Risk factors of neonatal hypoglycemia in neonates born to mothers with gestational diabetes.

Hypoglycemia is one of the most significant problems in neonates born to mothers with gestational diabetes (GDM). This study aimed to identify novel predictors of hypoglycemia in neonates born to mothers with GDM. A total of 443 term singleton infants from mothers diagnosed with GDM and cared for at Keio University Hospital between January 2013 and December 2019 were included in this study. Neonatal hypoglycemia was defined as hypoglycemia of less than 47 mg/dL at 1 or 2 or 4 h after birth, according to previous studies. Among 443 full-term singleton neonates born to mothers with GDM, 200 developed hypoglycemia (45%). Gestational weight gain (GWG), HbA1c at 1st trimester, HbA1c at GDM diagnosis, and the incidence of insulin therapy in the neonatal hypoglycemia group were significantly higher than those in the non-neonatal hypoglycemia group (p = 0.016, p = 0.032, p = 0.011, and p = 0.017, respectively). Regarding the multiple regression analysis adjusted for nulliparity, GWG, and gestational weeks at delivery, the odds ratio for maternal HbA1c ≥5.2% at 1st trimester was 1.63 (p = 0.034), and maternal insulin therapy during pregnancy was 1.72 (p = 0.015). In conclusion, HbA1c in the 1st trimester and insulin therapy during pregnancy were good predictors of hypoglycemia in neonates born to GDM mothers, especially when their HbA1c was 5.2% or more. Further research will be necessary to improve the perinatal management of hypoglycemia.

Mortality and morbidity of extremely low birth weight infants in Japan, 2015.

BACKGROUND: In Japan, the mortality rate of extremely low birth weight (ELBW) infants is notably low in comparison with other developed countries, but the prevalence of chronic lung disease (CLD) and retinopathy of prematurity (ROP) is relatively high. This study aimed to estimate the mortality and morbidity of ELBW infants born in 2015 who were admitted to neonatal intensive care units (NICUs) in Japan and to examine the factors that affected the short-term outcomes of these infants. We also compared the mortality of ELBW infants born in 2005, 2010, and 2015. METHODS: We analyzed the mortality, morbidity, and factors related to short-term outcomes of ELBW infants, using data from 2782 infants born in 2015 and registered at NICUs in Japan. RESULTS: The mortality rates during NICU stays were 17.0%, 12.0%, and 9.8% for ELBW infants born in 2005, 2010, and 2015, respectively. Among ELBW infants born in 2015, multiple logistic regression analysis showed that short gestational age and low birthweight Z-score contributed to the increased risk of death. Births by cesarean section and antenatal corticosteroid administration were significantly associated with a reduced risk of death. Among infants who survived, CLD was observed in 53.1% and ROP requiring treatment was observed in 30.4%. CONCLUSIONS: Mortality in ELBW infants decreased significantly from 2005 to 2015. As CLD and ROP may affect quality of life and long-term outcomes of infants who survived, prevention strategies and management for these complications are critical issues in neonatal care in Japan.

Genome Analysis in Sick Neonates and Infants: High-yield Phenotypes and Contribution of Small Copy Number Variations.

OBJECTIVE: To delineate the diagnostic efficacy of medical exome, whole exome, and whole genome sequencing according to primary symptoms, the contribution of small copy number variations, and the impact of molecular diagnosis on clinical management. STUDY DESIGN: This was a prospective study of 17 tertiary care centers in Japan, conducted between April 2019 and March 2021. Critically ill neonates and infants less than 6 months of age were recruited in neonatal intensive care units and in outpatient clinics. The patients underwent medical exome, whole exome, or whole genome sequencing as the first tier of testing. Patients with negative results after medical exome or whole exome sequencing subsequently underwent whole genome sequencing. The impact of molecular diagnosis on clinical management was evaluated through contacting primary care physicians. RESULTS: Of the 85 patients, 41 (48%) had positive results. Based on the primary symptoms, patients with metabolic phenotypes had the highest diagnostic yield (67%, 4/6 patients), followed by renal (60%, 3/5 patients), and neurologic phenotypes (58%, 14/24 patients). Among them, 4 patients had pathogenic small copy number variations identified using whole genome sequencing. In the 41 patients with a molecular diagnosis, 20 (49%) had changes in clinical management. CONCLUSIONS: Genome analysis for critically ill neonates and infants had a high diagnostic yield for metabolic, renal, and neurologic phenotypes. Small copy number variations detected using whole genome sequencing contributed to the overall molecular diagnosis in 5% of all the patients. The resulting molecular diagnoses had a significant impact on clinical management.

