Publications by authors named "Kougoro Iwanaga"

7 Publications

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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

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

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

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

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

Diagnostic value of salivary cortisol in the CRH stimulation test in premature infants.

J Clin Endocrinol Metab 2012 Mar 18;97(3):890-6. Epub 2012 Jan 18.

Department of Pediatrics, Graduate School of Medicine, Kyoto University, 54 Shogoin-kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan.

Context: According to a recent nationwide survey in Japan, a significant proportion of very low birth weight infants (VLBWI) develop late-onset circulatory collapse after the first week of life. Small doses of glucocorticoid are very effective in these patients, and relative adrenal insufficiency is suspected to be the main cause of the condition. Although the CRH test is required to evaluate the hypothalamic-pituitary-adrenal axis, obtaining multiple blood samples is invasive.

Objectives: The present study was carried out to validate the consistency of the cortisol profiles of matched serum and saliva samples collected as part of the CRH test from VLBWI.

Subjects/methods: In 23 VLBWI with a gestational age of less than 29 wk, we performed CRH tests at 2 wk after birth and at term. Their cortisol values were measured at the baseline and 30 min after the administration of a single dose of human CRH (1 μg/kg) using matched serum and saliva samples.

Results: In 26 CRH tests in 19 infants, we were able to measure both serum and salivary cortisol. Significant correlations were detected between the infants' serum and salivary cortisol values (r=0.78; P<0.0001), the increases in these values induced in response to the CRH test (r=0.81; P<0.0001), and their peak serum and salivary cortisol values (r=0.68; P=0.0001).

Conclusion: This study indicated that using salivary cortisol measurements for the CRH test could be a reliable method for evaluating the hypothalamic-pituitary-adrenal axis in VLBWI with gestational age of less than 29 wk.
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http://dx.doi.org/10.1210/jc.2011-1814DOI Listing
March 2012