Investigation of the effect of vitamin K1 prophylaxis on newborn screenings tests in newborns.

Background: Routine screening for hereditary disorders in newborns includes screening for treatable metabolic and endocrine disorders, such as biotidinase deficiency, galactosemia, maple syrup urine disease, hypothyroidism, and cystic fibrosis. Incorrect test results may be encountered due to the use of vitamin K1. To investigate the interference effect of vitamin K1 on neonatal screening tests and to raise awareness of erroneous measurements. Methods: Heel blood samples were taken from 25 newborns born in a neonatal intensive care unit. Dry blood C0, C2, C3, C4, C4DC, C5:1, C5OH, C5DC, C6, C6DC, C8, C8:1, C8DC, C10, C10:1, C10DC, C12, C14, C14:1, C14:2, C16, C16:1, C18, C18:1, C18:2, C18:OH, methylglutaryl, valine, leucine/isoleucine, methionine, phenylalanine, argininosuccinic acid, aspartate, alanine, arginine, citrulline, glycine, ornithine, and glutamate tests were studied using the tandem mass spectrometry (MS) method. The results of the heel blood samples obtained before and after the application of vitamin K1 (Phyto menadione) were compared. Results: In two studies conducted with in vitro and in vivo tests, C0, C2, C3, C4, C4DC, C5, C5OH, C6, C8, C10, C10:1, C14, C16, C16:1, C18, C18:1, methylglutaryl, phenylalanine, argininosuccinic acid, tyrosine, aspartate, arginine, citrulline, glycine, and glutamine were all significantly elevated (p < 0.05). Conclusions: Heel blood samples may yield false results due to vitamin K1 administration. In the case of doubtful results, a new sample should be taken and the measurement should be repeated.

Serum ADAMTS-9 Level in Newborn Babies with Congenital Heart Disease.

OBJECTIVE: A Disintegrin and Metalloproteinase with Thrombospondin-9 (ADAMTS-9), one of the ADAMTS enzymes, is expressed in all fetal tissues, unlike other ADAMTS enzymes, and is thus thought to play a role in fetal development. In this context, the objective of this study is to investigate the relationship between ADAMTS-9 activity and the development of congenital heart diseases (CHD) with a view to using ADAMTS-9 level as a biomarker for CHDs. STUDY DESIGN: Newborns diagnosed with CHD and healthy newborns were included in the study as the CHD and control groups, respectively. Gestational age, maternal age, and mode of delivery information pertaining to the mothers and Apgar score and birthweight information pertaining to the newborns were recorded. Blood samples were taken from all newborns to determine their ADAMTS-9 levels in the first 24 hours of life. RESULTS: Fifty-eight newborns with CHD and 46 healthy newborns were included in the study. Median ADAMTS-9 levels were 46.57 (interquartile range [IQR]: 33.31 [min: 26.92, max: 124.25]) and 23.36 (IQR: 5.48 [min: 11.7, max: 37.71]) ng/mL in the CHD and control groups, respectively. ADAMTS-9 levels in the CHD group were statistically significantly higher than in the control group (p = 0.000). ADAMTS-9 levels of the CHD and control groups were analyzed by the receiver operating characteristics curve. The area under the curve value for ADAMTS-9 levels of >27.86 ng/mL as the cut-off value for predicting the development of CHD in newborns was 0.836 (95% confidence interval [CI]: 0.753-0.900, p = 0.0001). ADAMTS-9 levels of >27.86 ng/mL were determined to predict the development of CHD in newborns with a sensitivity of 77.78% (95% CI: 65.5-87.38) and a specificity of 84.78% (95% CI: 71.1-93.60). CONCLUSION: In conclusion, it was found that the serum ADAMTS-9 levels were significantly higher in newborns with CHD than in healthy newborns. In parallel, ADAMTS-9 levels above a certain cut-off value were associated with CHD. KEY POINTS: · ADAMTS-9 is expressed in fetal tissues.. · Its level increases in congenital heart diseases.. · It can be used as a biochemical marker in diagnosis..

Evaluation of the efficacy of systemic inflammatory indices in determining mortality in very low birth weight infants.

OBJECTIVE: In our study, we aimed to investigate whether systemic inflammatory indices could be an indicator of mortality in very low birth weight (<1,500 g) preterm infants. METHODS: Very low birth weight preterm infants were included in our study, and patient data were recorded retrospectively. Neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, systemic immune-inflammation index, pan-immune-inflammation value, and systemic inflammation response index were calculated and recorded. The survivors and infants who died were compared for systemic inflammatory indices. RESULTS: A total of 1,243 very low birth weight infants were included in the study. Of the patients, 1,034 survived and 209 died. Neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, platelet-to-lymphocyte ratio, pan-immune-inflammation value, systemic immune-inflammation index, and systemic inflammation response index were found to be statistically significantly lower in the mortality group than those in the survivor group (p=0.039, p=0.001, p<0.001, p<0.001, p<0.001, and p=0.002, respectively). According to the receiver operating curve analysis, systemic immune-inflammation index with the highest area under the curve (0.844) was found to be the most effective systemic inflammatory indices in predicting mortality with a cutoff level of ≤28.87 (p=0.0001). Multiple regression analysis showed that a lower level of systemic immune-inflammation index (≤28.87) was independently associated with mortality (OR: 1.677, 95%CI 1.061-2.685, p=0.001). CONCLUSION: We have shown that low systemic immune-inflammation index value in very low birth weight preterm infants may be a novel systemic inflammatory index that can be used to predict mortality.

