Microbial diversity in the digestive tract of two different breeds of sheep.

AIMS: This work aims to determine the factors which play a role in establishing the microbial population throughout the digestive tract in ruminants and is necessary to enhance our understanding of microbial establishment and activity. METHODS AND RESULTS: This study used Terminal Restriction Fragment Length Polymorphism (TRFLP) to investigate the microbial profiles of 11 regions of the digestive tract of two breeds of sheep (Beulah and Suffolk). TRFLP data revealed that the regions of the digestive tract were highly significantly different in terms of the composition of the bacterial communities within three distinct clusters of bacterial colonization (foregut, midgut and hindgut). The data also show that breed was a significant factor in the establishment of the bacterial component of the microbial community, but that no difference was detected between ciliated protozoal populations. CONCLUSIONS: We infer that not only are the different regions of the tract important in determining the composition of the microbial communities in the sheep, but so too is the breed of the animal. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first time that a difference has been detected in the digestive microbial population of two different breeds of sheep.

Effect and mode of action of the Texel muscling QTL (TM-QTL) on carcass traits in purebred Texel lambs.

TM-QTL is a quantitative trait locus (QTL) on ovine chromosome 18 (OAR18) known to affect loin muscling in Texel sheep. Previous work suggested that its mode of inheritance is consistent with paternal polar overdominance, but this has yet to be formally demonstrated. This study used purebred Texel sheep segregating for TM-QTL to confirm its presence in the chromosomal region in which it was first reported and to determine its pattern of inheritance. To do so, this study used the first available data from a Texel flock, which included homozygote TM-QTL carriers (TM/TM; n=34) in addition to homozygote non-carriers (+/+; n=40 and, heterozygote TM-QTL-carriers inheriting TM-QTL from their sire (TM/+; n=53) or their dam (+/TM; n=17). Phenotypes included a wide range of loin muscling, carcass composition and tissue distribution traits. The presence of a QTL affecting ultrasound muscle depth on OAR18 was confirmed with a paternal QTL effect ranging from +0.54 to +2.82 mm UMD (s.e. 0.37 to 0.57 mm) across the sires segregating for TM-QTL. Loin muscle width, depth and area, loin muscle volume and dissected M. longissimus lumborum weight were significantly greater for TM/+ than +/+ lambs (+2.9% to +7.9%; P<0.05). There was significant evidence that the effect of TM-QTL on the various loin muscling traits measured was paternally polar overdominant (P<0.05). In contrast, there was an additive effect of TM-QTL on both live weight at 20 weeks and carcass weight; TM/TM animals were significantly (P<0.05) heavier than +/+ (+11.1% and +7.3%, respectively) and +/TM animals (+11.9% and +11.7%, respectively), with TM/+ intermediate. Weights of the leg, saddle and shoulder region (corrected for carcass weight) were similar in the genotypic groups. There was a tendency for lambs inheriting TM-QTL from their sire to be less fat with slightly more muscle than non-carriers. For example, carcass muscle weight measured by live animal CT-scanning was 2.8% higher in TM/TM than +/+ lambs (P<0.05), carcass muscle weight measured by carcass CT-scanning was 1.36% higher in TM/+ than +/+ lambs (P<0.05), and weight of fat trimmed from the carcass cuts was significantly lower for TM/+ than +/+ lambs (-11.2%; P<0.05). No negative effects of TM-QTL on carcass traits were found. Optimal commercial use of TM-QTL within the sheep industry would require some consideration, due to the apparently different mode of action of the two main effects of TM-QTL (on growth and muscling).

Effects of the Texel muscling quantitative trait locus on carcass traits in crossbred lambs.