A case of severe neonatal transient hyperinsulinemic hypoglycaemia without identifiable risk factors: a case report.

BACKGROUND: Neonatal hypoglycaemia is one of the major metabolic disorders that causes irreversible brain injury. Assessing for maternal glucose metabolism disorders can predict and avoid this perinatal complication. Accordingly, diagnosing maternal gestational diabetes mellitus (GDM) is important in protecting neonatal neurological prognosis. However, there are various methods of screening for maternal GDM. The intervention for neonatal hypoglycaemia also varies within each guideline. CASE PRESENTATION: A female infant was born at 37 weeks of gestation by vaginal delivery with no asphyxia. Her mother had no abnormal findings, including glucose metabolism disorders, upon periodic prenatal visits. Upon routine examination at the first hour of life, the baby was lethargic, pale, hypotonic, and rarely cried. An emergent systemic evaluation was performed, and she was diagnosed with severe hyperinsulinemic hypoglycaemia with blood glucose of 11 mg/dL and insulin of 2.7 µU/mL. She was soon fed with milk and her symptoms of hypoglycaemia was resolved before receiving intravenous glucose infusion. Her blood glucose level reached 78 mg/dL 3 h after delivery. She was discharged home with her mother on day 6 of age without relapse of hypoglycaemia. Upon review, we determined that the mother was diagnosed with GDM during her previous pregnancy but not during this current pregnancy. The infant had no developmental delay upon check-up at 6 months. CONCLUSIONS: The infant of this case was not a candidate for neonatal hypoglycaemia screening since her mother had no identifiable risk factors. This case suggests that previous maternal history of GDM might be the cause of neonatal hyperinsulinemic hypoglycaemia. Clinicians need to be aware of the possibility of hypoglycaemia among newborns with a maternal previous history of GDM, regardless of the mother's current diagnosis. Immediate oral feeding can be one of the treatments, even for symptomatic neonatal severe hypoglycaemia, when rapid intravenous access is difficult. The present case also suggests the necessity of considering neonatal outcomes as well as maternal ones when screening for maternal disorders of glucose metabolism.

Caspase-3 regulates ureteric branching in mice via cell migration.

Inhibition of caspase-3 (Casp3) reduces ureteric branching in organ culture but the mechanism remains unclear. Since Casp3 has non-apoptotic functions, we examined whether Casp3 regulates ureteric branching by promoting cell migration, using a ureteric bud (UB) cell line and Casp3-deficient (Casp3-/-) mice. Also, we examined whether Casp3 plays a role in the reduced ureteric branching of metanephroi from nutrient restricted mothers, in which Casp3 activity is suppressed. A Casp3 inhibitor Ac-DNLD-CHO reduced FGF2-induced cord formation of UB cells in 3D culture. UB cell migration assessed by Boyden chamber and wound healing assays was inhibited by Ac-DNLD-CHO. Glomerular number was reduced by ≈ 30%, and ureteric tip number was lower in Casp3-/- mice compared with controls. Maternal nutrient restriction decreased ureteric tip number in controls but not in Casp3-/-. In conclusion, Casp3 regulates ureteric branching by promoting UB cell migration. Inhibited ureteric branching by maternal nutrient restriction may be mediated by Casp3.

MicroRNA-26 regulates the expression of CTGF after exposure to ionizing radiation.

