Early-onset neonatal sepsis as a risk factor for peri-intraventricular hemorrhage in premature infants.

OBJECTIVE: To assess early-onset sepsis as a risk factor of peri-intraventricular hemorrhage in premature infants born at less than or equal to 34 weeks' gestation and admitted to a neonatal intensive care unit (NICU). METHODS: This retrospective cohort study included premature patients born at less than or equal to 34 weeks' gestation who were admitted to the NICU of a tertiary hospital in southern Brazil, and born from January 2017 to July 2021. Data were collected from patients' medical records. Early-onset sepsis was measured according to the presence or absence of diagnosis within the first 72 hours of life, whereas the outcome, peri-intraventricular hemorrhage, was described as the presence or absence of hemorrhage, regardless of its grade. RESULTS: Hazard ratios were calculated using Cox regression models. A total of 487 patients were included in the study, of which 169 (34.7%) had some degree of peri-intraventricular hemorrhage. Early-onset sepsis was present in 41.6% of the cases of peri-intraventricular hemorrhage, which revealed a significant association between these variables, with increased risk of the outcome in the presence of sepsis. In the final multivariate model, the hazard ratio for early-onset sepsis was 1.52 (95% confidence interval 1.01-2.27). CONCLUSION: Early-onset sepsis and the use of surfactants showed to increase the occurrence of the outcome in premature children born at less than or equal to 34 weeks' gestation. Meanwhile, factors such as antenatal corticosteroids and gestational age closer to 34 weeks' gestations were found to reduce the risk of peri-intraventricular hemorrhage.

Factors associated with neonatal hyperinsulinemic hypoglycemia, a case-control study.

OBJECTIVES: We aimed to identify perinatal risk factors associated with hyperinsulinemic hypoglycemia in neonates. Secondary objectives included an examination of clinical and biochemical characteristics at the time of diagnosis and an exploration of the duration of diazoxide therapy. METHODS: A case-control study was conducted, involving individual chart reviews of inborn infants diagnosed with hyperinsulinemic hypoglycemia (the HH group) between 2014 and 2021. These cases were paired with controls (the non-HH group) belonging to the same gestational age (GA) strata who did not exhibit HH or only had transient postnatal hypoglycemia. RESULTS: A total of 52 infants with HH were matched with corresponding controls. The mean GA in the HH group was 34.4 ± 3.1 weeks. Notably, the HH group exhibited lower mean minimum plasma glucose (PG) levels and required higher glucose infusion rates in comparison to the non-HH group (26.5 ± 15.6 vs. 49.1 ± 37.7 mg/dL and 12.9 ± 3.8 vs. 5.7 ± 2.1 mg/kg/min, respectively; p<0.001 for both). After adjusting for potential confounding factors, only two variables, fetal growth restriction (FGR) and neonatal sepsis, demonstrated significant associations with HH (adjusted odds ratio [95 % confidence interval]: 8.1 [2.1-31.0], p=0.002 and 6.3 [1.9-21.4], p=0.003, respectively). The median duration of diazoxide therapy for the HH group was 4 months. CONCLUSIONS: FGR and neonatal sepsis emerged as notable risk factors for HH. These infants exhibited lower PG levels and necessitated higher glucose infusion rates compared to their non-HH counterparts. Importantly, a substantial proportion of the HH group received diazoxide therapy, with a median treatment duration of 4 months.

Neonatal sepsis as a cause of retinopathy of prematurity: An etiological explanation.

Retinopathy of prematurity (ROP) is a complex neonatal disorder with multiple contributing factors. In this paper we have mounted the evidence in support of the proposal that neonatal sepsis meets all requirements for being a cause of ROP (not a condition, mechanism, or even innocent bystander) by means of initiating the early stages of the pathomechanism of ROP occurrence, systemic inflammation. We use the model of etiological explanation, which distinguishes between two overlapping processes in ROP causation. It can be shown that sepsis can initiate the early stages of the pathomechanism via systemic inflammation (causation process) and that systemic inflammation can contribute to growth factor aberrations and the retinal characteristics of ROP (disease process). The combined contribution of these factors with immaturity at birth (as intrinsic risk modifier) and prenatal inflammation (as extrinsic facilitator) seems to provide a cogent functional framework of ROP occurrence. Finally, we apply the Bradford Hill heuristics to the available evidence. Taken together, the above suggests that neonatal sepsis is a causal inducer of ROP.

