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.

Evaluating nocturnal polyuria in Japanese children with nocturnal enuresis.

BACKGROUND: The purpose of this study was to assess whether enuretic Japanese patients with nocturnal polyuria (NP) who met Hoashi's criteria (6-9 years: ≥200 mL; 10 years and older: ≥250 mL) met the International Children's Continence Society (ICCS; expected bladder capacity × 130%) and Rittig's criteria for nocturnal polyuria (>[age+9] × 20 mL). We also compared the effectiveness of 1-desamino-8-d-arginine vasopressin (DDAVP) with the three criteria. METHODS: Fifty-four patients who had NP with normal bladder capacity were enrolled: 36 boys (67%); median age, 8 (interquartile range: 7-9). We compared the diagnostic differences between the Hoashi's criteria and international standards (ICCS and Rittig's) for NP and the short-term effects of DDAVP. The patients received DDAVP for 8 weeks; we evaluated the association between each evaluation method and the effects of therapy. RESULTS: Only 17% of the patients met both Hoashi's and ICCS criteria, whereas 26% met both Hoashi's and Rittig's criteria. The therapeutic effect of DDAVP did not differ significantly between these two groups: there was an effective rate of 73% (Hoashi's criteria) versus 50% (ICCS criteria), P = 0.19, and an effective rate of 71% (Hoashi's criteria) versus 62% (Rittig's criteria), P = 0.84. CONCLUSIONS: Hoashi's criteria are widely used but, according to both the ICCS and Rittig's criteria, approximately 80% of the patients did not fulfill the definition of NP. However, 8 weeks after the DDAVP treatment began, no significant difference was observed in the therapeutic effect of DDAVP according to each set of criteria. The definition of NP should account for the physical disparities between Japanese people and Westerners.

Unsatisfactory Short-Term Neurodevelopmental Outcomes of Preterm Infants Who Received Polymyxin B-Immobilized Fiber Column-Direct Hemoperfusion for Septic Shock.

Sepsis and septic shock are associated with high mortality and neurodevelopmental impairment in preterm infants. Recently, endotoxin and mediator removal using a polymyxin B-immobilized fiber column for direct hemoperfusion (PMX-DHP) has been used for the management of septic shock even in neonates. Although early withdrawal from shock with PMX-DHP contributes to survival, its effect on neurodevelopment after discharge is unclear. This study aimed to examine short-term neurodevelopmental impairment in preterm infants with septic shock who were treated with PMX-DHP. We retrospectively assessed five infants who received treatment with PMX-DHP (median 25.5 [interquartile range: 24.8-28.3] weeks and 817 [interquartile range: 667-954] g). Neurodevelopmental outcomes were assessed with the Kyoto Scale of Psychological Development 2001 at a median 34.5 (interquartile range: 29.5-44.5) months of corrected age after discharge. The short-term neurodevelopmental prognosis of preterm infants treated with PMX-DHP for septic shock was delayed (overall developmental quotient < 70) with an average quotient of 57.3. Furthermore, four (80%) of five patients presented with intraventricular hemorrhage and another four (80%) with periventricular leukomalacia. In conclusion, preterm infants with septic shock treated with PMX-DHP had unsatisfactory short-term neurodevelopmental outcomes. Hence, the effect of PMX-DHP in improving neurodevelopmental prognosis even in preterm infants with septic shock should be further evaluated.

Clinical Effects and Outcomes After Polymyxin B-Immobilized Fiber Column Direct Hemoperfusion Treatment for Septic Shock in Preterm Neonates.

