Parental counseling in trisomy 18: Novel insights in prenatal features and postnatal survival.

Data on the outcome of trisomy T18 (T18) when diagnosed during pregnancy are lacking. We performed a retrospective study of pregnancies complicated by T18 diagnosed at our center and a literature search for publications on the topic, with pooled estimates of survival rates at different gestational and post-natal ages. In our series, all the 60 patients included in the analysis had prenatally detected ultrasound anomalies, which were evidenced in the first trimester or at the second trimester scan in 73% of cases. In the continued pregnancies, ultrasound findings did not correlate with prenatal or post-natal outcome. A meta-analysis of available literature and our data showed that 48% [37-60%] of fetuses were live born, and among these 39% [11-72%] survived beyond 48 hr and 11% [3-21%] beyond 1 month. Our results confirm that prenatal ultrasound has high sensitivity in detection of T18 but is not predictive of the outcome of the continued pregnancies. The data on survival support that T18, even when antenatally diagnosed, cannot be considered as a uniformly lethal syndrome.

Cell-free DNA analysis in maternal plasma in cases of fetal abnormalities detected on ultrasound examination.

OBJECTIVE: To evaluate the utility of noninvasive prenatal testing using cell-free circulating fetal DNA for detection of the three main autosomal fetal trisomies in the setting of ultrasonographically identified fetal anomalies. METHODS: Nine hundred patients at risk for fetal aneuploidy with or without ultrasonography anomalies and who underwent invasive procedures were included in the study. Cell-free DNA analysis was performed by massive parallel sequencing during a multicenter, noninterventional, prospective study and the results were compared with a fetal karyotype. RESULTS: Among all 900 pregnancies, cell-free DNA identified 76 of 76 (100%) fetal Down syndrome, 22 of 25 (88%) trisomy 18, and 12 of 12 (100%) trisomy 13. In those with a normal ultrasonogram and normal cell-free DNA analysis, karyotype identified 2 of 483 (0.4%) additional aneuploidies other than trisomies 13, 18, and 21. In those with an abnormal ultrasonogram and a normal cell-free DNA analysis, there were 23 of 290 (7.9%) additional pathogenic karyotypes. These additional aneuploidies included sex chromosome abnormalities and triploidy. The rates of additional aneuploidies not identifiable by standard cell-free DNA screening in the two groups is significantly different at P<.01. CONCLUSION: In women with fetal abnormalities by ultrasonography, the rate of pathogenic chromosome abnormalities missed by cell-free DNA was 8%. Noninvasive prenatal testing should not be offered to women with fetal abnormalities because a negative result is falsely reassuring. LEVEL OF EVIDENCE: III.

Repeated Measurement of Crown-Rump Length at 9 and 11-13 Weeks' Gestation: Association with Adverse Pregnancy Outcome.

AIMS: To clarify whether ultrasonographic measurements of crown-rump length (CRL) at 11-13 weeks - based on the number of gestational days determined using the CRL at 9 weeks - can predict fetal prognosis. METHODS: A prospective cohort study was conducted to evaluate the association between fetal growth in the first trimester and fetal prognosis. Fetal growth in the first trimester was evaluated measuring CRLs at 11-13 weeks determined using the CRL at 9 weeks. The subjects were divided into short CRL (s-CRL) and normal CRL (n-CRL). The prognoses were compared between the two groups. RESULTS: A total of 126 patients in the s-CRL group and 1,130 patients in the n-CRL group were enrolled. Abortion occurred in 7.1% of s-CRL and 0.9% of n-CRL subjects (p < 0.001). Among the patients with chromosomal abnormalities, the incidence of trisomy 18 was significantly greater in s-CRL (4.8 vs. 0.1%, p < 0.001). Without abortion, placental weight, frequency of small for gestational age (SGA) and birth weight in s-CRL were significantly higher than those in the n-CRL group (12.8 vs. 3.6%, p < 0.001). CONCLUSIONS: Measuring CRL at 9 weeks is useful for determining gestational days prior to measuring CRL at 11-13 weeks. After reconfirming the gestational age at 9 weeks, measuring CRL at 11-13 weeks is useful for predicting the incidence of trisomy 18 as well as SGA later in pregnancy.

Prenatal detection of structural cardiac defects and presence of associated anomalies: a retrospective observational study of 1262 fetal echocardiograms.