Radiation-induced fibrosis (RIF) is a serious complication that occurs after irradiation and which is caused by the deposition of extracellular matrix (ECM) proteins such as collagen. However, the underlying mechanisms, including the expression of the cytokines, that promote the RIF process, are not yet fully understood. MicroRNAs (miRNAs) have recently been suggested to act as post-transcriptional repressors for many genes; however, their role in the process of RIF remains to be elucidated. Our previous study showed that ionizing radiation increased the type I collagen expression through the activation of transforming growth factor (TGF)-ß, while miR-29 repressed this increase. This study aimed to investigate the mechanisms by which the expression of connective tissue growth factor (CTGF), a downstream mediator of TGF-ß, is controlled by miRNAs post-transcriptionally after exposure to ionizing radiation. The expression of CTGF in NIH-3T3 cells and mouse embryonic fibroblasts was increased by ionizing radiation. However, this increase was suppressed with a specific inhibitor of TGF-ß receptor. Among the predictable miRNAs that target the CTGF gene, the expression of miR-26a was downregulated after exposure to ionizing radiation and this regulation was negatively mediated by TGF-ß signaling. miR-26a negatively regulated the CTGF expression at the post-transcriptional level; however, ionizing radiation suppressed this negative regulation. In addition, the overexpression of miR-26a inhibited the expression of CTGF and type I collagen after irradiation. In conclusion, miR-26a modulates the expression of CTGF via TGF-ß signaling in irradiated fibroblasts. The results suggest the potential application of miR-26a in the treatment of RIF.

Tubular dysfunction in extremely low birth weight survivors.

BACKGROUND: Extremely low birth weight (ELBW) survivors may develop glomerulosclerosis due to low nephron number, whereas their tubular function remains unknown except for hypercalciuria and phosphaturia. METHODS: Fifty-three subjects (30 boys and 23 girls, aged 7 months-19 years, median 36 months) were studied retrospectively. The median gestational age and birth weight were 26 weeks (range 22-32) and 745 g (range 316-999), respectively. Urine calcium-to-creatinine ratio (Ca/Cr), N-acetyl-ß-D-glucosaminidase-to-creatinine ratio (NAG/Cr), ß2 microglobulin-to-creatinine ratio (ß2m/Cr), uric acid-to-creatinine ratio (UA/Cr), glucose-to-creatinine ratio (glu/Cr), and microalbumin-to-creatinine ratio (malb/Cr) were examined. We also assessed the association between urine parameters and current age, gestational age, birth weight, and predictors of renal injury. Follow-up data were analyzed in 43 subjects 4-6 years later. RESULTS: Ninety percent of subjects had at least one tubular dysfunction. Frequency of elevated values was NAG/Cr 77.5%, UA/Cr 54.1%, ß2m/Cr 38.2%, malb/Cr 30.4%, Ca/Cr 21.5%, and glu/Cr 20.5%. There were significant negative correlations between the current age and Ca/Cr, NAG/Cr, glu/Cr, and UA/Cr, suggesting tubular function maturation. Urine ß2M/Cr and glu/Cr were negatively correlated with the gestational age. There were significant associations between elevated glu/Cr and asphyxia or neonatal acute kidney injury, and elevated NAG/Cr and indomethacin use, although these were not confirmed by multivariate analysis. At follow-up, the frequency of elevated NAG/Cr, glu/Cr, UA/Cr, and malb/Cr was reduced but that of elevated Ca/Cr, IgG/Cr, and ß2m/Cr remained similar or increased. CONCLUSION: Tubular dysfunction is common in ELBW survivors. Some abnormalities resolved with age while some remained persistent or even increased.

Effects of Intrapartum Antibiotic Prophylaxis on Neonatal Acquisition of Group B Streptococci.

