Antenatal screening timeline and cutoff scores of the Edinburgh Postnatal Depression Scale for predicting postpartum depressive symptoms in healthy women: a prospective cohort study.

BACKGROUND: It is worthwhile to identify women at risk of developing postpartum depression during pregnancy. This study aimed to determine the optimal time and cutoff score for antenatal screening for prediction of postpartum depressive symptoms (PDS) using the Edinburgh Postnatal Depression Scale (EPDS) and to identify risk factors for PDS. METHODS: The target population was healthy pregnant women receiving antenatal care at a university hospital in Tokyo, Japan. During the first, second, and third trimesters, 3-4 days postpartum, and one month postpartum, they were asked to take the Japanese version of the EPDS questionnaire. The primary outcome of the study was PDS, defined as an EPDS score ≥ 9 at one month postpartum. The area under the receiver operating characteristics curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of EPDS scores at each antenatal screening time were calculated. RESULTS: From 139 pregnant women, 129 were successfully followed up throughout the study. The number of women with an EPDS score ≥ 9 during the first, second, and third trimesters, 3-4 days postpartum, and one month postpartum were 6/126 (4.8%), 9/124 (7.3%), 5/117 (4.3%), 17/123 (13.8%), and 15/123 (12.2%), respectively. Screening during the second trimester had the highest AUC to predict PDS (0.89) among antenatal screenings. The optimal EPDS cutoff score during the second trimester was 4/5 (sensitivity: 85.7%; specificity: 77.1%; PPV: 33.3%; NPV: 97.6%). An EPDS score ≥ 5 during the second trimester (adjusted odds ratio [aOR]: 15.9; 95% confidence interval [95%CI]: 3.2-78.1) and a family history of mental illness (aOR: 4.5; 95%CI: 1.2-17.5) were significantly associated with PDS. CONCLUSIONS: Our study suggests that the EPDS score at the second trimester with the cutoff value of 4/5 may be adequate for initial screening for prediction of PDS. Women with an EPDS score ≥ 5 at the second trimester require more elaborate follow-up.

Classification of factors involved in nonreportable results of noninvasive prenatal testing (NIPT) and prediction of success rate of second NIPT.

OBJECTIVE: To evaluate the reasons for nonreportable cell-free DNA (cfDNA) results in noninvasive prenatal testing (NIPT), we retrospectively studied maternal characteristics and other details associated with the results. METHODS: A multicenter retrospective cohort study in pregnant women undergoing NIPT by massively parallel sequencing (MPS) with failed cfDNA tests was performed between April 2013 and March 2017. The women's data and MPS results were analyzed in terms of maternal characteristics, test performance, fetal fraction (FF), z scores, anticoagulation therapy, and other details of the nonreportable cases. RESULTS: Overall, 110 (0.32%) of 34 626 pregnant women had nonreportable cfDNA test results after an initial blood sampling; 22 (20.0%) cases had a low FF (<4%), and 18 (16.4%) cases including those with a maternal malignancy, were found to have altered genomic profile. Approximately half of the cases with nonreportable results had borderline z score. Among the women with nonreportable results because of altered genomic profile, the success rate of retesting using a second blood sampling was relatively low (25.0%-33.3%). Thirteen (11.8%) of the women with nonreportable results had required hypodermic heparin injection. CONCLUSIONS: The classification of nonreportable results using cfDNA analysis is important to provide women with precise information and to reduce anxiety during pregnancy.

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.

A poor long-term neurological prognosis is associated with abnormal cord insertion in severe growth-restricted fetuses.

OBJECTIVE: To clarify and compare if the neurological outcomes of fetal growth restriction (FGR) cases with abnormal cord insertion (CI) are associated with a higher risk of a poor neurological outcome in subjects aged 3 years or less versus those with normal CI. METHODS: A multicenter retrospective cohort study was conducted among patients with a birth weight lower than the 3rd percentile, based on the standard reference values for Japanese subjects after 22 weeks' gestation, who were treated at a consortium of nine perinatal centers in Japan between June 2005 and March 2011. Patients whose birth weights were less than the 3rd percentile and whose neurological outcomes from birth to 3 years of age could be checked from their medical records were analyzed. The relationship between abnormal CI and neurological outcomes was analyzed. Univariate and multivariate models of multivariate logistic regression were employed to estimate the raw and odds ratio (OR) with 95% confidence intervals comparing marginal (MCI) and velamentous cord insertion (VCI) to normal CI. RESULTS: Among 365 neonates, 63 cases of MCI and 14 cases of VCI were observed. After excluding 24 cases with neonatal or infant death from the total FGR population, the assessment of the outcomes of the infants aged 3 years or younger showed the following rates of neurological complications: 7.3% (n=25) for cerebral palsy, 8.8% (n=30) for developmental disorders, 16.7% (n=57) for small-for-gestational-age short stature (SGA), 0.6% (n=2) for impaired hearing, 0.9% (n=3) for epilepsy, 1.2% (n=4). The ORs (95% confidence intervals) based on multivariate analysis were as follows: cerebral palsy=10.1 (2.4-41.5) in the VCI group and 4.3 (1.6-11.9) in the MCI group, developmental disorders=6.7 (1.7-26) in the VCI group and 3.9 (1.1-14.2) in the single umbilical artery (SUA) group, 5.1 (1.4-18.7) for birth weight <1000 g and 2.8 (1.2-6.7) for placental weight <200 g. CONCLUSIONS: The present results indicate that growth-restricted fetuses diagnosed with a birth weight below the 3rd percentile exhibiting abnormal umbilical CI are at a high risk for poor neurological outcomes, including cerebral palsy and/or developmental disorders.

