Diagnostic Accuracy of Biomarkers for Early-Onset Neonatal Bacterial Infections: Evaluation of Serum Procalcitonin Reference Curves

To date, no clinical studies have compared the accuracy of serum procalcitonin (PCT) reference curves. We aimed to validate the diagnostic accuracy of previously reported serum PCT reference curves and to determine which biomarkers among a cut-off value over the 95th percentile in the serum PCT reference curve, white blood cell (WBC) count, and C-reactive protein (CRP) and immunoglobulin M (IgM) levels, have the highest diagnostic accuracy for early-onset neonatal bacterial infections. This retrospective cohort study assessed 16 preterm and 23 term infants with suspected bacterial infections within 72 h after birth. Each infant group was divided into two subgroups: confirmed- and non-infection. The diagnostic accuracy was determined using the Youden index. The reference curves by Fukuzumi et al. in preterm and term infants had the highest Youden indexes: 1.000 and 0.324, respectively. Among preterm infants, the Youden index for PCT was 1.000. Among term infants, the Youden index for a combination of PCT, CRP, and WBC and/or IgM was 1.000. In conclusion, a serum PCT level over the 95th percentile on the reference curve for preterm infants and a combination of PCT and CRP levels with WBC count and/or IgM levels for term infants provided sufficient diagnostic accuracy.

Download Full-text

1012. Neutrophil Function Enhanced by Recombinant Interferon-Gamma in Newborns

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1206 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S597-S597

Author(s):

Ricardo Castillo-Galvan ◽

Nicole Soper ◽

Monique Bennett ◽

Isaac Thomsen

Keyword(s):

Preterm Infants ◽

Interferon Gamma ◽

Bacterial Infections ◽

Fungal Infections ◽

Three Dimensional ◽

Neutrophil Function ◽

Term Infant ◽

Term Infants ◽

Recombinant Interferon

Abstract Background Functional differences exist between neonatal and adult neutrophils. The incidence of infection is higher in preterm infants, and the severity of the immune impairment on the neonatal neutrophils is inversely related to gestational age. In order to recognize and combat life-threatening infections, neonates rely predominantly on the innate immune system.Neutrophils are an essential component of innate immunity, and they are the first responders against bacterial and fungal infections. Sepsis continues to be a prominent cause of neonatal mortality, especially among preterm infants. Recombinant interferon-gamma (IFNγ) effects on the immune system have included the upregulation of TLRs expression and stimulation of phagocytosis. They have been shown to reduce severe infections in children with chronic granulomatous disease. Methods After the protocol was IRB approved, we enrolled term infants in their first 48 hours of life (Table 1). We then obtained free flow whole-blood samples through venipuncture from the cephalic vein. Samples were incubated with and without IFNγ for 24 hours. Isolation of unperturbed neutrophils using immunomagnetics was performed for a final concentration of 1x106/mL. We then assessed the neutrophil-bacterial interaction using fluorescent GFP-Staphylococcus aureus, and quantified neutrophil killing function on a novel assay involving fibrin matrix as a more physiologic and three-dimensional (3D) environment than standard in vitro or culture-based assays. We evaluated normalized progressive ratios, 20μL/80μL, 30μL/70μL, 40μL/60μL of Neutrophil/GFP-S aureus respectively.Table 1 Results On the 20 samples, we observed significant differences demonstrating a considerably enhanced phagocytosis on those samples with the addition of IFNγ(p< 0.0001, Table 2 and Figures 1-3). Conclusion The phagocytic ability of neonatal neutrophils was greatly enhanced by the addition of IFNγ in term infant blood. Ongoing work will determine whether this remains true for preterm-infant neutrophils and will further delineate mechanisms of these differences. We recognized an opportunity for interferon-based immunomodulation in certain situations on this population at high risk for invasive bacterial infections. Disclosures Ricardo Castillo-Galvan, MD MPH, Karius Inc. (Consultant) Isaac Thomsen, MD, MSCI, Horizon Therapeutics (Consultant)

Download Full-text

Neonatal lung ultrasonography to evaluate need for surfactant or mechanical ventilation: a systematic review and meta-analysis

Archives of Disease in Childhood - Fetal and Neonatal Edition ◽

10.1136/archdischild-2019-316832 ◽

2019 ◽

Vol 105 (2) ◽

pp. 164-171 ◽

Cited By ~ 8

Author(s):

Abdul Razak ◽

Maher Faden

Keyword(s):

