Neurodevelopmental outcomes following possible serious bacterial infection in early infancy in Karachi, Pakistan: a prospective cohort study.

BACKGROUND: Pakistan reports a significant burden of neonatal mortality, with infections as one of the major causes. We aim to assess the long-term impact of early infancy infections on neurodevelopmental outcomes during later childhood. METHODS: We conducted a prospective follow-up study of the cohort enrolled at the Karachi site of the Aetiology of Neonatal Infection in South Asia (ANISA) during 2019-2020. Children with a possible serious bacterial infection (based on the WHO IMCI algorithm) at early infancy were assessed for neurodevelopment at 6-9 years of age and compared with healthy controls. The Ten Questions (TQS) questionnaire, Strengths and Difficulties Questionnaire (SDQ), and Parent's Evaluation of Developmental Stage Assessment Level (PEDS: DM-AL) neurodevelopmental assessment tools, were administered and scored by the research staff who were blinded to the child's exposure status. Generalized Structural Equation Modelling (GSEM) was employed to verify relationships and associations among developmental milestones, anthropometry, and sociodemographic variables. RESULTS: A total of 398 children (241 cases and 157 controls) completed neurodevelopmental and growth assessments. Cases had a significantly higher rate of abnormal TQS scores (54.5% vs. 35.0%, p-value 0.001), greater delays in motor milestones (21.2% vs. 12.1%, p-value 0.02), lower fine motor skills (78.4 ± 1.4 vs. 83.2 ± 1.5, p-value 0.02). The receptive language skills were well-developed in both groups. According to the logistic regression model, exposure to infection during the first 59 days of life was associated with delayed TQS milestones (ß = -0.6, 95% CI -1.2,-0.04), TQS hearing domain (ß = -0.3, 95% CI: -1.2 to 0.7), PEDS: DM-AL fine motor domain (ß = -1.3, 95% CI: -4.4 to 1.7), PEDS: DM-AL receptive language development (ß = -1.1, 95% CI: -3.7 to 1.4) and child anthropometric measurements such as weight and height (ß = -0.2, 95% CI: -0.4 to 0.01 and ß = -0.2, 95% CI: -0.4 to -0.01, respectively). Early pSBI exposure was positively associated with PEDS: DM-AL self-help domain (ß = 0.6, 95% CI: -1.2 to 2.4) and SDQ-P overall score (ß = 0.02, 95% CI: -0.3 to 0.3). CONCLUSION: Children exposed to PSBI during early infancy have higher rates of abnormal development, motor delays, and lower fine motor skills during later childhood in Pakistan. Socioeconomic challenges and limited healthcare access contribute to these challenges, highlighting the need for long-term follow-ups with integrated neurodevelopment assessments.

Host RNA Expression Signatures in Young Infants with Urinary Tract Infection: A Prospective Study.

Early diagnosis of infections in young infants remains a clinical challenge. Young infants are particularly vulnerable to infection, and it is often difficult to clinically distinguish between bacterial and viral infections. Urinary tract infection (UTI) is the most common bacterial infection in young infants, and the incidence of associated bacteremia has decreased in the recent decades. Host RNA expression signatures have shown great promise for distinguishing bacterial from viral infections in young infants. This prospective study included 121 young infants admitted to four pediatric emergency care departments in the capital region of Denmark due to symptoms of infection. We collected whole blood samples and performed differential gene expression analysis. Further, we tested the classification performance of a two-gene host RNA expression signature approaching clinical implementation. Several genes were differentially expressed between young infants with UTI without bacteremia and viral infection. However, limited immunological response was detected in UTI without bacteremia compared to a more pronounced response in viral infection. The performance of the two-gene signature was limited, especially in cases of UTI without bloodstream involvement. Our results indicate a need for further investigation and consideration of UTI in young infants before implementing host RNA expression signatures in clinical practice.

Implementation research to increase treatment coverage of possible serious bacterial infections in young infants when a referral is not feasible: lessons learnt.

