Search

Autoimmune hepatitis (AIH) is a severe chronic autoimmune disease and has a significant impact on the patient's quality of life, in particular regarding psychological problems such as anxiety and depression. Consistent evidence on which patient-related, disease-related or physician-related factors cause health-related quality of life (HRQoL) impairment in patients with AIH is lacking. Current studies on HRQoL in AIH are mainly single-centered, comprising small numbers of patients, and difficult to compare because of the use of different questionnaires, patient populations, and cutoff values. Literature in the pediatric field is sparse, but suggests that children/adolescents with AIH have a lower HRQoL. Knowledge of HRQoL and cohesive factors in AIH are important to improve healthcare for AIH patients, for example by developing an AIH-specific chronic healthcare model. By recognizing the importance of quality of life beyond the concept of biochemical and histological remission, clinicians allow us to seek enhancements and possible interventions in the management of AIH, aiming at improved health., Competing Interests: Conflict-of-interest statement: All authors report no potential conflicts that are relevant to the manuscript., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Introduction: Ongoing developments in prenatal anomaly screening necessitate continuous updating of counsellors' knowledge. We explored the effect of a refresher counselling course on participants' knowledge of prenatal screening., Methods: We investigated the association between knowledge and counsellors' working experience. Also, the association between knowledge and counsellors' attitude towards prenatal screening was determined. All counsellors in the North-West region of the Netherlands were invited to attend a refresher counselling course and fill in both a pre-course and a post-course questionnaire. The participants consisted of midwifes, sonographers and gynaecologists. A 55-item questionnaire assessed pre-course (T0) and post-course (T1) knowledge. At T0, counsellors' attitude towards the prenatal screening program was assessed and its association with knowledge analysed., Results: Of 387 counsellors, 68 (18%) attended the course and completed both questionnaires. Knowledge increased significantly from 77.7% to 84.6% (p<0.01). Scores were lowest regarding congenital heart diseases. Participants with ultrasound experience scored higher on T0, but improvement was seen in participants with and without ultrasound experience. Participants with a positive attitude towards a free-of-charge first trimester combined test had higher knowledge scores than participants with a negative attitude (62% vs 46%; p=0.002)., Conclusions: A refresher course improved counsellors' knowledge on prenatal screening. Ultrasound experience and a positive attitude towards free screening may be associated with higher knowledge levels. Participating in a mandatory refresher counselling course is useful for the continuous improvement of healthcare practitioners' knowledge. More research on the effect of knowledge and attitude on the quality of prenatal screening is necessary., Competing Interests: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none was reported., (© 2020 Jansen C. H. et al.)

