Second-trimester Serum Screening Research Articles

Identifying risk of stillbirth using machine learning

Previous predictive models using logistic regression for stillbirth do not leverage the advanced and nuanced techniques involved in sophisticated machine learning methods, such as modeling nonlinear relationships between outcomes. This study aimed to create and refine machine learning models for predicting stillbirth using data available before viability (22-24 weeks) and throughout pregnancy, as well as demographic, medical, and prenatal visit data, including ultrasound and fetal genetics. This is a secondary analysis of the Stillbirth Collaborative Research Network, which included data from pregnancies resulting in stillborn and live-born infants delivered at 59 hospitals in 5 diverse regions across the United States from 2006 to 2009. The primary aim was the creation of a model for predicting stillbirth using data available before viability. Secondary aims included refining models with variables available throughout pregnancy and determining variable importance. Among 3000 live births and 982 stillbirths, 101 variables of interest were identified. Of the models incorporating data available before viability, the random forests model had 85.1% accuracy (area under the curve) and high sensitivity (88.6%), specificity (85.3%), positive predictive value (85.3%), and negative predictive value (84.8%). A random forests model using data collected throughout pregnancy resulted in accuracy of 85.0%; this model had 92.2% sensitivity, 77.9% specificity, 84.7% positive predictive value, and 88.3% negative predictive value. Important variables in the previability model included previous stillbirth, minority race, gestational age at the earliest prenatal visit and ultrasound, and second-trimester serum screening. Applying advanced machine learning techniques to a comprehensive database of stillbirths and live births with unique and clinically relevant variables resulted in an algorithm that could accurately identify 85% of pregnancies that would result in stillbirth, before they reached viability. Once validated in representative databases reflective of the US birthing population and then prospectively, these models may provide effective risk stratification and clinical decision-making support to better identify and monitor those at risk of stillbirth.

Health economic evaluation of four prenatal screening strategies for Down syndrome in Changsha, China

To compare the clinical application and health economic values of non-invasive prenatal testing (NIPT) and second trimester serum screening (STSS). A retrospective analysis was carried out on 54 026 singleton pregnant women undergoing NIPT and STSS from March 1, 2018 to December 31, 2019 in Changsha Maternal and Child Health Care Hospital. For pregnant women with high-risk results of NIPT, prenatal diagnosis and follow-up of pregnancy outcomes were conducted. The data was grouped to 4 screening models, and their cost-benefit was analyzed. The sensitivity, specificity and positive predictive value of NIPT were all higher than STSS. Screening models 1 to 4 have prevented the birth of 71, 29, 52 and 54 patients with Down syndrome, respectively. The safety index of screening models 1 to 4 were 0.0036, 0.3944, 02215 and 0.1281, respectively. When the price of NIPT was decreased to 600 RMB, the cost-benefit of the screening models 1 to 4 was 0.46, 0.65, 0.44 and 0.40 million RMB, respectively. NIPT has a better detection performance than STSS. When the price of NIPT is 600 RMB, screening model 1 has the best screening effect and the highest accuracy, safety index and health economical value.

Health Supervision for Children and Adolescents With Down Syndrome.

Health Supervision for Children and Adolescents With Down Syndrome.

The impact of prenatal screening tests on prenatal diagnosis in Taiwan from 2006 to 2019: a regional cohort study

BackgroundThe purpose of this study is to evaluate the impact of prenatal screening tests on prenatal diagnosis in Taiwan’s 14 years from 2006 to 2019.MethodsThe prenatal screening methods evolved from the second-trimester serum screening to combined first-trimester screening (cFTS) and then followed by the non-invasive cell-free DNA prenatal test (NIPT). The data used by the Department of Statistics, the Ministry of Health and Welfare and Department of Household Registration, Ministry of the Interior public website.ResultsThis regional registry-based cohort retrospective study examined a total of 2,775,792 births from January 2006 to December 2019. The proportion of advanced maternal age (AMA) pregnancies increased from 11.63% in 2006 to 30.94% in 2019. Overall, invasive diagnostic testing was used in 87.22% of AMA pregnancies. The prenatal detection rate of trisomy 21 and 18 increased from 74.1% and 83.3% in 2006 to 96.9% and 98.8% in 2019, respectively.ConclusionDuring the second-trimester and cFTS periods, the percentage of AMA pregnancies increased every year and the number of invasive procedures also accompany with increased percentage of AMA. However, during the period that NIPT were implemented, the percentage of invasive procedures decreased.

