Screening For Neural Tube Defects Research Articles

Use of Maternal Race and Weight Provides Equitable Performance in Serum Screening for Open Neural Tube Defects.

Maternal serum alpha-fetoprotein (AFP) levels are used in screening for open neural tube defects (ONTD). Historical reports show that AFP levels and maternal weights are higher in self-reported Black than White individuals, but recent reports question the need to account for these variables in screening. Our study compares screening performance with and without accounting for race. Retrospective analysis was performed on deidentified prenatal screening records including maternal weight and self-reported race of White or Black. Gestational age-specific medians and weight-adjusted multiples of the median levels were calculated separately for each group and using a race-agnostic analysis. Outcome measures included the proportion of screen-positive results. Records for analysis (n = 13 316) had an ultrasound confirmed gestational age between 15 and 21 completed weeks, singleton pregnancy, and self-reported race. Race was Black for 26.3%. AFP levels for pregnancies in Black individuals were higher than in White individuals: 6% to 11% depending on gestational age. Race-specific gestational age and maternal weight analyses resulted in similar screen-positive rates for self-reported White and Black individuals at 0.74% vs 1.00%, respectively (P = 0.14). However, use of race-agnostic analyses resulted in a screen-positive rate that was 2.4 times higher in Black than White individuals (P < 0.001). These data show that the historical method of accounting for maternal race and weight in prenatal screening for ONTD provides equitable performance. Using a race-agnostic methodology results in an increased screen-positive rate and a disproportionate rate of required follow-up care for individuals who self-identify as Black.

Prenatal screening for neural tube defects: from maternal serum alpha-fetoprotein to ultrasonography.

The two main screening tests during pregnancy are those for chromosomal abnormalities and neural tube defects (NTDs). In particular, for NTDs, measurement of maternal serum alpha-fetoprotein (MSAFP) levels early in the second trimester (15-18 weeks of gestation) has been considered the gold standard screening test for the past 4 decades. However, with remarkable technological advancements and the widespread use of ultrasound during those periods, mid-trimester ultrasonography has gradually replaced the role of measuring MSAFP levels as a screening method for NTDs. This change was initiated more about 10 years ago in some countries, which have issued national guidelines to use mid-trimester ultrasonography instead of measuring MSAFP levels as a prenatal screening method for NTDs. However, no significant changes have occurred in Korea, where second-trimester ultrasonography is routinely performed with high-quality equipment. We aimed to provide information regarding the importance of changing the screening method for NTDs from MSAFP measurement to ultrasonography, and to detail methods of implementing mid-trimester ultrasonography for screening purposes. We also share our experience of operating a prenatal diagnostic program for NTDs without using MSAFP for more than 15 years.

Comparative study between 1st and 2nd trimester screening for neural tube defects using US markers and maternal serum alpha fetoportein

Background; Neural tube defects, the commonest central nervous system congenital anomalies, are a heterogeneous group of malformations resulting from failure of normal neural tube closure. Aim and objectives; to assess the potential value of combined maternal serum alpha-fetoprotein and ultrasound markers at 11-13weeks of gestation in early screening for fetal neural tube defects in comparison to the standard second trimester screening of neural tube defects. Subjects and methods; This prospective study will be conducted at the Prenatal Diagnosis and Fetal Medicine Department – National Research Centre and Obstetrics and Gynecology Department in Kasr Al Ainy Teaching Hospital. Result; Number of patients with MSAFP ≥ 2.0 MoM in the study population was 50 (25%). Number of patients with MSAFP &lt; 2.0 MoM in the study population was 150 (75%). Conclusion; Combined maternal serum alpha-fetoprotein and ultrasound markers at 11-13 weeks of gestation can be used as early screening for fetal neural tube defects as well as the standard second trimester screening of neural tube defects, the second trimester ultrasound is more sensitive than that of the first trimester for the diagnoses of neural tube defects.