Objective: To examine the accuracy and timing of diagnosis of fetal cleft lip with or without cleft palate (CL ± P) in the years following the introduction of a national screening program, and to assess the completeness and accuracy of information in The Netherlands Perinatal Registry., Methods: A list was obtained of cases with a prenatal or postnatal diagnosis of CL ± P from two fetal medicine units between 2008 and 2012. All cases of CL ± P were included irrespective of the presence or absence of additional anomalies. Cases were included if the estimated date of delivery was between 1 January 2008 and 31 December 2012., Results: During the study period, 330 cases of CL ± P were identified, with a prevalence of 15 per 10 000 pregnancies. The number of cases that were detected before 24 weeks' gestation increased during the study period, while the rate of termination of pregnancy did not change significantly (P = 0.511). CL ± P was isolated in 217 (66%) cases and karyotype was abnormal in 69 (21%) cases. In 5% of the cases in which CL ± P seemed to be isolated during the 18-23-week anomaly scan, postnatal array comparative genomic hybridization (array-CGH) revealed an abnormal karyotype and 50% of these cases had major additional anomalies. Examination of data from The Netherlands Perinatal Registry demonstrated that in 37% of cases CL±P was not recorded in the pregnancy records., Conclusion: CL ± P is increasingly being diagnosed prenatally, without a significant effect on the rate of pregnancy termination. Further improvement in the diagnostic accuracy may be achieved by advocating prenatal array-CGH to reduce the frequency of unexpected anomalies being diagnosed after birth. It is important that healthcare providers register accurately the presence or absence of anomalies in the birth records to ensure that, in the future, data from The Netherlands Perinatal Registry can be relied upon to monitor prevalence. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To examine the impact of introduction of the mid-trimester scan on pregnancy outcome in cases of open spina bifida in two regions of The Netherlands., Methods: This was a retrospective cohort study of 190 cases of open spina bifida diagnosed pre- or postnatally, with an estimated date of delivery between 2003 and 2011., Results: With implementation of the mid-trimester scan the percentage of cases of open spina bifida detected before the 24(th) week of pregnancy increased from 43% to 88%. The rise in prenatal detection rate was associated with a significant increase in the number of terminated pregnancies and a decrease in the rate of perinatal loss; the percentage of children born alive did not change significantly. In the subgroup that underwent a scan between 18 and 24 weeks of pregnancy, cranial signs were present in 94.4% of cases., Conclusion: Introduction of the mid-trimester scan has led to an increase in early identification of pregnancies complicated by open spina bifida. Pregnancies previously destined to end in perinatal loss are now terminated whilst pregnancies with a relatively good prognosis are frequently continued; the number of children with open spina bifida who are born alive has not changed significantly. Our study confirms that prenatal diagnosis is usually triggered by visualization of a lemon-shaped skull or a banana-shaped cerebellum., (Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To review the available literature on outcome of pregnancy when an isolated single umbilical artery (iSUA) is diagnosed at the time of the mid-trimester anomaly scan., Methods: We searched MEDLINE (1948-2012), EMBASE (1980-2012) and the Cochrane Library (until 2012) for relevant citations reporting on outcome of pregnancy with iSUA seen on ultrasound. Data were extracted by two reviewers. Where appropriate, we pooled odds ratios (ORs) for the dichotomous outcome measures: small for gestational age (SGA), perinatal mortality and aneuploidy. For birth weight we determined the mean difference with 95% CI., Results: We identified three cohort studies and four case-control studies reporting on 928 pregnancies with iSUA. There was significant heterogeneity between cohort and case-control studies. Compared to fetuses with a three-vessel cord, fetuses with an iSUA were more likely to be SGA (OR 1.6 (95% CI, 0.97-2.6); n = 489) or suffer perinatal mortality (OR 2.0 (95% CI, 0.9-4.2); n = 686), although for neither of the outcomes was statistical significance reached. The difference in mean birth weight was 51 g (95% CI, -154.7 to 52.6 g): n = 407), but again this difference was not statistically significant. We found no evidence that fetuses with iSUA have an increased risk for aneuploidy., Conclusion: In view of the non-significant association between iSUA and fetal growth and perinatal mortality, and in view of the heterogeneity in studies on aneuploidy, we feel that large-scale, prospective cohort studies are needed to reach definitive conclusions on the appropriate work-up in iSUA pregnancies. At present, targeted growth assessment after diagnosis of iSUA should not be routine practice., (Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.)

Objectives: Correct assessment of gestational age and fetal growth is essential for optimal obstetric management. The objectives of this study were, first, to develop charts for ultrasound dating of pregnancy based on crown-rump length and biparietal diameter and, second, to derive reference curves for normal fetal growth based on biparietal diameter, head circumference, transverse cerebellar diameter, abdominal circumference and femur length from 10 weeks of gestational age onwards., Methods: A total of 8313 pregnant women were included for analysis in this population-based prospective cohort study. All women had repeated ultrasound assessments to examine fetal growth., Results: Charts for ultrasound dating of pregnancy, based on crown-rump length and biparietal diameter, were derived. Internal validation with the actual date of delivery showed that ultrasound imaging provided reliable gestational age estimates. Up to 92% of deliveries took place within 37-42 weeks of gestation if gestational age was derived from ultrasound data, compared with 87% based on a reliable last menstrual period. The earlier the ultrasound assessment the more accurate the prediction of date of delivery. After 24 weeks of gestation a reliable last menstrual period provided better estimates of gestational age. Reference curves for normal fetal growth from 10 weeks of gestational age onwards were derived., Conclusions: Charts for ultrasound dating of pregnancy and reference curves for fetal biometry are presented. The results indicate that, up to 24 weeks of pregnancy, dating by ultrasound examination provides a better prediction of the date of delivery than does last menstrual period. The earlier the ultrasound assessment in pregnancy, preferably between 10 and 12 weeks, the better the estimate of gestational age., (Copyright (c) 2008 ISUOG. Published by John Wiley & Sons, Ltd.)

