneuploidy and the prediction of impending fetal death.

OBJECTIVES: To examine the clinical utility of the first-trimester markers of aneuploidy in their ability to predict future fetal loss. METHODS: We examined 54,722 singleton pregnancies with no chromosomal abnormality and with complete outcome data that had undergone screening for trisomy 21 by a combination of fetal nuchal translucency (NT) thickness, maternal serum free beta-human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A) at 11 + 0 and 13 + 6 weeks' gestation. The biochemical markers were converted to multiples of the expected normal median for a pregnancy of the same gestation (MoM) and the measurements of fetal NT were expressed as the difference (delta) from the normal median NT for crown-rump length (CRL). The association between free beta-hCG, PAPP-A and delta NT and the incidence of fetal loss prior to 24 weeks, at or after 24 weeks or at any time, was assessed by comparing the relative incidence at a number of MoM or delta NT cut-offs and at various centile cut-offs. At various marker levels the likelihood ratio (LR) for fetal loss was also calculated. RESULTS: The rate of fetal loss increased with decreasing maternal serum free beta-hCG and PAPP-A and increasing delta NT. At the 5th centile of the normal outcome group for free beta-hCG (0.41 MoM) the odds ratio for fetal loss before 24 weeks, at or above 24 weeks and at any gestation was 3.1, 1.8 and 2.6, respectively. The respective values for the 5th centile of PAPP-A (0.415 MoM) were 3.3, 1.9 and 2.8 and for the 95th centile of delta NT they were 2.5, 1.9 and 2.2, respectively. There was almost no correlation between reduced levels (<or=0.50 MoM) of PAPP-A and reduced levels of free beta-hCG in either the normal pregnancy group (r = 0.041) or the group with fetal death (r = 0.072), indicating relatively independent prediction by either biochemical marker. CONCLUSIONS: Low levels of maternal serum PAPP-A and free beta-hCG and increased fetal NT are associated, in the absence of an abnormal karyotype, with an increased risk of impending fetal death. The likelihood ratio profiles provided at various levels of PAPP-A or free beta-hCG may be of some help in counseling women with such results and raise awareness among health-care professionals for increased surveillance in such cases.

Adult↗
PubMed2005

Down syndrome screening marker levels in women with a previous aneuploidy pregnancy.

BACKGROUND: In Down syndrome screening programmes, women with a previous affected pregnancy are assumed to have the same marker distribution as those without a family history. This assumption needs to be tested. METHODS: Information on previous aneuploidy pregnancies was routinely sought on the test request forms in three centres, Leeds, Romford and the Fetal Medicine Centre, London. For each woman with a previous aneuploidy (case), five unaffected pregnancies to women without a history were selected as controls. The markers tested included maternal serum free beta-human chorionic gonadotrophin (hCG), pregnancy-associated plasma protein A (PAPP-A), alpha-fetoprotein, unconjugated estriol and ultrasound nuchal translucency thickness. RESULTS: There were 375 cases: 303 with previous Down syndrome, 63 with Edwards syndrome and 9 with Patau's syndrome. There was a statistically significant difference between cases and controls, in the distribution of free beta-hCG and PAPP-A levels, adjusted for gestation. On average, free beta-hCG was increased by 10% in a subsequent pregnancy after aneuploidy (p < 0.005, Wilcoxon rank sum test) and for PAPP-A the increase was 15% (p < 0.0001). No other marker was significantly different. CONCLUSION: Risk calculation algorithms need to be modified to take account of the increased marker levels. Until data from sufficient affected pregnancies are available for study, it would be prudent to assume that the same increase as in unaffected pregnancies applies.

Adult↗
PubMed2005

Second-trimester levels of pregnancy-associated plasma protein-A and free beta-hCG in pregnancies with trisomy 13.