Serum exosomal coronin 1A and dynamin 2 as neural tube defect biomarkers

No highly specific and sensitive biomarkers have been identified for early diagnosis of neural tube defects (NTDs). In this study, we used proteomics to identify novel proteins specific for NTDs. Our findings revealed three proteins showing differential expression during fetal development. In a rat model of NTDs, we used western blotting to quantify proteins in maternal serum exosomes on gestational days E18, E16, E14, and E12, in serum on E18 and E12, in neural tubes on E18 and E12, and in fetal neural exosomes on E18. The expression of coronin 1A and dynamin 2 was exosome-specific and associated with spina bifida aperta embryogenesis. Furthermore, coronin 1A and dynamin 2 were significantly downregulated in maternal serum exosomes (E12–E18), neural tubes, and fetal neural exosomes. Although downregulation was also observed in serum, the difference was not significant. Differentially expressed proteins were further analyzed in the serum exosomes of pregnant women during gestational weeks 12–40 using enzyme-linked immunosorbent assays. The findings revealed that coronin 1A and dynamin 2 showed potential diagnostic efficacy during gestational weeks 12–40, particularly during early gestation (12–18 weeks). Therefore, these two targets are used as candidate NTD screening and diagnostic biomarkers during early gestation.Key messagesWe used proteomics to identify novel proteins specific for NTDs.CORO1A and DNM2 showed exosome-specific expression and were associated with SBA.CORO1A and DNM2 were downregulated in maternal serum exosomes and FNEs.CORO1A and DNM2 showed good diagnostic efficacy for NTDs during early gestation.These two targets may have applications as NTD screening and diagnostic biomarkers.

Factors associated with US and Canadian genetic counselors' testing decisions during pregnancy.

Decision-making regarding prenatal screening and diagnostic testing has become more complex as the number of options has increased, with pregnant patients having access to more information about their pregnancies than ever before. Genetic counselors have extensive training in prenatal genetic screening and testing options, but personal decision-making in this well-informed population remains largely unstudied. This study describes the prenatal testing decisions genetic counselors made during their own pregnancies, and the factors identified as important when making those decisions. A web-based, mixed-methods survey was distributed to members of multiple professional societies for genetic counselors. A total of 318 genetic counselors across numerous specialties in the United States and Canada participated in this study. The satisfaction with decision scale was modified and applied to measure participants' decisional satisfaction. In their most recent pregnancies, most genetic counselors pursued carrier screening (77%) and aneuploidy and/or open neural tube defect screening (88%). A minority of genetic counselors (15%) utilized diagnostic testing. Common factors considered when making testing decisions included wanting information that could impact future decisions, test specifics (e.g., accuracy, methodology, and content), and knowledge gained from participants' genetic counseling background. The uptake of diagnostic testing among prenatal genetic counselors was significantly greater (p < 0.05) than the uptake among genetic counselors in other specialties. This informed study population largely self-directed their own prenatal care, leading to high satisfaction with their decisions. Data in this study provide evidence for promoting participation in prenatal screening and testing decision-making to maximize decisional satisfaction.

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.

A comparison of the maternal levels of serum proprotein convertase subtilisin/kexin type 9 in pregnant women with the complication of fetal open neural tube defects.

It was aimed to evaluate the levels of maternal serum proprotein convertase subtilisin/kexin type 9 (PCSK9) in pregnant women with a fetus diagnosed with open neural tube defects (NTDs). This case-control study included 38 pregnant women carrying fetuses with open NTDs and 44 age-matched, pregnant women with no specified risk factors. Comparisons were made of the groups in respect of demographic and clinical data and PCSK9 levels. To examine the performance of PCSK9 levels in the prediction of fetal open NTDs, receiver operating characteristic (ROC) curve analysis was used. In the first and second trimesters, PCSK9 levels were determined to be lower in the NTD group than in the control group (p=0.010 and p=0.015, respectively). In the first trimester, the lower PCSK9 levels in the NTD group were not statistically significant (p=0.575). In the second trimester, the ROC curve value with the best balance of sensitivity/specificity for PCSK9 was 71.9ng/ml (84.6% sensitivity, 51.7% specificity) and in the first and second trimester combined, 74.4ng/ml (81.6% sensitivity, 45.5% specificity) (p=0.015, p=0.036, respectively). PCSK9 may be involved in the etiopathogenesis of open NTDs at the critical steps of fetal neuronal differentiation. Although it has limitations, PCSK9 may be used as an additional biomarker for the screening of NTDs.

Point-of-Care Quantification of Serum Alpha-Fetoprotein for Screening Birth Defects in Resource-Limited Settings: Proof-of-Concept Study.

