Publications by authors named "Masahiko Kawai"

64 Publications

Longitudinal assessment of social attention in preterm and term infants: Its relation to social communication and language outcome.

Infancy 2021 Apr 15. Epub 2021 Apr 15.

Graduate School of Education, Kyoto University, Kyoto, Japan.

Preterm birth has been reported to be associated with an increased risk of social communication and language problems. Recently, we found that preterm infants showed atypical patterns of social attention compared with term infants. However, it is still unknown how social attention develops and whether the individual differences are associated with developmental outcomes for social communication and language in preterm infants. The social attention of preterm and term infants at 6, 12, and 18 months was investigated using two types of social attention tasks (human-geometric preference task and gaze-following task). The Modified Checklist for Autism in Toddlers (M-CHAT) and the MacArthur Communicative Development Inventory adapted for Japanese were measured at 18 months. We found that compared with term infants, preterm infants spent less time looking toward dynamic human images and followed another's gaze directions less frequently through 6, 12, and 18 months. Moreover, hierarchical multiple regression analysis revealed that less preference for dynamic human images and gaze-following abilities was associated with high M-CHAT and low language scores in preterm and term infants, respectively. These findings suggest that birth status affects development of social attention through 18 months and individual differences in social attention reflect differences in social communication and language outcomes.
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http://dx.doi.org/10.1111/infa.12402DOI Listing
April 2021

Effect of electrical activity of the diaphragm waveform patterns on SpO for extremely preterm infants ventilated with neurally adjusted ventilatory assist.

Pediatr Pulmonol 2021 Apr 6. Epub 2021 Apr 6.

Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Objective: This study aimed to evaluate the association between electrical activity of the diaphragm (Edi) waveform patterns and peripheral oxygen saturation (SpO ) in extremely preterm infants who are ventilated with neurally adjusted ventilatory assist (NAVA).

Study Design: We conducted a retrospective cohort study at a level III neonatal intensive care unit. Extremely preterm infants born at our hospital between November 2019 and November 2020 and ventilated with NAVA were included. We collected Edi waveform data and classified them into four Edi waveform patterns, including the phasic pattern, central apnea pattern, irregular low-voltage pattern, and tonic burst pattern. We analyzed the Edi waveform pattern for the first 15 h of collectable data in each patient. To investigate the association between Edi waveform patterns and SpO , we analyzed the dataset every 5 min as one data unit. We compared the proportion of each waveform pattern between the desaturation (Desat [+]) and non-desaturation (Desat [-]) groups.

Results: We analyzed collected data for 105 h (1260 data units). The proportion of the phasic pattern in the Desat (+) group was significantly lower than that in the Desat (-) group (p < .001). However, the proportions of the central apnea, irregular low-voltage, and tonic burst patterns in the Desat (+) group were significantly higher than those in the Desat (-) group (all p < .05).

Conclusion: Our results indicate that proportions of Edi waveform patterns have an effect on desaturation of SpO in extremely preterm infants who are ventilated with NAVA.
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http://dx.doi.org/10.1002/ppul.25396DOI Listing
April 2021

Spontaneous esophageal rupture managed with endoscopic closure using an over-the-scope clip: A case report.

Int J Surg Case Rep 2021 Mar 22;80:105691. Epub 2021 Feb 22.

Department of Surgery, Gifu Prefectural General Medical Center, 4-6-1 Noisshiki, Gifu-City, Gifu-Prefecture, 500-8717, Japan. Electronic address:

Introduction And Importance: Spontaneous esophageal rupture is a life-threatening condition caused by a sudden increase in the intraesophageal pressure. While surgery is the mainstay of management for spontaneous esophageal ruptures, in recent years, an increasing number of patients have been managed with endoscopic interventions. We report a case of spontaneous esophageal rupture managed with endoscopic closure using an over-the-scope clip (Ovesco Endoscopy AG, Tübingen, Germany).

Case Presentation: A 68-year-old female presented with epigastric pain and left-sided back pain following vomiting. A computed tomography scan revealed mediastinal emphysema and an esophagogram showed leakage from the left side of the lower thoracic esophagus into the mediastinum. The patient was diagnosed with spontaneous esophageal rupture localized to the mediastinum and was treated conservatively. However, she had persistent fever and continuing esophageal leakage on the esophagogram. On the 12th day of admission, a gastrointestinal endoscopy was performed, which found a 10-mm full-thickness longitudinal laceration on the left side of the lower esophagus. Endoscopic closure using an over-the-scope clip was performed. The next day, the patient became afebrile. One week later, esophagogram revealed slight residual leakage and an additional endoscopic closure using an over-the-scope clip was performed; the patient subsequently had an uneventful recovery and was discharged on the 44th day of admission.

Clinical Discussion: Endoscopic closure using an over-the-scope clip led to a good outcome in this patient with spontaneous esophageal rupture.

Conclusion: Endoscopic closure using an over-the-scope clip is an effective and minimally invasive technique for selected patients with spontaneous esophageal rupture.
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http://dx.doi.org/10.1016/j.ijscr.2021.105691DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933483PMC
March 2021

Effects of passage through the digestive tract on incretin secretion: Before and after birth.

J Diabetes Investig 2020 Oct 23. Epub 2020 Oct 23.

Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Aims/introduction: It was reported that fetuses secrete endogenous incretin; however, the stimulants of fetal incretin secretion are not fully understood. To investigate the association between the passage of amniotic fluid through the intestinal tract and fetal secretion of incretin, we analyzed umbilical cord incretin levels of infants with duodenum atresia.

Materials And Methods: Infants born from July 2017 to July 2019 (infants with duodenum atresia and normal term or preterm infants) were enrolled. We measured and compared the concentrations of glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide/glucose-dependent insulinotropic polypeptide (GIP) in the umbilical vein and preprandial blood samples after birth.