Role of Systemic Inflammatory Indices in the Prediction of Moderate to Severe Bronchopulmonary Dysplasia in Preterm Infants

Introduction: The role of systemic inflammatory indices in the diagnosis of bronchopulmonary dysplasia (BPD) is unknown. The aim of the study was to determine the possible clinical utility of systemic inflammatory indices in the prediction of moderate to severe BPD. Methods: Premature infants<32 weeks of gestational age were included in the study. Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), pan-immune-inflammation value (PIV), and systemic inflammation response index (SIRI) were calculated at birth and at the time of diagnosis of BPD (at 36th weeks of postmenstrual age). The patients were divided into two groups as no or mild BPD and moderate or severe BPD. Results: A total of 1146 infants were included in the study, 957 in Group 1 and 189 in Group 2. The SIRI value was significantly higher in moderate or severe BPD both at birth and at the 36th week of postmenstrual age (p<0.001 and p<0.001, respectively). The AUC value of SIRI was 0.809 and the cut-off value was>0.98 in the predictivity of BPD at birth. The AUC value of SIRI was 0.842 and the cut-off value was>1.33 for the diagnosis of BPD at 36th week of postmenstrual age. After multiple logistic regression analysis, SIRI was shown to be a significant parameter for the diagnosis of BPD (OR 2.847, 95% CI 1.557–4.875). Conclusions: SIRI may be a useful biomarker for predicting moderate to severe BPD and a marker of clinical importance in the follow-up of infants with BPD. (AU)

Hemoglobin/Red Cell Distribution width Ratio (HRR): A Novel and Promising Red Cell Parameter in Ductal Closure. / Proporção de Largura de Distribuição de Hemoglobina/Glóbulos Vermelhos (HRR): Um Novo e Promissor Parâmetro de Glóbulos Vermelhos no Fechamento Ductal.

BACKGROUND: It is still unclear how effective hematological parameters are in the closure of patent ductus arteriosus (PDA). OBJECTIVES: The primary aim of our study is to investigate the effect of hemoglobin (HB)-to-red cell distribution width (RDW) ratio (HRR) on the closure of PDA. METHODS: Premature babies with very low birth weight (VLBW: <1500 g) and <32 gestational weeks were included in the study, and all data were recorded retrospectively. Demographic characteristics, clinical results, red cell parameters, and HRR and their ratios were compared between hemodynamically significant PDA (hsPDA) and non-hsPDA groups. All results were statically analyzed, and P<0.05 was considered statistically significant. RESULTS: A total of 677 premature babies, 269 in the hsPDA group and 408 in the non-hsPDA group, were included in the study. Hemoglobin (HB), hematocrit (HCT), mean cell volume (MCV), red blood cell (RBC), red cell distribution width (RDW), mean platelet volume (MPV), MCV/RBC ratio, HB/RBC ratio, RDW/RBC ratio, and RDW/MPV ratio were found to be similar between hsPDA and non-hsPDA groups, (p>0.05). HRR was found to be significantly lower in the hsPDA group [median (Quartile 1 (Q1) - Q3) (Q1 - Q3): 0.93 (0.8-1.0)] compared to non-hsPDA [median ( Q1 - Q3): 1.07 (1.0-1.2)] (p<0.001). The AUC for the diagnostic value of HRR in hsPDA was 0.816, and the cutoff value was ≤0.98 (p<0.001, 95% [CI]: 0.785-0.845, sensitivity: 90%, specificity: 92%). CONCLUSIONS: HRR value was found to be both an effective and powerful parameter in diagnosing hsPDA.