Background:Maternal serum alpha-fetoprotein (MSAFP) concentration typically increases during pregnancy and is routinely measured during the second trimester as a part of screening for fetal neural tube defects and Down syndrome. However, most pregnancy screening tests are not available in the settings they are needed the most. A mobile device–enabled technology based on MSAFP for screening birth defects could enable the rapid screening and triage of high-risk pregnancies, especially where maternal serum screening and fetal ultrasound scan facilities are not easily accessible. Shifting the approach from clinic- and laboratory-dependent care to a mobile platform based on our point-of-care approach will enable translation to resource-limited settings and the global health care market.Objective:The objective of this study is to develop and perform proof-of-concept testing of a lateral flow immunoassay on a mobile platform for rapid, point-of-care quantification of serum alpha-fetoprotein (AFP) levels, from a drop of human serum, within a few minutes.Methods:The development of the immunoassay involved the selection of commercially available antibodies and optimization of their concentrations by an iterative method to achieve the required detection limits. We compared the performance of our method with that of commercially obtained human serum samples, with known AFP concentrations quantified by the Abbott ARCHITECT chemiluminescent magnetic microparticle immunoassay (CMIA).Results:We tested commercially obtained serum samples (N=20) with concentrations ranging from 2.2 to 446 ng/mL to compare the results of our point-of-care assay with results from the Abbott ARCHITECT CMIA. A correlation of 0.98 (P<.001) was observed on preliminary testing and comparison with the CMIA. The detection range of our point-of-care assay covers the range of maternal serum AFP levels observed during pregnancy.Conclusions:The preliminary test results from the AFP test on the mobile platform performed in this study represent a proof of concept that will pave the way for our future work focused on developing a mobile device–enabled quad-screen point-of-care testing with the potential to enable the screening of high-risk pregnancies in various settings. The AFP test on the mobile platform can be applied to enable screening for high-risk pregnancies, within a few minutes, at the point of care even in remote areas where maternal serum tests and fetal ultrasound scans are not easily accessible; assessment of whether clinical follow-up and diagnostic testing may be needed after a positive initial screening evaluation; and development of surveillance tools for birth defects.

Laboratory screening and diagnosis of open neural tube defects, 2019 revision: a technical standard of the American College of Medical Genetics and Genomics (ACMG)

Open neural tube defects (ONTDs) include open spina bifida (OSB) and anencephaly. These defects are caused by incomplete closure of the neural tube at about 4 weeks of pregnancy. Levels of early second-trimester maternal serum (ms) alpha-fetoprotein (AFP) are sufficiently elevated in affected pregnancies to be used as a population-based screening test. The basic screening methodology was described in the late 1970s and screening programs were active a few years later. By identifying pregnancies with the highest msAFP levels, about 80% of OSB and 95% of anencephaly can be identified as early as 16 weeks gestation. The interpretation of msAFP levels is complicated by the need to consider multiple factors such as gestational age, maternal weight, maternal race, multiple gestations, and more. Testing for AFP and acetylcholinesterase in amniotic fluid and/or identification of the lesion by targeted ultrasound is considered diagnostic of ONTD. When a diagnosis is made, options include termination, surgery after delivery, or in utero surgery, depending on factors such as location and size of the defect, and the presence of any additional anomalies. Screening for ONTD should be performed as part of a comprehensive program linking primary obstetrical care providers, laboratorians, and high-risk clinicians.

