Multicentre randomised trial of screening with sFlt1/PlGF and planned delivery to prevent pre-eclampsia at term: protocol of the PE37 study.

INTRODUCTION: Pre-eclampsia affects ~5%-7% of pregnancies. Although improved obstetric care has significantly diminished its associated maternal mortality, it remains a leading cause of maternal morbidity and mortality in the world. Term pre-eclampsia accounts for 70% of all cases and a large proportion of maternal-fetal morbidity related to this condition. Unlike in preterm pre-eclampsia, the prediction and prevention of term pre-eclampsia remain unsolved. Previously proposed approaches are based on combined third-trimester screening and/or prophylactic drugs, but these policies are unlikely to be widely implementable in many world settings. Recent evidence shows that the soluble fms-like tyrosine kinase-1 (s-Flt-1) to placental growth factor (PlGF) ratio measured at 35-37 weeks' gestation predicts term pre-eclampsia with an 80% detection rate. Likewise, recent studies demonstrate that induction of labour beyond 37 weeks is safe and well accepted by women. We hypothesise that a single-step universal screening for term pre-eclampsia based on sFlt1/PlGF ratio at 35-37 weeks followed by planned delivery beyond 37 weeks reduces the prevalence of term pre-eclampsia without increasing the caesarean section rates or worsening the neonatal outcomes. METHODS AND ANALYSIS: We propose an open-label randomised clinical trial to evaluate the impact of a screening of term pre-eclampsia with the sFlt-1/PlGF ratio followed by planned delivery in asymptomatic nulliparous women at 35-37 weeks. Women will be assigned 1:1 to revealed (sFlt-1/PlGF known to clinicians) versus concealed (unknown) arms. A cut-off of >90th centile is used to define the high risk of subsequent pre-eclampsia and offer planned delivery from 37 weeks. The efficacy variables will be analysed and compared between groups primarily following an intention-to-treat approach, by ORs and their 95% CI. This value will be computed using a Generalised Linear Mixed Model for binary response (study group as fixed effect and the centre as intercept random effect). ETHICS AND DISSEMINATION: The study is conducted under the principles of Good Clinical Practice. This study was accepted by the Clinical Research Ethics Committee of Hospital Clinic Barcelona on 20 November 2020. Subsequent approval by individual ethical committees and competent authorities was granted. The study results will be published in peer-reviewed journals and disseminated at international conferences. TRIAL REGISTRATION NUMBER: NCT04766866.

First alongside midwifery led unit in a high complexity public hospital in Spain: Maternal and neonatal outcomes.

PROBLEM: Midwifery led units are rare in Spain. BACKGROUND: Midwife-Led Care (MLC) is a widely extended model of care and, within this, the alongside midwifery-led units (AMLU) are those hospital-based and located in close connection with obstetric units. In Spain, CL is the first center belonging to the National Health System of these characteristics. AIM: To evaluate the first year of activity of this pioneering unit. METHODS: An observational cross-sectional study was carried out to assess maternal and neonatal outcomes of births facilitated at CL by comparing with those births that fulfilled the criteria to be admitted at the AMLU but were assisted at the standard obstetric care unit of the hospital. FINDINGS: 174 (20,3%) women and birthing people decided to give birth at CL, whereas 684 (79,7%) gave birth at the Obstetric Unit of the Hospital. Women assisted at the AMLU had lower intervention rates (episiotomy, epidural analgesia) and a higher rate of breastfeeding practice. There were no statistical differences in maternal outcomes (postpartum hemorrhage, third-or-four-degree laceration) or neonatal outcomes (Apgar< 7 at 5 min; birth weight < 2500 gr; macrosomia; shoulder dystocia, neonatal care transfer). DISCUSSION: There were differences in transfers from MLU to OU between nulliparous and multiparous; the main reason for transfer is the request for analgesia. Epidural analgesia should be considered when analyzing maternal outcomes. CONCLUSION: An alongside midwifery-led unit is a safe option with a low incidence of complications. This model of care can be positively implemented at the Public Healthcare System.

