First-trimester Aneuploidy Screening Research Articles

Implementation of a National Nuchal Translucency Education and Quality Monitoring Program

In 2004, leaders in first-trimester aneuploidy screening and a multidisciplinary group of experts established the Nuchal Translucency Quality Review Program, a national program to standardize education, credentialing, and quality monitoring of nuchal translucency. Since its inception, the program has credentialed more than 6,600 physician and ultrasonographer participants and collected more than 2.4 million nuchal translucency measurements. Ongoing quality monitoring is conducted through statistical analysis comparing the distribution and standard deviation of participants' nuchal translucency measurements against those obtained from a standard referent curve. Results of these analyses are distributed to participants quarterly and are used to track each participant's performance and to trigger performance improvement activities or mandatory remediation. This program could serve as a template for future education and credentialing programs that include partnerships with academic leaders, national professional organizations, and industry.

New directions in the prediction of pre-eclampsia

Pre-eclampsia remains an important worldwide cause of maternal and perinatal morbidity and mortality. Improved prediction of those destined to develop this condition would allow for timely initiation of prophylactic therapy, appropriate antenatal surveillance and better targeted research into preventive interventions. This paper reviews recent research into strategies for the prediction of pre-eclampsia, including the use of maternal risk factors, mean maternal arterial pressure, ultrasound parameters and biomarkers. The most promising strategies involve multiparametric approaches, which use a variety of individual parameters in combination, as has been established in first-trimester aneuploidy screening. The paper concludes with a discussion of the issues around the introduction of such testing into clinical practice.

First trimester detection of trisomy 16 using combined biochemical and ultrasound screening

What's already known about this topic? Four previously reported cases of trisomy 16 have shown reduced levels of pregnancy‐associated plasma protein‐A during first trimester screening for trisomy 21. Isolated increases in free β human chorionic gonadotrophin and nuchal translucency were observed in these four cases.What does this study add? During first trimester screening for aneuploidy, we observed a further 28 cases of trisomy 16, all of which had reduced levels of pregnancy‐associated plasma protein‐A consistent with previous reported cases. Increased free β human chorionic gonadotrophin and increased nuchal translucency were not a consistent finding in our 28 cases.

Reference Values for the Right and Left Fetal Choroid Plexus at 11 to 13 Weeks

The purpose of this study was to establish reference values for the length, area, and circumference of the right and left fetal choroid plexus at 11 to 13 weeks with respect to the fetal biparietal diameter and to compare the right to the left side. We conducted a prospective study on 114 fetuses at 11 to 13 weeks undergoing first-trimester screening for aneuploidy and structural fetal abnormalities. After the establishment of the fetal situs, the plane of the "butterfly" was obtained on all fetuses, from which the length, area, and circumference of both the right and left choroid plexus were obtained and the right and left sides compared. Using a paired t test, analysis of variance, scatterplots, and linear and logarithmic fittings, reference ranges and charts for the length, area, and circumference of the choroid plexus were then formulated according to their relationship to the fetal biparietal diameter. P < .05 was considered statistically significant. Reference values for the length, area, and circumference of the fetal choroid plexus, with respect to the fetal biparietal diameter, were established. There was a statistically significant difference between the right and left sides for all parameters, with all measurements statistically greater on the left side (P < .0001). Reference values for the length, area, and circumference of the fetal choroid plexus at 11 to 13 weeks are presented. These may prove to be of clinical importance in the early screening for central nervous system abnormalities. In addition, the statistically significant difference between the right and left sides may be an early sign of "developmental" laterality.

Efficiency of First‐Trimester Uterine Artery Doppler, A‐Disintegrin and Metalloprotease 12, Pregnancy‐Associated Plasma Protein A, and Maternal Characteristics in the Prediction of Preeclampsia