OBJECTIVES: To compare the effectiveness and mortality of early-onset sepsis or late-onset sepsis treatments with polymyxin B-immobilized fiber column direct hemoperfusion in terms of effectiveness and mortality in preterm infants with septic shock. DESIGN: Retrospective cohort study. SETTING: Neonatal ICU within a tertiary care hospital. PATIENTS: Of 1,115 patients, 49 had blood culture-proven sepsis between January 2013 and December 2018; six and five patients with septic shock had undergone polymyxin B-immobilized fiber column direct hemoperfusion treatment for early-onset sepsis (early-onset sepsis group) and late-onset sepsis (late-onset sepsis group), respectively. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Baseline demographic characteristics of both groups were similar. The time from decision to treatment induction was significantly shorter in the early-onset sepsis group than that in the late-onset sepsis group (p = 0.008). The mortality rate after 28 days of treatment and the hospital mortality were significantly lower in the early-onset sepsis group than in the late-onset sepsis group (p = 0.026 and 0.015, respectively). The PaO2/FIO2 ratio was significantly higher in the early-onset sepsis group than in the late-onset sepsis group at the end of the treatment (p = 0.035). In addition, median arterial-to-alveolar oxygen tension ratio significantly improved from 0.19 to 0.55, and median blood pressure also significantly improved from 32.5 to 40.0 mm Hg after the treatment in the early-onset sepsis group. Interleukin-6 levels significantly decreased after treatment in the early-onset sepsis group (p = 0.037). The Pediatric Risk of Mortality III score was similar between the early-onset sepsis and late-onset sepsis groups before and after the treatment. Intraventricular hemorrhage events occurred in both groups, but with no significant differences (p = 0.175). CONCLUSIONS: Polymyxin B-immobilized fiber column direct hemoperfusion treatment for preterm infants with septic shock due to early-onset sepsis is associated with earlier hemodynamic and respiratory status improvements and with lower mortality than that due to late-onset sepsis. Early neonatal septic shock detection and polymyxin B-immobilized fiber column direct hemoperfusion induction may improve the prognosis of affected infants.

The influence on renal function of ibuprofen treatment for patent ductus arteriosus in extremely low birthweight infants.

BACKGROUND: Ibuprofen (IBU) has been used recently for the treatment of patent ductus arteriosus (PDA) in Japan. We aimed to investigate the efficacy and adverse events of IBU and compare them with those of indomethacin (IND) as PDA treatment for extremely low-birthweight infants (ELBWIs), focusing on short-term renal function. METHODS: A case-control study was conducted on 16 ELBWIs. The data from eligible patients were divided into two groups. Ten patients had undergone IND treatment (IND group) between January 2017 and June 2018, whereas six had undergone IBU treatment (IBU group) for PDA between July 2018 and December 2018. The IND group received 0.1 mg/kg/12h IND IV infusion for three doses, whereas the IBU group received 10 mg/kg IV IBU infusion followed by 5 mg/kg/day for 2 days. We compared the efficacy for PDA closure and renal impairment between the two groups. RESULTS: No significant differences in primary closure rates and the PDA ligation required were observed between the two groups. No significant differences were observed between the incidence of intraventricular hemorrhage and gastrointestinal complications in both groups. Changes in urine volume (%) in the IBU group were significantly higher than in the IND group at 24-36 h post-administration. The urinary L-type fatty acid binding protein concentration level at 7 days of life was significantly lower in the IBU group than in the IND group. CONCLUSION: Although IBU was comparable to IND in PDA closure rate, IBU was superior to short-term renal injury in ELBWIs.

Marked thrombocytopenia in a neonate is associated with anti-HPA-5b, anti-HLA-A31, and anti-HLA-B55 antibodies.

Maternal antibodies against human platelet antigen (HPA) and/or human leukocyte antigen (HLA) cause fetal and neonatal alloimmune thrombocytopenia (FNAIT) in 0.09-0.15% of live births. Severe cases account for 5-31% and the frequency of multiple kinds of alloantibodies is 6.9-9% of FNAIT. We present a case of severe FNAIT associated with anti-HPA-5b, anti-HLA-A31, and anti-HLA-B55 antibodies, successfully treated with immunoglobulin and platelet transfusion. The anti-HLA-B55 antibody was detected in the newborn's serum, but disappeared on the 20th day, which was followed by an increase of the platelet count. These findings suggested the potential involvement of an anti-HLA antibody in the pathogenesis of FNAIT.

Association between the frequency of bedwetting and late preterm birth in children aged ≥5 years.

