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.)

Introduction: Mid-trimester uterine artery resistance measured with Doppler sonography is predictive for iatrogenic preterm birth. In view of the emerging association between hypertensive disease in pregnancy and spontaneous preterm birth, we hypothesized that uterine artery resistance could also predict spontaneous preterm birth., Material and Methods: We performed a cohort study of women with singleton pregnancies. Uterine artery resistance was routinely measured at the 18-22 weeks anomaly scan. Pregnancies complicated by congenital anomalies or intrauterine fetal death were excluded. We analyzed if the waveform of the uterine artery (no notch, unilateral notch or bilateral notch) was predictive for spontaneous and iatrogenic preterm birth, defined as delivery before 37 weeks of gestation. Furthermore, we assessed whether the uterine artery pulsatility index was associated with the risk of preterm birth., Results: Between January 2009 and December 2016 we collected uterine Doppler indices and relevant outcome data in 4521 women. Mean gestational age at measurement was 19 +6  weeks. There were 137 (3.0%) women with a bilateral and 213 (4.7%) with a unilateral notch. Mean gestational age at birth was 38 +6  weeks. Spontaneous and iatrogenic preterm birth rates were 5.7% and 4.9%, respectively. Mean uterine artery resistance was 1.12 in the spontaneous preterm birth group compared with 1.04 in the term group (P = 0.004) The risk of preterm birth was increased with high uterine artery resistance (OR 2.9 per unit; 95% CI 2.4-3.9). Prevalence of spontaneous preterm birth increased from 5.5% in women without a notch in the uterine arteries to 8.0% in women with a unilateral notch and 8.0% in women with a bilateral notch. For iatrogenic preterm birth, these rates were 3.9%, 13.6% and 23.4%, respectively. Likelihood ratios for the prediction of spontaneous preterm birth were 1.6 (95% CI 1.0-2.6) and 1.9 (95% CI 1.0-3.5) for unilateral and bilateral notches, respectively, and for iatrogenic preterm birth they were 3.6 (95% CI 2.5-5.2) and 6.8 (95% CI 4.7-9.9) for unilateral and bilateral notches, respectively. Of all women with bilateral notching, 31.4% delivered preterm., Conclusions: Mid-trimester uterine artery resistance measured at 18-22 weeks of gestation is a weak predictor of spontaneous preterm birth., (© 2019 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

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: The objective of this study is to assess the gestational age at detection and prevalence of anencephaly in the North of The Netherlands over a 5-year period., Methods: A case list of all cases of anencephaly from two fetal medicine units was compiled. Cases were included if the estimated due date was between 1 August 2008 and 31 July 2013., Results: Overall prevalence of anencephaly was 5.4 per 10.000 pregnancies (n = 110). The majority of cases (69%) was detected before 18 weeks' gestation. Factors determining successful early diagnosis were competence level of the sonographers, with a significantly higher detection rate when scans were performed by a sonographer licensed by the Fetal Medicine Foundation (FMF) for nuchal translucency measurement (p = 0.001), and gestational age at or beyond 11 weeks of gestation (p = 0.024)., Conclusion: Improving detection of anencephaly in the first trimester requires ultrasound screening at or after 11 weeks of gestation, performed by experienced sonographers trained in recognizing fetal anomalies. Sonographers should be instructed that the goal of the first trimester scan is not only to measure nuchal translucency thickness but also to exclude major anomalies., (© 2015 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: The aim of this study was to investigate the association of the first trimester screening variables nuchal translucency (NT), pregnancy associated plasma protein (PAPP-A), and free beta-human chorionic gonadotrophin (βhCG) and birth weight, with a focus on the prediction of macrosomia., Methods: The database of our Fetal Medicine Unit was searched for all singleton pregnancies, who underwent first trimester Down syndrome screening. Live born infants born at term without chromosomal or structural defects from non-diabetic mothers constituted the study population. Birth weight percentiles were corrected for gestational age at delivery, parity, and gender. Macrosomia was defined as birth weight ≥95th centile., Results: We included 6503 fetuses. Multivariate analysis demonstrated that birth weight centile was positively correlated with NT multiples of the median (MoM), PAPP-A MoM, and maternal body mass index, and it was negatively correlated with smoking. An NT ≥95th centile was present in 315 fetuses (4.8%). Although median birth weight centile was not significantly different between cases with NT ≥95th centile and those <95th (P54 vs P52), a birth weight >95th centile was more common (11% vs 7%) in the presence of NT ≥95th centile. Pregnancy associated plasma protein was elevated (≥95th centile) in 303 cases (7.9%). Median birth weight was higher (P56 vs P51, P = 0.03) in case of elevated PAPP-A compared with PAPP-A <95th centile. There was a trend toward higher macrosomia rate in case of PAPP-A ≥95th centile (7.4% vs 6.3%, P = 0.07). Area under the receiver operating characteristics (ROC) curve for the prediction of macrosomia (birth weight ≥95th centile) by NT MoM, PAPP-A MoM, maternal body mass index, and maternal smoking was 0.64 (P < 0.001)., Conclusions: First trimester PAPP-A MoM and NT MoM are significantly related to birth weight centiles. Enlarged NT is associated with macrosomia., (© 2013 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.)

