Neonatal Outcomes of Premature Infants Born to Women with the Novel Coronavirus (SARS-CoV-2) Infection: A Case Control Study.

OBJECTIVE: Novel coronavirus disease 2019 (COVID-19) is a disease associated with atypical pneumonia caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). The first cases of COVID-19 were reported in Wuhan at the end of 2019. Transmission usually occurs via infected droplets and close personal contact; the possibility of vertical transmission is still under debate. This retrospective study aimed to analyze clinical characteristics of premature infants born to mothers with symptomatic COVID-19 disease. STUDY DESIGN: This case control study compared the clinical and laboratory data of 20 premature infants born to mothers infected with SARS-CoV-2 with sex and gestational age-matched historical controls. RESULTS: The median gestational age and birth weight in both groups were similar. Respiratory distress developed in 11 (55.5%) infants in study group and 19 (47.5%) infants in control group. Mechanical ventilation and endotracheal surfactant administration rates were similar. Median duration of hospitalization was 8.5 (2-76) days in study group and 12 days in historical controls. Real-time reverse-transcription polymerase chain reaction tests (RT-PCR) of nasopharyngeal swab samples for SARS-CoV-2 were found to be negative twice, in the first 24 hours and later at 24 to 48 hours of life. No neutropenia or thrombocytopenia was detected in the study group. Patent ductus arteriosus, bronchopulmonary dysplasia, and necrotizing enterocolitis rates were similar between groups. No mortality was observed in both groups. CONCLUSION: To the best of our knowledge, this is one of the few studies evaluating the clinical outcomes of premature infants born to SARS-CoV-2 infected mothers. There was no evidence of vertical transmission of SARS-CoV-2 from symptomatic SARS-CoV-2-infected women to the neonate in our cohort. The neonatal outcomes also seem to be favorable with no mortality in preterm infants. KEY POINTS: · SARS-CoV-2 pandemic is a challenge for pregnant women.. · Neonatal outcomes of premature infants born to mothers infected with SARS-CoV-2 not well defined.. · SARS-CoV-2 infection seems to have no adverse effect on mortality and morbidity in premature infants..

Severity of Maternal SARS-CoV-2 Infection in Pregnancy Predicts Neonatal Outcomes.

OBJECTIVE: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak had an enormous global impact. Pregnant women with SARS-CoV-2 appear to have higher morbidity and mortality. This study aimed to evaluate the effect of the severity of maternal SARS-CoV-2 infection on neonatal outcomes. STUDY DESIGN: The clinical and laboratory data of 40 women and neonates evaluated retrospectively. RESULTS: This retrospective study showed that SARS-CoV-2 infection had an adverse impact on neonatal outcomes proportionally with the maternal disease severity including increased prematurity rates, postnatal resuscitation need, prolonged hospital stay and longer ventilatory support requirement in infants born to mothers with moderate or severe disease. CONCLUSION: Maternal disease severity had adverse effects on neonatal outcomes. The severity of maternal disease was found to be associated with increased rates of prematurity, requirement of postnatal resuscitation, prolonged hospital stay, and longer ventilatory support. KEY POINTS: · SARS-CoV-2 pandemic is a problem for pregnant women.. · Vertical transmission has been shown in limited studies.. · Maternal disease severity may have impact on neonatal outcomes..

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.

Vitamin D deficiency and its effect on respiratory distress syndrome in premature infants: results from a prospective study in a tertiary care centre.

BACKGROUND: The positive effects of steroids on lung development are well known, and 1,25-dihydroxy vitamin D3 has been shown to exert positive effects on fetal lung development. OBJECTIVE: We aimed to investigate the relationship between 25-hydroxyvitamin D [25(OH)D] levels and respiratory distress syndrome (RDS) in premature infants. METHODS: Infants aged ≤32 gestational weeks who were admitted to the neonatal intensive care unit (NICU) during 1 year were enrolled in this prospective study. 25(OH)D levels were obtained at the time of admission to NICU. Patients were divided into three groups according to their 25(OH)D levels: severe (group 1), moderate (group 2), and mild (group 3) 25(OH)D deficiencies. RESULTS: The study comprised 72 patients; of them, RDS was observed in 49 and not observed in 23 patients. The mean 25(OH)D levels were significantly lower in RDS patients (p=0.04). Multivariate analysis showed that patients with higher 25(OH)D levels can be preventive for the development of RDS (odds ratio 0.89; 95% confidence interval 0.8-0.99; p=0.04). CONCLUSION: Our study revealed that 25(OH)D deficiency is an independent risk factor for RDS in premature infants. However, further studies are necessary to explore the association between 25(OH)D deficiency and RDS.

