Outcomes of inborn and transported extremely premature very‐low‐birthweight infants in Hawai‘i

Background: Delivery of premature infants outside tertiary care centers is not always preventable. The aim of this study was to compare rates of survival and common morbidities in extremely premature babies transported to a level III facility versus those born at the level III center. Methods: Retrospective chart review was performed on all neonates born at ≤ 28 weeks of gestation with birthweight ≤1500 g who were admitted to the Newborn Intensive Care Unit at Kapi‘olani Medical Center for Women and Children (KMCWC) between 1 January 2000 and 31 December 2005. Infants were divided into two groups, those born at KMCWC (Inborn) and those born at level I institutions and subsequently transported (Transport) to KMCWC. Results: A total of 394 neonates met the study criteria; 349 were inborn while 45 were transported. Survival rates were identical for both groups. However, the Transport group survivors displayed a significantly longer mean length of stay and higher rate of severe retinopathy of prematurity than those in the Inborn group (P≤ 0.01). Conclusion: Identical rates of survival in both groups suggest that community medical professionals are providing satisfactory care to stabilize critical neonates without reducing their chances of survival. However, increased length of stay and higher rate of retinopathy of prematurity in the Transport group suggest that differences in medical management during the first few hours of life may adversely affect outcomes.     

Three‐dimensional visualization of renal artery stenosis by 64‐channel multiple detector‐row computed tomographical angiography: review of two paediatric cases

Three‐dimensional visualization of renal arteries has recently been established by helical contrast‐enhanced multiple detector‐row computed tomographical angiography (MDCTA) in adults. So far, no information is available on its use in children. We reported two children with renal artery stenosis detected by 64‐channel MDCTA. The first patient probably had fibromuscular dysplasia and the other neurofibromatosis type1. The technique showed a left renal artery stenosis with a small left kidney in the first patient and a right renal artery stenosis in the second. Conclusion: MDCTA is an accurate and noninvasive imaging technique, easily performed in children, and can be used as an alternative diagnostic modality in children with suspected renovascular hypertension.     

Interleukin‐6 polymorphism and bronchopulmonary dysplasia risk in very low‐birthweight infants

Background: The aim of the present study was to evaluate the role of interleukin (IL)‐6‐634 polymorphism in neonatal disorders such as bronchopulmonary dysplasia (BPD) and periventricular leukomalacia (PVL) in very low‐birthweight (VLBW) infants. Methods: This prospective cohort study included 202 infants (gestational age at birth, 23–34 weeks; birthweight, 500–1499 g). Genotypic analysis (polymerase chain reaction–restriction fragment length polymorphism) was performed with DNA extracted from whole‐blood samples. Results: Genotype distribution (66.8% CC, 28.2% CG, 5.0% GG) was similar to that in the adult Japanese population. BPD occurred in 85 infants (42.1%) among 202 VLBW infants. The duration of O₂ therapy in infants with CG/GG genotypes was significantly longer than that in infants with the CC genotype (CG/GG vs CC: 40.3 ± 52.2 days vs 28.4 ± 32.6 days, P < 0.05), but the prevalence of BPD was not associated with the CG/GG genotype (CG/GG, 40.0%; CC, 46.3%, P= 0.24). Infants with CG/GG genotypes were more likely to have received postnatal corticosteroid therapy for BPD than those with the CC genotype (CG/GG vs CC: 20.9% vs 11.1%, P= 0.05). PVL occurred in six infants (3.0%). There was no significant difference in the prevalence of PVL among IL‐6‐634 polymorphisms (CG/GG, 3.0%; CC, 3.0%, P= 0.65). Conclusions: IL‐6‐634 polymorphism is associated with duration of oxygen therapy in VLBW infants. This suggests that the IL‐6‐634 polymorphism G allele is an aggravating factor of BPD. IL‐6‐634 polymorphism is not associated with PVL.     

Medullary nephrocalcinosis in Schimke immuno‐osseous dysplasia

Schimke immuno‐osseous dysplasia (SIOD) is a rare hereditary disease characterized by skeletal dysplasia, immune deficiency and progressive renal disease. Kidney involvement mainly determines the prognosis. The most common renal pathology is focal segmental glomerulosclerosis (FSGS). Medullary nephrocalcinosis refers to the diffuse deposition of calcium salts in renal medulla and has not previously been identified in SIOD. Here we report the first case of a pediatric patient having typical features of SIOD with medullary nephrocalcinosis.     