Objective: To describe the incidence and the prognostic value of foetal ventriculomegaly identified between 18-23 weeks of gestational age in the northeastern part of the Netherlands during the 2002-2010 period., Design: Retrospective cohort study., Method: From the database of the University Medical Centre Groningen in the Netherlands, we selected all cases of singleton pregnancies in which ventriculomegaly was diagnosed at 18-23 weeks of gestation., Results: In 2002, ventriculomegaly was diagnosed prenatally in 1:7000 foetuses; the incidence increased to 1:1750 in 2010. In 33 (51%) of 65 affected foetuses, an associated severe physical abnormality was detected, in 5 (8%) a subtle sonomarker (subtle ultrasound finding) and in 8 (12%), a chromosomal defect. In 47% of the pregnancies where ventriculomegaly was associated with other defects, the parents opted for termination of pregnancy. In the group with isolated mild ventriculomegaly (10-12 mm), termination was performed in 1 of 19 cases; and in the group with the greater ventricular width of 13-14 mm, this decision was made for 5 of the 8 pregnancies. All continued pregnancies of foetuses with isolated ventriculomegaly resulted in live births. Isolated ventriculomegaly was diagnosed relatively more frequently in male foetuses., Conclusion: The introduction of ultrasound scans as part of standard prenatal care has resulted in an increased incidence of foetal ventriculomegaly. Important factors for predicting the outcome of the pregnancy are the degree of ventricular dilatation, the foetus' gender and the presence or absence of associated abnormalities. It is therefore important to use a standardised protocol for measuring ventricular width, record the biparietal diameter and foetal gender, perform a systematic physical examination and use karyotyping.

Objective: The aim of this study was to evaluate which of the following factors affect the uptake of the combined test (CT) in The Netherlands: women's socio-demographic background, attitude towards Down syndrome, attitude towards termination of pregnancy, counseling process, reimbursement policy, and knowledge on the aim of the CT., Methods: Cross-sectional survey in the Northwest (NW) and the Northeast (NE) region of The Netherlands., Results: Analyses were based on 820 questionnaires (73% response rate). Women from the NW region opted more often for the CT than women from the NE region (52.1% and 16.5%, respectively, p < 0.001). Women of 36 years and older opted more often for the CT than younger women (59.4% and 28.2%, respectively, p < 0.001). Women's socio-demographic background and their attitude towards Down syndrome and termination of pregnancy (TOP) had contributed independently on CT choice., Conclusion: The uptake of the CT in this study is low. The main reason for the low uptake is the relatively positive attitude towards Down syndrome and a negative attitude towards TOP. Moreover, the perception of maternal age as strong predictor of Down syndrome risk and the inequality of access to care, due to the financial threshold for younger women, are likely to affect participation in screening., (© 2012 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: To determine fetal growth in low risk pregnancies at the beginning of the third trimester and to assess the relative importance of fetal gender and maternal parity., Setting: Dutch primary care midwifery practice., Study Design: Retrospective cohort study on 3641 singleton pregnancies seen at a primary care midwifery center in the Netherlands. Parameters used for analysis were fetal abdominal circumference (AC), fetal head circumference (HC), gestational age, fetal gender and maternal parity. Regression analysis was applied to describe variation in AC and HC with gestational age. Means and standard deviations in the present population were compared with commonly used reference charts. Multiple regression analysis was applied to examine whether gender and parity should be taken into account., Results: The fetal AC and HC increased significantly between the 27th and the 33rd week of pregnancy (AC r2=0.3652, P<0.0001; HC r2=0.3301, P<0.0001). Compared to some curves, our means and standard deviations were significantly smaller (at 30+0 weeks AC mean=258+/-13 mm; HC mean=281+/-14 mm), but corresponded well with other curves. Fetal gender was a significant determinant for both AC (P<0.0001) and HC (P<0.0001). Parity contributed significantly to AC only but the difference was small (beta=0.00464)., Conclusion: At the beginning of the third trimester, fetal size is associated with fetal gender and, to a lesser extent, with parity. Some fetal growth charts (e.g., Chitty et al.) are more suitable for the low-risk population in the Netherlands than others.

