Predictive Accuracy of Infant Clinical Sign Algorithms for Mortality in Young Infants Aged 0 to 59 Days: A Systematic Review.

CONTEXT: Clinical sign algorithms are a key strategy to identify young infants at risk of mortality. OBJECTIVE: Synthesize the evidence on the accuracy of clinical sign algorithms to predict all-cause mortality in young infants 0-59 days. DATA SOURCES: MEDLINE, Embase, CINAHL, Global Index Medicus, and Cochrane CENTRAL Registry of Trials. STUDY SELECTION: Studies evaluating the accuracy of infant clinical sign algorithms to predict mortality. DATA EXTRACTION: We used Cochrane methods for study screening, data extraction, and risk of bias assessment. We determined certainty of evidence using Grading of Recommendations Assessment Development and Evaluation. RESULTS: We included 11 studies examining 26 algorithms. Three studies from non-hospital/community settings examined sign-based checklists (n = 13). Eight hospital-based studies validated regression models (n = 13), which were administered as weighted scores (n = 8), regression formulas (n = 4), and a nomogram (n = 1). One checklist from India had a sensitivity of 98% (95% CI: 88%-100%) and specificity of 94% (93%-95%) for predicting sepsis-related deaths. However, external validation in Bangladesh showed very low sensitivity of 3% (0%-10%) with specificity of 99% (99%-99%) for all-cause mortality (ages 0-9 days). For hospital-based prediction models, area under the curve (AUC) ranged from 0.76-0.93 (n = 13). The Score for Essential Neonatal Symptoms and Signs had an AUC of 0.89 (0.84-0.93) in the derivation cohort for mortality, and external validation showed an AUC of 0.83 (0.83-0.84). LIMITATIONS: Heterogeneity of algorithms and lack of external validation limited the evidence. CONCLUSIONS: Clinical sign algorithms may help identify at-risk young infants, particularly in hospital settings; however, overall certainty of evidence is low with limited external validation.

Efficacy of Antibiotic Regimens for Pneumonia in Young Infants Aged 0-59 Days: A Systematic Review.

CONTEXT: Pneumonia is a leading cause of death in young infants. OBJECTIVES: To evaluate the efficacy of different antibiotic regimens to treat young infant pneumonia on critical clinical outcomes. DATA SOURCES: MEDLINE, Embase, CINAHL, World Health Organization (WHO) Global Index Medicus, Cochrane Central Registry of Trials. STUDY SELECTION: We included randomized controlled trials of young infants aged 0 to 59 days with pneumonia (population) comparing the efficacy of antibiotic regimens (intervention) with alternate regimens or management (control) on clinical outcomes. DATA EXTRACTION: We extracted data and assessed risk of bias in duplicate. We used Grading of Recommendations, Assessment, Development, and Evaluation to assess certainty of evidence. LIMITATIONS: Trials were heterogeneous, which precluded data pooling. RESULTS: Of 2601 publications screened, 10 randomized controlled trials were included. Seven trials were hospital-based (n = 869) and 3 were nonhospital-based (n = 4329). No hospital-based trials evaluated WHO-recommended first-choice regimens. One trial found the WHO-recommended second-choice antibiotic, cefotaxime, to have similar rates of treatment success as non-WHO-recommended regimens of either amoxicillin-clavulanate (RR 0.99, 95% confidence interval 0.82-1.10) or amoxicillin-clavulanate/cefotaxime (RR 1.02, 95% confidence interval 0.86-1.12). Among 3 nonhospital-based trials comparing oral amoxicillin to alternate regimens to treat isolated tachypnea among infants aged 7-59 days, there were no differences in treatment failure between amoxicillin and alternate regimens. Certainty of evidence was low or very low for all primary outcomes. CONCLUSIONS: We found limited evidence to support the superiority of any single antibiotic regimen over alternate regimens to treat young infant pneumonia.

Efficacy of Antibiotic Regimens for Meningitis in Young Infants Aged 0-59 Days: A Systematic Review.

