Young Infant Mortality Associated with Preterm and Small-for-Gestational-Age Births in Rural Bangladesh: A Prospective Cohort Study.

OBJECTIVE: To assess the relative risk of mortality in infants born preterm and small for gestational age (SGA) during the first and second months of life in rural Bangladesh. STUDY DESIGN: We analyzed data from a cohort of pregnant women and their babies in Sylhet, Bangladesh, assembled between 2011 and 2014. Community health workers visited enrolled babies up to 10 times from birth to age 59 days. Survival status was recorded at each visit. Gestational age was estimated from mother's reported last menstrual period. Birth weights were measured within 72 hours of delivery. SGA was defined using the INTERGROWTH-21st standard. We estimated unadjusted and adjusted hazard ratios (HRs) and corresponding 95% CIs for babies born preterm and SGA separately for the first and second month of life using bivariate and multivariable weighted Cox regression models. RESULTS: The analysis included 17 643 singleton live birth babies. Compared with infants born at term-appropriate for gestational age, in both unadjusted and adjusted analyses, infants born preterm-SGA had the greatest risk of death in the first (HR 13.25, 95% CI 8.65-20.31; adjusted HR 12.05, 95% CI 7.82-18.57) and second month of life (HR 4.65, 95% CI 1.93-11.23; adjusted HR 4.1, 95% CI 1.66-10.15), followed by infants born preterm-appropriate for gestational age and term-SGA. CONCLUSIONS: The risk of mortality in infants born preterm and/or SGA is increased and extends through the second month of life. Appropriate interventions to prevent and manage complications caused by prematurity and SGA could improve survival during and beyond the neonatal period.

Bacterial coinfection in young febrile infants with SARS-CoV-2 infection.

We aimed to assess the prevalence of serious bacterial infections (SBIs) in febrile infants < 90 days of age with SARS-CoV-2 infection versus SARS-CoV-2-negative febrile infants. A retrospective cohort study was conducted in a tertiary pediatric emergency department between March 2020 and October 2022. Febrile infants < 90 days of age who underwent SARS-CoV-2 testing were included. SBIs were defined as urinary tract infection (UTI), bacteremia, and/or bacterial meningitis; bacteremia and bacterial meningitis were considered invasive bacterial infections (IBIs). SBIs rates were compared between SARS-CoV-2-positive and negative infants and stratified by age. We included 779 infants: 221 (28.4%) SARS-CoV-2-positive and 558 (71.6%) SARS-CoV-2-negative. The SBI rate in the SARS-CoV-2-positive group was 5.9% vs 22.9% in the SARS-CoV-2-negative group (p < 0.001; relative risk (RR) 0.26; [95% CI 0.15-0.44]); the most common infections were UTI (5.4% vs 22.0%; p < 0.001). The IBI rate was 0.5% in the SARS-CoV-2-positive group vs. 3.2% in the negative group (p = 0.024; RR 0.14 [95% CI 0.02-1.04]). There were no cases of bacterial meningitis in the positive infants. SARS-CoV-2-positive infants > 28 days of age had a decreased likelihood of SBI (RR 0.22 [95% CI 0.11-0.43]), with no cases of IBI identified.     Conclusions: Febrile infants < 90 days of age with SARS-CoV-2 infection are at significantly lower risk of SBIs than those who are SARS-CoV-2-negative. Nevertheless, the rate of UTI remains considerable in SARS-CoV-2-positive infants. SARS-CoV-2 detection may be relevant in considering IBI risk for well-appearing febrile infants 29-89 days of age. What is Known: • Febrile infants with laboratory-confirmed viral infections have a significantly lower risk of serious bacterial infections when compared to those without them. Data focusing on very young febrile infants with a SARS-CoV-2 infection is still limited. What is New: • Young febrile infants with SARS-CoV-2 infection are at significantly lower risk of serious bacterial infections than those who are SARS-CoV-2-negative. Nevertheless, the rate of urinary tract infection remains considerable. SARS-CoV-2 detection may be relevant in considering invasive bacterial infection risk for well-appearing febrile infants 29-89 days of age.

