消化管への物質の通過がインクレチン分泌に及ぼす影響の出生前後の変化

京都大学新制・論文博士博士(医学)乙第13450号論医博第2243号新制||医||1054(附属図書館)(主査)教授 稲垣 暢也, 教授 妹尾 浩, 教授 小濱 和貴学位規則第4条第2項該当Doctor of Medical ScienceKyoto UniversityDFA

Effect of doxapram on the electrical activity of the diaphragm waveform pattern of preterm infants

[Objective] This study aimed to evaluate the change in the waveform pattern of the electrical activity of the diaphragm (Edi) following the administration of doxapram in extremely preterm infants ventilated with neurally adjusted ventilatory assist (NAVA). [Study Design] We conducted this retrospective cohort study in our neonatal intensive care unit between November 2019 and September 2021. The study participants were extremely preterm infants under the gestational age of 28 weeks who were ventilated with NAVA and administered doxapram. We collected the data of the Edi waveform pattern and calculated the proportion. To analyze the change in the proportion of the Edi waveform pattern, we compared the proportion of the data for 1 h before and after doxapram administration. [Results] Ten extremely preterm infants were included. Almost all the patients’ respiratory condition improved after doxapram administration. The ventilatory parameters—Edi peak, Edi minimum, peak inspiratory pressure, time in backup ventilation, and number of switches to backup ventilation—did not change significantly. However, the proportion of phasic pattern significantly increased (before: 46% vs. after: 72%; p < 0.05), whereas the central apnea pattern significantly decreased after doxapram administration (before: 31% vs. after: 8.3%; p < 0.05). The proportion of irregular low-voltage patterns tended to decrease, albeit with no significant changes. [Conclusion] Our results indicated that the proportion of Edi waveform patterns changed following doxapram administration. Edi waveform pattern analysis could be a sensitive indicator of effect with other intervention for respiratory conditions

Effect of electrical activity of the diaphragm waveform patterns on SpO₂ for extremely preterm infants ventilated with neurally adjusted ventilatory assist

[Objective] This study aimed to evaluate the association between electrical activity of the diaphragm (Edi) waveform patterns and peripheral oxygen saturation (SpO2) 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 SpO2, 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 SpO2 in extremely preterm infants who are ventilated with NAVA

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

[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, T₁‐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 T₁‐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 Tmean/cord, Tmax/cord, and T_vol were evaluated using the Steel–Dwass test. Results: APmean/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). PPmean/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). Tmean/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). APmean/pons correlated positively with Tmean/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]:

Clinical Features of Neurodevelopmental Outcomes in Children with Preterm Severe Fetal Growth Restriction: A Retrospective Observational Study

Introduction: Fetal growth restriction (FGR) is a clinical condition wherein a fetus fails to achieve the expected growth potential. Although FGR is the leading cause of perinatal morbidity and mortality, there is a lack of knowledge about the long-term developmental outcomes of children who had FGR in Japan. Here, we sought to clarify the features of neurodevelopmental outcomes in preterm-born children with severe FGR (sFGR) and identify associated clinical factors. Methods: The clinical data of 26 preterm sFGR cases and 26 preterm appropriate for gestational age (AGA) cases with a similar gestational age distribution were reviewed retrospectively. Developmental quotient (DQ) scores assessed during the 1- and 2-year corrected ages using the Kyoto Scale of Psychological Development were analyzed. Results: sFGR was diagnosed at 26 (18-34) weeks of gestation, and the gestational age at delivery was 31 (25-36) weeks. The overall DQ scores of children in the sFGR group were significantly lower than those in the AGA group (80 vs. 90.5, P = 0.0127). Of the three areas that comprise the DQ (Postural-Motor, Cognitive-Adaptive, and Language-Social), the sFGR group only showed significantly lower DQ scores (72.5 vs. 88, P = 0.0255) in the Language-Social area. Both fetal body weight and fetal body weight Z score at birth significantly correlated with the DQ scores (r = 0.4912, P = 0.0108, and r = 0.5621, P = 0.0028), whereas neither the duration of fetal growth arrest nor the gestational age at birth correlated with the DQ scores (r = 0.3598, P = 0.0842, and r = 0.3522, P = 0.0776). Conclusions: Our results indicate that preterm-born children with sFGR have greater neurodevelopmental impairment than preterm-born children without FGR, specifically in terms of the DQ scores for the Language-Social area. It is imperative to encourage continuous long-term follow-up and appropriate interventions after birth

Severe Hemolytic Jaundice in a Neonate with a Novel COL4A1 Mutation

We report our experience with a preterm infant with severe hemolytic jaundice who required exchange transfusion just after birth. The patient was negative for alloimmune hemolysis as a result of maternal–fetal blood type incompatibility, and tests for inherited defects in erythrocyte metabolism, membrane function, and hemoglobin synthesis were normal. We also performed a bone marrow examination, but could not identify the cause of hemolysis. The patient had several other complications, including porencephaly, epilepsy, elevated serum levels of creatine kinase, and persistent microscopic hematuria. Later, we detected a genetic mutation in COL4A1, which was recently found to be associated with hemolytic anemia. We therefore believe that all of the patient's clinical features, including hemolytic anemia, were due to the mutation in COL4A1. Genetic testing for COL4A1 mutations is recommended in neonates who exhibit hemolytic disease of unknown etiology, especially when other complications compatible with COL4A1-related disorders are present

Relationship between brain metabolite concentrations/volumes during neonatal

[Purpose] It is well known that the premature birth is associated with increased risk of neurological and physical problems. The purpose of this study is to investigate whether the brain metabolite concentration (conc) and/or volumes in neonates can be an index of the prognosis for the premature birth.[Methods] Twenty-six subjects with premature birth (gestational age: 23-33 weeks) were included. At their postconceptional age of 34-40 weeks, they had brain MRI (Siemens 3T) including MRS (PRESS, TE 30ms, TR 5s). The metabolite conc were calculated using LCModel with water conc of 46.9M. Using T2W images (TE 119-123ms, TR 5s), the volumes were measured using ROI editor (John Hopkins). At a corrected age of 1.5 years, they had developmental quotient (DQ) by Kyoto Scale of Psychological Development. Correlations between the conc and DQ, and the volume and DQ were investigated using Spearman’s rank correlation coefficients. The conc change with development was considered. [Results] The creatine, choline, N-acetylaspartate, myo-inositol, and glutamate/glutamine complex conc were 5.4-9.0, 1.3-2.6, 3.0-6.4, 4.8-8.8, and 3.8-11.5mM, in the basal ganglia, respectively, and 3.8-5.9, 1.5-2.3, 2.4-6.1, 5.7-9.3, and 3.9-8.9mM, in the centrum semiovale. The supratentorial, cerebellum, and intracranial volumes were 222-332, 13-22, and 352-550mL, respectively; The DQ were 44-119. No correlations were found between the metabolite conc or volumes and DQ. [Discussion] The DQ is overall index, and in this study fine classification of the DQ was not considered. Also, the volume change with development was not considered. Although we could not find any correlation, more detail studies are needed to confirm whether the MR data in neonates can be an index of the prognosis for premature birth.第44回日本磁気共鳴医学会大