CONTEXT: Meningitis is associated with high mortality risk in young infants, yet the optimal treatment regimen is unclear. OBJECTIVES: To systematically evaluate the efficacy of antibiotic regimens to treat meningitis in young infants aged 0 to 59 days on critical clinical outcomes. DATA SOURCES: MEDLINE, Embase, CINAHL, WHO Global Index Medicus, and Cochrane Central Registry of Trials. STUDY SELECTION: We included randomized controlled trials (RCTs) of young infants with meningitis (population) comparing the efficacy of antibiotic regimens (interventions) with alternate regimens (control) on clinical outcomes. DATA EXTRACTION: We extracted data on study characteristics and assessed risk of bias in duplicate. Grading of Recommendations Assessment, Development, and Evaluation was used to assess certainty of evidence. RESULTS: Of 1088 studies screened, only 2 RCTs were identified. They included 168 infants from 5 countries and were conducted between 1976 and 2015. Neither study compared current World Health Organization-recommended regimens. One multisite trial from 4 countries compared intrathecal gentamicin plus systemic ampicillin/gentamicin to systemic ampicillin/gentamicin and found no difference in mortality (relative risk, 0.88; 95% confidence interval, 0.41-1.53; 1 trial, n = 98, very low certainty of evidence) or adverse events (no events in either trial arm). Another trial in India compared a 10-day versus 14-day course of antibiotics and found no difference in mortality (relative risk, 0.88; 95% confidence interval, 0.41-1.53; 1 trial, n = 98, very low certainty of evidence) or other outcomes. CONCLUSIONS: Trial data on the efficacy of antibiotic regimens in young infant meningitis are scarce. Rigorous RCTs are needed to inform recommendations for optimal antibiotic regimens for meningitis treatment in this vulnerable population, particularly within the context of changing epidemiology and increasing antimicrobial resistance.

Global Management of Serious Bacterial Infections in Young Infants Aged 0 to 59 Days: An Overview of Systematic Reviews.

BACKGROUND: To inform World Health Organization guidelines for the management of serious bacterial infection (SBI) (suspected or confirmed sepsis, pneumonia, or meningitis) in infants aged 0-59 days. OBJECTIVE: To conduct an "overview of systematic reviews" to: (1) understand which systematic reviews have examined diagnosis and management of SBI in infants aged 0-59 days in the last 5 years; and (2) assess if the reviews examined PICOs (population, intervention, comparator, outcomes) and regimens currently being recommended in low and middle income countries (LMICs) by the World Health Organization. DATA SOURCES: MEDLINE; Embase; Cochrane Library; Epistemonikos; PROSPERO. STUDY SELECTION: Systematic reviews of randomized controlled trials or observational studies of infants aged 0-59 days examining diagnostic accuracy and antibiotic regimens for SBI from January 1, 2018 to November 3, 2023. DATA EXTRACTION: Dual independent extraction of study characteristics, PICOs, and methodological quality. RESULTS: Nine systematic reviews met our criteria. Two reviews examined diagnostic accuracy for sepsis, and no reviews examined pneumonia or meningitis. Five reviews examined antibiotic effectiveness (sepsis [n = 4]; pneumonia [n = 1]), and no reviews examined meningitis. One review examined antibiotic duration for sepsis and one for meningitis, and no reviews for pneumonia. Only 4 of the 9 systematic reviews met criteria for high-quality. LIMITATIONS: Our review was limited to the last 5 years to inform current guideline updates. CONCLUSIONS: Few studies have examined antibiotic regimens currently being used in LMICs and quality is of concern in many studies. More high-quality data are needed to inform management of SBI in newborns, especially in LMICs.

Efficacy of Antibiotic Regimens for Sepsis or Possible Serious Bacterial Infection in Young Infants Aged 0 to 59 Days: A Systematic Review and Meta-analysis.