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.

In a multicenter screening study for trisomy 21 involving ultrasonographic measurement of fetal nuchal translucency thickness (NT) at 10-14 weeks of gestation, 100,311 singleton pregnancies with a live fetus were examined. There were 46 cases of trisomy 13, and in 33 (72%) of these, the NT was above the 95th centile. The estimated risk for trisomy 21, based on maternal age-related risk for this chromosomal abnormality and fetal NT, was above 1 in 300 in 37 (80.1%) of the trisomy 13 fetuses. The fetal crown-rump length was significantly reduced, but the fetal heart rate was increased, being above the 95th centile in 64% of cases. Additionally, 24% of trisomy 13 fetuses had holoprosencephaly and 10% had exomphalos. This study has demonstrated that at 10-14 weeks of gestation, about 80% of fetuses with trisomy 13 can be identified in a screening program for trisomy 21, based on a combination of maternal age and fetal NT., (Copyright 1999 Wiley-Liss, Inc.)

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.

Background: Prenatal diagnosis of trisomy 21 currently relies on assessment of risk followed by invasive testing in the 5% of pregnancies at the highest estimated risk. Selection of the high-risk group by a combination of maternal age and second-trimester maternal serum biochemistry gives a detection rate of about 60%. We investigated assessment of risk by a combination of maternal age and fetal nuchal-translucency thickness, measured by ultrasonography at 10-14 weeks of gestation., Methods: The risk of trisomy 21 was estimated for 96127 women of median age 31 years (range 14-49) with singleton pregnancies. Ultrasonography was done by 306 appropriately trained sonographers in 22 centres. Risk of trisomy 21 was calculated from the maternal age and gestational-age-related prevalence, multiplied by a likelihood ratio depending on the deviation from normal in nuchal-translucency thickness for crown-rump length. The distribution of risks was investigated and the sensitivity of a cut-off risk of 1 in 300 was calculated. Phenotype was assessed by fetal karyotyping or clinical examination of liveborn infants., Findings: The estimated trisomy-21 risk, from maternal age and fetal nuchal-translucency thickness, was 1 in 300 or higher in 7907 (8.3%) of 95476 normal pregnancies, 268 (82-2%) of 326 with trisomy 21, and 253 (77.9%) of 325 with other chromosomal defects. The 5% of the study population with the highest estimated risk included 77% of trisomy-21 cases., Interpretation: Selection of the high-risk group for invasive testing by this method allows the detection of about 80% of affected pregnancies. However, even this method of risk assessment requires about 30 invasive tests for identification of one affected fetus.

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.