Texel muscling quantitative trait locus (TM-QTL) is a QTL on chromosome 18, originally identified in purebred UK Texel sheep, which was reported to increase ultrasonically measured muscle depth at the third lumbar vertebra by around 4% to 7%. The objective of the present study was to comprehensively evaluate the TM-QTL and to determine whether it could provide benefits to the UK sheep industry through increased carcass meat yield in crossbred slaughter lambs. Effects of this QTL on a range of carcass traits, including those measured in vivo and by dissection, were evaluated in heterozygous carrier and non-carrier lambs produced by crossing heterozygous carrier Texel rams with non-carrier Mule (Bluefaced Leicester × Scottish Blackface) ewes from a lowland flock. The TM-QTL was found to increase loin muscling in crossbred lambs at a given live weight or carcass weight, as measured by ultrasound, X-ray computed tomography (CT) and carcass dissection. Depth of M. longissimus lumborum (MLL) was greater in TM-QTL carrier lambs compared to non-carriers as measured by both ultrasound at the third lumbar vertebra (+4.5%; P = 0.033) and CT scanning at the fifth lumbar vertebra (+6.7%; P = 0.004). Width and area of MLL measured using CT were also greater in TM-QTL carrier lambs compared to non-carriers (+3.0%; P = 0.013 and +5.1%; P = 0.047, respectively). Loin muscle volume measured using CT was greater in TM-QTL carriers than in non-carriers (+5.9%; P = 0.005) and the dissected weight of the MLL was +7.1% greater in TM-QTL carriers compared to non-carriers (P < 0.001). The proportion of the total carcass lean meat yield (LMY) that was contained within the loin region was slightly higher in TM-QTL carriers than in non-carriers (0.154 v. 0.145; P = 0.006). However, TM-QTL was found to have no significant effect on the total weight or proportion of LMY or of saleable meat yield in the carcass measured by dissection, or on muscling in the hind leg measured by CT or dissection. This work has verified that the inheritance of TM-QTL is associated with increased loin muscling in crossbred lambs, as has previously been reported for purebred Texel lambs.

In vivo prediction of carcass composition and muscularity in purebred Texel lambs.

A subjective assessment of the shape of the hind limb of purebred Texel lambs was evaluated as an in vivo predictor of carcass composition and muscularity. Lambs were taken from two flocks that were managed in a common environment, but which had either been selected for lean tissue growth rate or for improved conformation. Lambs were slaughtered at a mean age of 139 days at the end of an 11 week performance test in which they were reared indoors on a concentrate diet. Pre-slaughter measurements of live weight and ultrasonic muscle (UMD) and fat (UFD) depths at the position of the third lumbar vertebra, body length (L) and a subjective leg shape score were recorded. After slaughter, measurements were recorded for carcass side length (SL), leg length (T) and the maximum width (A) and depth (B) of the longissimus thoracis and lumborum (LTL) muscle. The side was fully dissected and various muscle weights and skeletal dimensions were used to calculate indices of muscularity as √(muscle weight/length) per unit length or as UMD/L, A/SL or B/SL. The leg shape score was positively correlated with lean weight (0.23) and proportion (0.24), lean:bone ratio (0.25), measures of LTL dimensions (0.27-0.38) and muscularity traits (0.27-0.57) but was not significantly (P>0.05) correlated with fat weights or proportions in the carcass. Live weight was the best single predictor of lean weight (RSD=0.403) and the addition of leg shape score (RSD=0.381) to prediction equations was less effective than the inclusion of UMD and UFD in combination (RSD=0.357). The addition of leg shape score to equations that included ultrasonic traits gave a significant (P<0.05) but marginal improvement in prediction (RSD=0.347). The leg shape score was the most useful in vivo predictor of carcass muscularity traits and, with R(2) in the range 0.30-0.50, had comparable predictive power to a leg muscularity score derived from muscle weight and femur length. It is concluded that the leg shape score showed potential as a predictor of carcass muscularity that was largely independent of live weight and fatness at a fixed age and was marginally associated with superior lean yield and lean:bone ratio.

Second trimester Doppler ultrasound screening of the uterine arteries differentiates between subsequent normal and poor outcomes of hypertensive pregnancy: two different pathophysiological entities?

