Search

The data collected by nation-wide study of noninvasive prenatal genetic testing (NIPT) for trisomy 21 from 21,610 pregnant women with advanced maternal age in Japan were reported. Among 188 NIPT-positive cases, 180 cases were true positive. The incidence of aneuploidy according to maternal age was estimated using a state-space model. Although, the frequency of trisomy increased exponentially with maternal age as previously reported, the maternal age-specific risk for trisomy 21 that was based on the clinical performance of NIPT was lower than the predicted risk in previous Western cohorts based on the data from invasive prenatal testing (Bayesian two-sided tail-area probability P = 0.0156). The empirical positive predictive value (PPV) of NIPT is likely to turn out higher than that of the theoretical PPV calculated from the sensitivity/specificity of the test and the incidence of trisomy 21 from this study.

Objective: The objective of our study was to describe our clinical experience in providing noninvasive prenatal testing (NIPT) for fetal aneuploidy to pregnant women, highlighting the degree of non-specific psychological distress., Methods: Data were collected from Japanese women who were offered and underwent NIPT after genetic counseling and control pregnant women who did not undergo NIPT as part of the Japan Environment and Children's Study Control A planning. The degree of mental distress was assessed using the Kessler 6 (K6) screening scale with a score of ≥10 indicating depression or anxiety disorder., Results: Among the 505 women who underwent NIPT because of advanced maternal age, 9.1% had a K6 score of ≥10. Compared with matched controls (n = 1010) adjusted for maternal age and gestational age, the NIPT group showed a trend toward higher K6 scores (odds ratio 1.44, 95% confidence interval 0.97-2.13, P = 0.07). Higher K6 scores were associated with women whose husbands were the primary decision makers during NIPT counseling (P = 0.06)., Conclusions: Women electing NIPT tend to have higher scores of depression/anxiety, and those with higher depression scores tended to defer the decision to their husbands., (© 2014 John Wiley & Sons, Ltd.)

Problem: In Japan, marital age and women's age at the first pregnancy are continuing to increase year by year. However, information concerning subsequent live birth rate according to maternal age and number of previous recurrent miscarriages is limited., Method of Study: We studied a total of 1250 unexplained patients suffering two or more consecutive miscarriages. We examined the live birth rate at the first pregnancy and the cumulative success rate for birth of at least one child after examination., Results: The live birth rate of women in their 40s was 58.1%, which was similar to that of women who were 35-39 years old (58.4%) at the first pregnancy, as found after examination. From logistic regression, women's age and the number of previous miscarriages independently decreased the live birth rate in subsequent pregnancies (p(s)) as well as cumulative pregnancies (p(c)), as follows: logit (p(s)) = 3.964 - 0.0652 x (age) - 0.408 x (previous number of miscarriages), logit(p(c)) = 6.806 - 0.1130 x (age) - 0.514 x (previous number of miscarriages)., Conclusion: The information concerning the live birth rate can be given to each patient before subsequent pregnancy.

Aim: This study is to investigate the role of amniocentesis for prenatal diagnosis before and after the beginning of noninvasive prenatal testing (NIPT) in Japan. Methods: We performed a retrospective analysis of genetic amniocentesis at mid‐trimester (15–20 gestational weeks) for fetal karyotype analysis at Nagoya City University between April 2006 and March 2020. The indications, test results, and the detection rate of fetal abnormal karyotype were compared before (phase 1, P1) and after (phase 2, P2) beginning of NIPT at April 2013. Results: A total of 2458 (P1: 1132, P2: 1326) amniocentesis were enrolled in this study. The most frequent indication was advanced maternal age in both phases (P1: 78.2% %, P2: 81.1%). In P2, 110 patients (8.3%) received amniocentesis after positive or nonreportable NIPT results. Other indications were fetal abnormal findings by ultrasounds (P1: 15.4%, P2: 17.7%), abnormal maternal serum screening results (P1: 8.0%, P2: 10%), previous child with fetal chromosome aberration (P1: 6.5%, P2: 3.5%), and translocation of either partner (P1:1.5%, P2: 2.1%). The detection rate for fetal chromosomal aberrations including all indications was significantly increased in P2 (15.9%, 95% CI 14.0–18.0) as compared to P1 (9.0%, 7.4–10.8). However, if the indication was only advanced maternal age, the positive detection rate kept low in both phases (P1: 5.2%, 3.7–7.1, P2: 4.2%, 2.9–5.9). Conclusion: Since the initiation of NIPT, the detection rate of fetal chromosomal abnormalities was higher in this study, suggesting that amniocentesis cannot be strongly recommended for advanced maternal age alone. [ABSTRACT FROM AUTHOR]