BACKGROUND: The objective was to achieve high coverage of possible serious bacterial infections (PSBI) treatment using the World Health Organization (WHO) guideline for managing it on an outpatient basis when referral to a hospital is not feasible. METHODS: We implemented this guideline in the programme settings at 10 Basic Health Units (BHU) in two rural districts of Sindh in Pakistan using implementation research. A Technical Support Unit supported the programme to operationalize guidelines, built capacity of health workers through training, monitored their clinical skills, mentored them and assured quality. The community-based health workers visited households to identify sick infants and referred them to the nearest BHU for further management. The research team collected data. RESULTS: Of 17 600 identified livebirths, 1860 young infants with any sign of PSBI sought care at BHUs and 1113 (59.8%) were brought by families. We achieved treatment coverage of 95%, assuming an estimated 10% incidence of PSBI in the first 2 months of life and that 10% of young infants came from outside the study catchment area. All 923 infants (49%; 923/1860) 7-59 days old with only fast breathing (pneumonia) treated with outpatient oral amoxicillin were cured. Hospital referral was refused by 83.4% (781/937) families who accepted outpatient treatment; 92.2% (720/781) were cured and 0.8% (6/781) died. Twelve (7.6%; 12/156) died among those treated in a hospital. CONCLUSION: It is feasible to achieve high coverage by implementing WHO PSBI management guidelines in a programmatic setting when a referral is not feasible.

Development a prediction model for identifying bacterial meningitis in young infants aged 29-90 days: a retrospective analysis.

BACKGROUND: The early diagnosis and treatment of bacterial meningitis (BM) in young infants was very critical. But, it was difficult to make a definite diagnosis in the early stage due to nonspecific clinical symptoms. Our objectives were to find the risk factors associated with BM and develop a prediction model of BM especially for young infants. METHODS: We retrospectively reviewed the clinical data of young infants with meningitis between January 2011 and December 2020 in Children's Hospital of Soochow University. The independent risk factors of young infants with BM were screened using univariate and multivariate logistic regression analyses. The independent risk factors were used to construct a new scoring model and compared with Bacterial Meningitis Score (BMS) and Meningitis Score for Emergencies (MSE) models. RESULTS: Among the 102 young infants included, there were 44 cases of BM and 58 of aseptic meningitis. Group B Streptococcus (22, 50.0%) and Escherichia coli (14, 31.8%) were the main pathogens of BM in the young infants. Multivariate logistic regression analysis identified procalcitonin (PCT), cerebrospinal fluid (CSF) glucose, CSF protein as independent risk factors for young infants with BM. We assigned one point for CSF glucose ≤ 1.86 mmol/L, two points were assigned for PCT ≥ 3.80 ng/ml and CSF protein ≥ 1269 mg/L. Using the not low risk criterion (score ≥ 1) with our new prediction model, we identified the young infantile BM with 100% (95% CI 91.9%-100%) sensitivity and 60.3% (95% CI 46.4%-72.9%) specificity. Compared with BMS and MSE model, our prediction model had larger area under receiver operating characteristic curve and higher specificity, the differences were statistically significant. CONCLUSION: Our new scoring model for young infants can facilitate early identification of BM and has a better performance than BMS and MSE models.

Quality of care assessment for small and sick newborns and young infants in Pakistan: findings from a cross-sectional study.

INTRODUCTION: Pakistan is facing a challenging situation in terms of high newborn mortality rate. Securing pregnancy and delivery care may not bring a substantial reduction in neonatal mortality, unless coupled with the provision of quality inpatient care for small and sick newborns and young infants (NYIs). We undertook this study to assess the availability and quality of newborn care services provided and the readiness of inpatient care for NYIs in Pakistan. METHODS: We conducted a cross-sectional study across Pakistan from February to June 2019, using a purposive sample of 61% (23) of the 38 sick newborn care units at public sector health care facilities providing inpatient care for small and sick NYIs. We interviewed facility managers and health care providers by using structured questionnaires. We observed facility infrastructure and relevant metrics related to the quality of inpatient care such as types of infant care units and essential equipment, drugs, staffing cadre and facility management practices, quality assurance activities, essential services for small and sick NYI care, discharge planning, and support, quality of NYIs care record, and health information system. RESULTS: Of the 23 facilities assessed, 83% had newborn intensive care units (NICUs), 74% reported Special Care Units (SCUs), and only 44% had Kangaroo Mother Care (KMC) Units. All facilities had at least one paediatrician, 13% had neonatologists and neonatal surgeons each. Around 61 and 13% of the facilities had staff trained in neonatal resuscitation and parental counseling, respectively. About 35% of the facilities monitored nosocomial infection rates, with management and interdisciplinary team meetings reported from 17 and 30% of the facilities respectively preceding the survey. Basic interventions for NYIs were available in 43% of the facilities, only 35% of facilities had system in place to monitor nosocomial infections for NYI care. Most (73%) of reviewed records of NYIs at 1-2 days had information on the birth weight, temperature recording (52%), while only a quarter (25%) of the observed records documented danger signs. Mechanism to support discharge care by having linkages with community workers was present in 13% of the facilities, while only 35% of the facilities have strategies to promote adherence after discharge. Majority (78%) of facilities reported monitoring any newborn/ neonatal care indicators, while none of the sub-units within facilities had consolidated information on stillbirths and neonatal deaths. CONCLUSION: The study has demonstrated important gaps in the quality of small and sick NYI inpatient care in the country. To avert neonatal mortality in the country, provincial and district governments have to take actions in improving the quality of inpatient care.