The effects of antibiotic therapy on neonatal sepsis-associated acute kidney injury.

AIM: Neonatal sepsis remains one of the most dangerous conditions in the neonatal intensive care units. One of the organs affected by sepsis is the kidney, making acute kidney injury (AKI) a common complication of sepsis. Treatment of sepsis almost always involves antibiotic therapy, which by itself may cause some adverse effects, including nephrotoxicity. We analyzed the mutual effect of antibiotic therapy and sepsis on AKI in an experimental and clinical study in infants and neonatal rats. MATERIALS AND METHODS: We evaluated the influence of therapy with different antibiotics on the appearance of AKI markers (blood urea nitrogen (BUN), neutrophil gelatinase-associated lipocalin (NGAL), clusterin, interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), monocyte chemoattractant protein 1 (MCP-1), calbindin, glutation-S-transferase subtype π (GST-π)) and liver injury markers in newborns with or without clinical signs of sepsis in the intensive care unit. In parallel, we analyzed the development of AKI in experimental lipopolysaccharide (LPS)-induced systemic inflammation in newborn rats accompanied by antibiotic therapy. KEY FINDINGS: We showed that therapy with metronidazole or ampicillin in combination with sulbactam had a beneficial effect in children with suspected sepsis, resulting in a decrease in AKI markers levels. However, treatment of newborns with netilmicin, cefepime, linezolid, or imipenem in combination with cilastatin worsened kidney function in these patients. SIGNIFICANCE: This prospective study indicates which antibiotics are preferable in neonatal sepsis and which should be used with caution in view of the risk of AKI development.

Paenibacillus spp infection among infants with postinfectious hydrocephalus in Uganda: an observational case-control study.

BACKGROUND: Paenibacillus thiaminolyticus is a cause of postinfectious hydrocephalus among Ugandan infants. To determine whether Paenibacillus spp is a pathogen in neonatal sepsis, meningitis, and postinfectious hydrocephalus, we aimed to complete three separate studies of Ugandan infants. The first study was on peripartum prevalence of Paenibacillus in mother-newborn pairs. The second study assessed Paenibacillus in blood and cerebrospinal fluid (CSF) from neonates with sepsis. The third study assessed Paenibacillus in CSF from infants with hydrocephalus. METHODS: In this observational study, we recruited mother-newborn pairs with and without maternal fever (mother-newborn cohort), neonates (aged ≤28 days) with sepsis (sepsis cohort), and infants (aged ≤90 days) with hydrocephalus with and without a history of neonatal sepsis and meningitis (hydrocephalus cohort) from three hospitals in Uganda between Jan 13, 2016 and Oct 2, 2019. We collected maternal blood, vaginal swabs, and placental samples and the cord from the mother-newborn pairs, and blood and CSF from neonates and infants. Bacterial content of infant CSF was characterised by 16S rDNA sequencing. We analysed all samples using quantitative PCR (qPCR) targeting either the Paenibacillus genus or Paenibacillus thiaminolyticus spp. We collected cranial ultrasound and computed tomography images in the subset of participants represented in more than one cohort. FINDINGS: No Paenibacillus spp were detected in vaginal, maternal blood, placental, or cord blood specimens from the mother-newborn cohort by qPCR. Paenibacillus spp was detected in 6% (37 of 631 neonates) in the sepsis cohort and, of these, 14% (5 of 37 neonates) developed postinfectious hydrocephalus. Paenibacillus was the most enriched bacterial genera in postinfectious hydrocephalus CSF (91 [44%] of 209 patients) from the hydrocephalus cohort, with 16S showing 94% accuracy when validated by qPCR. Imaging showed progression from Paenibacillus spp-related meningitis to postinfectious hydrocephalus over 1-3 months. Patients with postinfectious hydrocephalus with Paenibacillus spp infections were geographically clustered. INTERPRETATION: Paenibacillus spp causes neonatal sepsis and meningitis in Uganda and is the dominant cause of subsequent postinfectious hydrocephalus. There was no evidence of transplacental transmission, and geographical evidence was consistent with an environmental source of neonatal infection. Further work is needed to identify routes of infection and optimise treatment of neonatal Paenibacillus spp infection to lessen the burden of morbidity and mortality. FUNDING: National Institutes of Health and Boston Children's Hospital Office of Faculty Development.