The purpose of this study was to estimate the efficiency of first-trimester uterine artery Doppler, A-disintegrin and metalloprotease 12 (ADAM12), pregnancy-associated plasma protein A (PAPP-A), and maternal characteristics in the prediction of preeclampsia. We conducted a prospective cohort study of patients presenting for first-trimester aneuploidy screening between 11 and 14 weeks' gestation. Maternal serum ADAM12 and PAPP-A levels were measured by an immunoassay, and mean uterine artery Doppler pulsatility indices were calculated. Outcomes of interest included preeclampsia, early preeclampsia (defined as requiring delivery at <34 weeks' gestation), and gestational hypertension. Logistic regression analysis was used to model the prediction of preeclampsia using ADAM12 multiples of the median (MoM), PAPP-A MoM, and uterine artery Doppler pulsatility index MoM, either individually or in combination. The sensitivity, specificity, and area under the receiver operating characteristic curves were used to compare the screening efficiency of the models using nonparametric U statistics. Among 578 patients with complete outcome data, there were 54 cases of preeclampsia (9.3%) and 13 cases of early preeclampsia (2.2%). Median ADAM12 levels were significantly lower in patients who developed preeclampsia compared to those who did not (0.81 versus 1.01 MoM; P = .04). For a fixed false-positive rate of 10%, ADAM12, PAPP-A, and uterine artery Doppler parameters in combination with maternal characteristics identified 50%, 48%, and 52% of patients who developed preeclampsia, respectively. Combining these first-trimester parameters did not improve the predictive efficiency of the models. First-trimester ADAM12, PAPP-A, and uterine artery Doppler characteristics are not sufficiently predictive of preeclampsia. Combinations of these parameters do not further improve their screening efficiency.

The association between gestational diabetes mellitus and first trimester aneuploidy screening markers

To establish whether maternal serum first trimester concentrations of PAPP-A and free hCGβ are altered in pregnancies that subsequently are diagnosed by an oral glucose tolerance test (OGTT) with gestational diabetes mellitus (GDM). Over the period 2009 and 2011, the results for women who had first trimester screening for aneuploidy were matched with those having an oral glucose tolerance test at 22-26 weeks for suspected GDM. Free hCGβ, PAPP-A and NT MoMs were compared amongst the group having an OGTT with confirmed GDM and those in which GDM was not confirmed. A second comparison group consisted of all non-aneuploidy singleton pregnancies in which no OGTT was performed. During the three-year period, 27,660 singleton pregnancies were screened of which 7429 cases had an OGTT of which 870 cases were classed as GDM by WHO criteria. There was a significant 7-9% reduction in both PAPP-A and free hCGβ MoM in the GDM group compared with either the OGTT non-GDM group or the remaining pregnancies with no known risk factors for evidence of GDM. There was no difference in the NT measurements. First trimester concentrations of PAPP-A and free hCGβ are reduced in pregnancies that subsequently are diagnosed with GDM and may be useful in further screening algorithms for this disorder although the sensitivity alone is quite poor.

Nearly a Third of Abnormalities Found After First-Trimester Screening Are Different Than Expected

Objective This study aimed to assess the efficacy of first-trimester aneuploidy screening in a single clinical setting. Methods Maternal age, nuchal translucency, and maternal serum levels of pregnancy-associated plasma protein A and free beta human chorionic gonadotrophin comprised first-trimester risk assessment for Down syndrome and trisomies 13/18. Means, screen positive rates, detection rates, and predictive values were calculated for Down syndrome and trisomies 13/18. Results Of the 23 329 first-trimester screenings, 6.3% were screen positive: 5.7% for Down syndrome only, 0.4% for trisomies 13/18 only, and 0.3% for Down syndrome and trisomies 13/18. An abnormal karyotype was present in 3.9% of screen positives for Down syndrome, 13.8% of screen positives for trisomies 13/18, and 45.9% of screen positives for both Down syndrome and trisomies 13/18. Of the 97 pregnancies found to have an abnormal karyotype, 29.9% had chromosome abnormalities other than trisomy 13, 18, or 21, with expected clinical outcomes ranging from likely benign to uniformly lethal. Conclusion As expected, first-trimester screening is effective for detecting aneuploidy for chromosomes 13, 18, and 21; however, a significant number of chromosomally abnormal pregnancies initially identified by first-trimester screening have a different karyotype. With the possible exception of 47,XYY and 45,X, the dataset suggested that these different chromosome complements were likely to be randomly distributed. Nevertheless, prior to diagnostic testing, prospective parents should be counseled concerning the possibility of a chromosome abnormality other than the trisomies 13, 18, or 21. © 2013 John Wiley & Sons, Ltd.