Partner influences, breastfeeding, and body image and eating concerns: An expanded biopsychosocial model.

BACKGROUND: Recent research among postpartum women has considered body image and eating attitudes as well as exclusive breastfeeding within common theoretical models. However, these efforts have so far neglected to include partner-related constructs, which constitutes an important gap. Thus, the aim of this study was to examine an integrated model of body image and eating concerns, and exclusive breastfeeding among mothers of infants six months and younger, that included partner appearance influences as well as general postpartum support. METHODS: A sample of new mothers (N = 156), aged 20-47 years, mean = 32.7 (SD = 4.7) years, reported on postpartum partner support and appearance pressures, thin-ideal internalization and body dissatisfaction, symptoms of disordered eating, depression, breastfeeding self-efficacy and exclusive breastfeeding. Path analyses were conducted to test the hypothetical model. RESULTS: Findings revealed that the final model was a good fit to these data. Postpartum partner support was associated with lower depression and higher breastfeeding self-efficacy, through which it was related to higher reports of exclusive breastfeeding and lower eating disorder symptoms. In addition, partner appearance pressures and thin-ideal internalization were associated with higher body dissatisfaction, and thin-ideal internalization was also related to lower breastfeeding self-efficacy. CONCLUSIONS: Partner influences may be important to account for in models of body image and eating concerns among postpartum women, and exclusive breastfeeding, and further research on ways in which they can support mothers of young infants is warranted.

Using the Implementation Research Logic Model to design and implement community-based management of possible serious bacterial infection during COVID-19 pandemic in Ethiopia.

BACKGROUND: Community-based treatment of possible serious bacterial infection (PSBI) in young infants, when referral to a hospital is not possible, can result in high treatment coverage and low case fatality. However, in Ethiopia, the coverage of PSBI treatment remains low, worsened by COVID-19. To understand the challenges of delivery of PSBI treatment and design and test adaptative strategies to mitigate the impact of COVID-19 on neonatal mortality, we did implementation research (IR) employing Implementation Research Logic Model (IRLM). In this paper, we describe IRLM application experiences in designing, implementing, and evaluating strategies to improve community-based treatment of PSBI during the COVID-19 pandemic in Ethiopia. METHODS: This IR was conducted between November 2020-April 2022 at Dembecha and Lume woredas of Amhara and Oromia regions, respectively. We employed narrative reviews, formative assessment and facilitated stakeholder engagement to develop the PSBI treatment IRLM to identify barriers, understand the conceptual linkages among determinants, choose implementation strategies, elicit mechanisms, and link to implementation outcomes. In addition, we used the IRLM to structure the capture of emerging implementation challenges and resulting strategy adaptations throughout implementation. RESULTS: This IR identified COVID-19 and multiple pre-existing contextual factors. We designed and implemented implementation strategies to address these challenges. These adaptive strategies were implemented with sufficient strength to maintain the delivery of PSBI services and improve mothers' care-seeking behavior for their sick young infants. The IRLM offers us a clear process and path to prioritize implementation challenges, choose strategies informed by mechanisms of action, and where the adaptive implementation of community-based management of PSBI would lead to high-implementation fidelity and change in mother behavior to seek care for their sick young infants. The IRLM was also an effective tool for stakeholder engagement, easily explained and used to structure discussion and decision-making during co-design meetings. CONCLUSIONS: The use of the IRLM helps us to specify the conceptual links between the implementation challenges, strategies, mechanisms of action, and outcomes to explore the complex community-based management of PSBI during complex contexts to improve high-fidelity implementation and integration of PSBI treatment in the primary healthcare delivery systems through active engagement of stakeholders.