CONTEXT: Sepsis is a leading cause of young infant mortality. OBJECTIVE: To evaluate the efficacy of different antibiotic regimens to treat young infant sepsis or possible serious bacterial infection (PSBI) on clinical outcomes. DATA SOURCES: MEDLINE, Embase, CINAHL, World Health Organization Global Index Medicus, Cochrane Central Registry of Trials. STUDY SELECTION: We included randomized controlled trials (RCTs) of young infants 0 to 59 days with sepsis or PBSI (population) comparing the efficacy of antibiotic regimens (intervention) with alternate regimens or management (control) on clinical outcomes. DATA EXTRACTION: We extracted data and assessed risk of bias in duplicate. We performed random-effects meta-analysis, and used Grading of Recommendations, Assessment, Development, and Evaluation to assess certainty of evidence. RESULTS: Of 2390 publications, we included 41 RCTs (n = 18 054). Thirty-five trials were hospital-based and 6 were nonhospital-based. Meta-analysis of 4 trials demonstrated similar rates of treatment success with intramuscular/intravenous third generation cephalosporins versus intramuscular/intravenous penicillin or ampicillin + gentamicin (RR 1.03, 95% CI 0.93-1.13]; n = 1083; moderate certainty of evidence). Meta-analysis of 3 trials demonstrated similar rates of treatment failure with oral amoxicillin + intramuscular gentamicin versus intramuscular penicillin + gentamicin for nonhospital treatment of clinical severe illness (RR 0.86, 95% CI 0.72-1.02]; n = 5054; low certainty of evidence). Other studies were heterogeneous. LIMITATIONS: RCTs evaluated heterogeneous regimens, limiting our ability to pool data. CONCLUSIONS: We found limited evidence to support any single antibiotic regimen as superior to alternate regimens to treat young infant sepsis or PSBI.

Diagnostic Accuracy of Clinical Sign Algorithms to Identify Sepsis in Young Infants Aged 0 to 59 Days: A Systematic Review and Meta-analysis.

CONTEXT: Accurate identification of possible sepsis in young infants is needed to effectively manage and reduce sepsis-related morbidity and mortality. OBJECTIVE: Synthesize evidence on the diagnostic accuracy of clinical sign algorithms to identify young infants (aged 0-59 days) with suspected sepsis. DATA SOURCES: MEDLINE, Embase, CINAHL, Global Index Medicus, and Cochrane CENTRAL Registry of Trials. STUDY SELECTION: Studies reporting diagnostic accuracy measures of algorithms including infant clinical signs to identify young infants with suspected sepsis. DATA EXTRACTION: We used Cochrane methods for study screening, data extraction, risk of bias assessment, and determining certainty of evidence using Grading of Recommendations Assessment Development and Evaluation. RESULTS: We included 19 studies (12 Integrated Management of Childhood Illness [IMCI] and 7 non-IMCI studies). The current World Health Organization (WHO) 7-sign IMCI algorithm had a sensitivity of 79% (95% CI 77%-82%) and specificity of 77% (95% CI 76%-78%) for identifying sick infants aged 0-59 days requiring hospitalization/antibiotics (1 study, N = 8889). Any IMCI algorithm had a pooled sensitivity of 84% (95% CI 75%-90%) and specificity of 80% (95% CI 64%-90%) for identifying suspected sepsis (11 studies, N = 15523). When restricting the reference standard to laboratory-supported sepsis, any IMCI algorithm had a pooled sensitivity of 86% (95% CI 82%-90%) and lower specificity of 61% (95% CI 49%-72%) (6 studies, N = 14278). LIMITATIONS: Heterogeneity of algorithms and reference standards limited the evidence. CONCLUSIONS: IMCI algorithms had acceptable sensitivity for identifying young infants with suspected sepsis. Specificity was lower using a reference standard of laboratory-supported sepsis diagnosis.

Target product profile: aerosolized surfactant for neonatal respiratory distress.

Treatment with surfactant has been found to improve the survival rate of neonates with respiratory distress syndrome, particularly preterm infants. However, surfactant is usually administered by endotracheal intubation and generally only in level-3 neonatal intensive care units. Recent improvements in aerosolization technology have raised the possibility that aerosolized surfactant could now be given in wider range of settings, including resource-poor settings. Consequently, the World Health Organization has developed a target product profile for product developers that describes the optimal and minimal characteristics of an aerosolized surfactant for treating neonates with respiratory distress syndrome in low- and middle-income countries. Development of the target product profile involved a scoping review of systematic reviews and target product profiles of aerosolized surfactant, the constitution of an international expert advisory group, consultations with medical professionals from a wide range of countries and a public consultation. The resulting target product profile specifies that the surfactant and its associated aerosolization device should ideally, among other characteristics: (i) be at least as safe and effective as current intratracheal surfactant; (ii) produce a rapid clinical improvement; (iii) be easy to transport and use (e.g. by nurses in level-2 health-care facilities in low- and middle-income countries); (iv) be affordable for low- and middle-income countries; and (v) be stable when stored in hot and humid conditions. In addition, the aerosolization device should be capable of daily use for many years. The introduction of an effective aerosolized surfactant globally could substantially reduce neonatal mortality due to respiratory distress syndrome.

