Serum Screening For Down's Syndrome Research Articles

Results of the 2021 French National Perinatal Survey and trends in perinatal health in metropolitan France since 1995

To report results of the 2021 French National Perinatal Survey (ENP) in metropolitan France and assess trends in the main indicators of perinatal health, medical practices, and risk factors in France since 1995. All the samples included all women giving birth at a gestational age of at least 22 weeks of gestation and/or to an infant weighing at least 500 grams in all maternity units in metropolitan France during one week in 1995 (N=13048), 2003 (N=14324), 2010 (N=14546), 2016 (N=12553), and 2021 (N=12088). The data came from postpartum interviews of the women at the hospital and their medical records. Comparisons between surveys showed trends over time. Between 1995 and 2021, maternal characteristics changed. Maternal age and the frequency of women with obesity rose: in 2021, 24.6% of women were 35 years or older (21.1% in 2016, 19.2% in 2010, 15.9% in 2003 and 12.4% in 1995) and 14.4% were obese (11.8% in 2016, 9.9% in 2010 and 7.4% in 2003). Some antenatal prevention behaviors that improved in 2021 were not smoking during the third trimester, acid folic administration before pregnancy, and vaccination against influenza. The percentage of women with an early prenatal appointment ("4th month appointment"), implemented to facilitate screening of maternal vulnerability during pregnancy, has continued to rise. The percentage of women receiving prenatal care by midwives has risen markedly (39.0% in 2021 versus 11.7% in 2016). Serum screening for Down syndrome continues to increase (91.8% of women in 2021). The rate of induction of labor has risen significantly (20.2% in 1995 and 25.8% in 2021). The mode of delivery has not varied significantly since 2003; in 2021, the cesarean rate was 21.4% and the instrumental vaginal delivery rate 12.4%. Episiotomy was increasingly rare, among both primiparous and multiparous women (16.5% and 2.9% in 2021, respectively). The prevalence of coronavirus (SARS-CoV2) infection during pregnancy was 5.7%. Preterm live births increased regularly, slightly but significantly over the 1995-2016 period and then remained stable between 2016 and 2021 (7.0%). In 2021, 56.3% of women exclusively breastfed during their hospital stay, a modest increase in comparison with 2016 (54.6%). Routine national perinatal surveys highlight positive trends over time in some preventive practices, decreases in some medical interventions consistent with national guidelines, and the increasing role of midwives in prenatal care. Nonetheless, some indicators remain less than optimal and require more detailed analyses.

Incidence of Down Syndrome by maternal age in Chinese population.

Objective: This study aims to estimate the maternal age-related risk of Down syndrome in an Asian population. Methods: We performed a retrospective data analysis including a total of 206,295 pregnant women who presented for second-trimester maternal serum screening for Down syndrome at Hubei Maternal and Child Health Hospital for the years 2008–2017. Cases were assigned to three groups: ≤26 years of age, 27–33 years of age, and ≥34 years of age. The incidence of Down Syndrome was calculated for each age group. The differences between groups were tested using the chi-square (χ2) test. Results: The incidence of Down syndrome in women ≤26 years of age, 27–33 years of age, and ≥34 years of age was 0.67‰, 0.29‰, and 2.07‰ respectively. Statistically significant difference was found between the three age groups (χ2 = 79.748, p < 0.05). Conclusion: Down syndrome rate was significantly higher in women ≥34 years of age. Younger women (≤26 years of age) had a significantly higher risk for Down’s syndrome, compared to women aged 27–33.

Health economic evaluation of noninvasive prenatal testing and serum screening for down syndrome.