Heavy Malaria Parasitaemia in Young Nigerian Infants: Prevalence, Determinants and Implication for the Health System.

BACKGROUND: Infants who are aged six months and below are often protected from malaria and usually present with light parasitaemia when infected. However, complications following heavy malaria parasitaemia in this age group are being increasingly reported. This study set out to determine the prevalence, determinants and the public health implications of heavy malaria parasitaemia in young infants (aged one to six months) at the Wesley Guild Hospital, Ilesa (a unit of the Obafemi Awolowo University Teaching Hospitals Complex). METHODS: Ill infants aged one to six months in out-patient and in-patient care were recruited over an 11-month period. Clinical examinations and blood film for malaria parasite were done for all the study participants. Heavy parasitaemia was defined as > 5000 parasites/µl. Clinical predictors of heavy parasitaemia were determined. RESULTS: Heavy parasitaemia was observed in 16(23.9%) of the sixty-seven participants with malaria infection. Presence of fever at presentation (p=0.007), excessive crying (p=0.003) and pallor (p=0.001) were associated with heavy malaria parasitaemia. However, pallor (OR = 20.653; 95%CI 2.091-203.958; p=0.010) was the only independent predictor of heavy parasitaemia among the young infants. CONCLUSION: About one-in-four ill young infants with malaria had heavy parasitaemia, which was predicted by pallor. Hence, the presence of pallor and factors related to low parental socio-economic status should increase the suspicion of heavy malaria parasitaemia in ill young infants in malaria endemic settings.

CONTEXTE: Nourrissons âgés de six mois et moins sont souvent protégés du paludisme et généralement présents avec de la lumière parasitémie lorsqu'il est infecté. Cependant, les complications qui suivent une parasitémie palustre lourde dans ce groupe d'âge est en cours de plus en plus signalés. Cette étude visait à déterminer la prévalence, les déterminants et les répercussions de l'action sur la santé publique parasitémie palustre sévère chez les jeunes nourrissons (âgés de un à six ans)mois) à l'hôpital Wesley Guild, Ilesa (une unité de l'Obafemi Complexe des hôpitaux universitaires d'Awolowo). MÉTHODES: Nourrissons malades âgés de un à six mois en ambulatoire et les soins aux patients hospitalisés ont été recrutés sur une période de 11 mois. Les examens cliniques et le film sanguin pour le parasite du paludisme ont été fait pour tous les participants à l'étude. La parasitémie lourde était défini comme > 5000 parasites/µl. Prédicteurs cliniques de lourd la parasitémie a été déterminée. RÉSULTATS: Une parasitémie sévère a été observée chez 16 (23,9%) des soixante-sept participants atteints d'une infection palustre. Présence de fièvre à la présentation (p = 0,007), pleurs excessifs (p = 0,003) et la pâleur (p = 0,001) était associée à un paludisme lourdparasitémie. Cependant, pâleur (OR = 20,653; IC à 95 % 2,091-203.958; p=0,010) était le seul prédicteur indépendant de parasitémie chez les jeunes nourrissons. CONCLUSION: Environ un jeune nourrisson malade sur quatre atteint de paludisme avait une parasitémie lourde, qui était prédite par pâleur. D'où la présence de pâleur et de facteurs liés à un faible niveau parental le statut socio-économique devrait accroître la suspicion de lourd parasitémie palustre chez les jeunes nourrissons malades dans le paludisme endémique Paramètres. Mots-clés: Jeunes nourrissons, Parasitémie palustre, Parasite lourddensité, prévalence.

Predictors of grade 3-5 vesicoureteral reflux in infants ≤ 2 months of age with pyelonephritis.