Informed Decision‐Making in the Context of Prenatal Chromosomal Microarray

The introduction of chromosomal microarray (CMA) into the prenatal setting has involved considerable deliberation due to the wide range of possible outcomes (e.g., copy number variants of uncertain clinical significance). Such issues are typically discussed in pre-test counseling for pregnant women to support informed decision-making regarding prenatal testing options. This research study aimed to assess the level of informed decision-making with respect to prenatal CMA and the factor(s) influencing decision-making to accept CMA for the selected prenatal testing procedure (i.e., chorionic villus sampling or amniocentesis). We employed a questionnaire that was adapted from a three-dimensional measure previously used to assess informed decision-making with respect to prenatal screening for Down syndrome and neural tube defects. This measure classifies an informed decision as one that is knowledgeable, value-consistent, and deliberated. Our questionnaire also included an optional open-ended question, soliciting factors that may have influenced the participants' decision to accept prenatal CMA; these responses were analyzed qualitatively. Data analysis on 106 participants indicated that 49% made an informed decision (i.e., meeting all three criteria of knowledgeable, deliberated, and value-consistent). Analysis of 59 responses to the open-ended question showed that "the more information the better" emerged as the dominant factor influencing both informed and uninformed participants' decisions to accept prenatal CMA. Despite learning about the key issues in pre-test genetic counseling, our study classified a significant portion of women as making uninformed decisions due to insufficient knowledge, lack of deliberation, value-inconsistency, or a combination of these three measures. Future efforts should focus on developing educational approaches and counseling strategies to effectively increase the rate of informed decision-making among women offered prenatal CMA.

Normative Values of Intracranial Translucency (IT) Thickness as an Ultrasonographic Marker for Neural Tube Defect (NTD) Screening in the Iranian Singleton Pregnancies

Background: Neural tube defects are the second most common congenital anomalies following congenital heart defects. Once NTD is detected prenatally, different options are available including pregnancy termination, and intrauterine fetal surgery. Considering these facts, prenatal screening for NTDs is becoming a part of routine fetal care. Several ultrasonographic markers have been suggested for detection of NTD during pregnancy. Intracranial translucency (IT) is a relatively new ultrasonographic marker for NTD screening during first-trimester. It actually represents the fourth cerebral ventricle, seen as an anechoic structure in the mid-sagittal plane of the fetal face posterior to the brainstem. Its absence or obliteration can be an indirect sign of open spina bifida, which is caused secondary to the caudal displacement of brain in these fetuses. In this study, we aimed to determine the normative values of this marker in the Iranian population. Objectives: To determine the normative values of intracranial translucency (IT) thickness in the Iranian singleton pregnancies. Methods: 230 consecutive singleton pregnancies between 11 weeks and 13 weeks+6 days of gestation were included in the study during 9 months (June 2015 to February 2016) prospectively in Mahdieh and Sarem womens hospital, Tehran, Iran. Crown-rump length (CRL), nuchal translucency (NT) thickness, fetal heart rate, and nasal bone status were evaluated by ultrasound as parts of the routine first-trimester screening for aneuploidies. Precise gestational age was determined by the fetal CRL as well. In addition, IT thickness was measured in the mid-sagittal view of the fetal head between two echogenic horizontal lines: posterior border of the brainstem anteriorly and anterior aspect of the fourth ventricle choroid plexus posteriorly (figure 1). All the measurements were performed by a radiologist with four years of experience in fetal imaging. Ethnicities other than Iranian, multiple gestation pregnancies, and pregnancies conceived by assisted reproductive technology (ART) were not included in the study initially. Other exclusion criteria were any obvious anatomic fetal anomaly in the ultrasound examination, abnormal genetic or maternal serum biomarker test result, increased NT, and presence of open NTD in the post-partum follow-up. Results: : Of the 230 included singleton pregnancies, all of them resulted in healthy live births, except for two pregnancies terminated at 19 and 17 weeks of gestation due to severe skeletal dysplasia and an abnormal genetic test result compatible with Down syndrome, respectively. None of born babies had open NTD on post-partum follow-up. Five pregnancies were excluded from the final analysis, including a fetus with increased NT, two pregnancies with abnormal maternal serum biomarker test result (one of which confirmed to be trisomy 21), poor visualization due to maternal severe obesity in one case, and skeletal dysplasia diagnosed at 19 weeks of gestation in one of pregnancies. The median maternal age was 29 (range, 16 - 49) years. Median gestational age was 12 weeks + 5 days (range, 11 weeks + 2 days-13 weeks + 6 days). There were 68 cases per gestational week between 11 and 11 + 6 weeks, 84 cases between 12 and 12 + 6 weeks, and 73 cases between 13 and 13 + 6 weeks. Mean IT thickness was 1.94 - 0.73 mm (95% CI, 1.84 - 2.04) in all included pregnancies. This measurement was 1.57 - 0.34 mm (95% CI, 1.49 - 1.65) for fetuses between 11 and 11 + 6 weeks, 1.86 - 0.29 mm (95% CI, 1.80 - 1.92) for fetuses between 12 and 12 + 6 weeks, and 2.12 - 0.41 mm (95% CI, 2.02 - 2.22) for fetuses between 13 and 13 + 6 weeks. Kolmogorov-Smirnov analysis demonstrated normality of IT thickness distribution in the included cases (P > 0.10). Linear regression analysis demonstrated that there was a statistically significant positive linear association between IT thickness and gestational age (rs = 0.92, P = 0.021). Conclusions: We determined the normative values of IT thickness for the Iranian fetuses in a pilot study, which may be considered for NTD screening during the first-trimester in the national and international guidelines. It is important to determine normal measurements of different ultrasonographic and biochemistry markers nationally, since there are significant differences among various ethnicities. One should expect that IT thickness increases in a linear manner during first-trimester, and in case of its obliteration or absence open NTDs should be strongly suspected.

