Sodium Glycerophosphate Use in Parenteral Nutrition Improves Mineral Metabolism in Extremely Low Birth Weight Infants.

OBJECTIVE: To evaluate the clinical effect of sodium glycerophosphate (NaGP) in parenteral nutrition solutions on mineral metabolism in extremely low birth weight (ELBW) infants. STUDY DESIGN: NaGP was introduced for use in place of potassium phosphate (K3PO4) in January 2018; this retrospective cohort study included 95 ELBW infants treated with K3PO4 between January 2015 and December 2017 and 77 infants treated with NaGP between August 2018 and January 2021. Mineral intake over the first 14 days; changes in serum calcium, phosphorus, sodium, and alkaline phosphatase (ALP) levels over the first 1-3 months; and the rates of electrolyte imbalance and clinical morbidity were compared. High-risk infants who had nil per os (NPO) status for >14 days and prolonged parenteral nutrition exposure were further analyzed as a subgroup. RESULTS: The use of NaGP instead of K3PO4 significantly increased Ca and P intake, but intakes remained below the recommended range (Ca, 64-140 mg/kg/day; P, 50-108 mg/kg/day). Compared with levels in the K3PO4 group, the NaGP group had significantly higher serum Ca and P levels after day 14 and lower ALP levels after day 56. In the subgroup analysis, the NaGP group had significantly lower incidences of hypophosphatemia, hyponatremia, bronchopulmonary dysplasia, and ALP >500 IU/L. CONCLUSIONS: Although the administration of NaGP instead of K3PO4 in parenteral nutrition regimens still did not provide adequate Ca and P intake for ELBW infants, higher intake significantly improved serum Ca and P levels, especially in ELBW infants with prolonged parenteral nutrition exposure.

Microrna-486-5P Regulates Human Pulmonary Artery Smooth Muscle Cell Migration via Endothelin-1.

Pulmonary arterial hypertension (PAH) is a fatal or life-threatening disorder characterized by elevated pulmonary arterial pressure and pulmonary vascular resistance. Abnormal vascular remodeling, including the proliferation and phenotypic modulation of pulmonary artery smooth muscle cells (PASMCs), represents the most critical pathological change during PAH development. Previous studies showed that miR-486 could reduce apoptosis in different cells; however, the role of miR-486 in PAH development or HPASMC proliferation and migration remains unclear. After 6 h of hypoxia treatment, miR-486-5p was significantly upregulated in HPASMCs. We found that miR-486-5p could upregulate the expression and secretion of ET-1. Furthermore, transfection with a miR-486-5p mimic could induce HPASMC proliferation and migration. We also found that miRNA-486-5p could downregulate the expression of SMAD2 and the phosphorylation of SMAD3. According to previous studies, the loss of SMAD3 may play an important role in miRNA-486-5p-induced HPASMC proliferation. Although the role of miRNA-486-5p in PAH in in vivo models still requires further investigation and confirmation, our findings show the potential roles and effects of miR-486-5p during PAH development.

Intravitreal Bevacizumab Is Associated With Prolonged Ventilatory Support in Preterm Infants With Bronchopulmonary Dysplasia.

BACKGROUND: Intravitreal bevacizumab (IVB), an anti-vascular endothelial growth factor (VEGF) antibody, is a widely adopted treatment for retinopathy of prematurity (ROP). Although animal studies have demonstrated that IVB inhibits alveologenesis in neonatal rat lung, the clinical influence of IVB on respiratory outcomes has not been studied. RESEARCH QUESTION: Does IVB affect the respiratory outcome in preterm infants with bronchopulmonary dysplasia? STUDY DESIGN AND METHODS: We retrospectively assessed very low birth weight (VLBW) preterm infants admitted to our neonatal ICU between January 2016 and June 2021. Furthermore, we evaluated the short-term respiratory outcomes after IVB therapy in VLBW preterm infants requiring ventilatory support at 36 weeks' postmenstrual age (PMA). RESULTS: One hundred seventy-four VLBW preterm infants with bronchopulmonary dysplasia were recruited. Eighty-eight infants showed ROP onset before being ventilator free, and 78 infants received a diagnosis of the most severe ROP before being ventilator free. Among them, 32 received a diagnosis with type 1 ROP and received IVB treatment. After adjusting for gestational age, birth body weight, and baseline respiratory status, we discovered that IVB is associated significantly with prolonged ventilatory support and a lower likelihood of becoming ventilator free (hazard ratio, 0.53; P = .03). INTERPRETATION: IVB may have a short-term respiratory adverse effect in patients requiring ventilatory support at 36 weeks' PMA. Therefore, long-term follow-up for respiratory outcomes may be considered in VLBW infants who receive IVB treatment.

