Miwako Nagasaka

Association of a vascular endothelial growth factor polymorphism with the development of bronchopulmonary dysplasia in Japanese premature newborns

Our objective was to correlate vascular endothelial growth factor (VEGF) genetic polymorphisms with the risk of bronchopulmonary dysplasia (BPD) development in premature newborns. Fifty-five newborns with BPD (BPD: median gestational age [GA]: 27 weeks, birthweight [BW]: 786 g) and 42 newborns without BPD (non-BPD: median GA: 29 weeks, BW: 1,165 g), who were born at <32 weeks gestational age and were admitted to Kobe University Hospital, were included. BPD was defined as oxygen dependency at 36 weeks postmenstrual age. Genomic DNA was extracted from the umbilical cord, cord blood, or buccal mucosa. Six VEGF genotypes (-1498T > C, -1154G > A, -634C > G, -7C > T, 936C > T, and 1612G > A) were determined by DNA sequencing. Clinical characteristics, and allele and genotype frequencies of VEGF in the BPD and non-BPD groups were analyzed. G allele frequencies in -634C > G of the BPD group were significantly higher than in the non-BPD group (66.4% vs. 50%, P = 0.02). -634C > G genotype distributions differed significantly between the BPD and non-BPD groups (BPD: CC 7%/CG 53%/GG 40%; non-BPD: CC 24%/CG 52%/GG 24%; P = 0.04). Multivariate logistic regression showed that duration of ventilation, VEGF-634G > C G alleles, and male gender were independent risk factors for BPD. In conclusion, polymorphism VEGF -634C > G may influence the risk of BPD.

Incidence of short stature at 3 years of age in late preterm infants: a population-based study

Objectives This study aimed to investigate the incidence of short stature at 3 years of age in a Japanese cohort of late preterm infants who were born at 34–36 weeks’ gestational age (GA). We compared these late preterm infants with term infants (37–41 weeks’ GA), and evaluated the effect of birth weight on the incidence of short stature. Methods A longitudinal population-based study of 26 970 neonates who were born between 34 weeks’ and 41 weeks’ GA in 2006–2008 was conducted in Kobe, Japan. Of these neonates, 1414 were late preterm and 25 556 were term infants. The late preterm infants were then divided into three subgroups based on birth weight as determined by Japanese neonatal anthropometric charts for GA at birth: large-for-GA (n=140), appropriate-for-GA (AGA, n=1083), and small-for-GA (SGA, n=191). The incidence of short stature at 3 years of age was calculated in the late preterm group and compared with that in the term group, and between the AGA and SGA groups with late preterm birth. Results The incidence of short stature in the late preterm group was 2.9%, which was significantly higher than that in the term group (1.4%). Late preterm SGA infants developed short stature with a significantly higher (9.4%) incidence than that of late preterm AGA infants (2.1%). Conclusions The incidence of short stature in 3-year-old children who were late preterm infants has a 2-fold higher risk than that in term infants. The risk of developing short stature is increased 4.5-fold if they are SGA.

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.

Human CD134 (OX40) expressed on T cells plays a key role for human herpesvirus 6B replication after allogeneic hematopoietic stem cell transplantation

BACKGROUND CD134 (OX40), which is a cellular receptor for human herpesvirus-6B (HHV-6B) and expresses on activated T cells, may play a key role for HHV-6B replication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). OBJECTIVES Therefore, we examined the CD134 expression on T cells and HHV-6B replication after allo-HSCT, and analyzed the correlation between them. STUDY DESIGN Twenty-three patients after allo-HSCT were enrolled. The percentages of CD134-positive cells within the CD4+ and CD8+ cell populations were measured by flow cytometry, and the viral copy number of HHV-6B was simultaneously quantified by real-time PCR. The correlation between CD134 and HHV-6B viral load was then statistically analyzed. RESULTS HHV-6B reactivation occurred in 11 of 23 patients (47.8%). CD134 expression was seen on T cells and was coincident with the time of peak viral load. The percentage of CD134-positive cells decreased significantly when HHV-6B DNA disappeared (p = .005 in CD4+ T cells, p = .02 in CD8+ T cells). In the 4 patients who underwent umbilical cord blood transplantation (UCBT), the viral load varied with the percentage of CD134-positive cells. In the comparison between the HHV-6B reactivation group and non-reactivation group, maximum percentages of CD134-positive cells among CD4+ T cells in reactivation group were significantly higher than those in non-reactivation group (p = .04). CONCLUSIONS This is the first study to show that a correlation of CD134 expression on T cells with HHV-6B replication after allo-HSCT, especially in UCBT. The results possibly indicate that CD134 on T cells plays a key role for HHV-6B replication after allo-HSCT.