Neurofibromatosis type 1 families with first-degree relatives harbouring distinct NF1 pathogenic variants. Genetic counselling and familial diagnosis: what should be offered?

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder caused by pathogenic variants in NF1 Recently, NF1 testing has been included as a clinical criterion for NF1 diagnosis. Additionally, preconception genetic counselling in patients with NF1 focuses on a 50% risk of transmitting the familial variant as the risk of having a sporadic NF1 is considered the same as the general population. METHODS: 829 individuals, 583 NF1 sporadic cases and 246 patients with NF1 with documented family history, underwent genetic testing for NF1. Genotyping and segregation analysis of NF1 familial variants was determined by microsatellite analysis and NF1 sequencing. RESULTS: The mutational analysis of NF1 in 154 families with two or more affected cases studied showed the co-occurrence of two different NF1 germline pathogenic variants in four families. The estimated mutation rate in those families was 3.89×10-3, 20 times higher than the NF1 mutation rate (~2×10-4) (p=0.0008). Furthermore, the co-occurrence of two different NF1 germline pathogenic variants in these families was 1:39, 60 times the frequency of sporadic NF1 (1:2500) (p=0.003). In all cases, the de novo NF1 pathogenic variant was present in a descendant of an affected male. In two cases, variants were detected in the inherited paternal wild-type allele. CONCLUSIONS: Our results, together with previous cases reported, suggest that the offspring of male patients with NF1 could have an increased risk of experiencing de novo NF1 pathogenic variants. This observation, if confirmed in additional cohorts, could have relevant implications for NF1 genetic counselling, family planning and NF1 genetic testing.

Assessment of an intervention to optimise antenatal management of women admitted with preterm labour and intact membranes using amniocentesis-based predictive risk models: study protocol for a randomised controlled trial (OPTIM-PTL Study).

INTRODUCTION: The majority of women admitted with threatened preterm labour (PTL) do not delivery prematurely. While those with microbial invasion of the amniotic cavity (MIAC) represent the highest risk group, this is a condition that is not routinely ruled out since it requires amniocentesis. Identification of low-risk or high-risk cases might allow individualisation of care, that is, reducing overtreatment with corticosteroids and shorten hospital stay in low-risk women, while allowing early antibiotic therapy in those with MIAC. Benefits versus risks of amniocentesis-based predictor models of spontaneous delivery within 7 days and/or MIAC have not been evaluated. METHODS AND ANALYSIS: This will be a Spanish randomised, multicentre clinical trial in singleton pregnancies (23.0-34.6 weeks) with PTL, conducted in 13 tertiary centres. The intervention arm will consist in the use of amniocentesis-based predictor models: if low risk, hospital discharge within 24 hours of results with no further medication will be recommended. If high risk, antibiotics will be added to standard management. The control group will be managed according to standard institutional protocols, without performing amniocentesis for this indication. The primary outcome will be total antenatal doses of corticosteroids, and secondary outcomes will be days of maternal stay and the occurrence of clinical chorioamnionitis. A cost analysis will be undertaken. To observe a reduction from 90% to 70% in corticosteroid doses, a reduction in 1 day of hospital stay (SD of 2) and a reduction from 24% to 12% of clinical chorioamnionitis, a total of 340 eligible patients randomised 1 to 1 to each study arm is required (power of 80%, with type I error α=0.05 and two-sided test, considering a dropout rate of 20%). Randomisation will be stratified by gestational age and centre. ETHICS AND DISSEMINATION: Prior to receiving approval from the Ethics Committee (HCB/2020/1356) and the Spanish Agency of Medicines and Medical Devices (AEMPS) (identification number: 2020-005-202-26), the trial was registered in the European Union Drug Regulating Authorities Clinical Trials database (2020-005202-26). AEMPS approved the trial as a low-intervention trial. All participants will be required to provide written informed consent. Findings will be disseminated through workshops, peer-reviewed publications and national/international conferences. PROTOCOL VERSION: V.4 10 May 2021. TRIAL REGISTRATION NUMBERS: NCT04831086 and Eudract number 2020-005202-26.