Down syndrome (DS), also known as trisomy 21 (T21), is the most common genetic disorder associated with intellectual disability. There are two methods commonly used for prenatal testing of DS: serum screening (SS) for biomarkers in maternal serum and noninvasive prenatal testing (NIPT) for aneuploidy by cell-free DNA (cfDNA) in maternal plasma. However, cost-effectiveness analyses of these two methods are mostly based on data derived from simulations with various models, with theoretical values calculated. In this study, we statistically analyzed clinical DS screening data and pregnancy outcomes during the follow-up of pregnant women in Zhuhai City, China. The economics of the two mainstream prenatal DS screening methods was evaluated from a public health perspective. A retrospective analysis was performed on the data of 17,363 pregnant women who received SS and NIPT during gestation in Zhuhai from 2018 to 2019, and a cost-effectiveness analysis was performed with four screening strategies. In strategy I, all pregnant women received SS, and those with T21 risk ≥1/270 had invasive prenatal diagnosis (IPD). In strategy II, all pregnant women received SS, those with T21 risk ≥ 1/270 had IPD, and those with 1/270 > T21 risk ≥ 1/1,000 had NIPT; then, women at high risk based on NIPT also had IPD. In strategy III, all pregnant women received SS, and those with T21 risk ≥1,000 had NIPT; then, women at high risk based on NIPT results had IPD. In strategy IV, all pregnant women received NIPT and those at high risk based on NIPT results had IPD. Finally, to assess the cost and effectiveness of DS screening, the total costs were calculated as the sum of screening and diagnosis as well as the direct and indirect economic burden during the average life cycle of DS patients. A total of 22 of the 17,363 (1/789) pregnant women had DS, of which only one woman was over 35 years of age. SS detected 1,024 cases at high risk of T21 (≥1/270), 8 cases were true positive, with a positive predictive value of 0.78% and a detection rate of 36.4%. NIPT detected 27 cases at high risk of T21 (Z ≥ 3) and 22 cases of DS, with a positive predictive value of 81.5% and a detection rate of 100%. Strategy I had the largest total cost of 65.54 million CNY, strategy II and III had similar total costs of 40 million CNY, and strategy IV had the lowest total cost of 14.91 million CNY. By comparison, the screening strategy with NIPT alone had the highest health economic value for DS. SS was greatly affected by nuchal translucency and the accuracy of gestational age measured by ultrasonography. Unstandardized ultrasonography was an important reason for the low DS detection rate with SS. The influence of interfering factors on NIPT was much lower than in SS. NIPT can be used as an alternative to SS and as a primary screening strategy of prenatal DS screening for secondary prevention and control of birth defects. NIPT greatly decreased the frequency of IPD and the miscarriages associated with IPD, saved the limited medical and health resources, and greatly increased DS detection rate. Therefore, NIPT has great social and economic benefits.

Prenatal serum screening for Down syndrome and neural tube defects in the United States: Changes in utilization patterns from 2012 to 2020.

To compile current usage of serum-based prenatal screening for Down syndrome in the United States and compare it with results from a similar 2011/2012 survey. The College of American Pathologists maternal screening proficiency testing survey includes a supplemental question on the first of three yearly distributions. Information regarding tests offered and the monthly number of pregnancies tested for US-based laboratories were reviewed. Results were stratified by size of laboratory, tests offered, and pregnancies tested. Findings were compared to an earlier survey. Fifty-six laboratories reported they will have screened 1,131,336 pregnancies in 2020. Of these, 36% are screened by stand-alone first trimester testing, 48% by stand-alone second trimester testing, and 16% using tests that integrate results from both trimesters. Eighty percent of all serum screens were provided by the five laboratories that performed the most screens (at least 50,000). These five performed similar proportions of first or second trimester screens (42.2% and 41.8%, respectively). Compared to eight years earlier, there are now 54% fewer laboratories. Pregnancies screened using the first trimester, second trimester, and integrated protocols were lower by 27%, 69%, and 72%, respectively. The serum screening activity in the US showed a 62% decrease from 2012 levels. During 2012-2020, the number of cell-free DNA tests increased from negligible to 1,492,332. Maternal serum screening for common aneuploidies has changed significantly in eight years with fewer laboratories, a shift toward larger laboratories and a 2.5-fold reduction in pregnancies tested, likely due to the introduction of cell-free DNA screening.

Prenatal detection and molecular cytogenetic characterization of 19q13.42 microduplication: three reported cases and literature review

