Genetic autopsy and genetic counseling for a case of fatal oligohydramnios due to de novo 17q12 deletion syndrome.

We report here a fatal oligohydramnios case, which was suspected due to autosomal recessive polycystic kidney disease at first, but genetic analysis using chorionic tissue and umbilical cord after stillbirth led to the diagnosis of 17q12 deletion syndrome. Subsequent genetic analysis of the parents showed no 17q12 deletion. In this case, if the fetus had autosomal recessive polycystic kidney disease, the recurrence rate in the next pregnancy was suspected to be 25%, but since it was a de novo autosomal dominant disorder, the recurrence rate is extremely low.

Fetal Ultrasound and Magnetic Resonance Imaging Abnormalities in Congenital Cytomegalovirus Infection Associated with and without Fetal Growth Restriction.

Congenital cytomegalovirus infection (cCMV) can cause fetal growth restriction (FGR) and severe sequelae in affected infants. Clinicians generally suspect cCMV based on multiple ultrasound (US) findings associated with cCMV. However, no studies have assessed the diagnostic accuracy of fetal US for cCMV-associated abnormalities in FGR.

Prevalence of common aneuploidy in twin pregnancies.

The incidence of chromosomal abnormalities in twin pregnancies is not well-studied. In this retrospective study, we investigated the frequency of chromosomal abnormalities in twin pregnancies and compared the incidence of chromosomal abnormalities in dichorionic diamniotic (DD) and monochorionic diamniotic (MD) twins. We used data from 57 clinical facilities across Japan.

The Current Challenges in Developing Biological and Clinical Predictors of Congenital Cytomegalovirus Infection.

Congenital cytomegalovirus (CMV) infection may cause severe long-term sequelae. Recent studies have demonstrated that early antiviral therapy for infants with symptomatic congenital CMV (cCMV) infection may improve neurological outcomes; thus, accurate identification of newborns at high risk of cCMV infection may contribute to improved outcomes in affected children. However, maternal serological screening for cCMV infection by diagnosing primary infection during pregnancy, which is a popular screening strategy, is inefficient, because the number of cCMV infections with nonprimary causes, including reactivation of or reinfection with CMV, is larger than that of cCMV infections with primary causes.

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.

A cohort study of the universal neonatal urine screening for congenital cytomegalovirus infection.

Objectives: This prospective cohort study aimed to evaluate the efficacy of the universal neonatal urine screening, followed by diagnosis, workup and antiviral therapy for symptomatic congenital cytomegalovirus (CMV) infection to reduce neurological impairments and sequelae.

Methods: Neonates born in three facilities underwent the universal urine screening of PCR analyses for CMV-DNA. Neonates with symptomatic congenital CMV infection (cCMV) received oral valganciclovir (VGCV) of 32 mg/kg/day for six weeks or six months, and were evaluated for neurological outcomes including developmental quotient (DQ) and hearing function at around 18 months of corrected age.

Qualitative investigation of the factors that generate ambivalent feelings in women who give birth after receiving negative results from non-invasive prenatal testing.

Background: Women who receive negative results from non-invasive prenatal genetic testing (NIPT) may find that they later have mixed or ambivalent feelings, for example, feelings of accepting NIPT and regretting undergoing the test. This study aimed to investigate the factors generating ambivalent feelings among women who gave birth after having received negative results from NIPT.

Methods: A questionnaire was sent to women who received a negative NIPT result, and a contents analysis was conducted focusing on ambivalent expressions for those 1562 women who responded the questionnaire.

A cohort study of maternal screening for congenital Toxoplasma gondii infection: 12 years' experience.

Primary infection with Toxoplasma gondii (T. gondii) during pregnancy may cause congenital infection of the infant. This study evaluated whether screening using IgG avidity and multiplex-nested polymerase chain reaction (PCR) methods was effective for detecting a high-risk pregnancy for congenital T.

Clinical factor associated with congenital cytomegalovirus infection in pregnant women with non-primary infection.

The aim of this nested case-control study was to evaluate clinical factors associated with the occurrence of congenital cytomegalovirus (CMV) infection in pregnant women with non-primary CMV infection. In a cohort study of CMV screening for 2193 pregnant women and their newborns, seven newborns with congenital CMV infection were identified among 1287 pregnant women with non-primary CMV infection that was defined as negative IgM and positive IgG with IgG avidity index >45%. In the 1287 women with non-primary CMV infection, clinical findings and complications were compared between pregnancies with and without congenital CMV infection.

Universal Screening With Use of Immunoglobulin G Avidity for Congenital Cytomegalovirus Infection.

Background: The aim of this prospective cohort study was to evaluate the efficacy of maternal screening for congenital cytomegalovirus infection (CCI) using cytomegalovirus (CMV) immunoglobulin G (IgG) and the IgG avidity index (AI).

Methods: Pregnant women underwent screening of CMV IgG and AI measurements. IgG-negative women underwent remeasurement of IgG after educational intervention.