COVID-19 and pregnancy: An opportunity to correct an historic gender bias.

Current literature and clinical guidelines do not include pregnant women as an a priori risk group for COVID-19. However, a gender vision of health begs the question: Why are pregnant women not considered a risk group for COVID-19? The answer is clear: historically, most community scientific studies have not considered female gender, or pregnancy as a state, to be a focus of special interest or effort. Unfortunately, this bias seems to be maintained in the COVID-19 epidemic: most current guidelines for diagnosing SARS-CoV-2 infection during pregnancy apply the same standard criteria as for the general population.

Prenatal Evaluation of the Fetal Conus Medullaris on a Routine Scan.

OBJECTIVE: To assess the ability to identify the conus medullaris (CM) and measure the conus-sacrum distance (CS distance) on a routine scan and the relationship with maternal and fetal factors. METHODS: This was a prospective study. The assessment of the CM and the CS distance and the influence of the body mass index (BMI), gestational age (GA) and fetal position were analyzed. The correlation between the femur length (FL) and the GA with the CS distance was evaluated. RESULTS: A total of 696 fetuses were analyzed. The CM could be visualized in 82.3% of the cases, and the CS distance could be analyzed in 81.2% of the cases. The CM assessment was statistically associated with BMI and fetal position but not with GA. The CS distance assessment was statistically associated with BMI and GA but not with fetal position. We determined a significant association between the FL/CS distance and between the GA/CS distance. CONCLUSIONS: Assessment of the CM is possible on most routine scans. The CS distance could be introduced to routine scans for the assessment of prenatal skin-covered spinal dysraphism. High BMI, advanced GA and breech presentation could be potential factors limiting the feasibility of evaluating the CM.

Initial experience with non-invasive prenatal testing of cell-free DNA for major chromosomal anomalies in a clinical setting.

OBJECTIVE: To evaluate non-invasive prenatal testing (NIPT) of cell-free DNA (cfDNA) as a screening method for major chromosomal anomalies (CA) in a clinical setting. METHODS: From January to December 2013, Panorama™ test or Harmony™ prenatal test were offered as advanced NIPT, in addition to first-trimester combined screening in singleton pregnancies. RESULTS: The cohort included 333 pregnant women with a mean maternal age (MA) of 37 years who underwent testing at a mean gestational age of 14.6 weeks. Eighty-four percent were low-risk pregnancies. Results were provided in 97.3% of patients at a mean reporting time of 12.9 calendar days. Repeat sampling was performed in six cases and results were obtained in five of them. No results were provided in four cases. Four cases of Down syndrome were detected and there was one discordant result of Turner syndrome. We found no statistical differences between commercial tests except in reporting time, fetal fraction and MA. The cfDNA fraction was statistically associated with test type, maternal weight, BMI and log ßhCG levels. CONCLUSIONS: NIPT has the potential to be a highly effective screening method for major CA in a clinical setting.

Systematic review of screening for trisomy 21 in twin pregnancies in first trimester combining nuchal translucency and biochemical markers: a meta-analysis.

AIM: This article is a systematic review of the literature to establish the detection rate and false-positive rate of the combined test for the screening of trisomy 21 in twins. MATERIAL AND METHODS: We conducted a literature search (MEDLINE, EMBASE and ScienceDirect and Cochrane) to identify studies between 1995 and 2013 that provided data on the combined test in twins. Selected studies included data on maternal age, number of fetuses affected by Down syndrome, test strategy, sensitivity and specificity of the test. RESULTS: The combined test in twins had a pooled sensitivity of 0.893 [95% confidence interval (CI) 0.797-0.947] and a pooled specificity of 0.946 (95% CI 0.933-0.957). The performance of the test was good (summary receiver operating characteristic area under the curve: 0.817). In dichorionic twins, sensitivity and specificity were 0.862 (95% CI 0.728-0.936) and 0.952 (95% CI 0.942-0.96), respectively. In monochorionic twins, the sensitivity and specificity were 0.874% (95% CI 0.526-0.977) and 0.954% (95% CI 0.943-0.963), respectively. CONCLUSIONS: The results of this meta-analysis show that the accumulative evidence on the performance of the combined test in twin pregnancies is good. Nowadays, it seems to be the best first-trimester screening test available for twin pregnancies.

