Naomi Yoshikawa

The pilot study: Sphingomyelin-fortified milk has a positive association with the neurobehavioural development of very low birth weight infants during infancy, randomized control trial

AIM This study was a randomised control trial to examine the effects of sphingomyelin (SM), on the mental, motor and behavioural development of premature infants. PATIENTS AND METHODS Randomised, double-blind controlled trial, enroling infants born with a birth weight of less than 1500 g between January 2004 and October 2007 at Juntendo University Hospital, with follow-up to 18 months. Twenty-four preterm babies were randomly assigned; 12 were assigned to a test group and fed SM-fortified milk (SM 20% of all phospholipids in milk) and 12 were assigned to a control group (SM 13% of all phospholipids in milk). We analysed the composition of the plasma phospholipids and red-cell-membrane fatty acids, after which VEP, Fagan, BSID-II, attention and memory tests were performed. RESULTS The percentage of SM in the total phospholipids was significantly higher in the trial group than in the control group at 4, 6 and 8 weeks. The Behaviour Rating Scale of the BSID-II, the Fagan test scores, the latency of VEP, and sustained attention test scores at 18 months were all significantly better in the trial group than in the control group. CONCLUSION This study is the first to report that nutritional intervention via administration of SM-fortified milk has a positive association with the neurobehavioural development of low-birth-weight infants. However, detailed studies on the effects of SM on longer-term development are required.

Does breastfeeding in the neonatal period influence the cognitive function of very-low-birth-weight infants at 5 years of age?

AIM Breast milk is rich in docosahexaenoic acid (DHA), which is selectively concentrated in neuronal membranes and is thought to be necessary for optimal neurodevelopment. This study evaluated the relationship between breastfeeding, especially the resultant DHA level in the red blood cell (RBC) membranes of infants, and the cognitive function of very-low-birth-weight infants at 5 years of age. METHODS Eighteen patients were classified into groups that were breastfed or formula-fed or both. We measured the DHA concentration in the RBC membranes of 18 preterm infants at 4 weeks of age. To evaluate cognitive function at the age of 5 years, we asked the children to perform five tests: the Kaufman Assessment Battery for Children, Day-Night Test, Kansas Reflection Impulsivity Scale for Preschoolers (KRISP), Motor Planning Test, and Strengths and Difficulties Questionnaire. RESULTS The DHA level at 4 weeks after birth was significantly higher in the breastfed infants than in the formula-fed infants. The scores for the Day-Night Test, KRISP, and Motor Planning Test were significantly higher in the breastfed group. There were significant correlations between the scores for the Day-Night Test and for the KRISP and the level of DHA at 4 weeks of age. CONCLUSION Breastfeeding in the neonatal periods increases the DHA level in preterm infants and may have an important influence on brain development not only during early infancy but also during the preschool years, especially in terms of cognitive function.

IGF-I, leptin and active ghrelin levels in very low birth weight infants during the first 8 weeks of life

Aim:  We investigated the relationship between plasma insulin‐like growth factor I (IGF‐I), leptin, active ghrelin levels, and postnatal growth in very low birth weight (VLBW) infants.

Plasma levels of active ghrelin until 8 weeks after birth in preterm infants: relationship with anthropometric and biochemical measures

This study investigated the relationship between plasma levels of ghrelin and postnatal growth in preterm infants. The levels of active ghrelin in cord blood and in plasma in 25 very low birthweight (VLBW) infants were measured. The results indicate that the levels of circulating active ghrelin markedly increases after birth in VLBW infants, and suggest that the increased levels of ghrelin reflects the maturation of ghrelin production in the stomach and an increased physiological need for ghrelin.

Association between iron status and neurodevelopmental outcomes among VLBW infants

OBJECTIVE Our purpose was to evaluate iron status and neurodevelopmental outcomes in infants with and without extrauterine growth restriction (EUGR). METHODS This observational study evaluated 38 medically stable premature infants, with birth weights below 1500g. Iron status was determined by measuring venous levels of Hb, Fe, and serum ferritin. The infants were divided into EUGR and non-EUGR groups. At a corrected age of 18months, neurodevelopmental outcomes were checked using the Bayley scales, and body weight, body length, and head circumference were measured. RESULTS Hb levels at corrected ages of 1 and 3months and iron at a corrected age of 1 and 9months were significantly lower in the EUGR group compared with those of the non-EUGR group. There was no significant difference in the MDI score between the groups, but the PDI score at a corrected age of 18months was significantly lower in the EUGR group. We found a positive correlation between the serum level of Fe at 1month of age and PDI score at 18months of age. Head circumference at a corrected age of 18months did not differ between two groups, although body weight and length were lower in the EUGR group. CONCLUSIONS Developmental outcome in preterm infants at a corrected age of 18months may be influenced by nutritional factors, including iron status, during their early life.