Results: A total of 98 infants (47 term, 46 preterm and 5 with duodenum atresia) were included. In patients with duodenum atresia, umbilical vein GLP-1 and GIP levels were the same as those in normal infants. In postnatal samples, there were positive correlations between the amount of enteral feeding and preprandial serum concentrations of GLP-1 (r = 0.47) or GIP (r = 0.49).

Conclusions: Our results show that enteral feeding is important for secretion of GLP-1 and GIP in postnatal infants, whereas the passage of amniotic fluid is not important for fetal secretion of GLP-1 and GIP. The effect of ingested material passing through the digestive tract on incretin secretion might change before and after birth. Other factors might stimulate secretion of GLP-1 and GIP during the fetal period.
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http://dx.doi.org/10.1111/jdi.13447DOI Listing
October 2020

Signal Intensity and Volume of Pituitary and Thyroid Glands in Preterm and Term Infants.

J Magn Reson Imaging 2021 04 16;53(4):1151-1161. Epub 2020 Oct 16.

Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Background: Hypothalamic-pituitary-thyroid (HPT) maturation has not been extensively evaluated using neonatal MRI, even though both structures are visualized on MRI.

Hypothesis: That signal intensity and volume of pituitary and thyroid (T) glands on MRI in neonates may be interrelated.

Study Type: Retrospective.

Subjects: In all, 102 participants.

Field Strength/sequence: 3.0T, T -weighted pointwise encoding time reduction with radial acquisition (PETRA).

Assessment: The volume of interest of the anterior pituitary (AP), posterior pituitary (PP), and T on MRI were defined on T -PETRA by two radiologists, and volumes of AP (AP_vol) and thyroid (T_vol) were calculated. Gestational age (GA), chronological age (CA), GA+CA, birth weight (BW), and thyroid function were recorded. Mean and maximum signal intensities of AP, PP, and T were normalized using signals from the pons and spinal cord as follows: signal ratio of anterior pituitary/pons (AP/pons), signal ratio of posterior pituitary/pons (PP/pons), and signal ratio of thyroid/cord (T/cord) T/cord, respectively.

Statistical Tests: Correlations between signal intensity and volume measures and GA, CA, GA+CA, and BW were assessed using Pearson's correlation coefficient or Spearman's rank correlation coefficient. Thyroid function analysis and T /cord, T /cord, and T_vol were evaluated using the Steel-Dwass test.

Results: AP /pons correlated positively with GA (ρ = 0.62, P < 0.001) and BW (ρ = 0.74, P < 0.001), and negatively with CA (ρ = -0.86, P < 0.001) and GA+CA (ρ = -0.46, P < 0.001). PP /pons correlated positively with GA (ρ = 0.49, P < 0.001) and BW (ρ = 0.63, P < 0.001), and negatively with CA (ρ = -0.70, P < 0.001) and GA+CA (r = -0.38, P < 0.001). T /cord correlated positively with GA (ρ = 0.48, P < 0.001) and BW (ρ = 0.55, P < 0.001), and negatively with CA (ρ = -0.59, P < 0.001) and GA+CA (ρ = -0.22, P = 0.03). AP_vol correlated positively with GA (ρ = 0.68, P < 0.001) and BW (ρ = 0.73, P < 0.001), and negatively with CA (ρ = -0.72, P < 0.001). T_vol correlated positively with GA (ρ = 0.50, P < 0.001) and BW (ρ = 0.61, P < 0.001), and negatively with CA (ρ = -0.54, P < 0.001). AP /pons correlated positively with T /cord (ρ = 0.61, P < 0.001).

Data Conclusion: Signal and volume of pituitary and thyroid glands correlated positively with GA and BW, and negatively with CA in neonates.

Level Of Evidence: 4 TECHNICAL EFFICACY STAGE: 5.
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http://dx.doi.org/10.1002/jmri.27395DOI Listing
April 2021

Appropriate Phosphorus Intake by Parenteral Nutrition Prevents Metabolic Bone Disease of Prematurity in Extremely Low-Birth-Weight Infants.

JPEN J Parenter Enteral Nutr 2020 Aug 12. Epub 2020 Aug 12.

Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Background: Metabolic bone disease (MBD) is a common disorder in extremely low-birth-weight (ELBW) infants. However, no studies have investigated whether high-dose calcium (Ca) and phosphorus (P) supplementation by parenteral nutrition (PN) prevents MBD in ELBW infants. This study aimed to identify the effect of PN on MBD in ELBW infants.

Methods: We retrospectively analyzed ELBW infants who were admitted between April 2011 and March 2017. ELBW infants were divided into the low-P group (n = 22) and the high-P group (n = 26) according to the dose of parenteral P supply. Biochemical and radiological markers of MBD and treatments were analyzed.

Results: Mean daily parenteral intake of Ca and P in the first week was significantly higher in the high-P group than in the low-P group (both P ≤ .001). Serum alkaline phosphatase (ALP) levels were significantly higher in the low-P group than in the high-P group in the first month. ELBW infants in the low-P group received alfacalcidol much more frequently than those in the high-P group. There was a trend of a higher rate of x-ray changes in the low-P group than in the high-P group. No infants developed bone fractures.

Conclusion: Appropriate P intake by PN is required to ensure high Ca intake, reduce ALP levels in the first month, and prevent MBD from hyperparathyroidism and does not worsen x-ray findings in ELBW infants.
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http://dx.doi.org/10.1002/jpen.1993DOI Listing
August 2020

Prematurity at less than 24 weeks of gestation is a risk for prolonged hyperglycemia in extremely low-birth weight infants.

Endocrine 2020 10 2;70(1):71-77. Epub 2020 Jul 2.

Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.