Mechanical Ventilation ◽

Diagnostic Accuracy ◽

Respiratory Distress ◽

Preterm Infants ◽

Late Preterm ◽

Lung Ultrasonography ◽

Term Infants ◽

Surfactant Treatment ◽

Increased Risk

ContextLung ultrasonography (LUS) is increasingly used to identify various neonatal respiratory disorders. There is emerging evidence that it can identify infants with significant lung disease who need surfactant treatment or mechanical ventilation.ObjectiveTo systematically review the accuracy of LUS in determining the need for surfactant treatment or mechanical ventilation in infants with respiratory distress treated with nasal continuous positive airway pressure (NCPAP).MethodsDatabase search include EMBASE, Medline, CINAHL and Cochrane central from inception until 17 October 2018. Included is diagnostic accuracy studies reporting LUS evaluating surfactant therapy/mechanical ventilation. Two authors extracted data independently and assessed quality. Quality Assessment of Diagnostic Accuracy Studies-2 tool was used to determine the methodological quality.ResultsSix studies involving 485 infants included in the review. Three studies used LUS score, two used type 1 lung profile, and one used high-risk LUS to evaluate the outcome. The pooled sensitivity and specificity at LUS score cut-off >5–6 was 88% (95% CI 80% to 93%) and 82% (95% CI 74% to 89%), respectively. Infants with LUS score >5–6 were at significantly increased risk of surfactant treatment compared with infants with LUS score <5–6 (relative risk=7.51; 95% CI 4.16 to 13.58; two studies; participants=189; I2=0%). The diagnostic accuracy of type 1 lung profile was better in younger preterm infants (sensitivity 88.9%, specificity 100%) compared with late preterm and term infants (sensitivity 100%, specificity 28%).ConclusionsLUS, particularly LUS score, can be used accurately to determine the need for surfactant replacement treatment or mechanical ventilation in infants with respiratory distress treated with NCPAP support. The accuracy is better in younger preterm infants compared with late preterm and term infants.PROSPERO registration numberCRD42018115135.

Download Full-text

Neurodevelopmental Outcomes at 18 Months of Corrected Age for Late Preterm Infants Born at 34 and 35 Gestational Weeks

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18020640 ◽

2021 ◽

Vol 18 (2) ◽

pp. 640 ◽

Cited By ~ 1

Author(s):

Ruka Nakasone ◽

Kazumichi Fujioka ◽

Yuki Kyono ◽

Asumi Yoshida ◽

Takumi Kido ◽

...

Keyword(s):

Preterm Infants ◽

Late Preterm ◽

Psychomotor Development ◽

Youden Index ◽

Chromosomal Anomalies ◽

Clinical Factors ◽

Neurodevelopmental Outcomes ◽

Late Preterm Infants ◽

Significant Difference ◽

Severe Hyperbilirubinemia

To date, the difference in neurodevelopmental outcomes between late preterm infants (LPI) born at 34 and 35 gestational weeks (LPI-34 and LPI-35, respectively) has not been elucidated. This retrospective study aimed to evaluate neurodevelopmental outcomes at 18 months of corrected age for LPI-34 and LPI-35, and to elucidate factors predicting neurodevelopmental impairment (NDI). Records of all LPI-34 (n = 93) and LPI-35 (n = 121) admitted to our facility from 2013 to 2017 were reviewed. Patients with congenital or chromosomal anomalies, severe neonatal asphyxia, and without developmental quotient (DQ) data were excluded. Psychomotor development was assessed as a DQ using the Kyoto Scale of Psychological Development at 18 months of corrected age. NDI was defined as DQ < 80 or when severe neurodevelopmental problems made neurodevelopmental assessment impossible. We compared the clinical characteristics and DQ values between LPI-34 (n = 62) and LPI-35 (n = 73). To elucidate the factors predicting NDI at 18 months of corrected age, we compared clinical factors between the NDI (n = 17) and non-NDI (n = 118) groups. No significant difference was observed in DQ values at 18 months of corrected age between the groups in each area and overall. Among clinical factors, male sex, intraventricular hemorrhage (IVH), hyperbilirubinemia, and severe hyperbilirubinemia had a higher prevalence in the NDI group than in the non-NDI group, and IVH and/or severe hyperbilirubinemia showed the highest Youden Index values for predicting NDI. Based on the results of this study, we can conclude that no significant difference in neurodevelopmental outcomes at 18 months of corrected age was observed between LPI-34 and LPI-35. Patients with severe hyperbilirubinemia and/or IVH should be considered to be at high risk for developing NDI.