The clinical utility of a near patient care rapid microarray-based diagnostic test for influenza and respiratory syncytial virus infections in the pediatric setting.

We evaluated the potential clinical utility of an automated near patient molecular assay Verigene Respiratory Virus Plus (RV+) and rapid immunochromatographic antigen tests (RIAT) in the pediatric setting for diagnosis of influenza and respiratory syncytial virus infections when testing was performed by the pediatrician seeing the patient. Overall, with respect to influenza virus, sensitivity and specificity for RIAT were 70.8% and 100%, respectively, compared to 100% and 96.2%, respectively, for RV+. For respiratory syncytial virus, sensitivity and specificity for RIAT were 78.9% and 100%, respectively, compared to 100% and 100%, respectively, for RV+. When RIAT and RV+ sensitivity for influenza virus was compared based on the time the patient presented after onset of fever, the sensitivity of RIAT at 6 hours was 37.5% compared to 100% for RV+. At 12 hours, RIAT improved to 60.9%. This study confirms the clinical utility of RV+ in the pediatric setting.

Neurodevelopment in the offspring of Japanese systemic lupus erythematosus patients

OBJECTIVE To evaluate pregnancy outcome of systemic lupus erythematosus (SLE) and the neuropsychological outcomes in offspring of SLE mothers. STUDY DESIGN Pregnancy outcomes of SLE patients from 1989 to 2006 were determined and the neuropsychological development of the children born to SLE patients was examined suited for their age; Bayley Scales of Infant Development up to four years and Kauffmann Assessment Battery for Children from four years onwards. RESULTS Of the 233 deliveries, 58 (24.7%) were preterm, 72 (30.9%) were low-birth-weight, and 46 (19.7%) were IUGR. Twenty-six children enrolled in this study had normal intelligence. The mean MDI and PDI were 95.8+/-10.1 and 94.6+/-14.1, respectively. The mean scores for the Sequential Processing scale, Simultaneous Processing scale, and Mental Processing composite were 103.1+/-13.3, 104.2+/-10.2, and 104.2+/-12.2, respectively. In the children with anti-Ro/SS-A antibody-positive mothers, mean gestational age and birth weight were significantly lower (p<0.05), as a result, the mean score of Sequential Processing and Mental Processing were significantly lower than that of negative mothers. The presence of maternal antiphospholipid antibody was not related to gestational age, birth weight and any score on the intelligence tests, except for the rate of IUGR. CONCLUSION The rates of preterm delivery and IUGR were frequent in the SLE patients and careful monitoring and management of the disease during pregnancy are still necessary. We should examine the neurodevelopment of the children born from mothers with anti-Ro/SS-A antibody prospectively.

Effects of parenteral soybean oil lipid emulsion on the long-chain polyunsaturated fatty acid profile in very-low-birth-weight infants

Aim:  Conventional soybean lipid emulsions contain no docosahexaenoic acid (DHA) or arachidonic acid (AA). We investigated the relationship between blood DHA and AA status in 27 very‐low‐birth‐weight (VLBW) infants with or without parenteral lipid emulsion.

A severe form of epidermal nevus syndrome associated with brainstem and cerebellar malformations and neonatal medulloblastoma

Here we report a boy with epidermal nevus syndrome associated with brainstem and cerebellar malformations and neonatal medulloblastoma. The patient had epidermal nevi and complicated brain malformations including macrocephaly with polymicrogyria, dysmorphic and enlarged midbrain tectum, enlarged cerebellar hemispheres with small and maloriented folia. The patient died after surgical resection of medulloblastoma which was newly recognized on MRI at 51 days of age. Postmortem pathological examinations showed very unique and bizarre malformation of the midbrain and hindbrain. The cerebellar cortex exhibited a coarse, irregular and bumpy surface, blurred border between the Purkinje cell layer and internal granule cell layer, and many foci of heterotopia in the cerebellar white matter. The brainstem showed multiple anomalies, including enlargement of superior colliculi, hypoplasia of pyramidal tracts and dysplasia of inferior olivary nuclei. The unusual constellation of brain malformations of our patient will widen the spectrum of epidermal nevus syndrome.

Challenges in genetic counseling because of intra-familial phenotypic variation of oral-facial-digital syndrome type 1.

Oral‐facial‐digital syndrome type 1 (OFD1; MIM 311200) is characterized by multiple anomalies of the oral cavity, face and digits. We report a family with OFD1, where two female siblings and their mother shared the same mutation of the responsible gene (OFD1) c.1193_1196delAATC. Phenotypic variability was observed among them; the mother showed minimal features of OFD1, whereas her two daughters showed partial features and the full spectrum of OFD1, respectively. Thus, OFD1 was suspected only after a health check‐up during pregnancy of the second patient showing fetal brain anomaly and maternal polycystic kidney. For these reasons, there was a delay in the recognition of OFD1 in this family. Patients with OFD1 show phenotypic variability, which poses challenges for genetic counseling.