Mean Platelet Volume and Mean Platelet Volume/Platelet Count Ratio Are Predictors of Late-Onset Sepsis in Preterm Infants: A Case-Control Study.

Objective: Our aim was to assess mean platelet volume (MPV) and mean platelet volume to platelet count ratio (MPR) in the setting of late-onset sepsis (LOS) and their association with the type of bacteria causing LOS. Study design: The MPV and MPR levels were obtained at the onset of LOS and then assessed in intra/inter group analyses in preterm infants. Results: Overall, 136 preterm infants were enrolled. The MPV and MPR levels were higher during a LOS event (P < 0.001). A MPV cutoff of >9.2 was related with a sensitivity of 63% and a specificity of 73% for predicting LOS (P < 0.001). A MPR cutoff of >0.15 was related with a sensitivity of 88% and a specificity of 63% for predicting gram negative LOS (P < 0.001). Conclusion: Elevated MPV values and MPR ratios may be helpful in assessing LOS.

The Role of Low 25-Hydroxyvitamin D Levels in Preterm Infants with Late-Onset Sepsis.

IntroductionWe investigated the association between low 25-hydroxyvitamin D (25-OHD) levels and late-onset sepsis (LOS) in preterm infants (<37 weeks). Methods: Infants with culture-proven LOS were the study group, infants without LOS were the controls. 25-OHD levels were compared between these groups. Low vitamin D was defined as 25-OHD ≤15 ng/ml. Maternal 25-OHD levels were compared to their infant's level. Results: 108 infants were included. The study group was significantly younger (p = 0.02) with significantly lower 25-OHD levels (p < 0.001). Multivariable logistic regression analyses revealed that infants with low 25-OHD levels were 7.159 (95%CI: 1.402-36.553, p = 0.018) times more likely to develop LOS. A positive correlation was detected between maternal and neonatal 25-OHD levels for both study and control groups (r = 0.425, p = 0.009; r = 0.739, p < 0.001, respectively). Conclusions: Low 25-OHD levels are associated with an increased risk of developing LOS development in preterm infants.

Mannose-binding lectin gene polymorphism and its effect on short term outcomes in preterm infants / Polimorfismo do gene da lectina ligante de manose e seu efeito em desfechos de curto prazo em bebês prematuros

Abstract Objective: Mannose-binding lectin, which belongs to the collectin family, is an acute-phase reactant that activates the complement system. This study aimed to investigate the effect of MBL2 gene polymorphism on short-term outcomes in preterm infants. Method: Infants of <37 gestational weeks who were admitted to the neonatal intensive care unit during a two-year period were enrolled in this prospective study. The neonates were categorized into two groups according to their MBL2 genotypes. Normal MBL2 genotype was defined as MBL2 wild-type (AA genotype), whereas mutant MBL2 genotype was defined as MBL2 variant-type (AO/OO genotype). The relationship between MBL2 genotype and short-term morbidity and mortality was evaluated. Results: During the two-year study period, 116 preterm infants were enrolled in this study. In MBL2 variant-type, mannose-binding lectin levels were significantly lower and incidences of mannose-binding lectin deficiency (MBL level < 700 ng/mL) were higher (p < 0.001). In this group, the prevalence of respiratory distress syndrome and mortality was significantly higher (p < 0.001, p = 0.03 respectively). In the MBL2 wild-type group, the prevalence of necrotizing enterocolitis (NEC) was higher (p = 0.01). Logistic regression analyses revealed that MBL2 variant-type had a significant effect on respiratory distress syndrome development (odds ratio, 5.1; 95% confidence interval, 2.2-11.9; p < 0.001). Conclusions: MBL2 variant-type and mannose-binding lectin deficiency are important risk factors for respiratory distress syndrome development in preterm infants. Additionally, there is an association between MBL2 wild-type and NEC. Further studies on this subject are needed.