Sonographic evaluation of the fetal conus medullaris.

OBJECTIVE: The aim of this study is to determine the most reproducible method in the sonographic evaluation of the conus medullaris (CM) and its relationship with gestational age (GA). METHODS: This is a prospective study of singleton structurally normal fetuses between 20 and 30 weeks' gestation. Sonographic evaluation of the CM was performed using two methodologies: a qualitative assessment of the CM level in relation to the lumbar vertebrae and a quantitative measurement of the distance from the CM to the last spine ossification centre (conus-sacrum or CS distance). Both parameters were analysed offline by two operators using 3D stored volumes. Interobserver variability of methods, the relationship between CS and femur length (FL) or GA was evaluated. RESULTS: We analysed 101 3D volumes. Interobserver concordance was low for the CM level (k = 0.4, P < 0.05) and high for CS distance (ICC = 0.950). A significant correlation between CS and both FL and GA was observed. CONCLUSIONS: CS distance but not CM level is reproducible. CS distance is significantly correlated with both FL and GA. CS distance could be useful in the assessment of prenatal skin-covered spinal dysraphism.

Concordance between prenatal ultrasound and autopsy findings in a tertiary center.

OBJECTIVE: The aim of this study was to evaluate the ultrasound (US)/autopsy concordance in elective termination of pregnancies (TOP) due to fetal causes. METHODS: We performed a retrospective evaluation of elective TOP from 2004 to 2012. Inclusion criteria were gestational age at termination <24 weeks, fetal pathology and availability of US/autopsy data. Based on the US-autopsy concordance, cases were divided into four groups: Group 1: agreement; Group 2: autopsy confirmed all US findings but provided additional information; Group 3: autopsy didn't confirm all US findings; Group 4: disagreement. RESULTS: One hundred and fifty-one patients fulfilled the inclusion criteria during the study period. Central nervous system malformations (91.5%), cardiovascular anomalies (90.2%) and renal system malformations (91.3%) were confirmed by autopsy. We found less concordance in the abdominal and musculoskeletal anomalies (61.5% and 66.7%, respectively). There were 130 (86%) fetuses in group 1, 7 in group 2 (4.6%), 3 in group 3 (1.9%) and 11 in group 4 (7.2%). In 5.29% of cases, the autopsy added relevant information to the diagnosis and counselling. CONCLUSIONS: Diagnosis concordance between US and necropsy is achieved in almost 90% of cases. An autopsy may help to adjust the diagnosis and help in counselling the parents for a future pregnancy.

Cumulative sum plots and retrospective parameters in first-trimester ductus venosus quality assurance.

OBJECTIVE: This study aimed to evaluate the application of two quality assurance methods to the ductus venosus pulsatility index (DVPI), as a first-trimester aneuploidy marker, including retrospective assessment of distribution parameters and cumulative sum (CUSUM) plots. METHODS: The DVPI was measured in 14 444 singleton fetuses at 11+0 to 13+6 weeks in two Fetal Medicine centers during a 4-year period. Sonologist-specific quality assurance distribution parameters, previously described for nuchal translucency, were assessed: the median multiples of the median (MoM), the logarithmic standard deviation of DVPI MoMs and the weekly DVPI percent decrease. Quality assurance results were compared between median MoMs and MoM-based CUSUM plots. RESULTS: When sonologist-specific DVPI distribution parameters were retrospectively applied for quality assurance, a 1.0 median MoM, a 0.1 median logarithmic standard deviation and a 3.4 median weekly DVPI drop percentage were observed. CUSUM plots showed good agreement with 0.9-1.1 MoMs range for median MoM, in the assessment of sonologist-specific performances. CONCLUSION: Retrospective and prospective DVPI quality assurance methods appear to be applicable to DVPI at 11+0 to 13+6 weeks. Its use should be encouraged if DVPI is to be added to first-trimester Down syndrome or cardiac defects screening.