AIM: We examined the associations between late preterm (LPT) birth children aged ≥5 years and the frequency of bedwetting. Moreover, those who were born full-term/low birthweight (BW), LPT/low BW, LPT/normal BW and LPT/low BW were compared. METHODS: In total, we evaluated 614 patients who underwent assessments for frequent bedwetting at the three hospitals from January 2014 to December 2016. Data at the initial visit were collected from the electronic medical records. We assessed the patients' bladder diaries and questionnaires containing detailed information on demographics and frequency of bedwetting per month. Neonatal data were collected from the Maternal and Child Health Handbook. RESULTS: Frequency of bedwetting in the LPT/low BW group was higher than in the term/low BW group (28 vs. 22.5, p < 0.05). However, the frequency between the LPT/normal BW group and the LPT/low BW group was not significantly different (28 vs. 28, p = 1.00). Multiple regression analyses were conducted to eliminate potential confounding factors, attention-deficit/hyperactivity disorder and intellectual disability, but results were not changed. CONCLUSION: This study revealed that LPT/low BW was associated with increased frequency of bedwetting in children. The results suggest that gestational age should be considered when examining patients with severe bedwetting.

Effect of PMX-DHP for sepsis due to ESBL-producing E. coli in an extremely low-birthweight infant.

We report a case of early onset sepsis caused by (CTX for cefotaximase and M for Munich)-type extended-spectrum ß-lactamase-producing Escherichia coli (ESBL E. coli) in a preterm infant weighing 601 g. He was given meropenem and treated for endotoxin absorption with polymyxin B-immobilized fibers with only 8 mL of priming volume. The patient survived without any short-term neurological or respiratory sequelae. The choice of antibiotics is particularly important in seriously ill neonates with sepsis due to ESBL-producing organisms. Polymyxin B hemoperfusion might be an innovative therapy for severe neonatal sepsis and could improve outcome even in an extremely low-birthweight infant.

A case of congenital diaphragmatic hernia with intradiaphragmatic pulmonary sequestration: case report and literature review.

Extralobar pulmonary sequestration (EPS) can occasionally be found incidentally in congenital diaphragmatic hernia (CDH). Extralobar pulmonary sequestration usually arises in the chest or the abdomen; rarely in the diaphragm. We report a neonatal case of antenatally diagnosed CDH associated with intradiaphragmatic EPS.

False positive of an immunochromatography kit for detection of norovirus in neonatal feces.

Norovirus was detected in the feces from five neonates in the growing care unit by a rapid immunochromatography (ICG) kit. However, confirmation using reverse transcription polymerase chain reaction (RT-PCR), RT-loop-mediated isothermal amplification (RT-LAMP), and nested RT-PCR methods showed negative results from all the feces. In addition, the ICG test for the detection of norovirus was positive for four cases out of the 16 feces from other asymptomatic neonates/infants. Only one feces out of the four samples was positive by RT-LAMP. In this study, among the factors related to false positives with the norovirus ICG kit, there were no differences regarding the commencement of feeding, nutrition, and sample collection methods. Since the false positive rate of ICG in the diagnosis of norovirus infection in neonates and early infancy is high, ICG is not an appropriate method, and it is necessary to confirm the results using reliable methods like RT-PCR.

Two cases of partial dominant interferon-γ receptor 1 deficiency that presented with different clinical courses of bacille Calmette-Guérin multiple osteomyelitis.

We experienced two cases of unrelated Japanese children with bacille Calmette-Guérin (BCG) multiple osteomyelitis with partial interferon (IFN)-γ receptor 1 (IFNGR1) deficiency. Heterozygous small deletions with frame shift (811 del4 and 818 del4) were detected, which were consistent with the diagnosis of partial dominant IFNGR1 deficiency. Case 1: a 2-year-old boy visited us because of limb and neck pain. He had been vaccinated with BCG at 17 months of age. Multiple destructive lesions were observed in the skull, ribs, femur, and vertebral bones. Mycobacterium bovis (BCG Tokyo 172 strain by RFLP technique) was detected in the bone specimen. The BCG multiple osteomyelitis was treated successfully without recurrence. Case 2: an 18-month-old girl developed multiple osteomyelitis 9 months after BCG inoculation. Radiologic images showed multiple osteolytic lesions in the skull, ribs, femur, and vertebrae. M. bovis (BCG Tokyo 172 strain) was detected in the cultures from a bone biopsy. Her clinical course showed recurrent osteomyelitis and lymphadenitis with no pulmonary involvement. The effects of high-dose antimycobacterial drugs and IFN-γ administration were transient, and complete remission has since been achieved by combination antimycobacterial therapy, including levofloxacin. Partial dominant IFNGR1 deficiency is a rare disorder, but it should be considered when a patient presents with multiple osteomyelitis after BCG vaccination. The cases that are resistant to conventional regimens require additional second-line antituberculous drugs, such as levofloxacin.