Resumo Objetivo: A lectina ligante de manose (MBL, do inglês mannose-binding lectin), que pertence à família das colectinas, é um reagente de fase aguda que ativa o sistema complemento. Este estudo teve como objetivo investigar o efeito do polimorfismo do gene MBL2 em desfechos de curto prazo em prematuros. Método: Este estudo prospectivo incluiu crianças com menos de 37 semanas de gestação admitidas na unidade de terapia intensiva neonatal durante dois anos. Os neonatos foram categorizados em dois grupos de acordo com os genótipos do MBL2. O genótipo normal do gene MBL2 foi definido como MBL2 do tipo selvagem (genótipo AA), enquanto o genótipo mutante do gene MBL2 foi definido como o gene variante (genótipo AO/OO). Foi avaliada a relação entre o genótipo MBL2 e a morbidade e mortalidade em curto prazo. Resultados: Durante o período de dois anos, 116 bebês prematuros foram incluídos neste estudo. Os níveis de lectina ligante de manose foram significativamente menores nos variantes do MBL2 e as incidências de deficiência de lectina ligante de manose (nível de MBL < 700 ng/mL) foram maiores (p < 0,001). Nesse grupo, a prevalência de síndrome do desconforto respiratório (SDR) e a mortalidade foram significativamente maiores (p < 0,001, p = 0,03, respectivamente). No grupo MBL2 do tipo selvagem, a prevalência de enterocolite necrosante foi maior (p = 0,01). Análises de regressão logística revelaram que os genes variantes do MBL2 apresentaram um efeito significativo no desenvolvimento da síndrome do desconforto respiratório (odds ratio, 5,1; intervalo de confiança de 95%, 2,2-11,9; p < 0,001). Conclusões: As variantes do MBL2 e a deficiência de lectina ligante de manose são importantes fatores de risco para o desenvolvimento da síndrome do desconforto respiratório em neonatos prematuros. Além disso, existe uma associação entre MBL2 do tipo selvagem e a enterocolite necrosante. Mais estudos são necessários sobre esse assunto.

The effect of Yakson and Gentle Human Touch methods on pain and physiological parameters in preterm infants during heel lancing.

BACKGROUND: Various non-pharmacologic methods are used to alleviate pain in preterm infants who spend their first days in neonatal intensive care units (NICU) because they are exposed to numerous painful interventions. OBJECTIVE: To determine the effects of Yakson and Gentle Human Touch (GHT) methods on pain and physiologic parameters during heel lancing procedures in preterm infants. DESIGN AND METHODS: This was a randomised controlled trial. The study was conducted in a NICU between June 2018 and June 2019. A total of 90 preterm infants were divided into three groups: 30 infants in the Yakson group, 30 infants in the GHT group, and 30 infants in the control group. All preterm infants were randomly divided into groups. Pain responses were evaluated using the Neonatal Infant Pain Scale. RESULTS: It was found that pain scores and heart rates were significantly lower during and after heel lancing in preterm infants in the Yakson and GHT groups than in the control group, the difference was statistically significant (p < .001). PRACTICAL IMPLICATIONS: Yakson and GHT applied to preterm infants during heel lancing has positive effects on pain and physiologic parameters.

Red cell distribution width as a predictor of late-onset Gram-negative sepsis.

BACKGROUND: Late-onset sepsis (LOS) remains an important cause of morbidity and mortality in preterm infants. In this study, our aim was to investigate the red-cell distribution width (RDW) levels during a LOS episode, and its association with the type of growing microorganism and mortality. METHODS: Preterm infants with culture-proven sepsis during their neonatal intensive care unit stay were enrolled. Red-cell distribution width levels were obtained in the first 4 h of postnatal life and at the onset of the LOS episode, and compared for these time frames. The study cohort was divided into two groups according to the type of the growing microorganism. The RDW levels were then assessed in intra- and inter-group analyses. RESULTS: Eighty-six infants were included in the final analysis. RDW levels were increased in the study cohort after a LOS attack (P < 0.001). Infants with Gram-negative sepsis showed a significant increase in their RDW levels, but they remained unchanged in infants with Gram-positive sepsis (P < 0.001 and P = 0.4, respectively). An RDW cut-off of >19.50% was related with a sensitivity of 87% and a specificity of 81% for predicting late-onset Gram-negative sepsis (P < 0.001). Logistic regression analysis showed a positive association of RDW with mortality when adjusted for covariants (adjusted odds ratio: 1.40; 95% confidence interval: 1.02-1.80; P = 0.03). CONCLUSIONS: Our findings show that RDW levels increased during a LOS episode in preterm infants, which was especially evident in Gram-negative infections. We believe that these findings may be of importance in the early diagnosis and prognosis of LOS in preterm infants.

Mannose-binding lectin gene polymorphism and its effect on short term outcomes in preterm infants.