OBJECTIVE: The aim of this study is to document the detection of fetal congenital heart defect (CHD) in relation to the following: (1) indication for referral, (2) chromosomal and (3) extracardiac abnormalities. METHOD: All fetal echocardiograms performed in our institution from 2007 to 2011 were reviewed retrospectively. Indication for referral, cardiac diagnosis based on the World Health Organization International Classification of Diseases tenth revision criteria and the presence of chromosomal and extracardiac defects were recorded. RESULTS: Of 1262 echocardiograms, 287 (22.7%) had CHD. Abnormal anatomy scan in pregnancies originally considered to be at low risk of CHD was the best indicator for detecting CHD (91.2% of positive cardiac diagnoses), compared with other indications of family history (5.6%) or maternal medical disorder (3.1%). Congenital anomalies of the cardiac septa comprised the largest category (n = 89), within which atrioventricular septal defects were the most common anomaly (n = 36). Invasive prenatal testing was performed for 126 of 287 cases, of which 44% (n = 55) had a chromosomal abnormality. Of 232 fetuses without chromosomal abnormalities, 31% had an extracardiac defect (n = 76). CONCLUSIONS: Most CHDs occur in pregnancies regarded to be at low risk, highlighting the importance of a routine midtrimester fetal anatomy scan. Frequent association of fetal CHD and chromosomal and extracardiac pathology emphasises the importance of thorough evaluation of any fetus with CHD.

First trimester screening for other trisomies than trisomy 21, 18, and 13.

OBJECTIVE: The objective of the study was to evaluate the performance of first trimester combined screening in cases of placental/fetal, mosaic or non-mosaic, autosomal trisomy other than trisomy 21, 18, or 13, and in cases of aneuploidy for a marker chromosome with focus on biochemical markers. METHOD: We identified 66 cases in three large databases including 357 675 pregnancies from October 2003 to January 2014. RESULTS: Seventy-seven percent of the 66 cases were screened positive at the combined first trimester screening (cFTS) for trisomy 21 or trisomy 18 or 13. The multiple of median (MoM) of Pregnancy Associated plasma protein A (PAPP-A) of the different aneuploidy groups ranged from 0.2 to 0.5 MoM, whereas the MoM of maternal serum free - ß - human chorionic gonadotropin (FßhCG) was approximately 1.0 MoM. The exceptions being 0.2 MoM for cases involving chromosome 8 (n = 7) and 0.5 MoM for cases involving chromosome 9 (n = 3). The nuchal translucency MoM was approximately 1.0 MoM in all aneuploidy groups. CONCLUSION: The cFTS program for trisomy 21, 18, and 13 is also sensitive to a broad range of rare chromosomal trisomies and chromosomal mosaicisms, primarily because of a strong detection capacity of PAPP-A MoM.

Facial markers in second- and third-trimester fetuses with trisomy 18 or 13, triploidy or Turner syndrome.

OBJECTIVE: To examine the effectiveness of nasal bone (NB) evaluation (including NB length (NBL)), prenasal thickness (PT) measurement, the PT:NBL ratio and the prefrontal space ratio (PFSR) in the identification of fetuses with trisomy 18 or 13, triploidy or Turner syndrome. METHODS: This was a retrospective study using stored midsagittal two-dimensional images of the facial profile of fetuses with trisomy 18 or 13, triploidy or Turner syndrome in the second and third trimesters. For images of acceptable quality, measurements were obtained of NBL (where NB was present), PT, the PT:NBL ratio and PFSR, and these measurements were compared with previously published normal ranges. RESULTS: The search of databases identified 189 fetuses that met the study criteria: 132 (69.8%) with trisomy 18, 40 (21.2%) with trisomy 13, 10 (5.3%) with triploidy and seven (3.7%) with Turner syndrome. The NB was either absent or its measurement was below the 5(th) centile in 67 (50.8%), 20 (50.0%), five (50.0%) and two (28.6%) of the fetuses with trisomy 18, trisomy 13, triploidy and Turner syndrome, respectively. The PT measurement was above the 95(th) centile in 24 (18.2%), six (15.0%), one (10.0%) and one (14.3%) of the affected fetuses, respectively. The PFSR was abnormal in 72 (54.5%), 29 (72.5%), seven (70%) and four (57.1%) of the cases and the PT:NBL ratio was above the 95(th) centile or the nasal bone was absent in 72 (54.5%), 20 (50.0%), six (60.0%) and four (57.1%) cases, respectively. CONCLUSION: Although each of the facial markers considered provides some useful information in screening for trisomy 18, trisomy 13, triploidy and Turner syndrome, the performance of none of the markers appears to be as good as that in screening for trisomy 21.