State-wide utilization and performance of traditional and cell-free DNA-based prenatal testing pathways: the Victorian Perinatal Record Linkage (PeRL) study.

To perform individual record linkage of women undergoing screening with cell-free DNA (cfDNA), combined first-trimester screening (CFTS), second-trimester serum screening (STSS), and/or prenatal and postnatal cytogenetic testing with the aim to (1) obtain population-based estimates of utilization of prenatal screening and invasive diagnosis, (2) analyze the performance of different prenatal screening strategies, and (3) report the residual risk of any major chromosomal abnormality following a low-risk aneuploidy screening result. This was a retrospective study of women residing in the state of Victoria, Australia, who underwent prenatal screening or invasive prenatal diagnosis in 2015. Patient-funded cfDNA referrals from multiple providers were merged with state-wide results for government-subsidized CFTS, STSS and invasive diagnostic procedures. Postnatal cytogenetic results from products of conception and infants up to 12 months of age were obtained to ascertain cases of false-negative screening results and atypical chromosomal abnormalities. Individual record linkage was performed using LinkageWizTM . During the study period, there were 79 140 births and 66 166 (83.6%) women underwent at least one form of aneuploidy screening. Linkage data were complete for 93.5% (n = 61 877) of women who underwent screening, and of these, 73.2% (n = 45 275) had CFTS alone, 20.2% (n = 12 486) had cfDNA alone; 5.3% (n = 3268) had STSS alone, 1.3% (n = 813) had both CFTS and cfDNA, and < 0.1% (n = 35) had both STSS and cfDNA. CFTS had a combined sensitivity for trisomies 21 (T21), 18 (T18) and 13 (T13) of 89.57% (95% CI, 82.64-93.93%) for a screen-positive rate (SPR) of 2.94%. There were 12 false-negative results in the CFTS pathway, comprising 10 cases of T21, one of T18 and one of T13. cfDNA had a combined sensitivity for T21, T18 and T13 of 100% (95% CI, 95.00-100%) for a SPR of 1.21%. When high-risk cfDNA results for any chromosome (including the sex chromosomes) and failed cfDNA tests were treated as screen positives, the SPR for cfDNA increased to 2.42%. The risk of any major chromosomal abnormality (including atypical abnormalities) detected on prenatal or postnatal diagnostic testing after a low-risk screening result was 1 in 1188 for CFTS (n = 37) and 1 in 762 for cfDNA (n = 16) (P = 0.13). The range of chromosomal abnormalities detected after a low-risk cfDNA result included pathogenic copy-number variants (n = 6), triploidy (n = 3), rare autosomal trisomies (n = 3) and monosomy X (n = 2). Our state-wide record-linkage analysis delineated the utilization and clinical performance of the multitude of prenatal screening pathways available to pregnant women. The sensitivity of cfDNA for T21, T18 and T13 was clearly superior to that of CFTS. While there was no statistically significant difference in the residual risk of any major chromosomal abnormality after a low-risk CFTS or cfDNA result, there were fewer live infants diagnosed with a major chromosomal abnormality in the cfDNA cohort. These data provide valuable population-based evidence to inform practice recommendations and health policies. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Evolution of Down Syndrome Prenatal Screening Clinical Practices in Québec.

