Case report: a premature infant with severe intrauterine growth restriction, adrenal insufficiency, and inflammatory diarrhea: a genetically confirmed case of MIRAGE syndrome

IntroductionMIRAGE syndrome is a rare disease characterized by myelodysplasia, infection, growth restriction, adrenal hypoplasia, genital phenotypes, and enteropathy. Herein, we report the case of a girl with MIRAGE syndrome who presented with adrenal insufficiency and chronic diarrhea.Case presentationThe patient was born at 29 + 6 weeks of gestational age with a birth weight of 656 g (<3p). Her height and head circumference were also <3p. At birth, she presented with respiratory distress, meconium staining, and pneumomediastinum, which were managed with high-frequency ventilation and empirical antibiotics. Physical examination showed generalized hyperpigmentation and normal female genitalia. A few days after birth, polyuria and hypotension developed, and laboratory findings revealed hypoglycemia, hyponatremia, and hyperkalemia. Plasma adrenocorticotropic hormone levels were elevated with low serum cortisol levels and high plasma renin activity, which were suggestive of adrenal insufficiency. Hydrocortisone and fludrocortisone were introduced and maintained, and hyperpigmentation attenuated with time. Both kidneys looked dysplastic, and adrenal glands could not be traced on abdominal ultrasound. From the early days of life, thrombocytopenia and anemia were detected, but not to life-threatening level and slowly recovered up to the normal range. Despite aggressive nutritional support, weight gain and growth spurt were severely retarded during the hospital stay. Additionally, after introducing enteral feeding, she experienced severe diarrhea and subsequent perineal skin rashes and ulcerations. Fecal calprotectin level was highly elevated; however, a small bowel biopsy resulted in non-specific submucosal congestion. The patient was diagnosed with MIRAGE syndrome with SAMD9 gene mutation. She was discharged with tube feeding and elemental formula feeding continued, but chronic diarrhea persisted. By the time of the last follow-up at 15 months of corrected age, she was fortunately not subjected to severe invasive infection and myelodysplastic syndrome. However, she was dependent on tube feeding and demonstrated a severe developmental delay equivalent to approximately 5–6 months of age.ConclusionThe early diagnosis of adrenal crisis and hormone replacement therapy can save the life of -patients with MIRAGE syndrome; however, chronic intractable diarrhea and growth and developmental delay continue to impede the patient’s well-being

Validity of the Korean Developmental Screening Test for very-low-birth-weight infants

Purpose The importance of the neurodevelopmental outcomes of very-low-birth-weight (VLBW) infants has been emphasized as their mortality rate has markedly improved. This study aimed to assess the validity of the Korean Developmental Screening Test (K-DST), a developmental screening tool approved by the Korean Society of Pediatrics, for the timely diagnosis of neurodevelopmental delay in VLBW infants. Methods Subjects included VLBW infants enrolled in the Korean Neonatal Network database between January 2012 and December 2014. The collected data were analyzed for sensitivity, specificity, positive predictive value, and negative predictive value (NPV) in the K-DST compared to those in the Bayley Scales of Infant Development-II for VLBW infants. Results A total of 173 patients were enrolled. Their mean gestational age and mean birth weight were 27.5±2.8 weeks and 980.5±272.1 g, respectively. The frequency of failed psychomotor developmental index (PDI) <85 was similar to that in at least one domain of K-DST <1 standard deviation. Failure in more than one K-DST domain compared with a mental developmental index (MDI) <85 showed a sensitivity and NPV of 73.2% and 75.0%, respectively. Failure in more than one K-DST domain compared with PDI <85 showed a sensitivity and NPV of 60.3% and 71.6%, respectively. Each K-DST domain had a stronger correlation with predicting a failing MDI <85 than a failing PDI <85 (P<0.05). Conclusion K-DST could be a useful screening tool for predicting mental developmental delay in VLBW infants and referring them for neurodevelopmental assessments

Effects of Recombinant Human Erythropoietin Administration in Premature Infants with Severe Intraventricular Hemorrhage: A Single-Center Experience

