The importance of hyperhomocysteinemia, birth defects, and vascular diseases has been the subject of intense investigations. The polymorphic MTHFR mutations (C677T and A1298C) cause mild hyperhomocysteinemia, especially in homozygotes for C677T, but also in compound heterozygotes for C677T/A1298C. The subject of this report is the frequency of the polymorphic mutations in the MTHFR gene C677T, C1298A, and newly discovered mutation G1793A, as well as the association with MTRR polymorphic site A66G in different ethnic groups. Four ethnic groups were studied: African-Americans, Caucasians, Hispanics, and Ashkenazi Jews. There are statistically significant differences in the frequency of these alleles in the different populations studied, which impacts compound heterozygosity for such alleles in these populations. DNA samples obtained from the blood of healthy individuals of African-Americans, Hispanics, and Caucasians from south Texas were analyzed and compared to those obtained from Ashkenazi Jewish individuals. The polymorphic site, the G1793A allele, is least frequent among Ashkenazi individuals, 1.3%, compared to 6.9% among Caucasians (P = 0.001), 5.8% among Hispanics (P = 0.012), and 3.1% among African-Americans. The MTRR polymorphic site shows the lowest allele frequency among Hispanics, 28.6%, compared to 34% among African-Americans, 43.1% among Ashkenazi Jews (P = 0.002), and 54.4% among Caucasians (P < 0.0001). Statistically significant differences in allele frequencies of C677T and C1298A polymorphisms were also observed in these populations. Compound heterozygosity for multiple polymorphic alleles may play a role in birth defects and vascular diseases.

Urinary gonadotropin peptide (UGP; beta-core fragment), a major metabolite of human chorionic gonadotropin (hCG), was shown recently to be markedly elevated in Down syndrome pregnancy between 19 and 22 weeks of gestation. To confirm and extend this finding, we obtained maternal urine and matching maternal serum samples from 14 cases of Down syndrome and six other aneuploidies between 17 and 21 weeks of gestation. UGP was measured in all these samples and in 91 singleton control urines. Results were corrected for urinary creatinine level and expressed as multiples of the control median (MOM). hCG levels were assayed in all serum samples from the cases and compared with previously established reference values. The median UGP level in Down syndrome cases was 5.34 MOM (range 2.71-12.57); 88 per cent of the values were above the 95th centile of control levels after modelling. The median maternal serum hCG level for the same cases was 2.20 MOM (range 0.84-3.40); 36 per cent of the values were above the 95th centile. The level of UGP in every case including all other aneuploidies was higher than the comparable maternal serum hCG level. Elevated UGP measurements are strongly associated with fetal Down syndrome during the second trimester and could contribute to improved Down syndrome screening protocols that are more accessible and less expensive than are currently available.

Purpose: To assess nuchal translucency measurements that were performed as part of routine prenatal screening for Down syndrome. Methods: Collect ultrasound measurements of nuchal translucency and crown rump length provided by individual sonographers over a 6-month period to six North American prenatal screening laboratories, along with the laboratory's nuchal translucency interpretation in multiples of the median. For sonographers with 50 or more observations, compute three nuchal translucency quality measures (medians, standard deviations, and slopes), based on epidemiological monitoring. Results: Altogether, 23,462 nuchal translucency measurements were submitted by 850 sonographers. Among the 140 sonographers (16%) who submitted more than 50 observations, 76 (54%) were found to have all three quality measures in the target range. These 140 sonographers collectively accounted for 14,210 nuchal translucency measurements (61%). The most common single measure to be out of range was nuchal translucency multiples of the median, found for 29 of the 140 sonographers (21%). Nuchal translucency (NT) is defined as the collection of fluid behind the fetal neck occurring in the first trimester of pregnancy. 1-3 When measured and interpreted correctly, it is the most discriminatory marker for Down syndrome that has been reported in a routine setting. Univariately, NT measurements can identify about 60% of Down syndrome pregnancies in the first trimester at a 5% false-positive rate. 4 Detection increases to between 80% and 85%, when NT is combined with first trimester biochemical measurements of pregnancyassociated plasma protein-A (PAPP-A) and human chorionic gonadotropin (the intact, total, or free-␤ subunit forms). 4 When NT measurements are incorporated into the integrated test (NT and PAPP-A measurements in the first trimester) and the quadruple test (␣-fetoprotein, unconjugated estriol, human chorionic gonadotropin and dimeric inhibin-A in the second trimester), 85-90% detection is achievable at a false-positive rate of 2% or less. 5,6 Acquiring the skill to properly measure NT requires specialized training and oversight. 7 Recognizing this, several national and international programs have been established to train and qualify sonographers, and also to assess their ability to consistently and accurately quantify the NT thickness. 8 -11 The hands-on performance training is usually evaluated through still images submitted to one, or a panel of, expert sonographers. Several research trials using NT measurements have shown that such training, although necessary, is not sufficient to assure reproducibility of absolute measurements among sonographers. For example, both the Serum, Urine and Ultrasound Screening Study (SURUSS) 5 and First and Second Trimester Evaluation of Risk (FASTER) study 12 found that use of sonographer-specific reference data (medians) resulted in improved screening performance.In the current study, information was sought from screening laboratories regarding how they deal with NT measurements

The increased hCG levels as well as the slightly lower AFP and unconjugated E3 levels may contribute to the higher Down syndrome screen-positive rate in this IVF singleton population. These results may be due to the number of embryos transferred, the maternal hormonal environment of the IVF process, or other factors. Pregnancies conceived by IVF may be twice as likely to have a positive maternal serum screening test. As additional data are collected, corrected standards should be determined.