Le traitement par surfactant permet d'améliorer le taux de survie des nouveau-nés souffrant d'un syndrome de détresse respiratoire, en particulier les nourrissons prématurés. Pourtant, ce surfactant est généralement administré par intubation endotrachéale et, la plupart du temps, uniquement dans les unités de soins intensifs néonatals de niveau 3. Les récents progrès réalisés dans le domaine des technologies d'aérosolisation laissent entrevoir la possibilité d'administrer dorénavant un surfactant en aérosol dans d'autres cadres, y compris dans des lieux où les ressources sont limitées. L'Organisation mondiale de la Santé a donc développé un profil de produit cible à l'attention des laboratoires, qui détaille les caractéristiques minimales et optimales d'un surfactant en aérosol destiné à la prise en charge des nouveau-nés souffrant d'un syndrome de détresse respiratoire dans les pays à revenu faible et intermédiaire. Ce document est le fruit d'une analyse exploratoire de revues systématiques et de profils de surfactants en aérosol; un groupe consultatif d'experts internationaux a été constitué, des professionnels de la santé originaires de nombreux pays ont été sollicités, et une consultation publique a été organisée. Le profil de produit cible qui en résulte précise que le surfactant et son dispositif d'aérosolisation doivent idéalement présenter une série de caractéristiques, notamment: (i) être au moins aussi sûrs et efficaces que le surfactant intratrachéal actuel; (ii) entraîner une amélioration clinique rapide; (iii) être faciles à transporter et à utiliser (par exemple par le personnel infirmier de niveau 2, au sein d'établissements de santé dans des pays à revenu faible et intermédiaire); (iv) être abordables pour les pays à revenu faible et intermédiaire; et enfin, (v) demeurer stables quand ils sont stockés dans un environnement chaud et humide. En outre, le dispositif d'aérosolisation doit pouvoir être employé au quotidien pendant plusieurs années. Le lancement d'un surfactant en aérosol à l'échelle mondiale pourrait réduire considérablement la mortalité néonatale due au syndrome de détresse respiratoire.

Se ha observado que el tratamiento con sustancias tensioactivas mejora la tasa de supervivencia de los neonatos con síndrome de dificultad respiratoria, especialmente los prematuros. Sin embargo, la sustancia tensioactiva suele administrarse mediante intubación endotraqueal y, por lo general, solo en unidades de cuidados intensivos neonatales de nivel 3. Las mejoras recientes en la tecnología de aerosolización han planteado la posibilidad de que la sustancia tensioactiva en aerosol se pueda administrar ahora en más entornos, incluidos los de escasos recursos. En consecuencia, la Organización Mundial de la Salud ha desarrollado un perfil de producto específico para los desarrolladores de productos que describe las características óptimas y mínimas de una sustancia tensioactiva en aerosol para el tratamiento de neonatos con síndrome de dificultad respiratoria en países de ingresos bajos y medios. El desarrollo del perfil de producto específico implicó una revisión del alcance de las revisiones sistemáticas y los perfiles de producto específicos de la sustancia tensioactiva en aerosol, la constitución de un grupo asesor internacional de expertos, consultas con profesionales médicos de diversos países y una consulta pública. El perfil de producto específico obtenido indica que lo ideal sería que la sustancia tensioactiva y su dispositivo de aerosolización asociado tuvieran, entre otras, las siguientes características: (i) ser al menos tan seguros y eficaces como la sustancia tensioactiva intratraqueal actual; (ii) producir una mejora clínica rápida; (iii) ser fáciles de transportar y utilizar (p. ej. por el personal de enfermería de los centros sanitarios de nivel 2 de los países de ingresos bajos y medios); (iv) ser asequibles para los países de ingresos bajos y medios; y (v) ser estables cuando se almacenan en condiciones de calor y humedad. Además, el dispositivo de aerosolización se debería poder utilizar a diario durante muchos años. La introducción de una sustancia tensioactiva en aerosol eficaz a nivel mundial podría reducir de manera sustancial la mortalidad neonatal causada por el síndrome de dificultad respiratoria.