Quantification of plasma myo-inositol using gas chromatography–mass spectrometry

BackgroundMyo-inositol (MI) deficiency is associated with an increased risk for neural tube defects (NTDs), mental disorders and metabolic diseases. We developed a gas chromatography–mass spectrometry (GC–MS) method to detect MI in human plasma, which was accurate, relatively efficient and convenient for clinical application. MethodsAn external standard method was used for determination of plasma MI. Samples were analyzed by GC–MS after derivatization. The stable-isotope labeled internal standard approach was used to validate the method's accuracy. Alpha fetal protein (AFP) was detected by chemiluminescence immunoassay. ResultsThe method was validated by determining the linearity, sensitivity and recovery rate. There was a good agreement between the internal standard approach and the present method. The NTD-affected pregnancies showed lower plasma MI (P=0.024) and higher AFP levels (P=0.001) than control. Maternal MI level showed a better discrimination in spina bifida subgroup, while AFP level showed a better discrimination in anencephaly subgroup after stratification analysis. ConclusionsWe developed a sensitive and reliable method for the detection of clinical plasma MI, which might be a marker for NTDs screening, and established fundamental knowledge for clinical diagnosis and prevention for the diseases related to disturbed MI metabolism.

The International Prenatal Cardiology Collaboration Group - a new concept for global research study.

Congenital heart defects are among the most common congenital defects and contribute substantially to the mortality of newborns and young infants, in spite of well-developed medical and surgical treatments. It is estimated that the mortality of children with congenital heart defects in developing countries is as high as 20%, whereas the incidence of congenital heart defects is approximately 1/100 live births(1). Currently, there is an emphasis on early fetal screening for chromosomal abnormalities and neural tube defects, despite the fact that congenital heart defects are four times more frequent than chromosomal abnormalities and six times more frequent than neural tube defects(2). It should be noted that basic in-utero screening for heart defects is possible as early as the first trimester, which in some cases prompts further work-up and treatment(3). Throughout the world, second trimester screening remains the mainstay of prenatal diagnosis of cardiac anomalies. However, a comprehensive work-up for fetal heart defects can be associated with substantial psychological burden on the mother and her family. Moreover, the prevalence of misdiagnosis can be as high as 36%, thus prompting the need for further training and multidisciplinary team work(4). Furthermore, 33% of heart defects are accompanied by other anomalies(5). In 2006, the Polish Ministry of Health established a Register of Fetal Heart Defects (RFHD). The aim of this initiative was to enable cooperative gathering of data on fetal heart diseases, such as heart defects, significant cardiac arrhythmias, heart failure, heart ectopy and other significant heart conditions. RFHD is an internet database where the user can attach images, movies and other information to a given patient's file. Proofreading is performed by pediatric cardiologists from level C institutions – those that register at least 100 cases of heart defects annually. The data gathered so far have shown that heart defects are the weakest link in prenatal diagnosis. However, as physicians performing prenatal screening gain more experience, the number of diagnosed cases of congenital heart disease has grown steadily, both in Poland and worldwide(6). Analysis of data from Polish institutions confirms the need for multi-center and multidisciplinary collaboration in order to further develop screening for fetal heart defects, as well as to set goals for development of cardiac surgery of newborns. This type of collaboration contributes to both coordinated patient care and complex medical treatment, and is a scientific trend for the 21st century, helping to solve complicated scientific problems(7). Fortunately, the availability of current information and communication technologies allows partnership between different scientific centers around the world to be feasible(8). Therefore, we have established the International Prenatal Cardiology Collaboration Group (www.prenatalcardiology.org) with the aim of bringing together physicians of various specialties who are involved directly in the treatment of pregnant women and their fetuses, for further development of prenatal diagnosis. The IPCCG was established to join current worldwide efforts to improve the standard of care, management and outcomes for fetuses and neonates affected by congenital heart disease. The aim of our group is to establish research studies on a more expansive assembly of patients from different parts of the world. We plan to share our experience and create study protocols. Research to be conducted includes both retrospective and prospective studies, as well as metaanalyses. Through the IPCCG it may also be possible to gather a substantial amount of information on severe and very rare fetal heart defects, such as atrial aneurysms, ventricular aneurysms or coronary fistulas. This can enrich knowledge about these diseases, which can consequently improve patient outcome and contribute to the ever developing field of prenatal cardiology. Collaboration across centers and disciplines is also needed for other reasons. As published recently(9), treatment costs for rare heart conditions have been growing. Furthermore, it has been stressed that multidisciplinary cooperation can help decide which patents should be treated(9, 10). So far, there have been several established multi-center prenatal cardiology programs in Canada and the USA(11). Our aim was to create a similar program of collaboration among not only leading centers worldwide, but also with hospitals that want to further develop the fields of prenatal cardiology and prenatal diagnosis. The perspectives of each specialty are important in creating future standards of practice. We invite all physicians and non-physicians who are involved in prenatal care to collaborate with the IPCCG.