Hyperglycemia in extremely low-birth weight infants (ELBWIs) is frequently observed during the acute perinatal phase, (i.e., first 1-2 weeks postnatal period); however it can occasionally persists for >2 weeks, extending to the post-acute phase. Since such prolonged hyperglycemia (PH) is not typical for ELBWIs, the aim of the present study was to further understand the clinical details of PH. Twenty-five hyperglycemic ELBWIs born before 28 weeks of gestation from 2015 to 2018 were included in the study. Based on the duration of hyperglycemia, we separated the subjects into two groups: non-prolonged hyperglycemia (NPH) who achieved remission within ≤2 weeks [n = 18, median 3.0 (range, 2.0-4.0) days], and PH, whose hyperglycemia persisted for >2 weeks [n = 7, median 50.0 (range, 33.5-66.0) days]. Compared to the NPH group, glucose metabolism of the PH group was more deteriorate. The peak blood glucose level was significantly higher in the PH group [PH: median 472 mg/dL, NPH: median 275 mg/dL, p < 0.001], and a higher proportion of subjects in the PH group required insulin therapy [PH: 100% (7/7) vs. NPH: 22% (4/22)]. Multivariate analysis revealed that among perinatal factors, prematurity was the only independent risk factor for PH (glucocorticoid therapy: p = 0.884, gestational age: p = 0.006), with a cutoff of 23W4D determined by receiver operating characteristic analysis. Our data revealed distinctive clinical features of PH, suggesting a type different from the previously reported hyperglycemia in ELBWIs. Specifically, extreme prematurity, less than 24 weeks of gestation, is a risk for PH, and aggressive interventions, such as insulin would be required.
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http://dx.doi.org/10.1007/s12020-020-02393-3DOI Listing
October 2020

Antenatal corticosteroids for threatened labour facilitate thyroid maturation among preterm neonates.

Clin Endocrinol (Oxf) 2020 Nov 14;93(5):613-619. Epub 2020 Jul 14.

Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Objective: To examine the effect of antenatal corticosteroids (ANS) on the maturation of thyroid function in the preterm infants.

Context: ANS reduce mortality and morbidities in preterm neonates. Organ maturation by the glucocorticoids is the key, at least in part. However, the effect of ANS on thyroid is controversial.

Patients: A study group of 99 very low birthweight neonates (<34 weeks' gestational age) with the exception of those born more than 7 days after ANS administration were divided into a complete group (n = 49) whose mothers completed two doses of betamethasone and who were born more than 24 hours after the completion of ANS administration, and an incomplete group (n = 50) who were not exposed to any ANS or were born within 24 hours after the completion of ANS administration. Serum-free thyroxine and thyroid-stimulating hormone (TSH) levels were measured, and thyrotropin-releasing hormone (TRH) stimulation tests were performed at about 2 weeks of age.

Results: The incidence of hyperthyrotropinaemia (TSH > 15 mIU/L) in the complete group was significantly lower than in the incomplete group (6% vs 22%, P = .023). Exaggerated responses to TRH tests were more frequent in the incomplete group (17% vs 44%; P = .053). TSH was significantly lower in the complete group, (P = .046). Multivariate logistic regression analysis showed that the incidence of hyperthyrotropinaemia was associated with complete ANS administration (adjusted odds ratios 0.39).

Conclusions: ANS administration might facilitate thyroid maturation in preterm neonates.
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http://dx.doi.org/10.1111/cen.14272DOI Listing
November 2020

Response of preterm infants with transient hypothyroxinaemia of prematurity to the thyrotropin-releasing hormone stimulation test is characterized by a delayed decrease in thyroid-stimulating hormone after the peak.

Clin Endocrinol (Oxf) 2020 Nov 21;93(5):605-612. Epub 2020 Jun 21.

Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Objectives: We evaluated the response to the thyrotropin-releasing hormone (TRH) stimulation test in very low-birth weight (VLBW) infants to elucidate the aetiology of transient hypothyroxinaemia of prematurity (THOP).

Design And Methods: We performed TRH stimulation tests on 43 VLBW infants. Subjects were divided into two groups; a THOP group (N = 11; basal TSH < 15 mU/L and basal FT4 ≤ 0.8 ng/dL) and a non-THOP group (N = 32; basal TSH < 15 mU/L and basal FT4 > 0.8 ng/dL). Basal FT4 and FT3 were measured before, and TSH (0, 30, 60, 90, 120 and 180 minutes) was measured after, the administration of TRH (7 µg/kg). We calculated the ratio of TSH 180 minutes to THS 0 minute as the primary outcome. We also collected data on T3 and rT3 in this study.

Results: In both groups, TSH 30 minutes values were the highest. However, the ratios of TSH 180 minutes to THS 0 minutes in the non-THOP group and the THOP group were (median [IQR]) 1.3 [1.0-1.7] and 3.0 [1.5-5.3] (P < .01). No significant differences were observed in T3 (1.0 [0.8-1.3] and 0.7 [0.4-0.7] ng/mL, P = .06). However, in the THOP group, rT3 was significantly lower than that of the non-THOP group (168.0 [148.1-197.0] and 92.9 [74.7-101.6] pg/mL, P < .01).

Conclusions: The delayed decrease in the TSH concentration after the peak for the TRH tests and decreased levels of rT3 suggest that the main aetiology for THOP is suppression at the level of the hypothalamus, but not inactivation of peripheral thyroid hormone metabolism.
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http://dx.doi.org/10.1111/cen.14260DOI Listing
November 2020

A familial case of alveolar capillary dysplasia with misalignment of the pulmonary veins: the clinicopathological features and unusual glomeruloid endothelial proliferation.

Diagn Pathol 2020 May 9;15(1):48. Epub 2020 May 9.

Department of Diagnostic Pathology, Kyoto University Hospital, 54 Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.

