Timing and outcome of stoma closure in very low birth weight infants with surgical intestinal disorders.

PURPOSE: Very low birth weight infants (VLBWIs) are at risk of surgical intestinal disorders including necrotizing enterocolitis (NEC), focal intestinal perforation (FIP), and meconium-related ileus (MRI). We conducted this study to verify whether the timing of stoma closure and that of enteral nutrition establishment after stoma closure in VLBWIs differ among the most common disorders. METHODS: A retrospective multicenter study was conducted at 11 institutes. We reviewed the timing of stoma closure and enteral nutrition establishment in VLBWIs who underwent stoma creation for intestinal disorders. RESULTS: We reviewed the medical records of 73 infants: 21 with NEC, 24 with FIP, and 25 with MRI. The postnatal age at stoma closure was 107 (28-359) days for NEC, 97 (25-302) days for FIP, and 101 (15-264) days for MRI (p = 0.793), and the postnatal age at establishment of enteral nutrition was 129 (42-381) days for NEC, 117 (41-325) days for FIP, and 128 (25-308) days for MRI (p = 0.855). The body weights at stoma closure were 1768 (620-3869) g for NEC, 1669 (1100-3040) g for FIP, and 1632 (940-3776) g (p = 0.614) for MRI. There were no significant differences among the three groups. CONCLUSIONS: The present study revealed that the time and body weights at stoma closure and the postoperative restoration of bowel function in VLBWIs did not differ among the three diseases.

Detailed analysis of 26 cases of 1q partial duplication/triplication syndrome.

Partial 1q trisomy syndrome is a rare disorder. Because unbalanced chromosomal translocations often occur with 1q trisomy, it is difficult to determine whether patient symptoms are related to 1q trisomy or other chromosomal abnormalities. The present study evaluated genotype-phenotype correlations of 26 cases diagnosed with 1q partial trisomy syndrome. DNA microarray was used to investigate the duplication/triplication region of 16 cases. Although there was no overlapping region common to all 26 cases, the 1q41-qter region was frequently involved. One case diagnosed as a pure interstitial trisomy of chromosome 1q by G-banded karyotype analysis was instead found to be a pure partial tetrasomy by CytoScan HD Array. In four 1q trisomy syndrome cases involving translocation, the translocated partner chromosome could not be detected by DNA microarray analyzes despite G-banded karyotype analysis, because there were a limited number of probes available for the partner region. DNA microarray and G-banded karyotyping techniques were therefore shown to be compensatory diagnostic tools that should be used by clinicians who suspect chromosomal abnormalities. It is important to continue recruiting affected patients and observe and monitor their symptoms to reveal genotype-phenotype correlations and to fully understand their prognosis and identify causal regions of symptoms.

Risk factors for surgical intestinal disorders in VLBW infants: Case-control study.

BACKGROUND: Very low-birthweight (VLBW) infants (VLBWI) are at increased risk for surgical intestinal disorders including necrotizing enterocolitis (NEC), focal intestinal perforation (FIP) and meconium-related ileus (MRI). The aim of this study was to identify disease-specific risk factors for surgical intestinal disorders in VLBWI. METHODS: A retrospective multicenter case-control study was conducted at 11 institutes. We reviewed VLBWI who underwent laparotomy for intestinal disorders including perforation and intractable bowel obstruction. The surgical disorders were classified into four categories (NEC, FIP, MRI, others) based on the macroscopic findings at operation. In order to identify risk factors, two matched controls for each subject were chosen based on gestational age and birthweight. OR and 95%CI were calculated using a conditional logistic regression model and a multivariate model. RESULTS: A total of 150 cases (NEC, n = 44; FIP, n = 47; MRI, n = 42; others, n = 17) and 293 controls were identified. The cases and controls were similar in terms of gestational age and birthweight (cases/controls, 26.7 ± 2.5/26.5 ± 2.6 weeks; 790 ± 256/795 ± 257 g). On multivariate modeling, disease-specific risk factors were as follows: female (OR, 0.23; 95%CI: 0.06-0.89), respiratory distress syndrome (OR, 35.7; 95%CI: 2.48-514) and patent ductus arteriosus (OR, 10.9; 95%CI: 1.51-79.3) for NEC; outborn delivery (OR, 5.47; 95%CI: 1.48-20.2) for FIP; and twin pregnancy (OR, 4.25; 95%CI: 1.06-17.1), PROM (OR, 6.85; 95%CI: 1.33-35.4) and maternal steroid (OR, 0.23; 95%CI: 0.07-0.79) for MRI. CONCLUSIONS: Different risk factors were identified for NEC, FIP and MRI, suggesting that each disease has a different etiology, and that different strategies are required to prevent these diseases.

