A Case of Neonate with Split Cord Malformation Presenting with Hypoplasia of the Left Lower Extremity.

The frequency of split cord malformation (SCM) is approximately 1 in 5000 births; however, patients are rarely diagnosed with SCM in the neonatal period. Moreover, there have been no reports of SCM with hypoplasia of the lower extremities at birth. A 3-day-old girl was transferred to our hospital for a thorough examination of hypoplasia of the left lower extremity and lumbosacral abnormalities detected after birth. The spinal magnetic resonance imaging (MRI) revealed a split spinal cord in a single dural tube. Based on the MRI findings, the patient was diagnosed with SCM type II. Following discussions with the parents, pediatricians, neurosurgeons, psychologists, and social workers, we decided to perform untethering to prevent further neurological impairment after achieving a sufficient body weight. The patient was discharged on day 25 of life. Early diagnosis and intervention may improve the neurological prognosis in terms of motor function, bladder and bowel function, and superficial sensation; thus, clinicians should report infrequent findings that may lead to SCM diagnosis. SCM should be differentiated in patients with left-right differences in the appearance of the lower extremity, particularly in those with lumbosacral abnormalities.

Characteristics and antimicrobial choice of pediatric bacterial enteritis in the Kanto region of Japan: A multicenter retrospective observational study.

INTRODUCTION: There are few reports on the causative microorganisms of bacterial enteritis in children in Japan in recent years. The distribution of causative microorganisms is important for estimating pathogens and making decisions regarding the treatment plan, as antimicrobial agents are not required for mild bacterial enteritis cases but are used for severe cases or immunocompromised patients. METHODS: We retrospectively surveyed pediatric patients who underwent stool culture at eight hospitals in the Kanto region of Japan from 2014 to 2019 for patient characteristics, causative microorganisms, and prescribed antimicrobial agents. RESULTS: A total of 4,475 stool cultures were submitted, and the positivity rate for bacterial enteritis was 11%. The causative microorganisms were Campylobacter spp. in 338 cases (67.3%), Salmonella spp. in 85 cases (16.9%), enterohemorrhagic Escherichia coli O157 in 23 cases (4.6%), and Yersinia spp. in 45 cases (9.0%). Hospitals with pediatric infectious disease physicians had a lower rate of antimicrobial therapy for Campylobacter enteritis than hospitals without pediatric infectious disease physicians. CONCLUSIONS: Campylobacter spp. are the most common causative agent for bacterial enteritis in this study, and the presence of pediatric infectious disease physicians may promote the appropriate use of antimicrobial agents.

Associations between size at birth and size at 6 years among preterm infants: a retrospective cohort study.

BACKGROUND: Little is known about the relationship between fetal growth and size at school age in children born prematurely. We evaluated the relationships between gestational age and anthropometric z-scores at birth and size at 6 years of age in very-low-birthweight infants born at <30 weeks' gestation. METHODS: We collected data from the medical records of 187 preterm children at birth and 6 years of age. We evaluated correlations between gestational age and z-scores for weight, body length, and head circumference at birth and z-scores for weight, height, and body mass index at 6 years of age. RESULTS: Simple regression analysis showed that, in boys and the overall group, gestational age and z-scores for weight, body length, and head circumference at birth had significant association with z-scores for weight, height, and body mass index at 6 years of age. No significant associations were found in girls, except for weight z-scores at 6 years with gestational age and head circumference z-scores at birth. Multiple regression analysis showed that gestational age and length z-score at birth were significantly and independently associated with weight and height z-score at 6 years. Gestational age was also significantly and independently associated with body mass index z-score at 6 years. CONCLUSION: Gestational age and fetal growth in length (assessed with the birth-length z-score) were associated with anthropometric z-scores at 6 years in very-low-birthweight children born at <30 weeks of gestation, especially in boys.

Epidemiology of methicillin-resistant Staphylococcus aureus in a Japanese neonatal intensive care unit.