BACKGROUND: This study aimed to assess predictors for grade 3-5 vesicoureteral reflux (VUR) in infants ≤ 2 months of age admitted for first urinary tract infection (UTI). METHODS: Retrospective cohort study of 195 infants ≤ 2 months admitted to a pediatric ward for first UTI between 2006 and 2017. Clinical, laboratory, and imaging data were collected from electronic medical charts. We examined associations between grade 3-5 VUR and different patient characteristics. RESULTS: Twenty infants (10%) were diagnosed with grade 3-5 VUR; all had fever. Infants with grade 3-5 VUR had higher blood neutrophil percentage (BNP) (65% vs. 46%, P < 0.001), higher neutrophil-to-lymphocyte ratio (NLR) (2.6 vs. 1.3, P < 0.001), more renal ultrasound abnormalities (prenatal 26% vs. 5%, P = 0.007; postnatal 84% vs. 55%, P = 0.015), and Pseudomonas UTI (15% vs. 1%, respectively, P < 0.001). NLR > 1.65 showed sensitivity 100% and specificity 61% for detecting grade 3-5 VUR. BNP > 53% showed sensitivity 100% and specificity 60% for detecting grade 3-5 VUR. BNP was the best single marker for grade 3-5 VUR with area under the curve (AUC) of 0.82 (95% CI 0.75-0.89). In a multivariate model, AUC for combination of BNP and hydronephrosis was 0.86 (95% CI 0.79-0.93, P = 0.007). CONCLUSIONS: Infants ≤ 2 months of age admitted for a first UTI are at risk for grade 3-5 VUR and thus should undergo a voiding cystourethrography (VCUG) if their renal ultrasound is abnormal or if they have Pseudomonas UTI. Avoiding VCUG can be considered in afebrile infants and in infants with BNP < 53% or NLR < 1.65.

Ambulatory Treatment of Fast Breathing in Young Infants Aged <60 Days: A Double-Blind, Randomized, Placebo-Controlled Equivalence Trial in Low-Income Settlements of Karachi.

(See the Editorial Commentary by Jehan and Qazi on pages 190-1) BACKGROUND: Integrated Management of Childhood Illness recommends that young infants with isolated fast breathing be referred to a hospital for antibiotic treatment, which is often impractical in resource-limited settings. Additionally, antibiotics may be unnecessary for physiologic tachypnea in otherwise well newborns. We tested the hypothesis that ambulatory treatment with oral amoxicillin for 7 days was equivalent (similarity margin of 3%) to placebo in young infants with isolated fast breathing in primary care settings where hospital referral is often unfeasible. METHODS: This randomized equivalence trial was conducted in 4 primary health centers of Karachi, Pakistan. Infants presenting with isolated fast breathing and oxygen saturation ≥90% were randomly assigned to receive either oral amoxicillin or placebo twice daily for 7 days. Enrolled infants were followed on days 1-8, 11, and 14. The primary outcome was treatment failure by day 8, analyzed per protocol. The trial was stopped by the data safety monitoring board due to higher treatment failure rate and the occurrence of 2 deaths in the placebo arm in an interim analysis. RESULTS: Four hundred twenty-three infants fulfilled per protocol criteria in the amoxicillin arm and 426 in the placebo arm. Twelve infants (2.8%) had treatment failure in the amoxicillin arm and 25 (5.9%) in the placebo arm (risk difference, 3.1; P value .04). Two infants in the placebo arm died, whereas no deaths occurred in the amoxicillin arm. Other adverse outcomes, as well as the proportions of relapse, were evenly distributed across both study arms. CONCLUSIONS: This trial failed to show equivalence of placebo to amoxicillin in the management of isolated fast breathing without hypoxemia or other clinical signs of illness in term young infants. CLINICAL TRIALS REGISTRATION: NCT01533818.

Malaria Prevalence among Young Infants in Different Transmission Settings, Africa.

The prevalence and consequences of malaria among infants are not well characterized and may be underestimated. A better understanding of the risk for malaria in early infancy is critical for drug development and informed decision making. In a cross-sectional survey in Guinea, The Gambia, and Benin, countries with different malaria transmission intensities, the overall prevalence of malaria among infants <6 months of age was 11.8% (Guinea, 21.7%; The Gambia, 3.7%; and Benin, 10.2%). Seroprevalence ranged from 5.7% in The Gambia to 41.6% in Guinea. Mean parasite densities in infants were significantly lower than those in children 1-9 years of age in The Gambia (p<0.0001) and Benin (p = 0.0021). Malaria in infants was significantly associated with fever or recent history of fever (p = 0.007) and anemia (p = 0.001). Targeted preventive interventions, adequate drug formulations, and treatment guidelines are needed to address the sizeable prevalence of malaria among young infants in malaria-endemic countries.

