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Among patients with transient abnormal myelopoiesis (TAM) associated with Down syndrome, approximately 20% die within 6 months from multiorgan failure, especially liver fibrosis. We experienced three children with TAM who had low white blood cell counts but increased bilirubin levels. Here, we discuss the detailed clinical courses of these patients, including the pathological findings of liver biopsies. Our cases, together with previous literature, suggest that liver biopsy can be performed safely and provides useful information, especially regarding disease activities, and that low-dose cytarabine is a reasonable option to prevent early death in TAM patients with liver dysfunction.

DOI： 10.18926/AMO/65153

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Histidine-rich glycoprotein (HRG) has been reported to inhibit signaling leading to the release of high mobility group box 1 protein, a damage-associated molecular pattern. The present study aimed to determine the longitudinal change in HRG levels in extremely preterm infants and assess whether complications such as bronchopulmonary dysplasia (BPD) were associated with differences in HRG levels. In this multicenter, prospective, observational study, we measured serum HRG levels every 2 weeks from birth to 8 weeks of age. Serum HRG was measured using an enzyme-linked immunosorbent assay. We included 19 extremely preterm infants in the study and 74 samples were analyzed. The median gestational age was 26.0 weeks, and the median birth weight was 858 g. Serum HRG levels showed a significant upward trend after birth (p < 0.001); median HRG concentrations at birth and at 2, 4, 6, and 8 weeks of age were 1.07, 1.11, 2.86, 6.05, and 7.49 µg/mL, respectively. Onset of BPD was not associated with differences in serum HRG levels. Further, the serum HRG levels increased significantly after birth in extremely preterm infants.

DOI： 10.3390/biomedicines11010212

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BACKGROUND: Neonatal abstinence syndrome (NAS) induced by opiate use is common worldwide. While psychiatric drugs are a more common cause of NAS in Japan, infants of mothers taking psychiatric medications do not always develop NAS. The purpose of this study was to develop a practical model for predicting the onset of nonopiate-induced NAS using variables available at birth. METHODS: In this diagnostic study, prediction models were developed using multivariable logistic regression with retrospective data collected at our hospital between 2010 and 2019. NAS diagnosis was based on the Isobe score, and maternal medications were converted to dose equivalents. RESULTS: A total of 164 maternal and infant dyads met the inclusion criteria; 91 were included in the analysis, of whom 29 infants (32%) were diagnosed with NAS. Final models were created with and without the drug indices. The model without the drug indices consisted of neonatal head circumference in z-score and Apgar score at 5 minutes < 9, and the model with the drug indices included these, as well as antipsychotics and hypnotics indices. The C-statistics were 0.747 (95% CI: 0.638-0.856), and 0.795 (95% CI: 0.683-0.907), respectively, indicating good predictive accuracy of NAS onset for the models. CONCLUSIONS: This study developed models that predicted nonopiate-induced NAS with good accuracy, which may be further improved through the use of drug indices.

DOI： 10.1111/ped.15435

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Language：Japanese   Publisher：(株)メディカ出版  

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BACKGROUND: Children born preterm may be less physically active than children born term because of neurocognitive problems, reduced lung function, and poor physical fitness. We evaluated sports participation of children and adolescents who had been born preterm (<37 weeks) and early term (37-38 weeks) in 2001. METHODS: Data from a nationwide longitudinal survey (n = 47,015, including 2375 children born preterm) were analyzed. As indicators of sports participation, we used responses to questions about participation in sports clubs at 7 and 10 years old and in extracurricular school sports at 15 years old. RESULTS: Children born very preterm (25-31 weeks) and moderately to late preterm (32-36 weeks) were less likely to participate in sports clubs at 7, 10, and 15 years old than children born full term (39-41 weeks). Compared with children born full term, the adjusted risk ratios for participation in extracurricular school sports at 15 years old were 0.86 (95% confidence interval: 0.75-0.98) for children born very preterm, 0.92 (0.88-0.97) for children born moderately to late preterm, and 1.00 (0.98-1.02) for children born early term. CONCLUSIONS: Our findings suggest that preterm birth is associated with less participation in organized sports during childhood and adolescence than full-term birth. IMPACT: Research investigating associations between preterm birth and physical activity among children born in the 2000s is limited. This study shows that preterm birth was associated with less participation in organized sports during childhood and adolescence than full-term birth, especially in boys, and the participation in organized sports of children born preterm decreased as gestation shortened. During childhood, boys born early term were also less likely to participate in organized sports than boys born full term, suggesting a continuum with preterm births. These findings offer important additional insights into the limited evidence available for predicting future health outcomes for preterm infants.