Effect of early childhood development interventions delivered by healthcare providers to improve cognitive outcomes in children at 0-36 months: a systematic review and meta-analysis.

OBJECTIVE: To determine the effect of early childhood development interventions delivered by healthcare providers (HCP-ECD) on child cognition and maternal mental health. DESIGN: Systematic review, meta-analysis. SETTING: Healthcare setting or home. PARTICIPANTS: Infants under 1 month of age. INTERVENTIONS: HCP-ECD interventions that supported responsive caregiving, early learning and motor stimulation. MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Health Technology Assessment Database, Database of Abstracts of Reviews of Effects and Cochrane Database of Systematic Reviews were searched until 15 November 2021. Studies reporting prespecified outcomes were pooled using standard meta-analytical methods. MAIN OUTCOME MEASURES: Cognitive development in children at 0-36 months. RESULTS: Forty-two randomised controlled trials with 15 557 infants were included in the narrative synthesis. Twenty-seven trials were included in the meta-analyses. Pooled data from 13 trials suggest that HCP-ECD interventions may improve cognitive outcomes in children between 0 and 36 months (Bayley Scales of Infant Development version IIII (BSID-III) mean difference (MD) 2.65; 95% CI 0.61 to 4.70; 2482 participants; low certainty of evidence). Pooled data from nine trials suggest improvements in motor development (BSID-III MD 4.01; 95% CI 1.54 to 6.48; 1437 participants; low certainty of evidence). There was no evidence of improvement in maternal mental health (standardised MD -0.13; 95% CI -0.28 to 0.03; 2806 participants; 11 trials; low certainty of evidence). CONCLUSIONS: We report promising evidence, particularly for cognitive and motor outcomes, of the effect of HCP-ECD interventions. However, effect sizes were small, and the certainty of evidence ranged from very low to moderate. Additional high-quality research is required. PROSPERO REGISTRATION NUMBER: CRD42019122021.

Perspectives of health service providers in delivering best-practice care for Aboriginal mothers and their babies during the postnatal period.

BACKGROUND: Evidence suggests that Aboriginal babies in Western Australia are not receiving adequate primary health care in their first 3 months of life, leading to questions about enablers and constraints to delivering such care. This paper presents findings from a qualitative research project investigating health providers' perceptions and experiences of best and current practice in discharge planning, postnatal care and health education for Aboriginal mothers and their newborn babies. METHODS: Constructivist grounded theory guided this research involving 58 semi-structured interviews conducted with health providers who deliver care to Aboriginal mothers and infants. Participants were recruited from hospital-based and primary health sites in metropolitan Perth, and regional and remote locations in Western Australia. RESULTS: Structural factors enabling best practice in discharge planning, postnatal care, and health education for mothers included health providers following best practice guidelines and adequate staffing levels. Organisational enablers included continuity of care throughout pregnancy, birth and postnatally. In particular, good communication between services around discharge planning, birth notifications, and training in culturally respectful care. Structural and organisational constraints to delivering best practice and compromising continuity of care were identified as beyond individual control. These included poor communication between different health and social services, insufficient hospital staffing levels leading to early discharge, inadequate cultural training, delayed receipt of birth notifications and discharge summaries received by Aboriginal primary health services. CONCLUSION: Findings highlight the importance of examining current policies and practices to promote best practice in postnatal care to improve health outcomes for mothers and their Aboriginal babies.

Family-centred interventions for Indigenous early childhood well-being by primary healthcare services.