OBJECTIVE: Mannose-binding lectin, which belongs to the collectin family, is an acute-phase reactant that activates the complement system. This study aimed to investigate the effect of MBL2 gene polymorphism on short-term outcomes in preterm infants. METHOD: Infants of <37 gestational weeks who were admitted to the neonatal intensive care unit during a two-year period were enrolled in this prospective study. The neonates were categorized into two groups according to their MBL2 genotypes. Normal MBL2 genotype was defined as MBL2 wild-type (AA genotype), whereas mutant MBL2 genotype was defined as MBL2 variant-type (AO/OO genotype). The relationship between MBL2 genotype and short-term morbidity and mortality was evaluated. RESULTS: During the two-year study period, 116 preterm infants were enrolled in this study. In MBL2 variant-type, mannose-binding lectin levels were significantly lower and incidences of mannose-binding lectin deficiency (MBL level<700ng/mL) were higher (p<0.001). In this group, the prevalence of respiratory distress syndrome and mortality was significantly higher (p<0.001, p=0.03 respectively). In the MBL2 wild-type group, the prevalence of necrotizing enterocolitis (NEC) was higher (p=0.01). Logistic regression analyses revealed that MBL2 variant-type had a significant effect on respiratory distress syndrome development (odds ratio, 5.1; 95% confidence interval, 2.2-11.9; p<0.001). CONCLUSIONS: MBL2 variant-type and mannose-binding lectin deficiency are important risk factors for respiratory distress syndrome development in preterm infants. Additionally, there is an association between MBL2 wild-type and NEC. Further studies on this subject are needed.

Glutathione synthetase deficiency: a novel mutation with femur agenesis.

Introduction: Glutathione synthetase (GSS) deficiency is an autosomal recessive disorder (frequency < 1/1,000,000) with different varyingly severe clinical manifestations that include metabolic acidosis, hemolytic anemia, hyperbilirubinemia, neurological disorders and sepsis. Case report: This infant was small for gestational age, had hemolytic anemia, metabolic acidosis, bilateral subependymal pseudocysts and increased echogenicity of the basal ganglia. GSS deficiency was confirmed by genetic analysis. The patient also had unilateral right femur agenesis. Conclusion: By using next generation sequencing analysis, we identified a novel homozygous variant c.800G > A, p.Arg267Gln in the GSS gene of this patient. Femur agenesis had not previously been associated with GSS.

Elevated blood carboxyhemoglobin levels as an early predictor of phototherapy requirement in moderate and late preterm infants.

Objective: Preterm infants are prone to increased bilirubin burden and display adverse outcomes if left unmonitored; therefore, predicting an increased bilirubin production is of paramount importance.Methods: We aimed to evaluate carboxyhemoglobin (COHb) levels in moderate (GA: 320/7-336/7) and late preterm (GA: 340/7-366/7) infants to assess whether this molecule could be used as an early predictor of phototherapy requirement.Results: A total of 221 infants were enrolled in the study. On admission, carboxyhemoglobin levels of infants who received phototherapy were significantly higher than that of infants who did not require this treatment, and this difference persisted in the consecutive hours (median (min-max): 1.2% (0.3-1.7) versus 0.8% (0.4-1.1); p < .001). The initial and consecutive COHb levels showed positive correlation (r = 0.77, p < .001). In the post-hoc analysis, direct antiglobulin test positivity significantly affected phototherapy requirement (p < .001). Receiver operating characteristics analysis showed that a COHb level of ≥0.95% was found to have a sensitivity of 90% and a specificity of 88%. Multinomial logistic regression analysis demonstrated that high COHb levels on admission significantly increased the likelihood of phototherapy requirement when adjusted for covariants (adjusted odds ratio: 2.2; 95% confidence interval: 1.4-3.5; p < .001).Conclusion: Carboxyhemoglobin measurement can be simply used to predict preterm infants who will require phototherapy.

Serial Carboxyhemoglobin Levels and Its Relationship with Late Onset Sepsis in Preterm Infants: An Observational Cohort Study.

Objective: This study aimed at assessing the serial carboxyhemoglobin (COHb) levels in preterm infants during the first week of life and their variation with late-onset sepsis (LOS). Study Design: Infants with <37 gestational weeks were categorized into two groups according to the presence of culture proven LOS. Serial COHb levels were obtained during the first week of life, at the onset of the LOS episode, and upon blood culture negativity with response to antibiotics. Result: Overall 207 infants were enrolled. A LOS episode resulted in a significant increase in COHb levels (p < 0.001), which decreased to normal levels when the blood cultures were sterile (p < 0.001). At a cut of level of 1.35% COHb had a sensitivity of 56% and a specificity of 90% to confirm LOS (p < 0.001). Conclusion: In this study, we demonstrated an increase in COHb levels at the onset of LOS and a decrease with response to antibiotherapy.