Gestational Age-Dependent Increase of Survival Motor Neuron Protein in Umbilical Cord-Derived Mesenchymal Stem Cells.

Background: Spinal muscular atrophy (SMA) is the most common genetic neurological disease leading to infant death. It is caused by loss of survival motor neuron (SMN) 1 gene and subsequent reduction of SMN protein in motor neurons. Because SMN is ubiquitously expressed and functionally linked to general RNA metabolism pathway, fibroblasts (FBs) are most widely used for the assessment of SMN expression in SMA patients but usually isolated from skin biopsy samples after the onset of overt symptoms.

Prediction of Congenital Cytomegalovirus Infection in High-Risk Pregnant Women.

Background: This prospective study aimed to determine maternal clinical, laboratory, and ultrasound findings that effectively predict the occurrence of congenital cytomegalovirus (CMV) infection (CCI) in high-risk pregnant women.

Methods: Three hundred CMV immunoglobulin (Ig) M-positive pregnant women were enrolled. The maternal clinical and laboratory findings, including serum CMV IgM and IgG; IgG avidity index (AI); antigenemia assay (C7-HRP); polymerase chain reaction (PCR) for the detection of CMV-DNA in the maternal serum, urine, and uterine cervical secretion; and prenatal ultrasound findings, were evaluated.

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.

Telomeric Region of the Spinal Muscular Atrophy Locus Is Susceptible to Structural Variations.

Background: Most patients with spinal muscular atrophy lack the survival motor neuron 1 gene (SMN1) in the telomeric region of the spinal muscular atrophy locus on chromosome 5q13. On the other hand, the copy number of SMN2, a centromeric homolog of SMN1, is increased in many of these patients. This study aimed to clarify the mechanism underlying these structural variations.

A novel PIGN mutation and prenatal diagnosis of inherited glycosylphosphatidylinositol deficiency.

Glycosylphosphatidylinositol (GPI) anchors tether proteins to the extracellular face of eukaryotic plasma membranes. Defects in the human GPI anchor biosynthetic pathway cause inherited GPI deficiencies (IGDs) characterized by multiple congenital anomalies: dysmorphic faces, developmental delay, hypotonia, and epilepsy. We report the case of a 6-year-old boy with severe psychomotor developmental delay, epilepsy, and decreased granulocyte surface expression of GPI-anchored protein that suggested autosomal recessive GPI deficiency.

The IgG avidity value for the prediction of Toxoplasma gondii infection in the amniotic fluid.

Primary Toxoplasma gondii (T. gondii) infection during pregnancy may lead to congenital toxoplasmosis. Maternal screening using T.

Rapid increase in the serum Cytomegalovirus IgG avidity index in women with a congenitally infected fetus.

Background: Human Cytomegalovirus (CMV) is the virus most frequently responsible for severe diseases of the fetus and newborn. The reported intrauterine transmission rate of CMV following primary maternal infection is approximately 40%. Invasive techniques are needed for the prenatal diagnosis of congenital CMV infection.

Prenatal genetic testing for familial severe congenital protein C deficiency.

Severe congenital protein C (PC) deficiency is an autosomal recessive hereditary thrombophilia caused by mutations in PROC. The case manifested severe purpura fulminans, intracranial thrombosis or hemorrhage within 4 days after birth, resulting in blindness. We report the identification of inherited compound heterozygous mutations, including a novel nonsense mutation in PROC, and a prenatal genetic test for a subsequent pregnancy.

Nationwide survey of mother-to-child infections in Japan.

Objectives: The aim of this survey study was to evaluate a state of mother-to-child infections in Japan.

Methods: A nationwide survey on 2714 obstetric facilities where regular maternity checkups were carried out was conducted. A primary questionnaire assessed numbers of pregnancies including induced abortion, spontaneous abortion, still-birth as well as live-birth, which were affected by congenital infections of 6 pathogens during a year of 2011.

Prophylactic intravenous immunoglobulin injections to mothers with primary cytomegalovirus infection.

The aim of this trial study was to assess the preventive efficacy of immunoglobulin with a high titer of anti-CMV antibody for mother-to-fetus cytomegalovirus (CMV) transmission among pregnant women with primary/acute CMV infection. The primary CMV infection in mothers was diagnosed by a positive test for CMV IgM and/or low IgG avidity. Intact type immunoglobulin with a high titer of anti-CMV antibody was injected intravenously at a dosage of 2.

Risk factors for neonatal thyroid dysfunction in pregnancies complicated by Graves' disease.

Objective: To determine the factors related to adverse pregnancy outcomes and neonatal thyroid dysfunction in pregnancies complicated by Graves' disease.

Study Design: Thirty-five pregnancies complicated by Graves' disease were divided into two groups: adverse pregnancy outcome (n=15) and no adverse pregnancy outcome (n=20). Adverse pregnancy outcomes included spontaneous abortion, stillbirth, premature delivery, fetal growth restriction, and pregnancy-induced hypertension.