At 10-14 weeks of gestation more than 80 per cent of fetuses affected by trisomy 21 can be detected by a screening programme based on a combination of maternal age and fetal nuchal translucency thickness (NT). The screen positive group in such a programme also identifies fetuses with sex chromosome abnormalities. In this ongoing multicentre screening study, involving 61,972 singleton pregnancies, 53 cases of sex chromosome abnormalities were identified. The fetal NT was above the 95th centile in 87.9 per cent of the 33 cases with 45,XO, and in 40 per cent of the 20 cases with 47,XXX, 47,XYY or 47,XXX. However, it was estimated that at 12 weeks of gestation our population would contain 42 cases with 45,XO and 104 cases with 47,XXY, 47,XYY or 47,XXX. Since the rate of intra-uterine lethality, between 12 and 40 weeks of gestation, is about 65 per cent for 45,XO and four per cent for 47,XXY, 47,XYY or 47,XXX, the respective number of livebirths with these chromosomal abnormalities would have been 15 and 100, respectively, without prenatal diagnosis. Assuming that all intra-uterine deaths are from those with increased NT, screening for trisomy 21 by maternal age and fetal NT would have identified only 20 per cent of potential livebirths in the 45,XO group and nine per cent of those with 47,XXY, 47,XYY or 47,XXX.

Objective: To examine the possible association between increased fetal nuchal translucency thickness at 10-14 weeks and congenital diaphragmatic hernia., Methods: This was a multicenter ultrasound screening study for chromosomal defects in singleton pregnancies by a combination of maternal age and fetal nuchal translucency at 10-14 weeks' gestation. The prevalence of diaphragmatic hernia diagnosed prenatally or postnatally was calculated in the chromosomally normal group and in those pregnancies resulting in live births with no dysmorphic features suggestive of a chromosomal abnormality. We calculated the sensitivity of nuchal translucency above the 95th centile of the normal range in the detection of diaphragmatic hernia and the possible prognostic value of increased nuchal translucency in the prediction of outcome., Results: There were 78,639 pregnancies presumed to be normal chromosomally, including 19 with diaphragmatic hernia. In four cases, the parents opted for termination of the pregnancy. The other 15 pregnancies resulted in live births; nine infants survived after successful surgical repair of the hernia, but six neonates died because of pulmonary hypoplasia. At the 10- to 14-week scan, the fetal nuchal translucency was above the 95th centile for crown-rump length in seven (37%) cases of diaphragmatic hernia. The translucency was increased in five of the six cases that resulted in neonatal death, compared with two of the nine survivors (Z = 2.32, P < .05)., Conclusion: The prevalence of diaphragmatic hernia in chromosomally normal fetuses is about one in 4000, and nearly 40% of affected fetuses have increased nuchal translucency at 10-14 weeks' gestation. Increased nuchal translucency may be a marker of intrathoracic compression-related pulmonary hypoplasia.

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.

In an ultrasound screening study at 10 to 14 weeks of gestation for measurement of fetal nuchal translucency thickness there were 102 monochorionic and 365 dichorionic twin pregnancies. In the monochorionic compared with the dichorionic pregnancies there was a higher rate of fetal loss before 24 weeks of gestation (12.2% versus 1.8%), perinatal mortality (2.8% versus 1.6%), prevalence of delivery before 32 weeks (9.2% versus 5.5%), and prevalence of birthweight below the 5th centile in both twins (7.5% versus 1.7%). However, the proportion of pregnancies with a birthweight discordancy of more than 25% was similar in the two groups (11.3% versus 12.1%).

In singleton pregnancies at 10 to 14 weeks of gestation the prevalence of missed abortion is about 2%. In an ultrasound screening study at 10 to 14 weeks of gestation involving 492 twin pregnancies the prevalence of missed abortion was about twice as high as in singletons. The risk of subsequent miscarriage in twin pregnancies with one missed abortion was about ten times higher than in normal twin pregnancies. These findings may have important implications both in terms of counselling and for future research into the causes of miscarriage.