Prenatal screening for Down syndrome (DS) has evolved greatly over the last decades with the improvement of first- and second-trimester serum screening and the introduction of cell-free fetal DNA. This study aimed to estimate the impact of such changes on practices. This retrospective cohort study included fetuses and newborns diagnosed with DS between 2005-2007 and 2015-2017 in the single obstetrical care centre in Québec City. Data were collected on the prenatal screening method, diagnosis, and delivery. The median was compared between the study periods. Complete clinical data were available for only 78 (66%) of 119 cases of DS. Significant changes were observed in screening methods, including an increase in the use of first-trimester serum, ultrasound, and cell-free fetal DNA. No significant changes were noted in terms of gestational age at diagnosis (median [interquartile range; IQR]: 17.0 [16.0-20.9] weeks in 2005-2007 vs. 17.9 [16.3-22.5] weeks in 2015-2017; P = 0.49) and delivery or termination of pregnancy (median 20.9 [IQR 18.0-23.3] weeks in 2005-2007 vs. 21.3 [18.4-23.4] weeks in 2015-2017; P = 0.46). The methods of diagnosis did not change significantly over the decade, with amniocentesis used 85% and 79% of the time, respectively (P = 0.19). The increased use of first-trimester screening and cell-free fetal DNA tests was not associated with earlier diagnosis of DS or earlier delivery or termination of pregnancy. The use of chorionic villus sampling should be encouraged for DS diagnosis when indicated because it could reduce the gestational age at diagnosis and termination if requested.

OC01.03: State‐wide performance of traditional and cell‐free DNA‐based prenatal testing pathways: the Victorian Perinatal Record Linkage (PeRL) study

OBJECTIVES: Women's choices of prenatal screening and diagnostic pathways have increased in complexity since the introduction of cell-free DNA (cfDNA) screening and chromosomal microarrays. We performed individual record-linkage of women undergoing screening with cfDNA, combined first trimester screening (CFTS), second trimester serum screening (STSS), and/or prenatal and postnatal cytogenetic testing to (i) obtain population-based estimates on women's utilization of screening and diagnosis, (ii) analyse the performance of different screening strategies, and (iii) report the residual risks of any major chromosome abnormality following a low risk aneuploidy screen. METHODS: Retrospective study of women resident in Victoria, Australia, undergoing screening or prenatal diagnosis in 2015. Patient-funded cfDNA referrals from multiple providers were merged with state-wide results for government-subsidized CFTS, STSS and invasive diagnostic procedures. Postnatal cytogenetic results from products of conception and infants up to 12 months of age were obtained to ascertain cases of false negative screening results and atypical chromosome abnormalities. Individual record-linkage was performed with LinkageWizTM and statistical analyses with STATA v14.0. RESULTS: There were 79,140 births during the study period; 66,166 women (83.4%) underwent at least one form of aneuploidy screening. Linkage data were complete for 92.4% of women undergoing screening (n=61,911) and of these, 73.1% (n=45,275) used CFTS alone, 20.2% (n=12,520) used cfDNA alone; 5.3% (n=3268) used STSS alone, 1.3% (n=813) used both CFTS and cfDNA, and < 0.1% (n=35) used both STSS and cfDNA. CFTS had a combined sensitivity for trisomies 21, 13 and 18 of 89.57% (95%CI 82.64-93.93) for a screen positive rate (SPR) of 2.94%. There were 12 false negative results in the CFTS pathway (10 trisomy 21, 1 trisomy 18 and 1 trisomy 13). CfDNA had a combined sensitivity of 100% (95% CI 95.0-100.0) for trisomies 21, 13 and 18 for a 1.21% screen positive rate. When high risk cfDNA results for any chromosome, including the sex chromosomes, and failed cfDNA tests were treated as screen positives, the cfDNA SPR increased to 2.42%. The risk of any major chromosome abnormality (including atypical abnormalities) detected on prenatal or postnatal diagnostic testing after a low risk screening result was 1 in 1188 for CFTS (n=37) and 1 in 762 for cfDNA (n=16) (p= 0.13). The range of chromosome abnormalities detected after low risk cfDNA included pathogenic CNVs (n=6), triploidy (n=3), rare autosomal trisomies (n=3) and monosomy X (n=2). CONCLUSIONS: Our state-wide linkage analysis delineated the utilization and clinical performance of the multitude of screening pathways available to pregnant women. The sensitivity of cfDNA for trisomies 21, 13 and 18 was clearly superior to CFTS. While there was no statistically significant difference in the residual risk of any major chromosome abnormality after low risk CFTS or cfDNA result, there were fewer live infants diagnosed with a major chromosome abnormality in the cfDNA cohort. These data provide valuable population-based evidence to inform practice recommendations and health policy. This article is protected by copyright. All rights reserved.