The timing of minimally invasive surgery for prenatally diagnosed choledochal cysts.

OBJECTIVE: There are no clear evidence-based recommendations concerning when patients with prenatally diagnosed choledochal cysts (CCs) should undergo surgery. This study was primarily designed to explore the proper timing of minimally invasive surgery for prenatally diagnosed CC patients. METHODS: Seventy-three patients with prenatally diagnosed CC were enrolled in this study and divided into 4 subgroups according to age at surgery (15 patients in the < 1 month group, 27 in the 1-2 months group, 14 in the 2-3 months group and 17 in the > 3 months group). Eighty-five healthy infants were recruited and divided into 4 age groups (29 in the < 1 month group, 20 in the 1-2 month group, 19 in the 2-3 month group and 17 in the > 3 month group). Preoperative data were collected and compared between CC patients and healthy controls in 4 age groups. Additionally, 73 patients were divided into laparoscopic and open groups to compare postoperative recovery indices and the occurrence of complications to determine the safety and feasibility of laparoscopic CC application in neonates and young infants. RESULTS: Twenty-one of 73 (28.8%) patients who were prenatally diagnosed with CCs experienced various clinical symptoms, and 15 of 21 (71.4%) patients experienced clinical symptoms less than 2 months after birth. No differences were found in alanine transaminase (ALT), aspartate transaminase (AST) or aspartate transaminase (APRI) levels between CC patients and controls at ≤ 1 month or 1-2 months of age (all p > 0.05), while higher levels were found in CC patients at 2-3 months or > 3 months of age (all p < 0.05). ALT, AST and DBIL levels 1 week after surgery were significantly lower than those before surgery in CC patients who underwent laparoscopic CC excision at > 2 months of age, while DBIL levels 1 week after surgery were also significantly lower than those before surgery in patients who underwent CC excision at ≤ 2 months of age. The initial oral feeding time in the laparoscopic surgery group was significantly earlier than that in the open surgery group for both CC patients who underwent CC excision at ≤ 2 months of age and those > 2 months of age (all p < 0.05). No differences were found in the rates of anastomotic leakage or stricture formation between the laparoscopic and open surgery groups at ≤ 2 months or > 2 months of age. CONCLUSION: Most clinical symptoms attributed to CC occur less than 2 months after birth, while liver function and liver fibrosis may deteriorate after 2 months of age in patients with prenatally diagnosed CC. Laparoscopic surgery for CC in newborns and young infants (either less than or more than 2 months old) is safe and feasible and can shorten the initial oral feeding time without increasing complications such as postoperative anastomotic leakage or stricture. Thus, performing laparoscopic CC excisions within 2 months after birth in patients with prenatally diagnosed CC may be appropriate.

Urinary tract infections in young infants with a normal urine dipstick.

AIM: To assess missed urinary tract infections (UTI) in febrile infants ≤2 months when adhering to recent guidelines suggesting not to send a urine culture with a negative dipstick. METHODS: A retrospective cohort study of 308 infants ≤2 months with a positive urine culture admitted in 2013-2023, divided into subgroups without exposure to urine dipstick results: 'urosepsis' (UTI with bacteraemia), 'UTI' (positive urine culture, elevated inflammatory markers, no other cause of fever) and 'bacteriuria' (positive urine culture, not meeting the above-mentioned criteria). After retrieving the dipstick results, the 'missed UTI' group (UTI+ negative dipstick) was described. RESULTS: A negative dipstick was found in 2/20 (10%), 32/127 (25%) and 126/161 (78%) of infants with 'urosepsis', 'UTI' and 'bacteriuria', respectively. In the 'missed UTI' group (n = 34), there were more non-Escherichia coli UTI (68% vs. 9% with positive dipstick, p < 0.001), and lower inflammatory markers (leukocytes 15.5 vs. 17.2 k/µL, p = 0.007, C-reactive protein 21 vs. 58 mg/L, p < 0.001). Three infants had high-grade vesicoureteral reflux (VUR) and renal scarring. CONCLUSIONS: There is a non-negligible rate of infants ≤2 months with UTI and without pyuria, including those with urosepsis, VUR and renal scarring. We suggest obtaining a urine culture regardless of dipstick results.