BackgroundTrisomy 19q is a recognizable syndrome and associated with a wide spectrum of clinical phenotypes in clinic. The purpose of this study was to explore the prenatal phenotypes of 19q13.42 duplication, which was rarely reported in clinic.Case presentationThree pregnant women presenting diverse indications for prenatal diagnosis accepted amniocentesis: increased nuchal translucency and fetal pyelic separation (case 2) and high risk of maternal serum screening for Down syndrome (case 1 and case 3). Case 1 and case 2 shared similar duplicated locus in the region of 19q13.42, encompassing part NLRP12 gene. The latter inherited the chromosomal duplication from the mother with normal phenotypes. Case 3 carried a 1.445 Mb duplication in the 19q13.42q13.43 region. It was proposed that evolutionary duplication of NLRP12 gene could have a causative role in autoinflammatory diseases development. The genotype–phenotype correlation depends mainly on the duplicated size and functional genes involved, which is still yet to be determined. All pregnant women chose to continue the pregnancy and delivered healthy children with no apparent abnormalities.ConclusionsThe 19q13.42 microduplications in our study were the smallest fragments compared to previous literature. Our findings enriched the prenatal phenotypes for this chromosomal microscopic imbalance. It was proposed that long term follow up analysis should be guaranteed till adulthood to determine whether there will be other emerging clinical symptoms and developmental-behavioral disorders for such carriers.

Health economic evaluation of five prenatal screening strategies for Down's syndrome

Objective To investigate the cost-effectiveness and cost-benefit of five screening strategies for Down syndrome (DS) to optimize prenatal screening strategy. Methods A retrospective analysis was conducted in 26 803 gravidas, who underwent the second trimester maternal serum screening ( maternal serum α-fetoprotein and β-human chorionic gonadotropin) from 2002 to 2003, whom were classified into three groups according to the results of serum DS screening: high risk group (≥1/270), borderline risk group (≥1/1 000-<1/270) and elderly gravida group (age at expected date of confinement≥35 years old). TreeAge Pro 2011 sofware was used to set up the decision tree model for cost-effectiveness and cost-benefit analysis. Strategy 1: Maternal serum screening was carried out on all gravidas, and then prenatal diagnosis was performed for women in high risk group. Strategy 2: Non-invasive prenatal testing (NIPT) was carried out on all gravidas, and then prenatal diagnosis was offered for women with positive or suspected results. Strategy 3: NIPT was only carried out on gravidas of advanced maternal age and maternal serum screening was performed on the rest population. Gravidas with positive or suspected positive results in NIPT or classified into the high risk group underwent prenatal diagnosis. Strategy 4: Maternal serum screening was carried out on all gravidas. Those at high risk received prenatal diagnosis, while those at borderline risk underwent NIPT first and followed by prenatal diagnosis if positive or suspected positive NIPT results were identified. Strategy 5: Maternal serum screening was carried out on all gravidas. Those at high or borderline risk would undergo NIPT followed by prenatal diagnosis if they were positive or suspected positive for NIPT. Results (1) Among 26 803 gravidas, 1 244 were at high risk group (4.64%) with five having trisomy 21; 3 925 were at bordelrine risk (14.64%) with four having trisomy 21; 300 women were of advanced age (1.12%) with one having trisomy 21. (2) Cost-effectiveness analysis: the incremental cost-effectiveness ratios of strategy 3 and 4 were negative and that of strategy 1 was 0 with a cost-effectiveness ratio of 15 833 764.53. The incremental cost-effectiveness ratio of strategy 2 was 49 865 746.10, which was far greater than that of strategy 5 (63 049.56). The cost-effectiveness ratio of strategy 4 is 586 703.63, which was less than those of strategy 1,2 and 3 but higher than that of strategy 5. The average cost-effectiveness ratio of strategy 5 was the lowest (508 431.20) among these five strategies, which meant that for every diagnosis of DS, strategy 5 had the lowest cost (508 400 yuan). (3) Cost-benefit analysis: The benefits of strategy 4 and 5 were greater than their costs. Strategy 5 had the highest benefit-cost ratio, followed by strategy 4, 2, 3 and 1. (4) When other factors remained unchanged and only the acceptance rate of prenatal diagnosis was adjusted from 50% to 100%, strategy 1 had the least cost expectation, followed by strategy 3, 5, 4 and 2. When the cost of NIPT was below 82.4 yuan, the cost expectation of strategy 2 that performed on all gravidas was the lowest, while when it was between 82.4 and 1 827.2 yuan, the screening cost of strategy 5 was the lowest. Conclusions Strategy 5 has the best cost-effectiveness and cost-benefit. It would be the best screening strategy for DS, if the cost of NIPT is between 82.4-1 827.2 yuan. Key words: Down syndrome; Neonatal screening; Prenatal diagnosis; Costs and cost analysis; Cost-benefit analysis; High-throughput nucleotide sequencing

Second-trimester maternal serum screening for fetal Down syndrome: As a screening test for hemoglobin Bart's disease: A prospective population-based study.