We have examined maternal urine concentrations of beta core, free beta human chorionic gonadotrophin (hCG), and total oestriol in 373 control pregnancies and 43 pregnancies affected by aneuploidy (including 22 cases of Down's syndrome) in an attempt to see if any of the analytes have a value in Down's syndrome screening between the tenth and 14th week of pregnancy. We have compared the performance of these analytes against nuchal translucency measurement combined with maternal serum free beta hCG at the same period of pregnancy. Our results show that levels of urine free beta hCG and beta core are increased in Down's syndrome with average multiple of the median levels of 1.81 and 2.91, respectively. Urine total oestriol was reduced (0.83) whilst maternal serum free beta hCG was increased (1.72). In trisomy 18 the levels of all analytes were reduced, although serum free beta hCG was the most discriminating. The spread of results in the control and the Down's group for urine beta core was more than three times than that for serum free beta hCG and with urine free beta hCG it was two times wider. In combination with maternal age, urine total oestriol had a 32 per cent detection rate at a fixed 5 per cent false-positive rate; urine beta core 34 per cent, urine free beta hCG 36 per cent, maternal serum free beta hCG 44 per cent, and nuchal translucency 82 per cent. In combination with nuchal translucency, urine total oestriol added an extra 1 per cent detection, urine beta core an extra 2 per cent, urine free beta hCG an extra 3 per cent, and serum free beta hCG an extra 5 per cent. It is unlikely that any of the urine markers will be of value in first-trimester screening. Optimal first-trimester screening programmes will rely for the foreseeable future on nuchal translucency, serum free beta hCG, and possibly pregnancy-associated plasma protein A.

Maternal serum free beta-hCG was measured at 10 to 14 weeks of gestation in 136 normal twin pregnancies and in 12 twin pregnancies where one or both fetuses had trisomy 21. The values were compared with a normal range from 4181 singleton pregnancies. In the normal twins the median free beta-hCG (65 ng/mL) was about twice as high as in singletons (34 ng/mL z = -12.1, P < 0.0001). In the trisomy 21 group the median free beta-hCG (95 ng/mL) was significantly higher than in normal twins (z = 2.1, P < 0.05). However, only one of the trisomic pregnancies had a level above the 95th centile. In twin pregnancies maternal serum free beta-hCG at 10 to 14 weeks of gestation is unlikely to be useful in the prediction of fetal trisomy 21.

Objective: Our purpose was to investigate the role of ultrasonography and maternal serum human chorionic gonadotropin in the early prenatal diagnosis of triploid pregnancies., Study Design: A retrospective study on 61,314 consecutive singleton pregnancies examined by ultrasonography at 10 to 14 weeks' gestation was performed to identify the prenatal features of those complicated by triploidy. When available, the serum human chorionic gonadotropin level was measured and ascertained retrospectively. Cases lost to follow-up or for which no karyotype was available were excluded from the final analysis., Results: Overall there were 18 cases of triploidy identified in a population of 58,862 singleton pregnancies, giving a prevalence of 1 in 3270. Fetal defects were observed in 8 (44.4%) of these cases; these included holoprosencephaly (n = 4), exomphalos (n = 3), and posterior fossa cyst (n = 1). In 6 (33.3%) cases the placenta showed molar changes. The fetal crown-rump length was below the 5th percentile in 10 of the 16 (62.5%) cases for which the menstrual age was also available. Fetal nuchal translucency thickness was above the 95th percentile in 12 (66.7%) cases, and the fetal heart rate was below the 5th percentile in 4 of the 13 (30.8%) cases evaluated. The maternal human chorionic gonadotropin level was high in 11 of the 13 (84.6%) cases tested, with similar distribution of the high values in molar and nonmolar triploidies., Conclusion: The combination of ultrasonographic examination of the fetoplacental features and measurement of the maternal serum level of human chorionic gonadotropin enables the diagnosis of most cases of triploidy at 10 to 14 weeks' gestation.

