Maki Hyodo

Cell-free Fetal DNA in Maternal Circulation after Amniocentesis

After amniocentesis, 5–20% of patients have evidence of fetal-maternal hemorrhage as indicated by increases in maternal serum α-fetoprotein (1)(2)(3)(4)(5) or by the Betke–Kleihauer test (6)(7)(8). The Betke–Kleihauer test can differentiate fetal from maternal erythrocytes by the relative resistance of hemoglobin F-containing cells to acid elution, and it is the most popular method of diagnosing and assessing the severity of fetal-maternal hemorrhage (9). The reliability of this test has been questioned, however, because numerous sources of error are associated with it (10). These sources of error possibly contribute to the wide variation in the reported incidence of fetal-maternal hemorrhage; a more accurate method of assessing fetal-maternal hemorrhage is therefore required in the clinical setting of rhesus D-negative pregnant women. The discovery of cell-free fetal DNA in maternal serum and plasma has opened a new avenue for noninvasive prenatal diagnosis and has provided a useful marker of complicated pregnancies (11)(12)(13)(14)(15)(16). The analysis of fetal DNA in maternal serum or plasma has afforded diagnoses of fetal rhesus D status (12) and single-gene disorders (13), as well as the determination of fetal gender (14)(15). Cell-free DNA may be liberated directly from the fetal-placental interface into the maternal circulation (16), or it may be transferred into the maternal …

Fetal cell-free DNA fraction in maternal plasma is affected by fetal trisomy.

The purpose of this noninvasive prenatal testing (NIPT) study was to compare the fetal fraction of singleton gestations by gestational age, maternal characteristics and chromosome-specific aneuploidies as indicated by z-scores. This study was a multicenter prospective cohort study. Test data were collected from women who underwent NIPT by the massively parallel sequencing method. We used sequencing-based fetal fraction calculations in which we estimated fetal DNA fraction by simply counting the number of reads aligned within specific autosomal regions and applying a weighting scheme derived from a multivariate model. Relationships between fetal fractions and gestational age, maternal weight and height, and z-scores for chromosomes 21, 18 and 13 were assessed. A total of 7740 pregnant women enrolled in the study, of which 6993 met the study criteria. As expected, fetal fraction was inversely correlated with maternal weight (P<0.001). The median fetal fraction of samples with euploid result (n=6850) and trisomy 21 (n=70) were 13.7% and 13.6%, respectively. In contrast, the median fetal fraction values for samples with trisomies 18 (n=35) and 13 (n=9) were 11.0% and 8.0%, respectively. The fetal fraction of samples with trisomy 21 NIPT result is comparable to that of samples with euploid result. However, the fetal fractions of samples with trisomies 13 and 18 are significantly lower compared with that of euploid result. We conclude that it may make detecting these two trisomies more challenging.

Current status of non‐invasive prenatal testing in Japan

The purpose of this study was to report the 3‐year experience of a nationwide demonstration project to introduce non‐invasive prenatal testing (NIPT) of maternal plasma for aneuploidy, and review the current status of NIPT in Japan.

A survey on awareness of genetic counseling for non-invasive prenatal testing: The first year experience in Japan

The purpose of this study is to summarize the results from a survey on awareness of genetic counseling for pregnant women who wish to receive non-invasive prenatal testing (NIPT) in Japan. As a component of a clinical study by the Japan NIPT Consortium, genetic counseling was conducted for women who wished to receive NIPT, and a questionnaire concerning both NIPT and genetic counseling was given twice: once after pre-test counseling and again when test results were reported. The responses of 7292 women were analyzed. They expressed high satisfaction with the genetic counseling system of the NIPT Consortium (94%). The number of respondents who indicated that genetic counseling is necessary for NIPT increased over time. Furthermore, they highly valued genetic counseling provided by skilled clinicians, such as clinical geneticists or genetic counselors. The vast majority (90%) responded that there was sufficient opportunity to consider the test ahead of time. Meanwhile, women who received positive test results had a poor opinion and expressed a low-degree satisfaction. We confirmed that the pre-test genetic counseling that we conducted creates an opportunity for pregnant women to sufficiently consider prenatal testing, promotes its understanding and has possibilities to effectively facilitate informed decision making after adequate consideration. A more careful and thorough approach is considered to be necessary for women who received positive test results.

Fetal cell-free DNA fraction in maternal plasma for the prediction of hypertensive disorders of pregnancy

OBJECTIVE The purpose of this study is to compare the fetal fractions during non-invasive prenatal testing (NIPT) in singleton pregnancies according to gestational age and maternal characteristics to evaluate the utility of this parameter for the prediction of pregnancy complications including gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDP). STUDY DESIGN This study was a multicenter prospective cohort study. The present data were collected from women whose NIPT results were negative. The relationships between the fetal fractions and the gestational age, maternal weight and height, and incidences of miscarriage, preterm delivery, and pregnancy complications including GDM, HDP and placental abruption were assessed. RESULTS A total of 5582 pregnant women with verified NIPT negative results were registered in the study. The demographic characteristics of the study populations were statistically analyzed, and the women with HDP tended to have a low fetal fraction in samples taken during early gestation. The area under the curve (AUC) in a receiver operating characteristic curve (ROC) analysis was 0.608 for women with HDP. CONCLUSION A low fetal fraction on NIPT might be correlated with future HDP. However, predicting HDP during early pregnancy in women with a low fetal fraction might be difficult.