The purpose of this study is to determine the effectiveness of second-trimester maternal serum screening for Down syndrome as a screening test for fetal hemoglobin (Hb) Bart's disease among an unselected population. A secondary analysis of a large prospective database (20254 pregnancies) was conducted to compare the levels of maternal serum screening, alpha-fetoprotein (AFP), free beta-human chorionic gonadotropin, and unconjugated estriol between pregnancies with Hb Bart's disease and unaffected pregnancies. The median AFP levels were much higher among affected fetuses (1.96 vs 1.12 multiple of the median; P<.001), yielding a sensitivity of 81.6% and specificity of 86.4%. Thus, AFP measurement is effective in predicting fetal Hb Bart's disease among an unselected population when using a cutoff value of 1.5 multiple of the median. The serum free beta-human chorionic gonadotropin levels were slightly, but significantly, higher in the affected pregnancies, while the serum unconjugated estriol levels were minimally, but significantly, lower among the affected pregnancies. Second-trimester maternal serum AFP levels were significantly elevated in cases of fetal Hb Bart's disease. Pregnancies with unexplained elevated serum AFP levels in areas of high prevalence of Hb Bart's disease should always undergo a detailed ultrasound examination to detect any early signs of fetal anemia before development of hydrops fetalis.

Prenatal diagnosis and molecular cytogenetic characterization of mosaicism for a small supernumerary marker chromosome derived from chromosome 16

ObjectiveWe present prenatal diagnosis and molecular cytogenetic characterization of a small supernumerary marker chromosome (sSMC) derived from chromosome 16. Case reportA 28-year-old woman underwent amniocentesis at 17 weeks of gestation because of abnormal maternal serum screening for Down syndrome. Amniocentesis revealed a karyotype of 47,XY,+mar[5]/46,XY[9]. Parental karyotypes were normal. Prenatal ultrasound findings were unremarkable. Array comparative genomic hybridization (aCGH) analysis of cultured amniocytes revealed a de novo 16% gene dosage increase of 16q11.2-q22.1. Repeat amniocentesis at 21 weeks of gestation revealed a karyotype of 47,XY,+mar[10]/46,XY[31]. aCGH analysis of uncultured amniocytes revealed a result of arr 16q11.2q22.1 (46,492,626–68,867,969) × 2.20 with a log2 ratio of 0.15 encompassing RPGRIP1L, FTO, SLC6A2, BBS2 and CDH1. Interphase fluorescence in situ hybridization (FISH) analysis on uncultured amniocytes detected partial trisomy 16q in 36/137 (26.3%) of uncultured amniocytes. Polymorphic DNA marker analysis on amniocytes and parental bloods excluded uniparental disomy 16. Premature labor occurred at 25 weeks of gestation, and a 585-g male baby without craniofacial dysmorphism was delivered and survived. At age 1½ years, pediatric follow-ups revealed normal psychomotor development, normal body weight, short stature, congenital hypothyroidism, hearing impairment and hypospadias in the neonate, and the peripheral blood had a karyotype of 46,XY in 40 cultured lymphocytes. ConclusionaCGH, interphase FISH and polymorphic DNA marker analyses of uncultured amniocytes are useful for confirmation of prenatally detected mosaic sSMCs at amniocentesis.

Men's Knowledge About Maternal Serum Screening for Down Syndrome and their Attitude Towards Amniocentesis.

The present study aimed to assess (i) the impact of screening consultation on male partner's knowledge about second trimester maternal serum screening for Down syndrome and on their attitudes toward amniocentesis, and (ii) the concomitant effect of men's involvement in pregnancy on both knowledge and attitudes. The study included 164 men who accompanied their partners to the screening appointment. Knowledge Questionnaire and Partner's Involvement in Pregnancy Scale with two dimensions, support and distance, were administered. Involvement in pregnancy was determined using two factors; support and distance. Findings revealed a significant post-consultation improvement in men's knowledge about the test, but less-educated men and those who were more distanced from partner and pregnancy were less knowledgeable even post-consultation. Compared to before the consultation, most men had a positive attitude toward amniocentesis and were willing to suggest it to their partners in case of positive test results (77% and 42%, respectively). The remainder would either leave the decision to their partners (20%) or were undecided (3%). Higher perception of distance was associated with men's unwillingness to be involved in amniocentesis decisions, particularly before consultation. However, the consultation had considerable potential to engage men with this attitude in the decision-making process. The study highlights the need to change woman-oriented prenatal screening practices for Down syndrome to involve their male partners in the consultation.