Standard values for the urine HVA/VMA ratio in neonates as a screen for Menkes disease

BACKGROUND Menkes disease is a lethal disorder associated with copper metabolism. Although early treatment with copper-histidine injections can improve outcomes, early diagnosis is difficult because the clinical features of Menkes disease are subtle or do not manifest in affected neonates. Previous report stated that the low activity of dopamine β-hydroxylase, a copper-dependent enzyme, leads to increases in the urine homovanillic acid/vanillylmandelic acid (HVA/VMA) ratios in patients with Menkes disease, and indicated that a urine HVA/VMA ratio cut-off value of >4 is useful in screening for Menkes disease. METHODS We examined the standard values of the urine HVA/VMA ratio in unaffected neonates and assessed its use as a screening parameter for Menkes disease among neonates. In total, 112 neonates, aged between 1 and 6 days, were enrolled in the study and were classified into 2 groups based on their urine HVA/VMA ratios: high (>4) and low (⩽ 4). RESULTS Multivariate logistic analysis revealed that mechanical ventilation was an independent risk factor for a high urine HVA/VMA ratio (odds ratio: 21.94; 95% confidence interval: 2.82-247.03; p=0.004). The mean urine HVA/VMA ratio was 2.47 ± 0.67 among 92 neonates who did not receive mechanical ventilation. CONCLUSION This study established standard values for the urine HVA/VMA ratio in newborn babies that could be useful in screening for Menkes disease among neonates.

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

1 Ovadia D, Ezra E, Ben-Sira L et al. Primary pyomyositis in children: A retrospective analysis of 11 cases. J. Pediatr. Orthop. 2007; 16: 153–9. 2 Falagas ME, Rafalidis PI, Kapaskelis A et al. Pyomyositis associated with hematological malignancy: Case report and review of the literature. Int. J. Infect. Dis. 2008; 12: 120–5. 3 Pannaraj PS, Hulten KG, Gonzalez BE et al. Infective pyomyositis and myositis in children in the era of community-acquired, methicillin-resistant Staphylococcus aureus infection. Clin. Infect. Dis. 2006; 43: 953–60. 4 Trusen A, Beissert M, Schultz G et al. Ultrasound and MRI features of pyomyositis in children. Eur. Radiol. 2003; 13: 1050–5. 5 Lyn MY, Rezai K, Schwartz DN. Septic pulmonary emboli and bacteremia associated with deep tissue infections caused by community-acquired methicillin-resistant Staphylococcus aureus. J. Clin. Microbiol. 2008; 46: 1553–5. Fig. 1A Radionuclide scan showing left thoracic pyomyositis: (a–e) axial slices; (f–l) coronal slices.

Dried umbilical cord is a potential material for retrospective diagnosis of intrauterine enterovirus infection

Abstract Objective: To determine whether dried umbilical cords (UCs) are useful for retrospective diagnosis of intrauterine enterovirus (EV) infection. Methods: Dried UCs in two patients with neonatal EV sepsis and 10 neonates without infectious signs were enrolled. Viral RNA was extracted from their dried UCs, and nested reverse transcription polymerase chain reaction (RT-PCR) was performed. Results: Infection routes estimated by the clinical course were intrauterine infection in Case 1 and post-natal horizontal infection in Case 2. EV-RNA was detected from dried UC in Case 1, but not in Case 2 and 10 neonates. Conclusions: This report showed the potential use of dried UCs for retrospective diagnosis of intrauterine EV infection.

Postnatal serum concentrations of endogenous free fatty acids in newborns admitted to the neonatal intensive care unit: effects on unbound bilirubin

Background Few studies have reported the characterization of postnatal serum concentrations of endogenous free fatty acids (FFAs) in high-risk newborns and their effects on unbound bilirubin (UB). Methods Serum concentrations of FFA, albumin (Alb), UB and total bilirubin (TB) were measured in 713 samples obtained within 5 days after birth from 439 newborns without intravenous lipid supplementation admitted to the neonatal intensive care unit (NICU). Serum FFA was reported as the day-specific percentile-based curve. Serum FFA and FFA/Alb ratios were compared in term and preterm patients. To assess the impact of FFA on UB, daily changes in FFA/Alb and UB/TB ratios were compared in term patients without receiving phototherapy or any drugs, and linear regression analysis was performed between FFA/Alb ratio and serum UB concentration or UB/TB ratio using 140 sera with hyperbilirubinemia of term and preterm patients. Results A percentile-based curve showed that serum FFA peaked at 1 day of age and progressively decreased. Serum FFA and the FFA/Alb ratio were significantly higher in term than in preterm patients at birth and 1 and 3 days of age. FFA/Alb ratio significantly changed over 5 days after birth, but UB/TB ratio remained constant. FFA/Alb ratio did not correlate with serum UB concentration or UB/TB ratio in sera with hyperbilirubinemia. Conclusions We assessed postnatal concentrations of serum FFA in a large number of high-risk newborns admitted to the NICU. The concentration of endogenous FFAs in newborns admitted to the NICU was not rising until it influenced UB.

Corrigendum: Novel missense mutation in DLL4 in a Japanese sporadic case of Adams–Oliver syndrome

This corrects the article DOI: 10.1038/jhg.2017.48