Facial profile markers in second- and third-trimester fetuses with trisomy 18.

OBJECTIVES: To evaluate nasal bone length (NBL), maxilla-nasion-mandible (MNM) angle, fetal profile (FP) line, prenasal thickness (PT), prenasal thickness to nasal bone length (PT:NBL) ratio and prefrontal space ratio (PFSR) as markers of trisomy 18 in the second and third trimesters of pregnancy. METHODS: The NBL, MNM angle, FP line, PT, PT:NBL ratio and PFSR were measured retrospectively from stored two-dimensional images or three-dimensional volumes of trisomy-18 fetuses, and were compared with our previously reported normal ranges for euploid fetuses. Additional ultrasound findings were noted at initial routine second-trimester scan and at subsequent advanced ultrasound examination performed after referral for karyotyping. RESULTS: A total of 43 trisomy-18 fetuses were included in the analysis. At initial examination, median gestational age was 21 + 2 weeks. NBL and PT were correlated with gestational age (P < 0.001), but the other markers were not. Mean NBL, MNM angle, PT, PT:NBL ratio and PFSR were 3.76 mm, 16.67°, 4.25 mm, 1.39 and 0.87, respectively. The FP line was zero (normal) in 53.7% of cases and negative (abnormal) in 46.3%. All markers were significantly associated with trisomy 18, with the PT:NBL ratio yielding the highest detection rate (88.4%) followed by NBL (83.7%), MNM angle (56.4%), FP line (46.3%), PT (27.9%) and the PFSR (20.5%) (for a 5% false-positive rate for the continuous variables). Various combinations of the four best markers (NBL, FP line, MNM angle and PT:NBL ratio) yielded detection rates of between 72% and 95%. Structural anomalies were not detected in 22% of fetuses at the initial scan and in 2% at the advanced scan. CONCLUSIONS: The PT:NBL ratio and NBL are robust second- and third-trimester markers for trisomy 18. A negative FP line has a 0% false-positive rate and the potential to differentiate between trisomy 18 and Down syndrome, as in the latter the FP line is often positive. No major anomaly was observed at the initial scan in about a quarter of trisomy-18 fetuses, underlining the role of second-trimester facial marker evaluation.

Retrospective cohort of trisomy 18 (Edwards syndrome) in southern Brazil.

CONTEXT AND OBJECTIVE: Trisomy 18 (T18), or Edwards syndrome, is a chromosomal disease characterized by a broad clinical picture and a poor prognosis. Our aim was to describe clinical, radiological and survival data of a cohort of patients prenatally diagnosed with T18. DESIGN AND SETTING: Retrospective single cohort in the Fetal Medicine Service of Hospital Materno Infantil Presidente Vargas (HMIPV). METHODS: All sequential patients with T18 registered at the Fetal Medicine Service of HMIPV between January 2005 and September 2013 were considered. We gathered their clinical, radiological and survival data and used the Kaplan-Meier test for survival analysis. RESULTS: Ten patients were diagnosed with T18, of whom seven (70%) were female. The majority (90%) were referred due to malformations seen on ultrasound. The mean gestational age at the first evaluation was 25.5 weeks. At karyotyping, the defects were considered multiple in only four patients (40%). All the fetuses presented full trisomy of chromosome 18. The main abnormality observed was congenital heart disease (n = 7). Intrauterine death occurred in half of the patients (50%). All live patients (n = 5) were born through cesarean section presenting low weight and low Apgar scores. The median length of survival after birth was 18 days. CONCLUSIONS: T18 is associated with a high risk of fetal and neonatal death. The majority of the patients present major malformations identified through ultrasound, such as congenital heart defects, which could help in identifying such cases prenatally.

Screening for chromosomal abnormalities by first trimester combined screening and noninvasive prenatal testing.