Validation of the Postnatal Growth and Retinopathy of Prematurity Screening Criteria in a Taiwanese Cohort.

PURPOSE: To validate the performance of Postnatal Growth and Retinopathy of Prematurity (G-ROP) screening criteria in a Taiwanese cohort. DESIGN: Screening evaluation with retrospective data. METHOD: Premature infants who underwent retinopathy of prematurity (ROP) screening between January 2015 and April 2019 at a tertiary hospital were examined. Infants with known final ROP results and complete longitudinal weight records were included. G-ROP screening criteria, both original and simplified (G-ROP 180 g), were applied as the prediction model for type 1 ROP; sensitivity and specificity were analyzed. The reduction in the number of infants requiring ROP screening and the number of funduscopic examinations were calculated. RESULT: A total of 303 infants with documented ROP outcomes and complete weight gain records were examined. Of these, 103 infants developed ROP, of whom 29 developed type 1 ROP, whereas the other 200 did not develop ROP. For the detection of type 1 ROP, the sensitivity and specificity of the original G-ROP screening criteria were 96.6% and 42.3%, and 100% and 31%, for the simplified G-ROP 180 g model, respectively. The reduction in the number of infants requiring screening and funduscopic examinations was 32.6% and 33.5% for the original G-ROP criteria, and 28.1% and 23.2% for the G-ROP 180 g model, respectively. CONCLUSION: Both the original G-ROP and G-ROP 180 g criteria attained high sensitivities in detecting type 1 ROP in the current Taiwanese cohort, with the G-ROP 180-g model outperforming the original one. Validation and modification may be required before applying G-ROP screening criteria to different populations.

Comparison of risk scores for predicting intravenous immunoglobulin resistance in Taiwanese patients with Kawasaki disease.

BACKGROUND/PURPOSE: Kawasaki disease (KD) is the most common type of acquired heart disease in children, and intravenous immunoglobulin (IVIG) therapy is the preferred treatment. Several risk scoring systems have been developed to predict IVIG resistance, which is important in KD management, including the Kobayashi, Egami, and Formosa scores. We evaluated the performance of these scoring systems with a KD patient cohort from Taiwan. METHODS: We retrospectively analyzed the medical records of all KD patients admitted to our institution from 2012 to 2017. We compared the characteristics of IVIG-resistant and non-resistant patients and evaluated the predictive ability of the scoring systems for IVIG resistance. RESULTS: We included 84 patients, with 73 receiving IVIG therapy. Eight patients were unresponsive to the first IVIG course. Compared to those with good response to therapy or spontaneous improvement, IVIG-resistant patients had a higher C-reactive protein level (16.1 mg/dL vs. 8.6 mg/dL, p < 0.001), higher percentage of segmented leukocytes (75.7% vs. 61.7%, p = 0.008), and lower albumin level (2.98 mg/dL vs. 3.78 mg/dL, p = 0.001). In determining IVIG resistance, the sensitivity and specificity varied among scoring systems (Kobayashi, 37.5% and 86.8%; Egami, 37.5% and 84.2%; and Formosa, 87.5% and 73.7%, respectively). The positive and negative predictive values of the Formosa score were 25.9% and 98.2%, respectively. CONCLUSION: The Formosa score had the highest sensitivity in determining IVIG resistance. Although the positive predictive value was low, the negative predictive value could reach 98.2%. The Formosa score was superior to other scoring systems in predicting IVIG resistance in Taiwanese KD patients.

Linear growth of corpus callosum and cerebellar vermis in very-low-birth-weight preterm infants.

BACKGROUND/PURPOSE: Impaired growth of the corpus callosum (CC) and cerebellar vermis (CV) is associated with poorer neurodevelopmental outcomes in preterm infants. However, references on the postnatal growth rate of the CC and CV by sonography are limited. The aim of this study is to assess the normal linear growth of CC and CV using a serial cranial ultrasound. METHODS: We prospectively enrolled preterm infants with very low birth weight from September 2008 to December 2009 after excluding those with congenital anomalies or diseases affecting the brain parenchyma. Serial sonographic measurements of the CC and CV were performed according to the standard protocol. Scheduled comprehensive neurodevelopmental evaluations were performed till the corrected age of 2 years. We excluded those with significant brain damages or poor neurodevelopmental outcomes in the final analysis. The growth rate was estimated using the loess smoothing curve and linear regression analysis. RESULTS: Among the 86 enrolled neonates, 14 with significant brain damage and 8 with poor neurodevelopmental outcomes were excluded from the final analysis. The growth rate of the CC length was 1.72 (95% confidence interval [CI]: 1.24-2.20) and 0.57 (95% CI: 0.33-0.80) mm per week before and after the postmenstrual age of 30.5 weeks, respectively. The growth rate of the CV length was 0.78 (95% CI: 0.68-0.89) mm per week. CONCLUSION: We proposed reference values of the normal linear growth rate of the CC and CV lengths in very-low-birth-weight preterm infants using the serial cranial ultrasound.