OBJECTIVE: To examine the levels of free beta-human chorionic gonadotrophin (free beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A) in second-trimester maternal serum from pregnancies affected by trisomy 13 and compare these with the known reduced levels of these markers in first-trimester cases in an attempt to better understand the pathophysiology of changes in marker levels in chromosomally abnormal pregnancies between the first and second trimester. METHODS: Using the Kryptor immunoassay system, we measured free beta-hCG and PAPP-A in 32 singleton pregnancies affected by trisomy 13 between 14 and 20 weeks of gestation. Using medians established in a previous study, these results were compared against 450 normal singleton pregnancies over the same gestational range. The data were combined with data from 82 cases of trisomy 13 previously examined in the first trimester (11-13 weeks) and an analysis of analyte trend was performed. RESULTS: The median free beta-hCG in multiples of the appropriate gestational median (MoM) in the second-trimester samples was not significantly different from the controls (1.15 (95% CI 0.827-1.651) vs 1.00). The median PAPP-A MoM in the second-trimester samples was significantly lower (p<0.001) than in controls (0.25 (95% CI 0.164-0.373) vs 1.00). Seventy-eight percent of cases were below the 5th centile of normal for PAPP-A. The combined cases in the first trimester had a median free beta-hCG MoM of 0.58 (95% CI 0.454-0.668) and a median PAPP-A MoM of 0.26 (95% CI 0.218-0.320). For PAPP-A, there was no significant change in median across the gestational period of 11 to 20 weeks, whilst for free beta-hCG, there was a significant increase with gestation (r=0.458, p<0.001). CONCLUSIONS: Although PAPP-A levels are reduced in trisomy 13 pregnancies in the second trimester, this isolated lower marker value is unlikely to be of value in screening for trisomy 13 in the second trimester. The aetiology of reduced levels of PAPP-A in cases with trisomy 13 may be similar to that in cases with trisomy 18, but different from that in cases with trisomy 21 since the temporal pattern in trisomies 13 and 18 are different from that in trisomy 21.

Adult↗
PubMed2005

Ethnicity and the need for correction of biochemical and ultrasound markers of chromosomal anomalies in the first trimester: a study of Oriental, Asian and Afro-Caribbean populations.

OBJECTIVES: To assess whether there is a need to correct first-trimester biochemical markers (free beta-hCG and pregnancy-associated plasma protein-A (PAPP-A)) or first-trimester fetal nuchal translucency thickness (NT) in different ethnic groups, when screening for Downs syndrome at 11-14 weeks of gestation. METHODS: Free beta-hCG, PAPP-A and fetal NT were measured at 11-14 weeks of gestation in a group of women presenting for first-trimester screening in two OSCAR centres. The group comprised 61 219 sets of data from Caucasian women (the reference group); 4835 sets of data from South Asian women; 3450 sets of data from Oriental women and 2727 sets of data from Afro-Caribbean women. The Oriental data set was supplemented with a further 480 cases collected in Hong Kong and the Afro-Caribbean data set was supplemented with 216 cases collected from Kings College. The difference in marker values between the reference group and the other ethnic groups was compared before and after weight correction for the biochemical markers using standard statistical techniques. A correction factor for ethnic origin was applied for all three markers and the screen-positive rate before and after correction was assessed for the various groups. RESULTS: After maternal weight correction, in Afro-Caribbean women, the median PAPP-A was increased by 55% and the free beta-hCG increased by 11%. In south Asian women, the PAPP-A was increased by 8% and the free beta-hCG decreased by 7.5%. In Oriental women, the PAPP-A was increased by 9% and the free beta-hCG by 6%. For delta NT in Afro-Caribbean women, the values were 0.064 mm lower on average than in Caucasian women and for south Asian women 0.045 mm lower. The difference of -0.012 for Oriental women was not significant. Before correcting for ethnic origin, these changes resulted in the screen-positive rates being lower in the Afro-Caribbean group (3.7% vs 5.6%), the south Asian group (4.3% vs 5.6%) and Oriental group (4.9% vs 5.6%). After correction, the screen-positive rates were largely similar in the four groups. CONCLUSION: Differences in median PAPP-A, free beta-hCG and, to a lesser extent, in NT exist in Afro-Caribbean, South Asian and Oriental women. In populations where the medians and delta NT reference ranges are established in predominantly Caucasian populations, some correction for ethnicity is appropriate and can redress differences in screen-positive rates between these different groups.

Adult↗
PubMed2005

First and second-trimester biochemical markers of chromosomal anomalies and their relationship to maternal haemoglobin levels.