Cell-free Fetal DNA Analysis in Maternal Plasma as Screening Test for Trisomies 21, 18, and 13 in Twin Pregnancy

(Abstracted from Ultrasound Obstet Gynecol 2018;52(3):318–324) Increased use of fertility treatment and advanced maternal age contribute to the increased prevalence of twin pregnancy, which is currently approximately 3% in the United States. Screening for trisomy 21 in twins largely relies on maternal age and nuchal translucency measurement in the first trimester, as well as first- and second-trimester serum screening.

Prenatal diagnosis and socioeconomic status in the non-invasive prenatal testing era: A population-based study.

Advances in technology can bring great benefits to human health, but their implementation may be influenced by socioeconomic factors, particularly in the field of prenatal screening for Down syndrome. To analyse screening test indications for, and diagnostic yield of, invasive prenatal diagnostic testing (PNDx) according to socioeconomic status. Retrospective analysis of population-based data on PNDx and karyotype results for 2014-2015 in the Australian state of Victoria. Women having PNDx<25weeks due to combined first trimester screening (CFTS), second trimester serum screening (STSS), or noninvasive prenatal testing (NIPT) results were included. PNDx data were analysed by indication and maternal Index of Relative Socio-economic Advantage and Disadvantage (IRSAD), the latter determined by postcode. There were 145206 births in 2014-2015; 1906 women underwent PNDx for the indication of CFTS (70.1%), NIPT (17.8%) or STSS (12.0%). Covariates positively associated with NIPT-indicated PNDx, compared with CFTS-indicated testing, were residence in a region of socioeconomic advantage, metropolitan status and maternal age. Women from the most advantaged regions had higher adjusted odds ratios (aOR) of NIPT-indicated testing compared with women from disadvantaged regions (aOR 5.72, 95% CI: 2.95-11.09). The diagnostic yield of PNDx increased with socioeconomic region, from 14% in the lowest IRSAD quintile to 31.2% in the highest (P<0.0001). Population-based data reveal significant disparities in screening indications for PNDx and hence, in diagnostic yield, according to socioeconomic region. This finding may have ethical and policy implications for prenatal screening in Australia.

Critical congenital heart defects and abnormal levels of routinely collected first- and second-trimester biomarkers.

We examined the association between maternal characteristics, routinely collected first- and second-trimester biomarkers and the risk of having an infant with a critical congenital heart defect (CCHD). Included were women who participated in the California Prenatal Screening Program who had nuchal translucency (NT) measurement and first- and second-trimester serum screening. All pregnancies ended in a live birth of an infant without aneuploidy or a neural tube defect. Poisson regression analyses were used to estimate the relative risk and 95% confidence interval of a CCHD by maternal characteristics, first- and second-trimester serum biomarkers or NT measurements. The sample included 118,194 mother-infant pairs; 284 infants had a CCHD. Women with preexisting diabetes were three-times as likely to have an infant with a CCHD. After adjusting for preexisting diabetes, women with first-trimester human chorionic gonatotropin (hCG) measurement <10th centile were 1.6-times as likely to have an infant with a CCHD (P = 0.011). Women with a NT measurement ≥95th centile were at two- to threefold higher risk of having an infant with a CCHD (P's = 0.004-0.007). Pregnancies with two risk factors for an infant with a CCHD were 5.6-times more likely to have an infant with a CCHD than women with no identified risk factors (P < 0.001). Despite the increased risk, performance testing demonstrated low sensitivity and specificity for screening use of these risk factors. Of the women with an infant with a CCHD, only 21.8% had an identified risk factor. © 2016 Wiley Periodicals, Inc.

Efficacy of the Genetic Sonogram in a Stepwise Sequential Protocol for Down Syndrome Screening