Factors associated with utilization of maternal serum screening for Down syndrome in mainland China: a cross-sectional study.

BackgroundKnowledge of the factors that influence maternal serum screening (MSS) service utilization can be used to develop health policies to promote equitable access to MSS and further diagnostic tests. The purpose of this study was to find the factors associated with utilization of MSS as well as the current status of service utilization in mainland China.MethodsThis was a hospital-based cross-sectional study with respondents interviewed with a questionnaire designed based on Andersen’s behavioral model. Descriptive statistics, univariate analysis, and multilevel logistic regression analysis were used to identify the factors associated with MSS utilization, and to explore potential methods to improve screening uptake.ResultsA total of 8110 women who had given birth within the previous 7 days in one of 111 participating institutions from six provinces in mainland China were interviewed. Approximately 36 % of the participants had used MSS. Women between 20 and 35 years, who resided in urban areas, were educated, were in a stable occupation, who had health knowledge, who attended maternal preparation classes, who had received eight or more prenatal checkups, who were from a region of higher social economic status, and who delivered in a tertiary healthcare institution were significantly more likely to use MSS than their counterparts. As compared with other factors, insufficient education is the single most important demographic factor for service underutilization.ConclusionsEfforts should not only be made to target the population that underuses MSS, but the overall organization of MSS service delivery should be assessed during policy development to make access to MSS equitable to the entire population of mainland China.

A cost-effectiveness analysis of cell free DNA as a replacement for serum screening for Down syndrome.

The aim of this article is to determine the cost effectiveness of cell free DNA (cfDNA) as a replacement for integrated screening using a societal cost perspective. This study used Monte-Carlo simulation with one-way and probabilistic sensitivity analysis. Cell free DNA is more effective and less costly than integrated screening. The incremental cost-effectiveness ratio for cfDNA relative to the integrated test was -$277 955 per case detected (95th percent confidence interval -$881 882 to $532 785). Cell free DNA screening is a cost-effective replacement for maternal serum screening when the lifetime costs of Down syndrome live births are considered. The adoption of cfDNA screening would save approximately $277 955 for each additional case detected over integrated screening.

A tradeoff analysis of risk cutoffs for the quadruple serum screen for Down syndrome

In maternal serum screening for Down syndrome, a cutoff of 1 : 270 is often used as a decision point to recommend invasive confirmatory testing. However, it has not been established how well this or any other cutoff relates to patient preferences, that is, the values that pregnant women attach to various screening outcomes. The purpose of this study was to examine the clinical and economic tradeoffs of a wide range of risk cutoffs for the quadruple screen. Screening costs and outcomes for multiple risk cutoffs were modeled using a Monte Carlo simulation. The optimal cutoff for maternal serum screening depends on the relative values placed by the patient on different outcomes. Total societal costs were similar across the range of cutoffs. Given that different screening outcomes are optimized by different cutoff values, a one-size-fits-all approach may not be appropriate.

Absent cavum with intact septum pellucidum and corpus callosum may indicate midline brain abnormalities