OBJECTIVE: To evaluate a previous hypothesis that maternal serum biochemical markers used in the assessment of Down syndrome risk are related to maternal haemoglobin concentrations. METHODS: A series of 1306 second-trimester prenatal screening records were retrieved including information on marker levels (AFP and fbetahCG MoMs), Down's risk, a priori age risk, maternal weight and maternal height. Each individual record was merged with data from haematological investigations on samples collected on the same day. A similar series of 1688 first-trimester screening records were also retrieved including the maker levels for PAPP-A, and fbetahCG MoMs were merged with data from haematological investigations carried out on the same day. The two groups were categorised according to their haemoglobin levels; anaemic (less than 11.0 g/dL in first trimester and 10.5 g/dL in the second trimester), high haemoglobin (greater than 14.0 g/dL and 13.2 g/dL) or normal (between these ranges). An analysis was made of marker levels in the various groups before and after correction for ethnicity and of the screen-positive rate in the various groups. Using a formula based on maternal height and weight, variation of marker levels with plasma volume was assessed. RESULTS: In the first trimester, 12.6% of the pregnant population was anaemic and 1.6% had elevated haemoglobin levels. In the second trimester this was 12.7 and 3.9%. These figures varied considerably with ethnic origin, with Asian and Afro-Caribbean women being more anaemic than Caucasian women. Haemoglobin levels declined by 7% between the 11- and 21-week period. Maternal plasma volume (as calculated by a widely used maternal height and weight relationship) was not correlated with weight-corrected biochemical marker MoMs in either trimester. A weak but significant correlation of maternal plasma volume and haemoglobin concentration was observed. There was no significant correlation between biochemical marker MoMs and haemoglobin concentration. Although the proportion of pregnancies designated screen positive decreased as haemoglobin levels increased, this was paralleled by a decrease in the maternal age a priori risk. CONCLUSIONS: There is no relationship between maternal haemoglobin levels and the levels of Down syndrome markers in either the first or second trimester. Biochemical marker levels do not need to be corrected for haemoglobin concentrations when used in screening for Down syndrome.

Adult↗
PubMed2005

Multicenter study of first-trimester screening for trisomy 21 in 75 821 pregnancies: results and estimation of the potential impact of individual risk-orientated two-stage first-trimester screening.

OBJECTIVES: To evaluate the performance of first-trimester screening for trisomy 21 by a combination of maternal age, fetal nuchal translucency (NT) and maternal serum free beta-human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A). In addition, the potential impact of a new individual risk-orientated two-stage approach to first-trimester screening was examined. METHODS: First-trimester combined screening for trisomy 21 was carried out in 75 821 singleton pregnancies with live fetuses at 11 + 0 to 13 + 6 gestational weeks. The detection and false-positive rates for different risk cut-offs were calculated. To examine the potential impact of an individual risk-orientated two-stage approach to first-trimester screening it was assumed that, after first-trimester combined screening, chorionic villus sampling (CVS) would be performed in all patients with a risk estimate of 1 in 100 or more and in none of those with a risk estimate of less than 1 in 1000. Those in the intermediate-risk category, with a risk estimate of between 1 in 101 and 1 in 1000, would have further assessment of risk by first-trimester ultrasound examination to determine presence/absence of the nasal bone, presence/absence of tricuspid regurgitation or normal/abnormal Doppler velocity waveform in the ductus venosus, and CVS would be performed if their adjusted risk became 1 in 100 or more. RESULTS: Fetal NT and maternal serum free beta-hCG and PAPP-A were successfully measured in all cases. The median maternal age was 31 (range, 13-49) years, the median gestation at screening was 12 (range, 11 + 0 to 13 + 6) weeks and the median fetal crown-rump length was 62 (range, 45-84) mm. Chromosomal abnormalities were identified in 544 pregnancies, including 325 cases of trisomy 21. The estimated risk for trisomy 21 was 1 in 300 or greater in 5.2% of normal pregnancies, in 92.6% of those with trisomy 21, in 88.5% of those with trisomy 18 or 13 and in 85.6% of those with other chromosomal defects. The detection rates for trisomy 21 were about 75% and 80% for respective false-positive rates of 1% and 2%. In the proposed individual risk-orientated two-stage screening for a risk cut-off of 1 in 100 the total false-positive rate would vary with the method used for the second stage of screening from 2.1% for absence of the nasal bone to 2.7% for increased impedance in the ductus venosus and 2.7% for tricuspid regurgitation and the respective detection rates would be 92.0%, 94.2% and 91.7%. CONCLUSIONS: First-trimester combined screening for trisomy 21 is associated with a detection rate of about 90% for a false-positive rate of 5%. Individual risk-orientated two-stage screening for trisomy 21 can potentially identify, in the first trimester of pregnancy, more than 90% of affected fetuses for a false-positive rate of 2-3%.