PURPOSE: To examine combined first trimester screening (FTS), noninvasive prenatal testing (NIPT) and a two-step policy that combines FTS and NIPT in screening for aneuploidy. MATERIALS AND METHODS: Retrospective study involving 21,052 pregnancies where FTS was performed at the Praxis Praenatal.de in Duesseldorf, Germany. In each case, the sum risk of trisomy 21, 18 and 13 was computed. We assumed that NIPT detects 99 %, 98 %, 90 % and 99 % of cases with trisomy 21, 18, 13 and sex chromosomal abnormalities and that the false-positive rate is 0.5 %. The following screening policies were examined: NIPT or FTS with sum risk cut-offs of 1 in 50 and 1 in 250 in all patients or a two-step-policy with FTS in all patients followed by NIPT in the intermediate sum risk group. For the intermediate risk group, sum risk cut-offs of 1 in 50 and 1 in 1000 and 1 in 150 and 1 in 500 were used. RESULTS: There were 127, 34, 13 and 15 pregnancies with trisomy 21, 18, 13 and sex chromosomal abnormalities. 23 fetuses had other chromosomal abnormalities with an increased risk for adverse outcome that are not detectable by NIPT. 20,840 pregnancies were classified as normal as ante- and postnatal examinations did not show any signs of clinically significant chromosomal abnormalities. FTS with a sum risk cut-off of 1 in 50 and 1 in 250 detects 81 % and 91 % for all aneuploidies. NIPT detects 88 % of the respective pregnancies. The 2-step approach with sum risk cut-offs of 1 in 50 and 1 in 1000 detects 94 % of all aneuploidies. With sum risk cut-offs of 1 in 150 and 1 in 500, the detection rate is 93 %. CONCLUSION: A 2-step policy with FTS for all patients and NIPT in the intermediate risk group results in the highest detection rate of all aneuploidies.

A new model for providing cell-free DNA and risk assessment for chromosome abnormalities in a public hospital setting.

OBJECTIVE: Cell-free DNA (cfDNA) offers highly accurate noninvasive screening for Down syndrome. Incorporating it into routine care is complicated. We present our experience implementing a novel program for cfDNA screening, emphasizing patient education, genetic counseling, and resource management. STUDY DESIGN: Beginning in January 2013, we initiated a new patient care model in which high-risk patients for aneuploidy received genetic counseling at 12 weeks of gestation. Patients were presented with four pathways for aneuploidy risk assessment and diagnosis: (1) cfDNA; (2) integrated screening; (3) direct-to-invasive testing (chorionic villus sampling or amniocentesis); or (4) no first trimester diagnostic testing/screening. Patients underwent follow-up genetic counseling and detailed ultrasound at 18-20 weeks to review first trimester testing and finalize decision for amniocentesis. RESULTS: Counseling and second trimester detailed ultrasound were provided to 163 women. Most selected cfDNA screening (69%) over integrated screening (0.6%), direct-to-invasive testing (14.1%), or no screening (16.6%). Amniocentesis rates decreased following implementation of cfDNA screening (19.0% versus 13.0%, P < 0.05). CONCLUSION: When counseled about screening options, women often chose cfDNA over integrated screening. This program is a model for patient-directed, efficient delivery of a newly available high-level technology in a public health setting. Genetic counseling is an integral part of patient education and determination of plan of care.

Biparietal diameter at 11 to 13 weeks' gestation in fetuses with holoprosencephaly.

OBJECTIVE: Studies have suggested that fetuses with holoprosencephaly have smaller head size, demonstrated as early as the first trimester. However, the majority of these cases were diagnosed in the second or third trimesters. The aim of this study was to investigate biparietal diameter (BPD) measured at 11 to 13 weeks' gestation in fetuses with holoprosencephaly. METHODS: This was a retrospective study in which BPD was measured at 11 to 13 weeks in 34 fetuses with prenatal diagnosis of holoprosencephaly and 7775 unaffected controls. BPD values were converted into multiples of the expected median (MoM) after adjustment for crown-rump length and maternal characteristics. RESULTS: The median gestational age at the BPD recording was 12.6 (interquartile range 12.3-13.0) weeks. The nuchal translucency was increased (≥3mm) in 58.8% of the cases. Aneuploidy was confirmed in 73.5% of the cases; the commonest was trisomy 13 (50.0%). BPD values at 11 to 13 weeks were below the 5(th) centile in 32.4% of cases and below the 50(th) centile in 67.6%. BPD MoM values were significantly smaller than in the control group (median: 0.98; interquartile range: 0.90-1.06 vs 1.00; 0.96-1.04 MoM, p = 0.03). CONCLUSION: Fetuses with holoprosencephaly have a smaller BPD in the first trimester. This property may be useful in early diagnosis.