Objectives: The objectives of this study were to determine ethnic differences in prenatal growth and to examine their association with differences in maternal and fetal characteristics such as maternal height, weight, age, parity and fetal gender., Methods: A total of 1494 women from Rotterdam, The Netherlands, with a low-risk pregnancy who participated in a population-based cohort study, the Generation R Study, were offered three ultrasound examinations during pregnancy. Multilevel modeling was applied to determine ethnic differences in (estimated) fetal weight (including birth weight) and in the separate biometric variables that were used to calculate the estimated fetal weight (abdominal circumference, head circumference and femur length). Additionally the association of ethnic differences with maternal and fetal characteristics (i.e. maternal weight, height, age, parity and fetal gender) was studied., Results: Turkish, Cape Verdian, Surinamese-Creole and Surinamese-Hindustani women had on average smaller fetuses than the native Dutch women. The differences became more pronounced towards term. In the Turkish group the differences were no longer statistically significant when adjusted for maternal weight, height, age, parity and fetal gender. In the Cape Verdian, Surinamese-Creole and Surinamese-Hindustani groups the differences decreased after adjustment (31%, 16% and 39%, respectively)., Conclusions: This study shows that there are ethnic differences in fetal growth, which to a large extent may be attributed to differences in maternal weight, height, age and parity. For some ethnic groups, however, additional factors are involved, as differences remain significant after correction for fetal and maternal characteristics., (Copyright 2005 ISUOG. Published by John Wiley & Sons, Ltd.)

Objective: To describe the process of training for measuring nuchal translucency at five clinical centers in North America and to evaluate methods of quality assurance and feedback., Design: Throughout a period of 18 months, the performance of sonographers in measuring fetal nuchal translucency was monitored using qualitative and quantitative methods of review. After 12 months, different approaches (written and personal feedback) were used to inform sonographers of technical aspects that needed to or could be improved., Results: On initial qualitative review, discrepancies in judgment from different reviewers coincided with suboptimal magnification, failure to visualize the amniotic membrane and/or use of cross-shaped calipers. At subsequent global review, 13 (29%) images of nuchal translucency measurements were considered unacceptable. Quantitative assessment revealed that, during the first part of the study, the means from four sonographers were significantly smaller and the mean from the fifth sonographer was significantly larger than expected on the basis of findings from The Fetal Medicine Foundation (P < 0.0001). Following feedback, sonographers who underestimated nuchal translucency and who received a written report only did not change measurements overall (P = 0.9759). In contrast, those who received additional intervention showed a marked difference (P < 0.0001)., Conclusions: Global qualitative review of images from one sonographer may be preferable to assessment of individual aspects of images. Results from global qualitative review correspond well with findings from quantitative analysis, indicating that the latter can be applied for ongoing audit. Observation of divergent results should prompt extensive personal feedback, rather than a written report, to prevent sonographers from settling in their own, inappropriate technique.

Objectives: To evaluate the extent that associated findings aid in the differential diagnosis and/or prognosis of fetal echogenic bowel., Methods: Medical history, obstetric records and outcome details were examined for 131 consecutive pregnancies with fetal hyperechogenic bowel., Results: In 62 (47%) cases, there were no visible anomalies other than hyperechogenic bowel and no evidence of growth restriction. This group included four (7%) pregnancies with Down syndrome, 15 (24%) with infection or a recent episode of influenza and eight (13%) with blood staining of amniotic fluid. In the remaining 69 (53%) cases, hyperechogenic bowel was accompanied by hydrops or nuchal edema (n = 16, 12.2%), growth restriction (n = 9, 6.9%), other markers for chromosome anomalies (n = 33, 25.2%) or multiple structural anomalies (n = 11, 8.4%). In this group, the prevalence of Down syndrome was 12%, infection or influenza was reported in 14 (20%) cases and there was blood staining of amniotic fluid in seven (10%). Cystic fibrosis screening was performed in 65 (50%) pregnancies; the results were negative in all cases and clinical assessment did not indicate cystic fibrosis in any of the 91 infants who were born alive. Maternal serum screening was performed in 41 (31%) pregnancies. High alpha-fetoprotein levels were associated with multiple abnormalities or severe growth restriction., Conclusions: In many pregnancies with fetal hyperechogenic bowel, there are multiple factors that may explain these findings. Thus identification of one potential underlying cause should not preclude further testing. Once chromosome defects, cystic fibrosis, structural abnormalities, infection and growth restriction have been excluded, parents can be counseled that the prognosis is good, irrespective of the presence or absence of blood stained amniotic fluid.