BACKGROUND: There have been few reports on the genetic structure of the current population of methicillin-resistant Staphylococcus aureus (MRSA) from neonatal intensive care units (NICUs) in Japan. In the present study we conducted a molecular epidemiological analysis based on whole genome sequencing against MRSA strains in a Japanese NICU. METHODS: We performed genotyping by whole genome sequencing, polymerase chain reaction-based typing of Staphylococcal cassette chromosome mec (SCCmec) and polymerase chain reaction-based open-reading frame typing against 57 MRSA strains from fecal or nasal specimens from NICU patients in Juntendo University Shizuoka Hospital in 2013-2014. RESULTS: Forty-nine MRSA strains (86.0%) exhibited a clonal complex (CC) 1, and were divided into three sequence types (STs): ST2725 (n = 25), ST2764 (n = 21), and ST1 (n = 3). All CC1 MRSA strains had SCCmec IVa, and were resistant to new quinolones, which are limited in pediatric use, suggesting that these strains were derived from adult MRSA clones. Single nucleotide polymorphism differences of both ≤10 and >100 nucleotides were observed by pairwise, single nucleotide polymorphism analysis among ST2725 and ST2764 MRSA strains, respectively. Seven ST8 MRSA strains (12.2%) were isolated, and no strain exhibiting the Japanese hospital-associated MRSA genotype (ST5/SCCmec II) was isolated in this study. CONCLUSIONS: Our molecular epidemiological analysis suggested that ST2725 and ST2764 MRSA strains had genetic diversity that could not be explained only by a recent transmission event in the NICU. These MRSA clones might be disseminated in other Japanese hospital facilities as new endemic clones. Our results are expected to contribute to the improvement of infection control measures of MRSA in NICUs.

Amoxicillin effect on bacterial load in group A streptococcal pharyngitis: comparison of single and multiple daily dosage regimens.

BACKGROUND: Culture tests have demonstrated that once-daily administration of amoxicillin may be effective in the treatment of group A streptococcal (GAS) pharyngitis. However, culture methods do not allow accurate assessments of bacterial load changes because of the suppressive effect of the antibiotic on bacterial growth. In this study, we used real-time PCR to compare the effectiveness of once-daily and multiple-daily amoxicillin treatment for pediatric patients with GAS pharyngitis. METHODS: The subjects were children (≧3 years of age) diagnosed with GAS pharyngitis. Amoxicillin was administered at a dose of 40-50 mg/kg/day, divided into one (QD), two (BID), or three (TID) daily doses, for 10 days. Throat swabs were collected before treatment (visit 1), 1 to 3 days after treatment (visit 2), and 9 to 11 days after treatment (visit 3), and GAS copies were quantified by real-time PCR. The main compared parameters were the rate of negative PCR results and the number of GAS determined by PCR in throat swabs between each regimen. RESULTS: Samples were collected from 34 patients (QD, 12; BID, 15; TID, 7) at visit 1, 32 patients (QD, 11; BID, 14; TID, 7) at visit 2, and 25 patients (QD, 7; BID, 11; TID, 7) at visit 3. The rates of negative PCR result for QD, BID, and TID regimens were 18.2, 0, and 14.3% at visit 2, and 85.7, 72.7, and 85.7% at visit 3, respectively. The median values of bacterial load for QD, BID, and TID groups at visit 1 were 1.4 × 106, 8.2 × 105, and 5.4 × 105 copies/µL. At visit 2, they comprised 3.8 × 103, 1.1 × 103, and 2.8 × 103 copies/µL, respectively, whereas at visit 3, GAS copies were mostly undetectable. There was no statistical difference in the negative results and median value of GAS copies between regimens at any stage. CONCLUSIONS: Our results obtained by a molecular biology approach indicated that the QD regimen was as effective in eradicating GAS infection as BID or TID. TRIAL REGISTRATION: UMIN000036083 / March 12, 2019.

Breast-feeding regulates immune system development via transforming growth factor-ß in mice pups.

BACKGROUND: Breast milk contains important nutrients and immunoregulatory factors that are essential for newborn infants. Recently, epidemiological studies suggested that breast-feeding prevents a wide range of infectious diseases and lowers the incidence of infant allergic diseases. METHODS: To examine the effects of breast milk on immunological development in infancy, we established an artificial rearing system for hand-feeding mice and compared mouse pups fed with either breast milk or milk substitute. All mice were killed at 14 days of age and immune cells in the thymus, spleen, and small intestine were examined on flow cytometry. RESULTS: The number of thymocytes was higher whereas that of total immune cells of peripheral lymphoid tissues was lower in mice fed breast milk compared with milk substitute-fed mice. In peripheral lymphoid tissues, the proportion of B cells was higher and that of CD8+ T cells, macrophages, dendritic cells, and granulocytes was significantly lower in breast milk-fed mice. The same alteration in immune cells of the thymus and peripheral lymphoid tissues in milk substitute-fed mice was also observed in pups reared by mother mice treated with anti-transforming growth factor-ß (anti-TGF-ß) monoclonal antibody. CONCLUSIONS: Breast milk regulates the differentiation and expansion of innate and adaptive immune cells partly due to TGF-ß. Hence, TGF-ß in breast milk may be a new therapeutic target for innate immune system-mediated diseases of infancy.