First-trimester screening for trisomies 21, 18 and 13 by ultrasound and biochemical testing.

OBJECTIVE: To examine the performance of screening for trisomies 21, 18 and 13 at 11-13 weeks' gestation using specific algorithms for these trisomies based on combinations of fetal nuchal translucency thickness (NT), fetal heart rate (FHR), ductus venosus pulsatility index for veins (DV PIV), and serum free ß-human chorionic gonadotropin (ß-hCG), pregnancy-associated plasma protein A (PAPP-A), placental growth factor (PLGF) and α-fetoprotein (AFP). METHODS: Model-based estimates of screening performance were produced for the distribution of maternal ages in England and Wales in 2011, and prospectively collected data on fetal NT, FHR, DV PIV, ß-hCG, PAPP-A, PLGF and AFP from singleton pregnancies undergoing aneuploidy screening. RESULTS: In screening by NT, FHR, free ß-hCG and PAPP-A, using specific algorithms for trisomy 21 and trisomies 18 and 13 at the risk cutoff of 1:100, the estimated detection rate (DR) was 87.0% for trisomy 21 and 91.8% for trisomies 18 and 13, at a false-positive rate (FPR) of 2.2%. Addition of PLGF, AFP and DV PIV increased the DR to 93.3% for trisomy 21 and 95.4% for trisomies 18 and 13 and reduced the FPR to 1.3%. CONCLUSIONS: Effective screening for trisomies can be achieved using specific algorithms based on NT, FHR, DV PIV, ß-hCG, PAPP-A, PLGF and AFP.

Frontomaxillary facial angle measurement in screening for trisomy 18 at 11 + 0 to 13 + 6 weeks of pregnancy: a double-centre study.

OBJECTIVE: The aim of this study was to evaluate the effectiveness of prenatal screening for trisomy 18 with the use of the frontomaxillary facial angle (FMF angle) measurement. MATERIAL AND METHODS: The study involved 1751 singleton pregnancies at 11-13 + 6 weeks, examined between 2007 and 2011. Serum PAPP-A and free beta-hCG levels were assessed, and crown-rump length, nuchal translucency, and FMF angle were measured in all patients. 1350 fetuses with known follow-up were included in the final analysis. RESULTS: Highly significant (P < 0.01) negative correlation between the CRL and the FMF angle was found. There were 30 fetuses with trisomy 18. FMF angle was highly significantly larger (P < 0.0001) in fetuses with trisomy 18 as compared to chromosomally normal fetuses. Two models of first trimester screening were compared: Model 1 based on maternal age, NT, and first trimester biochemistry test (DR 80-85% and FPR 0.3-0.6%), and Model 2 = Model 1 + FMF angle measurement (DR 87.3-93.3% and FPR 0.8-1.3%). CONCLUSIONS: The use of FMF angle measurement increases the effectiveness of the screening for trisomy 18. Introduction of the FMF angle as an independent marker for fetal trisomy 18 risk requires further prospective research in large populations.

A very rare entity of diabetes insipidus associated with Edwards syndrome.

Edwards syndrome is the second most commonly seen trisomy. It was first described by John Hamilton Edwards in 1960. Although most cases result in termination or foetal loss, live births have been documented in 5%. Edwards syndrome is characterized by multisystem anomalies, of which holoprosencephaly (HPE) is observed in 4-8% of cases. The clinical findings correspond to the degree of HPE malformation. Convulsions and endocrinopathies are among the severe clinical findings. The most common endocrinopathies are central diabetes insipidus (DI), hypothyroidism, hypocortisolism and growth hormone deficiency. The coexistence of holoproencephaly and DI in Edwards syndrome was discussed under the light of literature.

Thymic-thoracic ratio in fetuses with trisomy 21, 18 or 13.