Objective: This study assesses two methods used to define relatively short femur in screening for trisomy 21 and examines changes in performance of screening with gestational age., Design: Retrospective analysis of data on menstrual age, femur length (FL) and biparietal diameter (BPD) in 49 trisomy 21 pregnancies and 6069 normal controls. Reference ranges were derived for BPD/FL versus menstrual age and for FL versus BPD. Two methods of defining short femur (BPD/FL and observed-to-expected FL ratio) were examined for false-positive rates and detection rates for trisomy 21 at different gestational ages., Results: In the control group the BPD/FL ratio and its standard deviation decreased with menstrual age. Trisomy 21 was associated with a significantly higher BPD/FL ratio (P < 0.001) and the deviation increased significantly with menstrual age (P < 0.05). Eleven percent of 28 fetuses examined at 15-17 weeks had a BPD/FL above the 95th centile compared with 24% of 21 fetuses examined at 18-20 weeks (P = 0.40). The median observed-to-expected FL ratio in the control group was 1.0 throughout the gestational age range but the standard deviation decreased significantly with menstrual age (P < 0.01). Trisomy 21 was associated with a significantly reduced observed-to-expected FL ratio (P < 0.001) and the deviation increased significantly with menstrual age (P < 0.05). A fixed cut-off of 0.91 for observed-to-expected FL ratio provided a false-positive rate of 12% at 15-17 weeks compared with 6% at 18-20 weeks of gestation (P < 0.001) with detection rates of 29 and 38%, respectively (P = 0.73)., Conclusion: Irrespective of the definition used to define the condition, relatively short femur is a poor marker for trisomy 21 particularly when the assessment takes place before 18 weeks of gestation.

Objective: To provide estimates of maternal age- and gestational age-related risks for trisomy 21., Methods: The prevalence of trisomy 21 was examined in 57,614 women who had fetal karyotyping at 9-16 weeks of gestation for the sole indication of maternal age of 35 years or more. On the basis of the maternal age distribution and the reported maternal age-related risk for trisomy 21 at birth, the expected number of trisomy 21 cases was calculated for each gestational age subgroup (9-10 weeks, 11-14 weeks and 15-16 weeks). The ratio of the observed to expected number of cases of trisomy 21 was then calculated and regression analysis was applied to derive a smoothened curve. The formula for maternal age- and gestational age-related risk was then applied to a population of 96,127 pregnancies that were examined at 10-14 weeks to calculate the expected number of trisomy 21 pregnancies, and this number was compared to the observed number of 326., Results: In the 57,614 pregnancies there were 538 cases of trisomy 21. The relative prevalences of trisomy 21, compared to a prevalence of 1.0 at 40 weeks, was 10 exp(0.2718 x log(10)(gestation)2 - 1.023 x log10(gestation) + 0.9425). On the basis of the estimated maternal age- and gestational age-related risks, the expected number of trisomy 21 cases at 10-14 weeks of gestation in the 96,127 pregnancies was 329 (95% confidence interval 291-361), which was not significantly different from the observed number of 326 cases (chi2 = 0.02)., Conclusion: The risk for trisomy 21 increases with maternal age and decreases with gestation. The prevalence of trisomy 21 at 12 and 16 weeks of gestation is higher than the prevalence at 40 weeks by 30% and 21%, respectively.

Increased fetal nuchal translucency thickness at 10-14 weeks of gestation is a common phenotypic expression of fetal chromosomal defects, structural abnormalities and genetic syndromes. This study reports on the prevalence of structural abnormalities and genetic syndromes in 4116 chromosomally normal pregnancies with increased fetal nuchal translucency thickness and reviews the relevant literature. In fetuses with increased nuchal translucency thickness, the prevalence of major cardiac defects, diaphragmatic hernia, exomphalos, body stalk anomaly and fetal akinesia deformation sequence is substantially higher than expected in the general population. In addition, there may be an association between increased nuchal translucency thickness and a wide range of rare skeletal dysplasias and genetic syndromes that are usually found in less than one in 10,000 pregnancies; however, the number of affected cases, both in the present and in previous series of fetuses with increased nuchal translucency thickness, is too small for definite conclusions to be drawn. The rates of miscarriage and perinatal death increase, whereas the rate of survival and the prevalence of live births with no obvious abnormalities decrease with increasing nuchal translucency thickness.

In a multicenter project of screening for chromosomal defects by fetal nuchal translucency thickness and maternal age at 10-14 weeks, 14 of 106,727 fetuses examined had body stalk anomaly. The ultrasonographic features were a major abdominal wall defect, severe kyphoscoliosis and a short umbilical cord. In all cases, the upper part of the fetal body was in the amniotic cavity, whereas the lower part was in the celomic cavity. The nuchal translucency thickness was above the 95th centile in ten (71.4%) of the cases, but the fetal karyotype was normal in all 12 fetuses evaluated. The findings suggest that early amnion rupture before obliteration of the celomic cavity is a possible cause of the syndrome.