Objective: To determine the relation between maternal serum inhibin-A and free beta-hCG concentrations in chromosomally normal pregnancies and to compare the two biochemical markers for their sensitivity in identifying trisomy 21 pregnancies., Sample: Inhibin-A and free beta-hCG were measured in maternal serum samples from 800 chromosomally normal singleton pregnancies at 10 to 14 weeks of gestation and 76 singleton pregnancies with fetal trisomy 21., Results: In the normal group maternal serum inhibin-A was significantly associated with both maternal weight and gestational age (F = 11.2, P < 0.0001). In pregnancies with trisomy 21 the maternal serum inhibin-A and free beta-hCG concentrations were significantly increased (mean difference inhibin = 0.51 SD, F = 18, P < 0.0001 and mean difference free beta-hCG = 1.13 SD, F = 80, P < 0.0001). For a 5% false positive rate, the sensitivity of maternal serum free beta-hCG in identifying pregnancies with trisomy 21 was 28.9% compared with 12.8% for maternal serum inhibin-A. Delta inhibin-A was significantly associated with delta-free beta-hCG (r = 0.345, P < 0.01) and the deviation from the normal mean for free beta-hCG was significantly greater than the deviation for inhibin-A (t = 4.0, P < 0.0001). For a 5% false positive rate, the sensitivity achieved by combining information from delta inhibin-A and delta free beta-hCG was similar to the sensitivity of free beta-hCG alone (30.3% compared with 28.9%)., Conclusion: At 10 to 14 weeks of gestation fetal trisomy 21 is associated with increased maternal serum inhibin-A and free beta-hCG levels. However, the degree of elevation of inhibin-A is less than that of free beta-hCG, and there is a significant association between levels of the two proteins. The sensitivity for trisomy 21 achieved with the combination of maternal serum inhibin-A and free beta-hCG is not significantly different from that achieved with maternal serum free beta-hCG alone.

Objective: To investigate the relation between increased fetal nuchal translucency thickness at 10-14 weeks of gestation and maternal-fetal infection., Design: Prospective study., Setting: Harris Birthright Research Centre for Fetal Medicine., Population: Four hundred and twenty-six chromosomally normal pregnancies with increased fetal nuchal translucency thickness at 10-14 weeks of gestation and 63 with 'unexplained' second or third trimester fetal nuchal oedema or hydrops., Methods: Maternal serum infection screening and investigations for fetal infection in those with evidence of recent maternal infection., Main Outcome Measures: Maternal and fetal infection., Results: Evidence of recent maternal infection was present in six of the 426 pregnancies (1.4%) with increased fetal nuchal translucency thickness at 10-14 weeks, but in all cases a healthy infant was born with no evidence of infection. In contrast, 'unexplained' second or third-trimester fetal hydrops was associated with maternal infection in six of the pregnancies (9.5%) and in all cases there was evidence of fetal infection., Conclusions: Maternal-fetal infection is one of the causes of second or third trimester nuchal oedema or fetal hydrops. In contrast, the presence of increased nuchal translucency in the first trimester is not a marker of either maternal or fetal infection.

Objective: To examine options of management and outcome of twin pregnancies affected by fetal trisomies., Design: Retrospective study., Setting: Research Centre for Fetal Medicine., Population: Twenty-seven twin pregnancies affected by fetal trisomy., Methods: A computer search was made of our database for twin pregnancies concordant or discordant for trisomies. The data were reviewed for gestation at diagnosis of the chromosomal abnormality, management and pregnancy outcome., Main Outcome Measures: Pregnancy management and outcome in relation to type and gestation at diagnosis of the trisomies., Results: There were seven cases where both fetuses were trisomies and in these the parents opted for termination of pregnancy; termination was also performed in another pregnancy where one fetus had trisomy 18 and the chromosomally normal co-twin had a major facial cleft. In 19 cases one fetus had either trisomy 21 (n = 14) or trisomy 18 (n = 5) and the other was normal. Selective fetocide was carried out in 13 of 14 pregnancies discordant for trisomy 21 and in one of the five with trisomy 18. In the four cases discordant for trisomy 18 that were managed expectantly, the trisomic baby died in utero or in the neonatal period, whereas the normal co-twin was liveborn at 33 to 40 weeks (median 37). In the 14 cases of selective fetocide, the chromosomally normal co-twin was live born at 24 to 41 weeks of gestation (median 38), and there was a nonsignificant inverse correlation between the gestation at fetocide and gestation at delivery., Conclusions: In twin pregnancies discordant for fetal trisomies the main determinant in deciding whether to perform selective fetocide or adopt expectant management is the degree of lethality of the chromosomal defect.