FUNDAMENTO: Ainda não está clara a eficácia dos parâmetros hematológicos no fechamento da persistência do canal arterial (PCA). OBJETIVOS: O objetivo principal do nosso estudo é investigar o efeito da proporção (HRR) de largura de distribuição de hemoglobina (HB) para glóbulos vermelhos (RDW) no fechamento do PCA. MÉTODOS: Bebês prematuros com muito baixo peso ao nascer (MBPN: <1.500 g) e <32 semanas gestacionais foram incluídos no estudo, e todos os dados foram registrados retrospectivamente. Características demográficas, resultados clínicos, parâmetros de hemácias e HRR e suas proporções foram comparados entre grupos de PCA hemodinamicamente significativa (hsPDA) e não-hsPDA. Todos os resultados foram analisados estatisticamente, e p<0,05 foi considerado estatisticamente significativo. RESULTADOS: Um total de 677 bebês prematuros, 269 no grupo hsPDA e 408 no grupo não-hsPDA, foram incluídos no estudo. Hemoglobina (HB), hematócrito (HCT), volume celular médio (VCM), glóbulos vermelhos (RBC), largura de distribuição dos glóbulos vermelhos (RDW), volume plaquetário médio (VPM), relação VCM/RBC, relação HB/RBC, RDW A razão /RBC e a razão RDW/VPM foram semelhantes entre os grupos hsPDA e não hsPDA, (p>0,05). HRR foi significativamente menor no grupo hsPDA [mediana (Quartil 1 (Q1) - Q3) (Q1 - Q3): 0,93 (0,8-1,0)] em comparação com não-hsPDA [mediana (Q1 - Q3): 1,07 ( 1,0-1,2)] (p<0,001). A AUC para o valor diagnóstico de HRR em hsPDA foi de 0,816 e o valor de corte foi ≤0,98 (p<0,001, 95% [IC]: 0,785-0,845, sensibilidade: 90%, especificidade: 92%). CONCLUSÕES: O valor de HRR foi considerado um parâmetro eficaz e poderoso no diagnóstico de hsPDA.

Evaluation of the Effectiveness of Systemic Inflammatory Indices in the Diagnosis of Respiratory Distress Syndrome in Preterm with Gestational Age of ≤32 Weeks.

OBJECTIVE: It is not yet known whether systemic inflammatory indices affect the development of respiratory distress syndrome (RDS) in premature infants. We aimed to evaluate the relationship between systemic inflammatory indices obtained on the first day of life and the development of RDS in premature infants. STUDY DESIGN: Premature infants with gestational age of ≤32 weeks were included in the study. Six systemic inflammatory indices involving neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), pan-immune-inflammation value (PIV), and systemic inflammation response index (SIRI) were measured in the first 1 hour after birth and compared in premature infants with and without RDS. RESULTS: A total of 931 premature infants, 579 infants in the RDS group and 352 infants in the non-RDS group, were included in the study. MLR, PLR, and SIRI values were similar between the groups (p > 0.05 for all parameters). NLR, PIV, and SII values in the RDS group were significantly higher than those in the non-RDS group (p = 0.005, p = 0.011, and p < 0.001, respectively). In the predictivity of RDS, the AUC value of SII was 0.842 and the cut-off value was ≥78.200. Multiple logistic analysis showed that a higher level of SII (≥78.2) was independently associated with RDS (odds ratio: 3.03, 95% confidence interval: 1.761-5.301). CONCLUSION: Our results demonstrated that a higher SII level (≥78.2) may be a predictor for the development of RDS in premature infants with gestational age of ≤32 weeks. KEY POINTS: · It is not yet known whether systemic inflammatory indices affect the development of RDS.. · Our results demonstrated high SII levels may be a predictor for the development of RDS.. · SII may provide an advantage as a low-cost, easy-to-detect, useful and powerful parameter in RDS..

Role of Systemic Inflammatory Indices in the Prediction of Moderate to Severe Bronchopulmonary Dysplasia in Preterm Infants.

INTRODUCTION: The role of systemic inflammatory indices in the diagnosis of bronchopulmonary dysplasia (BPD) is unknown. The aim of the study was to determine the possible clinical utility of systemic inflammatory indices in the prediction of moderate to severe BPD. METHODS: Premature infants<32 weeks of gestational age were included in the study. Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), pan-immune-inflammation value (PIV), and systemic inflammation response index (SIRI) were calculated at birth and at the time of diagnosis of BPD (at 36th weeks of postmenstrual age). The patients were divided into two groups as no or mild BPD and moderate or severe BPD. RESULTS: A total of 1146 infants were included in the study, 957 in Group 1 and 189 in Group 2. The SIRI value was significantly higher in moderate or severe BPD both at birth and at the 36th week of postmenstrual age (p<0.001 and p<0.001, respectively). The AUC value of SIRI was 0.809 and the cut-off value was>0.98 in the predictivity of BPD at birth. The AUC value of SIRI was 0.842 and the cut-off value was>1.33 for the diagnosis of BPD at 36th week of postmenstrual age. After multiple logistic regression analysis, SIRI was shown to be a significant parameter for the diagnosis of BPD (OR 2.847, 95% CI 1.557-4.875). CONCLUSIONS: SIRI may be a useful biomarker for predicting moderate to severe BPD and a marker of clinical importance in the follow-up of infants with BPD.

Phototherapy-induced hypocalcemia and hypoparathyroidism in icteric term newborns.