OBJECTIVES: To assess the incidence of colonization with group B streptococci (GBS) among neonates as influenced by maternal GBS carriage and intrapartum antibiotic prophylaxis (IAP). STUDY DESIGN: Between October 2014 and May 2015, nasopharyngeal and rectal swab samples were collected from 730 neonates at 1 week and 1 month after birth. GBS and capsular serotype were identified by real-time polymerase chain reaction and by culture. IAP at delivery was determined retrospectively from hospital records. RESULTS: Sixty-four neonates (8.8%) were GBS-positive by real-time polymerase chain reaction and culture. Among neonates born to mothers who were GBS carriers (n = 107), 94.4% (101/107) had maternal IAP; 19.6% nonetheless were GBS-positive, compared with 6.5% of neonates born to noncarrier mothers (P <.01). Among neonates born to mothers receiving IAP, more were positive only at 1 month of age than at both 1 week and 1 month. The frequency of GBS in neonates born to mothers receiving IAP was significantly lower than that in neonates born to mothers not receiving IAP (P <.05). Capsular serotypes V (25%) and III (23.4%) were common, followed by Ib (15.6%), Ia (14.1%), II (7.8%), IV (6.3%), nontypeable (4.7%), and VI and VIII (each 1.6%). CONCLUSIONS: Delayed colonization with GBS occurs in infants born to GBS carrier mothers receiving IAP. GBS should be considered in all infants at 1 month after birth with signs of infection.

GABA promotes elastin synthesis and elastin fiber formation in normal human dermal fibroblasts (HDFs).

The multiple physiological effects of γ-aminobutyric acid (GABA) as a functional food component have been recently reported. We previously reported that GABA upregulated the expression of type I collagen in human dermal fibroblasts (HDFs), and that oral administration of GABA significantly increased skin elasticity. However, details of the regulatory mechanism still remain unknown. In this study, we further examined the effects of GABA on elastin synthesis and elastin fiber formation in HDFs. Real-time PCR indicated that GABA significantly increased the expression of tropoelastin transcript in a dose-dependent manner. Additionally, the expression of fibrillin-1, fibrillin-2, and fibulin-5/DANCE, but not lysyl oxidase and latent transforming factor-ß-binding protein 4, were also significantly increased in HDFs. Finally, immunohistochemical analysis confirmed that treatment with GABA dramatically increased the formation of elastic fibers in HDFs. Taken together, our results showed that GABA improves skin elasticity in HDFs by upregulating elastin synthesis and elastin fiber formation.

Maternal nutrient restriction inhibits ureteric bud branching but does not affect the duration of nephrogenesis in rats.

BACKGROUND: Maternal nutrient restriction produces offspring with fewer nephrons. We studied whether the reduced nephron number is due to the inhibition of ureteric branching or early cessation of nephrogenesis in rats. Signaling pathways involved in kidney development were also examined. METHODS: The offspring of dams given food ad libitum (control (CON)) and those subjected to 50% food restriction (nutrient restriceted (NR)) were examined. RESULTS: At embryonic day 13 (E13), there was no difference between NR and CON in body weight or kidney size. Ureteric buds branched once in both NR and CON. At E14 and E15, body and kidney size were significantly reduced in NR. Ureteric bud tip numbers were also reduced to 50% of CON. On the other hand, the disappearance of nephrogenic zone and a nephron progenitor marker Cited1 was not different between CON and NR. The final glomerular number of NR was 80% of CON. Activated extracellular signal-regulated kinase (ERK), p38, PI3K, Akt, and mammallian target of rapamycin (mTOR), and protein expression of ß-catenin were downregulated at E15. CONCLUSION: Ureteric branching is inhibited and developmentally regulated signaling pathways are downregulated at an early stage by maternal nutrient restriction. These changes, not early cessation of nephrogenesis, may be a mechanism for the inhibited kidney growth and nephrogenesis.

Survival and unique clinical practices of extremely preterm infants born at 22-23 weeks' gestation in Japan: a national survey.