In a recent publication of a series of cases of absence of a visible cavum detected prenatally, Malinger et al.1 concluded that this finding is not always associated with callosal anomalies and may represent a variation of normal development with good postnatal outcome. Although this may be true in a proportion of cases, we would like to point out that absence of fluid in the cavum, with intact septum pellucidum and corpus callosum, potentially indicates subtle midline brain abnormalities that may have significant implications for perinatal management and postnatal neurological development. A 28-year-old woman presented for screening ultrasound at 19 + 4 weeks' gestation following isolated low unconjugated estriol level (0.29 multiples of the median) on serum screening for Down syndrome. Transvaginal sonography demonstrated absence of fluid within the cavum septi pellucidi but normal ventricular and callosal appearance. Follow-up ultrasound at 21 + 4 weeks confirmed these findings. Karyotyping performed on cultured amniocytes was normal. Smith–Lemli–Opitz syndrome was excluded by normal amniotic fluid 7-dehydrocholesterol level. A follow-up scan at 23 weeks showed no fluid within the cavum septi pellucidi (Figure 1). Transvaginal visualization of the corpus callosum demonstrated normal length, with possible subtle dysmorphic appearance of the splenium (Figure 2). A male infant was delivered by Cesarean section at 41 weeks after three failed inductions. Apgar scores were 3, 5 and 7 at 1, 5 and 10 min, respectively, and cord pH was 7.09. Respiratory effort was poor and he was transferred to the nursery due to mild respiratory distress. His blood glucose on arrival was < 1 mmol/L. He required two boluses of D10W and remained on D10W infusion for 48 h to achieve stabilization before discharge. He was readmitted at 11 days of age with persistent hyperbilirubinemia, low blood glucose level and weight loss. A diagnosis of cortisol deficiency, growth hormone deficiency and hypothyroidism was made, as well as, subsequently, diabetes insipidus. The adrenal insufficiency explained the prenatally detected low unconjugated estriol. Optic nerve hypoplasia was apparent on ophthalmological examination. Magnetic resonance imaging at 10 months of age showed vestigial prechiasmatic optic nerves and optic chiasm, as well as complete absence of pituitary tissue. There was posterior callosal dysgenesis. At the time of writing, he was 2 years old and was being followed for global developmental delay, hypotonia, panhypopituitarism, optic hypoplasia associated with visual impairment and symptomatic seizures. We believe that this case illustrates the need for caution in interpreting the significance of subtle midline intracranial abnormalities in the fetal brain, particularly when there is an aberration in development of the septum pellucidum. It has been well documented that visualization of the cavum septi pellucidi is a reliable means of confirming integrity of midline intracranial anatomy on screening ultrasound examination2. However, the septum pellucidum itself has not been well characterized histopathologically during fetal life, and pathogenesis in development is not well understood3. A hypothetical etiological association between septal agenesis and other midline brain anomalies has been postulated4. This is ascribed to possible vascular incidents which would explain the associated findings in embryologically disparate events. It could be extrapolated that an anomaly involving midline brain development, specifically development of the septum pellucidum, could be associated with other midline brain abnormalities. This case illustrates the importance of awareness of the possibility of pituitary and chiasmatic abnormalities, which may be difficult to detect with antenatal imaging and may result in significant clinical neonatal morbidity and developmental disability. D. Pugash*†, S. Langlois‡, P. Power§ and M. Demos¶ †Radiology, University of British Columbia, Ultrasound 1 T48, BC Women's Hospital, 4500 Oak St., Vancouver, British Columbia V6H 3 N1, Canada; ‡Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada; §Medical Genetics, British Columbia Women's Hospital, Vancouver, British Columbia, Canada; ¶Pediatrics and Neurology, University of British Columbia, Vancouver, British Columbia, Canada *Correspondence. (e-mail: dpugash@cw.bc.ca)

A multifactorial relationship exists between total circulating cell‐free DNA levels and maternal BMI

A multifactorial relationship exists between total circulating cell‐free DNA levels and maternal BMI

Overview of maternal serum screening for down syndrome

This presentation will cover the principles of Down syndrome screening and the progress of screening from the use of age, second trimester and later first trimester screening tests. Refinements of first trimester screening will be discussed, including the timing of blood and ultrasound components, accreditation of sonologists, addition of nasal bone and ductus venosus to risk assessments and progress towards measuring precision and bias in ultrasound. The benefits and disadvantages of first and second trimester screening tests will be compared. Newer developments assessing risk of neural tube defects at first trimester including loss of intracranial translucency, caudal midbrain displacement and first trimester AFP will be covered. Screening programs can also assess risk for other chromosomal abnormalities such as Edward, Pataus and sex chromosomal anomalies. Prediction of other adverse outcomes such as preterm birth, low birth weight and pre-eclampsia have also been studied. Practical issues in a screening program, such as interferences and confounding factors are important to recognise and will be briefly discussed. The lecture will conclude with recognition that screening is an individual ethical choice. Pre-test information and counselling are important and the implications of the follow-up diagnostic tests should be understood.