DOI： 10.1038/s41390-021-01808-9

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BACKGROUND: No relationship has been reported between nonopiate neonatal abstinence syndrome (NAS) and anthropometric indices, including head circumference (HC). The purpose of this study was to determine the relationship between maternal nonopioid drug use and HC at birth in neonates with NAS. METHODS: This retrospective observational study included neonates born between January 1, 2010 and March 31, 2019, whose mothers had been taking antipsychotic, antidepressant, sedative, or anticonvulsant medications. The outcome measures were HCs of NAS infants and controls. RESULTS: Of 159 infants, 33 (21%) were diagnosed with NAS. There was no maternal opioid use among mothers during pregnancy. The HCs in the NAS group were significantly smaller than those in the control group. The median z-scores for HC at birth were -0.20 and 0.29 in the NAS group and the control group, respectively (P = .011). The median HCs at birth were 33.0 and 33.5 cm in the NAS group and the control group, respectively. Multivariate analysis revealed that maternal antipsychotic drug use and selective serotonin reuptake inhibitors were independently associated with NAS (P < .001 and P = .004, respectively). Notably, benzodiazepine use and smoking were not independent risk factors. CONCLUSIONS: The results suggest an association between maternal antipsychotic drug use and NAS, which was further associated with decreased HC. Careful monitoring of maternal drug use should be considered to improve fetal outcomes.

DOI： 10.1017/S1092852920001522

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Late-onset circulatory collapse (LCC) in preterm infants is presumably caused by relative adrenal insufficiency. Because eosinophilia is known to be associated with adrenal insufficiency, we attempted to clarify the relation-ship between eosinophilia and LCC in preterm infants. We divided the cases of the infants (born at < 28 weeks' gestation) admitted to our neonatal intensive care unit in 2008-2010 into 2 groups: those diagnosed with LCC that received glucocorticoids (LCC group), and those who did not receive glucocorticoids (control group). We compared eosinophil counts between the 2 groups and between before and after glucocorticoid treatment in the LCC group. A total of 28 infants were examined: LCC group (n = 12); control group (n = 16). The peak eosin-ophil counts of the LCC group were significantly higher than those of the control group (median: 1.392 × 109/L vs. 1.033 × 109/L, respectively; p = 0.02). Additionally, in the LCC group, the eosinophil counts declined significantly after glucocorticoid treatment (0.877 × 109/L vs. 0.271 × 109/L, p = 0.003). Eosinophil counts in the LCC group were significantly higher than in the control group and decreased rapidly after gluco-corticoid treatment. These results indicate that eosinophilia may be a factor associated with LCC caused by adrenal insufficiency.