OBJECTIVES: To investigate prognosis and clinical practices of infants born at 22-23 weeks' gestational age (wkGA) in Japan. DESIGN: A national institutional-level electronic questionnaire surveys performed in September 2021. SETTING: All perinatal centres across Japan. PATIENTS: Infants born at 22-23 wkGA in 2018-2020. MAIN OUTCOME MEASURES: Proportion of active resuscitation and survival at neonatal intensive care unit (NICU) discharge, and various clinical practices. RESULTS: In total, 255 of 295 NICUs (86%) responded. Among them, 145 took care of infants born at 22-23 wkGA and answered the questions regarding their outcomes and care. In most NICUs (129 of 145 (89%)), infants born at 22+0 wkGA can be actively resuscitated. In almost half of the NICUs (79 of 145 (54%)), infants born at ≥22+0 wkGA were always actively resuscitated. Among 341 and 757 infants born alive at 22 and 23 wkGA, respectively, 85% (291 of 341) and 98% (745 of 757) received active resuscitation after birth. Among infants actively resuscitated at birth, 63% (183 of 291) and 80% (594 of 745) of infants born at 22 and 23 wkGA survived, respectively. The survey revealed unique clinical management for these infants in Japan, including delivery with caul in caesarean section, cut-cord milking after clamping cord, immediate intubation at birth, hydrocortisone use for chronic lung disease, analgesia/sedation use for infants on mechanical ventilation, routine echocardiography and brain ultrasound, probiotics administration, routine glycerin enema and skin dressing to prevent pressure ulcers. CONCLUSIONS: Many 22-23 wkGA infants were actively resuscitated in Japan and had a high survival rate. Various unique clinical practices were highlighted.

Severe congenital lipodystrophy and a progeroid appearance: Mutation in the penultimate exon of FBN1 causing a recognizable phenotype.

Recently, three marfanoid patients with congenital lipodystrophy and a neonatal progeroid appearance were reported. Although their phenotype was distinct from that of classic Marfan syndrome, they all had a truncating mutation in the penultimate exon, i.e., exon 64, of FBN1, the causative gene for Marfan syndrome. These patients might represent a new entity, but the exact phenotypic and genotypic spectrum remains unknown. Here, we report on a girl born prematurely who exhibited severe congenital lipodystrophy and a neonatal progeroid appearance. The patient exhibited a characteristic growth pattern consisting of an accelerated growth in height with a discrepant poor weight gain. She had a characteristic facial appearance with craniosynostosis. A mutation analysis identified c.8175_8182del8bp, p.Arg2726Glufs*9 in exon 64 of the FBN1 gene. A review of similar, recently reported patients revealed that the cardinal features of these patients include (1) congenital lipodystrophy, (2) premature birth with an accelerated linear growth disproportionate to the weight gain, and (3) a progeroid appearance with distinct facial features. Lines of molecular evidence suggested that this new progeroid syndrome represents a neomorphic phenotype caused by truncated transcripts with an extremely charged protein motif that escapes from nonsense-mediated mRNA decay, altering FBN1-TGF beta signaling, rather than representing the severe end of the hypomorphic phenotype of the FBN1-TGF beta disorder spectrum. We propose that this marfanoid entity comprised of congenital lipodystrophy, a neonatal progeroid appearance, and a peculiar growth profile and caused by rare mutations in the penultimate exon of FBN1, be newly referred to as marfanoid-progeroid syndrome.

Efficacy and safety of a telemedicine system in subjects with gestational diabetes mellitus (TELEGLAM): Study protocol for a randomized controlled trial.

