Shunji Hikino

Physical Growth and Retinopathy in Preterm Infants: Involvement of IGF-I and GH

GH and IGF-I are important for physical growth. We measured serum levels of these factors in preterm infants. The study population (n = 81) was divided into three groups according to the gestational age. We evaluated differences in serum GH and IGF-I levels among groups with regard to physical growth and development of retinopathy of prematurity. Serum GH levels in extremely preterm infants born at <28 wk of gestational age were significantly higher than levels in those born between 28 and 34 wk at 1 and 2 mo of age. In contrast, serum IGF-I levels in extremely preterm infants remained low, whereas those in the other two groups gradually increased. Evaluation of the effects of GH and IGF-I on physical growth in very low birth weight infants (<1500 g) showed that IGF-I concentrations were positively related to physical growth for several months after birth, whereas no relationship was observed between GH and physical growth. Multivariate analysis demonstrated that high GH concentration at 1 mo of age was significantly associated with development of severe retinopathy of prematurity. In conclusion, persistent low serum IGF-I levels may explain the slow physical growth during neonatal life, and exposure of high GH may cause, at least in part, severe retinopathy of prematurity in preterm infants.

Microarray analysis of human milk cells: persistent high expression of osteopontin during the lactation period

To continue the search for immunological roles of breast milk, cDNA microarray analysis on cytokines and growth factors was performed for human milk cells. Among the 240 cytokine‐related genes, osteopontin (OPN) gene ranked top of the expression. Real‐time PCR revealed that the OPN mRNA levels in colostrum cells were approximately 100 times higher than those in PHA‐stimulated peripheral blood mononuclear cells (PBMNCs), and 10 000 times higher than those in PB CD14+ cells. The median levels of OPN mRNA in early milk or mature milk cells were more than three times higher than those in colostrum cells. Western blot analysis of human milk showed appreciable expression of full‐length and short form proteins of OPN. The concentrations of full‐length OPN in early milk or mature milk whey continued to be higher than those in colostrum whey and plasma as assessed by ELISA. The early milk (3–7 days postpartum) contained the highest concentrations of OPN protein, while the late mature milk cells (1 years postpartum) had the highest expression of OPN mRNA of all the lactating periods. The results of immunohistochemical and immunocytochemical staining indicated that OPN‐producing epithelial cells and macrophages are found in actively lactating mammary glands. These results suggest that the persistently and extraordinarily high expression of OPN in human milk cells plays a potential role in the immunological development of breast‐fed infants.

Long-term outcome of 51 liveborn neonates with non-immune hydrops fetalis.

To search for an efficient method of management of non‐immune hydrops fetalis (NIHF), the clinical outcome of 51 newborns with NIHF was retrospectively assessed in a single centre. As the short‐term outcome, the mortality rate was mainly dependent on the causes of NIHF and the presence of pleural effusion. The survival rate of the patients with pleural effusion (7/28; 25%) was significantly lower than that of those without it (14/23; 61%) (p < 0.02). All 7 survivors with pleural effusion were diagnosed antenatally after 29 weeks of gestation and were delivered after 31 weeks of gestation. With respect to the long‐term outcome, 13 (68.4%) of 19 patients who survived beyond 1 y of age showed normal development, 2 mild developmental delay at 1 y of age and 1 mental retardation at 8 y of age, while 3 (15.8%) had severe psychomotor retardation with marked growth failure. Two of these three patients were born as very‐low‐birthweight infants. The follow‐up results indicate that pleural drainage in utero and prevention of premature delivery should be proposed to improve the outcome of NIHF patients.

Food allergy and atopic dermatitis in low birthweight infants during early childhood

The prevalence rates of food allergy and atopic dermatitis in low birthweight infants were evaluated. In Fukuoka City, Japan, between July 1994 and September 1997, sufficient information including birthweight, gestational age, sex, feeding method and a history of food allergy was obtained from questionnaires at the well‐baby check‐ups of 21766 infants (18 mo of age) and 4378 children (3 y of age). All the children were examined by pediatricians with regard to the existence of atopic dermatitis. The prevalence rate (8.1%) of food allergy in infants with low birthweight (<2500 g) was significantly lower than that (11.2%) in infants with normal birthweight (>2500 g) at 18 mo of age (p= 0.0002). Atopic dermatitis was also observed at a lower prevalence rate (1.2%) in infants with low birthweight than in those with normal birthweight (2.3%) at the same age (p= 0.0041). However, this significance was lost at 3 y of age. Other characteristics including male sex and breast‐feeding showed independent risks for the development of food allergy and atopic dermatitis at both ages.