Intestinal neuronal dysplasia‐like histopathology in infancy

The present patient was delivered at a gestational age of 27 weeks. She had abdominal bloating with symptoms of respiratory distress. We suspected Hirschsprung disease (HD) or small intestinal stricture, but examinations were not definitive. Exploratory laparotomy was performed at 97 days of age. Intraoperative findings showed no evidence of small intestinal stricture or changes in intestinal caliber. A transanal drainage tube was inserted, and decompression therapy and intestinal lavage were started. Rectal mucosal biopsy was performed at 184 days of age, and HE and acetylcholinesterase staining showed intestinal neuronal dysplasia (IND)‐like pathological findings. At 15 months, giant ganglia were no longer present on follow‐up rectal mucosal biopsy, and the pathological diagnosis was normoganglionosis. It should be recognized that while the enteric nervous system is developing, IND‐like pathological findings may be seen as a pathological condition during the maturation process.     

Two siblings with cortical dysplasia: Clinico‐electroencephalographic features

The older of two siblings began to have spasms and partial seizures at 1 month of age. Head magnetic resonance imaging showed an abnormal area in the left temporo‐parieto‐occipital region. Interictal electroencephalogram (EEG) showed a suppression–burst pattern. Adrenocorticotropic hormone stopped the spasms, but the seizures continued. Clonazepam, carbamazepine, zonisamide, and clobazam were ineffective. She underwent focal resection at age 8 months. Postoperatively, the seizures disappeared. Histopathologically, the lesion appeared to be focal cortical dysplasia type IIa. The younger sibling had spasms from birth. Head magnetic resonance imaging showed left hemi‐megalencephaly. Interictal EEG showed a suppression‐burst pattern. Phenobarbital, valproic acid, and zonisamide were ineffective. He underwent hemispherotomy at age 2 months and became seizure free. The histopathological features were consistent with those of hemi‐megalencephaly. The siblings’ EEG and clinical courses had some similarities. These siblings’ conditions may have the same genetic background.     

Interferon‐gamma reduces the proliferation of M. tuberculosis within macrophages from a patient with a novel hypomorphic NEMO mutation

X‐linked ectodermal dysplasia with immunodeficiency (XL‐EDA‐ID) is caused by mutations in the nuclear factor‐kappa B essential modulator (NEMO) gene. Here, we report the clinical and genetic features of a XL‐EDA‐ID patient who developed bacillus Calmette–Guérin infection. Patient lymphocytes failed to degrade IκB‐α, and sequencing of NEMO identified the novel mutation c.1238A>C/p.H413P. Furthermore, patient monocyte‐derived macrophages ingested Mycobacterium tuberculosis normally, but failed to control the intracellular proliferation of bacilli, a defect which was improved in the presence of interferon‐gamma (IFN‐γ). This work expands the genetic spectrum of XL‐EDA‐ID and demonstrates improvement in macrophage function in a NEMO‐deficient patient by IFN‐γ.     

Eltrombopag (thrombopoietin‐receptor agonist) and plasmapheresis as rescue therapy of acute post‐renal transplant immune thrombocytopenia in a child with Schimke immuno‐osseous dysplasia—case report

SIOD is rare disorder related to SMARCAL1 or SMARCAL2 gene mutation, including (among other comorbidities) T‐cell immunodeficiency, nephrotic syndrome, and renal failure. Up to 22% of primary patients may develop various autoimmune disorders. We report the case of 11‐year‐old male with SIOD, who presented ITP at 2 years after renal transplantation with decrease in platelet count (from normal) to 56 000/μL and then (gradually) to 2000/μL. There was no effect of iv. methylprednisolone/dexamethasone. As the presence of antibodies against GPIIb/IIIa, GPIb, and GPIaIIa platelet glycoproteins was confirmed, patient was given 50 g of IVIG and then was put on plasmapheresis; however, both showed poor direct effect. As we were afraid to give rituximab (due to expected overimmunosuppression), we prescribed the oral TPO‐receptor agonist (eltrombopag). Patient responded after 17 days of therapy, to the final dose of 50 mg/d (approx. 2 mg/kg). The antiplatelet antibodies disappeared after four plasmapheresis. Overall, the therapy was continued for 7 weeks and was stopped at platelet count of 433 000/μL. Platelet count remained stable in 8‐month follow‐up. Combination of plasmapheresis and TPO‐receptor agonist was effective in post‐renal transplant acute ITP in patient with SIOD.     