Background: Strict glycemic control is important to prevent perinatal complications in patients with gestational diabetes mellitus (GDM). Patients often require insulin injection, and frequent hospital visits are necessary to adjust the dose of insulin, which is considered burdensome for pregnant patients. Telemedicine may reduce the burden of hospital visits, and previous studies have reported its safety in GDM patients. This study aimed to evaluate the efficacy of telemedicine in GDM patients, focusing on patient satisfaction and health economic indicators. Methods: This is a single-center, two-arm, randomized, open-label parallel-group study. Subjects will be selected from the patient population attending the Department of Endocrinology, Metabolism, and Nephrology, Keio University School of Medicine, Japan. Patients diagnosed with GDM by an oral glucose tolerance test (OGTT) by 29 weeks and 6 days of gestation who have undergone self-monitoring of blood glucose (SMBG) and insulin injection are eligible for inclusion. In the intervention group, telemedicine will be administered using the MeDaCa telemedicine system developed by the Medical Data Card, Inc., Tokyo, Japan. Subjects in the control group will be examined face-to-face every 2-3 weeks, as usual. We set health economic indicators and patient satisfaction as the primary endpoints, and will perform a cost-consequence analysis. Glycemic control indicators and perinatal outcomes will be evaluated as secondary endpoints. Conclusions: Eligible patients are currently being recruited. Recruitment will be completed when the expected number of patients are enrolled.

Potential benefit of rapid genetic testing for Pallister-Hall syndrome.

Pallister-Hall syndrome (PHS) is defined as a group of characteristic manifestations caused by a monoallelic GLI3 pathogenic variant. A two-month-old infant was referred to our institution because of undetermined sex. The infant had atypical genitalia with postaxial polysyndactyly, a hypothalamic mass, and an imperforate anus. We identified a known pathogenic variant of the GLI3 gene within one week and diagnosed the infant with PHS. The parents assigned the infant as male, considering the 46,XY karyotype, normal testosterone secretion, possible male identity, and the natural history of PHS. In infants with atypical genitalia and other malformations, such as polydactyly, a hypothalamic mass, or an imperforate anus, rapid GLI3 testing may provide information for planning lifelong management, including sex assignment.

Less-Invasive Diagnostic Approaches for Infants with Suspected Differences of Sex Development: A Case Report of a 297-g Neonate with Ambiguous Genitalia.

Less-invasive diagnostic approaches for low-birthweight preterm neonates with suspected differences of sex development have not been established. Herein, we describe our diagnostic approaches for a 297-g neonate with ambiguous genitalia. Using a fiberscope, the external genitalia were inspected in an incubator to minimize the risk of hypothermia and infection. Endotracheal aspirate, collected during routine care, was used for genetic testing to avoid anemia and vital signs fluctuations caused by peripheral blood sampling. Array comparative genomic hybridization indicated a 46,XY karyotype. No pathogenic variants of AR and SRD5A2 were found. Endocrinological data could not be evaluated owing to the absence of reference data. Identification and structural evaluation of the internal genitalia and gonads were difficult. On postnatal day 42, the parents assigned their baby's sex as male. Our less-invasive diagnostic approaches of inspection and genetic testing are useful for management, including sex assignment in extremely low-birthweight preterm neonates with ambiguous genitalia.

DNA methylation analysis of cord blood samples in neonates born to gestational diabetes mothers diagnosed before 24 gestational weeks.

INTRODUCTION: Genome-wide methylation analyses of gestational diabetes mellitus (GDM) diagnosed after 24 gestational weeks (late GDM (L-GDM)) using cord blood have been reported. However, epigenetic changes in neonates born to mothers with GDM diagnosed before 24 gestational weeks (early GDM (E-GDM)) have not been reported. We investigated DNA methylation in neonates born to mothers with E-GDM using cord blood samples. RESEARCH DESIGN AND METHODS: Genome-wide DNA methylation analysis was performed using an Illumina EPIC array to compare methylation rates of 754 255 autosomal sites in cord blood samples from term neonates born to 162 mothers with GDM (E-GDM: n=84, L-GDM: n=78) and 60 normal glucose tolerance (normal OGTT) pregnancies. GDM was diagnosed based on Japan Society of Obstetrics and Gynecology criteria modified with International Association of Diabetes in Pregnancy Study Group criteria. In this study, all GDM mothers underwent dietary management, while self-monitoring of blood glucose and insulin administration was initiated when dietary modification did not achieve glycemic control. RESULTS: There were no significant differences in genome-wide DNA methylation of cord blood samples between the GDM (E-GDM and L-GDM) groups and normal OGTT group or between the E-GDM and normal OGTT groups, L-GDM and normal OGTT groups, and E-GDM and L-GDM groups. CONCLUSIONS: This is the first report to determine the DNA methylation patterns in neonates born to mothers with E-GDM. Neonates born to mothers with GDM, who were diagnosed based on Japan Society of Obstetrics and Gynecology criteria, may not differ in DNA methylation compared with those born to normal OGTT mothers.