OBJECTIVES: Phototherapy is demonstrated to cause hypocalcemia by decreasing melatonin levels and increasing cortisol levels. However, the relationship between parathyroid hormone (PTH) level and calcium has not been previously evaluated in patients receiving phototherapy. Our study aimed to evaluate the effect of phototherapy on ionized calcium (iCa), total calcium (tCa), corrected calcium (cCa), magnesium (Mg), phosphorus (P), 25-hydroxyvitamin D (25(OH)D), and PTH levels. METHODS: Infants who were born at term and received inpatient phototherapy for indirect hyperbilirubinemia were included in our study. The patients' gestational age, birth weight, and phototherapy durations were recorded. Total bilirubin, albumin, iCa, tCa, cCa, Mg, 25(OH)D, and PTH levels before and after phototherapy were compared. Laboratory results were also compared between patients who received phototherapy for ≤24 h, 25-47 h, and ≥48 h. RESULTS: A total of 166 term infants were included in the study. The mean duration of phototherapy was 31.9 ± 9.2 h. Albumin levels before and after phototherapy were similar (p=0.246). However, there were significant decreases in iCa, tCa, cCa, Mg, 25(OH)D, and PTH levels after phototherapy (p<0.001), while P level was significantly increased after phototherapy (p<0.001). In addition, P levels increased with >24 h of phototherapy, while iCa, tCa, cCa, Mg, 25(OH)D, and PTH levels decreased significantly with ≥48 h of phototherapy (p=0.002, p=0.008, p=0.001, p=0.012, and p<0.001, respectively). CONCLUSIONS: This study demonstrates that PTH suppression is one of the causes of phototherapy-induced hypocalcemia.

Proporção de Largura de Distribuição de Hemoglobina/Glóbulos Vermelhos (HRR): Um Novo e Promissor Parâmetro de Glóbulos Vermelhos no Fechamento Ductal / Hemoglobin/Red Cell Distribution width Ratio (HRR): A Novel and Promising Red Cell Parameter in Ductal Closure

Resumo Fundamento Ainda não está clara a eficácia dos parâmetros hematológicos no fechamento da persistência do canal arterial (PCA). Objetivos O objetivo principal do nosso estudo é investigar o efeito da proporção (HRR) de largura de distribuição de hemoglobina (HB) para glóbulos vermelhos (RDW) no fechamento do PCA. Métodos Bebês prematuros com muito baixo peso ao nascer (MBPN: <1.500 g) e <32 semanas gestacionais foram incluídos no estudo, e todos os dados foram registrados retrospectivamente. Características demográficas, resultados clínicos, parâmetros de hemácias e HRR e suas proporções foram comparados entre grupos de PCA hemodinamicamente significativa (hsPDA) e não-hsPDA. Todos os resultados foram analisados estatisticamente, e p<0,05 foi considerado estatisticamente significativo. Resultados Um total de 677 bebês prematuros, 269 no grupo hsPDA e 408 no grupo não-hsPDA, foram incluídos no estudo. Hemoglobina (HB), hematócrito (HCT), volume celular médio (VCM), glóbulos vermelhos (RBC), largura de distribuição dos glóbulos vermelhos (RDW), volume plaquetário médio (VPM), relação VCM/RBC, relação HB/RBC, RDW A razão /RBC e a razão RDW/VPM foram semelhantes entre os grupos hsPDA e não hsPDA, (p>0,05). HRR foi significativamente menor no grupo hsPDA [mediana (Quartil 1 (Q1) - Q3) (Q1 - Q3): 0,93 (0,8-1,0)] em comparação com não-hsPDA [mediana (Q1 - Q3): 1,07 ( 1,0-1,2)] (p<0,001). A AUC para o valor diagnóstico de HRR em hsPDA foi de 0,816 e o valor de corte foi ≤0,98 (p<0,001, 95% [IC]: 0,785-0,845, sensibilidade: 90%, especificidade: 92%). Conclusões O valor de HRR foi considerado um parâmetro eficaz e poderoso no diagnóstico de hsPDA.

Abstract Background It is still unclear how effective hematological parameters are in the closure of patent ductus arteriosus (PDA). Objectives The primary aim of our study is to investigate the effect of hemoglobin (HB)-to-red cell distribution width (RDW) ratio (HRR) on the closure of PDA. Methods Premature babies with very low birth weight (VLBW: <1500 g) and <32 gestational weeks were included in the study, and all data were recorded retrospectively. Demographic characteristics, clinical results, red cell parameters, and HRR and their ratios were compared between hemodynamically significant PDA (hsPDA) and non-hsPDA groups. All results were statically analyzed, and P<0.05 was considered statistically significant. Results A total of 677 premature babies, 269 in the hsPDA group and 408 in the non-hsPDA group, were included in the study. Hemoglobin (HB), hematocrit (HCT), mean cell volume (MCV), red blood cell (RBC), red cell distribution width (RDW), mean platelet volume (MPV), MCV/RBC ratio, HB/RBC ratio, RDW/RBC ratio, and RDW/MPV ratio were found to be similar between hsPDA and non-hsPDA groups, (p>0.05). HRR was found to be significantly lower in the hsPDA group [median (Quartile 1 (Q1) - Q3) (Q1 - Q3): 0.93 (0.8-1.0)] compared to non-hsPDA [median ( Q1 - Q3): 1.07 (1.0-1.2)] (p<0.001). The AUC for the diagnostic value of HRR in hsPDA was 0.816, and the cutoff value was ≤0.98 (p<0.001, 95% [CI]: 0.785-0.845, sensitivity: 90%, specificity: 92%). Conclusions HRR value was found to be both an effective and powerful parameter in diagnosing hsPDA.