Adolescent↗
PubMed2004

Factors affecting women's preference for type of prenatal screening test for chromosomal anomalies.

OBJECTIVE: To ascertain, by means of a questionnaire, women's preferences for four different approaches to prenatal screening for Down syndrome. METHODS: Women attending antenatal clinics at six UK maternity units were asked to put in order of preference four different approaches to screening for Down syndrome all of which had the same false positive rate of 5%. The options were: (1) first-trimester testing, 90% detection of Down syndrome with results available in 1 h at one-stop clinics for the assessment of risk (OSCAR); (2) first-trimester testing, 90% detection and results available within 2-3 days (combined screening); (3) first-trimester testing plus second-trimester testing, 93% detection and results available within 2-3 days of second test (integrated testing); (4) second-trimester testing, 75% detection and results available within 2-3 days. RESULTS: Over 1100 women attending antenatal clinics at six maternity units across the UK returned the questionnaire. A total of 75% of women selected a first-trimester test (option 1 or option 2) as their first choice with 68.2% expressing a preference for the OSCAR approach and a further 6.8% for combined screening. Twenty-four percent of women opted for integrated testing as their first choice with only 1% expressing a preference for second-trimester screening. CONCLUSIONS: A first-trimester test is preferred by the majority of women over a test with marginally higher detection rate that delivers results later in pregnancy. Timing and rapid reporting of results appear to influence women's choice of test.

Biomarkers↗
PubMed2004

Uterine artery Doppler and mid-trimester maternal plasma homocysteine in subsequent pre-eclampsia.

OBJECTIVE: To investigate whether mid-trimester maternal plasma homocysteine concentration is elevated in women who develop pre-eclampsia and in those women identified at high risk by abnormal uterine artery Doppler examination. METHODS: This was a multicenter study involving healthy women undergoing screening for pre-eclampsia by uterine artery Doppler velocimetry at 22-24 weeks' gestation. Abnormal uterine artery blood flow was defined as a mean pulsatility index (PI) above the 95th centile (1.6). Controls (mean PI < 1.6) were matched for gestational age and date of blood sample collection. Maternal plasma homocysteine concentration was measured retrospectively using a chemiluminescent immunoassay. RESULTS: In total, 683 women were recruited. Maternal plasma homocysteine concentration did not vary with gestation. Maternal plasma homocysteine concentration in women who subsequently developed pre-eclampsia (n = 80, 12%) was not significantly different from women with uncomplicated pregnancies (n = 536, 78%) (median 5.1, range 2.7-14.1 micromol/l vs. median 5.5, range 1.9-27.9 micromol/l, p = 0.44). There were no significant differences in the maternal plasma homocysteine concentration in women with abnormal uterine artery Doppler findings (n = 275) compared with controls (n = 408), (median 5.6, range 2.6-17.7 micromol/l vs. median 5.4, range 1.9-27.9 micromol/l, p = 0.13). CONCLUSION: Mid-trimester maternal plasma homocysteine concentration is not elevated in women who developed pre-eclampsia even in those at high risk defined by abnormal uterine artery Doppler velocimetry.

Adolescent↗
PubMed2004

Second-trimester sex hormone-binding globulin and subsequent development of pre-eclampsia.