Stunting at birth: recognition of early-life linear growth failure in the western highlands of Guatemala.

OBJECTIVE: Measurements of length at birth, or in the neonatal period, are challenging to obtain and often discounted for lack of validity. Hence, classical 'under-5' stunting rates have been derived from surveys on children from 6 to 59 months of age. Guatemala has a high prevalence of stunting (49.8%), but the age of onset of growth failure is not clearly defined. The objective of the study was to assess length-for-age within the first 1.5 months of life among Guatemalan infants. DESIGN: As part of a cross-sectional observational study, supine length was measured in young infants. Mothers' height was measured. Length-for-age Z-scores (HAZ) were generated and stunting was defined as HAZ <-2 using WHO growth standards. SETTING: Eight rural, indigenous Mam-Mayan villages (n 200, 100% of Mayan indigenous origin) and an urban clinic of Quetzaltenango (n 106, 27% of Mayan indigenous origin), Guatemala. SUBJECTS: Three hundred and six newborns with a median age of 19 d. RESULTS: The median rural HAZ was -1.56 and prevalence of stunting was 38%; the respective urban values were -1.41 and 25%. Linear regression revealed no relationship between infant age and HAZ (r = 0.101, r(2) = 0.010, P = 0.077). Maternal height explained 3% of the variability in HAZ (r = 0.171, r(2) = 0.029, P = 0.003). CONCLUSIONS: Stunting must be carried over from in utero growth retardation in short-stature Guatemalan mothers. As linear growth failure in this setting begins in utero, its prevention must be linked to maternal care strategies during gestation, or even before. A focus on maternal nutrition and health in an intergenerational dimension is needed to reduce its prevalence.

Acquired methaemoglobinaemia in infancy associated with acute diarrhoea: A case series.

Acute diarrhoeal illness remains a common medical problem in children with nearly 1.7 billion cases globally every year. We report five infants who, following severe diarrhoea, developed methaemoglobinemia. This is an altered state of haemoglobin presenting with cyanosis and can pose a diagnostic dilemma. It should be suspected in young infants without cyanotic heart disease presenting with severe diarrhoea, sepsis and cyanosis disproportionate to their clinical status. Its outcome depends on prompt treatment, the severity of underlying sepsis and co-morbidity.

Characterization of young infants with fecal carriage of multidrug-resistant Escherichia coli in Southern Taiwan.

BACKGROUND: The accelerating prevalence of extended-spectrum ß-lactamase (ESBL)-producing and multidrug-resistance (MDR) Escherichia coli(E. coli) become a public health challenge worldwide. This study aimed to discuss the prevalence of drug-resistant E. coli colonization and analyze its risk factors and clinical characteristics among young infants in Southern Taiwan. METHODS: Stool samples were collected from young infants, aged less than three months, within three days of their hospitalization from September to December 2019 in a tertiary hospital. A questionnaire was designed for parents to complete. E. coli colonies were selected and analyzed for antimicrobial susceptibility. PCR-based multilocus sequence typing was to detect the presence of sequence type ST131 and blaCTX-M genes. RESULTS: Among 100 enrolled infants, 36% had fecal carriage of E. coli isolates, of which twenty nine (80.5%) were MDR, thirteen (36.1%) were ESBL-producing isolates and five (13.8%) and ten (27.7%) were ST131 and strains carrying CTX-M-14 gene, respectively. Compared to non-ST131 and non-CTX-M-14 gene carrier, isolates of ST131 and CTX-M-14 gene carrier showed a significantly higher resistance rate to cefixime, ceftriaxone, and gentamycin, with p value all <0.05. CONCLUSION: The prevalence of ESBL-producing and MDR E. coli fecal carriage were both high in young infants. The most common sequence type is ST131, of which all are strains carrying CTX-M-14. Further surveillance and investigation to control for the high prevalence of antimicrobial-resistant E. coli fecal carriage among infants in Taiwan are warranted.

Young Infants Clinical Signs Study 8-sign Algorithm for Identification of Sick Infants Adapted for Routine Home Visits: A Systematic Review and Critical Appraisal of its Measurement Properties.