Combined screening for open spina bifida at 11-13 weeks using fetal biparietal diameter and maternal serum markers

Screening at 11-13 weeks with ultrasound biparietal diameter (BPD) can detect half of open spina bifida cases. Maternal serum α-fetoprotein (AFP) levels at 15-19 weeks are increased 3- to 4-fold, in open spina bifida. We assessed whether combined screening using BPD, AFP, and other serum markers at 11-13 weeks would increase detection. Maternal AFP levels were measured on serum stored at 11-13 weeks in 44 open spina bifida and 182 unaffected pregnancies, and results were expressed in multiples of the median (MoM) for gestational age. All samples had been measured for free β-human chorionic gonadotropin (β-hCG) and pregnancy-associated plasma protein (PAPP)-A. A multivariate Gaussian model was used to predict screening performance from the serum data and BPD measurements on 80 cases, including 36 previously published. The median AFP level in cases was 1.201 MoM, significantly higher than in unaffected pregnancies (P < .01, 1 tail). The median free β-hCG was significantly reduced to 0.820 MoM (P < .02), but the median PAPP-A was similar in cases and controls. Modeling predicted the following: BPD alone would detect 50% of cases for a 5% false-positive rate or 63% for 10%; adding AFP increases detection by 2%; and a combined test with BPD, AFP, and free β-hCG detects 58% for 5% or 70% for 10%. Combining AFP and BPD with free β-hCG as part of first-trimester aneuploidy screening would also allow early detection about two-thirds of cases with open spina bifida.

The impact of utilization of early aneuploidy screening on amniocenteses available for training in obstetrics and fetal medicine

First-trimester aneuploidy screening has high detection rates and low false-positive rates. Their use as well as the implementation of non-invasive prenatal testing may affect specialty training in prenatal diagnosis procedures. Descriptive study of first-trimester aneuploidy screening and amniocentesis in an obstetric training program. Screening methods were tracked from their introduction in 2004 through 2011. The volume of amniocentesis procedures from 2000 to 2011 was evaluated. First-trimester screening tests increased from 283 to 1225 between 2005 and 2011, whereas genetic amniocenteses declined from 460 to 168 during the same period. The percent of older women who chose a first-trimester screen test rose from 12.7% to 44.2% First-trimester screening options reduce genetic amniocenteses available for training. Fetal medicine and general obstetrics training programs need to evaluate their clinical experience and determine whether simulation training methods are needed for education.

Nearly a third of abnormalities found after first‐trimester screening are different than expected:10‐year experience from a single center

This study aimed to assess the efficacy of first-trimester aneuploidy screening in a single clinical setting. Maternal age, nuchal translucency, and maternal serum levels of pregnancy-associated plasma protein A and free beta human chorionic gonadotrophin comprised first-trimester risk assessment for Down syndrome and trisomies 13/18. Means, screen positive rates, detection rates, and predictive values were calculated for Down syndrome and trisomies 13/18. Of the 23 329 first-trimester screenings, 6.3% were screen positive: 5.7% for Down syndrome only, 0.4% for trisomies 13/18 only, and 0.3% for Down syndrome and trisomies 13/18. An abnormal karyotype was present in 3.9% of screen positives for Down syndrome, 13.8% of screen positives for trisomies 13/18, and 45.9% of screen positives for both Down syndrome and trisomies 13/18. Of the 97 pregnancies found to have an abnormal karyotype, 29.9% had chromosome abnormalities other than trisomy 13, 18, or 21, with expected clinical outcomes ranging from likely benign to uniformly lethal. As expected, first-trimester screening is effective for detecting aneuploidy for chromosomes 13, 18, and 21; however, a significant number of chromosomally abnormal pregnancies initially identified by first-trimester screening have a different karyotype. With the possible exception of 47,XYY and 45,X, the dataset suggested that these different chromosome complements were likely to be randomly distributed. Nevertheless, prior to diagnostic testing, prospective parents should be counseled concerning the possibility of a chromosome abnormality other than the trisomies 13, 18, or 21.

Marcadores bioquímicos de cromosomopatía, pregnancy associated plasma proteína-A y fracción β de hormona gonadotropina coriónica humana, como predictores de alteraciones del crecimiento fetal

ObjectiveThe principal aim of this study was to analyze the possible association between prenatal biochemical markers used in prenatal screening for aneuploidy, (pregnancy associated plasma protein A [PAPP-A] and beta-human chorionic gonadotropin) and low birth weight. MethodsWe performed a retrospective cohort study of patients who underwent first trimester screening for aneuploidies. The first and fifth percentiles in our population were calculated for each main variable. We used the chi-square test to assess the relationship between the distinct variables. ResultsA total of 987 patients were included. There were three stillbirths (0.3%) and 10 midtrimester miscarriages (1%). Of 974 live births, body weight was under the 10th percentile (p) in 84 (8.5%) and was under the third percentile in 21 (2.1%). There was a statistically significant association between low maternal serum PAPP-A and low birth weight. ConclusionOur results demonstrate that the biochemical markers used in prenatal screening for aneuploidy also predict low birth weight and can be used in clinical practice to provide an early diagnosis and improve the management of this entity.

