Usefulness of combined NGS and QF-PCR analysis for product of conception karyotyping.

Purpose: Since chromosomal abnormalities can be detected in more than half of miscarriages, cytogenetic testing of the product of conception (POC) can provide important information when preparing for a subsequent pregnancy. Conventional karyotyping is the common diagnostic method for a POC but can be problematic due to the need for cell culture. Methods: We here conducted shallow whole-genome sequencing (sWGS) using next-generation sequencing (NGS) for alternative POC cytogenomic analysis. Since female euploidy samples can include 69,XXX triploidy, additional QF-PCR was performed in these cases. Results: We here analyzed POC samples from miscarriages in 300 assisted reproductive technology (ART) pregnancies and detected chromosomal abnormalities in 201 instances (67.0%). Autosomal aneuploidy (151 cases, 50.3%) was the most frequent abnormality, consistent with prior conventional karyotyping data. Mosaic aneuploidy was detected in seven cases (2.0%). Notably, the frequency of triploidy was 2.3%, 10-fold lower than the reported frequency in non-ART pregnancies. Structural rearrangements were identified in nine samples (3%), but there was no case of segmental mosaicism. Conclusions: These data suggest that NGS-based sWGS, with the aid of QF-PCR, is a viable alternative karyotyping procedure that does not require cell culture. This method could also assist with genetic counseling for couples who undergoes embryo selection based on PGT-A data.

Incidence of and risk factors for severe maternal complications associated with hypertensive disorders after 36 weeks' gestation in uncomplicated twin pregnancies: A prospective cohort study.

AIM: To elucidate the incidence of and risk factors for severe hypertensive disorders (HD) and related maternal complications in uncomplicated twin pregnancies that reached 36 weeks' gestation. METHODS: We conducted a prospective cohort study of twin pregnancies delivered after 36 weeks' gestation. Cases of twin-twin transfusion syndrome, twin anemia-polycythemia sequence, malformed fetuses, monoamniotic twins, selective reduction, fetal therapy and HD or fetal death before 35 weeks' gestation were excluded. The study's primary outcome was the incidence of severe maternal complications, including severe HD, eclampsia, placental abruption, HELLP (hemolysis, elevated liver enzyme and low platelet) syndrome, pulmonary edema and cerebrovascular disease. Perinatal factors associated with the primary outcome were identified using a multivariate logistic regression model. RESULTS: In 330 enrolled women, the number of cases with the primary outcome was 28 (8.5%; 95% confidence interval 5.9-12.0), including 25 cases of severe HD and each one case of placental abruption, HELLP syndrome and eclampsia. The rate of severe maternal complications significantly increased with gestational age, demonstrating 1.2% at 36 weeks, 3.9% at 37 weeks and 6.4% at 38 weeks. Only gestational proteinuria was identified as the independent risk factor for severe maternal complications (adjusted odds ratio 17.1 [95% confidence interval 6.71-45.4]). CONCLUSION: Severe maternal HD and related complications increased from late preterm to early term; particularly, patients with gestational proteinuria were at high risk.

Transient amniotic fluid leakage after fetoscopic laser photocoagulation for twin-twin transfusion syndrome.

AIM: Iatrogenic premature rupture of membrane (PROM) is one of the major complications related to fetoscopic laser photocoagulation (FLP) for twin-twin transfusion syndrome (TTTS). However, amniotic fluid leakage (AFL) sometimes spontaneously disappears. This study evaluated the incidence and clinical characteristics of transient AFL after FLP. METHODS: We retrospectively reviewed pregnancies that underwent FLP for TTTS at a single center. Patients with apparent AFL within 2 weeks after FLP were divided into two groups: transient AFL, defined by the disappearance of fluid leakage within a week; and PROM, if AFL persisted continuously for more than a week or premature birth occurred, including miscarriage, within a week of the first symptom of AFL. RESULTS: Among 201 monochorionic twin pregnancies that underwent FLP during the study period, nine patients (4.5%) were diagnosed with AFL within a week after FLP. Four patients (2.0%) were classified as transient AFL and five as PROM. Median gestational age at FLP was not significantly different between the groups; operative time in the PROM group was significantly longer (P = 0.01). The surgery to delivery interval and median gestational age at delivery were greater in the transient AFL group (87.8 vs 17.6 days, P = 0.01; 32.5 vs 23.6 weeks, P = 0.01, respectively). CONCLUSIONS: The incidence of transient AFL after FLP was 2%. Perinatal outcomes of transient AFL might be better than that of PROM.