Evaluation of the efficacy of systemic inflammatory indices in determining mortality in very low birth weight infants

SUMMARY OBJECTIVE: In our study, we aimed to investigate whether systemic inflammatory indices could be an indicator of mortality in very low birth weight (<1,500 g) preterm infants. METHODS: Very low birth weight preterm infants were included in our study, and patient data were recorded retrospectively. Neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, systemic immune-inflammation index, pan-immune-inflammation value, and systemic inflammation response index were calculated and recorded. The survivors and infants who died were compared for systemic inflammatory indices. RESULTS: A total of 1,243 very low birth weight infants were included in the study. Of the patients, 1,034 survived and 209 died. Neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, platelet-to-lymphocyte ratio, pan-immune-inflammation value, systemic immune-inflammation index, and systemic inflammation response index were found to be statistically significantly lower in the mortality group than those in the survivor group (p=0.039, p=0.001, p<0.001, p<0.001, p<0.001, and p=0.002, respectively). According to the receiver operating curve analysis, systemic immune-inflammation index with the highest area under the curve (0.844) was found to be the most effective systemic inflammatory indices in predicting mortality with a cutoff level of ≤28.87 (p=0.0001). Multiple regression analysis showed that a lower level of systemic immune-inflammation index (≤28.87) was independently associated with mortality (OR: 1.677, 95%CI 1.061-2.685, p=0.001). CONCLUSION: We have shown that low systemic immune-inflammation index value in very low birth weight preterm infants may be a novel systemic inflammatory index that can be used to predict mortality.

Qual Deve Ser o Tratamento de Primeira Linha para o Fechamento de Persistência de Canal Arterial Hemodinamicamente Significativo em Bebês Prematuros? / What Should be the First-line Treatment for the Closure of Hemodynamically Significant Patent Ductus Arteriosus in Premature Infants?

Resumo Fundamento É importante saber qual medicamento usar como tratamento de primeira linha para fechar o duto. Objetivos O objetivo deste estudo é comparar a eficácia e os efeitos colaterais das formas intravenosas (IV) de ibuprofeno e paracetamol e contribuir para a literatura investigando o primeiro medicamento selecionado no tratamento clínico da persistência do canal arterial (PCA). Métodos Nosso estudo foi realizado entre janeiro de 2017 e dezembro de 2019. Foram incluídos no estudo bebês prematuros com peso ao nascer (PN) ≤1500 g e idade gestacional (IG) ≤32 semanas. No período do estudo, todos os bebês com persistência do canal arterial hemodinamicamente significativa (hsPCA) receberam ibuprofeno intravenoso (IV) como resgate como tratamento clínico primário ou tratamento com paracetamol IV se houvesse contraindicações para o ibuprofeno. Os pacientes foram divididos em dois grupos: pacientes que receberam ibuprofeno IV e pacientes que receberam paracetamol IV. Resultados Desses pacientes, 101 receberam paracetamol IV e 169 receberam ibuprofeno IV. A taxa de sucesso do fechamento da PCA com o primeiro curso do tratamento foi de 74,3% no grupo de paracetamol IV e 72,8% no grupo de ibuprofeno IV (p=0,212). Conclusões Nossos resultados mostram que o paracetamol IV é tão eficaz quanto o ibuprofeno IV no tratamento de primeira linha de hsPCA, podendo se tornar o tratamento preferencial para o controle de hsPCA.

Abstract Background It is important which medicine to use as a first-line treatment to close the duct. Objectives The aim of this study is to compare the effectiveness and side effects of intravenous (IV) forms of ibuprofen and paracetamol and to contribute to the literature investigating the first drug selected in the medical treatment of patent ductus arteriosus (PDA). Methods Our study was conducted between January 2017 and December 2019. Premature infants with birth weight (BW) ≤1500 g and gestational age (GA) ≤32 weeks were included in the study. In the study period, all infants with hemodynamically significant patent ductus arteriosus (hsPDA) were given rescue intravenous (IV) ibuprofen as a primary medical treatment or IV paracetamol treatment if there were contraindications for ibuprofen. The patients were divided into two groups: patients receiving IV ibuprofen and patients receiving IV paracetamol. Results Of these patients, 101 were given IV paracetamol and 169 were given IV ibuprofen. The success rate of PDA closure with first-course treatment was 74.3% in the IV paracetamol group and 72.8% in the IV ibuprofen group (p=0.212). Conclusions Our results show that IV paracetamol is as effective as IV ibuprofen in the first-line treatment of hsPDA, and can become the preferred treatment for the management of hsPDA.