Sharad Gogate: Guidelines and Standards for Maternal Serum Screening for Down’s Syndrome, Neural Tube Defects, and Other Obstetric Problems

Maternal serum screening for birth defects began in the early 1970s with the discovery of serum alpha-fetoprotein in the second trimester. It was found to be increased in fetuses with only open neural tube defects [1]. The book explains the advent of the serum screening for open neural tube defects. Indeed, the use of multiples of median (MoMs) to report results was partly adopted because of vast interlaboratory differences [1]. However, now in today’s era of excellent USG machines and experts in the field of imaging, we have now shifted our focus from

Identification of Biomarkers by Proteomics for Prenatal Screening for Neural Tube Defects

Neural tube defect (NTD) is a serious congenital defect, but current methods for identifying NTD are limited. We used proteomic analysis of maternal serum to identify NTD-specific proteins whose levels differed between women with NTD fetuses (n = 50) and those with healthy fetuses (n = 40). Three NTD-specific protein peaks (8,130.6, 15,941.7, and 3,960.3 m/z) were identified using MALDI-TOF-mass spectrophotemetry, and were included in a diagnostic model developed using Biomarker Patterns software. The model used cut-offs for the relative intensity of the three peaks to indicate if a case had or did not have NTD. The model identified 48 of the 50 NTD cases and 36 of the 40 control cases correctly, resulting in the sensitivity of 96.0% (48/50) and the specificity of 90.0% (36/40). The diagnostic model was also tested on 105 clinical cases at high risk for NTD, as determined by having high alpha-fetoprotein levels, resulting in the sensitivity of 100% (101/101) and the specificity of 75.0% (3/4). Using the International Protein Index database, we identified proteins with a molecular mass of 8,130.6 Da as ADP-ribosylation factor 1 and a protein similar to cold agglutinin FS-1 antibody light-chain. The 15,941.7-Da peak corresponded to vitamin K3 protein, and the identity of the 3,960.3-Da protein was unclear. Thus, this study developed a diagnostic model consisting of the three peaks which may be indicators of NTD. This new assay may be at least as accurate for diagnosing NTD compared with the commonly used clinical test that assesses alpha-fetoprotein levels.

Identification of PCSK9 as a novel serum biomarker for the prenatal diagnosis of neural tube defects using iTRAQ quantitative proteomics.