Aim: We aimed to evaluate the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of noninvasive prenatal testing (NIPT) in high‐risk pregnant women. Methods: Pregnant women who underwent GeneTech NIPT, the most commonly used NIPT in Japan, between January 2015 and March 2019, at Japan NIPT Consortium medical sites were recruited for this study. The exclusion criteria were as follows: pregnant women with missing survey items, multiple pregnancy/vanishing twins, chromosomal abnormalities in the fetus other than the NIPT target disease, and nonreportable NIPT results. Sensitivity and specificity were calculated from the obtained data, and maternal age‐specific PPV and NPV were estimated. Results: Of the 45 504 cases, 44 263 cases fulfilling the study criteria were included. The mean maternal age and gestational weeks at the time of procedure were 38.5 years and 13.1 weeks, respectively. Sensitivities were 99.78% (95% confidence interval [95% CI]: 98.78–99.96), 99.12% (95% CI: 96.83–99.76), and 100% (95% CI: 88.30–100) for trisomies 21, 18, and 13, respectively. Specificities were more than 99.9% for trisomies 21, 18, and 13, respectively. Maternal age‐specific PPVs were more than 93%, 77%, and 43% at the age of 35 years for trisomies 21, 18, and 13, respectively. Conclusion: The GeneTech NIPT data showed high sensitivity and specificity in the detection of fetal trisomies 21, 18, and 13 in high‐risk pregnant women, and maternal age‐specific PPVs were obtained. These results could provide more accurate and improved information regarding NIPT for genetic counseling in Japan. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: To investigate the rates of termination of pregnancy (TOP) for fetal chromosomal abnormalities and factors related to such parental decision in Japan.Methods: A multicenter retrospective cohort study of chromosomal abnormalities diagnosed before 22 weeks of gestation between April 2008 and March 2015. The pregnancy outcomes and parental decisions were investigated.Results: Among 931 fetuses with chromosome abnormalities, the total TOP rate was 75.1% (699/931). TOP rates were 89.3% (585/655) in autosomal aneuploidies and 40.8% (51/125) in sex chromosome aneuploidies. Trisomy 21 showed the highest TOP rate (93.8% [390/416]) followed by trisomy 18 (84.5% [163/193]) and trisomy 13 (71.9% [23/32]). Indications for karyotyping were related to a parental decision for TOP (p < 0.01): in cases of autosomal aneuploidy, with fetal abnormal ultrasound findings as the reference value, diagnoses made following positive results at non-invasive prenatal testing (adjusted odds ratio [OR]: 13.7, 95% confidence interval [CI] 4.07-45.9) and those because of advanced maternal age (adj. OR 2.91, 95% CI 1.15-7.35) were significantly more frequent.Conclusions: In Japan, pregnancies with fetal trisomy 21 are more likely to result in TOP when diagnosed in utero than any other chromosome anomaly. The indications for prenatal karyotyping strongly affect the decision to TOP. © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Aim Our purpose was to assess the background of couples who were undergoing non-invasive prenatal testing (NIPT) in Japan. Methods The characteristics of 2486 women who had visited Nagoya City University Hospital for NIPT were compared with Japanese Demographic Trends as controls. The questionnaire included items regarding the maternal and paternal age, maternal age at marriage, age at first live birth, and conception mode. Results Compared with the controls, the percentage of women who were 4 or more years older than their partners was larger in the NIPT group (11.8% vs 6.5%). The maternal age at marriage, age at first live birth, and the duration between marriage and first birth tended to be greater in the NIPT group (32.6 years vs 29.3 years, 36.9 years vs 30.4 years, and 3.6 years vs 2.4 years, respectively), and the percentage of women who underwent assisted reproductive technology tended to be higher in the NIPT group (35-39 years: 21.2% vs 7.5%, 40-45 years: 36.2% vs 12.6%), compared with the controls. Conclusion Knowing the specific backgrounds of couples who have undergone NIPT may be important for improving the quality of genetic counseling for NIPT. [ABSTRACT FROM AUTHOR]