A beneficial consequence of screening for trisomy 21 by a combination of maternal age and fetal nuchal translucency thickness (NT) at 10-14 weeks is the early diagnosis of trisomy 18. In a multicenter study of 91,091 singleton pregnancies there were 106 fetuses with trisomy 18 and 83% were identified by NT screening. Trisomy 18 was also associated with early onset intrauterine growth retardation, decreased fetal heart rate and the presence of exomphalos.

In three cases of lumbosacral spina bifida diagnosed at 12, 13 and 14 weeks of gestation there was an associated lemon sign, or scalloping of the frontal bones, and in one case the fetal nuchal translucency was increased. In a multicenter ultrasound screening study at 10-14 weeks there were 61,972 singleton pregnancies including 29 cases of spina bifida, none of which was diagnosed at the routine first-trimester scan, but 28 of the 29 cases were detected by ultrasonography at 16-22 weeks; in one case the diagnosis was missed at the 20-week scan and the defect was identified at 32 weeks during a scan for localization of the placenta. The fetal nuchal translucency was above the 95th centile in only one of the cases (3.4%). It is possible that the majority of fetuses with spina bifida have a lemon sign in the first trimester, but the sensitivity of the 10-14-week scan in the diagnosis of spina bifida and the prevalence of the lemon sign at this gestation will only be established by further studies incorporating early systematic examination of the head and spine.

Gestation at delivery, birthweight and pregnancy outcome of surviving fetuses from 127 multifetal pregnancies undergoing embryo reduction to twins were compared to 354 chromosomally normal non-reduced dichorionic twin pregnancies. First-trimester embryo reduction was carried out by intracardiac injection of KCl. In 16 (12.6%) of the 127 multifetal pregnancies reduced to twins, there was miscarriage of both fetuses before 24 weeks of gestation. The median interval between reduction and fetal loss was 5 weeks (range 1-12). In livebirths, the median gestation at delivery was 36 weeks (range 24-41) and the median difference in birthweight from the appropriate mean was -0.94 SD (range -3.89-1.73 SD). Both fetal loss before 24 weeks and the interval between embryo reduction and delivery were significantly associated with the gestation at reduction (r = 0.40, P < 0.001 and r = -0.57, P < 0.001 respectively). In the pregnancies reduced to twins compared to the non-reduced twins, the percentage of miscarriages was higher (12.6 compared to 2.5%; chi 2 = 19.2, P < 0.001), the median gestation at delivery was lower (36 compared to 37 weeks; t = -1.74, P < 0.05), and the median birthweight deficit was greater (-0.94 compared to -0.65 SD: t = -4.1, P < 0.001).

In an ongoing study involving seven hospitals in London and surrounding areas, 55,237 fetuses were examined by ultrasound at 10-14 weeks of gestation. There were 47 fetuses (1 in 1175) with anencephaly which presented with acrania with varying degrees of cerebral degeneration. The first audit of results was performed in April 1995. During the first phase of the study 34,830 fetuses were examined and in eight of the 31 with anencephaly the diagnosis was not made at the 10-14-week scan. Following the audit, 20,407 fetuses were examined and in all 16 with anencephaly the diagnosis was made at the 10-14-week scan (p = 0.03). These findings demonstrate that anencephaly can be reliably diagnosed at the routine 10-14-week ultrasound scan, provided a specific search is made for the sonographic features for this condition.

During the study period, 24,492 pregnant women attended the Harris Birthright Research Centre at 10-14 weeks of gestation, at which time, in addition to the measurements of nuchal translucency thickness and crown-rump length (CRL), data on fetal abnormalities were recorded onto a computer database. Cases of megacystis were identified and the records were reviewed. Additionally, the relationship of the longitudinal bladder diameter with the CRL and the bladder diameter/CRL ratio (expressed as a percentage) were examined with the use of data from 300 normal fetuses at 10-14 weeks. Megacystis was present in 15 of the 24,492 pregnancies (1 in 1,633) and in these cases the minimum longitudinal bladder diameter was 8 mm and the minimum bladder diameter/CRL ratio was 13%. In the 300 control fetuses the bladder was visualized in 278 (92.7%) of the cases and the longitudinal bladder diameter increased with the CRL (bladder diameter = 0.065 x CRL - 0.69; r = 0.47, p < 0.001), none of the measurements was more than 6 mm and the median bladder diameter/CRL ratio was 5.4% (range 0-10.4%) which did not change significantly with gestation (r = 0.1, p = 0.09). The bladder was visible in all cases with a minimum CRL of 67 mm. In three of the 15 cases with megacystis, there were chromosomal abnormalities. In the chromosomally normal group, there were seven cases with spontaneous resolution, whereas in four cases there was progression to severe obstructive uropathy. The bladder diameter was 8-12 mm and the bladder diameter/CRL ratio 13-22% in all cases with resolution and in one case with progressive megacystis; in the other three cases with progressive obstruction, the bladder length was more than 16 mm and the bladder diameter/CRL ratio was more than 28%.