Purpose We investigated the effects of early postnatal administration of erythropoietin (EPO) on neurodevelopmental outcomes and morbidities in preterm infants with severe grades of intraventricular hemorrhage (IVH). Methods We retrospectively reviewed the medical records of preterm infants of gestational age 23+0 weeks to 31+6 weeks, who were diagnosed with severe grades of IVH and received EPO over at least 2 weeks. We compared clinical characteristics, major complications, and neurodevelopmental impairment between the two groups. The primary outcome was severe neurodevelopmental impairment at 18 to 26 months of corrected age. Severe neurodevelopmental impairment was defined as a mental developmental index or psychomotor developmental index of <70 on the Bayley Scales of Infant Development II or diagnosis of cerebral palsy. Results The study included 33 preterm infants (mean gestational age 25.2±1.6 weeks and mean birth weight 775.1±224.5 g). EPO was administered at a dose of 400 or 1,000 IU/kg thrice weekly and was maintained over a mean period of 58.6± 25.9 days beginning from 10.7±6.9 days after birth. We observed no difference in perinatal characteristics between the EPO (n=14) and the control group (n=19). Similarly, severe neurodevelopmental impairment rates did not differ between the EPO (85.7%) and control groups (78.9%). The incidence of neonatal morbidities including bronchopulmonary dysplasia, necrotizing enterocolitis, and retinopathy of prematurity was also similar between the EPO and control groups. Conclusion Early administration of EPO did not reduce the risk of severe neurodevelopmental impairment in preterm infants with severe IVH

Association of Moderate Hypothermia at Admission with Short-Term and Long-Term Outcomes in Extremely Low Birth Weight Infants

Purpose Extremely low birth weight (ELBW) infants exhibit immature thermoregulation and are easily exposed to hypothermia. We investigated the association between hypothermia on admission with short- and long-term outcomes. Methods Medical records of ELBW infants admitted to the neonatal intensive care unit of a tertiary medical center between June 2012 and February 2017 were retrospectively analyzed. Upon admission, the axillary body temperature was measured. Moderate hypothermia was defined as admission temperature below 36 ℃. Results A total of 208 infants with gestational age of 26.4±2.3 weeks and birth weight of 746.7±154.9 g were included. Admission temperature ranged from 33.5 to 36.8 ℃ (median 36.1 ℃). Univariate analyses of maternal and infant characteristics were performed for moderately hypothermic and control (normothermic to mildly hypothermic) infants. Lower gestational age, lower birth weight, and vaginal delivery correlated with moderate hypothermia. Logistic regression analyses adjusted for confounders revealed that the incidence of hemodynamically significant patent ductus arteriosus (hsPDA) was associated with moderate hypothermia in ELBW infants. Moreover, abnormal mental developmental index scores on the Bayley Scales of Infant Development II at a corrected age of 18 to 24 months were associated with moderate hypothermia, but not with the psychomotor developmental index, incidence of blindness, deafness, or cerebral palsy. Conclusion Moderate hypothermia at admission is not only correlated with short-term neonatal morbidities such as hsPDA, but may also be associated with long-term neurodevelopmental impairment in ELBW infants. Future large-scale studies are required to clarify the long-term consequences of hypothermia upon admission

Risk Factors for Periventricular-Intraventricular Hemorrhage in Premature Infants

Periventricular-intraventricular hemorrhage (PV-IVH) is a major cause of neurological disabilities in preterm newborns. This study aimed to determine the perinatal factors associated with PV-IVH. We conducted a retrospective case-control study from preterm infants born at ≤34 weeks of gestation and admitted to Neonatal Intensive Care Units of Seoul National University Children's Hospital and Seoul National University Bundang Hospital between June 2003 and December 2007. Neonates with no cranial sonographic data or infants transferred from other centers after three days of age were excluded. Of 1,044 eligible subjects, 59 infants with PV-IVH grade 2, 3, and 4 were allocated to the case group. The control group consisted of 118 infants without PV-IVH who were matched for gestational age and birth weight to each case of PV-IVH. At the multivariate logistic regression model, metabolic acidosis (odds ratio [OR]: 6.94; 95% confidence interval [CI]: 1.12-43.23) and use of inotropes (OR: 3.70; 95% CI: 1.16-11.84) were associated with an increased risk of PV-IVH. Maternal use of antenatal corticosteroids decreases the risk of PV-IVH (OR: 0.36; 95% CI: 0.14-0.92)

A Part Recognition System for FMS based on single Image Data

In this paper, we developed a prototype part recognition system for FMS (Flexible Manufacturing System) by comparing the features extracted from CAD data and the features obtained from the image through a single camera, Good or distinct features with high recognition efficiency for a specific part are obtained automatically and intelligently according to the rules from CAD data. Since the selection of distinct features are done automatically without any human interference, the developed system seems to be quite robust. Fourther, since it uses only a few distinct features on-line among many features and all the time-consuming calculations are done off-line, it is possible to recognize each part quickly and accurately. In order to evaluate the performance and the effectiveness of the developed system, two example(L and T shaped parts) are tested and the results are reported.clos

Feature Extraction for the Part Recognition System of FMC

This paper presents a methodology for automatic feature extraction used in a vision system of FMC (flexible Manufacturing Cell). To implement a robot vision system, it is important to make a feature database for object recognition, location, and orientation. For industrial applications, it is necessary to extract feature information from CAD database since the detail information about an object is described in CAD data. Generally, CAD description is three dimensional information but single image data from camera is two dimensional information. Because of this dimensiional difference, many problems arise. Our primary concern in this study is to convert three dimensional data into two dimensional data and to extract some features from them and store them into the feature database. Secondary concern is to construct feature selecting system that can be used for part recognition in a given set of objects