The purpose of this study was to evaluate the efficacy of the genetic sonogram in Down syndrome screening for women who have received the stepwise sequential test. This retrospective cohort study included women with singleton pregnancies who underwent stepwise sequential (first-trimester combined and second-trimester serum) screening and then had a genetic sonogram between March 2005 and January 2010. Stepwise sequential Down syndrome risks were multiplied by either a positive or negative likelihood ratio based on the second-trimester sonographic findings to determine the final Down syndrome risk. A final Down syndrome risk of 1:270 or higher was considered screen positive. A total of 6286 women fulfilled our criteria, including 17 with Down syndrome-affected fetuses. After stepwise sequential testing, the Down syndrome detection rate was 88.2% (15 of 17), and after the genetic sonogram, there was a non-significant reduction in detection to 82.4% (14 of 17; P > .05). For the 6269 unaffected pregnancies, the genetic sonogram converted 58 screen-negative results (1%) to positive and 183 screen-positive results (3.1%) to negative. The net effect was a change in the false-positive rate from 6.2% (390 of 6269) after stepwise sequential screening to 4.2% (266 of 6269) after the genetic sonogram. The genetic sonogram should be applied cautiously for women who have received prior prenatal screening tests. Women with screen-positive results need to be counseled that a negative sonographic result can be falsely reassuring. Conversely, for women with screen-negative results who have a risk close to the cutoff, a sonographic examination could assist in the decision of whether to accept or reject amniocentesis.

Prenatal screening for fetal aneuploidies during the first and second trimester of pregnancy

Prenatal screening for chromosomal defects during the first and second trimesters of pregnancy has become an established part of obstetric practice in many countries. The goal of current maternal serum screening programmes is to identify women who are at an increased risk of having a baby affected with Down syndrome (trisomy 21), Edwards syndrome (trisomy 18) or neural tube defects and who will benefit from such diagnostic tests. The most commonly used test for genetic diagnosis is amniocentesis; however, the rate of spontaneous fetal loss caused by this test averages at about 1 in every 200 procedures. Because of this risk, serum analyte testing has become an important and non-invasive first step in detecting patients at risk of carrying a child with congenital abnormalities. The non-invasive screening options which are currently available to patients include combining maternal age with one of the following: first-trimester serum screening [nuchal translucency (NT) and maternal serum biochemistry markers]; second-trimester serum screening (maternal serum biochemistry markers such as the triple test and the quadruple test); or the two-step integrated screening, which comprises first- and second-trimester serum screening with or without NT.

Imaging clues in the prenatal diagnosis of syndromes and aneuploidy

Advances in fetal sonography and MRI have increased both the range and diagnostic accuracy of detectable fetal anomalies, with many anomalies detectable earlier in pregnancy. The presence of structural anomalies greatly raises the risk that the fetus has a syndrome or abnormal karyotype. In addition, new techniques in maternal serum screening have greatly increased the ability to identify pregnant patients at risk for anomalies and syndromes. This paper reviews maternal first- and second-trimester serum screening and imaging and covers many of the most common fetal karyotypic and structural anomalies.

Physicians' Communication of Down Syndrome Screening Test Results: The Influence of Physician Numeracy

Second-trimester screening for Down syndrome identifies pregnant women with a fetus at increased risk usually defined as a risk above 1 in 200, 1 in 250, or 1 in 300. Such screening tests identify a population at increased risk, but additional diagnostic tests such as amniocentesis are required to confirm whether a fetus does or does not have Down syndrome. The communication format used by clinicians to explain the results of a confirmed diagnosis may influence the patient's perception of risk. Supplementing the quantitative (numerical) results of Down syndrome screening tests with qualitative labels such as “abnormal” and “positive” is associated with increased patient anxiety and greater perceived risk, and it may influence subsequent healthcare decisions. Interestingly, in a number of studies, physicians have been shown to have problems with understanding statistics (e.g., P values, risk ratios). It is not surprising that some clinicians have difficulty both estimating and explaining the likelihood that a fetus has Down syndrome after a positive screening test. The aim of this study was to assess how obstetric clinicians communicate results of the second-trimester serum screening tests to their patients. The investigators conducted a survey to determine (1) how positive and negative test results are communicated, (2) whether quantitative or qualitative information is used in reporting screening test results, and (3) whether understanding of numeracy (health literacy) influences the communication strategy used to present quantitative or qualitative information. Practicing members of the American College of Obstetricians and Gynecologists were invited to participate in the survey. The response rate was 55.6% (n = 203). The respondents answered questions about their communication strategy used to present Down syndrome screening results, which were evaluated on the Objective Numeracy Scale and the Subjective Numeracy Scale. The Subjective Numeracy Scale scores predicted the use of quantitative information. In contrast to the Subjective Numeracy Scale scores, the Objective Numeracy Scale scores did not predict use of the actual numbers. There were gender differences: the Subjective Numeracy Scale scores and the Subjective Numeracy Scale–Ability Subscale scores were greater among men than women when controlling for age. Response to open-ended questions showed that communication strategies used by clinicians to explain test results vary. Approximately 1 in 3 provided numerical information, the most commonly reported format. These findings indicate that patients of physicians with low subjective numeracy may receive only quantitative risk information, which may inflate their perceived risk. The communication strategy used by clinicians to explain test results may have implications for health decisions by patients and their quality of care.