First-Trimester Prediction of Birth Weight

To determine whether the parameters used in first-trimester screening for aneuploidies contribute significantly to the prediction of birth weight. In this retrospective cohort study (n = 4110), nuchal translucency (NT), free β-chorionic gonadotropin (fβ-hCG), and pregnancy-associated plasma protein-A (PAPP-A) blood concentrations were measured between 11 + 0 and 13 + 6 weeks. Multiple pregnancies, chromosomal anomalies, major fetal defects, and deliveries before 24 weeks were excluded. NT (0.95 versus 0.98 multiples of the expected median [MoM], p < 0.001) and PAPP-A (0.93 versus 1.06 MoM, p = 0.005) were significantly lower in small-for-gestational-age (SGA) newborns (<10th percentile) than the unaffected group, but not fβ-hCG (0.89 versus 0.93 MoM, p = 0.113). NT was significantly higher (1.03 versus 0.98 MoM, p < 0.001) in the large-for-gestational-age (LGA) group (>90th percentile) compared with the unaffected group, and biomarkers did not differ. After controlling for gestational age, maternal weight, smoking status, ethnicity, and fetal sex, first-trimester markers contributed to the prediction of birth weight in a multiple linear model but did not significantly improved the prediction of SGA and LGA compared with maternal characteristics alone. Parameters used in first-trimester screening for aneuploidies contribute to the prediction of birth weight but their clinical utility to detect women at risk of SGA or LGA baby is limited.

Assessment of Foetal DNA in Maternal Blood – A Useful Tool in the Hands of Prenatal Specialists

Over the last few years, first trimester screening between 11+ and 13+ weeks of gestation has become one of the most important ultrasound examinations in pregnancy, as it allows physicians to predict several pregnancy complications including pre-eclampsia or pre-term birth. Screening for trisomies 21/18 and 13 using maternal and gestational age, foetal nuchal translucency, and maternal serum biochemistry was formerly the main reason for first trimester screening. However, today this is only one part of the overall examination. In the near future, the analysis of foetal DNA obtained from maternal blood will be used to supplement first trimester screening for aneuploidy or even replace current screening methods. In this review we show how prenatal medicine specialists can use foetal DNA analysis.

Temporal effects of maternal and pregnancy characteristics on serum pregnancy‐associated plasma protein‐A and free β‐human chorionic gonadotropin at 7–14 weeks' gestation

The aim of this study was to investigate gestational age-dependent effects of racial origin, smoking status and mode of conception on maternal serum levels of free β-human chorionic gonadotropin (β-hCG) and pregnancy-associated plasma protein-A (PAPP-A) at 7-14 weeks' gestation. This was an analysis of data from prospective first-trimester combined screening for aneuploidies in singleton pregnancies, with β-hCG and PAPP-A measured at 7 + 1 to 14 + 3 weeks' gestation. We included 27,908 pregnancies from three centers in the U.K. and 125,461 pregnancies from 22 centers in Denmark, all with known normal fetal karyotype or resulting in the birth of a phenotypically normal neonate. Multiple regression modelling of log10 -transformed marker concentrations was used to produce log10 multiple of the median (MoM) values for free β-hCG and PAPP-A and to examine pregnancy characteristics that have significant effects on marker concentrations. Serum free β-hCG and PAPP-A concentrations were significantly affected by gestational age, maternal weight, racial origin, parity, smoking and mode of conception. There were significant gestational age-dependent effects attributed to Afro-Caribbean race, smoking and conception through in-vitro fertilization (IVF) on PAPP-A and free β-hCG levels. In women of Afro-Caribbean race there was a weekly increase in PAPP-A of 5.3% and in free β-hCG of 1.8%. In smokers there was a weekly decrease in PAPP-A of 2.4% and in free β-hCG of 1.6%. In cases of IVF conceptions there was a weekly increase in PAPP-A of 4.5% and in free β-hCG of 4.6%. Serum free β-hCG and PAPP-A concentrations at 7-14 weeks' gestation are affected by several pregnancy characteristics. The effects of Afro-Caribbean race, smoking and IVF conception change with gestational age.