Mannose-Binding Lectin Levels in Late-Onset Sepsis in Preterm Infants: Results from a Prospective Study in a Tertiary Care Center.

Introduction: This study aimed to determine the association between serum mannose-binding lectin (MBL) levels, gene polymorphisms and late-onset sepsis (LOS) in preterm infants. Methods: Infants with <37 gestational weeks were categorized into two groups according to the presence of LOS during their hospitalization. An MBL level <700 ng/ml was defined as deficiency, <400 ng/ml as severe deficiency. Codon 54 and 57 polymorphisms of MBL2 gene were analyzed. Results: Overall, 153 preterm infants were included. MBL deficiency was found to be more common in the LOS group (p = 0.02). The rate of Gram-negative sepsis was higher in MBL2 variant-type (p = 0.01). In the logistic regression analysis, MBL levels <700 ng/ml were found to have a significant effect on LOS development (odds ratio: 2.692, 95% confidence interval 1.196-5.8, p = 0.02). Conclusions: MBL deficiency is an important risk factor for the development of LOS. Furthermore, there is an association between MBL2 gene polymorphism and Gram-negative sepsis.

The effectiveness of serum amyloid A for prediction of neonatal cholestasis associated with parenteral nutrition in premature infants.

Özkan H, Köksal N, Dogan P, Güney-Varal I, Bagci O, Özgür T. The effectiveness of serum amyloid A for prediction of neonatal cholestasis associated with parenteral nutrition in premature infants. Turk J Pediatr 2019; 61: 26-33. Parenteral nutrition (PN) has been widely used in premature infants untill enteral feeding can be tolerated. Cholestasis is an important complication of PN. The objective of this study was to evaluate the role of serial measurements of serum amyloid A (SAA) during PN and compare its` effectiveness with C-reactive protein (CRP) and procalcitonin (PCT). We also aimed to determine the risk factors for PN associated cholestasis (PNAC). Premature infants ( < 34 weeks` gestational age) who were started on PN during hospitalization were included in this prospective study. SAA, CRP and PCT levels were measured on days 0, 3, 7, 14, and 21 of PN in all infants. Infants who had PN for less than 2 weeks, who developed sepsis and/or necrotizing enterocolitis were excluded. A total of 85 infants were included. The mean birth weight was 1226±329 g, and the mean gestational age was 29.4±1.8 weeks. The birth weight of infants who developed cholestasis were significantly lower. Enteral nutrition was started significantly later in infants with cholestasis. CRP and PCT did not correlate with conjugated bilirubin levels at any time point. SAA levels on days 7 and 14 showed a significant correlation with conjugated bilirubin levels. SAA levels on day 7 was found to have the highest sensitivity for prediction of PNAC. Low birth weight, late commencement of enteral feeding, and prolonged PN were the main risk factors for PNAC development. This is the first study that shows the predictive value of SAA for PNAC development. We suggest that SAA may be used as an accurate and useful biomarker for prediction of PNAC in high risk premature infants receiving PN.

A novel mutation leading to the lethal form of carnitine palmitoyltransferase type-2 deficiency.

Background The clinical phenotypes of carnitine palmitoyltransferase type-2 deficiency (CPT2D) are classified into lethal neonatal, severe infantile and muscle forms. The rarest form is the lethal neonatal form. Case presentation The patient was hypotonic and bradycardic at admission. Blood urea nitrogen and creatinine were high. He had polycystic kidneys, patent foramen ovale and aortic valve insufficiency. Cranial magnetic resonance imaging (MRI) revealed increased signal intensities in the periventricular white matter. Tandem mass spectrometry (MS) analysis was compatible with CPT2D. We found a homozygous in-frame deletion in the CPT2 gene using next-generation sequencing. Conclusions We identified a novel mutation leading to the lethal form of CPT2D with polycystic kidney, cardiac malformation and cranial MRI findings. Our findings expand the spectrum of causative mutations and clinical findings in CPT2D.

New-generation fish oil and olive oil lipid for prevention of oxidative damage in preterm infants: Single center clinical trial at university hospital in Turkey.