What Should be the First-line Treatment for the Closure of Hemodynamically Significant Patent Ductus Arteriosus in Premature Infants? / Qual Deve Ser o Tratamento de Primeira Linha para o Fechamento de Persistência de Canal Arterial Hemodinamicamente Significativo em Bebês Prematuros?

BACKGROUND: It is important which medicine to use as a first-line treatment to close the duct. OBJECTIVES: The aim of this study is to compare the effectiveness and side effects of intravenous (IV) forms of ibuprofen and paracetamol and to contribute to the literature investigating the first drug selected in the medical treatment of patent ductus arteriosus (PDA). METHODS: Our study was conducted between January 2017 and December 2019. Premature infants with birth weight (BW) ≤1500 g and gestational age (GA) ≤32 weeks were included in the study. In the study period, all infants with hemodynamically significant patent ductus arteriosus (hsPDA) were given rescue intravenous (IV) ibuprofen as a primary medical treatment or IV paracetamol treatment if there were contraindications for ibuprofen. The patients were divided into two groups: patients receiving IV ibuprofen and patients receiving IV paracetamol. RESULTS: Of these patients, 101 were given IV paracetamol and 169 were given IV ibuprofen. The success rate of PDA closure with first-course treatment was 74.3% in the IV paracetamol group and 72.8% in the IV ibuprofen group (p=0.212). CONCLUSIONS: Our results show that IV paracetamol is as effective as IV ibuprofen in the first-line treatment of hsPDA, and can become the preferred treatment for the management of hsPDA.

FUNDAMENTO: É importante saber qual medicamento usar como tratamento de primeira linha para fechar o duto. OBJETIVOS: O objetivo deste estudo é comparar a eficácia e os efeitos colaterais das formas intravenosas (IV) de ibuprofeno e paracetamol e contribuir para a literatura investigando o primeiro medicamento selecionado no tratamento clínico da persistência do canal arterial (PCA). MÉTODOS: Nosso estudo foi realizado entre janeiro de 2017 e dezembro de 2019. Foram incluídos no estudo bebês prematuros com peso ao nascer (PN) ≤1500 g e idade gestacional (IG) ≤32 semanas. No período do estudo, todos os bebês com persistência do canal arterial hemodinamicamente significativa (hsPCA) receberam ibuprofeno intravenoso (IV) como resgate como tratamento clínico primário ou tratamento com paracetamol IV se houvesse contraindicações para o ibuprofeno. Os pacientes foram divididos em dois grupos: pacientes que receberam ibuprofeno IV e pacientes que receberam paracetamol IV. RESULTADOS: Desses pacientes, 101 receberam paracetamol IV e 169 receberam ibuprofeno IV. A taxa de sucesso do fechamento da PCA com o primeiro curso do tratamento foi de 74,3% no grupo de paracetamol IV e 72,8% no grupo de ibuprofeno IV (p=0,212). CONCLUSÕES: Nossos resultados mostram que o paracetamol IV é tão eficaz quanto o ibuprofeno IV no tratamento de primeira linha de hsPCA, podendo se tornar o tratamento preferencial para o controle de hsPCA.

Two Useful Umbilical Biomarkers for Therapeutic Hypothermia Decision in Patients with Hypoxic Ischemic Encephalopathy with Perinatal Asphyxia: Netrin-1 and Neuron Specific Enolase.

Hypoxic-ischemic encephalopathy (HIE) has a high risk of mortality in addition to serious neurological damage. In this study, we investigated the values of umbilical cord netrin-1 (NT-1) and neuron specific enolase (NSE) levels in the early diagnosis of HIE stage II/III induced by neonatal asphyxia.In the study group, infants with gestational age ≥ 36 weeks who were diagnosed with HIE II/III were included. NT-1 and NSE levels were measured from the umbilical cord immediately after birth. Results were compared between HIE II/III and the healthy control group. Cutoff values for serum NT-1 and NSE were determined with receiver-operating characteristics curves and the area under the curve (AUC) was used to determine the diagnostic value of NT-1 and NSE levels in infants diagnosed with HIE II/III.NT-1 (358.3 ± 108.3 pg/mL) and NSE (52.97 ± 17.8 ng/mL) levels in the cord blood in the HIE group were significantly higher (p = .030, p = .001, respectively) than cord blood values in the control group (NT-1 (275.1 ± 84.6 pg/mL) and NSE (28.7 ± 16.3 ng/mL)). NT-1 cutoff value for HIE was 292.3 pg/mL and 34.7 ng/mL for NSE (AUC: 990, sensitivity: 94%, specificity 100% and AUC: 1.0, sensitivity: 100% vs. specificity 100%, respectively).NT-1 and NSE represent candidate biomarkers with high reliability in the prediction in newborns with moderate-to-severe HIE.