Coming in Hot: A quality improvement approach to improving care of febrile infants.

Background and Objectives: Significant practice variation exists in managing young infants with fever. Quality improvement strategies can aid in risk stratification and standardization of best care practices, along with a reduction of unnecessary interventions. The aim of this initiative was to safely reduce unnecessary admissions, antibiotics, and lumbar punctures (LPs) by 10% in low-risk, febrile infants aged 29 to 90 days presenting to the emergency department (ED) over a 12-month period. Methods: Using the Model for Improvement, a multidisciplinary team developed a multipronged intervention: an updated clinical decision tool (CDT), procalcitonin (PCT) adoption, education, a feedback tool, and best practice advisory (BPA) banner. Outcome measures included the proportion of low-risk infants that were admitted, received antibiotics, and had LPs. Process measures were adherence to the CDT and percentage of PCT ordered. Missed bacterial infections and return visits were balancing measures. The analysis was completed using descriptive statistics and statistical process control methods. Results: Five hundred and sixteen patients less than 90 days of age were included in the study, with 403 patients in the 29- to 90-day old subset of primary interest. In the low-risk group, a reduction in hospital admissions from a mean of 24.1% to 12.0% and a reduction in antibiotics from a mean of 15.2% to 1.3% was achieved. The mean proportion of LPs performed decreased in the intervention period from 7.5% to 1.8%, but special cause variation was not detected. Adherence to the CDT increased from 70.4% to 90.9% and PCT was ordered in 92.3% of cases. The proportion of missed bacterial infections was 0.3% at baseline and 0.5% in the intervention period while return visits were 6.7% at baseline and 5.0% in the intervention period. Conclusions: The implementation of a quality improvement strategy, including an updated evidence-based CDT for young infant fever incorporating PCT, safely reduced unnecessary care in low-risk, febrile infants aged 29 to 90 days in the ED. Purpose: To develop and implement a multipronged improvement strategy including an evidence-based CDT utilizing PCT to maximize value of care delivered to well-appearing, febrile infants presenting to EDs.

Outpatient and oral management is suitable for infants 60-90 days old with urinary tract infections at low risk of bacteremia.

One previous study recommended oral and outpatient management for those infants aged 60-90 days with urinary tract infection (UTI) meeting the low-risk criteria identified: to be well-appearing and to have a procalcitonin value of < 0.7 ng/mL. A retrospective study was conducted, including infants aged 29 to 90 days with UTI from 2014 to 2019, to validate these low-risk criteria identified and determine the adherence to the new algorithm for managing these patients at the Emergency Department. Two hundred one patients were included; 105 (52.2%) were aged 60 to 90 days. Twelve (6%, 95% CI 3.4-10.1%) had bacteremia. One hundred thirty-six (67.7%) infants met low-risk criteria; none had a positive blood culture (0%, 95% CI 0-2.7%). Overall protocol adherence was 90.6%. One hundred and forty-four (71.6%) infants were admitted to the hospital; all patients meeting high-risk criteria were hospitalized. Among the 57 (28.4%) infants initially sent home, 4 (7.0%) required later hospital admission.Conclusions: A prediction rule including general appearance and procalcitonin is highly accurate in identifying young infants with UTI at low risk for bacteremia. Outpatient management with appropriate follow-up is safe for these infants. What is Known: • Patients under 2-3 months of age with a presumptive urinary tract infection (UTI) are commonly hospitalized because of concerns regarding concomitant bacteremia. What is New: • A prediction rule including general appearance and procalcitonin is highly accurate in identifying young infants with UTI at low risk for bacteremia. Outpatient management with appropriate follow-up is safe for these infants.

Incidence and aetiology of serious viral infections in young febrile infants.