Clinical Risk Factors for Early-Onset Sepsis in Neonates: An International Delphi Study.

Background: Despite growing evidence, there is still uncertainty about potentially modifiable risk factors for neonatal early-onset sepsis (EOS). This study aimed to identify potential clinical risk factors for EOS based on a literature review and expert opinions. Methods: A literature search was conducted in PubMed (MEDLINE), Cochrane, Embase, and Scopus databases. Articles in English, published up to May 2021, on clinical risk factors for neonatal EOS were included. Initially, a questionnaire on risk factors for EOS was developed and validated. The fuzzy Delphi method (FDM) was used to formulate the final version of the questionnaire. The validity of the risk factors was assessed using the Chi square test. P<0.05 was considered statistically significant. Results: In the review phase, 30 risk factors were approved by two neonatologists and included in the FDM phase. In total, 25 risk factors met the consensus criteria and entered the validation phase. During the observational study, 114 neonates (31 with and 83 without EOS) were evaluated for two months. The results of the Chi square test showed that cesarean section was not a significant risk factor for EOS (P=0.862). The need for mechanical ventilation and feed intolerance was observed in about 70% of neonates with EOS, and therefore considered significant risk factors for EOS (P<0.001). Finally, 26 potential clinical risk factors were determined. Conclusion: Neonatal-related risk factors for EOS were birth weight, one-min Apgar score, and prematurity. Maternal-related risk factors were gestational age and urinary tract infection. Delivery-related risk factors were premature rupture of membranes, chorioamnionitis, and intrapartum fever.

Multiple pneumatoceles and lung abscesses caused by early-onset E. coli sepsis in a preterm neonate.

Early-onset sepsis (EOS) is a serious and fatal illness in neonates, Group B Streptococcus and Escherichia coli are major causative pathogens. We report a case of EOS and pneumonia caused by E. coli in a preterm neonate with multiple pneumatoceles and lung abscesses. A male neonate weighing 1670g was delivered at 33 6/7 weeks' gestation by a mother with clinical chorioamnionitis. He showed respiratory distress soon after birth and developed septic shock. He was intubated and mechanical ventilation was started. E.coli was detected in blood culture obtained from both the patient and his mother. He developed multiple pneumatoceles and lung abscesses. Surgical drainage was complicated, cefotaxime was thus continued until day 74. Pneumatoceles and lung abscesses are complications of neonatal pneumonia, rarely reported by E. coli. Multiple lung abscesses in our patient are distinct from single abscesses in previous case studies of neonatal lung abscesses. We speculate that bacteremia along with pneumatoceles led to multiple lung abscesses in our patient. These complications require long-term antibiotic therapy, to minimize morbidity and mortality, and should thus be considered when managing EOS caused by E. coli.

Acute kidney injury and early fluid load in a retrospective cohort of neonatal sepsis.

