Establishment of a Novel Fetal Growth Restriction Model and Development of a Stem-Cell Therapy Using Umbilical Cord-Derived Mesenchymal Stromal Cells.

Fetal growth restriction (FGR) is a major complication of prenatal ischemic/hypoxic exposure and affects 5%-10% of pregnancies. It causes various disorders, including neurodevelopmental disabilities due to chronic hypoxia, circulatory failure, and malnutrition via the placenta, and there is no established treatment. Therefore, the development of treatments is an urgent task. We aimed to develop a new FGR rat model with a gradual restrictive load of uterus/placental blood flow and to evaluate the treatment effect of the administration of umbilical cord-derived mesenchymal stromal cells (UC-MSCs). To create the FGR rat model, we used ameroid constrictors that had titanium on the outer wall and were composed of C-shaped casein with a notch and center hole inside that gradually narrowed upon absorbing water. The ameroid constrictors were attached to bilateral ovarian/uterine arteries on the 17th day of pregnancy to induce chronic mild ischemia, which led to FGR with over 20% bodyweight reduction. After the intravenous administration of 1 × 105 UC-MSCs, we confirmed a significant improvement in the UC-MSC group in a negative geotaxis test at 1 week after birth and a rotarod treadmill test at 5 months old. In the immunobiological evaluation, the total number of neurons counted via the stereological counting method was significantly higher in the UC-MSC group than in the vehicle-treated group. These results indicate that the UC-MSCs exerted a treatment effect for neurological impairment in the FGR rats.

Parechovirus-A3 encephalitis presenting with focal seizure mimicking herpes simplex virus infection.

BACKGROUND: Febrile neonates and young infants presenting with seizure require immediate evaluation and treatment. Herein we experienced two young infants with parechovirus-A3 (PeV-A3) encephalitis, initially presented with focal seizure suspecting herpes simplex virus (HSV) encephalitis. CASES: We have experienced 2 infantile cases, initially presented with focal seizure. At presentation, HSV encephalitis was strongly suspected and empiric acyclovir therapy was started; however, serum and/or cerebrospinal fluid (CSF) PCR for HSV were negative. Instead, serum and/or CSF PCR for parechovirus-A was positive. PeV-A3 infection was confirmed by genetic sequence analyses. Both cases required multiple anticonvulsant therapy and intensive care for intractable seizure. Diffusion-weighted imaging of brain magnetic resonance imaging (MRI) showed distinct findings; high-intensity lesions in the gray matter of parietal and occipital lobes in Case 1, and bilateral decreased diffusion of the deep white matter and corpus callosum in Case 2. We have followed two cases more than four years; Case 1 developed epilepsy, has been on an anticonvulsant to control her seizure. Case 2 has significant neurodevelopmental delay, unable to stand or communicate with language. CONCLUSIONS: PeV-A3 encephalitis needs to be in differential diagnosis when neonates and young infants present with focal seizure, mimicking HSV encephalitis. Special attention may be necessary in patients with PeV-A3 encephalitis given it could present with intractable seizure with high morbidity in a long-term.

Risk factors for absence of catch-up growth in small for gestational age very low-birthweight infants.

BACKGROUND: Many small for gestational age (SGA) infants have catch-up growth during the first 2 years of life, but approximately 10% have no catch-up growth, and short stature continues into adulthood. Identification of risk factors for absence of catch-up growth at an early age may be useful for earlier diagnosis and earlier treatment. METHODS: This was a retrospective multicenter study. The subjects were SGA infants with very low-birthweight (VLBW), who were followed up until the age of 3 years. The risk factors for absence of catch-up growth were identified on statistical analysis. RESULTS: Of the 217 SGA infants in this study, 181 were in the catch-up group and 36 were in the no catch-up group. The catch-up rate was 83%. On multivariate analysis adjusted for gestational age, birthweight, birth height, and birth head circumference, multipara, Z and ΔZ scores of length at 12 months of corrected age, and the Z score of height at 24 months of corrected age were risk factors for lack of catch-up at 3 years. CONCLUSIONS: The length Z and ΔZ scores at 12 months of corrected age may be useful for an earlier diagnosis and earlier initiation of growth hormone treatment in VLBW infants.

Time-Series Analysis Comparing the Prevalence of Antibodies against Nine Viral Species Found in Umbilical Cord Blood in Japan.

In this study, we investigated the prevalence of antibodies against 9 viral species found in umbilical cord blood from 561 neonates in 2013. Serum IgG antibodies against the following viruses were measured: herpes simplex virus (HSV), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus 6 (HHV-6), measles virus (MV), rubella virus (RV), mumps virus (MuV), and human parvovirus B19 (HPV B19). A survey questionnaire regarding past medical history and maternal immunization status for the vaccine-preventable diseases of varicella, measles, rubella, and mumps was simultaneously administered. The results were compared with previous data collected in 2001-2002 from 378 umbilical cord blood samples. Viral seroprevalence data were: HSV, 54%; VZV, 96%; EBV, 96%; CMV, 67%; HHV-6, 100%; MV, 95%; RV, 94%; MuV, 64%; and HPV B19, 55%. The seroprevalence of CMV, MV, and MuV were significantly lower in 2013 than in 2001-2002 (CMV, 76%; MV, 98%; MuV, 93%). Compared with the 2001-2002 data, the mean IgG antibody values of the 4 vaccine-preventable diseases were significantly lower, and vaccination coverage for those diseases among mothers was significantly higher. Thus, attention should be paid to antibody levels in women of childbearing age in the future.