Quantitative analysis of glucose-6-phosphate translocase gene expression in various human tissues and haematopoietic progenitor cells

We investigated the quantitative expression of the human glucose-6-phosphate translocase gene (G6PT1) and its splicing variants in human tissues. The G6PT1 gene was strongly expressed in liver, kidney and haematopoietic progenitor cells, which might explain major clinical symptoms such as hepatomegaly, nephromegaly and neutropenia in glycogen storage diseases type Ib. Reverse transcriptase-mediated PCR amplification of G6PT1 cDNA revealed several splicing variants in tissue-specific manners. The brain-specific isoform, which has an additional 22 amino acids between exons 6 and 8, was also identified in heart and skeletal muscle. A new splicing variant, although less prominent in quantity and lacking polypeptide loops corresponding to exons 2 and 3, may have a distinct substrate affinity or specificity in leukocytes and haematopoietic progenitors. In conclusion, the G6PT1 gene was expressed in various tissues, and alternative splicing variants exist in tissue-specific manners.

An echovirus type 18 outbreak in a neonatal intensive care unit

We describe an outbreak of echovirus type 18 infection involving 20 neonatal intensive care unit (NICU) patients and the results of virological investigations are presented. RT-PCR demonstrated a widespread transmission of the virus in NICU patients during the outbreak. Separation care and additional infection control measures seemed to be effective in preventing further spread of the virus.

Fetal Germinal Matrix and Intraventricular Hemorrhage

Subependymal germinal matrix with intraventricular hemorrhage (GMIVH) is a common complication associated with delivery in preterm neonates but has rarely been observed in the fetus. Clinical and neuroradiological findings of 5 patients who were diagnosed as having fetal GMIVH with prenatal ultrasonographic examinations (US) and MRI, and postnatal MRI were reviewed retrospectively. During a seemingly uneventful pregnancy, fetal GMIVH occurred at approximately 30–33 weeks of gestation, with the absence of any known factor predisposing to fetal hemorrhage. Routine obstetric US revealed an intraventricular lesion in the enlarged ventricles. Prenatal MRI clearly demonstrated parenchymal change such as intracerebral hematoma adjacent to the subependymal and intraventricular hematoma, and periventricular leukomalacia as well as GMIVH. Although patients without parenchymal destruction (hemosiderin deposit alone) had a favorable neurodevelopmental outcome, encephalomalacia and periventricular leukomalacia contributed to long-term neurodevelopmental deficits. Evaluating parenchymal damage with prenatal MRI can therefore help to predict neurodevelopmental prognosis of the fetus with GMIVH.

Cervical (myelo)meningocoele: report of 2 cases

Two cases with posterior protruding cervical dysraphic lesions are presented; neuroimaging and clinical features of this rare clinical entity are discussed.

Increased inflammatory markers are associated with early periventricular leukomalacia

The aim of the study was to investigate whether inflammatory markers are associated with the occurrence of periventricular leukomalacia (PVL). Superoxide (O2‐) production of neutrophils and plasma antioxidative superoxide dismutase (SOD) activity in umbilical cord blood were studied. Participants were preterm infants with early PVL (n=6; three males, three females; mean birthweight 1458g [SD 517], range 620–2040g; mean gestational age 29.8wks [SD 2.9], range 27–34wks); and preterm control infants without PVL (n=10; five males, five females; mean birthweight 1838g [SD 664], range 925–2748g; mean gestational age 30.6wks [SD 3.1], range 26–34wks). In addition, pro‐inflammatory cytokine levels were measured in the umbilical cord blood. N‐formyl‐methionyl‐leucyl‐phenylalanine‐induced O2‐ production by neutrophils in infants with early PVL was significantly higher than that in the control group. In contrast, there was no significant difference in concentrations of copper/zinc‐SOD and SOD activity between groups. Concentrations of interleukin (IL)‐1β and tumour necrosis factor‐α (but not IL‐6, IL‐8, or granulocyte‐colony stimulating factor) were significantly higher in infants with early PVL than in control infants. The excess O2‐ produced by activated neutrophils with increased pro‐inflammatory cytokine production could play a role in the molecular cascade leading to white matter damage in PVL.

Liposteroid against refractory pulmonary haemorrhage in idiopathic pulmonary haemosiderosis

We describe two Japanese children with idiopathic pulmonary haemosiderosis (IPH), whose refractory haemorrhages were treated with an intravenous lipid emulsion containing dexamethasone (liposteroid). A 22-month-old boy and a 14-month-old girl have been observed with similar symptoms; periodic bouts of anaemia, reticulocytosis, diffuse infiltrates on chest X-ray and the finding of siderophages in sputum or gastric lavage fluid. The MRI of the lung was useful for the diagnosis. Methylprednisolone pulse therapy was successful in treating acute massive bleeding. Subsequent oral prednisolone could not prevent chronic recurrent haemorrhages. However, the intermittent administration of liposteroid (0.05 mg/kg/dose IV) led to a cessation of bleeding; the haemoglobin concentration rose to normal levels. This observation emphasizes the usefulness of liposteroid in the management of refractory IPH.