Fetal Therapy Model of Myelomeningocele with Three-Dimensional Skin Using Amniotic Fluid Cell-Derived Induced Pluripotent Stem Cells.

Myelomeningocele (MMC) is a congenital disease without genetic abnormalities. Neurological symptoms are irreversibly impaired after birth, and no effective treatment has been reported to date. Only surgical repairs have been reported so far. In this study, we performed antenatal treatment of MMC with an artificial skin using induced pluripotent stem cells (iPSCs) generated from a patient with Down syndrome (AF-T21-iPSCs) and twin-twin transfusion syndrome (AF-TTTS-iPSCs) to a rat model. We manufactured three-dimensional skin with epidermis generated from keratinocytes derived from AF-T21-iPSCs and AF-TTTS-iPSCs and dermis of human fibroblasts and collagen type I. For generation of epidermis, we developed a protocol using Y-27632 and epidermal growth factor. The artificial skin was successfully covered over MMC defect sites during pregnancy, implying a possible antenatal surgical treatment with iPSC technology.

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.

Increased interleukin-1ß and basic fibroblast growth factor levels in the cerebrospinal fluid during human herpesvirus-6B (HHV-6B) encephalitis.

Human herpesvirus 6B (HHV-6B) causes exanthema subitum in infants and is known to be mildly pathogenic. However, HHV-6B infection can induce febrile seizures in a high percentage of patients, and in rare cases, result in encephalitis. We detected higher levels of interleukin (IL)-1ß and basic fibroblast growth factor (bFGF) in the cerebrospinal fluid (CFS) of patients with HHV-6B encephalitis when compared to those in patients with non-HHV-6B-induced febrile seizures. In vitro, IL-1ß and bFGF enhanced HHV-6B gene expression in infected U373 astrocytes during the initial and maintenance phases of infection, respectively. These findings indicated that IL-1ß and bFGF contribute to HHV-6B growth and the onset of encephalitis.

Prenatal Diagnosis of Isolated Agnathia-Otocephaly: A Case Report and Review of the Literature.

Agnathia is a rare disease characterized by the absence of a mandible. Few cases of prenatally diagnosed isolated agnathia have been reported. We present a case report and review of the literature of prenatally diagnosed agnathia. A 38-year-old woman (gravida 0, para 0) was referred to our hospital at 28 weeks and 3 days of gestation for fetal evaluation because of polyhydramnios and suspected facial anomalies. Three-dimensional ultrasonography and MRI indicated agnathia. Premature rupture of the membranes occurred before the parents could reach a decision on the postnatal treatment. We performed emergency cesarean section on the second day of the 33rd week of gestation. The neonate was deemed nonresuscitable and he died of airway obstruction shortly after birth. Because agnathia is associated with very poor prognosis, accurate prenatal diagnosis and detailed counseling should be promptly provided before unexpected delivery to the parents for the determination of postnatal treatment.

Significance of oligohydramnios in preterm small-for-gestational-age infants for outcome at 18 months of age.

AIM: The aim of this study was to evaluate the association between oligohydramnios and other perinatal factors in preterm small-for-gestational-age (SGA) infants who had cerebral palsy at 18 months of age or who had died before this age. METHODS: This retrospective study included 320 infants with birthweights < 3rd percentile delivered between 22 and 33 complete weeks of gestation. We evaluated the incidence of CP at 18 months of age and of death before this age. The significant risk factors, including oligohydramnios, of CP or death of preterm SGA infants were evaluated by logistic regression analysis. RESULTS: The incidence of CP or death was 47/320 (14.7%), consisting of 24/320 (7.5%) cases of CP and 23/320 (7.2%) cases of death. Oligohydramnios (adjusted odds ratio, 2.18; 95% confidence interval, 1.07-4.45) and gestational age (adjusted odds ratio, 0.76; 95% confidence interval, 0.66-0.87) were independently correlated with outcome. CONCLUSION: The incidence of adverse outcomes was approximately 15% in preterm SGA infants. SGA infants born with oligohydramnios may be at increased risk for CP or death compared to those with normal amniotic volume.

Prenatal risk stratification of severe small-for-gestational-age infants: a Japanese multicenter study.

OBJECTIVE: To establish a prenatal prognostic classification of severe small-for-gestational-age (SGA) infants based on gestational age and fetal findings. METHODS: A retrospective cohort study of 366 singleton infants (birth weight <3rd percentile) delivered between 22 and 34 weeks' gestation at nine tertiary perinatal centers. A decision tree model was developed for the prediction of death or severe morbidity. RESULTS: There were 35 infants with poor outcome. Prematurity was the most powerful factor in those born before 27.9 weeks' gestation, while oligohydramnios was the most powerful factor in those born at 27.9 weeks or after. The rate of poor outcome in infants born before 25.1 weeks, between 25.1 and 27.9 weeks, at 27.9 weeks or after with oligohydramnios, at 27.9 weeks or after without oligohydramnios, was 53.9%, 18.2%, 13.6% and 3.2%, respectively. CONCLUSIONS: Risk stratification based on gestation of 25 weeks, 28 weeks and oligohydramnios may aid in prognosis of severe SGA infants.

Usefulness of ultrasonography and MRI for diagnosis of fetal pulmonary agenesis: case report and review of the literature.

A pregnant Japanese female was referred to our hospital due to intrauterine fetal growth restriction. A prenatal diagnosis of right pulmonary agenesis could be made using ultrasonography and fetal magnetic resonance imaging, and a Caesarian section was performed at 34 weeks of gestation. The infant developed a respiratory disorder immediately, received systemic management in the neonatal intensive care unit (NICU), and was discharged at age of 103 days without any severe sequelae.