Perinatal and one-year outcomes of non-immune hydrops fetalis by etiology and age at diagnosis.

AIM: The prognosis for non-immune hydrops fetalis (NIHF) is still poor despite progress in perinatal care. We have examined perinatal and 1-year outcomes for NIHF in relation to gestational age at diagnosis and underlying etiology in order to identify predictors of mortality. METHODS: A retrospective review was conducted of 92 pregnancies with NIHF managed in hospital between 2000 and 2012. The gestational age at diagnosis, etiology, perinatal outcome, and 1-year outcome were recorded, and their associations assessed. RESULTS: A total of 41 of 92 cases (45%) resulted in fetal death, 33 patients (36%) survived to 1 year, but only 15 of the 33 survivors were developmentally intact. Aneuploidy was the most common cause of NIHF (27%; 25/92). Of the 34 patients who were diagnosed before 22 weeks, 29 fetuses (85%) died, and four (12%) survived to 1 year without developmental delay. Meanwhile, of the 26 patients diagnosed after 30 weeks, 18 (69%) survived to 1 year. Of those 18, seven (27%) were developmentally intact. Approximately half of the pregnancies with cardiac anomalies (8/13) resulted in intrauterine fetal death (IUFD) or early neonatal death. Aneuploidy was associated with a high frequency of IUFD, and of the remaining five surviving newborns, three had developmental delay. CONCLUSION: The prognosis for NIHF differs according to underlying etiology and gestational age at diagnosis. NIHF diagnosed early in gestation is associated with poor outcome. Knowledge of the primary etiology is important for counseling and therapy.

Associated anomalies in congenital diaphragmatic hernia: perinatal characteristics and impact on postnatal survival.

OBJECTIVE: We aimed to investigate the clinical characteristics and postnatal outcomes of fetuses with congenital diaphragmatic hernia (CDH) and additional anomalies. MATERIALS AND METHODS: We reviewed the charts of fetuses with CDH managed between 2005 and 2013. Patients were divided into complex and isolated groups based on the presence of additional anomalies. We analyzed the respective polyhydramnios, liver herniation, stomach position, lung to thorax transverse area ratio (LTR), and prognoses of the two groups. The survival rates of both groups were assessed based on the LTR as well as on stomach and liver positions. RESULTS: CDH was diagnosed in 65 fetuses, and additional anomalies were found in 23. The incidences of liver herniation, polyhydramnios, and death were significantly higher, and LTR was significantly lower, in the complex group. The mortality rate of fetuses with a LTR <0.08 was lower than that of fetuses with a LTR of ≥0.08 in the complex group. Further, the survival rate of fetuses with intrathoracic liver was lower than those without liver herniation. CONCLUSIONS: The prognosis of complex CDH is poor. This may result from both the associated anomalies and the severity of CDH itself. Even in complex CDHs, intrathoracic liver and LTR values are useful in estimating postnatal outcome.

Adverse perinatal outcomes related to the delivery mode in women with monochorionic diamniotic twin pregnancies.

AIMS: The association between the planned delivery mode and adverse perinatal outcomes of monochorionic diamniotic (MCDA) twin pregnancies at ≥36 weeks' gestation was evaluated. METHODS: This retrospective cohort study included uncomplicated MCDA twin pregnancies delivered after 36 weeks' gestation during a 10-year period. Cases were classified into the trial of labor (TOL) or cesarean section (CS) group according to the planned delivery mode. The primary outcome was a composite of adverse outcomes for at least one twin, including intrauterine fetal death (IUFD) after 36 weeks, neonatal death, umbilical artery pH<7.1, 5-min Apgar scores<7, hypoxic ischemic encephalopathy (HIE), meconium aspiration syndrome (MAS), respiratory distress syndrome (RDS), or acute feto-fetal hemorrhage (AFFH). The relationship between outcomes and the planned delivery mode was evaluated using a multiple logistic regression analysis. RESULTS: We included the 310 pregnancies delivered after 36 weeks' gestation. After excluding 15 patients, the final analysis included 295 MCDA pregnancies: 63% had delivered through TOL and 37% through CS. The incidences of composite adverse outcomes in the TOL and CS groups were 4.3% and 1.9%, respectively. No IUFD, neonatal death, MAS, RDS, or AFFH was observed; two infants in each group developed HIE. Adverse outcomes were not significantly associated with any risk factor, including delivery through TOL. CONCLUSION: TOL may not influence the perinatal outcomes of MCDA twin pregnancies delivered at ≥36 weeks' gestation.