Association of zinc and copper with clinical parameters in the preterm newborn.

BACKGROUND: Given that preterm infants are born at a time of rapid fetal growth, they are at risk of deficiency of essential nutrients for brain development, including zinc (Zn) and copper (Cu). This study evaluate the relationship between serum Cu or Zn, gestational age (GA) and anthropometric parameters at birth in preterm infants. METHODS: This was a retrospective study of infants <35 weeks' GA from January 2010 to August 2012. We collected the data from medical records of 59 preterm infants at birth with regard to GA, anthropometric parameters, and serum Cu and Zn levels. Correlation of Cu, Zn, and GA with anthropometric parameters at birth was then done. RESULTS: Zn was inversely correlated with GA, bodyweight (BW), body length (BL), and head circumference (HC), and Cu was inversely correlated with the standard deviation (SD) score for BW, BL, and HC. On stepwise multiple regression analysis, GA was a significant independent predictor of Zn level, and HC SD score was a significant independent predictor of Cu level. CONCLUSIONS: Prematurity influences Zn, and intrauterine head growth restriction influences Cu at birth in preterm infants. Further research is needed to evaluate the relationship between intrauterine growth restriction and brain Cu metabolism.

Clinically silent seizures in a neonate with tuberous sclerosis.

Although seizures during infancy in patients with tuberous sclerosis complex are common, seizures in neonates are infrequent. Here, we report the clinical course and electroencephalography (EEG) findings of a neonate with tuberous sclerosis complex associated with clinically silent seizures. The patient was a girl in whom cardiac tumors were detected on fetal ultrasonography. Brain magnetic resonance imaging during the neonatal period showed subependymal and cortical tubers. Routine EEG indicated unexpected ictal changes with no noticeable clinical symptoms. Ictal EEG was associated with a subtle increase in heart rate and a brief increase in chin electromyogram. These changes were difficult to identify clinically. The patient later developed focal seizures and epileptic spasms and had severe psychomotor delay. The present case suggests the occurrence of clinically silent seizures before the appearance of epileptic spasms in infants with tuberous sclerosis, and that EEG is an option for neonates with a prenatal diagnosis.

Lipid profile and atherogenic indices soon after birth in Japanese preterm infants.

AIM: The intra-uterine environment affects the risk of development of cardiovascular disease in adulthood. The aim of this study was to determine the influence of prematurity and foetal growth restriction on lipid metabolism, by assessing atherogenic indices soon after birth in preterm infants. METHODS: Blood samples were collected within 20 min of birth from 80 preterm infants with a gestational age of ≤35 weeks. Serum total cholesterol (TC), low-density lipoprotein cholesterol (LDLc), high-density lipoprotein cholesterol (HDLc), apolipoprotein-A1 (apoA1) and apolipoprotein-B (apoB) levels were measured. The ratio of TC/HDLc, LDLc/HDLc and apoB/apoA1 were also calculated. Correlations between these indices and gestational age, birth weight and the standard deviation (SD) score for birth weight were also determined. RESULTS: Gestational age, birth weight and SD score for birth weight were negatively correlated with the TC/HDLc, LDLc/HDLc and apoB/apoA1 ratios. CONCLUSION: In preterm infants, prematurity and poor foetal growth may influence lipid and apolipoprotein metabolism and affect atherogenic indices at birth.

Oxidative stress early in infancy and neurodevelopmental outcome in very low-birthweight infants.

BACKGROUND: Reactive oxygen species may be involved in serious diseases in premature infants. The objective of this study was to assess the relationship between neurodevelopmental outcome and oxidative stress marker level in the urine of very low-birthweight (VLBW) infants. METHODS: Spot urine samples were collected from 35 VLBW infants. Urinary excretion of 8-hydroxy-2″-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, and 8-iso-prostaglandin F2α (8-isoPGF), a marker of lipid peroxidation, was measured at 1, 2, 4, and 6 weeks of age. Neurodevelopmental outcome at 18 months' corrected age was assessed using the Bayley Scales of Infant Development (BSID)-II. RESULTS: Significant correlations were found between urinary 8-OHdG at 2 and 4 weeks and the Mental Development Index of the BSID-II. No significant correlation was found between urinary 8-isoPGF and indices of the BSID-II. CONCLUSIONS: In VLBW infants, urinary 8-OHdG level correlated with mental development rather than psychomotor development at 18 months' corrected age; urinary 8-OHdG might be a predictive marker of neurodevelopmental outcome in VLBW infants.