To identify candidate serum molecule biomarkers for the non-invasive early prenatal diagnosis of neural tube defects (NTDs), we employed an iTRAQ-based quantitative proteomic approach to analyze the proteomic changes in serum samples from embryonic day (E) 11 and E13 pregnant rats with spina bifida aperta (SBA) induced by all-trans retinoic acid. Among the 390 proteins identified, 40 proteins at E11 and 26 proteins at E13 displayed significant differential expression in the SBA groups. We confirmed 5 candidate proteins by ELISA. We observed the space-time expression changes of proprotein convertase subtilisin/kexin type 9 (PCSK9) at different stages of fetal development, including a marked decrease in the sera of NTD pregnancies and gradual increase in the sera of normal pregnancies with embryonic development. PCSK9 demonstrated the diagnostic efficacy of potential NTD biomarkers [with an area under the receiver operating characteristic curve of 0.763, 95% CI: 065–0.88]. Additionally, PCSK9 expression in the spinal cords and placentas of SBA rat fetuses was markedly decreased. PCSK9 could serve as a novel molecular biomarker for the non-invasive prenatal screening of NTDs and may be involved in the pathogenesis of NTDs at critical periods of fetal development.

Rates of prenatal screening across health care regions in Ontario, Canada: a retrospective cohort study.

It is recommended that all pregnant women be offered screening for Down syndrome and open neural tube defects, but emerging prenatal tests that are not publicly insured may compromise access. We evaluated screening rates for publicly insured screening tests across health care regions in the province of Ontario and determined whether maternal, provider or regional characteristics are associated with screening uptake. We conducted a population-based retrospective cohort study involving pregnant women in Ontario who were at or beyond 16 weeks' gestation in 2007-2009. We ascertained prenatal screening rates using linked health administrative and prenatal screening datasets. We examined maternal, provider and regional characteristics associated with screening uptake. Rate ratios (RRs) were estimated. Of the 264 737 women included in the study, 62.2% received prenatal screening; uptake varied considerably by region (range 27.8%-80.3%). A greater proportion of women initiated screening in the first rather than the second trimester (50.0% v. 12.2%). Factors associated with lower screening rates included living in a rural area versus an urban area (adjusted rate ratio 0.64, 95% confidence interval [CI] 0.63-0.66), receiving first-trimester care from a family physician or midwife versus an obstetrician (adjusted rate ratio 0.91, 95% CI 0.90-0.92, and 0.40, 95% CI 0.38-0.43, respectively) and being in a lower income quintile (adjusted RR for lowest v. highest 0.95, 95% CI 0.94-0.96). Being an immigrant or a refugee was associated with higher screening rates. There were significant maternal, provider and regional differences in the uptake of prenatal screening across the province. With discrepancies expected to increase with the emergence of noninvasive prenatal tests paid for out of pocket by many women, policy efforts to reduce barriers to prenatal screening and optimize its availability are warranted.

RETIRED: Prenatal Screening, Diagnosis, and Pregnancy Management of Fetal Neural Tube Defects

This document has been archived because it contains outdated information. It should not be consulted for clinical use, but for historical research only. Please visit the journal website for the most recent guidelines.

Screening for abnormal placentation and adverse pregnancy outcomes with maternal serum biomarkers in the second trimester

Second trimester biomarkers were initially introduced with the intent of screening for neural tube defects and then subsequently for Down syndrome. It was soon realized that these markers can be indirect evidence of abnormal placentation and, therefore, can be used for screening for adverse pregnancy outcomes. Several new biomarkers have subsequently been described with conflicting findings regarding their efficiency for screening for adverse pregnancy outcomes. Although a biologically feasible mechanism has been proposed for the role of these biomarkers, they still fall short of an ideal screening test to be clinically useful.

Improving knowledge about prenatal screening options: can group education make a difference?

Objective: To determine if the addition of group education regarding maternal serum screening and diagnostic testing for aneuploidy and neural tube defects improves patient knowledge and affects the uptake of testing compared to individual education alone.Method: We conducted a prospective study of 443 obstetric patients to assess knowledge of prenatal testing options based on individual provider counseling (n = 331) or provider counseling with supplemental group education (n = 112). We used a chi-square test to compare the number of correct survey answers between the two groups.Results: There was no difference in baseline knowledge. Patients receiving group education showed a statistically significant improvement in knowledge. After initiation of group education, the uptake of maternal serum screening declined while the uptake of amniocentesis remained unchanged.Conclusion: Group education in addition to individual counseling to discuss prenatal testing options appears to be effective in improving knowledge compared to individual provider counseling alone. Improved knowledge may affect uptake of prenatal screening tests due to more informed decision making.