BACKGROUND: Sepsis and acute kidney injury (AKI) are associated with mortality in the newborn intensive care unit (NICU). There is a paucity of studies that describe AKI and fluid overload in neonatal sepsis and their association with mortality. METHODS: Retrospective study of neonates with culture positive sepsis admitted to the NICU between June 2020 and June 2021 was conducted. Primary outcome was in-hospital mortality according to AKI as defined by the neonatal modified Kidney Diseases Improving Outcomes criteria. Secondary outcomes were early fluid overload and vasopressor use. RESULTS: Thirty-three percent of neonates had AKI with sepsis, and 57% of cases were severe AKI. AKI was associated with mortality after adjusting for variables that were different between survivors and non-survivors (aOR 5.7 [95% CI 1.1-36], p = 0.04). Early fluid overload occurred in 27% of neonates who were at higher risk of having AKI with sepsis (OR 7.4 [95% CI 1.6-26.0], p = 0.01) and higher risk of mortality (aOR 17.8 [95% CI 2-7545], p = 0.02). CONCLUSIONS: AKI and early fluid overload are associated with mortality in sepsis in our retrospective cohort. Mitigating AKI and early fluid overload in sepsis might be a fruitful strategy in reducing mortality with sepsis. A higher resolution version of the Graphical abstract is available as Supplementary information.

Preterm sepsis is associated with acute lung injury as measured by pulmonary severity score.

BACKGROUND: Sepsis related acute lung injury (ALI) is established in adults but has not been investigated in premature infants. Herein, we used pulmonary severity score (PSS) trajectories and C-reactive protein (CRP) to examine the relation between sepsis and ALI in premature infants. METHODS: This retrospective study identified 211 sepsis and 123 rule out (RO) events in 443 infants born <31 weeks and <1500 grams. The PSS was calculated prior to, at the time of, and up to 1 week after each event. Initial and peak CRP values were collected for each event. RESULTS: PSS significantly increased at 0 h from baseline (-72h) and remained increased at all subsequent time points (all p < 0.002) in sepsis events. Mean PSS in sepsis episodes were also higher compared to RO events at +24 h, +48 h, +72 h, and +168 h (all p < 0.004). A positive correlation was noted between peak CRP values in sepsis events and PSS at 0 h, +24 h, +48 h, and +72 h. CONCLUSIONS: The temporal PSS trends and correlation with CRP levels observed in sepsis but not in RO events supports the hypothesis that neonatal sepsis is associated with ALI and contributes to the accumulating evidence that neonatal ARDS occurs. IMPACT: To evaluate pulmonary severity scores and c-reactive protein values over time to establish an association between preterm neonatal sepsis and acute lung injury (ALI). Though sepsis is well established as the most common indirect cause of ALI leading to acute respiratory distress syndrome (ARDS) in adults and pediatrics, this phenomenon remains undefined in neonates. This study validates the proposal by the Neonatal ARDS Project that ARDS also occurs in neonates by demonstrating acute and sustained changes in markers of pulmonary injury temporally related to a diagnosis of neonatal sepsis in preterm infants.

Incidence of Retinopathy of Prematurity in Neonates with Neonatal Sepsis.

BACKGROUND: One of the most important complications of premature birth is retinopathy of prematurity (ROP). Sepsis may increase the incidence of this complication. The aim of this study is to compare the incidence of ROP in neonates with and without sepsis. METHODS: In a retrospective case-control study, preterm infants admitted to the neonatal intensive care unit (NICU) of Ghaem hospital from 2014 to 2022 were examined. The case group consisted of 155 preterm infants with definite sepsis (positive blood culture and clinical signs of sepsis) and the control group included 145 preterm infants without sepsis whose maternal and neonatal characteristics were collected; they were examined by a retinologist and evaluated for ROP at 32 weeks or four weeks after birth. Finally, we used the chi-square and the t test to compare the two groups. RESULTS: Out of 155 preterm infants with sepsis, 70% and out of 145 preterm infants without sepsis, 58% had ROP (P=0.023). Also, low birth weight, low initial Apgar score and low 5-minute Apgar score were significantly associated with ROP (P<0.05). CONCLUSION: Based on the results of this study, sepsis is a serious risk factor for ROP. We can reduce its incidence and complication by preventing sepsis in premature infants.

Risk factors for neonatal sepsis in Sub-Saharan Africa: a systematic review with meta-analysis.