Fetal growth restriction and a single umbilical artery are independent predictors of hypospadias during pregnancy.

INTRODUCTION: Little is known about the association between hypospadias and small fetuses, as well as the pathological implications of fetal growth restriction (FGR). Thus, we aimed to investigate the association between hypospadias and small fetuses using a database of fetal ultrasound and obstetric events. METHODS: A cohort of male singleton infants delivered after 22 weeks of gestation at Keio University Hospital between 2013 and 2019 was retrospectively reviewed. FGR was defined according to the Delphi criteria. Logistic regression analysis was performed to identify the significant predictors of hypospadias. Placental pathology was reviewed in cases with hypospadias. RESULTS: Of the 2,040 male infants included in the present study, 23 had hypospadias. The prevalences of a single umbilical artery (SUA), small for gestational age, maternal hypertensive disorders of pregnancy, and a small placenta, were significantly higher in infants with hypospadias. Multiple logistic regression analysis revealed that FGR (odds ratio [OR] = 9.39; 95% confidence interval [CI], 2.50-35.3) and the presence of a SUA (OR = 33.4; 95% CI, 8.00-139.5) were independently and significantly associated with hypospadias. When FGR was stratified by the time of onset, its association with hypospadias was significant regardless of the time of onset. Moreover, placental histological findings suggested that fetal vascular malperfusion might play a role in hypospadias. DISCUSSION: FGR and SUAs are independent prenatal predictors of the development of hypospadias, and fetal vascular malperfusion of the placenta may be involved in the etiology of hypospadias.

Midodrine, an Oral Alpha-1 Adrenoreceptor Agonist, Successfully Treated Refractory Congenital Chylous Pleural Effusion and Ascites in a Neonate.

A trisomy 21 neonate presented with congenital chylous pleural effusion and ascites that was refractory to conventional pharmacotherapy. Midodrine, an oral alpha-1-adrenoreceptor agonist, achieved remission of chylous effusion without any adverse effects. To the best of our knowledge, this is the first neonatal case of successful management of congenital chylous pleural effusion and ascites with midodrine.

Epigenetic Changes in Neonates Born to Mothers With Gestational Diabetes Mellitus May Be Associated With Neonatal Hypoglycaemia.

The detection of epigenetic changes associated with neonatal hypoglycaemia may reveal the pathophysiology and predict the onset of future diseases in offspring. We hypothesized that neonatal hypoglycaemia reflects the in utero environment associated with maternal gestational diabetes mellitus. The aim of this study was to identify epigenetic changes associated with neonatal hypoglycaemia. The association between DNA methylation using Infinium HumanMethylation EPIC BeadChip and neonatal plasma glucose (PG) level at 1 h after birth in 128 offspring born at term to mothers with well-controlled gestational diabetes mellitus was investigated by robust linear regression analysis. Cord blood DNA methylation at 12 CpG sites was significantly associated with PG at 1 h after birth after adding infant sex, delivery method, gestational day, and blood cell compositions as covariates to the regression model. DNA methylation at two CpG sites near an alternative transcription start site of ZNF696 was significantly associated with the PG level at 1 h following birth (false discovery rate-adjusted P < 0.05). Methylation levels at these sites increased as neonatal PG levels at 1 h after birth decreased. In conclusion, gestational diabetes mellitus is associated with DNA methylation changes at the alternative transcription start site of ZNF696 in cord blood cells. This is the first report of DNA methylation changes associated with neonatal PG at 1 h after birth.