Objective: Our purpose was to examine the feasibility of diagnosing the Meckel-Gruber syndrome at 11 to 14 weeks' gestation, both in high-risk pregnancies and during routine ultrasonographic screening for fetal chromosomal abnormalities., Study Design: The high-risk population consisted of 9 pregnancies in 7 women with previous pregnancies affected by the Meckel-Gruber syndrome. At 11 to 14 weeks' gestation, systematic ultrasonographic examinations of the fetal skull, brain, kidneys, bladder, hands, and feet were undertaken in each case. The low-risk population consisted of 21,477 self-referred pregnancies undergoing first-trimester ultrasonographic screening for chromosomal defects at 11 to 14 weeks' gestation., Results: The triad of fetal occipital encephalocele, bilateral polycystic kidneys, and postaxial polydactyly was detected by transabdominal ultrasonography and confirmed by transvaginal scanning in 4 of the 9 pregnancies in the high-risk group. The parents were counseled of the likely recurrence of the Meckel-Gruber syndrome, and all elected to terminate the pregnancy by transcervical evacuation at 12 to 13 weeks. In the low-risk population the only case of Meckel-Gruber syndrome was identified at 13 weeks; in the remaining screened pregnancies there were no other cases of termination of pregnancy or neonatal death with the diagnosis of Meckel-Gruber syndrome., Conclusion: This report demonstrates that the Meckel-Gruber syndrome can be confidently detected at the 11- to 14-week scan in both high- and low-risk populations.

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%.

Objective: To determine the prevalence of increased fetal nuchal translucency thickness in twin pregnancies and to evaluate screening for trisomy 21 by a combination of translucency thickness and maternal age., Design: Prospective screening study at 10 to 14 weeks of gestation., Setting: Fetal Medicine Centre., Population: 22,518 self-selected pregnant women at 10 to 14 weeks of gestation, including 21,477 singleton and 448 twin pregnancies with live fetuses., Methods: Fetal nuchal translucency thickness was measured by ultrasound examination at 10-14 weeks. Sensitivity and false positive rates of screening for trisomy 21 by a combination of fetal nuchal translucency thickness and maternal age were calculated., Main Outcome Measures: Prevalence of increased nuchal translucency thickness and detection of trisomy 21., Results: In the 448 twin pregnancies the nuchal translucency thickness was above the 95th centile of the normal range (for crown-rump length in singletons) in 65/896 fetuses (7.3%), including 7/8 (88%) with trisomy 21. Increased translucency was also present in four fetuses with other chromosomal abnormalities. In the chromosomally normal twin pregnancies the prevalence of increased nuchal translucency was higher in fetuses from monochorionic (8.4%; 16/190) than in those with dichorionic pregnancies (5.4%; 37/688). The minimum estimated risk for trisomy 21, based on maternal age and fetal nuchal translucency thickness, was 1 in 300 in 19.5% (175/896) of the twins including all eight of those with trisomy 21., Conclusions: In twin pregnancies the sensitivity of fetal nuchal translucency thickness in screening for trisomy 21 is similar to that in singleton pregnancies, but the specificity is lower because translucency is also increased in chromosomally normal monochorionic twin pregnancies.

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%.

Objective: To evaluate screening for chromosomal defects by a combination of fetal nuchal translucency thickness and maternal age., Design: A prospective multicentre screening study where fetal nuchal translucency thickness was measured at 10 to 14 weeks of gestation., Subjects: 20,804 women with singleton pregnancies screened at 10 to 14 weeks of gestation from 1 September 1992 to 28 October 1994., Main Outcome Measures: Trisomy 21 and other chromosomal defects identified by increased nuchal translucency thickness and by a combination of nuchal translucency thickness and maternal age., Results: In normal fetuses nuchal translucency thickness increased significantly with crown-rump length. The nuchal translucency was above the 95th centile in 77% (66 of 86) of fetuses with trisomy 21 and in 78% (61 of 78) of those with other chromosomal defects. On the basis of the distribution of nuchal translucency measurements in normal fetuses and those with trisomy 21, a new method of screening is proposed which involves assessment of individual risk based on the combination of fetal nuchal translucency, crown-rump length and maternal age. The minimum risk was 1/100 in 4.9% of the normal pregnancies, in 80% of those with trisomy 21 and in 77% of those with other chromosomal defects., Conclusion: Screening for fetal trisomy 21 can be carried out effectively during the first trimester of pregnancy.