The validity of the criteria for primary infection of Chlamydophila pneumoniae in children by measuring ELISA IgM antibodies.

As IgM antibody measurement by enzyme-linked immunosorbent assay (ELISA) has become possible for the serological diagnosis of Chlamydophila pneumoniae (C. pn) infection, the HITAZYME-ELISA method has become widely employed in Japan. However, in children, when the diagnostic criterion of primary infection is set at ID ≥1.1, the positive rate is higher than expected, and the potential for inaccurate reflection of the prevalence has been raised. In this study, we performed ROC analysis involving 136 pediatric patients with acute airway symptoms (0-14 years of age), considering a 32-fold or higher micro-immunofluorescence IgM antibody titer against C. pn as positive. Setting the cut-off value for ELISA C. pn IgM antibody ID at 2.0, the specificity was 100%, with no false positivity. The maximum (sensitivity + specificity)/2 was obtained when the cut-off value was set at 1.5. Therefore, IgM ID ≥2.0 was regarded as definitely positive and an IgM ID between 1.5 and 2.0 was regarded as indeterminate as diagnostic criteria for the primary infection. When the prevalence was investigated in 3,108 children (0-15 years of age) with airway symptoms based on these criteria, 542 cases (17.4%) were positive, and the median duration of IgM antibody positivity was five months. Long-term positivity (ten cases) for more than 12 months and recurrent positivity (eight cases) were also observed, but it may be appropriate to set a new criterion of IgM antibody ID ≥2.0 for the diagnosis of primary Chlamydophila pneumoniae infection in children.

An infant of 26 weeks gestation with congenital miliary tuberculosis complicated by chronic lung disease requiring CPAP was diagnosed on Day 104 of life: congenital tuberculosis was confirmed by detection of calcified ovaries in his mother.

INTRODUCTION: Early diagnosis of tuberculosis (TB) in infants is important but is commonly missed because the symptoms are often non-specific. CASE PRESENTATION: A Nepalese male infant born at 26 weeks gestation and weighing 1227 g (97th centile) was admitted to the neonatal intensive care unit (NICU) immediately after birth for the management of his prematurity. After extubation on Day 8, his oxygen saturation became unstable and he required nasal continuous positive airway pressure with oxygen for 3 months. On Day 104, further detailed evaluation was required because there was no improvement in his respiratory condition. A computed tomography (CT) scan demonstrated scattered miliary nodules in both lung fields. Acid-fast staining for the mycobacteria and TB polymerase chain reaction (PCR) of the sputum obtained directly by laryngeal aspiration confirmed Mycobacterium tuberculosis. On Day 105, he was therefore transferred to a tertiary care hospital for further intensive care. Pathology findings suggested placental involvement with TB owing to chronic endometrial infection. In addition, a maternal abdominal CT scan demonstrated bilateral calcified lesions in the ovaries. He completed antituberculous chemotherapy and was discharged 3 months later. At 18 months of age there are no sequelae and his development is almost normal. None of the infants or medical personnel who were exposed in the NICU developed secondary TB. CONCLUSION: In neonates with persistent respiratory distress, neonatologists should consider TB infection as a differential diagnosis. ABBREVIATIONS: CLD: chronic lung disease; CRP: C-reactive protein; CT: computed tomography; IGRA: interferon-γ release assay; IVF-ET: in vitro fertilisation-embryo transfer; N-CPAP: nasal continuous positive airway pressure; NICU: neonatal intensive care unit; PCR: polymerase chain reaction; PROM: premature rupture of membranes; TB: tuberculosis; WBC: white blood cells.

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.

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.