BACKGROUND: Parenteral nutrition (PN) has been widely used in preterm infants. The lipid solutions used for PN, however, are associated with oxidative stress and morbidity. The aim of this study was to compare the effectiveness of a new-generation lipid emulsion (SMOFLipid) and olive-oil based lipid emulsion for prevention of PN-associated oxidative damage. METHODS: Preterm infants < 32 weeks of gestational age were included in this prospective randomized study. All infants were randomized to SMOFlipid or olive-oil based lipid emulsion (ClinOleic). Lipid peroxidation products were evaluated in all infants. In addition, total antioxidant capacity (TAC), and both pro- and anti-inflammatory cytokines were studied at days 0, 7 and 14. RESULTS: A total of 89 infants (SMOFlipid, n = 42; ClinOleic, n = 47) were enrolled. TAC was higher in the SMOFlipid group compared with the ClinOleic group at all time points, and the difference on day 7 was statistically significant. Although the anti-inflammatory cytokine interleukin-10 was higher in the SMOFlipid group, this difference was not significant. Bronchopulmonary dysplasia (BPD) was lower in the SMOFlipid group (14.1%) than in the ClinOleic group (31.2%), but this finding was non-significant p > 0.05. The rate of severe BPD was significantly lower in the SMOFlipid group. CONCLUSION: To our best of knowledge, this is the first study to suggest that SMOFlipid might decrease oxidative damage and oxidative-stress-associated morbidity compared with olive oil-based emulsion in preterm infants.

Potential use of multi-strain synbiotics for improving postnatal head circumference.

Background & Objective: Preterm infants need nutritional and medical requirements in accordance with the physiologic maturity at birth and maintaining optimal postnatal corporal and cerebral growth is one of the main targets of medical caregivers. However, only a few strategies exist to improve the outcomes of infants in a pathogen-rich and nutrient-poor neonatal intensive care unit environment. In this pilot study, we hypothesize that synbiotics may enhance brain growth, which is reflected indirectly by an increase in head circumference through several signalling molecules. Methods: A pilot study was conducted in preterm infants with a gestational age of ≤32 weeks and a birth weight of ≤1500 grams at neonatal intensive care unit of Uludag Univeristy Medical Faculty (NICU) for one-year period. Following the randomization of the infants, a prepared commercial synbiotic solution containing multi-combined probiotics and prebiotics was administered enterally to the study group. Results: The odds of a patient having a lower body weight and head circumference below the 10th percentile were significantly lower in the probiotic group (p=0.001, p=0.03, respectively). Moreover, the infants in the synbiotics group had a more optimal head circumference (between the 50th and 90th percentiles, p=0.001). Conclusions: Our results show that if we can maintain optimal gut microbiota, we might achieve better neuro-development via the beneficial effects of synbiotics on cytokines, neurotransmitters, and the cellular immunity of the nervous system. Further investigational models are needed to demonstrate the beneficial effects of synbiotics on the central nervous system.

The effect of early administration of combined multi-strain and multi-species probiotics on gastrointestinal morbidities and mortality in preterm infants: A randomized controlled trial in a tertiary care unit.

Güney-Varal I, Köksal N, Özkan H, Bagci O, Dogan P. The effect of early administration of combined multi-strain and multi-species probiotics on gastrointestinal morbidities and mortality in preterm infants: A randomized controlled trial in a tertiary care unit. Turk J Pediatr 2017; 59: 13-19. Necrotizing enterocolitis (NEC) is a gastrointestinal emergency of the neonatal period. The aim of this study was to demonstrate the use of multistrain and multispecies probiotic on gastrointestinal morbidities and mortality. The study was organized as a randomized controlled, prospective study in premature infants (≤32 week and ≤1500 gram). The ready commercial preparations which contain multi-combined probiotics of Lactobacillus rhamnosus (4.1x108 cfu) + Lactobacillus casei (8.2x108 cfu) + Lactobacillus plantorum (4.1x108 cfu) + Bifidobacterium animalis (4.1x108 cfu) together with 383 mg of fructooligosaccharides and 100 mg of galactooligosaccharides as the prebiotic content, was administered enterally to the probiotic group (n=70); control group constituted of 40 preterms. Primary outcomes of the present study were ≥ Stage 2 NEC and the mortality. Secondary outcomes were culture-proven sepsis and days to reach full enteral feeding. All cases of NEC were seen in group 2 as 3.6% (n=4) of all infants. The mortality was found to be 1.4% (n=1) in Group 1 and 22.5% (n=9) in Group 2. The incidence of NEC and the mortality rate were found to be significantly lower in Group 1 (p=0.016, p=0.001, respectively). In Group 1, the NEC-related mortality rate and sepsis-related mortality rate were significantly lower than that of the control group (p=0.046, p=0.023). In this study, we showed that using probiotic strains in combined multistrain and multispecies forms at higher doses and for prolonged duration had positive effects on gastrointestinal complications, sepsis and mortality in premature infants.