Glucocorticoids in a Neonatal Hyperoxic Lung Injury Model: Pulmonary and Neurotoxic effects.

BACKGROUND: We aimed to compare the effect of dexamethasone (Dex), hydrocortisone (Hc), and methylprednisolone (Mpz) at equivalent doses on somatic growth, lung healing, and neurotoxicity in a hyperoxic rat model. We hypothesized that Mpz and Hc would be superior to Dex with less neurotoxicity by exerting similar therapeutic efficacy on the injured lung. METHODS: Neonatal rats were randomized to control, bronchopulmonary dysplasia (BPD), Dex, Hc, and Mpz groups. All drugs were administered daily following day 15 over 7 days. Histopathological and immunohistochemical analyses of the lung and brain were performed on day 22. RESULTS: All types had much the same impact on lung repair. Oxidative markers in the lung were similar in the steroid groups. While nuclear factor erythroid 2-related factor and heat-shock protein 70 dropped following steroid treatment, no difference was noted in other biochemical markers in the brain between the study groups. Apoptotic activity and neuron loss in the parietal cortex and hippocampus were noted utmost in Dex, but alike in other BPD groups. CONCLUSIONS: Mpz does not appear to be superior to Dex or Hc in terms of pulmonary outcomes and oxidative damage in the brain, but safer than Dex regarding apoptotic neuron loss. IMPACT: This is the first study that compared the pulmonary efficacy and neurotoxic effects of Dex, Hc, and Mpz simultaneously in an established BPD model. This study adds to the literature on the importance of possible antioxidant and protective effects of glucocorticoid therapy in an oxidative stress-exposed brain. Mpz ended up with no more additional neuron loss or apoptosis risk by having interchangeable effects with others for the treatment of established BPD. Mpz and Hc seem safe as a rescue therapy in terms of adverse outcomes for established BPD in which lung and brain tissue is already impaired.

Relationship between Gentamicin Administration and Ductal Patency in Very Low Birth Weight Infants.

BACKGROUND: Patent Ductus Arteriosus (PDA) is associated with adverse clinical outcomes in very low birth weight (<1500g) infants. OBJECTIVE: In our study, it was aimed to investigate the effect of gentamicin treatment, which is frequently used for early-onset sepsis on ductal patency. METHODS: We performed a single-center retrospective review of charts of preterm infants <32 weeks gestation with birth weight <1500 grams born between June 1, 2015 and December 31, 2019 at the neonatal intensive care unit. All infants underwent an echocardiogram (ECHO) at 72 hours. To determine the effect of gentamicin treatment on hemodynamically significant PDA (hsPDA), we compared the frequency and duration of gentamicin administration between infants with hsPDA and without hsPDA. RESULTS: During the study period, 792 patients were evaluated. Gentamicin was given to more infants with hsPDA than to those without hsPDA (89.2% vs. 64.6%, p<0.001), and the duration of therapy was longer in those infants with hsPDA (7 days vs. 9 days, p<0.001). The area under the curve for duration of gentamicin was 0.772 (%95 CI: 0.742-0.804, P=0.0001), sensitivity: 59 (%95 CI: 53-65), specificity: 82 (%95 CI: 78-88), with a cut-off day for duration of gentamicin >7 days. CONCLUSION: In our study, it was found that ductal contraction decreased and hsPDA rate increased as the rate and duration of gentamicin increased.

Inhibition of Interleukin-6 signaling: A novel therapeutic approach to necrotizing enterocolitis.

OBJECTIVES: This study investigated the effects of tocilizumab on the prevention and treatment of experimental necrotizing enterocolitis (NEC) in newborn rats. METHODS: Forty-two newborn Sprague-Dawley rats were randomly separated into three groups: NEC + placebo, NEC + tocilizumab, and the control group. NEC + placebo and NEC + tocilizumab groups were given 1 mg/kg lipopolysaccharide intraperitoneally once only on the first day, were fed with a special rodent formula every 3 h, inhaled 100% CO2 for 10 min, were exposed to cold stress at + 4 °C for 5 min, and 97% O2 for 5 min twice a day for 3 days. NEC + tocilizumab group was treated with 8 mg/kg/day tocilizumab (Actemra®) intraperitoneally, while NEC + placebo group was given intraperitoneal 0.9% saline at a dose of 2 mL/kg/day from the first day to the end of the study. All newborn rats were sacrificed on day 4. Specimens were taken for histopathologic, immunohistochemical and biochemical evaluation from the ileum and proximal colon. RESULTS: NEC + tocilizumab group had higher weight gain and survival rate compared to NEC + placebo group and clinical sickness score was reduced in NEC + tocilizumab group (p < 0.05). Lower tissue damage and apoptosis were found in the NEC + tocilizumab group compared to the NEC + placebo group (p < 0.01). Tissue Interleukin-6, Interleukin-1ß, TNF-α, myeloperoxidase and caspase-3 levels were significantly decreased in the NEC + tocilizumab group (p < 0.01). CONCLUSIONS: Tocilizumab could be a potential option in the prevention and treatment of NEC.