Background: Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare disorder of pulmonary vascular abnormality with persistent pulmonary hypertension of the newborn. The symptom usually presents within hours after birth, leading to an early demise. Heterozygous de novo point mutations and genomic deletions of the FOXF1 (forkhead box F1) gene or its upstream enhancer have been identified in most patients with ACD/MPV. Most cases of ACD/MPV are sporadic; however, familial cases are also reported in 10% of patients.

Case Presentation: We herein report a case of familial ACD/MPV that showed unusual glomeruloid proliferation of endothelial cells. In this family, three of the four siblings died within two to 3 days after birth because of persistent pulmonary hypertension and respiratory failure. Only the second child remains alive and healthy. An autopsy was performed for the third and fourth children, resulting in a diagnosis of ACD/MPV based on the characteristic features, including misalignment of smaller pulmonary veins and lymphangiectasis. In both of these children, glomeruloid endothelial proliferation of vessels was noted in the interlobular septa. The vessels were immunohistochemically positive for D2-40, CD31, Factor VIII, and ERG, suggestive of differentiation for both lymphatic and blood vessels.

Conclusions: Unusual glomeruloid endothelial proliferation was observed in a familial ACD/MPV case. This histologic feature has not been described previously in ACD/MPV or any other pulmonary disease. Although the histogenesis of this histologic feature is unclear, this finding may suggest that ACD/MPV is a compound vascular and lymphovascular system disorder that exhibits various histologic features.
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http://dx.doi.org/10.1186/s13000-020-00972-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7211333PMC
May 2020

Antenatal Glucocorticoids Reduce the Incidence of Refractory Hypotension in Low Birthweight Infants during the Early Neonatal Period, but Do Not Affect It beyond This Time.

Am J Perinatol 2020 Feb 18. Epub 2020 Feb 18.

Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Objective:  This study aimed to clarify the effect of antenatal glucocorticoids (AGs) on the incidence of refractory hypotension (RH) in very low birthweight (VLBW) infants after the first week of life.

Study Design:  We included VLBW infants born at a gestational age of <30 weeks and divided them into three groups: the complete group (born within 7 days of completing a single course [two doses] of AGs), the incomplete group (born without complete course), and the late delivery group (born at ≥8 days after a single course). We compared the incidence and period of onset of RH among the three groups.

Results:  A total of 115 infants were enrolled. The incidence of RH in the first week of life was significantly lower in the complete group than in the other groups. However, there was no significant difference in the incidence of RH after the first week of life among the groups.

Conclusion:  AGs contribute to circulatory stabilization during the first week of life, but this effect does not last after 1 or 2 weeks of administration. In infants who receive AGs, physicians should consider that the risk of RH after the first week of life is not low.
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http://dx.doi.org/10.1055/s-0040-1701608DOI Listing
February 2020

Genetic abnormalities in a large cohort of Coffin-Siris syndrome patients.

J Hum Genet 2019 Dec 17;64(12):1173-1186. Epub 2019 Sep 17.

Asahikawa-Kosei General Hospital, Hokkaido, Japan.

Coffin-Siris syndrome (CSS, MIM#135900) is a congenital disorder characterized by coarse facial features, intellectual disability, and hypoplasia of the fifth digit and nails. Pathogenic variants for CSS have been found in genes encoding proteins in the BAF (BRG1-associated factor) chromatin-remodeling complex. To date, more than 150 CSS patients with pathogenic variants in nine BAF-related genes have been reported. We previously reported 71 patients of whom 39 had pathogenic variants. Since then, we have recruited an additional 182 CSS-suspected patients. We performed comprehensive genetic analysis on these 182 patients and on the previously unresolved 32 patients, targeting pathogenic single nucleotide variants, short insertions/deletions and copy number variations (CNVs). We confirmed 78 pathogenic variations in 78 patients. Pathogenic variations in ARID1B, SMARCB1, SMARCA4, ARID1A, SOX11, SMARCE1, and PHF6 were identified in 48, 8, 7, 6, 4, 1, and 1 patients, respectively. In addition, we found three CNVs including SMARCA2. Of particular note, we found a partial deletion of SMARCB1 in one CSS patient and we thoroughly investigated the resulting abnormal transcripts.
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http://dx.doi.org/10.1038/s10038-019-0667-4DOI Listing
December 2019

Reliability of real-time continuous glucose monitoring in infants.

Pediatr Int 2019 Oct 17;61(10):1001-1006. Epub 2019 Oct 17.

Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Background: Neonatal hypoglycemia is a common and treatable risk factor for neurological impairment. Real-time continuous glucose monitoring (RT-CGM) can show glucose concentration in real time. Using an RT-CGM alarm, physicians can be alerted and intervene in hypoglycemia. No reports, however, have evaluated the reliability of RT-CGM at low glucose levels in infants. This study therefore investigated the difference between blood glucose (BG) and RT-CGM sensor data at low glucose levels and assessed the optimum method of using a hypoglycemic alarm in infants.

Methods: We enrolled infants whose glycemic management was difficult. We calculated the mean absolute difference (MAD) and mean absolute relative difference (MARD) between BG and RT-CGM sensor data. We compared the MAD and MARD between the low BG fluctuation and high BG fluctuation groups.

Results: We used RT-CGM for 12 patients (29 times) and investigated 448 pairs of BG and RT-CGM sensor data. The MAD between these pairs was 9.3 ± 8.9 mg/dL, and the MARD was 11.5%. The MAD at low glucose was 7.7 ± 6.0 mg/dL, and the MARD was 16.2%. The MAD and MARD were 6.8 ± 5.4 mg/dL and 7.8% in the low fluctuation group and 10.1 ± 9.5 mg/dL and 12.7% in the high fluctuation group, respectively.