BACKGROUND: Primary healthcare, particularly Indigenous-led services, are well placed to deliver services that reflect the needs of Indigenous children and their families. Important characteristics identified by families for primary health care include services that support families, accommodate sociocultural needs, recognise extended family child-rearing practices, and Indigenous ways of knowing and doing business. Indigenous family-centred care interventions have been developed and implemented within primary healthcare services to plan, implement, and support the care of children, immediate and extended family and the home environment. The delivery of family-centred interventions can be through environmental, communication, educational, counselling, and family support approaches. OBJECTIVES: To evaluate the benefits and harms of family-centred interventions delivered by primary healthcare services in Canada, Australia, New Zealand, and the USA on a range of physical, psychosocial, and behavioural outcomes of Indigenous children (aged from conception to less than five years), parents, and families. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 22 September 2021. SELECTION CRITERIA: We included randomised controlled trials (RCTs), cluster RCTs, quasi-RCTs, controlled before-after studies, and interrupted time series of family-centred care interventions that included Indigenous children aged less than five years from Canada, Australia, New Zealand, and the USA. Interventions were included if they met the assessment criteria for family-centred interventions and were delivered in primary health care. Comparison interventions could include usual maternal and child health care or one form of family-centred intervention versus another. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. overall health and well-being, 2. psychological health and emotional behaviour of children, 3. physical health and developmental health outcomes of children, 4. family health-enhancing lifestyle or behaviour outcomes, 5. psychological health of parent/carer. 6. adverse events or harms. Our secondary outcomes were 7. parenting knowledge and awareness, 8. family evaluation of care, 9. service access and utilisation, 10. family-centredness of consultation processes, and 11. economic costs and outcomes associated with the interventions. We used GRADE to assess the certainty of the evidence for our primary outcomes. MAIN RESULTS: We included nine RCTs and two cluster-RCTs that investigated the effect of family-centred care interventions delivered by primary healthcare services for Indigenous early child well-being. There were 1270 mother-child dyads and 1924 children aged less than five years recruited. Seven studies were from the USA, two from New Zealand, one from Canada, and one delivered in both Australia and New Zealand. The focus of interventions varied and included three studies focused on early childhood caries; three on childhood obesity; two on child behavioural problems; and one each on negative parenting patterns, child acute respiratory illness, and sudden unexpected death in infancy. Family-centred education was the most common type of intervention delivered. Three studies compared family-centred care to usual care and seven studies provided some 'minimal' intervention to families such as education in the form of pamphlets or newsletters. One study provided a minimal intervention during the child's first 24 months and then the family-centred care intervention for one year. No studies had low or unclear risk of bias across all domains. All studies had a high risk of bias for the blinding of participants and personnel domain. Family-centred care may improve overall health and well-being of Indigenous children and their families, but the evidence was very uncertain. The pooled effect estimate from 11 studies suggests that family-centred care improved the overall health and well-being of Indigenous children and their families compared no family-centred care (standardised mean difference (SMD) 0.14, 95% confidence interval (CI) 0.03 to 0.24; 2386 participants). We are very uncertain whether family-centred care compared to no family-centred care improves the psychological health and emotional behaviour of children as measured by the Infant Toddler Social Emotional Assessment (ITSEA) (Competence domain) (mean difference (MD) 0.04, 95% CI -0.03 to 0.11; 2 studies, 384 participants). We assessed the evidence as being very uncertain about the effect of family-centred care on physical health and developmental health outcomes of children. Pooled data from eight trials on physical health and developmental outcomes found there was little to no difference between the intervention and the control groups (SMD 0.13, 95% CI -0.00 to 0.26; 1961 participants). The evidence is also very unclear whether family-centred care improved family-enhancing lifestyle and behaviours outcomes. Nine studies measured family health-enhancing lifestyle and behaviours and pooled analysis found there was little to no difference between groups (SMD 0.16, 95% CI -0.06 to 0.39; 1969 participants; very low-certainty evidence). There was very low-certainty evidence of little to no difference for the psychological health of parents and carers when they participated in family-centred care compared to any control group (SMD 0.10, 95% CI -0.03 to 0.22; 5 studies, 975 parents/carers). Two studies stated that there were no adverse events as a result of the intervention. No additional data were provided. No studies reported from the health service providers perspective or on outcomes for family's evaluation of care or family-centredness of consultation processes. AUTHORS' CONCLUSIONS: There is some evidence to suggest that family-centred care delivered by primary healthcare services improves the overall health and well-being of Indigenous children, parents, and families. However, due to lack of data, there was not enough evidence to determine whether specific outcomes such as child health and development improved as a result of family-centred interventions. Seven of the 11 studies delivered family-centred education interventions. Seven studies were from the USA and centred on two particular trials, the 'Healthy Children, Strong Families' and 'Family Spirit' trials. As the evidence is very low certainty for all outcomes, further high-quality trials are needed to provide robust evidence for the use of family-centred care interventions for Indigenous children aged less than five years.

Effectiveness of universal newborn hearing screening: A systematic review and meta-analysis.