Download Full-text

Bone Mineral Density, Body Composition, and Metabolic Health of Very Low Birth Weight Infants Fed in Hospital Following Current Macronutrient Recommendations during the First 3 Years of Life

Nutrients ◽

10.3390/nu13031005 ◽

2021 ◽

Vol 13 (3) ◽

pp. 1005

Author(s):

Walter Mihatsch ◽

Izaskun Dorronsoro Martín ◽

Vicente Barrios-Sabador ◽

María L. Couce ◽

Gabriel Á. Martos-Moreno ◽

...

Keyword(s):

Bone Mineral Density ◽

Health Outcome ◽

Body Composition ◽

Preterm Infants ◽

Bone Mineral ◽

Very Low Birth Weight ◽

Metabolic Health ◽

Mineral Density ◽

Term Infants ◽

Vlbw Infants

The present study longitudinally evaluated growth, bone mineral density, body composition, and metabolic health outcome in very low birth weight (VLBW) infants whose in-hospital target nutrient intake was within recent recommendations. From six months to three years, bone mineral density (dual-energy X-ray absorptiometry, DXA), body composition, and metabolic health outcome were compared with a reference group of term infants. The aim was to test whether in-hospital achieved weight gain until 36 weeks of gestation (light or appropriate for term equivalent age; LTEA or ATEA) predicts later growth, bone mineral density (BMD), abdominal obesity, or metabolic health outcomes such as insulin resistance, relative to term infants, during the first three years of life. Target in-hospital energy and protein intake was not achieved. Growth in weight, length and head circumference, mid arm circumference, adiposity, fat free mass (FFM), and bone mineralization in VLBW infants was less than those in term infants and influenced by nutritional status at discharge. Preterm infants had poorer motor and cognitive outcomes. Post-discharge body composition patterns indicate FFM proportional to height but lower fat mass index in LTEA preterm infants than term infants, with no evidence of increased truncal fat in preterm infants. The hypothesis of early BMD catch-up in VLBW infants after discharge was not supported by the present data. The clinical significance of these findings is unclear. The data may suggest a reduced obesity risk but an increased osteoporosis risk. Since postnatal growth restriction may have permanent negative health effects, LTEA VLBW infants would especially appear to benefit from targeted preventive interventions. Further follow-up of the infants is required.

Download Full-text

Neonatal and Postneonatal Pulmonary Hypertension

Children ◽

10.3390/children8020131 ◽

2021 ◽

Vol 8 (2) ◽

pp. 131

Author(s):

Satyan Lakshminrusimha

Keyword(s):

Pulmonary Hypertension ◽

Preterm Infants ◽

Ductus Arteriosus ◽

Right Ventricular Dysfunction ◽

Fold Increase ◽

Pulmonary Vein Stenosis ◽

Term Infants ◽

Pulmonary Vasodilators ◽

Non Invasive Ventilation ◽

Early Closure

During transition at birth with ventilation of the lungs, pulmonary vascular resistance (PVR) decreases from high fetal values, leading to an 8 to 10-fold increase in pulmonary blood flow (Qp). In some infants, this transition does not occur, resulting in pulmonary hypertension (PH). In infants, PH can present as: (a) primary PH in term neonates (idiopathic), (b) PH secondary to lung disease or hypoplasia in term infants, (c) acute PH in preterm infants with respiratory distress syndrome (RDS), (d) chronic PH with bronchopulmonary dysplasia (BPD) in preterm infants and (e) post-neonatal PH. A hemodynamically significant patent ductus arteriosus (PDA) can exacerbate PH in preterm infants due to increased Qp. Pulmonary vein stenosis (PVS) can complicate BPD with PH. Diagnosis of PH is based on clinical features, echocardiography and, in some intractable cases, cardiac catheterization. Therapy of PH includes oxygen, invasive or non-invasive ventilation, correction of acidosis, surfactant and selective and non-selective pulmonary vasodilators such as inhaled nitric oxide and sildenafil, respectively. Early closure of a hemodynamically significant PDA has the potential to limit pulmonary vascular remodeling associated with BPD and PH. The role of thiamine in pathogenesis of PH is also discussed with the recent increase in thiamine-responsive acute pulmonary hypertension in early infancy. Recognition and prompt therapy of PH can prevent right ventricular dysfunction, uncoupling and failure.