The 'classical' concept that pregnancy-induced hypertension (PIH) and pre-eclampsia (PE) primarily originate from defective placentation in early pregnancy has been challenged recently. There is growing evidence that other factors, including maternal predisposing conditions, also play a significant role in the pathophysiology of PIH and PE. The aim of the present study was to test the hypothesis that PIH and PE with an early onset and poor pregnancy outcome is associated with defective placentation, e.g. inadequate spiral artery dilatation and subsequent reduced uteroplacental perfusion, whereas PIH and PE with normal pregnancy outcome is not. Using Doppler ultrasound, we measured the uterine artery pulsatility index (PI) in a population of 531 nulliparous women in the 22nd week of gestation. Uterine artery PI was used as an index of resistance to blood flow in the uteroplacental circulation. Outcome measures were PIH/PE with or without poor pregnancy outcome, preterm birth and intra-uterine growth restriction (IUGR). The results revealed a striking difference between PI values for PIH/PE with and without poor pregnancy outcome. Uterine artery PI in the 22nd week was increased significantly in pregnancies which developed early-onset (before 35 weeks) PIH/PE with a poor pregnancy outcome. In contrast, uterine artery PI values were normal in women who developed PIH/PE, but had a good pregnancy outcome. There was a significant correlation between 22nd week uterine artery PI and subsequent preterm birth or IUGR. Our results indicate that only PIH/PE with poor pregnancy outcome is associated with defective placentation, whereas PIH/PE with good outcome is not. These findings support the concept of heterogeneous causes of hypertensive disorders of pregnancy.

Variation in semen parameters derived from computer-aided semen analysis, within donors and between donors.

The development of computer-aided semen analysis (CASA) has made it possible to study sperm motility characteristics objectively and longitudinally. In this 2-year study of 8 sperm donors, we used CASA to measure 7 semen parameters (concentration, percentage of motile spermatozoa, curvilinear velocity, average path velocity, straight-line velocity, amplitude of lateral head displacement, and beat/cross frequency). The frequency distributions of the 7 parameters in the semen samples of each donor were investigated. All parameters but one were normally distributed; concentration was distributed log-normally. Variation within individual donors and between donors was studied. Analysis of variance demonstrated that variation between donors was not explained by the longitudinal variation within individual donors. Variations in motility characteristics between donors were substantial, which may make motility characteristics of limited value as a tool for establishing fertility. Strong correlations were found between the 7 parameters, partly because by definition, motility characteristics are interdependent. Fisher's discriminant analysis demonstrated that each donor appeared to have his own set of semen characteristics and, more specifically, his own motility signature. From this data set it can be predicted that in order to find population means among sperm, it may be more efficient to measure more subjects than to increase the number of samples per subject.

First-trimester maternal serum human thyroid-stimulating hormone in chromosomally normal and Down syndrome pregnancies.

Maternal serum human thyroid-stimulating hormone (TSH) levels were investigated in chromosomally normal and Down syndrome pregnancies to determine whether TSH can be used as a marker for Down syndrome in the first trimester. Measurements were conducted on stored serum samples collected from 23 Down syndrome pregnancies and 115 unaffected pregnancies before chorionic villus sampling (CVS), between 9 and 11 completed weeks of pregnancy. The samples were matched for gestational age, maternal age, maternal weight and duration of storage of the serum sample. Maternal TSH concentration was slightly decreased in Down syndrome pregnancies, with a median of 0.84 multiples of the median (MoM). Maternal serum human chorionic gonadotropin (hCG) concentration was slightly elevated in Down syndrome pregnancies, with a median of 1.03 MoM. Both differences were not significant applying matched rank analysis (p=0.50 for TSH and p=0.43 for hCG). The association between TSH and hCG in unaffected pregnancies was also measured. The Spearman correlation coefficient between TSH and hCG was -0.21 which was statistically significant (p=0.02, 95% confidence interval -0.38 to -0.03). However, it was concluded that TSH is not a useful marker for distinguishing Down syndrome-affected pregnancies from normal pregnancies in the first trimester.

Anatomical and functional changes in the lower urinary tract during pregnancy.