AIM: While the incidence and aetiology of serious bacterial infections among febrile infants younger than 90 days old are well studied, those concerning viral infection are not. There are severe life-threatening viral infections requiring immediate intense therapy. The objective of the study is to describe the incidence and aetiology of serious viral infections (SVI) among young febrile infants. METHODS: A retrospective audit was performed covering all the febrile infants younger than 90 days old admitted to a paediatric emergency department in Japan from 2011 to 2013. SVI was defined as a viral illness that may result in permanent organ dysfunctions or life-threatening complications. Diagnostic investigation consisted of urine and blood culture for all infants, cerebrospinal fluid cultures for infants who do not fulfil the low-risk criteria, rapid antigen tests for several viruses in infants with specific symptoms and blood and/or cerebrospinal fluid polymerase chain reaction of possible viruses for infants with fever without a localising source. RESULTS: Of 275 cases, 32 and 45 cases were diagnosed as serious viral and bacterial infections, respectively. Intensive care unit admission occurred for three viral and four bacterial infections. Viral aetiology consisted of respiratory syncytial virus (11 cases), aseptic meningitis (9 cases), enterovirus (6 cases), influenza virus (3 cases), rotavirus (2 cases) and herpes simplex virus-1 (1 case). Respiratory (14 cases), central nervous (12 cases) and circulatory (6 cases) systems were affected. CONCLUSION: SVI was observed in 11.6% of febrile young infants in a paediatric emergency department.

Inpatient and outpatient treatment for acute malnutrition in infants under 6 months; a qualitative study from Senegal.

BACKGROUND: Treatment of acute malnutrition in infants under 6 months is a relevant topic regarding the global problem of maternal and child malnutrition. While treatment for older age groups has shifted more towards an outpatient, community based approach, young infants are mostly treated in hospital. This study aims to describe barriers and facilitators for outpatient and inpatient treatment of malnourished infants under 6 months in Senegal. METHODS: This qualitative descriptive study uses in-depth interviews with health workers and focus group discussions with mothers of malnourished infants, conducted from June to September 2015 in two case clinics. In data analysis, Collins' 3 key factors for a successful nutrition program were used as a theoretical framework: access, quality of care and community engagement. RESULTS: Within Collins' 3 key factors, 9 facilitators and barriers have emerged from the data. Key factor access: Outpatient care was perceived as more accessible than inpatient concerning distance and cost, given that there is a milk supplement available. Trust could be more easily generated in an outpatient setting. Key factor quality of care: The cup and spoon re-lactation technique was efficiently used in outpatient setting, but needed close supervision. Basic medical care could be offered to outpatients provided that referral of complicated cases was adequate. Health education was more intensive with inpatients, but could be done with outpatients. Key factor community engagement: The community appeared to play a key role in treating malnourished young infants because of its influence on health seeking behaviour, peer support and breastfeeding practices. CONCLUSIONS: Outpatient care does facilitate access, provided that an affordable milk supplement is available. Quality of care can be guaranteed using an appropriate re-lactation technique and a referral system for complications. The community has the potential to be much engaged, though more attention is required for breastfeeding education. In view of the magnitude of the health problem of young infant malnutrition and its strong relationship with breastfeeding practices, an outpatient community-based treatment approach needs to be considered.

Predicting serious bacterial infection in febrile young infants utilizing body temperature.

BACKGROUND: Febrile young infants have a high risk of serious infection. Although measuring vital sign parameters can serve as a rapid and effective assessment in these patients, their predictive value for serious bacterial infection (SBI) has not been fully investigated. METHODS: This retrospective observational study enrolled febrile (>38.0°C) infants aged <90 days at the time of presentation. Data from the emergency room triage database at Tokyo Metropolitan Children's Medical Center for the period 1 November 2011-30 November 2013, were reviewed. Variables included patient age, gender, and vital sign data, including body temperature, pulse rate, oxygen saturation, definitive diagnosis, and disposition. RESULTS: Two hundred and sixty-nine patients were included, with a mean age of 55 days, and 158 (58.7%) were male. Of the total, 43 patients had an SBI. On logistic regression, body temperature ≥38.5°C (OR, 2.80; 95%CI: 1.37-5.74) was a significant predictor of SBI. CONCLUSION: High-grade fever was found to be a significant predictor of SBI in febrile young infants.