Download Full-text

Infant–Father Attachment in Infants Born Preterm - A Brief Report

International Journal of Developmental Science ◽

10.3233/dev-200299 ◽

2021 ◽

pp. 1-6

Author(s):

Ruediger Kissgen ◽

Sebastian Franke ◽

Nino Jorjadze ◽

Bernhard Roth ◽

Angela Kribs

Keyword(s):

Preterm Infants ◽

Full Term ◽

Strange Situation ◽

Term Infants ◽

Attachment Quality ◽

Attachment Research ◽

Neurodevelopmental Problems ◽

Strange Situation Procedure ◽

Father Attachment

This study examines the infant–father attachment in infants born preterm (< 1500 g at birth and/or < 37 weeks gestation) in comparison to full-term infants. The infant–father attachment was assessed using the Strange Situation Procedure at a (corrected) age of 15 months. We found at least half of preterm and full-term infants (50.0% and 56.5 % respectively) securely attached to their fathers, and no significant overall difference was observed concerning the distribution of attachment quality comparing the two groups. In light of the fact that preterm infants tend to have numerous neurodevelopmental problems, it is encouraging that significant differences were not found in the distribution of the attachment quality among the groups. Therefore, from the perspective of attachment research, it would be highly beneficial to include fathers in the care of their preterm infants.

Download Full-text

Novel HAX1 Gene Mutation in a Vietnamese Boy with Severe Congenital Neutropenia

Case Reports in Pediatrics ◽

10.1155/2018/2798621 ◽

2018 ◽

Vol 2018 ◽

pp. 1-4

Author(s):

Tham Thi Tran ◽

Quang Van Vu ◽

Taizo Wada ◽

Akihiro Yachie ◽

Huong Le Thi Minh ◽

...

Keyword(s):

Early Onset ◽

Bacterial Infections ◽

Complete Blood Count ◽

Hereditary Diseases ◽

Severe Neutropenia ◽

Sequencing Analysis ◽

Severe Congenital Neutropenia ◽

Congenital Neutropenia ◽

Direct Dna Sequencing ◽

Life Threatening

Severe congenital neutropenia (SCN) is a rare disease that involves a heterogeneous group of hereditary diseases. Mutations in the HAX1 gene can cause an autosomal recessive form of SCN-characterized low blood neutrophil count from birth, increased susceptibility to recurrent and life-threatening infections, and preleukemia predisposition. A 7-year-old boy was admitted due to life-threatening infections, mental retardation, and severe neutropenia. He had early-onset bacterial infections, and his serial complete blood count showed persistent severe neutropenia. One older sister and one older brother of the patient died at the age of 6 months and 5 months, respectively, because of severe infection. Bone marrow analysis revealed a maturation arrest at the promyelocyte/myelocyte stage with few mature neutrophils. In direct DNA sequencing analysis, we found a novel homozygous frameshift mutation (c.423_424insG, p.Gly143fs) in the HAX1 gene, confirming the diagnosis of SCN. The patient was successfully treated with granulocyte colony-stimulating factor (G-CSF) and antibiotics. A child with early-onset recurrent infections and neutropenia should be considered to be affected with SCN. Genetic analysis is useful to confirm diagnosis. Timely diagnosis and suitable treatment with G-CSF and antibiotics are important to prevent further complication.

Download Full-text

Introduction and feeding practices of solid food in preterm infants born in Salzburg!

BMC Pediatrics ◽

10.1186/s12887-021-02505-6 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Edda Hofstätter ◽

Verena Köttstorfer ◽

Patricia Stroicz ◽

Sebastian Schütz ◽

Lorenz Auer-Hackenberg ◽

...

Keyword(s):

Celiac Disease ◽

Preterm Infants ◽

Complementary Feeding ◽

Study Group ◽

Early Weaning ◽

Structured Interviews ◽

Term Infants ◽

The Mean ◽

The Difference

Abstract Background It is shown that meeting the increased nutritional demand of preterm infants from birth is not only important for survival but essentially contributes to the infants` overall development and long-term health. While there are established guidelines for weaning term infants, evidence regarding preterm infants is scarce and less precise. The aim of this study was to identify the current practices on introducing solids to preterm infants amongst caregivers in Salzburg and determine potential reasons for early weaning. Methods Altogether 68 infants born between 24 0/7 and 36 6/7 weeks were recruited and detailed structured interviews with the caregivers were conducted at 17 weeks corrected age. Weight, height and head circumference were collected. Results 52% of the study group received solids before the recommended 17 weeks corrected age. For this group the mean age being 13.77 ± 1.11 weeks corrected age. Premature introduction of solids significantly correlates with exclusively and early formula-feeding. 34% were weaned due to recommendation by their paediatrician. 23% of the preterm infants even received solids before 12 weeks corrected age, putting them at risks for developing obesity, celiac disease and diabetes. Conclusions This study shows the necessity for clear guidelines regarding the introduction of complementary feeding in preterm infants as well as the importance of their implementation. Caregivers should receive information on this topic early enough and they should fully understand the difference between chronological and corrected age.

Download Full-text