OBJECTIVE: To assess the prevalence and the development of urinary incontinence in nulliparous pregnant women, both subjectively and objectively, and to investigate the relation of incontinence with the mobility of the urethro-vesical junction measured by perineal ultrasound. DESIGN: A prospective longitudinal study. SETTING: University Hospital and Martini Hospital Groningen, the Netherlands. POPULATION: A cohort of 117 nulliparous pregnant women and 27 nulliparous non-pregnant controls. METHODS: Urinary incontinence was measured by a questionnaire and by a 24-hour pad test. The position of the urethro-vesical junction and its mobility were measured by perineal ultrasound. MAIN OUTCOME MEASURE: Prevalence of urinary incontinence; mobility of the urethro-vesical junction, indicated by the displacement/pressure coefficient. RESULTS: Up to 35% of the women reported urinary incontinence in pregnancy, and 20% of the women had a positive pad test. The angle of the urethro-vesical junction angle at rest and the displacement/pressure coefficient during coughing showed a significant increasing trend during pregnancy, but no changes were seen during the Valsalva manoeuvre. No relationship was found between subjective and objective incontinence data and the position and mobility of the urethro-vesical junction. CONCLUSION: The prevalence of incontinence in nulliparous women as found by the pad test was significantly higher in pregnancy (20%) than in the non-pregnant control group (4%). Perineal ultrasound of the urethrovesical junction showed lowering of the pelvic floor occurring as early as 12-16 weeks of pregnancy. Serial measurements of the displacement/pressure coefficient suggest that the dynamic characteristics of the connective tissues of the pelvic floor remain unaltered,whereas a significant decrease in pelvic floor muscle contraction occurs. Since no relation was found between measurements of the urethro-vesical junction and incontinence, urinary incontinence in pregnancy is most likely explained by other factors.

Doppler ultrasound screening predicts recurrence of poor pregnancy outcome in subsequent pregnancies, but not the recurrence of PIH or preeclampsia.

OBJECTIVE: To assess the role of Doppler uterine artery screening in the prediction of recurring hypertensive disorders in a high-risk population. METHODS: Ninety-four women with a history of hypertensive disorders in previous pregnancies underwent ultrasound color Doppler to analyze blood flow in the uterine arteries at 21-22 weeks of gestation. We evaluated the performance of the Pulsatility Index (PI) as well as the diastolic notch to predict recurring hypertensive disorders. Outcome measures were the recurrence of hypertensive disorders, and poor pregnancy outcome due to intrauterine death growth retardation, intrauterine death, placental abruption, hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome, eclampsia, or premature birth. Onset of symptoms was before 35 weeks in all cases of poor pregnancy outcome. RESULTS: Doppler flow recordings were obtained from a well-defined location in both uterine arteries. The predictive value of the uterine artery PI for recurring hypertensive disease was poor and not significant; interestingly, however, the predictive values for poor pregnancy outcome were good (sensitivity 83%, specificity 71%, p < 0.001). The PI also provides a good test for intrauterine growth retardation (sensitivity 80%, specificity 69%, p < 0.01). The "diastolic notch" did not perform as well as the PI. CONCLUSIONS: Uterine artery screening did significantly predict the recurrence of poor pregnancy outcome due to hypertensive complications in this high-risk group. In contrast, gestational hypertension and preeclampsia with normal pregnancy outcome were not significantly predicted by uterine artery screening.

Trends in live birth prevalence of down syndrome in the Northern Netherlands 1987-96: the impact of screening and prenatal diagnosis.

In the Northern Netherlands, we examined the live birth prevalence of Down syndrome (DS) and the impact of maternal serum screening (MSS) and prenatal cytogenetic diagnosis (PCD) during the period 1987-96. In this period the live birth prevalence, based on the maternal age distribution and the age specific risk of delivering a child with DS was expected to increase from 1.26 in 1987 to 1.62 in 1996. The introduction of MSS in 1991 made PCD available to women of all ages. Nevertheless, the utilization of PCD remained very stable. In 1991, 4.7% of pregnant women underwent a diagnostic test. In 1996 this percentage was 6.4%. As a result of MSS and PCD, the live birth prevalence of DS was 19% lower than expected (p<0.01). Despite utilization of PCD based on opting-in and a discouraging government policy regarding the offer of MSS, the percentage of DS cases detected by PCD increased from of 17% during the period 1987-90 to 27% in the period 1991-96 when MSS was available. The percentages have been corrected for spontaneous pregnancy loss. From a medical and financial point of view, MSS was the most cost-effective indication for PCD. However, the potential of reducing the birth prevalence of DS is limited by the low utilization of MSS and PCD by pregnant women.