Clostridium septicum arthritis in a young infant: A case report.

Septic arthritis is one of the most serious conditions leading to grave consequences in all age groups, with a number of cases seen in infancy and childhood. Although septic arthritis in neonates is a known clinical entity, it is a diagnostic dilemma for the paediatricians. Of the reported causes of bacterial arthritis, anaerobic bacteria account for only 1%. Anaerobic bacterial septic arthritis may be more common than appreciated and therefore anaerobic as well as aerobic cultures should be done in all cases of septic arthritis. We report the first documented case of spontaneous septic arthritis due to Clostridium septicum in an infant with successful outcome.

Impact of Enteroviral Polymerase Chain Reaction Testing on Length of Stay for Infants 60 Days Old or Younger.

OBJECTIVE: To determine the impact of a cerebrospinal fluid enterovirus polymerase chain reaction (PCR) test performance on hospital length of stay (LOS) in a large multicenter cohort of infants undergoing evaluation for central nervous system infection. STUDY DESIGN: We performed a planned secondary analysis of a retrospective cohort of hospitalized infants ≤60 days of age who had a cerebrospinal fluid culture obtained at 1 of 18 participating centers (2005-2013). After adjustment for patient age and study year as well as clustering by hospital center, we compared LOS for infants who had an enterovirus PCR test performed vs not performed and among those tested, for infants with a positive vs negative test result. RESULTS: Of 19 953 hospitalized infants, 4444 (22.3%) had an enterovirus PCR test performed and 945 (21.3% of tested infants) had positive test results. Hospital LOS was similar for infants who had an enterovirus PCR test performed compared with infants who did not (incident rate ratio 0.98 hours; 95% CI 0.89-1.06). However, infants PCR positive for enterovirus had a 38% shorter LOS than infants PCR negative for enterovirus (incident rate ratio 0.62 hours; 95% CI 0.57-0.68). No infant with a positive enterovirus PCR test had bacterial meningitis (0%; 95% CI 0-0.4). CONCLUSIONS: Although enterovirus PCR testing was not associated with a reduction in LOS, infants with a positive enterovirus PCR test had a one-third shorter LOS compared with infants with a negative enterovirus PCR test. Focused enterovirus PCR test use could increase the impact on LOS for infants undergoing cerebrospinal fluid evaluation.

Risk factors for possible serious bacterial infection in a rural cohort of young infants in central India.

BACKGROUND: Possible serious bacterial infection (PBSI) is a major cause of neonatal mortality worldwide. We studied risk factors for PSBI in a large rural population in central India where facility deliveries have increased as a result of a government financial assistance program. METHODS: We studied 37,379 pregnant women and their singleton live born infants with birth weight ≥ 1.5 kg from 20 rural primary health centers around Nagpur, India, using data from the 2010-13 population-based Maternal and Newborn Health Registry supported by NICHD's Global Network for Women's and Children's Health Research. Factors associated with PSBI were identified using multivariable Poisson regression. RESULTS: Two thousand one hundred twenty-three infants (6 %) had PSBI. Risk factors for PSBI included nulliparity (RR 1.13, 95 % CI 1.03-1.23), parity > 2 (RR 1.30, 95 % CI 1.07-1.57) compared to parity 1-2, first antenatal care visit in the 2nd/3rd trimester (RR 1.46, 95 % CI 1.08-1.98) compared to 1st trimester, administration of antenatal corticosteroids (RR 2.04, 95 % CI 1.60-2.61), low birth weight (RR 3.10, 95 % CI 2.17-4.42), male sex (RR 1.20, 95 % CI 1.10-1.31) and lack of early initiation of breastfeeding (RR 3.87, 95 % CI 2.69-5.58). CONCLUSION: Infants who are low birth weight, born to mothers who present late to antenatal care or receive antenatal corticosteroids, or born to nulliparous women or those with a parity > 2, could be targeted for interventions before and after delivery to improve early recognition of signs and symptoms of PSBI and prompt referral. There also appears to be a need for a renewed focus on promoting early initiation of breastfeeding following delivery in facilities. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov ( NCT01073475 ).