DOI： 10.18926/AMO/62403

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OBJECTIVE: To examine the association of specific Z-score categories of birth weight for gestational age with child health and neurodevelopment using a large nationwide survey in Japan, focusing on term infants. STUDY DESIGN: We included 36 321 children born in 2010. Hospitalization up to 66 months of age was used as an indicator of health status, and responses to questions about age-appropriate behaviors at 30 and 66 months of age were used to indicate neurobehavioral development. We conducted binomial log-linear regression analyses, controlling for child and parental variables. A restricted cubic spline function was used to model the relationship. RESULTS: Compared with children with birth weight appropriate for gestational age (-1.28 to 1.28 SDs of expected birthweight for gestational age), children who were small for gestational age (SGA) (<-1.28 SD) had higher risks of hospitalization and unfavorable neurobehavioral development, and the risks increased as SGA status became more severe. Compared with the appropriate for gestational age group, the adjusted risk ratios for hospitalization for all causes were 2.5 (95% CI, 1.7-3.6), 1.3 (95% CI, 1.1-1.6), and 1.1 (95% CI, 1.0-1.2) for children who were severely, moderately, and mildly SGA and 1.0 (95% CI, 0.9-1.1), 1.1 (95% CI, 0.9-1.2), and 1.4 (95% CI, 0.9-2.1) for children who were mildly, moderately, and severely large for gestational age, respectively. Severely large for gestational age children also had higher risks of unfavorable neurobehavioral development. These results were supported by spline analyses. CONCLUSIONS: Among term infants, the risks of unfavorable child health and neurodevelopment increased with the severity of SGA.

DOI： 10.1016/j.jpeds.2020.06.075

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DOI： 10.1111/ped.13908

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Nager syndrome is a rare disease involving severe micrognathia and upper limb shortening. In this report, we describe a case in which micrognathia of the fetus was suspected based on the observation of upper limb shortening during detailed B mode and 3D/4D ultrasonographic observation, and combined fetal MRI and 3D-CT led to a prenatal diagnosis of Nager syndrome. Upon birth, because severe micrognathia caused airway obstruction and made it difficult to spread the larynx for intubation, effective ventilation could not be carried out and a tracheostomy was necessary. Since a differential diagnosis of Nager syndrome can be made based on the fact that micrognathia typically co-occurs with upper limb shortening, it is possible to diagnose the disease before birth and prepare for life-saving measures accordingly.

DOI： 10.18926/AMO/56872

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Most cases of transient abnormal myelopoiesis (TAM) in neonates with Down syndrome (DS) resolve spontaneously; however, DS-TAM neonates with hydrops fetalis (HF) show poor clinical outcomes. We report three infants with DS-TAM and HF who were treated with exchange transfusion (ET) followed by low-dose cytarabine (LD-CA). All of them survived without developing liver failure, acute leukemia, or other serious adverse events. Our results suggest that this combination treatment with ET and LD-CA would be safe, tolerable and effective as an novel approach for DS-TAM patients with HF.

DOI： 10.18926/AMO/56655

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AIM: We examined the effects of being born small for gestational age (SGA) on the risk of being hospitalised for common diseases during childhood. METHODS: This Japanese nationwide, population-based longitudinal survey followed babies born before 42 weeks of gestation from 10 to 17 January and from 10 to 17 July 2001, using data from the Government's Longitudinal Survey of Babies in the 21st Century. Our study followed 41 268 children until 5.5 years of age: 39 107 full term (8.7% SGA) and 2161 preterm (15.5% SGA). We evaluated the relationship between SGA status and hospitalisation using their history of hospitalisation for common diseases and comparing full-term or preterm births. Logistic regression analysis, adjusted for potential confounders, estimated the odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The full-term and preterm children who were born SGA were more likely to be hospitalised during infancy and early childhood than those born non SGA. The ORs for hospitalisation from six months to 18 months of age were 1.23 (95% CI: 1.10-1.37) for full-term and 1.67 (95% CI: 1.23-2.25) for preterm subjects. Higher risks of hospitalisation due to bronchitis, pneumonia, bronchial asthma and diarrhoea were also observed. CONCLUSION: Being born SGA was associated with all-cause and cause-specific hospitalisation in early childhood, particularly for term infants.