Background: Permanent bilateral hearing loss (PBHL) is a serious condition in newborns, with a prevalence of at least one per 1000 live births. However, there has been no recent systematic review and meta-analysis of the effectiveness of universal newborn hearing screening programs (UNHS). Methods: We registered our study protocol on PROSPERO CRD42020175451. Primary outcomes were any identification of PBHL (ie, PBHL diagnosed at any time), age of identification of PBHL, and neurodevelopment. Two reviewers searched standard databases to March 2022 and extracted data. We used fixed and random effects meta-analysis to pool data and graded the certainty of evidence using standard methods. Results: The search retrieved 2834 records. We identified five studies reporting on the effects of UNHS vs no UNHS in 1 023 610 newborns. The relative risk of being identified with PBHL before nine months in infants with UNHS compared to infants without UNHS was 3.28 (95% confidence interval (95% CI) = 1.84, 5.85, one study, 1 023 497 newborns, low certainty evidence). The mean difference in the age of identification of PBHL in infants with UNHS compared to infants without UNHS was 13.2 months earlier (95% CI = -26.3, -0.01, two studies, 197 newborns, very low certainty evidence). The relative risk of infants eventually being identified with PBHL in infants with UNHS compared to infants without UNHS was 1.01 (95% CI = 0.89, 1.14, three studies, 1 023 497 newborns, low certainty evidence). At the latest follow-up at 3-8 years, the standardised mean difference (SMD) in receptive language development between infants with UNHS compared to infants without UNHS was 0.60 z scores (95% CI = 0.07, 1.13, one study, 101 children, low certainty evidence) and the mean difference in developmental quotients was 7.72 (95% CI = -0.03, 15.47, three studies, 334 children, very low certainty evidence). The SMD in expressive language development was 0.39 z scores (95% CI = -0.20, 0.97, one study, 87 children, low certainty evidence) and the mean difference in developmental quotients was 10.10 scores (95% CI = 1.47, 18.73, 3 studies, 334 children, very low certainty evidence). Conclusions: UNHS programs result in earlier identification of PBHL and may improve neurodevelopment. UNHS should be implemented across high-, middle-, and low-income countries. Registration: PROSPERO (CRD42020175451).

Enteral Multiple Micronutrient Supplementation in Preterm and Low Birth Weight Infants: A Systematic Review and Meta-analysis.

OBJECTIVES: To assess effects of supplementation with 3 or more micronutrients (multiple micronutrients; MMN) compared to no MMN in human milk-fed preterm and low birth weight (LBW) infants. RESULTS: Data on a subgroup of 414 preterm or LBW infants from 2 randomized controlled trials (4 reports) were included. The certainty of evidence ranged from low to very low. For growth outcomes in the MMN compared to the non-MMN group, there was a small increase in weight-for-age (2 trials, 383 participants) and height-for-age z-scores (2 trials, 372 participants); a small decrease in wasting (2 trials, 398 participants); small increases in stunting (2 trials, 399 participants); and an increase in underweight (2 trials, 396 participants). For neurodevelopment outcomes at 78 weeks, we found small increases in Bayley Scales of Infant Development, Version III (BISD-III), scores (cognition, receptive language, expressive language, fine motor, gross motor) in the MMN compared to the non-MMN group (1 trial, 27 participants). There were no studies examining dose or timing of supplementation. CONCLUSIONS: Evidence is insufficient to determine whether enteral MMN supplementation to preterm or LBW infants who are fed mother's own milk is associated with benefit or harm. More trials are needed to generate evidence on mortality, morbidity, growth, and neurodevelopment.

Family Involvement in the Routine Care of Hospitalized Preterm or Low Birth Weight Infants: A Systematic Review and Meta-analysis.