Conclusions: The difference between BG and RT-CGM sensor data changes with the degree of fluctuation in BG. When physicians set the hypoglycemic alarm, consideration of this difference and a change in the alarm setting according to the degree of fluctuation in BG may be useful.
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http://dx.doi.org/10.1111/ped.13961DOI Listing
October 2019

Audiovisual speech perception and language acquisition in preterm infants: A longitudinal study.

Early Hum Dev 2019 01 9;128:93-100. Epub 2018 Dec 9.

Graduate School of Education, Kyoto University, Kyoto, Japan.

Background: Preterm infants have a higher risk of language delay throughout childhood. The ability to integrate audiovisual speech information is associated with language acquisition in term infants; however, the relation is still unclear in preterm infant.

Aim And Methods: This study longitudinally investigated visual preference for audiovisual congruent and incongruent speech during a preferential looking task using eye-tracking in preterm and term infants at 6, 12, and 18 months of corrected age. The infants' receptive and expressive vocabulary at 12 and 18 months were obtained by parent report, using the Japanese MacArthur Communicative Development Inventory.

Results: We found that preterm infants did not clearly show visual preference for the congruent audiovisual display at any age, whereas term infants looked at the congruent audiovisual display longer than the incongruent audiovisual display at 6 and 18 months. Preterm infants' receptive and expressive vocabulary scores were lower than those of term infants at 12 and 18 months. Furthermore, the proportion of looking time toward the congruent audiovisual display at 6 months was positively correlated with receptive vocabulary scores at 12 and 18 months for both groups.

Conclusions: These findings suggest that better audiovisual speech perception abilities are one factor that results in better language acquisition in preterm as well as term infants. Early identification of behaviors associated with later language in preterm infants may contribute to planning intervention for developmental problems.
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http://dx.doi.org/10.1016/j.earlhumdev.2018.11.001DOI Listing
January 2019

Endoscopic duodenal stent versus surgical gastrojejunostomy for gastric outlet obstruction in patients with advanced pancreatic cancer.

Pancreatology 2018 Jul 3;18(5):601-607. Epub 2018 May 3.

First Department of Internal Medicine, Gifu University Hospital, Gifu, Japan.

Background: Malignant gastric outlet obstruction (GOO) often develops in patients with advanced pancreatic cancer (APC). It is not clear whether endoscopic duodenal stenting (DS) or surgical gastrojejunostomy (GJJ) is preferable as palliative treatment.

Aims: To compare the efficacy and safety of GJJ and DS for GOO with APC.

Methods: Consecutive 99 patients who underwent DS or GJJ for GOO with APC were evaluated. We compared the technical and clinical success rates, the incidence of adverse event (AE), the time to start chemotherapy and discharge and survival durations between DS and GJJ. Prognostic factors for overall survival (OS) were investigated on the multivariate analysis.

Results: GOO was managed with GJJ in 35 and DS in 64. The technical and clinical success rates were comparable. DS was associated with shorter time to start oral intake and earlier chemotherapy start and discharge. No difference was seen in the early and late AE rates. Multivariate analyses of prognostic factors for OS showed that performance status ≧2, administration of chemotherapy, and presence of obstructive jaundice to be significant factors. There were no significant differences in survival durations between the groups, regardless of the PS.

Conclusions: There were no significant differences in the technical and clinical success and AE rates and survival duration between DS and GJJ in management of GOO by APC. DS may be a preferable option over GJJ given that it will lead to an earlier return to oral intake, a shortened length of hospital stay, and finally an earlier referral for chemotherapy.
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http://dx.doi.org/10.1016/j.pan.2018.04.015DOI Listing
July 2018

Reevaluation of Protein Intake for Preterm Infants.

Authors:
Masahiko Kawai

Am J Perinatol 2018 10 24;35(12):1138-1141. Epub 2018 Apr 24.

Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Growth failure caused by undernutrition is considered one of the major causes for psychomotor delay in extremely preterm infants, and the concept for "aggressive nutritional approach" is widely accepted worldwide. Based on this, postnatal early catch-up growth due to sufficient supply of nutrients including sufficient amounts of amino acids is believed to be essential for a better outcome; however, there is no definitive evidence of aggressive nutrition on better outcomes in mortality, growth, and neurodevelopment. On the contrary, epidemiological evidence suggests that low birth weight and a rapid catch-up growth after birth are major risk factors for insulin resistance and diabetes in later life; higher protein intake during postnatal period relates to higher cardiovascular risk in later life. Considering these, optimal nutrition, especially protein administration, should be reevaluated. In this review, current opinions on the nutrition for the preterm infants are surveyed. In addition, I propose a new concept for optimized protein amount for the preterm infants based on the difference of amino acid metabolism between fetuses and preterm infants.
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http://dx.doi.org/10.1055/s-0038-1645859DOI Listing
October 2018

Lobulated esophageal schwannoma resected with concurrent approach from the thorax and cervix.

World J Surg Oncol 2018 Feb 13;16(1):29. Epub 2018 Feb 13.

Department of Surgery, Gifu Prefectural General Medical Center, 4-6-1 Noisshiki, Gifu, Japan.

Background: Esophageal schwannomas are rare esophageal submucosal tumors. We herein report a case of a lobulated esophageal schwannoma resected with concurrent approach from the thorax and cervix.

Case Presentation: A 74-year-old woman visited our hospital with complaint of loss of consciousness, and a lobulated mediastinal tumor was discovered by chance in computed tomography. Upper gastrointestinal endoscopy showed a smooth elevated lesion at a position of 23-28 cm from the incisor teeth. A hypermetabolic appearance was noted on positron emission tomography. Based on these data, a gastrointestinal stromal tumor was suspected. The tumor was enucleated at the thoracic cavity while being pushed from the cervical incision. Pathological examination showed an esophageal schwannoma.