First‐trimester prediction of preterm birth using ADAM12, PAPP‐A, uterine artery Doppler, and maternal characteristics

The objective of this study was to estimate the efficiency of first-trimester a disintegrin and metalloprotease 12 (ADAM12), pregnancy-associated plasma protein A (PAPP-A), uterine artery Doppler, and maternal characteristics in the prediction of preterm birth (PTB). This was a prospective cohort study of patients presenting for first-trimester aneuploidy screening. Maternal serum ADAM12 and PAPP-A levels were measured by immunoassay, and mean uterine artery Doppler pulsatility indices were calculated. The primary outcome was PTB <34 weeks' gestation, and the secondary outcome was PTB <37 weeks' gestation. Logistic regression was used to model the prediction of PTB using ADAM12, PAPP-A, uterine artery Doppler, and maternal characteristics, individually and in combination. Sensitivity, specificity, and area under the receiver-operating characteristic curves were compared between models. Of 578 patients, 36 (6.2%) delivered <34 weeks, and 78 (13.5%) delivered <37 weeks. For a 20% fixed false positive rate, ADAM12, PAPP-A, and uterine artery Doppler identified 58%, 52%, and 62% of patients with PTB <34 weeks and 42%, 48%, and 50% of patients with PTB <37 weeks, respectively. Combining these first-trimester parameters did not improve the predictive efficiency of the models. First-trimester ADAM12, PAPP-A, and uterine artery Doppler are each modestly predictive of PTB; however, combinations of these parameters do not further improve their screening efficiency.

First‐trimester diagnosis of cleft lip and palate using three‐dimensional ultrasound

To determine whether systematic examination of primary and secondary palates using three-dimensional (3D) ultrasound aids in the identification of orofacial clefts in the first trimester. 3D datasets were acquired prospectively from women undergoing first-trimester ultrasound screening for aneuploidy. Multiplanar mode display was used for offline analysis of (1) the primary palate in the coronal plane at the base of the retronasal triangle and (2) the secondary palate by virtual navigation in the axial plane. In addition, 3D datasets from three fetuses with a cleft palate diagnosed in the first trimester were retrospectively identified and included randomly in the study group. A total of 240 3D datasets from 237 pregnancies (including three sets of twins), 89% of which were obtained transabdominally and 11% transvaginally, were examined independently by three operators. The quality of the 3D datasets was classified subjectively as good, fair and poor in 76%, 20% and 4% of cases, respectively. Seven fetuses had an orofacial cleft; all involved both the primary palate and the secondary palate. Using 3D offline analysis, the primary palate was classified as intact in 229 (95%), cleft in nine (4%) and indeterminate in two (1%). Seven of the nine fetuses suspected to have a cleft affecting the primary palate had the cleft confirmed at birth or at postmortem examination (false-positive rate 0.9% (2/231)). The secondary palate was classified as intact in 217 (90%), cleft in six (3%) and indeterminate in 17 (7%). Clefts of the secondary palate were confirmed in all six suspected cases and missed in one, which was diagnosed at 16 weeks. The visualization rate was affected by the quality of the 3D dataset (P < 0.001) and gestational age at evaluation (P < 0.01). In our series, all cases of clefting of the primary palate and 86% of cases involving the secondary palate were visualized using 3D ultrasound with a satisfactory false-positive rate. Virtual navigation of the fetal palate using the multiplanar mode display seems to be useful in the diagnosis of clefting in the first trimester.

A Mixture Model of Ductus Venosus Pulsatility Index in Screening for Aneuploidies at 11–13 Weeks’ Gestation

Objective: To assess the value of ductus venosus pulsatility index for veins (DV PIV) in screening for aneuploidies at 11–13 weeks’ gestation. Methods: Fetal DV PIV was measured in singleton pregnancies undergoing first-trimester screening for aneuploidies. In euploid (n = 44,756) and aneuploid (202 cases of trisomy 21, 72 cases of trisomy 18 and 30 cases of trisomy 13) fetuses, DV PIV was best described by a mixture model of distributions. Performance of screening for aneuploidies by DV PIV alone and in combination with fetal nuchal translucency (NT) thickness and serum free β-hCG and PAPP-A was estimated. Results: In euploid pregnancies there was a bimodal distribution of DV PIV with a dominant crown-rump length (CRL)-dependent part, accounting for around 97% of cases in Caucasians and around 93% in Afro-Caribbeans, and a smaller CRL-independent distribution. In aneuploidies the dominant part was the CRL-independent distribution, which accounted for around 85% cases of trisomies 21 and 18 and 70% of cases of trisomy 13. In screening for trisomy 21 by maternal age, NT and biochemistry at a risk cutoff of 1 in 100, the detection rate was 89.7% and false positive rate was 2.74%; with addition of DV PIV, the values were 93.5 and 1.63%, respectively. Conclusions: Measurement of DV PIV improves the performance of first-trimester combined test for aneuploidies.