Hyperinsulinemic hypoglycemia of infancy in Sotos syndrome.

Sotos syndrome (OMIM #117550) is a congenital syndrome characterized by overgrowth with advanced bone age, macrocephaly, and learning difficulties. Endocrine complications of this syndrome have not yet been fully described in previous reports. We here investigated the clinical manifestations of Sotos syndrome in Japanese patients who presented with hyperinsulinemic hypoglycemia of infancy. We recruited patients diagnosed as having Sotos syndrome who presented with the complication of hyperinsulinemia during the neonatal period using a survey of the abstracts of Pediatric Meetings in domestic areas of Japan from 2007 to 2011. As a result, five patients (four females and one male) were recruited to evaluate the clinical presentation of Sotos syndrome by reference to the clinical record of each patient. A 5q35 deletion including the NSD1 gene was detected in all patients. Major anomalies in the central nervous, cardiovascular, and genito-urinary systems were frequently found. Hypoglycemia occurred between 0.5 and 3 hr after birth and high levels of insulin were initially found within 3 days of birth. The patients were treated with intravenous glucose infusion at a maximum rate of 4.6-11.0 mg/kg/min for 12-49 days. Three of the five patients required nasal tube feeding. One patient received medical treatment with diazoxide. This study shows that patients with Sotos syndrome may present with transient hyperinsulinemic hypoglycemia in the neonatal period.

Lymphangiography as a Treatment for Refractory Congenital Chylothorax Due to RASopathies: A Report of Two Cases.

In this study, we report two cases in which intranodal lymphangiography helped improve congenital chylothorax due to RASopathies. We performed lymphangiography after conservative treatments failed to improve chylothorax in an 8-year-old girl with cardiofaciocutaneous syndrome and a 2-month-old boy with Noonan syndrome. Inguinal lymph nodes were punctured with 25-gauge needles under ultrasonographic guidance, and 4 and 1 mL of iodized oil were injected, respectively, showing a backflow of iodized oil into the lungs. Chylothorax had improved in both patients after nodal lymphangiography. However, the second child experienced worsening of disease-associated extremity edema and died of sepsis 4 months later.

A sutureless technique using cyanoacrylate adhesives when creating a stoma for extremely low birth weight infants.

PURPOSE: Intestinal perforation and necrotizing enterocolitis (NEC) are neonatal intestinal emergencies that are especially common in premature infants. While prompt surgical intervention, including stoma creation, is often required, the optimal surgical treatment has been controversial because of the substantial risks related to the stoma creation and management. The use of a tissue adhesive may have some advantages over the use of sutures when creating an intestinal stoma in extremely low birth weight (ELBW) infants. The purpose of this report was to present a novel approach for creating a stoma using a tissue adhesive in ELBW infants. METHODS: A total of eight ELBW infants that underwent laparotomy with the creation of intestinal stomas using cyanoacrylate adhesive at our institution between 2009 and 2014 were enrolled. The clinical parameters, including the length of the operation, intra- and postoperative complications and the outcomes were evaluated. RESULTS: The median body weight and gestational age at birth were 630 g and 24.3 weeks, respectively. The median age at referral was 11.5 days. The median length of the procedure was 58.5 min, including the inspection and resection of the intestine. All procedures were completed without any intraoperative complications. There were no postoperative complications associated with the stoma. Two patients died of the associated septic status. CONCLUSIONS: Sutureless enterostomy using cyanoacrylate adhesive is a simple technique which has the potential to reduce the incidence of complications related to the intestinal stoma in ELBW infants.

Prenatal diagnosis of Kniest dysplasia with three-dimensional helical computed tomography.