OBJECTIVES: To assess thymic size expressed as the thymic-thoracic ratio (TT-ratio) in fetuses with trisomy 21, 18 or 13. METHODS: The TT-ratio, the quotient of the anteroposterior thymic and the intrathoracic mediastinal diameter, was measured in 65 trisomic fetuses between 15 and 36 weeks' gestation, including 30 cases with trisomy 21, 19 with trisomy 18 and 16 with trisomy 13. In addition these 65 fetuses were divided into two groups, according to whether they showed growth that was appropriate-for-gestational age (AGA) (n = 39) or intrauterine growth restriction (IUGR) (n = 26). Measurements were compared with reference ranges from 302 normal fetuses. RESULTS: The TT-ratio was low in 27.7% (n = 18) of the 65 fetuses with aneuploidy. In comparison to normal fetuses (mean TT-ratio, 0.44), those with trisomy 18 or 21 had a significantly smaller TT-ratio (mean, 0.38 (P < 0.001) and 0.40 (P < 0.05), respectively), while those with trisomy 13 did not (mean, 0.43). These values were not as low as those observed previously in fetuses with del.22q11, suggesting a mechanism involving accelerated thymic involution rather than primary thymic hypoplasia. Furthermore, the TT-ratio was significantly lower than normal in both AGA (P < 0.05) and IUGR (P < 0.001) fetuses. CONCLUSION: Fetuses with trisomy 18 or 21, but not trisomy 13, have a small thymus, suggesting accelerated thymic involution in utero. IUGR may contribute to the reduced thymic size in trisomy 18 fetuses. Trisomy 21 fetuses seem to have additional factors leading to a small thymus which could be a possible confirmation of the reduced immune response observed in fetuses and neonates with Down syndrome.

A mixture model of nuchal translucency thickness in screening for chromosomal defects: validation of a single operator dataset.

OBJECTIVE: (1) To validate the mixture model in a single operator dataset and (2) to compare the detection rates for fetal chromosomal defects obtained from the mixture model with those obtained from either the delta nuchal translucency (NT) or log multiple of the median (MoM) approach. METHODS: Database query, viable singletons [crown-rump length (CRL) 45-84 mm corresponding to 11-13(+6) weeks], December 1997 to November 2006, examined by Adam Gasiorek-Wiens, the statistical mixture model was applied. RESULTS: Seventy-four of 4171 were lost to follow-up (1.8%), 4097 singleton pregnancies included trisomy 21 (n = 34, 0.8%), trisomy 18 (n = 20, 0.5%), trisomy 13 (n = 8, 0.2%), Turner syndrome (n = 9, 0.2%) and other chromosomal abnormalities (n = 14, 0.3%). The main findings are that (1) the log-transformed NT measurements follow a mixture of two Gaussian distributions and (2) the criteria to apply either the delta-NT or log MoM models are not met. In the normal group, the majority of NT measurements were dependent on the CRL, a small group showed a median independent of the CRL. In the abnormal group it was the opposite. For a 5% false-positive rate (FPR), the trisomy 21 detection rate was 83%. CONCLUSIONS: The use of the mixture model in a single operator dataset produces results compatible with the original study. The mixture model has thus been validated.

Prenatal diagnosis of 18q-syndrome: a case of fetal mosaicism with a normal karyotype in chorionic villi.

We report a case of fetoplacental discrepancy with normal karyotype on chorionic villi and deletion of the long arm of chromosome 18 on amniotic fluid. Cytogenetic tests were repeated because of a short corpus callosum on ultrasound examination. This 18q-syndrome has been reported to be associated with poor neurodevelopmental outcome.

First-trimester risk assessment for trisomies 21 and 18 in twin pregnancy.

OBJECTIVE: Our objective was to describe performance of first-trimester combined risk assessment in twin pregnancies. STUDY DESIGN: Twin pregnancies that underwent risk assessment in our ultrasound unit from 2003-2006 were included. Adjusted risks for trisomies 21 and 18 that were based on age, nuchal translucency (NT), and biochemistry were provided for each twin. Detection rates for Down syndrome and trisomy 18 were calculated for age/NT, and age/NT/biochemistry at a screen-positive rate of 5% of pregnancies. RESULTS: Five hundred thirty-five pregnancies were included. Median maternal age was 34 years, with 47% of women > or = 35 years old. There were 7 fetuses in 6 dichorionic pregnancies with Down syndrome and 3 fetuses in 3 pregnancies with trisomy 18. For a 5% false-positive rate, age/NT identified 83.3% of Down syndrome and 66.7% of Trisomy 18 pregnancies. Adding biochemistry resulted in 100% detection rates for both conditions. CONCLUSION: The addition of biochemistry may enhance first-trimester risk assessment in twin pregnancies. Further studies with larger numbers of affected pregnancies are needed.