Improved diagnostic accuracy by using secondary ultrasound markers in the first‐trimester screening for trisomies 21, 18 and 13 and Turner syndrome

The aim of this study was to examine the effectiveness of a combination of parameters at first-trimester screening for fetal aneuploidies, including ultrasound assessment of the nasal bone (NB), blood flow in the ductus venosus (DV) and flow across the tricuspid valve. Screening for aneuploidy was carried out in 4172 singleton pregnancies between January 2006 and December 2010. Diagnostic accuracy of combined screening [inclusive of maternal age, fetal nuchal translucency (NT) thickness and maternal serum free beta-human chorionic gonadotropin and pregnancy-associated plasma protein A] and of secondary ultrasound markers [NB, tricuspid regurgitation (TR) and Doppler studies of the DV] obtained at the same visit was assessed using the receiver operating characteristic (ROC) curve analysis. The individual areas under the ROC curves of NT, NB, DV or TR ranged between 0.7 and 0.8, representing acceptable discrimination. The area under the ROC curve of combined first-trimester screening was 0.87, whereas the addition of secondary ultrasound markers increased the area under the curve to 0.92, which represents excellent discrimination. At a risk cutoff of 1 : 275, the detection rate for aneuploidy increased from 87% to 92% (z statistic = 1.78, P = 0.076), and the false positive rate decreased from 5.3% to 4.8%. The addition of secondary ultrasound markers (NB, DV and TR) to combined first-trimester screening showed a tendency toward improved accuracy of the screening.

Efficiency of first‐trimester growth restriction and low pregnancy‐associated plasma protein‐A in predicting small for gestational age at delivery

To evaluate the efficiency of first-trimester fetal growth restriction (FGR), low pregnancy-associated plasma protein A (PAPP-A), and their combination for predicting small for gestational age (SGA) at delivery. Retrospective cohort study of women undergoing first-trimester aneuploidy screening. Fetal crown-rump lengths (CRLs) were at 10 to 14 weeks' gestation and converted to gestational age adjusted Z-scores. Low PAPP-A was defined as levels<5th percentile for GA. Receiver-operating characteristic curves were used to assess screening efficiencies. Among 3269 pregnancies meeting the inclusion criteria 185 (5.7%) infants were SGA. CRL Z-score< -1.0 standard deviation was identified as the optimal definition of early FGR. Using either CRL Z-score< -1.0 standard deviation or PAPP-A<5th percentile had the highest sensitivity (33%) with a specificity of 82.1% when screening for SGA. Using a combination resulted in an increased association (adjusted odds ratio 4.23[confidence interval 1.37-13.03]) at the expense of significantly reduced sensitivity (3.13%). First-trimester FGR and PAPP-A<5th percentile are associated with delivery of an SGA infant. Neither of these parameters or the combination of the two are sufficient powerful predictors of SGA to be clinically useful screening tools.

Factors Influencing Visualization of the Intracranial Translucency during First-Trimester Screening for Aneuploidy

Neural tube defects occur in 1/2000 live births. Imaging of the intracranial translucency (IT) during first-trimester screening has been proposed as an early screen for open neural tube defects (ONTD). This study evaluates visualization of the IT and factors influencing its visualization during first-trimester ultrasound screening for aneuploidy. Ultrasound images for patients undergoing first-trimester screening for aneuploidy from January 1, 2009, through July 31, 2009, were reviewed for IT visualization, defined as an intracranial translucency parallel to the nuchal translucency. Second-trimester ultrasounds and delivery records were reviewed for the presence of fetal ONTD. The IT was visualized in 74.8% of 759 gestations studied at a mean gestational age of 12 weeks, 5 days. Among gestations where the IT was visualized, we found a larger crown-rump length, lower maternal weight, and more fetuses in the supine position (p < 0.0001). Predictive models for visualization of the IT were formulated based on these factors. The IT can be visualized in the majority of patients in the standard midsagittal plane used for measurement of the nuchal translucency. Visualization is significantly associated with crown-rump length, gestational age, maternal weight, and fetal position. Visualization of the IT is feasible.