OBJECTIVES: To identify the risk factors for neonatal sepsis in Sub-Saharan Africa. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, Embase, Web of Science, African Index Medicus and ClinicalTrials.gov were searched for observational studies from January 2010 to August 2020. SETTING: Sub-Saharan Africa, at all levels of healthcare facilities. PARTICIPANTS: 'Neonates' (<28 days of age) at risk of developing either clinical and/or laboratory-dependent diagnosis of sepsis. OUTCOME MEASURES: Identification of any risk factors for neonatal sepsis. RESULTS: A total of 36 studies with 23 605 patients from secondary or tertiary level of care facilities in 10 countries were included. Six studies were rated as good quality, 8 as fair and 22 as poor. Four studies were omitted in the meta-analysis due to insufficient data. The significant risk factors were resuscitation (OR 2.70, 95% CI 1.36 to 5.35), low birth weight <1.5 kg (OR 3.37, 95% CI 1.59 to 7.13) and 1.5-2.5 kg (OR 1.36, 95% CI 1.01 to 1.83), low Apgar score at the first minute (OR 3.69, 95% CI 2.34 to 5.81) and fifth minute (OR 2.55, 95% CI 1.46 to 4.45), prematurity <37 weeks (OR 1.91, 95% CI 1.27 to 2.86), no crying at birth (OR 3.49, 95% CI 1.42 to 8.55), male sex (OR 1.30, 95% CI 1.01 to 1.67), prolonged labour (OR 1.57, 95% CI 1.08 to 2.27), premature rupture of membranes (OR 2.15, 95% CI 1.34 to 3.47), multiple digital vaginal examinations (OR 2.22, 95% CI 1.27 to 3.89), meconium-stained amniotic fluid (OR 2.72, 95% CI 1.58 to 4.69), intrapartum maternal fever (OR 2.28, 95% CI 1.18 to 4.39), foul-smelling vaginal discharge (OR 3.31, 95% CI 2.16 to 5.09) and low socioeconomic status (OR 1.93, 95% CI 1.11 to 3.35). We found considerable heterogeneity in the meta-analysis of 11 out of 15 identified risk factors. CONCLUSION: Multiple risk factors for neonatal sepsis in Sub-Saharan Africa were identified. We revealed risk factors not listed by the WHO guidelines. The included studies overall had high risk of bias and high heterogeneity and thus, additional research of high quality is needed. PROSPERO REGISTRATION NUMBER: CRD42020191067.

NT-Pro-BNP and echocardiography for the early assessment of cardiovascular dysfunction in neonates with sepsis.

To investigate the predictive manner of N-terminal fragment of brain natriuretic peptide (NT-Pro-BNP) and echocardiography in the early assessment of cardiovascular dysfunction (CVD) in neonates with sepsis, we recruited 108 neonates with sepsis in intensive care units and divided them into a sepsis with CVD (sepsis + CVD) group (n = 48) and a sepsis only group (n = 60). Neonates with other infections (n = 65) constituted the control group. Clinical, laboratory, and bedside echocardiography findings were evaluated. Compared to both the sepsis only and control groups, the sepsis + CVD group showed an earlier onset of symptoms [52.94 (0-185.6) h], higher NT-Pro-BNP levels (P = .02), a higher Tei index (0.52 + 0.03; P = .03), and lower ejection fraction (62.61% ± 12.31%, P < .05). Compared to the control group, the sepsis + CVD group exhibited hematogenous etiology (P < .05), lower albumin (ALB) levels (P = .04), lower white blood cell counts (P = .03), a higher high-sensitivity C-reactive protein/ALB ratio, and a larger right-ventricle-inner diameter (10.74 + 2.42 mm; P = .01). CVD in the septic neonates could be predicted by either NT-Pro-BNP levels (cut-off: 12,291.5 pg/L; sensitivity, 80%; specificity, 79%; area under the curve-receiver operating characteristic, 0.81) or Tei index (cut-off: 0.45; sensitivity, 74%; specificity, 77%; area under the curve-receiver operating characteristic, 0.78). NT-Pro-BNP levels and echocardiography can be used to determine early onset of CVD in neonatal sepsis, which facilitates timely pharmacological interventions and treatment.