DOI： 10.1111/apa.14507

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BACKGROUND: The prevalence of multiple births has recently increased. However, the association between gestational age and long-term morbidity among twins remains unclear. AIMS: To examine the association of gestational age with child health and neurological development in early childhood among twins. STUDY DESIGN: Population-based longitudinal study. SUBJECTS: We included 947 children from 479 pairs of twins with information on gestational age. OUTCOME MEASURES: Hospitalization was used as an indicator of physical health, and responses to questions about age-appropriate behaviors were used as an indicator of neurobehavioral development. We conducted binomial log-linear regression analyses, controlling for both child and maternal variables in the model. We accounted for correlations within the pairs with generalized estimating equations. RESULTS: The early term group (i.e., 37 to 38 weeks of gestation) had a lower risk of poor child health and unfavorable neurodevelopment compared with the full term group (≥39 weeks of gestation) and preterm group (<37 weeks of gestation). Compared with the early term group, the adjusted risk ratios for hospitalization for all causes during the period from 7 to 18 months of age was 2.2 (95% confidence interval: 1.3-3.8) for very preterm children (<32 weeks of gestation), 1.1 (0.8-1.6) for moderately and late preterm children (32 to 36 weeks of gestation), and 1.8 (1.0-3.2) for full term children. CONCLUSION: We observed a U-shaped association of gestational age with child health and neurodevelopment. The early term group had the lowest risk of poor outcomes among twins.

DOI： 10.1016/j.earlhumdev.2018.11.005

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SCI PRINTERS & PUBL INC  

BACKGROUND: Anti-muscle-specific tyrosine kinase (MuSK)-positive myasthenia gravis (MG) has a late onset in the 4th decade of life and a poor response to medical treatment. Few cases of pregnancy with anti-MuSK-positive MG have been described. We report a case of pregnancy with anti-MuSK-positive MG that was diagnosed during pregnancy.CASE: A 46-year-old healthy primiparous woman was referred to Okayama University Hospital at 23 weeks' gestation because of antiMuSK-positive MG that was diagnosed during pregnancy in the first trimester. Emergent cesarean section was performed at 30 weeks' gestation because of severe preeclampsia and pre-crisis of MG. She received medication and plasmapheresis for hypertension and severe MG symptoms and was discharged on day 35 after delivery. The neonate had no symptoms of transient neonatal MG, and anti-MuSK antibody was positive at birth and then decreased to the normal range at 5 months old.CONCLUSION: Our case and previous reports indicate that pregnancy with anti-MuSK-positive MG might have the same or a relatively higher risk for the mother and neonate as compared with anti-AChR-positive MG. Multidisciplinary management throughout the perinatal period should be provided for pregnancy with anti-MuSK-positive MG.

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We studied the etiology of pediatric acute encephalitis/encephalopathy (pAEE) using epidemiological data obtained from a nationwide survey in Japan. Two-step questionnaires were sent to the pediatric departments of hospitals throughout the country in 2007, querying the number of the cases during 2005-2006 as the first step, and asking for the details of clinical information as the second step. In all, 636 children with pAEE (age ≤ 15 years) were enrolled. For the known etiology of pAEE (63.5% of the total cases), 26 microbes and 2 clinical entities were listed, but the etiology of 36.5% remained unknown. Influenza virus (26.7%), exanthem subitum (12.3%), and rotavirus (4.1%) were the most common, and the incidence of pAEE peaked at the age of 1 year. This trend was common among all etiologies. Among the neurological symptoms observed at the onset of pAEE, seizures were observed more often in patients aged ≤ 3 years, although abnormal speech and behavior were also common in older children. Undesirable outcomes (death and neurological sequelae) occurred at high rates in patients with any known etiology other than mycoplasma. In conclusion, these findings provide comprehensive insight into pAEE in Japan.

DOI： 10.18926/AMO/56170

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Language：Japanese   Publisher：(一社)日本周産期・新生児医学会  

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The cover image, by Kei Tamai et al., is based on the Clinical Report Fetal ultrasonographic findings including cerebral hyperechogenicity in a patient with non-lethal form of Raine syndrome, DOI: 10.1002/ajmg.a.38598.

