Evaluation of deep gray matter for early brain development using quantitative susceptibility mapping.

OBJECTIVES: To evaluate susceptibility values associated with iron accumulation in the deep gray matter during postnatal development and to compare magnetic susceptibility between patients with normal and delayed development. METHODS: Patients with postmenstrual age (PMA) ≤ 1000 days underwent MR scans between August 2015 and April 2020 at our hospital. Quantitative susceptibility mapping (QSM) was performed, and magnetic susceptibility was measured using three-dimensional volumes of interest (VOIs) for the caudate nucleus (CN), globus pallidus (GP), putamen (PT), and ventrolateral thalamic nucleus (VL). Cross-sectional analysis was performed for 99 patients with normal development and 39 patients with delayed development. Longitudinal analysis was also performed to interpret changes over time in 13 patients with normal development. Correlations between magnetic susceptibility in VOIs and PMA or chronological age (CA) were assessed. RESULTS: Susceptibility values for CN, GP, PT, and VL showed positive moderate correlations with both PMA (ρ = 0.45, 0.69, 0.62, and 0.33, respectively) and CA (ρ = 0.53, 0.69, 0.66, and 0.39, respectively). The slope of the correlation between susceptibility values and age was highest in the GP among the four gray matter areas. Susceptibility values for the CN, GP, PT, and VL were higher with normal development than with delayed development at early postnatal age, although a significant difference was only observed for the CN. Susceptibility values also increased with age in the longitudinal analysis. CONCLUSIONS: Magnetic susceptibility values in deep gray matter increased with age ≤ 1000 days. The normal development group showed higher susceptibility values than the delayed development group at early postnatal age (PMA ≤ 285 days). KEY POINTS: • Magnetic susceptibilities in deep gray matter nuclei increased with age (postmenstrual age ≤ 1000 days) in a large number of pediatric patients. • The normal development group showed higher susceptibility values than the delayed development group in the basal ganglia and ventrolateral thalamic nucleus at early postnatal age (PMA ≤ 285 days).

Glucocorticoid Receptor Expression Pattern in Very Low Birth Weight Infants Changes Drastically within the First Week of Life.

INTRODUCTION: We herein examined changes in expression levels of the glucocorticoid receptor subtypes GRα and GRß in very low birth weight (VLBW) and term infants to clarify time-dependent changes in glucocorticoid sensitivity after birth. METHODS: Whole blood samples were collected at birth and on postnatal days 4-7, and the mRNA expression levels of GRα and GRß were measured using RT-qPCR. The relative gene expression levels of GRα and GRß as the target genes normalized to actin beta as the endogenous control were calculated by the comparative cycle threshold method. RESULTS: The GRα/GRß expression ratio at birth was significantly lower in 32 VLBW cesarean section (CS) infants than in term planned CS infants (median [IQR], 1.5 [1.1-1.8]- and 1.1 [0.7-1.6]-fold change, p < 0.05). Furthermore, the GRα/GRß expression ratio increased from day 0 to days 4-7 (1.0 [0.6-1.4]- and 1.7 [0.6-1.4]-fold change, p < 0.01) in 43 VLBW infants. DISCUSSION/CONCLUSION: The present results suggest that glucocorticoid sensitivity in VLBW infants increases after birth and this rapid change may play a role in surviving critical postnatal events.

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: 5.

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

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). TSH30 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.

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.

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.