Multiplex PCR in noninvasive prenatal diagnosis for FGFR3‐related disorders

Thanatophoric dysplasia and achondroplasia are allelic disorders caused by a constitutively active mutation in the FGFR3 gene. Because thanatophoric dysplasia is a lethal disorder and achondroplasia is non‐lethal, they need to be distinguished after ultrasound identification of fetal growth retardation with short limbs. Accordingly, we have developed a noninvasive prenatal test using cell‐free fetal DNA in the maternal circulation to distinguish thanatophoric dysplasia and achondroplasia. A multiplex PCR system encompassing five mutation hotspots in the FGFR3 gene allowed us to efficiently identify the responsible mutation in cell‐free DNA in all examined pregnancies with a suspected thanatophoric dysplasia or achondroplasia fetus. This system will be helpful in the differential diagnosis of thanatophoric dysplasia and achondroplasia in early gestation and in couples concerned about the recurrence of thanatophoric dysplasia due to germinal mosaicism.     

Early diagnosis of asymptomatic neurocutaneous melanosis (60 month follow‐up)

Neurocutaneous melanosis (NCM) is a rare, sporadic, congenital neuroectodermal dysplasia. Large congenital melanocytic nevi (CMN) can evolve in a certain percentage of patients to NCM. Meningeal deposits are benign, but can be prone to malignant transformation in some cases. We describe the case of an infant with asymptomatic NCM, and typical magnetic resonance imaging (MRI) findings. The diagnosis was established shortly after delivery, and the patient was followed for 60 months. At that time, the girl did not have any neurologic symptoms; she reached normal developmental milestones and did not show mental retardation and did not develop malignant melanoma; further follow‐up will be needed, although there are no reliable guidelines as to the time range of follow up of asymptomatic NCM in the literature. We report the typical MRI signal abnormalities of the brain, and present a review of the literature regarding this rare and mysterious congenital disorder.     

Non‐invasive renal artery embolization for renal dysplasia accompanied by hypertension

Renovascular hypertension caused by renal dysplasia often is resistant to drug therapy. For a 14‐year‐old girl with such refractory hypertension, a non‐invasive right renal ablation by embolization with anhydrous ethanol using a shepherd ‘s‐crook’ balloon catheter, was done. Blood pressure then rapidly normalized. Apart from mild fever after the procedure, no adverse effects occurred. In patients with mild renal artery stenosis and hypertension resistant to anti‐hypertensive drug therapy, renal artery embolization may be a useful option.     

Implementation of a multidisciplinary guideline‐driven approach to the care of the extremely premature infant improved hospital outcomes

Aim: To test the hypothesis that implementing guidelines for the standardized care of the extremely premature infant (<27 weeks) in the first week of life would improve patient outcomes in an all referral NICU. Methods: Data were collected on all infants <27 weeks gestational age and <7 days of age on admission cared for using these small baby guidelines (SBG), as well as on all age‐matched infants admitted the year prior (comparison). Results: Thirty‐seven patients were cared for utilizing the SBG and 40 patients were in the comparison group. There were no differences between the groups in gestational age, birthweight or age on admission. There was no difference in survival to discharge (73% SBG, 70% comparison). The mean length of stay for survivors was 112 ± 38 days SBG and 145 ± 76 days (p < 0.05) comparison group. Survival without BPD was greater in the SBG group (24%) than in the comparison group (9%; p < 0.05), and survival without severe IVH was greater in the SBG group (65%) than in the comparison group (38%; p < 0.01). Conclusions: These data demonstrate that applying a unified approach to the care of the extremely premature infant in the first week of life resulted in a decrease in the length of hospitalization and improved patient outcomes.     

Ellis–van Creveld syndrome associated with chronic intestinal pseudo‐obstruction

Ellis–van Creveld (EVC) syndrome is a rare autosomal recessive disorder characterized by hypoplastic nails, polydactyly, and achondroplasia. Patients usually exhibit normal cognitive function and no remarkable developmental delay. We herein present an unusual case of EVC syndrome. A Japanese 2‐year‐old boy was born at term, but immediately developed severe respiratory failure due to thorax deformity, postaxial polydactyly and nail hypoplasia. We identified a novel pattern of germinal compound heterozygous nonsense EVC2 mutations of c.1814C > A (p. S605X) and c.2653C > T (p. R885X), leading to the diagnosis of EVC syndrome. Interestingly, he also had severe developmental delay, and suddenly developed excessive abdominal distension at the age of 2. On surgery, extensive necrotic bowel with chronic intestinal pseudo‐obstruction was noted. This is, to our knowledge, a most severe phenotype of EVC syndrome, illustrating that the specific pattern of EVC2 compound heterozygous mutations may cause severe developmental delay and intestinal malfunction.