The therapeutic effect of Apocynin against hyperoxy and Inflammation-Induced lung injury.

Lung damage due to hyperoxia and inflammation are important causes of bronchopulmonary dysplasia (BPD). We aimed to investigate the beneficial effects of Apocynin (Apo) on rat pups exposed to hyperoxia and inflammation. Forty-eight rat pups were randomly divided into 3 groups as hyperoxia (95% O2) + lipopolysaccharide (LPS), hyperoxia + LPS + Apo treated and control (21% O2). Rat pups in the Apo group received Apo at a daily dose of 40 mg/kg. Histopathological (Hematoxylin-Eosin, Masson trichrome), immunochemical (surfactant B and C protein staining) evaluations and biochemical studies incluiding, total antioxidant status (TAS), total oxidant status (TOS), OSI (oxidant stress index), AOPP (advanced protein degradation product), Lipid hydroperoxide (LPO), 8-OHdG, NADPH oxidase activity (NOX), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), myeloperoxidase (MPO), tumor necrosis factor-alpha (TNF- α), interleukin-1 beta (IL-1ß), IL-18, IL-6, caspase-1 and 3, nuclear factor erythroid 2-related factor 2 (NFR2), Nod-like receptor pyrin domain-containing 3 (NLRP3) activities were studied. After Apo treatment, AOPP, LPO, 8-OHdG, NOX, TOS, OSI levels decreased; SOD, CAT, GSH and TAS levels increased (P < 0.05). Apo reduced inflammatory cell infiltration and proinflammatory cytokines with reduction in NLRP3 inflammasome in addition to increased Nrf2 levels. Moreover, caspase-1 and 3 levels decreased with Apo (P < 0.05). Apo was found to provide preventive and therapeutic effects by reducing oxidant stress, blocking inflammation and increasing antioxidant status. Beyond anti-oxidative effects, Apo also have anti-inflammatory effects by suppressing NLRP3 inflammasome activation and inducing Nrf2 as well. Therefore, Apo might be a potential option in the treatment of BPD.

Case Report of Severe COVID-19 Pneumonia in a Term Newborn.

Coronavirus disease (COVID-19) has been shown to affect all age groups. The data in the literature usually admit a milder form of disease in infants and newborns than adults. COVID-19 is rarely seen in newborns and an urgent diagnosis should be made in any suspicious situation. A 6-day-old female newborn was admitted to our hospital with fever and dyspnea without cough. A rapid reverse-transcription polymerase chain reaction COVID-19 showed a positive result. Chest computed tomography revealed bilateral and widespread pulmonary involvement. After support therapy, the newborn was successfully discharged. We should carefully consider the new type of coronavirus as an agent for pneumonia in newborns with fever and dyspnea together with non-symptomatic family history. Our case was one of the interesting reported cases of severe pneumonia presenting in the perinatal period.

An Unknown Risk Factor for Sepsis in Very Low Birth Weight Preterms: ABO Blood Groups (BGaPS Study).

OBJECTIVE: There is insufficient study of the association of blood groups with neonatal diseases. The aim of this study was to evaluate the blood groups associated with sepsis and blood groups in preterm infants. STUDY DESIGN: This retrospective study was conducted between January 1, 2010 and November 31, 2018 in the neonatal intensive care unit (NICU). This study was done in single-center tertiary NICU. Infants born at gestational age (GA) <32 weeks with birth weight (BW) <1,500 g were included in the study. RESULTS: A total of 2,548 infants were included. The culture-proven sepsis ratio (30.2%) was the lowest in the O blood group and the highest in the AB blood group (37.5%) (p = 0.045). Meningitis ratio (6.5%) was significantly higher, and hospital stay (64.1 ± 33.9 days) was significantly longer in B blood group (respectively, p = 0.005, p < 0.001). In the AB blood group, GA (27.68 ± 1.12 weeks) was the lowest and early onset sepsis (EOS) (40.1%) and mortality (28.9%) ratio were found to be statistically higher (p < 0.001 for all groups). The AB group was significantly related to higher frequency of EOS (odds ratio [OR] = 2.93, 95% confidence interval [CI] = 1.68-5.12, p = 0.000), in addition to mortality (OR = 1.1, 95% CI = 0.55-2.19, p = 0.001). The O group was found to be associated with lower risk of late onset sepsis (LOS) (OR = 1.67, 95% CI = 1.06-3.058, p = 0.003) according to the model with corrected risk factor including GA, BW, and time of hospitalization. CONCLUSION: Our study was the first study showing a relationship between certain blood groups and EOS/LOS in premature infants as well as meningitis.