Undiagnosed hypothyroidism in pregnant women may adversely affect their fetuses; therefore, screening for thyroid deficiency during pregnancy may be warranted.

No abstract

Purpose:To determine whether maternal plasma cell–free DNA sequencing can effectively identify trisomy 18 and 13.Methods:Sixty-two pregnancies with trisomy 18 and 12 with trisomy 13 were selected from a cohort of 4,664 pregnancies along with matched euploid controls (including 212 additional Down syndrome and matched controls already reported), and their samples tested using a laboratory-developed, next-generation sequencing test. Interpretation of the results for chromosome 18 and 13 included adjustment for CG content bias.Results:Among the 99.1% of samples interpreted (1,971/1,988), observed trisomy 18 and 13 detection rates were 100% (59/59) and 91.7% (11/12) at false-positive rates of 0.28% and 0.97%, respectively. Among the 17 samples without an interpretation, three were trisomy 18. If z-score cutoffs for trisomy 18 and 13 were raised slightly, the overall false-positive rates for the three aneuploidies could be as low as 0.1% (2/1,688) at an overall detection rate of 98.9% (280/283) for common aneuploidies. An independent academic laboratory confirmed performance in a subset.Conclusion:Among high-risk pregnancies, sequencing circulating cell–free DNA detects nearly all cases of Down syndrome, trisomy 18, and trisomy 13, at a low false-positive rate. This can potentially reduce invasive diagnostic procedures and related fetal losses by 95%. Evidence supports clinical testing for these aneuploidies.

The possibility of improving the effectiveness of antenatal screening for Down's syndrome by measuring human chorionic gonadotrophin concen- IntroductionDown's syndrome is the most common congenital cause of severe mental retardation, with an incidence at birth of about 1-3 per 1000. The current method of antenatal screening is to select women for a diagnostic amniocentesis on the basis of advanced age. Age is, however, a poor basis for screening and has had little impact on the incidence at birth. With age as a basis for screening only about 30% of all Down's syndrome pregnancies can be detected by carrying out amniocentesis on the 5% of women most at risk-that is, those aged 36 years or greater-though in practice fewer than 15% of affected pregnancies are detected because fewer than half of these older women actually have amniocentesis.' Additional antenatal screening tests such as maternal serum measurements of c fetoprotein and unconjugated oestriol can increase the rate of detection to about 45% if the 5% of pregnant

Objective-To examine the relation between certain pregnancy complications and thyroid stimulating hormone (TSH) measurements in a cohort of pregnant women. Methods-TSH was measured in sera obtained from women during the second trimester as part of routine prenatal care. Information was then collected about vaginal bleeding, premature delivery, low birthweight, abruptio placentae, pregnancy induced hypertension, need for cesarean section, low Apgar scores, and fetal and neonatal death. Results-Among 9403 women with singleton pregnancies, TSH measurements were 6 mU/l or greater in 209 (2.2%). The rate of fetal death was significantly higher in those pregnancies (3.8%) than in the women with TSH less than 6 mU/l (0.9%, odds ratio 4.4, 95% confidence interval 1.9-9.5). Other pregnancy complications did not occur more frequently Conclusion-From the second trimester onward, the major adverse obstetrical outcome associated with raised TSH in the general population is an increased rate of fetal death. If thyroid replacement treatment avoided this problem this would be another reason to consider population screening. (J Med Screen 2000;7:127-130) Keywords: thyroid stimulating hormone; pregnancy; fetal death Although clinically apparent maternal hypothyroidism during pregnancy has long been known to be associated with both maternal and fetal complications, most of the studies documenting those problems have focused on patients in specialty or high risk clinics. The present study assesses the impact of maternal hypothyroidism in a cohort of pregnant women being managed in primary care settings. In 1991, our group reported thyroid stimulating hormone (TSH) measurements in a cohort of 2000 pregnant women whose sera were being obtained for -fetoprotein measurements at 15-18 weeks' gestation as part of routine care. 1 TSH measurements were at, or above, 6 mU/l in 49 of the women (2.4%). In six of these 49 women the thyroxine (T 4 ) and/or free T 4 measurements were suYciently abnormal (more than two standard deviations below the average) for clinical manifestations to be anticipated. It was not possible to gather individual information about health status in this cohort, because all identifiers were removed from the serum samples before the thyroid measurements were performed. Given the frequency of thyroid deficiency identified in this pregnancy population, it was decided that its possible impact on late pregnancy and delivery should be evaluated. To accomplish this, it was necessary to study a second, larger cohort of pregnant women. Materials and methodsThe Foundation for Blood Research oVers prenatal serum screening services for open neural tube defects and Down's syndrome to all primary care prenatal practices in Maine. The testing is generally performed between 15 and 18 weeks' gestation. Approximately two thirds of the women receiving prenatal care in Maine opt for those services.Between July 1990 and June 1992 the order form for the prenatal screening test contained a supplementary consent form, asking women...

The Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Initiative, established by the National Office of Public Health Genomics at the Centers for Disease Control and Prevention, supports the development and implementation of a rigorous, evidence-based process for evaluating genetic tests and other genomic applications for clinical and public health practice in the United States. An independent, non-federal EGAPP Working Group (EWG), a multidisciplinary expert panel selects topics, oversees the systematic review of evidence, and makes recommendations based on that evidence. This article describes the EGAPP processes and details the specific methods and approaches used by the EWG.

Maternal plasma contains circulating cell-free DNA fragments originating from both the mother and the placenta. The proportion derived from the placenta is known as the fetal fraction. When measured between 10 and 20 gestational weeks, the average fetal fraction in the maternal plasma is 10% to 15% but can range from under 3% to over 30%. Screening performance using next-generation sequencing of circulating cell-free DNA is better with increasing fetal fraction and, generally, samples whose values are less than 3% or 4% are unsuitable. Three examples of the clinical impact of fetal fraction are discussed. First, the distribution of test results for Down syndrome pregnancies improves as fetal fraction increases, and this can be exploited in reporting patient results. Second, the strongest factor associated with fetal fraction is maternal weight; the false negative rate and rate of low fetal fractions are highest for women with high maternal weights. Third, in a mosaic, the degree of mosaicism will impact the performance of the test because it will reduce the effective fetal fraction. By understanding these aspects of the role of fetal fraction in maternal plasma DNA testing for aneuploidy, we can better appreciate the power and the limitations of this impressive new methodology.

CRC is a common disease responsible for an estimated 52,000 deaths in the United States in 2007. In about 3% of newly diagnosed CRC, the underlying cause is a mutation in a MMR gene (Lynch syndrome) that can be reliably identified with existing laboratory tests. Relatives inheriting the mutation have a high (about 45% by age 70) risk of developing CRC. Evidence suggests these relatives will often accept testing and increased surveillance.