Quantification of the diastolic notch in Doppler ultrasound screening of uterine arteries.

OBJECTIVE: To investigate a new method of quantification of the diastolic notch of the flow velocity waveforms of uterine arteries in the prediction of hypertensive disorders of pregnancy. METHODS: Pulsed-wave Doppler was used to obtain flow velocity waveforms (FVWs) from the uterine arteries at 21-22 weeks of gestation from 531 nulliparous women and 94 multiparous women at high risk. From the FVWs, both the pulsatility index (PI) and the notch index (NI) were calculated and the predictive values for both indices were compared using logistic regression analysis for mild and severe early onset hypertensive pregnancy complications. RESULTS: Both the PI and the NI were poor predictors for mild gestational hypertension and pre-eclampsia; predictive values for severe early onset disease, however, were much better. Logistic regression analysis showed the NI has no additional value compared with the PI in the prediction of either mild or severe disease. CONCLUSIONS: The NI offers the possibility to quantify the diastolic notch in uterine artery analysis. Compared to the PI, this does not lead to better predictive values for hypertensive disorders of pregnancy.

Schwangerschafts protein 1 (SP1) adds little to the age-related detection of fetal Down syndrome in the first trimester of pregnancy.

Schwangerschafts Protein 1 (SP1), being a placental protein appearing in the maternal circulation early in pregnancy, has been investigated as a potential marker for Down syndrome in the first trimester. Our study compared SP1 levels in 15 pregnancies with a Down syndrome fetus and 97 matched controls. Although the median MoM in Down syndrome pregnancies (0.49) was lower than in controls, its use as a marker added very little to the detection rate above the maternal age alone.

Maternal serum levels of free beta-hCG and PAPP-A in the first trimester of pregnancy are not associated with subsequent fetal growth retardation or preterm delivery.

The purpose of this case-control study was to examine the association of first-trimester concentrations of free beta-human chorionic gonadotropin (free beta-hCG) and pregnancy-associated plasma protein A (PAPP-A) in maternal serum with subsequent preterm delivery or small-for-gestational age (SGA) fetuses. We collected all the blood samples before chorionic villus sampling in the first trimester. Concentrations of free beta-hCG and PAPP-A were expressed in multiples of the median (MOM) for gestational age. We compared the levels of both analytes in 73 SGA pregnancies (birth weight below the fifth percentile) with those in 292 normal controls, who were matched for gestational age, maternal age, parity, maternal weight, and smoking habits. We also compared the levels in 87 pregnancies with a preterm delivery (delivery before 37 completed weeks) with those in 348 matched controls. The median concentrations of PAPP-A and free beta-hCG, expressed in MOMs, in the 73 SGA pregnancies were 0.83 and 0.95, respectively, compared with 0.98 and 1.01, respectively, in the 292 matched controls (P=0.08 and 0.19, respectively). In the 87 pregnancies with a preterm delivery, the median concentrations of PAPP-A and free beta-hCG were 0.98 and 0.94, respectively, compared with 0.99 and 0.99, respectively, in the 348 matched controls (P=0.82 and 0.10, respectively). In contrast with the maternal serum analytes used in second-trimester screening--alpha-fetoprotein and human chorionic gonadotropin--this study showed that concentrations of PAPP-A and free beta-hCG in the first trimester were not associated with subsequent fetal growth retardation or preterm delivery.

A demographic approach to the assessment of Down syndrome screening performance.