[Etiology and clinical course of urinary tract infections in infants less than 3 months-old]. / Etiología y curso clínico de la infección del tracto urinario en los lactantes menores de 3 meses.

BACKGROUND: Infants less than 3 months of age with urinary tract infection are usually hospitalized. Recent studies show that a less aggressive management for those patients aged ≥ 29 days may be feasible. OBJECTIVES: To determine the complication rate in infants<3 months of age with urinary tract infection, and to identify the causative agents and their antibiotic susceptibility. METHODS: A retrospective study was conducted on infants<3 months of age with positive urinalysis results, together with a positive urine culture from a catheterized specimen and seen in the Emergency Department from 2007 to 2012. Demographics, clinical and microbiology (microorganism isolated and antibiotic susceptibility) data were collected. The complications rate (bacteremia, bacterial meningitis, renal abscess, surgical intervention, Intensive Care Unit admission, or death) were calculated for the overall sample and for different age groups (<29, 29-60, and 61-90 days). RESULTS: A total of 460 patients are included; 137 (29.8%)<29, 166 (36.1%) 29-60, and 157 (34.1%) 61-90 days of age. Twenty four (5.4%; 95% CI: 3.6-7.8) had bacteremia; 15 (10.9%; 95% CI: 6.7-17.3) were<29 days; 8 (4.9%; 95% CI: 2.5-9.4) were 29-60 days, and one (0.7%; 95% CI: 0.1-3.7) was 61-90 days of age (P<.001). One neonate (0.8%; 95% CI: 0.1-4.1) had bacterial meningitis, and 2, renal abscess. Escherichia coli was the common pathogen identified (87.2%) in the urine culture, with a susceptibility to amoxicillin-clavulanate, gentamicin, and cefixime of 89.2, 97.0, and 96.0%, respectively. CONCLUSION: Complications are low in infants<3 months of age with UTI, especially in those ≥ 29 days of age. The identification of patients at very low risk for complications would allow a less aggressive management. Escherichia coli antibiotic susceptibility remains stable, but continuing careful surveillance is essential to optimize empirical antibiotic treatment.

Uropathogens and clinical manifestations of pyuria-negative urinary tract infections in young infants: A single center cross-sectional study.

BACKGROUND: Urine leukocyte count under microscopy is one of the most frequently used routine screening tests for urinary tract infection (UTI). Nevertheless, it is observed that pyuria is lacking in 10-25% of children with UTI. This study aims to determine the factors related to pyuria-negative UTI in young infants aged under four months old. METHOD: This retrospective cross-sectional study was conducted on 157 patients aged under 4 months old with UTI. All subjects had paired urinalysis and urine culture, which were collected via transurethral catheterization. According to the results of their urinalysis, the patients were then classified as UTI cases with pyuria and UTI cases without pyuria. The clinical characteristics and outcomes of both groups were analyzed. RESULT: Among the 157 UTI patients, the prevalence of pyuria-negative UTI was 44%. Significant risk factors associated with pyuria-negative UTI included non-E.coli pathogens, younger age, shorter duration of fever prior to hospital visit, lower white blood cell (WBC) count upon hospital visit, and absence of microscopic hematuria. CONCLUSIONS: We found that non-E.coli uropathogens were the strongest factor related to pyuria-negative UTI. The absence of pyuria cannot exclude the diagnosis of UTI in young infants, and it's reasonable to perform both urinalysis and urine culture as a part of the assessment of febrile or ill-looking young infants.

Explainable deep learning model to predict invasive bacterial infection in febrile young infants: A retrospective study.