Fetal heart rate was measured routinely as part of a prospective study examining the efficacy of screening for trisomy 21 by fetal nuchal translucency thickness and maternal age. In 6903 normal singleton pregnancies the fetal heart rate decreased from a mean of 171 bpm at 10 weeks of gestation to 156 bpm at 14 weeks (r = 0.413, p < 0.0001). In 85 trisomy 21 pregnancies, the mean heart rate was significantly higher than in the normal group (mean difference 0.67 SD, 95% confidence interval 0.42-0.92, t = 5.3, p < 0.001). The fetal heart rate in trisomy 18 and triploid fetuses was significantly lower and in trisomy 13 and Turner syndrome was higher than normal. There was no significant association between delta fetal heart rate and delta nuchal translucency thickness in either the normal (r = -0.018) or the trisomy 21 (r = -0.031) pregnancies. Consequently, the risk for chromosomal defects can be derived by combining data from maternal age, fetal nuchal translucency and fetal heart rate. The effectiveness of screening by this method was examined in a self-selected population with completed pregnancies that had undergone first-trimester scanning. This population contained 6903 normal and 29 trisomy 21 fetuses. For a false-positive rate of about 5%, the sensitivity for trisomy 21 was 48% by maternal age, 26% by fetal heart rate, 72% by nuchal translucency thickness, 59% by maternal age and fetal heart rate, 76% by maternal age and nuchal translucency thickness and 83% by a combination of maternal age, nuchal translucency thickness and fetal heart rate.

In an ultrasound screening study at 10-13 weeks of gestation involving 17,870 women, the prevalence of early pregnancy failure was 2.8% (501 cases), including 313 (62.5%) missed abortions and 188 (37.5%) anembryonic pregnancies. Lower gestation and higher maternal age were associated with a higher prevalence (chi 2 = 143.5; p < 0.001 and chi 2 = 53.3; p < 0.0001, respectively). The prevalence was higher in women with a history of vaginal bleeding (chi 2 = 141.5; p < 0.0001), but there was no significant association with previous pregnancy losses (chi 2 = 2.8), parity (chi 2 = 0.6) or cigarette smoking (chi 2 = 0.0). Recent evidence suggests that the most effective method of screening for chromosomal abnormalities is measurement of fetal nuchal translucency thickness at 10-13 weeks, and therefore ultrasound examination at this gestation is likely to become universally available. As shown in this study, an additional advantage of such a scan is the diagnosis of early pregnancy failure, which will be found in about 3% of patients examined. Elective evacuation of retained products of conception is likely to be more cost effective and potentially safer than emergency surgery in a patient presenting during miscarriage.

This study investigates whether first-trimester screening for trisomy 21 by fetal nuchal translucency thickness preferentially identifies those fetuses destined to die in utero and examines the potential impact of such a method of screening on the live birth incidence of trisomy 21. In 70 pregnancies, trisomy 21 was diagnosed at 12 (range 11-14) weeks of gestation and the parents opted for elective termination which was carried out at 14 (12-20) weeks. In all cases, viability was established by ultrasound scan at the time of chorion villus sampling (CVS) and just before termination of pregnancy. Eight (11.4%) fetuses died in the interval between CVS and termination of pregnancy and this rate of lethality was higher than the 6.9% estimated rate for an unselected population of trisomy 21 fetuses. This 4.5% increase may, in part, be attributed to the effects of CVS and may also be due to patient selection on the basis of increased nuchal translucency. The rate of lethality increased with translucency thickness from 5.3% for those with translucency of 1-3 mm to 23.5% for translucency of > 7 mm. In trisomy 21, the rate of intrauterine lethality is associated with nuchal translucency thickness. Nevertheless, a policy of screening by maternal age and fetal nuchal translucency followed by selective termination of affected fetuses would still result in a more than 70% reduction in the live birth incidence of trisomy 21.