DOI： 10.1002/ajmg.a.38642

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Raine syndrome is a rare osteosclerotic bone dysplasia characterized by craniofacial anomalies and intracranial calcification. Most patients with Raine syndrome are of Arab ancestry and die during the neonatal period. We herein report a Japanese patient with non-lethal Raine syndrome who presented with characteristic cerebral hyperechogenicity and a hypoplastic nose by fetal ultrasonography. She was admitted to the NICU due to pyriform aperture stenosis. Craniofacial abnormalities, intracranial calcification, osteosclerosis, chondrodysplasia punctata, and a mutation of FAM20C was identified. She was subsequently discharged without surgical intervention and is now 2 years old with mild neurodevelopmental delays. Images of cerebral hyperechogenicity by fetal ultrasonography in a non-lethal case were described herein for the first time. This patient represents a rare occurrence of a child with Raine syndrome born to Japanese parents and confirms that this syndrome is not always lethal. Even if Raine syndrome is suspected in a fetus due to cerebral hyperechogenicity and a hypoplastic nose, cerebral hyperechogenicity without pulmonary hypoplasia does not always predict lethality or severe neurodevelopmental delays. The information provided herein will be useful for prenatal counseling.

DOI： 10.1002/ajmg.a.38598

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We herein report the case of a 46-year-old pregnant woman with anti-muscle specific kinase (MuSK) antibody-positive myasthenia gravis (MG) who showed pregnancy-induced hypertension and developed respiratory failure at 30 weeks and 5 days of pregnancy, and who underwent an emergency caesarean section (CS). Her MG symptoms gradually improved in the subsequent weeks. The premature baby with positive MuSK antibodies was successfully delivered, but the male baby required temporary artificial ventilation. However, his condition also gradually improved over time. The present case suggests that an emergency CS could rescue both the mother, who was in critical condition, and the prematurely born baby, even when suffering from acute respiratory insufficiency.

DOI： 10.2169/internalmedicine.8636-16

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Language：Japanese   Publisher：(一社)日本周産期・新生児医学会  

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Language：Japanese   Publisher：(一社)日本周産期・新生児医学会  

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OBJECTIVE: To compare local and systemic profiles between different disease pathologies (pneumonia and encephalitis) induced by influenza A virus (IAV). METHODS: An IAV pneumonia model was created by intranasal inoculation of C57BL/6 mice with influenza A/WSN/33 (H1N1) virus. Lung lavage and blood collection were performed on day 3 after IAV inoculation. Similarly, an IAV encephalitis mouse model was created by direct intracranial IAV inoculation. Cerebrospinal fluid (CSF) and blood collection were conducted according to the same schedule. Cytokine/chemokine profiles were produced for each collected sample. Then the data were compared visually using radar charts. RESULTS: Serum cytokine profiles were similar in pneumonia and encephalitis models, but local responses between the bronchoalveolar lavage fluid (BALF) in the pneumonia model and CSF in the encephalitis model differed. Moreover, to varying degrees, the profiles of local cytokines/chemokines differed from those of serum in both the pneumonia and encephalitis models. CONCLUSION: Investigating local samples such as BALF and CSF is important for evaluating local immune responses, providing insight into pathology at the primary loci of infection. Serum data alone might be insufficient to elucidate local immune responses and might not enable clinicians to devise the most appropriate treatment strategies.