BACKGROUND: Machine learning models have demonstrated superior performance in predicting invasive bacterial infection (IBI) in febrile infants compared to commonly used risk stratification criteria in recent studies. However, the black-box nature of these models can make them difficult to apply in clinical practice. In this study, we developed and validated an explainable deep learning model that can predict IBI in febrile infants ≤ 60 days of age visiting the emergency department. METHODS: We conducted a retrospective study of febrile infants aged ≤ 60 days who presented to the pediatric emergency department of a medical center in Taiwan between January 1, 2011 and December 31, 2019. Patients with uncertain test results and complex chronic health conditions were excluded. IBI was defined as the growth of a pathogen in the blood or cerebrospinal fluid. We used a deep neural network to develop a predictive model for IBI and compared its performance to the IBI score and step-by-step approach. The SHapley Additive Explanations (SHAP) technique was used to explain the model's predictions at different levels. RESULTS: Our study included 1847 patients, 53 (2.7%) of whom had IBI. The deep learning model performed similarly to the IBI score and step-by-step approach in terms of sensitivity and negative predictive value, but provided better specificity (54%), positive predictive value (5%), and area under the receiver-operating characteristic curve (0.87). SHapley Additive exPlanations identified five influential predictive variables (absolute neutrophil count, body temperature, heart rate, age, and C-reactive protein). CONCLUSION: We have developed an explainable deep learning model that can predict IBI in febrile infants aged 0-60 days. The model not only performs better than previous scoring systems, but also provides insight into how it arrives at its predictions through individual features and cases.

Have we got the optimal treatment for refractory Kawasaki disease in very young infants? A case report and literature review.

A small group of patients with Kawasaki disease (KD) demonstrates resistance to standard therapy, putting them at high risk for an unfavorable prognosis, especially regarding coronary artery aneurysms. Although adding corticosteroids to first-line i.v. immunoglobulins (IVIGs) is considered beneficial, and despite timely treatment initiation, very young infants, in particular, can present an unfavorable clinical course. We report on a 3-month-old boy with a clinically severe KD phenotype involving the early development of giant coronary artery aneurysms. Because of his poor response to the first course of IVIG and prednisolone, we administered infliximab. His clinical condition improved after that, and his temperature dropped. Inflammatory markers however did not recover completely, and he remained subfebrile. In addition, as the coronary artery dimensions deteriorated, a second IVIG course was administered and prednisolone continued at the initial dosage. Although fever and routine inflammatory parameters normalized, close follow-up investigations revealed both still increasing coronary artery dimensions and renewed rise in inflammatory parameters, necessitating two more infliximab administrations in addition to continuous prednisolone. Because of the coronary artery dimensions (left anterior descending artery, 4.9 mm, Z-score 11.1; right coronary artery 5.8 mm, Z-score 15.5), dual platelet inhibitory therapy with ASA and later clopidogrel combined with low-molecular heparin was indicated. Four weeks after his initial KD diagnosis, we detected no renewed increase in inflammatory markers; at that time, we observed a slight reduction in coronary dimensions. In summary, despite timely guideline-fulfilling therapy, the prolonged clinical course of this very young infant with KD entailing the development of giant coronary artery aneurysms makes us question whether this age group may benefit from early, even more intense therapy.

Zinc Supplementation and the Prevention and Treatment of Sepsis in Young Infants: A Systematic Review and Meta-Analysis.

BACKGROUND: Prematurity and low birth weight are major risk factors for neonatal sepsis. Zinc supplements have been previously shown to be beneficial in pregnancy and small for gestational age birth outcomes. There is sparse information, however, on the potential benefits of zinc supplementation to prevent or treat serious infections in this age group. OBJECTIVE: The aim of this study was to assess the efficacy of preventive and therapeutic zinc supplementation in young infant (<4 months) sepsis. METHODS: MEDLINE, Cochrane CENTRAL, and other databases were searched from inception until 18 June 2021. Studies assessing preventive and therapeutic zinc supplementation in young infants in relation to incidence and outcomes of suspected sepsis were included. Meta-analyses of pooled effects were calculated for sepsis-related outcomes. RESULTS: Nine randomized controlled trials involving 2,553 infants were included. Six studies reported therapeutic efficacy, whereas 3 evaluated preventive benefits of zinc supplementation. Preventive studies suggest a protective effect of zinc supplementation on neonatal mortality rate (NMR) (risk ratio (RR) 0.28; 95% CI 0.12-0.67, LOW certainty), but with no effect on the incidence of sepsis, both in preterm neonates. Among young infants, therapeutic zinc was associated with significant reductions in treatment failure (RR 0.61; 95% CI 0.44-0.85; MODERATE certainty) and further subgroup analysis showing significant reduction in infant mortality rate with 3 mg/kg/twice a day dosage only (RR 0.49; 95% CI 0.27-0.87, LOW certainty). Therapeutic zinc supplementation in neonates did not show any effect on hospital stay or NMR. CONCLUSION: Zinc supplementation could potentially reduce mortality and treatment failure in young infants but has no noteworthy influence on hospital stay and in the prevention of sepsis. Further studies with larger sample sizes are needed to confirm the direction and magnitude of effects if any.

