Chromosomal microarray analysis in fetuses with high-risk prenatal indications: A retrospective study in China.

OBJECTIVE: The present study aimed to determine the diagnostic value of prenatal chromosomal microarray analysis (CMA) for fetuses with several indications of being at high risk for various conditions. MATERIALS AND METHODS: This retrospective analysis included 1256 pregnancies that were prenatally evaluated due to high-risk indications using invasive CMA. The indications for invasive prenatal diagnosis mainly included ultrasound anomalies, high-risk for maternal serum screening (MSS), high-risk for non-invasive prenatal tests (NIPT), family history of genetic disorders or birth defects, and advanced maternal age (AMA). The rate of clinically significant genomic imbalances between the different groups was compared. RESULTS: The overall prenatal diagnostic yield was 98 (7.8%) of 1256 pregnancies. Clinically significant genomic aberrations were identified in 2 (1.5%) of 132 patients with non-structural ultrasound anomalies, 36 (12.7%) of 283 with structural ultrasound anomalies, 2 (4.5%) of 44 at high-risk for MSS, 38 (26.6%) of 143 at high-risk for NIPT, 11 (3.8%) of 288 with a family history, and 7 (2.1%) of 328 with AMA. Submicroscopic findings were identified in 29 fetuses, 19 of whom showed structural ultrasound anomalies. CONCLUSION: The diagnostic yields of CMA for pregnancies with different indications greatly varied. CMA could serve as a first-tier test for structural anomalies, especially multiple anomalies, craniofacial dysplasia, urinary defects, and cardiac dysplasia. Our results have important implications for genetic counseling.

Effect of hyperemesis gravidarum on gestational diabetes mellitus screening.

OBJECTIVE: To clarify the effect of starvation due to hyperemesis gravidarum on the screening of gestational diabetes mellitus (GDM). METHODS: A retrospective study was undertaken of pregnant women who delivered at Tsukuba University Hospital, Japan, between October 1, 2010, and September 30, 2013. GDM screening was performed in the first trimester using the random blood glucose test with a cutoff value of 5.2mmol/L and in the second trimester using a 50-g glucose challenge test with a cutoff value of 7.8mmol/L. If the screening was positive, a 75-g oral glucose tolerance test was performed for a definite diagnosis. RESULTS: Among 2112 eligible women, 33 (1.6%) required hospitalization for hyperemesis; the remaining 2079 women formed the control group. In the first trimester, the positive GDM screening rate was significantly higher in the hyperemesis group than in the control group (13 [39.4%] vs 115 [5.5%]; P<0.001). Additionally, the positive predictive value was significantly lower in the hyperemesis group (23.1% vs 73.9%; P<0.001). In the second trimester, no significant differences were observed between groups. CONCLUSION: Hyperemesis gravidarum affects the positive GDM screening rate in the first trimester.

Preference-sensitive risk-cutoff values for prenatal-integrated screening test for Down syndrome.

OBJECTIVE: For a pregnant woman considering prenatal screening for early detection of Down Syndrome (DS), there are at least two major outcomes of interest: undetected DS live births and euploid procedure-related fetal losses. The risk-cutoff value of 1/270 has been commonly used for recommending a diagnostic test. The objective of this study was to assess the impact of women's preferences for different pregnancy outcomes on the optimal risk-cutoff values for integrated screening. METHOD: We built a Monte Carlo simulation model of 100,000 singleton second-trimester pregnancies to assess the probabilities of DS live births and euploid procedure-related fetal losses for various risk-cutoff values. To capture how undesirable some women may view an undetected DS live birth relative to a euploid procedure-related fetal loss, we used a ratio W1 : W2 of weights (penalties) assigned to these two adverse pregnancy outcomes. RESULTS: As the relative weight changes, the optimal risk-cutoff value changes significantly. CONCLUSION: A one-size-fits-all risk-cutoff value, such as 1/270, may not always be the best choice, depending on the preferences of women. Preference-sensitive risk-cutoff values for DS screening have the potential to improve the pregnancy outcomes and patient satisfaction.

An Overview on Prenatal Screening for Chromosomal Aberrations.

This article is a review of current and emerging methods used for prenatal detection of chromosomal aneuploidies. Chromosomal anomalies in the developing fetus can occur in any pregnancy and lead to death prior to or shortly after birth or to costly lifelong disabilities. Early detection of fetal chromosomal aneuploidies, an atypical number of certain chromosomes, can help parents evaluate their pregnancy options. Current diagnostic methods include maternal serum sampling or nuchal translucency testing, which are minimally invasive diagnostics, but lack sensitivity and specificity. The gold standard, karyotyping, requires amniocentesis or chorionic villus sampling, which are highly invasive and can cause abortions. In addition, many of these methods have long turnaround times, which can cause anxiety in mothers. Next-generation sequencing of fetal DNA in maternal blood enables minimally invasive, sensitive, and reasonably rapid analysis of fetal chromosomal anomalies and can be of clinical utility to parents. This review covers traditional methods and next-generation sequencing techniques for diagnosing aneuploidies in terms of clinical utility, technological characteristics, and market potential.