The aim of this prospective study was to measure the contribution of maternal serum free beta-human chorionic gonadotropin (beta-hCG) in a screening program for fetal trisomy 21 based on fetal nuchal translucency in the first trimester of pregnancy. The maternal serum was collected at the time of the ultrasound scan and assayed without knowledge of the nuchal translucency measurement or karyotype. A total of 2529 pregnancies were examined (normal group, n = 2427; trisomy 21 group, n = 102). Maternal serum free beta-hCG was significantly associated with gestational age and maternal weight. In the trisomy 21 group the free beta-hCG was significantly higher than in the normals, being above the 95th centile in 29% of the cases. There was no significant association between the deviation from the mean for free beta-hCG and nuchal translucency thickness in either the normal or the trisomy 21 groups. When maternal serum free beta-hCG was added to a model based on maternal age and fetal nuchal translucency thickness, the detection rate for trisomy 21 was increased from 80% to 85%.

During a 7-year period (1988-94), we diagnosed 102 fetuses with trisomy 18, and 54 with trisomy 13; in 6.9% of the trisomy 18 and in 40.7% of the trisomy 13 fetuses, there was a facial cleft. On the basis of (1) these frequencies of facial cleft in trisomic fetuses; (2) the reported prevalence of facial cleft in mid-trimester fetuses; and (3) estimates of the prevalence of trisomies 18 and 13 at 20 weeks of gestation in a population with the maternal age distribution of all deliveries in England and Wales, it was calculated that 6.5% of fetuses with a facial cleft would have trisomy 18 or 13. This estimated frequency of trisomies was significantly lower than the 26% observed in 111 fetuses with a facial cleft that were referred to our unit for fetal karyotyping. These findings suggest that the patients with a facial cleft examined in a referral center are preselected in favor of those with multiple abnormalities, and therefore a higher frequency of associated chromosomal defects. In the future, with improving quality of ultrasound equipment and standards of scanning, it is likely that more cases of isolated facial cleft will be identified and, consequently, the observed frequency of chromosomal defects should decrease.

In an ultrasound screening study involving 15,726 viable, singleton pregnancies at 11-14 weeks of gestation, exomphalos was diagnosed in 0.11% of the cases and, in those with exomphalos, the frequency of trisomy 18, trisomy 13 or triploidy was 61%. The corresponding frequencies of exomphalos of fetuses with these chromosomal defects were 22.5%, 9.1% and 12.5%, respectively. The median maternal age of the screened population was 33 (range 15-48) years, which is higher than in all pregnancies in England and Wales. Expected prevalences of trisomy 18, trisomy 13 and triploidy in the total population were derived on the basis of the age distribution of all deliveries in England and Wales and maternal and gestational age-specific risks for these chromosomal defects. From these numbers and the observed frequencies of exomphalos in association with the various chromosomal defects, it was estimated that the prevalence of exomphalos in a population with the maternal age distribution of all deliveries in England and Wales was 7.4 per 10,000 at 12 weeks of gestation, and this decreased to 3.5 at 20 weeks and 2.9 in live births. The estimated frequency of chromosomal defects in fetuses with exomphalos decreased from 39.4% at 12 weeks of gestation to 27.5% at 20 weeks and 14.4% in live births. The prevalence of chromosomal defects in 153 fetuses with exomphalos referred to our center at 16-26 (median 20) weeks of gestation was not significantly different from that predicted in an unselected population. However, the reported frequency of chromosomal defects in a total of 299 neonates with exomphalos (9.3%) was significantly lower than expected in an unselected population. This study demonstrates that the prevalence of a fetal abnormality and the frequency of associated chromosomal defects depends on the maternal age and gestational age distributions of the populations examined.

Increased fetal nuchal translucency thickness at 10-14 weeks of gestation can identify 80% of trisomy 21 pregnancies. However, a potential disadvantage of screening in the first trimester of pregnancy is that earlier screening preferentially identifies those chromosomally abnormal pregnancies that are destined to miscarry. In this study, we report on the outcome of six fetuses with increased nuchal translucency thickness and trisomy 21 whose parents chose to continue with the pregnancy. During the second trimester, the nuchal translucency resolved in five of the cases and in one it evolved into nuchal edema. Therefore, resolution of translucency with advancing gestation is not indicative of a normal karyotype. All pregnancies resulted in live births, suggesting that increased nuchal translucency does not necessarily identify those trisomic fetuses that are destined to die in utero.