Echogenic Bowel on Second-Trimester Ultrasonography

To estimate if echogenic bowel diagnosed on second-trimester ultrasonography has an independent risk association with intrauterine growth restriction (IUGR) and intrauterine fetal demise. This is a retrospective cohort study of all patients with singleton gestations who presented to our institution for second-trimester ultrasonography between 1990 and 2008. Study groups were defined by the presence or absence of echogenic bowel. Primary outcomes were IUGR, defined as birth weight less than the 10th percentile for gestational age and intrauterine fetal demise at 20 weeks or more of gestation. Univariable and multivariable logistic regression analyses were used to estimate the risk of intrauterine fetal demise and IUGR in fetuses with echogenic bowel. Analyses were repeated after excluding cases of aneuploidy, cytomegalovirus (CMV) infection, other major congenital anomalies, and abnormal second-trimester serum screening results. Of 64,048 patients, the incidence of echogenic bowel was 0.4%. Of these, echogenic bowel was an isolated finding in 188 (72.3%) cases. There were 579 (0.9%) cases of intrauterine fetal demise and 8,173 (12.8%) cases of IUGR in the entire cohort. After excluding cases of aneuploidy and CMV infection, the incidence of intrauterine fetal demise was 7.3% in the echogenic bowel group compared with 0.9% in the nonechogenic bowel group, translating to an absolute risk increase of 6.4%. The incidence of IUGR in the echogenic bowel group was 19.5% compared with 12.9% in the nonechogenic bowel group (absolute risk increase, 6.6%). After controlling for potential confounders, echogenic bowel was significantly associated with both intrauterine fetal demise (adjusted odds ratio [OR] 9.6, 95% confidence interval [CI] 5.8-15.9) and IUGR (adjusted OR 2.1, 95% CI 1.5-2.9). This risk association remained significant even when evaluating echogenic bowel as an isolated sonographic finding. The presence of echogenic bowel on ultrasonography is independently associated with an increased risk for both IUGR and intrauterine fetal demise. Serial growth assessment and antenatal testing may be warranted in these patients.

The history of the second‐trimester sonographic markers for detecting fetal Down syndrome, and their current role in obstetric practice

This review summarizes the development, history and use of second-trimester sonographic markers for the detection of fetal Down syndrome over three decades. Starting with the nuchal fold thickening in 1985 and culminating in the genetic sonogram in the 1990 s. The combination of second-trimester serum screening with the ultrasound markers improved the detection rate of affected fetuses but also allowed patients to decrease their risk of carrying a fetus with Down syndrome if the genetic sonogram was normal. More recently the role of the genetic sonogram and its markers have changed with the wide spread use of first-trimester screening. This prior screening ultimately decreases the prevalence of fetal Down syndrome in the second trimester to less than 85% of what it was in the first-trimester as most fetuses with Down syndrome are now identified early. Current interpretation of the second-trimester Down syndrome markers must be based on the result of the first trimester and combined screening to achieve the most accurate risk estimate of an affected fetus.

Genetic sonography: the historical and clinical role of fetal echocardiography

The association of congenital heart defects with trisomy 21 was reported over 50 years ago and heart defects remain one of the most common and lethal abnormalities present postnatally in individuals affected by Down syndrome1–4. The purpose of this Editorial is to review the use of second-trimester fetal echocardiography as an adjunct to the genetic sonogram from a clinical perspective, based on my experience over the past 20 years5–13. The following topics are discussed as they relate to trisomy 21: (1) the incorporation of ultrasound evaluation of the fetal heart as part of the genetic sonogram and comparison of it with other screening modalities from a historical perspective; (2) the postnatal incidence of congenital heart defects; (3) the prenatal incidence of structural and functional heart abnormalities; (4) the relative risk for various cardiac findings; and (5) the suggested use of fetal echocardiography as part of the genetic sonogram given current screening technologies.