Population pharmacokinetics-pharmacodynamics of ceftazidime in neonates and young infants: Dosing optimization for neonatal sepsis.

Ceftazidime is a third-generation cephalosporin with high activity against many pathogens. But the ambiguity and diversity of the dosing regimens in neonates and young infants impair access to effective treatment. Thus, we conducted a population pharmacokinetic study of ceftazidime in this vulnerable population and recommended a model-based dosage regimen to optimize sepsis therapy. Totally 146 neonates and young infants (gestational age (GA): 36-43.4 weeks, postnatal age (PNA): 1-81 days, current weight (CW): 900-4500 g) were enrolled based on inclusion and exclusion criteria. Ceftazidime bloods samples (203) were obtained using the opportunistic sampling strategy and determined by the high-performance liquid chromatography. The population pharmacokinetic-pharmacodynamic analysis was conducted by nonlinear mixed effects model (NONMEM). A one-compartment model with first-order elimination best described the pharmacokinetic data. Covariate analysis showed the significance of GA, PNA, and CW on developmental pharmacokinetics. Monte Carlo simulation was performed based on above covariates and minimum inhibitory concentration (MIC). In the newborns with PNA ≤ 3 days (MIC=8 mg/L), the dose regimen was 25 mg/kg twice daily (BID). For the newborns with PNA > 3 days (MIC=16 mg/L), the optimal dose was 30 mg/kg three times daily (TID) for those with GA ≤ 37 weeks and 40 mg/kg TID for those with GA > 37 weeks. Overall, on the basis of the developmental population pharmacokinetic-pharmacodynamic analysis covering the whole range of neonates and young infants, the evidence-based ceftazidime dosage regimens were proposed to optimize neonatal early-onset and late-onset sepsis therapy.

Using Machine Learning to Predict Invasive Bacterial Infections in Young Febrile Infants Visiting the Emergency Department.

BACKGROUND: The aim of this study was to develop and evaluate a machine learning (ML) model to predict invasive bacterial infections (IBIs) in young febrile infants visiting the emergency department (ED). METHODS: This retrospective study was conducted in the EDs of three medical centers across Taiwan from 2011 to 2018. We included patients age in 0-60 days who were visiting the ED with clinical symptoms of fever. We developed three different ML algorithms, including logistic regression (LR), supportive vector machine (SVM), and extreme gradient boosting (XGboost), comparing their performance at predicting IBIs to a previous validated score system (IBI score). RESULTS: During the study period, 4211 patients were included, where 126 (3.1%) had IBI. A total of eight, five, and seven features were used in the LR, SVM, and XGboost through the feature selection process, respectively. The ML models can achieve a better AUROC value when predicting IBIs in young infants compared with the IBI score (LR: 0.85 vs. SVM: 0.84 vs. XGBoost: 0.85 vs. IBI score: 0.70, p-value < 0.001). Using a cost sensitive learning algorithm, all ML models showed better specificity in predicting IBIs at a 90% sensitivity level compared to an IBI score > 2 (LR: 0.59 vs. SVM: 0.60 vs. XGBoost: 0.57 vs. IBI score >2: 0.43, p-value < 0.001). CONCLUSIONS: All ML models developed in this study outperformed the traditional scoring system in stratifying low-risk febrile infants after the standardized sensitivity level.