OBJECTIVE: To investigate whether maternal plasma sex hormone-binding globulin (SHBG) concentrations are reduced in women who subsequently develop pre-eclampsia. METHODS: This was a cross-sectional study, carried out at antenatal clinics in seven hospitals in and around London. Healthy women underwent uterine artery Doppler velocimetry as a screening method for pre-eclampsia at 22-24 weeks of gestation. The first group (408 women) had normal uterine artery Doppler waveforms (mean uterine artery pulsatility index (PI) below 1.6). The second group (274 women) had increased impedance to flow in the uterine arteries (mean PI above the 95th centile, 1.6). Maternal plasma SHBG concentrations were measured retrospectively using a competitive chemiluminescent immunoassay. Pre-eclampsia was as defined by the International Society for the Study of Hypertension in Pregnancy. RESULTS: Plasma SHBG concentrations in the 80 (11.7%) women who subsequently developed pre-eclampsia were significantly lower than in the 585 (85.8%) women with normal pregnancy outcomes (median 336, range 142-674 nmol/l vs. median 336, range 142-674 nmol/l, p = 0.001). There was a strong correlation between SHBG concentrations and body mass index (r =-0.232246, p < 0.0001). There were no significant differences in maternal plasma SHBG concentrations in women with abnormal uterine artery Doppler (n = 274) compared with controls (n = 408) (median 324, range 101-635 nmol/l vs. median 336, range 142-674 nmol/l, p = 0.09). CONCLUSION: Maternal plasma SHBG concentrations are reduced in women who subsequently develop pre-eclampsia.

Adult↗
PubMed2004

First-trimester maternal serum activin A in pre-eclampsia and fetal growth restriction.

OBJECTIVE: To investigate whether the reported increase in maternal serum activin A concentration in pre-eclampsia is evident from the first trimester. DESIGN: This was a case-control study carried out in antenatal clinics among singleton pregnancies at 10-14 weeks of gestation. METHODS: Activin A concentration was measured in stored maternal serum samples obtained at 11-14 weeks of gestation from 131 women who subsequently developed pre-eclampsia, 77 who developed non-proteinuric pregnancy-induced hypertension, 141 with fetal growth restriction in the absence of hypertensive complications and from 494 normotensive controls. RESULTS: Compared to the median activin A level in the control group (1.00 MoM), the median MoM in the patients who subsequently developed pre-eclampsia and pregnancy-induced hypertension (1.49 MoM and 1.32 MoM, respectively) was significantly increased (p < 0.001), and in patients with fetal growth restriction (1.02 MoM) it was not significantly different (p = 0.57). In the pre-eclampsia group (n = 131) the disease was considered to be sufficiently severe to necessitate iatrogenic delivery before 35 weeks in 25 patients, and in this group the median MoM was 1.92. CONCLUSION: Maternal serum activin A concentration at 12 weeks of gestation in pregnancies which subsequently develop hypertensive disease is increased, whereas in those complicated by fetal growth restriction it is normal.

Activins↗
PubMed2004

Public awareness of risk factors and screening for colorectal cancer in Europe.

Colorectal cancer (CRC) is the commonest site for malignancy in Europe. The Commissioner for Health wishes to promote screening for colorectal, breast and cervical cancer in Europe. The aim of this study was to assess public knowledge of CRC in Europe and likely take up of free screening. To this end 20710 members of the public from 21 European countries were interviewed by means of a regular survey amongst consumers (Omnibus survey) using 13 stem questions. Forty-eight per cent thought the population were at equal risk of CRC, only 57% were aware of age and 54% of family history as risk factors. Although 70% were aware of dietary factors, only 30% knew that lack of exercise might be a risk factor. Only 51% had knowledge of CRC screening but 75% were 'very', or 'quite interested, in taking up faecal occult blood (FOB) screening if offered free. Barriers to screening were lack of awareness of risk (31%), youth (22%) and an un-anaesthetic test (19%). There was a big cultural difference in willingness of the public to discuss bowel symptoms: there was a major barrier in Finland (91%), Britain (84%), Luxembourg (82%), Poland (81%) and Portugal (80%); less of a barrier in Spain (49%), Italy (44%) and Iceland (39%). In conclusion, the challenge of achieving high compliance for CRC screening must be a major objective amongst EU member states and non-aligned countries of Europe in the next decade, because it is known that the non-compliant group are those at greatest risk of death from CRC. This study has shown that awareness of CRC is low in Europe and that an educational programme will be essential to achieve high compliance for CRC screening as a means of reducing deaths from bowel cancer.

Adult↗