Clinical assessment of neutrophil gelatinase-associated lipocalin as a potential diagnostic marker for neonatal sepsis: a prospective cohort study.

Sepsis is a life-threatening condition associated with high morbidity and mortality rates among neonates. Clinical diagnosis is limited due to the neonates' unspecific signs and symptoms as well as the long time required to obtain the blood culture results. Consequently, there is an urgent need for new biomarkers to early diagnose neonatal sepsis. We aimed to evaluate Neutrophil Gelatinase-Associated Lipocalin (NGAL) diagnostic performance to detect neonatal sepsis. We enrolled 30 neonates with sepsis admitted to the neonatal intensive care units and 30 age- and sex-matched healthy neonates recruited from the neonatal outpatient clinic during their routine follow-up visits. We measured NGAL levels by sandwich enzyme-linked immunosorbent assay, the C-reactive protein (CRP) with nephelometry technique using BN II nephelometer, and the complete blood count by Mindray BC-6800 analysers. NGAL, CRP, TLC, haemoglobin, and platelet levels showed significant differences between cases and control (all p < .001). Of the 30 neonates with sepsis, 17 neonates (56.7%) survived. At 0 h, the NGAL level showed no statistically significant difference between the non-survivors and survivors' groups; however, after 96 h, NGAL was significantly higher in the non-survivors group (p ˂ .001). Our diagnostic analysis showed that NGAL levels have strong discrimination power to early differentiate neonates with sepsis; at the 475.00 pg/ml cut-off value, NGAL showed both sensitivity and specificity of 100% with an area under curve of 100%. Conclusion: Our study suggests that NGAL could be a promising biomarker for neonatal sepsis detection. Further studies with larger sample sizes and survival analysis are warranted to confirm this finding and to clarify the efficacy of NGAL in survival prediction. Key findingsNGAL level was high in neonates with sepsisNGAL level was high in non-survived neonatesNGAL could be a promising diagnostic marker for sepsis.

Sepsis precoz, osteoartritis y meningitis: a propósito de un caso clínico / Early sepsis, osteoarthritis and meningitis: a clinical case / Sepse precoce, osteoartrite e meningite: relato de caso

Se expone el caso de un recién nacido que desarrolló sepsis connatal precoz a Streptococcus agalactiae, con meningitis aguda supurada y osteoartritis de rodilla izquierda. Como factor de riesgo la madre no tenía realizado el exudado rectovaginal, pesquisa que detecta la colonización por estreptococo del grupo B (EGB). Se aisló el germen en hemocultivo y en líquido de punción articular. Recibió tratamiento antibiótico adecuado a la sensibilidad del microorganismo y según pauta de sepsis con meningitis, evolucionando favorablemente. En este trabajo se describe la epidemiología de la sepsis neonatal y los cambios ocurridos luego de la implementación de la profilaxis antibiótica en el preparto.

We hereby present the case of a newborn with early connatal sepsis due to Streptococcus agalactiae, with acute suppurative meningitis and left knee osteoarthritis. As a risk factor, the mother had not performed the rectus vaginal exudate screening that detects colonization by Group B Streptococcus (GBS). The germ was isolated in blood culture and in joint puncture fluid. The patient received germ-sensitive antibiotic treatment for meningitis sepsis and evolved favorably. This paper describes the epidemiology of neonatal sepsis and the changes that have occurred after the administration of the antibiotic prophylaxis during pregnancy.

Apresentamos o caso de um recém-nascido com sepse neonatal precoce por Streptococcus agalactiae, com meningite supurativa aguda e osteoartrite de joelho esquerdo. Como fator de risco, a mãe não realizou teste de exsudato vaginal do reto que detecta a colonização por estreptococos do grupo B (SGB). O germe foi isolado em hemocultura e líquido de punção articular. A paciente recebeu tratamento com antibióticos germinativos para padrão meningite sepse e evoluiu favoravelmente. Este artigo descreve a epidemiologia da sepse neonatal e as mudanças ocorridas após a administração da profilaxia antibiótica durante a gravidez.