OBJECTIVE: Fetal three-dimensional helical computed tomography (3D-CT) has attracted attention in the diagnosis of fetal skeletal dysplasias because of limited diagnostic capabilities of standard ultrasonography to delineate the skeleton. Here we report the first instance of diagnosing Kniest dysplasia with 3D-CT. METHODS: Fetal 3D-CT was performed for a fetus at 28 weeks' gestation after ultrasonography at 24 weeks had shown moderate shortening of the limbs, mild narrow thorax, and polyhydramnios. The imaging parameters were set so as to reduce estimated fetal irradiation dose to 12.39 mGy of the CT dose index volume and 442 of the dose length product. RESULTS: Fetal 3D-CT revealed dumbbell-shaped femora and platyspondyly with coronal cleft of the lumbar vertebral body. This warranted a diagnosis of Kniest dysplasia and corresponded well with postnatal radiographic findings. In retrospect, however, spinal deformation was somewhat underestimated due to image smoothing associated with image processing in 3D-CT. Genetic testing for COL2A1 confirmed Kniest dysplasia; i.e., a de novo mutation of A-C transversion at the splice acceptor site of the 3' end of intron 16. CONCLUSIONS: The combined use of 3D-CT with ultrasonography is a power tool for the prenatal diagnosis of congenital skeletal dysplasias.

MRI tight posterior fossa sign for prenatal diagnosis of Chiari type II malformation.

INTRODUCTION: Chiari type II malformation (CMII) is one of three hindbrain malformations that display hydrocephalus. We have observed that cerebrospinal fluid (CSF) signal in the posterior fossa, which is always apparent on normal fetal MR images, is not visible in a fetus with CMII. We use the term 'tight posterior fossa' for this MR imaging finding, and evaluate the diagnostic value of this finding on fetal MR images. METHODS: Included in the study were 21 fetuses which underwent brain MR imaging at 1.5 T using two-dimensional balanced turbo-field-echo (2-D balanced-TFE) in the axial and sagittal planes. Postnatal diagnoses were CMII (n=5), CNS abnormalities other than CMII (n=8), and no abnormality (n=8). A tight posterior fossa was defined as an absent or slit-like water signal space around the hindbrain in the posterior fossa on both sagittal and axial MR images. RESULTS: All CMII fetuses displayed a tight posterior fossa on MR images. Hydrocephalus was visualized in all CMII fetuses and myelomeningocele in four fetuses, but hindbrain herniation was visualized only in two of five fetuses. The CSF signal surrounding the hindbrain was clearly visible in all the other 16 fetuses, including five with hydrocephalus not associated with CMII, although it was slightly narrower in a fetus with a cloverleaf skull than in the normal fetuses. CONCLUSION: Tight posterior fossa in the presence of hydrocephalus is a useful and characteristic finding of CMII on fetal MRI.

Possible correlation between high levels of IL-18 in the cord blood of pre-term infants and neonatal development of periventricular leukomalacia and cerebral palsy.

Periventricular leukomalacia (PVL) is a neonatal white matter damage of the brain of pre-term infants that often leads to cerebral palsy (CP). At present, diagnosis of PVL can be done by magnetic resonance imaging (MRI) and ultrasonography only when the infant is at least one week of age. No biochemical methods are available to identify high-risk infants at birth. Cytokines are usually not present in the cord blood but recently an elevation of IL-6 and TNF-alpha levels has been reported in amniotic fluid, cord blood and brain sections of infants with white matter damages. Levels of interleukin-18 (IL-18), a pleiotropic cytokines expressed in the brain and many other tissues, are highly sensitive to pathophysiological changes to raise the possibility that IL-18 may provide a useful indicator of PVL. The cord blood from 17 pre-term infants with PVL, 38 pre-term infants without PVL, and 30 normal full-term infants were retrospectively analysed for IL-18, IL-6, IL-1beta, and TNF-alpha. The possible factors involved in alteration of IL-18 concentration in relation to PVL and CP were examined. IL-18 is undetectable in the cord blood of normal full-term infants. However, high levels of IL-18 exist in the cord blood samples obtained from pre-term infants who neonatally developed PVL followed by CP. For pre-term infants under 35 weeks of gestation, seven out of eight showing more than 200 pg/ml of IL-18 (87.5%) developed PVL neonatally, with five of them subsequently developing CP. In contrast, only five out of 38 pre-term infants with less than 100 pg/ml of IL-18 (13.2%) developed PVL. For pre-term infants with less than 30 weeks of gestation, eight out of nine showing more than 100 pg/ml of IL-18 (88.9%) developed PVL, with six of these eight (75%) developing CP later. In conclusion, the presence of high levels of IL-18 in the cord blood of the pre-term infants is correlated with the incidence of PVL and CP and may provide a prognostic marker applicable at birth.