Measurement of Nuchal Translucency and the Prenatal Diagnosis of Down Syndrome

To estimate the sensitivity of nuchal-translucency measurement and compare it with that of second-trimester serum screening using population-based data and to evaluate the effect of nuchal-translucency measurement on the gestational age at prenatal diagnosis of Down syndrome and pregnancy termination. We used The Paris Registry of Congenital Malformation data on 594 cases of Down syndrome (live births, fetal deaths, and pregnancy terminations) from 2001-2006. Analyses were done separately for women younger than 38 years and women aged 38 years or older. Analyses included binomial regression and fractional polynomials to model time trends in gestational age at diagnosis and at pregnancy termination. Ninety percent of the fetuses had undergone nuchal-translucency measurement as compared with only 22% that underwent second-trimester serum screening. This was principally because half of the pregnant women were given a diagnosis of Down syndrome during the first trimester after an abnormal result of nuchal-translucency measurement. Second-trimester serum screening had a higher sensitivity than did nuchal-translucency measurement (72% compared with 56%). The increasing use of nuchal-translucency measurement led to an increase in early diagnosis of Down syndrome in women younger than 38 years of age; diagnosis before 15 weeks of gestation increased from 21.7% in 2001 to 51.6% in 2006 (P=.016). Pregnancy termination before 15 weeks also increased from 18.8% in 2001 to 47.5% in 2006 (P=.02). The main effect of the increased use of nuchal-translucency measurement was a substantial increase in the early detection of Down syndrome, principally in younger women. This is an important advantage because several studies have shown that women prefer early diagnosis of Down syndrome. III.

Management and Outcome of Pregnancies with Parvovirus B19 Infection over Seven Years in a Tertiary Fetal Medicine Unit

Objectives: To determine rates of fetal anaemia and pregnancy outcome in susceptible pregnant women infected with human parvovirus B19 infection in a tertiary fetal medicine department over a 7-year period. Additional features enabling identification of fetuses that progress to severe anaemia were also investigated. Methods: Forty-seven susceptible, pregnant women with confirmed parvovirus infection referred to a regional fetal medicine unit, over a 7-year period (1999–2006), were identified. Where possible maternal serum AFP measurements were obtained from second-trimester serum screening and the presence or absence of echogenic bowel noted. Results: Of the 47 cases, one was excluded. Of the remaining 46 cases, 34 (74%) showed no signs of fetal anaemia and delivered at term. The remaining 12 (26%) showed signs of fetal anaemia. Eight of the 12 developed hydrops and underwent fetal blood sampling and transfusion (median pretransfusion Hb 3.6 g/dl). Seven of the 8 transfused fetuses were thrombocytopenic with a platelet count <150 × 10⁹/l, with 2 fetuses having platelet counts <50 × 10⁹/l. The median gestation age at transfusion was 22 weeks (range 18–27 weeks). The median number of weeks between seroconversion and transfusion was 6 (range 3–12). The signs of anaemia resolved after one transfusion in 5 of the 8 transfused fetuses and they subsequently delivered at term. There were 2 fetal deaths during or shortly after transfusion and one neonatal death following delivery at 28 weeks gestation due to severe pre-eclampsia, 5 days after successful transfusion. Conclusions: Following parvovirus seroconversion, the incidence of significant fetal anaemia requiring transfusion was 17%. Seroconversion after 21 weeks did not result in severe fetal anaemia. Significant anaemia requiring intervention did not occur 12 weeks after maternal seroconversion. We did not demonstrate a correlation with either maternal serum AFP or the presence of fetal echogenic bowel and the development of severe fetal anaemia. Because of the association between fetal anaemia and severe thrombocytopenia, it may be prudent to have compatible platelets available at the time of fetal blood sampling.

OP15.01: Association between first- and second-trimester serum screening markers and pregnancy outcomes

OP15.01: Association between first- and second-trimester serum screening markers and pregnancy outcomes