Keiji Yamana

Prevalence of small for gestational age (SGA) and short stature in children born SGA who qualify for growth hormone treatment at 3 years of age: Population-based study

To treat children born small for gestational age (SGA) with severe short stature, treatment with growth hormone (GH) has been approved in the USA, Europe, and Japan, but no population‐based studies have reported their prevalence. The aims of this study were to investigate the prevalence of SGA and short stature in children born SGA who qualify for GH treatment at 3 years of age in a Japanese population.

Extremely preterm infants small for gestational age are at risk for motor impairment at 3 years corrected age

BACKGROUND Few studies have targeted psychomotor development and associated perinatal risk factors in Japanese very low birth weight (VLBW) infants who are severely small for gestational age (SGA). DESIGN/SUBJECTS A single-center study was conducted in 104 Japanese VLBW infants who were born preterm, due to maternal, umbilical cord, or placental abnormalities, between 2000 and 2007. Psychomotor development as a developmental quotient (DQ) was assessed using the Kyoto Scale of Psychological Development at 3 years corrected age. Severely SGA was defined as birth weight or length below -2 standard deviation values of the mean values at the same gestation. VLBW infants were divided into 2 subgroups based on gestational age at birth: ⩾28 weeks (n=64) and <28 weeks (n=40). DQs of infants with severe SGA were compared with those of infants who were appropriate for gestational age (AGA). Factors associated with developmental disabilities in VLBW infants with severe SGA (n=23) were determined. RESULTS In the group born at ⩾28 weeks gestation, infants with severe SGA had normal DQ values and did not significantly differ from those with AGA. However, in the group born at <28 weeks gestation, severe SGA infants had significantly lower postural-motor DQ values than AGA infants. Gestational age <28 weeks was an independent factor for low postural-motor DQ, regardless of the cause of severe SGA or pregnancy termination. CONCLUSIONS Extremely preterm newborns with severe SGA are at risk of motor developmental disability at age 3 years.

Fluorescent protein-based detection of unconjugated bilirubin in newborn serum

Increased serum levels of unconjugated bilirubin are associated with the development of brain damage in newborns. In current clinical settings, there are no methods for directly determining serum levels of unconjugated bilirubin. UnaG, a fluorescent protein from Japanese eel muscle that specifically binds to unconjugated bilirubin was used in this study. Linear regression analysis was carried out to compare unconjugated bilirubin levels measured by UnaG and conventional bilirubin oxidase methods. Unconjugated bilirubin levels in the serum of newborns who were untreated or treated with phototherapy were compared. Effects of interfering factors in the serum (conjugated bilirubin, hemoglobin, and lipid) on unconjugated bilirubin concentration measured by the UnaG method were also evaluated. Unconjugated bilirubin levels measured by the UnaG method were highly correlated with those determined by the bilirubin oxidase assay. Unconjugated bilirubin levels determined by bilirubin oxidase and UnaG assays were similar in serum samples containing conjugated bilirubin. The performance of the UnaG assay was unaffected by phototherapy and the presence of serum hemoglobin and lipid emulsion. These results demonstrate the clinical applicability of the UnaG method for direct measurement of unconjugated bilirubin levels in newborn serum.

Case of harlequin ichthyosis with a favorable outcome: Early treatment and novel, differentially expressed, alternatively spliced transcripts of the ATP-binding cassette subfamily A member 12 gene

Harlequin ichthyosis (HI) is the most severe form of autosomal recessive congenital ichthyosis, with a high mortality rate. Recent advances in neonatal care and the early administration of retinoids have improved the survival rate of HI. Here, we present a case of HI who was successfully treated with early administration of etretinate and showed good prognosis. Next‐generation sequencing identified novel mutations of the ATP‐binding cassette subfamily A member 12 gene (ABCA12), c.5884+4_+5delAA and c.7239G>A, which caused skipping of exons 39 and 48, respectively. Transcripts with exon 48 skipping, which cause a deletion in the second ATP‐binding cassette of ABCA12, were dominantly expressed in the skin. Besides the early administration of etretinate, the differential expression of the mutant protein with limited segmental deletion of ABCA12 may be related to the favorable outcome of our patient.

Involvement of WNT Signaling in the Regulation of Gestational Age-Dependent Umbilical Cord-Derived Mesenchymal Stem Cell Proliferation

Mesenchymal stem cells (MSCs) are a heterogeneous cell population that is isolated initially from the bone marrow (BM) and subsequently almost all tissues including umbilical cord (UC). UC-derived MSCs (UC-MSCs) have attracted an increasing attention as a source for cell therapy against various degenerative diseases due to their vigorous proliferation and differentiation. Although the cell proliferation and differentiation of BM-derived MSCs is known to decline with age, the functional difference between preterm and term UC-MSCs is poorly characterized. In the present study, we isolated UC-MSCs from 23 infants delivered at 22–40 weeks of gestation and analyzed their gene expression and cell proliferation. Microarray analysis revealed that global gene expression in preterm UC-MSCs was distinct from term UC-MSCs. WNT signaling impacts on a variety of tissue stem cell proliferation and differentiation, and its pathway genes were enriched in differentially expressed genes between preterm and term UC-MSCs. Cell proliferation of preterm UC-MSCs was significantly enhanced compared to term UC-MSCs and counteracted by WNT signaling inhibitor XAV939. Furthermore, WNT2B expression in UC-MSCs showed a significant negative correlation with gestational age (GA). These results suggest that WNT signaling is involved in the regulation of GA-dependent UC-MSC proliferation.