Effect of probiotics on mother-to-neonate vertical transmission of group B streptococci: A prospective open-label randomized study.

BACKGROUND: Group B Streptococci (GBS) are common vaginal bacteria found in 20-30% of pregnant women and a significant cause of invasive infections in newborns. Recently, attention has been focused on the efficacy of probiotics during the perinatal period. However, the effect of probiotic intake on the mother-to-child transmission (MTCT) of GBS remains unknown. METHODS: Pregnant women with positive GBS results from vaginal and rectal swab cultures at 35-37 weeks of gestation were randomly assigned to the probiotic group or the control group in an open-label manner at the Department of Obstetrics and Gynecology, San-ikukai Hospital, Tokyo, Japan. The probiotic group received Lactobacillus reuteri during antenatal checkups from 35 to 37-week gestation to 1 month after delivery. Rectal swabs were obtained from the newborns at 5 days and at 1 month of age. Whole-genome sequencing was performed to test for GBS strains in the mother, whose newborn carried GBS at the 1-month checkup. Multi-locus sequence typing and single nucleotide polymorphism analyses were performed to identify MTCT. RESULTS: Overall, 67 mother-infant pairs were included, with 31 in the probiotic group and 36 in the control group. The positivity rate of GBS in newborns at 1 month of age was 10% (n = 3) in the probiotic group and 28% (n = 10) in the control group. In newborns carrying GBS at 1 month of age, genetic analysis revealed that the MTCT rate was 6% in the probiotic group and 22% in the control group, although the difference was not statistically significant (p = 0.0927). CONCLUSION: No statistically significant difference was found; however, the consumption of L. reuteri by women with GBS-positive pregnancies may inhibit the MTCT of GBS.

Whole-exome sequencing of a unique brain malformation with periventricular heterotopia, cingulate polymicrogyria and midbrain tectal hyperplasia.

We report a case of an infant with unique and unreported combinations of brain anomalies. The patient showed distinctive facial findings, severe delay in psychomotor development, cranial nerve palsy and seizures. Brain magnetic resonance imaging performed at 5 days of age revealed complex brain malformations, including heterotopia around the mesial wall of lateral ventricles, dysmorphic cingulate gyrus, and enlarged midbrain tectum. The patient unexpectedly died at 13 months of age. Postmortem pathological findings included a polymicrogyric cingulate cortex, periventricular nodular heterotopia, basal ganglia and thalamic anomalies, and dysmorphic midbrain tectum. Potential candidate genes showed no abnormalities by traditional PCR-based sequencing. Whole-exome sequencing confirmed the presence of novel gene variants for filamin B (FLNB), guanylate binding protein family member 6, and chromosome X open reading frame 59, which adapt to the autosomal recessive mode or X-linked recessive mode. Although immunohistochemical analysis confirmed the expression of FLNB protein in the vessel walls and white matter in autopsied specimens, there may be functional relevance of the compound heterozygous FLNB variants during brain development.

Evaluation of the transmission of SARS-CoV-2 through breast milk: a case series.

Whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted through breast milk remains controversial. This study aimed to determine the presence of SARS-CoV-2 in breast milk and assess its transmissibility to the child in infancy. Eleven samples were obtained from nine mothers with coronavirus disease 2019 (COVID-19). All but one sample had negative results on a reverse transcription-quantitative polymerase chain reaction. Among nine children, five were diagnosed with COVID-19, including one child whose mother's milk tested positive. Although SARS-CoV-2 RNA was detected in breast milk, its possible transmission via breastfeeding could not be established. Thus, we conclude that the physical attachment between mother and child is a conceivable transmission route.

Subtelomeric deletions of 1q43q44 and severe brain impairment associated with delayed myelination.

Subtelomeric deletions of 1q44 cause mental retardation, developmental delay and brain anomalies, including abnormalities of the corpus callosum (ACC) and microcephaly in most patients. We report the cases of six patients with 1q44 deletions; two patients with interstitial deletions of 1q44; and four patients with terminal deletions of 1q. One of the patients showed an unbalanced translocation between chromosome 5. All the deletion regions overlapped with previously reported critical regions for ACC, microcephaly and seizures, indicating the recurrent nature of the core phenotypic features of 1q44 deletions. The four patients with terminal deletions of 1q exhibited severe volume loss in the brain as compared with patients who harbored interstitial deletions of 1q44. This indicated that telomeric regions have a role in severe volume loss of the brain. In addition, two patients with terminal deletions of 1q43, beyond the critical region for 1q44 deletion syndrome exhibited delayed myelination. As the deletion regions identified in these patients extended toward centromere, we conclude that the genes responsible for delayed myelination may be located in the neighboring region of 1q43.