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.

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.

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.

Low serum IGF-1 and increased cytokine levels in tracheal aspirate samples are associated with bronchopulmonary dysplasia.

Yilmaz C, Köksal N, Özkan H, Dorum BA, Bagci O. Low serum IGF-1 and increased cytokine levels in tracheal aspirate samples are associated with bronchopulmonary dysplasia. Turk J Pediatr 2017; 59: 122-129. Despite developments in the perinatal and neonatal care, bronchopulmonary dysplasia (BPD) is still the most frequently seen long-term complication in preterm infants. The aim of this prospective study is to investigate the association between the development of BPD and serial measurements of IGF-1 levels and their relationship with levels of IGF-1 and cytokine in tracheal aspirate fluids. A total of 40 premature infants, born at a gestational age of ≤ 32 weeks, were enrolled in the study. On postnatal day-1, 3, 7, 21 and 28 serum IGF-1 levels and IGF-1 levels, IL-6, IL-8, IL-10 and TNF-alpha levels in tracheal aspirate fluid samples of intubated cases were examined. Mean gestational age of 40 patients included in the study was 29.41 ± 2.23 weeks, and their mean birth weight was 1,256.85 ± 311.48 g. BPD was detected in 35% of cases. Mean gestational week and birth weight of the cases that developed BPD were 30 ± 3 weeks and 1,150 ± 295 g, respectively. Serum IGF-1 levels on postnatal day-1, 3, 7, 21 and 28 in cases who developed BPD were significantly lower when compared with those without BPD (p < 0.01). Levels of IL-6, IL-8, IL-10, and TNF-alpha in tracheal aspirate samples were significantly higher in cases with BPD compared to those without BPD (p < 0.05). IGF-1 levels in tracheal aspirate fluid samples did not differ significantly based on the presence of BPD (p > 0.05). Severity of BPD was associated with decreased serum IGF-1 levels and increased cytokine levels in tracheal aspirate samples.

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.

Very Low Birth Weight Infant Necessitating Nissen Fundoplication for Weaning off the Mechanical Ventilator.

Gastro-esophageal reflux (GER) is one of the common problems of neonatal intensive care units. Although this condition does not always need to be treated, it occasionally causes clinically serious consequences. Initial management is medical; however, in some cases surgery might be required. A premature neonate with birth weight of 1370 grams was managed in our ICU. The patient was mechanical ventilator dependent due to GER. The patient needed Nissen fundoplication for successfully weaning off the ventilator.

A child with primary Sjögren syndrome and a review of the literature.

Primary Sjögren syndrome (pSS) is an uncommon disease in childhood. Childhood pSS might have different clinical manifestations than adult pSS. We describe a 13-year-old girl with multiple episodes of bilateral parotid swelling lasting 2 years. Her history included severe arthralgia, local edema, and purpura episodes since 9 years of age. During her 3-week hospitalization, 2 episodes of parotid swelling occurred, which both resolved in 48 hours. Ultrasonography and magnetic resonance images of parotid glands showed parenchymal inhomogeneity related to adipose degeneration and nodular pattern. Investigations showed elevated erythrocyte sedimentation rate, the presence of hypergammaglobulinemia, positive antinuclear antibody, and elevated rheumatoid factor, anti-Sjögren syndrome antigen A, and anti-Sjögren syndrome antigen B. Histopathologic examination of labial minor salivary glands revealed focal periductal lymphocytic infiltrate and sialoduct ectasia. She was diagnosed as having pSS. Recurrent parotid swelling is a more characteristic feature of disease in children, and this finding should alert the clinician to the possible diagnosis of pSS.