Conclusions: We experienced a case of lobulated esophageal schwannoma with fluorodeoxyglucose accumulation. We resected the tumor with concurrent approach from the thorax and cervix.
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http://dx.doi.org/10.1186/s12957-018-1334-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5812219PMC
February 2018

Fundamental Frequency Variation of Neonatal Spontaneous Crying Predicts Language Acquisition in Preterm and Term Infants.

Front Psychol 2017 22;8:2195. Epub 2017 Dec 22.

Graduate School of Education, Kyoto University, Kyoto, Japan.

Spontaneous cries of infants exhibit rich melodic features (i.e., time variation of fundamental frequency [ ]) even during the neonatal period, and the development of these characteristics might provide an essential base for later expressive prosody in language. However, little is known about the melodic features of spontaneous cries in preterm infants, who have a higher risk of later language-related problems. Thus, the present study investigated how preterm birth influenced melodic features of spontaneous crying at term-equivalent age as well as how these melodic features related to language outcomes at 18 months of corrected age in preterm and term infants. At term, moderate-to-late preterm (MLP) infants showed spontaneous cries with significantly higher variation and melody complexity than term infants, while there were no significant differences between very preterm (VP) and term infants. Furthermore, larger variation within cry series at term was significantly related to better language and cognitive outcomes, particularly expressive language skills, at 18 months. On the other hand, no other melodic features at term predicted any developmental outcomes at 18 months. The present results suggest that the additional postnatal vocal experience of MLP preterm infants increased variation and the complexity of spontaneous cries at term. Additionally, the increases in variation may partly reflect the development of voluntary vocal control, which, in turn, contributes to expressive language in infancy.
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http://dx.doi.org/10.3389/fpsyg.2017.02195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5744644PMC
December 2017

Corticotrophin-releasing hormone stimulation tests for the infants with relative adrenal insufficiency.

Clin Endocrinol (Oxf) 2017 Dec 4;87(6):660-664. Epub 2017 Sep 4.

Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Background: Very low birthweight (VLBW) infants are considered to be vulnerable to relative adrenal insufficiency (RAI); however, diagnosis is difficult in some clinical settings. Considering this background, it is necessary to establish a diagnosis of RAI in preterm infants.

Objective: In this study, we attempted to clarify the difference in response to CRH stimulation tests for preterm infants with or without RAI.

Methods: Between June 2009 and December 2015, we performed CRH stimulation tests for preterm infants born at a gestational age of <30 weeks at around 2 weeks of age. Retrospectively, subjects were classified into two groups: infants with RAI (n = 9) or without RAI (n = 17) based on the clinical symptoms and responsiveness to hydrocortisone.

Results: We found no difference in base or peak serum cortisol levels related to CRH stimulation tests between the two groups; however, delta cortisol levels and responsive ratio (peak-to-base ratio) were significantly reduced in infants with RAI. 140 nmol/L for delta cortisol or 1.5 times for peak-to-base ratio may be cut-off levels in preterm infants.

Conclusion: This study provides evidence that base cortisol levels of preterm infants with RAI were not different from those without RAI; however, CRH stimulation tests may be a useful tool for the diagnosis of RAI in preterm infants.
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http://dx.doi.org/10.1111/cen.13446DOI Listing
December 2017

Preference for Dynamic Human Images and Gaze-Following Abilities in Preterm Infants at 6 and 12 Months of Age: An Eye-Tracking Study.

Infancy 2017 Mar 31;22(2):223-239. Epub 2016 Mar 31.

Graduate School of Education, Kyoto University.

Preterm children are reported to be at higher risk of social communication problems such as autism spectrum disorder compared with full-term infants. Although previous studies have suggested that preference for social stimuli in infancy is a possible indicator of later social communication development, little is known about this relation in preterm infants. We examined the gaze behavior of low-risk preterm and full-term infants at 6 and 12 months' corrected ages using two types of eye-tracking tasks, which measured 1) preference for social stimuli by biological motion and human geometric preference and 2) ability to follow another's gaze direction. We found that preterm (compared with full-term) infants at both 6 and 12 months of age spent less time looking toward dynamic human images, followed another's gaze less frequently, and looked for a shorter time at an object cued by another. Moreover, we found a positive correlation between looking time toward dynamic human images and frequency of gaze following at 12 months of age in full-term, but not preterm, infants. We discuss the relation between the atypical patterns of gaze behavior in preterm infants and their higher risk of later social communication problems.
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http://dx.doi.org/10.1111/infa.12144DOI Listing
March 2017

Late-onset circulatory collapse of prematurity.

Authors:
Masahiko Kawai

Pediatr Int 2017 Apr;59(4):391-396

Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Late-onset circulatory collapse (LCC) is a refractory hypotension occurring after the early neonatal period (>day 7), in very low-birthweight infants. Typically, infants stabilized within the early neonatal period develop sudden onset of circulatory collapse after the early neonatal period. The underlying pathophysiology of LCC is considered to be relative adrenal insufficiency, which is well known in Japan, but is not widely accepted in North America or Europe. The current increase in LCC in Japan suggests that the principal trigger is related to recent trends in neonatal medicine and/or newly introduced treatments for preterm infants, but the pathophysiology has not been fully elucidated. In this review, based on current knowledge regarding LCC, the pathophysiology is discussed.
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http://dx.doi.org/10.1111/ped.13242DOI Listing
April 2017

Hyperinsulinemic hypoglycemia in Beckwith-Wiedemann, Sotos, and Kabuki syndromes: A nationwide survey in Japan.

Am J Med Genet A 2017 Feb 7;173(2):360-367. Epub 2016 Nov 7.

Department of Pediatrics, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan.

Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth syndrome that is occasionally associated with hyperinsulinemic hypoglycemia (HH) in the neonatal period. Sotos syndrome (SS) and Kabuki syndrome (KS) are other malformation syndromes that may be complicated with HH, however, the detailed clinical characteristics of HH accompanied with these syndromes remain unclear. We herein conducted a nationwide questionnaire survey in Japan. We sent a primary questionnaire concerning the clinical experience for these syndromes to 347 perinatal care institutions. As a result, 222 departments or hospitals returned the questionnaires and the total numbers of BWS, SS, and KS patients were 113, 88, and 51, respectively. We sent a secondary questionnaire to 31 institutions where patients with these syndromes presented with HH during infancy. The secondary questionnaires were returned from the institutions and the numbers of patients were 16 for BWS, 9 for SS, and 3 for KS, respectively. Then, we compared the clinical characteristics of infants suffering from transient HH with and without these dysmorphic syndromes. As a result, BWS, SS, and KS patients showed significantly larger body size, lower Apgar scores, higher insulin levels at HH, and shorter durations of HH than non-dysmorphic infants with transient HH. We propose that a careful observation for the signs of HH, even if not specific to the syndromes, is important for the diagnosis of patients with BWS, SS, and KS in the postnatal period. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/ajmg.a.38011DOI Listing
February 2017

Screening for secondary hyperparathyroidism in preterm infants.

Pediatr Int 2016 Oct 8;58(10):988-992. Epub 2016 Jun 8.

Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Background: The major cause of osteopathy of prematurity is dietary phosphate deficiency, but secondary hyperparathyroidism caused by calcium deficiency or vitamin D deficiency is also important. Because parathyroid hormone (PTH) mobilizes calcium and phosphate from the bone, hyperparathyroidism worsens osteopathy of prematurity. In order to identify useful markers to screen for and diagnose hyperparathyroidism in preterm infants, we measured serum and urinary biochemical markers.

Methods: Several biomarkers, including serum intact PTH (iPTH), were measured in urine and serum samples obtained from 95 preterm infants, and the relationship between serum iPTH and the other parameters was analyzed.

Results: Mean gestation was 33.2 ± 2.9 weeks, and mean birthweight was 1705 ± 402 g. Samples were collected around postnatal day 17.3 ± 7.4. Fourteen infants (14.7%) had iPTH >65 pg/mL. Cut-offs for serum alkaline phosphatase (ALP) and percent tubular reabsorption rate of phosphate (%TRP) were fixed at 1300 IU/L and 93%, respectively using receiver operating characteristic curves with iPTH cut-off of 65 pg/mL. Serum ALP was proven to be a good marker: ALP had a sensitivity of 78.6% and a specificity of 86.4%, while %TRP itself was not: %TRP had a sensitivity of 64.3% and a specificity of 58.0%. Combined measurement of serum ALP (>1300 IU/L) and %TRP (≤93%), however, had a specificity of 93.8% for detecting elevated iPTH.

Conclusion: Measurement of serum ALP (>1300 IU/L) is considered as an effective screening method to detect hyperparathyroidism. In addition, combined assessment of ALP(>1300 IU/L) and %TRP(≤93%) is a good indicator of elevated iPTH in preterm infants.
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http://dx.doi.org/10.1111/ped.12961DOI Listing
October 2016

[Neonatal diabetes mellitus].

Authors:
Masahiko Kawai

Nihon Rinsho 2016 Apr;74 Suppl 2:485-9

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April 2016

Associations between respiratory arrhythmia and fundamental frequency of spontaneous crying in preterm and term infants at term-equivalent age.

Dev Psychobiol 2016 09 31;58(6):724-33. Epub 2016 Mar 31.

Graduate School of Education, Kyoto University, Kyoto, Japan.

This study investigated whether lower vagal function in preterm infants is associated with increased fundamental frequency (F0 ; frequency of vocal fold vibration) of their spontaneous cries. We assessed respiratory sinus arrhythmia (RSA) during quiet sleep as a measure of vagal function, and its relationship with the F0 of spontaneous cries in healthy preterm and term infants at term-equivalent age. The results showed that preterm infants have significantly lower RSA, and higher overall F0 than term infants. Moreover, lower RSA was associated with higher overall F0 in preterm infants, whereas higher RSA was positively associated with mean and maximum F0 , and a larger F0 range in term infants. These results suggest that individual differences in vagal function may be associated with the F0 of spontaneous cries via modulation of vocal fold tension in infants at an early developmental stage. © 2016 The Authors. Developmental Psychobiology Published by Wiley Periodicals, Inc. Dev Psychobiol 58:724-733, 2016.
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http://dx.doi.org/10.1002/dev.21412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5071706PMC
September 2016

A case of carcinoma of the papilla of Vater in a young man after subtotal colectomy for familial adenomatous polyposis.

World J Surg Oncol 2016 Feb 24;14(1):47. Epub 2016 Feb 24.

Department of Surgery, Gifu Prefectural General Medical Center, 4-6-1 Noisshiki, Gifu, 500-8717, Japan.

Background: Carcinoma and adenoma of the duodenum, including the papilla of Vater, are problematic diseases in patients with familial adenomatous polyposis (FAP).

Case Presentation: A 36-year-old man underwent a periodic medical examination for early colon cancer originating from FAP for which laparoscopic-assisted subtotal colectomy with a J-shaped ileal pouch-rectal anastomosis was performed 3 years earlier. A tumor was detected at the papilla of Vater along with elevation of total bilirubin and hepatobiliary enzymes. Although cytology did not determine the tumor to be an adenocarcinoma, we suspected adenocarcinoma due to its hypervascularity shown by contrast-enhanced computed tomography. Pylorus-preserving pancreaticoduodenectomy with modified Imanaga reconstruction and regional lymph node dissection (D2) was performed. The pathological study showed that the tumor was a papillary and moderately differentiated tubular adenocarcinoma. The patient is currently in good health without recurrence, weight loss, or severe diarrhea at 12 months after surgery.