DOI： 10.1155/2017/2594231

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Language：Japanese   Publisher：中国四国産科婦人科学会  

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Language：Japanese   Publisher：(一社)日本周産期・新生児医学会  

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BACKGROUND: Late-onset circulatory collapse (LCC) is a disorder in which blood pressure decreases and oliguria suddenly occurs in preterm infants who have survived the acute stage, leading to shock, without contributing underlying factors. In order to evaluate hemodynamic changes during LCC, the correlation between myocardial functions and organ blood flow was investigated with echography. METHODS: Seven very-low-birthweight infants were given a diagnosis of LCC during the study period. Cardiovascular and organ flow parameters of the infants were recorded prospectively, once a week, and compared with eight control very-low-birthweight infants with matching gestational age. Echographic study was performed before LCC, at the onset of LCC, and after LCC among infants with LCC. RESULTS: A significant increase in ejection fraction and a significant decrease in end systolic wall stress were observed in infants with the LCC condition. At the same time, the mean blood flow velocity increased significantly in the superior mesenteric artery, while it decreased in the anterior cerebral artery. Systolic blood flow velocity increased and mean velocity was maintained in the renal artery during LCC. CONCLUSION: LCC is a distributive shock, characterized by a hyperdynamic state and decreased afterload. Echographic examination of organ flow during LCC is useful in understanding the pathophysiology of the disorder.

DOI： 10.1111/ped.12114

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BACKGROUND: The aim of this study was to evaluate the efficacy and safety of early administration of Bifidobacterium bifidum OLB6378 (B. bifidum) on accelerating enteral feeding and bacterial colonization in very-low-birthweight (VLBW) infants. METHODS: We conducted a single-center prospective pilot study. Thirty-six VLBW infants were randomly divided into two groups: group E, wherein B. bifidum was supplemented within 48 h of birth, and group L, wherein it was supplemented more than 48 h after birth. RESULTS: Group E and group L reached a total feeding volume of 100 mL/(kg/day) after 10 [7-13] days and 11 [10-15] days, respectively (median [quartile]). The daily bodyweight gain in group E was significantly higher (21.4 ± 3.2 g/day vs 18.3 ± 4.0 g/day, P < 0.02; 11.1 ± 1.5 g/kg/day vs 10.4 ± 1.2 g/kg/day, P < 0.04). No significant differences were found in the fecal Bifidobacterium level between the groups quantitated with a real-time polymerase chain reaction assay at 1 and 4 weeks of age. However, the highest colonization rate of Bifidobacterium was observed when the supplementation started between 24 and 48 h after birth. The incidence of morbidities between the groups was similar. CONCLUSION: The early administration of B. bifidum to VLBW infants seems effective in promoting growth during the stay in the neonatal intensive care unit without increasing the incidence of morbidity. Furthermore, the preferable timing of starting the probiotic supplementation for VLBW infants is at latest less than 48 h after birth.

DOI： 10.1111/j.1442-200X.2012.03649.x

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BACKGROUND: The long-term effects of hydrocortisone (HDC) used for very-low-birthweight (VLBW) infants with chronic lung disease (CLD) are not fully understood. The aim of this study was to examine the short-term clinical effects and long-term impact of a physiological replacement dose of HDC on acute deterioration of CLD in VLBW infants. METHODS: This prospective case-control study included 110 of the 174 VLBW infants admitted to our facility between 2003 and 2006 who were followed up to a corrected age of 18 months. Infant deaths and infants with congenital deformities were excluded from the study. The infants were classified into the following three groups: infants with CLD and treated with HDC (1-2 mg/kg/dose) due to progressive deterioration in oxygenation (CLD treatment group; n = 24); infants with CLD but not treated with HDC (CLD untreated group; n = 40); and infants without CLD (non-CLD group; n = 46). RESULTS: The fraction of inspired oxygen (F(I) O(2) ) in the CLD treatment group improved significantly after treatment (P < 0.01). There were no significant differences among the three groups in terms of growth and neurodevelopmental quotient at the corrected age of 18 months following adjustment for birthweight, sex, and presence of light-for-date infants. There were also no significant intergroup differences in all three areas of developmental quotient. CONCLUSIONS: Physiological doses of HDC replacement are effective in treating acute deterioration in oxygenation in VLBW infants with CLD. Furthermore, this treatment modality did not adversely affect the growth and development of infants at the corrected age of 18 months.

DOI： 10.1111/j.1442-200X.2012.03601.x

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