In 1015 fetuses undergoing first-trimester karyotyping because of increased nuchal translucency thickness, the incidence of chromosomal abnormalities increased with both maternal age and nuchal translucency thickness. The observed numbers of trisomies 21, 18 and 13 in fetuses with nuchal translucency thicknesses of 3 mm, 4 mm, 5 mm and > or = 6 mm were approximately 3 times, 18 times, 28 times and 36 times higher than the respective numbers expected on the basis of maternal age. The incidences of Turner syndrome and triploidy were 9-fold and 8-fold higher but the incidence of other sex chromosome aneuploidies was similar to that of an unselected population of women undergoing first-trimester fetal karyotyping for maternal age. In the chromosomally normal group, the incidence of structural defects, mainly cardiac, diaphragmatic, renal and abdominal wall, was approximately 4%, which is higher than would be expected in an unselected population. The rates of fetal loss in the groups with nuchal translucency thickness of 3 mm and 4 mm were 2% and 4%, respectively, which is similar to the 2.3% rate of fetal loss observed in a group of fetuses with normal nuchal translucency thickness undergoing chorion villus sampling. For fetal nuchal translucency thickness of > or = 5 mm, the rate of fetal loss was 13%.

The aim of this prospective screening study was to evaluate the implementation of an additional ultrasound examination, incorporating the measurement of fetal nuchal translucency thickness, at 10-13 weeks' gestation in two maternity units providing routine antenatal care. During the 1 year prior to the introduction of the first-trimester scan, the major indication for fetal karyotyping was maternal age > or = 35 years and only two out of the total of 11 cases of trisomy 21 were identified. In the first 5 months of the study, 70% of the women delivering in these hospitals attended for measurement of fetal nuchal translucency thickness and the measurement was obtained in all cases. This was achieved without an increase in the number of sonographers or ultrasound machines. The incidence of fetal nuchal translucency thickness > or = 2.5 mm was 3.6% (63 of 1763), and this group included three of the four fetuses with trisomy 21. The findings of this study demonstrate the feasibility of introducing scanning at 10-13 weeks' gestation and the measurement of fetal nuchal translucency thickness in routine maternity units. The sensitivity and specificity of this method of screening are at present being evaluated in a large multicenter study.

Normal ranges for a wide variety of biometrical parameters were established from cross-sectional data on 1040 normal singleton pregnancies resulting in livebirth at term of normal, and appropriately grown infants. Patients were selected so that the birth weight distribution was similar to that reported by Yudkin and colleagues' and the ranges can, therefore, be used for any population that has a similar birth weight distribution., (Copyright 1994 International Society of Ultrasound in Obstetrics and Gynecology)

The effect of fetal anaemia on the total and differential leucocyte counts was studied by examining blood samples obtained by cordocentesis from 177 previously untransfused rhesus affected fetuses at 17-36 weeks' gestation. The mean fetal total leucocyte, lymphocyte, and monocyte counts were significantly lower than the corresponding values in normal controls and there were significant associations between the decrease in these cells and the degree of fetal anaemia. Possible mechanisms for leucopenia include (i) stimulation of erythroid progenitor production at the expense of production of myeloid progenitors, (ii) non-specific haemophagocytosis, or (iii) general suppression of haemopoiesis. Further understanding of the underlying mechanism and the implications of leucopenia as well as the previously reported thrombocytopenia and anaemia may provide a basis for improved antenatal and/or postnatal treatment.

Total and differential leucocyte counts were measured in cord blood samples obtained by cordocentesis (n = 316) or at elective caesarean section (n = 11) from normal fetuses of between 18 and 40 weeks' gestation. The total fetal leucocyte count increased exponentially from 2.8 x 10(9)/l at 18 weeks to 11.8 x 10(9)/l at term. The lymphocyte and monocyte counts increased linearly and the number of neutrophils increased exponentially from a mean value of 0.2 x 10(9)/l at 18 weeks to 0.8 x 10(9)/l at 31 weeks and then 8.5 x 10(9)/l at term. Early myeloid cells, eosinophils, and basophils were observed in 24%, 55%, and 15% of the blood films respectively; they contributed less than 2% to the total leucocyte count and there were no significant changes with gestation. The physiological leucopenia observed in fetuses early in the third trimester may partly explain the predisposition of premature neonates to infection.