Conclusions: Awareness of biliary-pancreatic symptoms and periodic gastroduodenoscopy might contribute both to the early detection of duodenal or periampullary polyps and cancer and to the radical treatment of FAP. Modified Imanaga reconstruction has the potential to become one of the more effective procedures for providing good quality of life to FAP patients with duodenal or periampullary cancer.
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http://dx.doi.org/10.1186/s12957-016-0806-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4765038PMC
February 2016

Fetal growth restriction but not preterm birth is a risk factor for severe hypospadias.

Pediatr Int 2016 Jul 4;58(7):573-7. Epub 2016 Feb 4.

Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Background: Hypospadias has multifactorial causes and occurs at a high frequency among very low-birthweight infants. Placental insufficiency is hypothesized to be one cause of hypospadias; that is, decreased human chorionic gonadotropin (hCG) secretion caused by placental insufficiency is suspected to result in abnormal male external genitalia, but there is little direct evidence to support this. The aim of this study was therefore to identify the features of hypospadias and to clarify the male genital abnormalities caused by fetal growth restriction (FGR).

Methods: We reviewed the clinical data of boys who underwent hypospadias repair between 2005 and 2011 at Kyoto University Hospital.

Results: Twenty boys were included in this study. Fifteen (75%) of the subjects were preterm or low-birthweight infants. Thirteen (65%) had FGR, 60% of whom had severe hypospadias regardless of gestational age. In addition, 92% of the FGR infants also had other genital anomalies, such as cryptorchidism, bifid scrotum, or micropenis. In contrast, only 14% and 43% of the non-FGR infants had severe hypospadias or genital anomalies other than hypospadias, respectively. Placental histopathology was available in eight FGR infants, in seven of whom it was suggestive of blood flow deficiency such as infarction and single umbilical artery.

Conclusions: Infants with FGR have a high incidence of hypospadias. FGR caused by placental dysfunction, but not low birthweight, is a risk factor for severe hypospadias associated with multiple genital anomalies.
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http://dx.doi.org/10.1111/ped.12864DOI Listing
July 2016

Intraday glucose fluctuation is common in preterm infants receiving intermittent tube feeding.

Pediatr Int 2016 May 2;58(5):359-62. Epub 2016 Feb 2.

Department of Pediatrics, Kitano Hospital, Tazuke Kofukai Medical Research Institute, Osaka, Japan.

Background: We previously reported on three preterm infants with blood glucose abnormalities after reaching full enteral feeding. Recently, it has been shown that clinically stable preterm infants may have large fluctuations in blood glucose after the establishment of enteral nutrition. We hypothesized that intraday glucose fluctuation is a common finding in preterm infants, but improves at term post-conceptual age. This report describes a case series.

Methods: From June 2010 to July 2012, 13 preterm infants (29.5 ± 2.1 post-conceptual weeks, 1144 ± 319 g) were enrolled in this study. Continuous glucose monitoring (CGM) was conducted on average at 33.5 ± 1.4 post-conceptual weeks, when they received gastric tube feeding every 3 h in the absence of i.v. glucose supply.

Results: Eight infants (62%) had large intraday glucose fluctuation with repeated hyperglycemic (>150 mg/dL) and hypoglycemic (<50 mg/dL) events. In five infants, follow-up CGM at 36-38 weeks post-conceptual age showed more stable glycemic changes without any abnormal glucose levels.

Conclusions: On CGM, in some preterm infants intermittent tube feeding resulted in large intraday glucose fluctuation at 31-35 post-conceptual weeks, but the pattern disappeared before discharge (36-38 post-conceptual weeks).
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http://dx.doi.org/10.1111/ped.12838DOI Listing
May 2016

Fetal Erythroblastosis May Be an Indicator of Neonatal Transient Hyperinsulinism.

Neonatology 2015 2;108(2):88-92. Epub 2015 Jun 2.

Department of Pediatrics, Medical Research Institute, Kitano Hospital Tazuke Kofukai, Osaka, Japan.

Background: Small for gestational age and birth asphyxia are associated with neonatal transient hyperinsulinism (THI). Some newborns with THI showed marked erythroblastosis on admission to our neonatal intensive care unit.

Objective: This study was designed to test our hypothesis that fetal erythroblastosis may be a risk factor for developing THI.

Methods: The records of all babies admitted to our neonatal intensive care unit within 24 h of birth between January 2010 and May 2014, and who were born after 34 weeks of gestation, were retrospectively reviewed. Hyperinsulinism was diagnosed as hypoglycemia concomitant with high serum insulin in babies requiring >6 mg/kg/min intravenous glucose and THI as hyperinsulinism without maternal diabetes or genetic disorders. The following three possible risk factors for THI were evaluated: (1) birth weight z-score, (2) 1-min Apgar score and (3) absolute nucleated red blood cell (aNRBC) count on admission.

Results: Of 705 infants, 8 were diagnosed with THI. Multivariate logistic regression analysis revealed that the aNRBC count was the most significant risk factor for THI. The median aNRBC count was 181/µl (interquartile range 0-538/µl), and 8 of 71 infants (11.3%) having an aNRBC count >1,413/µl (90th percentile in this study) had THI. The aNRBC counts in the 8 cases with THI were significantly higher than those in the 5 cases with hyperinsulinism caused by maternal diabetes or genetic disorders.

Conclusions: This study showed that the aNRBC count was strongly associated with subsequent THI. Fetal erythroblastosis, characterized by chronic fetal hypoxia, may be an indicator of perinatal stress sufficient to cause THI.
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http://dx.doi.org/10.1159/000381701DOI Listing
May 2016