Progress on the development of FMC control software for CIM

This paper presents an architecture and control logic of a Flexible Manufacturing Cell (FMC) which is one of the important elements under Computer Integrated Manufacturing (CIM) environment. To implement FMC, it is very important to develop a software which can control and monitor the overall system in an integrated environment. Our primary concern in this research is not to develop individual systems, but to integrate them in the hierarchical control level. Progress on the research of integrating CAD/CAM, Process Planning, Off-line Robot Programming and Simulation module into FMC control system is reported. FMC hardware system used here has an Automated Storage &amp; Retrieval System (AS/RS), a conveyor system, a transfer robot, a CNC milling machine, a bar-code system, and an IBM PC/AT as Cell Control System (CCS). In order to demonstrate the operational result, the name plates, text-carved aluminium plates, are manufactured by this system

Prevention of human milk-acquired cytomegalovirus infection in very-low-birth-weight infants

Abstract Background The aim of the study was to determine the rate of cytomegalovirus virolactia in the human milk (HM) of mothers of VLBW infants, compare the CMV infection rates and the changes in CMV DNA viral load and nutrient profile among different HM preparation methods. Methods A prospective randomized controlled study was performed in infants with gestational age < 32 weeks or birth-weight < 1500 g admitted to neonatal intensive care unit of Asan Medical Center and Haeundae Paik Hospital who were given mother’s own milk. Enrolled infants were randomized into three groups according to the HM preparation methods: freezing-thawing (FT), FT + low-temperature Holder pasteurization (FT + LP), and FT + high-temperature short-term pasteurization (FT + HP). Urine CMV culture and PCR were obtained at birth and at 4, 8, and 12 weeks. HM CMV culture and PCR were obtained at birth and at 3, 6, 9, and 12 weeks. Changes in macronutrients in HM was obtained at 4 ~ 6 weeks. Results Of 564 infants, 217 mothers (38.5%) produced CMV PCR positive milk. After exclusion, a total of 125 infants were randomized into the FT (n = 41), FT + LP (n = 42), and FT + HP (n = 42) groups, whose rate of HM-acquired CMV infection was 4.9% (n = 2), 9.5% (n = 4), and 2.4% (n = 1), respectively. Out of seven CMV infected infants, two infants fed with FT + LP HM developed CMV infection- associated symptoms. Ages at diagnoses were earlier (28.5 days after birth) and at younger post conceptional age (< 32 weeks) in comparison to infants with asymptomatic CMV infection. CMV DNA viral load significantly decreased after pasturizations, especially in FT + HP group. Conclusions HM-acquired symptomatic CMV infection rate is low and its impact on clinical course was not serious in our VLBW infants. However, evidences showing poor neurodevelopmental outcome in later life, we need to generate a guideline to protect VLBW infant form HM transmitted CMV infection. Based on our small sized study, we did not find any superiority in pasteurizing HM with frequently used LP in comparison to frozen or HP HM. More research is needed to determine the method and duration of pasteurization to reduce the HM-acquired CMV infection

Early echocardiographic pulmonary artery measurements as prognostic indicators in left congenital diaphragmatic hernia

Abstract Background To predict whether the left pulmonary artery (LPA) to the main pulmonary artery (MPA) ratio measured by echocardiography in left congenital diaphragmatic hernia (CDH) was related to death or need for extracorporeal membrane oxygenation (ECMO). Methods This retrospective study analyzed neonates with left CDH born between 2018 and 2022 in a single tertiary medical institution. Echocardiography was performed immediately after birth. The diameter of the LPA was measured at the bifurcation, and the diameter of the MPA was measured at the maximal dimension during the systolic phase. The Nakata index, McGoon ratio, and ejection fraction (EF) were analyzed and compared with the LPA: MPA ratio as predictive values. Results Seventy-two neonates with left CDH were included, 19 (26.4%) died or needed ECMO, and 53 (73.6%) survived without ECMO. The lower observed/expected lung-to-head ratio, lower EF, lower LPA: MPA ratio, lower RPA: MPA ratio, lower Nakata index, and lower McGoon ratio were associated with death or need for ECMO. By multivariate analysis, lower LPA: MPA ratio, RPA: MPA ratio, and Nakata index were independent postnatal risk factors for death or need for ECMO. Among the measurements, the LPA: MPA ratio had the highest area under the curve (0.957) with a sensitivity of 84.2% and specificity of 96.3% at a cut-off value of 31.2%. Conclusion In patients with left CDH, the LPA: MPA ratio measured by echocardiography could be used as an independent postnatal predictor of death or need for ECMO