Evaluation of BiliCare™ transcutaneous bilirubin device in Japanese newborns

Non‐invasive transcutaneous bilirubin (TcB) monitoring has been widely used to screen for hyperbilirubinemia. TcB measured using the recently developed BiliCare™ system, however, has not been fully evaluated.

Gestational age-dependency of height and body mass index trajectories during the first 3 years in Japanese small-for-gestational age children

Gestational age (GA) is thought to affect height growth in small-for-gestational age (SGA) children. However, the GA-specific trajectories in body mass index (BMI) and early appearances of adiposity rebound (AR) have not been fully investigated in a cohort of Japanese SGA children. A longitudinal cohort study was conducted with 1063 SGA children born in Kobe, Japan, with sufficient records from birth to 3 years of age. Subjects were divided into subgroups based on GA: 39–41 weeks GA (n = 723), 37–38 weeks GA (n = 256), 34–36 weeks GA (n = 62), and <34 weeks GA (n = 22). Height and BMI were assessed at 4 months, 9 months, 1.5 years, and 3 years of age. The catch-up rate for height was GA-dependent. Most children with 39–41 weeks GA (91%) caught up by 4 months of age; however, lower GA was associated with a slower elevation in the catch-up rate. The BMI trajectory during the first 3 years was also GA-dependent, with a change in GA dependency at a boundary of 37 weeks GA. Approximately 7% of SGA children had already developed AR before 3 years of age. In conclusion, growth patterns during infancy and early childhood in SGA children differ depending on GA.

How long is transient tachypnea of the newborn dependent on oxygen supplementation

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Hepatitis B vaccine: Immunogenicity in an extremely low-birthweight infant

From 2013, infants born to mothers carrying serum hepatitis B (HB) surface antigen (HBsAg) receive HB immunoglobulin at birth and HB vaccine at birth, and at 1 and 6 months of age in Japan (prevention protocol for mother-to-child HB virus infection). Due to immature immune response to HB vaccine, the American Academy of Pediatrics and Japan Pediatric Society recommend that infants <2,000 g birthweight are given an additional HB vaccination at 2 months of age. No previous case report, however, has described the trajectory of the immunogenic response for this prevention protocol, including an additional dose at 2 months of age, in extremely lowbirthweight (ELBW) infants. The present case is reported with informed consent. The present patient was born to a 29-year-old Chinese mother (gravida 0, para 0) with HBsAg. At 20 weeks of gestational age, serum HBsAg, HB envelope antigen, HB virus core-related antigen, and HB virus DNA were positive (67 878 IU/mL, 1,531.9 sample relative light units/cut-off, >7.0 log U/mL, and 9.7 log copies/mL, respectively). Both serum HB surface antibody (HBsAb) and HB envelope antibody were negative. The HB virus genotype was type C. A male newborn weighing 918 g was born at 25 weeks and 4 days of gestational age via cesarean section due to fetal distress. He was admitted to the neonatal intensive care unit due to ELBW. Along with respiratory and circulatory treatment, i.v. immunoglobulin (IVIG; 500 mg/10 mL, Venoglobulin IHTM, Japan Blood Products Organization, Tokyo, Japan) was administered soon after birth because of hypoimmune globulinemia (serum total IgG, 280 mg/dL). At 11 h after birth, a total of 200 U/mL HB immune globulin (Dried HB globulin NichiyakuTM; Nihon Pharmaceutical, Tokyo, Japan) was injected i.m. in the right and left femoral muscles (100 U/0.5 mL in each side), and HB vaccine (0.25 mL, BimmugenTM; Kaketsuken, Kumamoto, Japan) was injected s.c. in the left upper arm. No side-effects, such as redness, swelling, or induration were observed. HB vaccine was again administered at 1 and at 2 months of age. The infant was reared on breast milk and was discharged at 4 months of age. The fourth HB vaccine was injected at 6 months of age. The HBsAb titer reached a peak at 1 month of age, and decreased to the lowest level at 4 months of age, but HBsAb was >10 mIU/mL (Fig. 1). Then, the HBsAb titer gradually increased, and after the fourth HB vaccine, it finally increased to >100 mIU/mL at 12 months of age. Serum HBsAg was negative at 12 months of age. We herein report the HBsAb titer in an ELBW infant who received four doses of HB vaccine. In the present case, the prevention protocol for mother-to-child HB virus infection with an additional dose at 2 months of age (0, 1, 2, and 6 months of age) achieved sufficient seropositivity of HBsAb at 12 months of age. The infant had an HBsAb titer of 47 mIU/mL at the time of discharge, even with an additional vaccine at 2 months of age. Because ELBW infants are usually discharged from hospital at 3–4 months of age, and are

Loss of Surfacten® During Bolus Administration Using a Feeding Catheter

Surfactant replacement therapy is widely used for treating neonatal respiratory distress syndrome, but insufficient evidence is available on the use of Surfacten® (S‐TA). This study investigated the inadvertent loss of S‐TA during instillation via feeding catheters with different bore sizes.