Objective. The 8-sign algorithm adapted from the Young Infants Clinical Signs Study (YICSS) is widely used to identify sick infants during home visits (YICSS-home algorithm). We aimed to critically appraise the development and evidence of measurement properties, including sensibility, reliability, and validity, of the YICSS-home algorithm. Methods. Relevant studies were identified through a systematic literature search. Results. The YICSS-home algorithm has good sensibility. The algorithm demonstrated at least moderate inter-rater reliability and sensitivity ranging from 69% to 80%. However, the algorithm was developed among sick infants brought for care to a health facility and not initially developed for use by community health workers (CHWs) during home visits. Some important risk factors were omitted at item generation. Inter-CHW reliability and construct validity have not been estimated. Conclusion. Future research should build on the strengths of the YICSS-home algorithm and address its limitations to develop a new algorithm with improved predictive accuracy.

Development and in vitro evaluation of an infant friendly self-nanoemulsifying drug delivery system (SNEDDS) loaded with an amphotericin B-monoacyl phosphatidylcholine complex for oral delivery.

Until relatively recently, the pediatric population has largely been ignored during the development of new drug products, which has led to a high level of "off-label" use of drugs in this particular population. In this study, an infant friendly self-nanoemulsifying drug delivery system (SNEDDS) was developed for oral delivery of a commonly used "off-label" drug - amphotericin B (AmB). AmB was complexed with monoacyl-phosphatidylcholine (MAPC) by lyophilization, transforming crystalline AmB into its amorphous state in the AmB-MAPC complex (APC). The APC-loaded SNEDDS (APC-SNEDDS) showed excellent self-emulsifying properties; after dispersion of the APC-SNEDDS in purified water, nanoscale emulsion droplets were formed within 1 min with a z-average size of 179 ± 1 nm. In vitro pediatric gastrointestinal (GI) digestion and dissolution results showed that the APC-SNEDDS significantly increased the amount of AmB solubilized in aqueous phase and that the precipitated AmB from the APC-SNEDDS re-dissolved faster, compared with crystalline AmB in SNEDDS (AmB-SNEDDS), the complex without the SNEDDS (APC), the physical mixture of AmB and MAPC (AmB/MAPC PM), and crystalline AmB alone (AmB). Overall, the present in vitro results suggest that integrating the APC into an infant friendly SNEDDS is a promising approach for oral delivery of AmB to young pediatric patients.

Biliary atresia in preterm infants: a single center experience and review of literature.

Introduction: The diagnosis of biliary atresia (BA) remains challenging, and there is still uncertainty regarding the optimal time to perform a Kasai portoenterostomy (KPE). Little is known about the difficulties in the diagnosis and outcomes of BA in preterm infants (PBA). This study, which represents the first Italian report of preterm infants with BA, aims to describe a single-center experience of BA in preterm newborns. Methods: We retrospectively reviewed all infants consecutively diagnosed with BA who underwent a Kasai procedure at the Bambino Gesù Children's Hospital between January 1998 and December 2021. Prematurity was defined as a gestational age (GA) of <37 weeks. Demographic, laboratory, and histology data were recorded, and the main outcomes considered were clearance of jaundice (COJ), native liver survival, and mortality. Results: A total of 21 PBA were compared with 117 term BA controls (TBA). The median GA of PBA was 35.1 (32-36.1) weeks, with a mean birth weight of 2,100 (1,897-2,800) g. Age at first presentation was significantly lower in PBA patients: 46 (22-68) vs. 61 (44-72) days; p = 0.02. The median age at KPE was similar between the two groups: 70 days (33 corrected) for PBA vs. 67 in TBA; p = 0.8. At the time of surgery, median serum bilirubin was lower in the PBA group (7.7 vs. 8.6 mg/dl, p = 0.04). Similarly, the median APRi at the time of KPE was lower but not significant in the PBA group: 1.09 vs. 1.16; p = 0.8. No differences were found in terms of COJ between the PBA and TBA groups: n = 9 (43%) vs. 34 (35%); p = 0.2. Overall native liver survival was similar between the two groups: 8.6 (4.8-12.2) for the PBA group vs. 7.6 (5.6-9.5) years for the TBA group with no significant differences; p = 0.45. Post-KPE native liver survival was similar between the two groups: 38% vs. 52% at 5 years for the TBA and PBA groups, respectively; p = 0.54. Conclusion: The PBA and TBA groups appear to have similar outcomes in terms of COJ, overall native liver survival, and 5-year liver survival. Considering the corrected GA, early KPE is related to lower cholestatic damage. Further multicenter studies are required.