The aim of this article is to examine the performance of screening for fetal Down syndrome (DS) in the context of demographic variation in time and place, using population and fertility data for several European countries. Two screening approaches are distinguished: one on the basis of maternal serum screening with human chorionic gonadotropin (hCG) and alpha-fetoprotein (AFP) in combination with maternal age, and one on the basis of maternal age only. Screening performance, as measured by detection and false-positive ratios, is shown to be the result of the screening approach chosen and of the demographic characteristics of the population under consideration. A proper distinction between these two determinants of DS screening performance should be made, in order to distinguish between an improvement in screening performance that is brought about by a new screening approach and an improvement that is brought about by demographic change. We recommend that measures of DS screening performance be standardized for demographic variation. The methodology and demographic data presented in this article can be used for this purpose.

The HELLP syndrome: its association with unexplained elevation of MSAFP and MShCG in the second trimester.

In this study, we examined the relationship between concentrations of maternal serum alpha-fetoprotein (MSAFP) and maternal serum human chorionic gonadotropin (MShCG) in the second trimester and the haemolysis, elevated liver enzymes, low platelet count (HELLP) syndrome. The concentrations of both serum markers, expressed in multiples of the median (MOM), in 16 women with the HELLP syndrome were compared with those in 10443 women without this syndrome who were screened for Down's syndrome and neural tube defects. All the women with a singleton pregnancy and a known pregnancy outcome were included in this study. At a cut-off level of 2.5 MOM, 37.5 per cent of the pregnancies with the HELLP syndrome had an elevated MShCG level, compared with 4.8 per cent in the whole population (P < 0.0001). 12.5 per cent of the women with the HELLP syndrome had an elevated MSAFP level, compared with 1.3 per cent in the whole population (P < 0.025). Women with a combined elevation of MSAFP and MShCG levels (0.3 per cent of the screened population) had a 47 time greater risk of developing the HELLP syndrome than the others (P < 0.01). The HELLP syndrome should be taken into account in the case of unexplained elevated levels of MShCG and MSAFP, especially in the rare event of combined elevation of both markers.

The association between hypertensive disorders of pregnancy and abnormal second-trimester maternal serum levels of hCG and alpha-fetoprotein.

OBJECTIVE: To examine the association between hypertensive disorders of pregnancy and second-trimester maternal serum alpha-fetoprotein (MSAFP) and hCG levels. METHODS: The proportions of abnormal second-trimester MSAFP and hCG levels in the serum samples from 65 women with true pregnancy-induced hypertension or preeclampsia (cases) were compared to the proportions of abnormal levels in all 1943 women without this disorder in the same cohort in a hospital setting. Maternal serum alpha-fetoprotein and hCG levels of the 65 cases also were compared to those of 325 completely uncomplicated matched control pregnancies, selected from the same cohort. Fisher exact test and Student t test were used for statistical analysis and P < .05 was considered statistically significant. RESULTS: An MSAFP level at least 2.5 multiples of the median (MoM) was found in two of 65 cases (3.1%) and in 27 of 1943 women (1.4%) in the rest of the cohort, a nonsignificant difference (relative risk [RR] = 2.2; P = .24). The statistical power to identify a significant difference for this RR was .27. An hCG level of at least 2.5 MoM was found in six cases (9.2%) and in 89 (4.6%) of women in the rest of the cohort, also a nonsignificant difference (RR = 2.0; P = .12). The statistical power to identify a significant difference for this RR was .38. The mean (+/-standard deviation) logarithms of the MSAFP and hCG MoMs in the 65 cases (0.039 +/- 0.191 and 0.048 +/- 0.265, respectively) were not significantly different from those in the 325 matched controls (0.006 +/- 0.148 and -0.010 +/- 0.244, respectively; P = .12 and .08, respectively). CONCLUSION: Although a weak association cannot be excluded, this study found no clinically important increase in risk of developing subsequent hypertensive disorders of pregnancy among women with abnormal second-trimester levels of MSAFP or hCG.

Maternal urinary beta-core hCG in chromosomally abnormal pregnancies in the first trimester.