Analysis of three different strategies in prenatal screening for Down's syndrome in twin pregnancies.

OBJECTIVES: To compare the performance of three different strategies in prenatal screening for Down's syndrome in twins [nuchal translucency, the combined test, the combined test + ductus venosus pulsatility index (DVPI)]. METHODS: We included 277 twin pregnancies with two cases of trisomy 21 (both dichorionic). We performed a computer simulation of Down's syndrome NT screening, combined test screening and the combined test with the addition of DVPI screening using the commercialized software SsdwLab6. The strategies were compared using the area under the receiver operating characteristic curve. RESULTS: NT screening false-positive rate (FPR) was 10.9% (95% CI: 8.3-13.5). The combined test FPR was 6.2% (95% CI: 4.1-8.2%) and the combined test plus DVPI was 6% (95% CI: 4-8). FPR was higher in advanced maternal age patients. Detection rate was 100% in all cases. The area under the curve was 0.987 (95% CI: 0.972-0.994) in NT screening; 0.987 (95% CI: 0.978-0.997) in the combined test and 0.983 (95% CI: 0.977-0.996) in the combined test + DVPI. CONCLUSIONS: Down's syndrome screening is feasible in twins with low FPR. The results of this study are similar to the results achieved in singletons. The combined test appears to be the most effective. The addition of DVIP does not significantly improve the prenatal screening for trisomy 21.

Updated reference ranges for the ductus venosus pulsatility index at 11-13 weeks.

OBJECTIVE: To update the reference ranges for the ductus venosus pulsatility index (DVPI) at 11+0 to 13+6 gestational weeks. METHODS: DVPI was calculated in 14,444 singleton fetuses at 11+0 to 13+6 weeks in two Fetal Medicine Centers, during a 4-year period. Using previously described medians, DVPI evolution was assessed both over the study period on a yearly basis and over gestation, grouping fetuses according to 5-mm crown-rump length (CRL) ranges. Weighted DVPI medians, the 5th and 95th percentiles and distribution parameters for unaffected and trisomy 21 fetuses were newly calculated. RESULTS: A significant DVPI multiple of the median decrease was observed over both the study period (p < 0.01) and over gestation (p < 0.01) using previous medians, in the two centers. Newly calculated weighted medians were lower than those previously described, decreasing with CRL. Distribution parameters calculated using the new medians were different from those previously described. CONCLUSION: DVPI reference ranges were lower than those previously reported and decreased with CRL. Updated medians and distribution parameters should be considered to include the DVPI as a Gaussian marker in trisomy 21 screening and for quality control purposes.

First trimester risk assessment for trisomy 21 in twin pregnancies combining nuchal translucency and first trimester biochemical markers.

OBJECTIVE: The aim is to describe the performance of first-trimester combined risk assessment in twin pregnancies. METHODS: Maternal serum free beta-human chorionic gonadotrophin and pregnancy-associated plasma protein A (PAPP-A) were determined at 8 to 12 weeks and fetal nuchal translucency (NT) was measured at 11 to 13+6 weeks. The individual risk was estimated for each fetus using the combined test in dichorionic twins. In monochorionic twins, the mean risk assessment of the two fetuses was used. An invasive diagnostic procedure was offered when the risk was ≥ 1 : 270 in either one of the fetuses. RESULTS: From February 2007 to June 2011, 447 twin pregnancies were enrolled in this study. There were 402 (89.9%) dichorionic and 45 (10.1%) monochorionic twins. In dichorionic twins, mean crown-rump length (CRL) was 63.9 mm; median NT multiples of the median (MoM) was 0.97; median Β-hCG was MoM 1.74; median PAPP-A was 1.72. In monochorionic twins, mean CRL was 61.9 mm; median NT MoM was 0. 98; median Β-hCG MoM was 1.44; and median PAPP-A was 1.51. Two pregnancies with Down syndrome were detected by first trimester screening, both in dichorionic twins. The false positive rate was 5.7% (95% confidence interval 4.1-7.3) and 4.4% (95% confidence interval 0.1-8.8%) in dichorionic and monochorionic twins, respectively. CONCLUSIONS: The combined test in twins appears to be a good method for Down syndrome screening with a high detection rate and an acceptable false-positive rate.

