Evaluation of the clinical performance of noninvasive prenatal testing at a Japanese laboratory.

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.

Current status of non-invasive prenatal testing in Japan.

AIM: 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. METHODS: Tests were conducted to detect aneuploidy in high-risk pregnant women, and adequate genetic counseling was provided. The clinical data, test results, and pregnancy outcomes were recorded. We discuss the problems of NIPT on the basis of published reports and meta-analyses. RESULTS: From April 2013 to March 2016, 30 613 tests were conducted at 55 medical sites participating in a multicenter clinical study. Among the 30 613 women tested, 554 were positive (1.81%) and 30 021 were negative (98.1%) for aneuploidy. Of the 289, 128, and 44 women who tested positive for trisomies 21, 18, and 13, respectively, and underwent definitive testing, 279 (96.5%), 106 (82.8%), and 28 (63.6%) were determined to have a true-positive result. For the 13 481 women with negative result and whose progress could be traced, two had a false-negative result (0.02%). The tests were performed on the condition that a standard level of genetic counseling be provided at hospitals. CONCLUSION: Here, we report on the 3-year nationwide experience with NIPT in Japan. It is important to establish a genetic counseling system to enable women to make informed decisions regarding prenatal testing. Moreover, a welfare system is warranted to support women who decide to give birth to and raise children with chromosomal diseases.

Factors affecting parental decisions to terminate pregnancy in the presence of chromosome abnormalities: a Japanese multicenter study.

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.

Management of the occiput posterior presentation: a single institute experience.

AIM: We have examined the risk factors and management processes of the persistent occiput posterior (pOP) position by analyzing medical records from our hospital. MATERIAL AND METHODS: Medical records and delivery notes from January 2007 to December 2009 were reviewed and 103 patients were identified as having the pOP position during active labor. A total of 1054 patients who had occiput anterior (OA) deliveries were used as control. RESULTS: There was no significant difference in population background between the pOP and control groups. Fifty-eight (56%) cases of pOP were identified before the birth of the fetal head whereas 45 were found to be in pOP at the birth. Among these cases identified as pOP before the birth, 30 (52%) patients underwent an attempt to rotate pOP to OA manually. A total of 14 (47%) attempts were successful and delivered OA vaginally. Of 16 cases whose attempts failed, five (31%) had cesarean delivery and 11 had vaginal OP delivery. The overall cesarean rate in this group was 16.7%. Twenty-eight patients who did not have any corrective intervention had a significantly higher rate of cesarean section (60.7%, P<0.001 by χ(2) analysis). The advanced head station and the wider dilatation resulted in a successful manual rotation. CONCLUSIONS: Attempts to correct pOP by manual rotation have better results when the head is in the mid-pelvis. Also, posture change reduces cesarean section rate. The current data suggest attempts to correct pOP to OA reduce cesarean section rate.

Primary amenorrhea due to juvenile granulosa-cell tumor of the ovary: a case report.

In general, primary amenorrhea is caused by gonadal dysgenesis, anomalies of internal or external genitalia with or without chromosomal anomalies, and sometimes by hormonal abnormalities that affect the hypothalamus, pituitary, ovaries, adrenals or thyroid, or by chronic or metabolic diseases. We report a rare case of a juvenile granulosa-cell tumor of the ovary that caused primary amenorrhea in a 16-year-old girl. Her hormonal profiles before the operation were characterized by an extremely low level of follicle-stimulating hormone (FSH), a relatively low level of estradiol and a high level of inhibin B. The patient had menarche after the removal of the tumor. Her elevated serum FSH after the operation was the result of a decreased serum level of inhibin that had been produced by the tumor. The present case highlights that a granulosa-cell tumor, known as an inhibin-secreting tumor, should be considered when treating primary amenorrheic girls.

Hypertensive disorders of pregnancy by oocyte donation pregnancy in Japanese women aged 40 years or older: a single-center retrospective cohort study.

This study aimed to examine the incidence of hypertensive disorders of pregnancy (HDP) among Japanese women with oocyte donation pregnancy (ODP) aged 40 years or older and estimate whether the women with ODP were more likely to develop HDP than those with autologous oocyte pregnancy (AOP) and spontaneous pregnancy (SP). In our study (N = 1361), the proportions of women who developed HDP were 20.5%, 12.8%, and 7.6% for ODP, AOP, and SP, respectively. After adjustment of covariables, the women with ODP were more likely to develop HDP than those with AOP or SP.

Retrospective details of false-positive and false-negative results in non-invasive prenatal testing for fetal trisomies 21, 18 and 13.

OBJECTIVE: Maternal characteristics and neonatal outcomes associated with cell-free DNA (cfDNA) results were analysed retrospectively to assess the details of false-positive and false-negative results after initial blood sampling in non-invasive prenatal testing (NIPT). STUDY DESIGN: A multicentre retrospective study was performed for women undergoing NIPT who received discordant cfDNA results between April 2013 and March 2018. The NIPT data obtained using massive parallel sequencing were studied in terms of maternal background, fetal fraction, z-scores, invasive procedure results and neonatal outcomes after birth. RESULTS: Of the 56,545 women who participated in this study, 54 false-positive (0.095 %) and three false-negative (0.006 %) cases were found. Seven of the 54 false-positive cases (13.0 %) had vanishing twin on ultrasonography. Among the 18 false-positive cases of trisomy 18, confined placental mosaicism (CPM) was confirmed in three cases (16.7 %), while CPM was present in one of the three false-negative cases of trisomy 21. CONCLUSION: These data suggest that the incidence of women with false-positive or false-negative results is relatively low, that such false results can often be explained, and that vanishing twin and CPM are potential causes of NIPT failure. Genetic counselling with regard to false results is important for clients prior to undergoing NIPT.

Clinical management and outcome of pregnancies complicated by previous abruption.

OBJECTIVES: We studied the clinical management and prognosis of pregnant women with a history of abruption, as well as the associated risk factors. METHODS: We reviewed the cases of 23 patients with a history of abruption and 66 patients with abruption. RESULTS: The recurrence rate of abruption was 4.3%. Intentional care prolonged gestational age in most patients. Although the incidence of abruption was low (0.44%), the consequences could be perinatal death and maternal disseminated vascular coagulation (DIC). CONCLUSION: To prevent abruption recurrence, careful monitoring during hospitalization is important. Both clinical findings and transabdominal echography are useful in diagnosing abruption.