A CLINICAL CASE OF ARTERIAL THROMBOSIS IN A PREMATURE BOY WITH NEONATAL SEPSIS AND HIGH RECTAL ATRESIA.

Occlusion of the venous or arterial vessels in childhood is rather rare but dangerous complication. Occurrence of neonatal thrombosis is 0.5 per 10 000 of live newborns. Promoting factors include congenital defects of coagulation, maternal diabetes, neonatal sepsis, necrotic enterocolitis, asphyxia, and metabolic diseases. More than 90 % cases of neonatal thrombosis are associated with catheterization (umbilical arterial or venous, other central venous lines). Acute arterial thrombosis caused by a peripheral venous catheter is very rare complication, but it can result in severe consequences. The article contains a clinical case of right brachial artery thrombosis in a premature boy with extremely low body weight complicated by development of dry gangrene and amputation of the limb. Complex risk factors promoting development of neonatal arterial thrombosis were found: preterm birth, neonatal sepsis, possible incorrect insertion of a peripheral venous catheter. Associative factors were congenital developmental defects of the intestine (high rectal atresia) and heart (bicuspid aortal valve, open oval foramen), and maternal factors. The authors emphasize their attention on the necessity to continuous education of the medical staff concerning the technique of catheter insertion and care of them, absolute implementation of safety policy concerning nosocomial infection, adequate provision of ultrasound examination devices with high rarefaction sensors, involvement of a multi-disciplinary team of specialists to manage complicated clinical cases.

Emphysematous gastritis in a newborn: Is it very rare or do we just miss it?

Emphysematous gastritis is a rare and life-threatening condition caused by gastric inflammation and intramural gas formation, most often diagnosed through radiological evidence of a radiolucent shadow in the stomach wall in the clinical scenario of severe sickness. We report a case of emphysematous gastritis secondary to early-onset neonatal sepsis in a newborn which, to the best of our knowledge, has not otherwise been reported. Is it very rare or do we just miss it?

Paediatric and neonatal sepsis and inflammation.

Sepsis has a huge impact on global mortality and has been declared as a priority by the World Health organisation the WHO.1 Children have a high incidence of sepsis especially in the neonatal with an estimated 3 million babies affected worldwide and mortality ranges from 11 to 19%.2 In addition, long-term neurodevelopmental outcomes are affected but this is largely unquantified. However, challenges remain in the early recognition, diagnosis and standardised management of sepsis. This series on Sepsis and inflammation in children reviews the conundrums of diagnostic criteria, biomarkers, management and future strategies to improve outcomes.

Clinical chorioamnionitis and histologic placental inflammation: association with early-neonatal sepsis.