Is the addition of the ductus venosus useful when screening for aneuploidy and congenital heart disease in fetuses with normal nuchal translucency?

OBJECTIVE: The aim of this study was to examine the possible role of Doppler ultrasound assessment of ductus venosus (DV) blood flow at 11⁺°-13⁺6 weeks' gestation in fetuses with normal nuchal translucency (NT) in screening for autosomal trisomies (AT) and for congenital heart diseases (CHD) in chromosomally normal fetuses. METHODS: First-trimester combined screening for trisomy 21 (T21) was carried out prospectively for 7 years in singleton pregnancies. NT and the pulsatility index for DV (DVPI) were calculated. The DV was analyzed according to its association with AT and CHD. The detection rate (DR), false-positive rate (FPR), positive predictive value (PPV), and odds ratio (OR) for abnormal DV were calculated. RESULTS: Abnormal DV as an early marker of euploid CHD gives a DR of 12.5%, an FPR of 4.3%, a PPV of 1.4%, and a negative predictive value (NPV) of 99.5%, with an OR of 3.1 (95% CI 1.3-7.4). Moreover, abnormal DV as an early marker of AT shows a DR of 35.7%, an FPR of 4.3%, a PPV of 1.2%, an NPV of 99.9%, and an OR of 12.3 (95% CI 4.1-36), and the values are 33.3, 4.3, 0.97, and 99.9% and 11 (95% CI 3.2-36.9), respectively, for T21. CONCLUSIONS: Our data supports the association between increased DVPI and CHD or AT. The sensitivity of this marker is not strong enough to be used a screening test.

Early first-trimester free-ß-hCG and PAPP-A serum distributions in monochorionic and dichorionic twins.

OBJECTIVE: To examine the distribution of first-trimester biochemical markers of aneuploidy in twins according to chorionicity. METHODS: Maternal serum free-ß-human chorionic gonadotropin (hCG) and pregnancy-associated plasma protein A (PAPP-A) were measured between 8-13 + 6 weeks as a part of a routine first-trimester screening program in conjunction with fetal nuchal translucency measured at 11 to 13 + 6 weeks' gestation. Data from 279 twin pregnancies were extracted from our fetal databases. Down syndrome cases were excluded. Individual marker concentrations were expressed as weight, ethnicity, smoking and maternal diabetes corrected. To compare the distributions of the biochemical parameters, a generalized additive model was used adjusted to a smoothing regression model with the values transformed with base 10'' logarithm using R software (generalized additive model-smoothing spline regression). RESULTS: Free-ß-hCG and PAPP-A distributions, analyzed with a generalized additive model adjusted to a smoothing regression model, were significantly different depending on the chorionicity. We graphically displayed the relationship between the predicted concentration of the free-ß-hCG and PAPP-A and the gestational age in days for monochorionic and dichorionic twins adjusted by weight. CONCLUSION: Pregnancy-associated plasma protein A and free-ß-hCG values are gestational age specific. It is necessary to make a distinction between monochorionic and dichorionic twins because biochemical markers are lower in monochorionic than in dichorionic twins.

Three-dimensional yolk and gestational sac volume. A prospective study of prognostic value.