Use of Head and Chest Circumference Ratio as an Index of Fetal Growth Retardation in Preterm Infants.

We evaluated the relationship between fetal growth in preterm babies using the head circumference (HC)/chest circumference (CC) ratio and other anthropometric parameters at birth and at school age. Data were collected from 187 very low birth weight (VLBW) children born at less than 30 weeks of gestational age (GA) at birth and at 6 years. We assessed the correlation between the HC/CC ratio and body weight (BW), body length (BL), and HC z-scores at birth, and BW, body height (BH), and body mass index (BMI) z-scores at 6 years. Multiple regression analysis showed that BW z-score, BL z-score, and HC z-score at birth were significantly associated with HC/CC at birth. The BMI z-score at 6 years was also significantly associated with HC/CC at birth. The HC/CC ratio at birth is a reliable parameter for evaluating fetal growth restriction and a possible predictor of physical growth in VLBW children.

A COL4A1 variant in a neonate with multiple intracranial hemorrhages and congenital cataracts.

A 2-day-old neonate presented with seizures, multiple intracranial hemorrhages, and bilateral congenital cataracts. Targeted next-generation sequencing of the collagen type IV alpha 1 chain (COL4A1) gene revealed a heterozygous de novo missense variant (NM_001845.6:c.2291G>A/p.Gly764Asp). This missense variant adds to the compendium of COL4A1 variants and is associated with a COL4A1-related disorder.

Growth Trajectories during the First 6 Years in Survivors Born at Less Than 25 Weeks of Gestation Compared with Those between 25 and 29 Weeks.

We aimed to determine the differences in the growth trajectories of the youngest gestational survivors (<25 weeks' gestation) up to 6 years of age compared to those of older gestational ages. Preterm infants were divided into two groups: 22−24 weeks' gestation (male (M) 16, female (F) 28) and 25−29 weeks' gestation (M 84, F 59). Z-scores of body weight (BW), body length (BL), and body mass index (BMI) were derived from Japanese standards at 1, 1.5, 3, and 6 years of corrected age. Comparisons between the two groups by sex were made using the Wilcoxon test and linear regression analysis to examine the longitudinal and time-point associations of anthropometric z-scores, the presence of small for gestational age (SGA), and the two gestational groups. BW, BL, BMI, and z-scores were significantly lower in the 22−24 weeks group at almost all assessment points. However, there were no significant differences in BW, BL, BMI, and z-scores between the two female groups after 3 years. BMI z-scores were significantly associated with the youngest gestational age and the presence of SGA at all ages in males, but not in females. The youngest gestational age had a greater influence in males on the z-score of anthropometric parameters up to 6 years of age.

Clinical Features of Children with COVID-19 in Initial Time of Pandemic.

Objectives: COVID-19 (Coronavirus Disease 2019) is now a global pandemic. Although children are said to have mild symptom, their clinical features are not known well. We conducted a retrospective study during initial term of pandemic to understand the difference of clinical features including clinical symptoms and patients' characteristics of COVID-19 children and those without COVID-19. Materials: To compare clinical features between children with and without COVID-19, we collected data on children who received a COVID-19 test between March 25th and October 31st, 2020. All data were collected from medical records. Methods: There were three groups of patients in the study sample; patients with COVID-19, patients with close COVID-19 contact and performed COVID-19 tests, and patients suspected COVID-19 but tested negative. We analyzed the clinical features of the groups. Results: A total of 108 patients were included in this study, of whom 30 were patients with COVID-19, 25 were patients with close COVID-19 contact, 51 were suspected COVID-19 but tested negative, and two were excluded because they were infants born from COVID-19 mothers. The statistical analysis showed that children with COVID-19 had contact with COVID-19 patients had fewer clinical symptoms including cough and fever compared to children with a negative test of COVID-19. Sensitivity analysis showed that fever, cough, fever and/or cough could not distinguish children with COVID-19 from those without COVID-19. As conclusion, children with COVID-19 have less symptoms as fever or cough and the clinical symptoms cannot distinguish them from children with other diseases.