Preeclampsia and Retinopathy of Prematurity in Very-Low-Birth-Weight Infants: A Population-Based Study.

Preeclampsia and retinopathy of prematurity (ROP) are associated with impaired angiogenesis. Previous studies on the relationship between preeclampsia and ROP have produced conflicting results. The goal of this study was to evaluate the association between maternal preeclampsia and ROP using a large population-based cohort of very-low-birth-weight (VLBW) infants from 21 neonatal departments registered in the database of the Premature Baby Foundation of Taiwan. Multivariable logistic regression analysis was used to estimate the adjusted odds ratios (OR) and 95% confidence intervals (CI) for preeclampsia with reference to ROP and severe ROP. A total of 5,718 VLBW infants (844 cases with maternal preeclampsia) were included for analysis. The overall incidences of mild and severe ROP were 36.0% and 12.2%, respectively. Univariable analysis showed lower GA and lower birth weight, vaginal delivery, non-SGA, RDS, PDA, sepsis, transfusion, and absence of maternal preeclampsia to be associated with mild and severe ROP development. However, OR (95% CI) adjusted for the variables that were significant according to univariable analysis showed the risks of developing any-stage ROP and severe ROP for maternal preeclampsia to be 1.00 (0.84-1.20) and 0.89 (0.63-1.25), respectively. The results remained unchanged in stratified analyses according to SGA status. Our data showed that maternal preeclampsia was not associated with the subsequent development of any stage or severe ROP in VLBW infants.

Model to predict hyperbilirubinemia in healthy term and near-term newborns with exclusive breast feeding.

BACKGROUND: The aim of this study was to identify high-risk newborns who will subsequently develop significant hyperbilirubinemia Days 4 to 10 of life by using the clinical data from the first three days of life. METHODS: We retrospectively collected exclusively breastfeeding healthy term and near-term newborns born in our nursery between May 1, 2002, to June 30, 2005. Clinical data, including serum bilirubin were collected and the significant predictors were identified. Bilirubin level ≥15mg/dL during Days 4 to 10 of life was defined as significant hyperbilirubinemia. A prediction model to predict subsequent hyperbilirubinemia was established. This model was externally validated in another group of newborns who were enrolled by the same criteria to test its discrimination capability. RESULTS: Totally, 1979 neonates were collected and 1208 cases were excluded by our exclusion criteria. Finally, 771 newborns were enrolled and 182 (23.6%) cases developed significant hyperbilirubinemia during Days 4 to 10 of life. In the logistic regression analysis, gestational age, maximal body weight loss percentage, and peak bilirubin level during the first 72 hours of life were significantly associated with subsequent hyperbilirubinemia. A prediction model was derived with the area under receiver operating characteristic (AUROC) curve of 0.788. Model validation in the separate study (N = 209) showed similar discrimination capability (AUROC = 0.8340). CONCLUSION: Gestational age, maximal body weight loss percentage, and peak serum bilirubin level during the first 3 days of life have highest predictive value of subsequent significant hyperbilirubinemia. We provide a good model to predict the risk of subsequent significant hyperbilirubinemia.

Perinatal tuberculosis in a 73-day-old infant.

A 73-day-old female infant presented with cough and fever. A chest roentgenogram showed a pneumonic patch, but empirical antibiotic treatment failed. The pathology of an excisional biopsy specimen confirmed pulmonary tuberculosis. We emphasize that tuberculosis should be considered for neonates or infants with unresponsive pneumonia because delayed diagnosis is associated with a fatal outcome.

Implication of cord blood myeloperoxidase but not of soluble p-selectin levels in preterm deliveries.

Although maternal amniotic and vaginocervical cytokines are known to play a role in triggering preterm delivery, the effects of activating fetal phagocytes and platelets are not clear. In an attempt to clarify this issue, we measured levels of myeloperoxidase (MPO), a phagocyte activation marker, and soluble p-selectin (sCD62p), a platelet activation marker, in umbilical cord blood samples from 2200 consecutive cord blood collections, 106 of which were from preterm infants. MPO and sCD62p levels were correlated to gestational age and preterm delivery. It was found that MPO levels were significantly higher in preterm infants and were not significantly correlated to gestational age. In contrast, sCD62p levels were lower in preterm infants and were negatively correlated to gestational age. In summary, we showed that fetal phagocyte activation as demonstrated by higher cord blood MPO levels is associated with preterm delivery, but platelet activation as shown by lower sCD62p levels is not. This suggests that fetal phagocyte activation may be implicated in preterm delivery, and subsequently in prematurity-related inflammatory insults.