OBJECTIVE: To evaluate the relative prognostic value of ultrasound findings during the first-trimester scan by univariate and logistic regression analysis in a group of asymptomatic women. STUDY DESIGN: A total of 125 asymptomatic pregnant women with a singleton conceptus, concordance between menstrual age and crown-rump length, and documented fetal activity, 25 for each gestational age between 6 and 10 weeks, were enrolled in the study and underwent a transvaginal sonographic examination. The following data were collected: yolk sac mean diameter and volume, gestational sac mean diameter and volume, fetal heart rate, maternal age, gestational age and presence of a retrochorial hematoma. The outcome variable was abortion, defined as pregnancy loss at any time up to 20 weeks' gestation. Normograms were constructed for volumes, mean diameters and fetal heart rate. Receiver-operator characteristic curves were performed in order to dichotomize maternal and gestational age. Univeriate analysis was performed by Fisher's exact test. Logistic regression was performed to test the relationship between independent variables and pregnancy outcome. RESULTS: In univariate analysis, the variables significantly associated with spontaneous abortion were maternal age > 34 years, yolk sac volume outside the 5th to 95th percentile, gestational sac volume < the 5th percentile and fetal heart rate outside the 5th to 95th percentile. In regression analysis only maternal age > 34 years, gestational sac mean diameter < 5th percentile and fetal heart rate outside the 5th to 95th percentile were significant in predicting abortion. CONCLUSION: Our data suggest that new three-dimensional parameters are of no clinical benefit in the prediction of abortion in nonbleeding, first-trimester pregnancy, when conventional sonographic parameters are used.

Measurement of nuchal translucency as a single strategy in trisomy 21 screening: should we use any other marker?

OBJECTIVE: To evaluate the role of nuchal translucency thickness as a single marker in screening for trisomy 21 at 10-16 weeks' gestation. METHODS: From December 1996 to October 2001, nuchal translucency was measured in 11,281 consecutive early second trimester fetuses referred to our unit for prenatal care and delivery. Scans were performed by eight experienced ultrasonographers, under strict methodological criteria. RESULTS: Chromosomal abnormalities were found in 118 cases (52 trisomy 21). Using nuchal translucency greater than the 95th centile as a cut-off, the overall detection rate was 71.2% with a specificity of 95.4%, and a positive predictive value of 14%. In the trisomy 21 selected group, detection rate, specificity, and positive predictive value for nuchal translucency were 92.3%, 95.4%, and 8.5%, respectively. The detection rate of trisomy 21 reached 100% when nuchal translucency was measured between 10 and 14 weeks' gestation, maintaining the same specificity. CONCLUSION: Early second trimester nuchal translucency measurement can achieve prenatal detection rates of trisomy 21 greater than 95% with a 5% false-positive rate. With a detection rate so high, the benefits of using additional markers may be less than previously considered. Although maternal age, other sonographic or Doppler markers, and maternal serum biochemistry might play a role in prenatal strategies to detect fetal chromosomal abnormalities, the high detection rate of trisomy 21 fetuses using nuchal translucency as a single parameter suggests that early nuchal translucency measurement between 10 and 14 weeks' gestation can be a simple screening strategy for this condition.

References intervals for fetal biometrical parameters.

OBJECTIVE: To establish normal reference intervals for biparietal diameter, head circumference, abdominal circumference, and length of femur, a cross-sectional study. STUDY DESIGN: Five hundred singleton fetuses for each week at gestations between 23 and 41 weeks with a total of 9500 fetuses. Antenatal ultrasound measurements from all consecutive pregnant women referred to the ultrasound unit for scanning of fetal condition are prospectively entered in a data bank. For the purpose of this study, sonographic measurements were collected retrospectively and each fetus contributed just one value to the reference sample. RESULTS: The mean curve of the four biometrical parameters varied with gestational age, with flattening of the curves at the end of gestation and increased width of normal ranges with increasing gestational age. Maximal weekly increases occurred at 24 weeks' gestation for head circumference, abdominal circumference, and length of femur and at 26 weeks' gestation for biparietal diameter. The four biometrical parameters, however, showed 50% increases in size at 33 weeks' gestation. CONCLUSIONS: These fetal size reference intervals are clinically relevant and can be used for populations with epidemiological features and distribution of neonatal birth weights similar to our data.