Overview of maternal serum screening for down syndrome

This presentation will cover the principles of Down syndrome screening and the progress of screening from the use of age, second trimester and later first trimester screening tests. Refinements of first trimester screening will be discussed, including the timing of blood and ultrasound components, accreditation of sonologists, addition of nasal bone and ductus venosus to risk assessments and progress towards measuring precision and bias in ultrasound. The benefits and disadvantages of first and second trimester screening tests will be compared. Newer developments assessing risk of neural tube defects at first trimester including loss of intracranial translucency, caudal midbrain displacement and first trimester AFP will be covered. Screening programs can also assess risk for other chromosomal abnormalities such as Edward, Pataus and sex chromosomal anomalies. Prediction of other adverse outcomes such as preterm birth, low birth weight and pre-eclampsia have also been studied. Practical issues in a screening program, such as interferences and confounding factors are important to recognise and will be briefly discussed. The lecture will conclude with recognition that screening is an individual ethical choice. Pre-test information and counselling are important and the implications of the follow-up diagnostic tests should be understood.

Prenatal diagnosis of Milroy disease

We present the case of a 31-year-old woman, para 0, gravida 1, with no notable medical history. Both parents are from the Middle East and not consanguineous. The first ultrasound scan at 12weeks documented a normal nuchal translucency (50 th percentile), but also showed an anechoic intra-abdominal feature probably corresponding to moderate bowel dilatation. The second trimester maternal serum screening for Down syndrome was in the low risk zone. The second-trimester ultrasound at 23weeks showed lower limb oedema affecting the dorsum of both feet (Figure 1), with mild prefrontal oedema (5mm) and no other malformations. Fetal karyotyping after amniocentesis was normal: 46, XX. The father reported a personal history of bilateral lymphedema of the feet from birth, which improved during the first years of life, but with persistent oedema up to the ankle and ungueal dysplasia. At 15years of age, he had undergone surgery for a hydrocele. His 3-year-old niece presented lymphedema, which in retrospect was typical for Milroy disease affecting both feet at birth, and one of his brothers had been treated twice for lymphangitis.

Screening for adverse pregnancy outcome at early gestational age

In the past two decades second-trimester maternal serum screening for Down syndrome has been the most common strategy for prenatal diagnosis of chromosomal aneuploidies. More recently, screening for and diagnosis of chromosomal abnormalities have increasingly been performed in the first trimester. With improvements and technological advances in ultrasound, it is now possible to identify many fetal anomalies at 11-13 weeks of gestation. During the same period biochemical markers in maternal serum (PAPP-A and hCGβ) combined with sonographic measurement of nuchal translucency achieve a Down syndrome detection rate of 85% with a 5% false-positive rate. We describe here the potential of first-trimester markers to screen for Down syndrome as well as other adverse outcomes such as fetal loss, pre-eclampsia, intrauterine growth retardation, and preterm delivery. This early consultation may be the opportunity to help counsel patients and to screen for other adverse complications during pregnancy, such as pre-eclampsia, and to manage potential adverse pregnancy outcomes.

Maternal Serum Screening for Down Syndrome: Effect of Different Set of Distribution Parameters on Efficacy and Reliability of System

Maternal Serum Screening for Down Syndrome: Effect of Different Set of Distribution Parameters on Efficacy and Reliability of System

Informed Consent for Antenatal Serum Screening for Down Syndrome

Respect for patients' autonomy is a principle issue in medical ethics. Patients' understanding of antenatal serum screening for Down syndrome upon informed consent has barely been assessed. Our objective was to evaluate pregnant women's perceived level of understanding of this serum screening. Pregnant women between the 15(th) and 21(st) gestational week were randomized into control and experimental groups, and were asked to complete a questionnaire before and after genetic counselling provided by researchers. The primary endpoints were the perceived level of understanding of serum screening for Down syndrome and the autonomy of the decision making for this serum screening. The secondary endpoints were the anxiety and depression levels of these women. Participants in the experimental group (n = 96) had a significantly higher perceived level of understanding of antenatal serum screening for Down syndrome than participants in the control group (n = 97). There were significantly more respondents in the experimental group making the decision themselves to undergo serum screening than women in the control group. Anxiety and depression levels were not significantly different between the women in the two groups. Pregnant women should be offered more information to allow them to make an informed decision before they undergo antenatal serum screening for Down syndrome. Comprehensive genetic counseling improved pregnant women's autonomy in deciding whether to participate in serum screening. Health service providers should make effort to fulfill the ethical requirements of informed consent.