OBJECTIVE: Chorioamnionitis and fetal inflammatory response syndrome (FIRS) are significant risk factors for early onset sepsis (EOS). Recently, the use "Intrauterine Inflammation or Infection or both" or triple I has been proposed, classifying cases into an isolated maternal fever, suspected triple I, or confirmed chorioamnionitis. Evidence suggests that the association between suspected chorioamnionitis and confirmed histological chorioamnionitis (HCA) is not consistent, as well as the impact of HCA on the development of EOS.We aimed to evaluate the association between suspected chorioamnionitis and HCA, the impact of HCA on EOS, and the effect of antepartum antibiotic prophylaxis on EOS. METHODS: We retrospectively reviewed the medical records of all infants admitted to our institution, between 2017 and 2018, with a diagnosis of chorioamnionitis. We recorded the clinical evidence of chorioamnionitis, the histologic report of the placenta, the maternal and neonatal data, the neonatal inflammatory markers including C-reactive protein (CRP), and the incidence of EOS. The impact of antepartum antibiotic prophylaxis on the infants' CRP and EOS was calculated, and the logistic regression model was performed to estimate the association of confirmed HCA with EOS, while controlling for FIRS stage, gestation age, birth weight, maternal fever, foul-smelling amniotic fluid, and prolonged rupture of membranes. RESULTS: During the study period, a total of 266 infants were identified; 81 (30%) infants had a confirmed HCA (HCA-present cases), and 185 (70%) infants were diagnosed with suspected triple I (HCA-absent cases). Antepartum antibiotics had been commenced in a significantly higher proportion in HCA-present cases (46%) in comparison to 14% of HCA-absent cases (p < .001). HCA-present infants were of significantly lower gestation (31.6 ± 4weeks versus 33.3 ± 4weeks, p = .004), and birth weight (1826 ± 840 g versus 2092 ± 849 g, p = .019), they had a significantly higher rate of clinical symptoms (31% versus 6%, p < .001), and a higher CRP at birth and 24 h (1.4 ± 1.5 mg/dL versus 0.3 ± 0.2 mg/dL, p < .001, and 2.1 ± 2.3 mg/dL versus 0.4 ± 0.6 mg/dL, p < .001, respectively). All HCA-present cases had evidence of FIRS; 43% were stage I, 25% stage II, and 32% were FIRS stage III. A significantly higher proportion of HCA-present infants were diagnosed with EOS (46% as compared to 6%, p < .001). The antepartum antibiotic administration was related to a significantly lower CRP at birth and 24 h only in HCA-present cases, albeit not with any reduction ιn EOS incidence. HCA was significantly associated with EOS (RR 3.18, 95% CI 2.81-5.18, p < .001). After adjusting for perinatal factors, the presence of HCA (OR 7.89, 95% CI 1.19-23.34, p = .032) and an advanced FIRS stage (OR 10.35, 95% CI 4.23-25.32, p < .001) were significantly associated with EOS. CONCLUSIONS: Amongst infants with suspected chorioamnionitis, the diagnosis is partially supported by histological confirmation, and that is more prominent in pregnancies of a lower gestation. The presence of HCA and an advanced FIRS stage predispose to an increased risk of EOS after adjusting for other perinatal and neonatal factors. The antepartum prophylaxis against intra-amniotic infection was related to a significantly lower CRP in HCA-present cases.

Exposure to intrauterine inflammation and late-onset sepsis in very preterm infants.

BACKGROUND: Late-onset sepsis is an important cause of mortality and morbidity in preterm infants. As these infants rely mostly on their innate immune system to fight off infection, enhancing this immune system by appropriate stimuli may prevent late-onset sepsis. However, it remains unclear which stimuli can enhance the neonatal immune system. This study aims to investigate the influence of intrauterine inflammation on late-onset sepsis. METHODS: This is a retrospective cohort study in a Neonatal Intensive Care Unit in the Netherlands. Between 2005 and 2016, 1014 infants with ≤32 weeks gestational age and/or with a birth weight ≤1500 g were included. Intrauterine inflammation was subdivided into histological chorioamnionitis, fetal inflammatory response, and funisitis. Logistic and Cox regression analyses were performed to investigate the influence of intrauterine inflammation on late-onset sepsis. RESULTS: Thirty-six percent of the included infants developed late-onset sepsis; 24% of placentas showed intrauterine inflammation. Late-onset sepsis incidence did not differ between infants with or without exposure to intrauterine inflammation after adjustment for gestational age (histological chorioamnionitis aHR 0.928 [CI: 0.727-1.185], p = 0.551; fetal inflammatory response aHR 1.011 [CI: 0.793-1.288], p = 0.930); funisitis aHR 0.965 [CI: 0.738-1.263], p = 0.797). CONCLUSIONS: Late-onset sepsis in very preterm infants seems not to be associated with intrauterine inflammation. IMPACT: Intrauterine inflammation is not protective of developing late-onset sepsis in premature infants. A large cohort study on the effect of intrauterine inflammation on neonatal outcome. This study adds to existing knowledge on finding appropriate stimuli to enhance the immune system of premature infants to improve neonatal outcome.