BACKGROUND AND OBJECTIVES: Preterm and low birth weight (LBW) infants are often separated from parents during hospitalization. Our objective was to assess effects of interventions to increase family involvement in the routine newborn care of preterm or LBW infants compared with standard NICU care on infant and parental outcomes. METHODS: Data sources include Medline, Embase, CINAHL, and World Health Organization Global Index Medicus to August 2021. The study selection included randomized controlled trials (RCTs) of family involvement intervention packages. Data were extracted and pooled with random-effects models. RESULTS: We included 15 RCTs with 5240 participants. All interventions included direct parental bedside care; packages varied with respect to additional components. Family involvement interventions decreased retinopathy of prematurity (odds ratio 0.52, 95% confidence interval [CI]: 0.34, 0.80; 8 RCTs), length of hospital stay (mean difference [MD] -2.91 days; 95% CI: -5.15,-0.82; 11 RCTs), and parental stress and anxiety (Parental Stress Scale: MD -0.29 points, 95% CI: -0.56,-0.01, 2 RCTs; Anxiety State-Trait scale: MD -1.79, 95% CI: -3.11,-0.48; 2 RCTs). Family involvement increased weight gain velocity (MD 2.09 g/day; 95% CI: 1.27, 2.91; 3 RCTs), neurobehavioral exam scores (MD: 1.11; 95% CI: 0.21, 2.01; 2 RCTs) and predominant or exclusive breastmilk intake (odds ratio 1.34; 95% CI: 1.01, 1.65; 3 RCTs). It may decrease rates of bronchopulmonary dysplasia, infection, and intraventricular hemorrhage. There were no effects on mortality or necrotizing enterocolitis. Certainty of evidence ranged from low to moderate. CONCLUSIONS: Family involvement has a beneficial role on several infant and parental outcomes.

Early Enteral Feeding for Preterm or Low Birth Weight Infants: a Systematic Review and Meta-analysis.

CONTEXT: Early enteral feeding has been associated with adverse outcomes such as necrotizing enterocolitis in preterm and low birth weight infants. OBJECTIVES: To assess effects of early enteral feeding initiation within the first days after birth compared to delayed initiation. DATA SOURCES: Medline, Scopus, Web of Science, CINAHL from inception to June 30, 2021. STUDY SELECTION: Randomized trials (RCTs) were included. Primary outcomes were mortality, morbidity, growth, neurodevelopment, feed intolerance, and duration of hospitalization. DATA EXTRACTION: Data were extracted and pooled with random-effects models. RESULTS: We included 14 randomized controlled trials with 1505 participants in our primary analysis comparing early (<72 hours) to delayed (≥72 hours) enteral feeding initiation. Early initiation likely decreased mortality at discharge and 28 days (1292 participants, 12 trials, relative risk 0.69, 95% confidence interval [95% CI] 0.48-0.99, moderate certainty evidence) and duration of hospitalization (1100 participants, 10 trials, mean difference -3.20 days, 95%CI -5.74 to -0.66, moderate certainty evidence). The intervention may also decrease sepsis and weight at discharge. Based on low certainty evidence, early feeding may have little to no effect on necrotizing enterocolitis, feed intolerance, and days to regain birth weight. The evidence is very uncertain regarding the effect of initiation time on intraventricular hemorrhage, length, and head circumference at discharge. CONCLUSIONS: Enteral feeding within 72 hours after birth likely reduces the risk of mortality and length of hospital stay, may reduce the risk of sepsis, and may reduce weight at discharge.

Mother's Own Milk Compared With Formula Milk for Feeding Preterm or Low Birth Weight Infants: Systematic Review and Meta-analysis.

OBJECTIVES: We assessed the effect of feeding preterm or low birth weight infants with infant formula compared with mother's own milk on mortality, morbidity, growth, neurodevelopment, and disability. METHODS: We searched Medline (Ovid), Embase (Ovid), and Cochrane Central Register of Controlled Studies to October 1, 2021. RESULTS: Forty-two studies enrolling 89 638 infants fulfilled the inclusion criteria. We did not find evidence of an effect on mortality (odds ratio [OR] 1.26, 95% confidence interval [CI] 0.91-1.76), infection (OR 1.52, 95% CI 0.98-2.37), cognitive neurodevelopment (standardized mean difference -1.30, 95% CI -3.53 to 0.93), or on growth parameters. Formula milk feeding increased the risk of necrotizing enterocolitis (OR 2.99, 95% CI 1.75-5.11). The Grading of Recommendations Assessment, Development, and Evaluation certainty of evidence was low for mortality and necrotizing enterocolitis, and very low for neurodevelopment and growth outcomes. CONCLUSIONS: In preterm and low birth weight infants, low to very low-certainty evidence indicates that feeding with infant formula compared with mother's own milk has little effect on all-cause mortality, infection, growth, or neurodevelopment, and a higher risk of developing necrotizing enterocolitis.