We evaluated urinary beta-core human chorionic gonadotropin (beta-core hCG) in the detection of fetal Down's syndrome (DS) in the first trimester of pregnancy. Urine was collected prior to performing chorionic villous sampling (CVS) between 10 and 12 completed weeks from the last menstrual period. In the 9 months of the study, there were 15 chromosomal abnormalities detected by CVS: five trisomy 21, four monosomy X, two trisomy 18, and four cases of confined placental mosaicism (CPM). In these 15 aneuploid pregnancies, the levels of urinary beta-core hCG were expressed as multiples of the median (MOM) of the ratio of beta-core hCG/creatinine for gestational age. The MOMs of this ratio in each of the five DS pregnancies were 0.2, 0.5, 1.3, 1.4, and 1.7. No difference was found between fetuses with DS or any of the other chromosomal abnormalities tested and normal fetuses. Contrary to optimistic reports of urinary beta-core hCG in the second-trimester detection of fetal DS, our data suggest that this is not a useful screening test for DS in the first trimester of pregnancy.

Nuchal translucency cannot be used as a screening test for chromosomal abnormalities in the first trimester of pregnancy in a routine ultrasound practice.

We decided to assess the practicability of introducing nuchal translucency (NT) measurements as a screening programme for fetal Down's syndrome in the first trimester of pregnancy, within the population of women who receive ultrasound examinations in our department. Over a 1-year period, measurements were made in 923 fetuses at < or = 13 weeks' gestation. Fifty-two per cent of the mothers were 36 years or older or had a past history of a chromosomally abnormal fetus or child. Measurements were only successful 58 per cent of the time; this improved to 74 per cent if the fetus was > or = 10 weeks' gestation. Inter-observer variability did not cause a major problem. There were 36 fetuses with an NT > or = 3 mm. Two of these fetuses had a chromosomal abnormality (both trisomy 21). The translucency in these two cases was so large that they would have been detected and offered prenatal diagnosis even prior to this study. There was a total of ten aneuploidies in the study group. Only two of these fetuses were detected by this screening method; five had an NT measurement < 3 mm and in three fetuses (all trisomy 21), measurements were not successful. We outline the practical problems that could be expected by introducing ultrasound screening in a routine setting. Although the efficacy of the test in a research setting may seem good, the effectiveness in everyday usage appears much less impressive, making its uptake as a screening technique in a general ultrasound practice at this stage imprudent.

Placental mosaicism is associated with unexplained second-trimester elevation of MShCG levels, but not with elevation of MSAFP levels.

In this patient-control study, we examined the impact of placental mosaicism on the concentrations of maternal serum human chorionic gonadotropin (MShCG) and maternal serum alpha-fetoprotein (MSAFP) in the second trimester of pregnancy. Patient and control groups were selected from 2347 women with a singleton pregnancy, who underwent chorionic villous sampling in the first trimester and from whom second-trimester serum samples had been collected. The concentrations of both serum markers, expressed in multiples of the median (MOM), in 35 women with confined placental mosaicism (CPM) were compared with those in 70 controls with uncomplicated pregnancies. Elevated MSAFP or MShCG was defined as a concentration of > or = 2.0 MOM. Of the 35 pregnancies with CPM, none had an elevated MSAFP level, as opposed to two out of the 70 women (2.9 per cent) in the control group (P = NS). Nine women in the placental mosaicism group (26 per cent) had an MShCG level of > or = 2.0 MOM, compared with five in the control group (7.1 per cent; P = 0.0135). Nineteen women in the placental mosaicism group (54 per cent) were screen-positive for Down's syndrome (cut-off 1:250), compared with 17 women (24 per cent) in the control group (P = 0.0042; relative risk = 2.3). The three highest MShCG levels were found in pregnancies with CPM that involved trisomy 16; all these women delivered a small-for-gestational age (SGA) infant. CPM, especially with trisomy 16, is associated with elevated levels of MShCG, but not with elevated levels of MSAFP. It is an important cause of false-positive results in serum screening programmes for fetal Down's syndrome. It is possible that abnormal MShCG levels in pregnancies with CPM result from dysfunctional placenta, caused by chromosomally abnormal areas. We therefore recommend increased surveillance of pregnancies with unexplained elevated MShCG levels.