Subgroup analysis of phase 2 study of ceftolozane/tazobactam in neonates and young infants with pyelonephritis.

Ceftolozane/tazobactam is approved for the treatment of patients from birth to <18 y old with complicated urinary tract infections (cUTI). This post hoc analysis evaluated the safety, efficacy, and pharmacokinetics (PK) of ceftolozane/tazobactam compared with meropenem in neonates and young infants. NCT03230838 was a phase 2, randomized, active comparator-controlled, double-blind study of patients from birth to <18 y of age with cUTI, including pyelonephritis, given ceftolozane/tazobactam or meropenem in a 3:1 ratio. This subset analysis included only neonates and young infants < 3 mo of age. The microbiologic modified intent-to-treat population (mMITT) included 20 patients (ceftolozane/tazobactam, n = 14; meropenem, n = 6). All patients had pyelonephritis at baseline; two patients in each treatment group had bacteremia (overall 4/20, 20%). Escherichia coli was the most common baseline pathogen (overall 16/20, 80%). Safety and efficacy results were similar between treatment groups and consistent with the overall pediatric population. There were no serious drug-related adverse events (AEs), no discontinuations due to AEs, and no AEs leading to death in either treatment group. For the ceftolozane/tazobactam and meropenem treatment groups, clinical cure rates in the mMITT population were 92.9% and 100%, respectively. The population PK analysis of neonates and young infants demonstrated similar ceftolozane and tazobactam exposures to those of adults, achieving pharmacodynamic targets associated with clinical and microbiologic cure. Ceftolozane/tazobactam has a favorable safety profile and achieves high clinical cure and microbiologic eradication rates in neonates and young infants < 3 mo of age with cUTI and pyelonephritis. IMPORTANCE Extrapolation of antibacterial agent pharmacokinetics from adults to newborns and young infants may not be appropriate; similarly, the clinical manifestations of infectious diseases and outcomes following antibacterial treatment may not be similar. Ceftolozane/tazobactam is an antibacterial drug combination active against Pseudomonas aeruginosa and other multidrug-resistant gram-negative bacteria. A clinical study led to the approval for ceftolozane/tazobactam in patients from birth to 18 y of age who have complicated urinary tract infections, including those with serious kidney infections. Based on data collected during that clinical study, we compared newborns and young infants who were treated with ceftolozane/tazobactam (14 patients) and those who were treated with meropenem (6 patients). We found that ceftolozane/tazobactam treatment of newborns and young infants up to 3 mo of age who have complicated urinary tract infections demonstrated a favorable safety profile and high clinical cure and microbiologic eradication rates, similar to meropenem.

Perception of care givers regarding danger signs of illness and practices followed in young infants (0-2 months) as per IMNCI at selected areas of Amritsar, Punjab: A qualitative study.

Background: In India, neonatal mortality contributes to over 64% of infant deaths, mostly occurring during the first week of life. Mortality rate in second month of life is also higher than at later ages. Delay in identification of warning signs of neonatal illness naturally postpones the initiation of treatment and referral to hospital. Materials and Methods: The study aimed to explore the perception of care givers regarding danger signs of illness and practices followed in young infants. Care givers who cared for the sick young infants during last six months were recruited using a convenient sampling technique and qualitative research approach. Five semi-structured interviews and one FGD were conducted using an interview and FGD guide. Data was analyzed manually by reading and rereading the transcribed verbatim leading to the emergence of themes, subthemes, and codes. Results: Data explored that excessive crying was perceived as a danger sign by entire mothers, and many of them were unable to recognize important warning signs. The delay in decision making for medical care-seeking also shows dwindling awareness. Additionally, mothers were adapting few unhygienic practices as home remedies leading to worsening the symptoms and making a call for additional infections which needs to be addressed by the health authorities at community level. Conclusion: Pronounced efforts are expected to raise mindfulness of mothers toward the significance of early identification of neonatal danger signs to stave off the high magnitude of neonatal mortality. Inclusion of excessive crying as neonatal danger sign is recommended as well.

Case Report: Two Cases of Pulmonary Artery Dissection in Young Infants.

Pulmonary artery dissection (PAD) is a rare disease. This article reports the treatment of PAD in young infants for the first time. Both cases of the infants were treated with surgery. Different surgical methods achieve different results, which provide ideas for treating PAD in young infants.