Risk and rates of hospitalisation in young children: A prospective study of a South African birth cohort.

Children in sub-Saharan Africa (SSA) are disproportionately affected by morbidity and mortality. There is also a growing vulnerable population of children who are HIV-exposed uninfected (HEU). Understanding reasons and risk factors for early-life child hospitalisation will help optimise interventions to improve health outcomes. We investigated hospitalisations from birth to two years in a South African birth cohort study. Mother-child pairs in the Drakenstein Child Health Study were followed from birth to two years with active surveillance for hospital admission and investigation of aetiology and outcome. Incidence, duration, cause, and factors associated with child hospitalisation were investigated, and compared between HEU and HIV-unexposed uninfected (HUU) children. Of 1136 children (247 HEU; 889 HUU), 314 (28%) children were hospitalised in 430 episodes despite >98% childhood vaccination coverage. The highest hospitalisation rate was from 0-6 months, decreasing thereafter; 20% (84/430) of hospitalisations occurred in neonates at birth. Amongst hospitalisations subsequent to discharge after birth, 83% (288/346) had an infectious cause; lower respiratory tract infection (LRTI) was the most common cause (49%;169/346) with respiratory syncytial virus (RSV) responsible for 31% of LRTIs; from 0-6 months, RSV-LRTI accounted for 22% (36/164) of all-cause hospitalisations. HIV exposure was associated with increased incidence rates of hospitalisation in infants (IRR 1.63 [95% CI 1.29-2.05]) and longer hospital admission (p = 0.004). Prematurity (HR 2.82 [95% CI 2.28-3.49]), delayed infant vaccinations (HR 1.43 [95% CI 1.12-1.82]), or raised maternal HIV viral load in HEU infants were risk factors for hospitalisation; breastfeeding was protective (HR 0.69 [95% CI 0.53-0.90]). In conclusion, children in SSA experience high rates of hospitalisation in early life. Infectious causes, especially RSV-LRTI, underly most hospital admissions. HEU children are at greater risk of hospitalisation in infancy compared to HUU children. Available strategies such as promoting breastfeeding, timely vaccination, and optimising antenatal maternal HIV care should be strengthened. New interventions to prevent RSV may have additional impact in reducing hospitalisation.

Latent Classes of Anthropometric Growth in Early Childhood Using Uni- and Multivariate approaches in a South African Birth Cohort.

Background: Conventional methods for modelling longitudinal growth data focus on the analysis of mean longitudinal trends or the identification of abnormal growth based on cross-sectional standardized z-scores. Latent Class Mixed Modelling (LCMM) considers the underlying heterogeneity in growth profiles and allows for the identification of groups of subjects that follow similar longitudinal trends. Methods: LCMM was used to identify underlying latent profiles of growth for univariate responses of standardized height, standardized weight, standardized body mass index and standardized weight-for-length/height measurements and multivariate response of joint standardized height and standardized weight measurements from birth to five years for a sample of 1143 children from a South African birth cohort, the Drakenstein Child Health Study (DCHS). Allocations across latent growth classes were compared to better understand the differences and similarities across the classes identified given different composite measures of height and weight as input. Results: Four classes of growth within standardized height (n1=516, n2=112, n3=187, n4=321) and standardized weight (n1=263, n2=150, n3=584, n4=142), three latent growth classes within Body Mass Index (BMI) (n1=481, n2=485, n3=149) and Weight for length/height (WFH) (n1=321, n2=710, n3=84) and five latent growth classes within the multivariate response of standardized height and standardized weight (n1=318, n2=205, n3=75, n4=296, n5=242) were identified, each with distinct trajectories over childhood. A strong association was found between various growth classes and abnormal growth features such as rapid weight gain, stunting, underweight and overweight. Conclusions: With the identification of these classes, a better understanding of distinct childhood growth trajectories and their predictors may be gained, informing interventions to promote optimal childhood growth.

Risk and rates of hospitalisation in young children: a prospective study of a South African birth cohort.

Introduction: Children in sub-Saharan Africa (SSA) are disproportionately affected by morbidity and mortality; there is also a growing vulnerable population of children who are HIV-exposed uninfected (HEU). Understanding reasons and risk factors for early-life child hospitalisation will help optimise interventions to improve health outcomes. We investigated hospitalisations from birth to two years in a South African birth cohort. Methods: Mother-child pairs in the Drakenstein Child Health Study were followed from birth to two years with active surveillance for hospital admission and investigation of aetiology and outcome. Incidence, duration, cause, and factors associated with child hospitalisation were investigated, and compared between HEU and HIV-unexposed uninfected (HUU) children. Results: Of 1136 children (247 HEU; 889 HUU), 314 (28%) children were hospitalised in 430 episodes despite >98% childhood vaccination coverage. The highest hospitalisation rate was from 0-6 months, decreasing thereafter; 20% (84/430) of hospitalisations occurred in neonates at birth. Amongst hospitalisations subsequent to discharge after birth, 83% (288/346) had an infectious cause; lower respiratory tract infection (LRTI) was the most common cause (49%;169/346) with respiratory syncytial virus (RSV) responsible for 31% of LRTIs; from 0-6 months, RSV-LRTI accounted for 22% (36/164) of all-cause hospitalisations. HIV exposure was a risk factor for hospitalisation in infants (IRR 1.63 [95% CI 1.29-2.05]) and longer hospital admission (p=0.004). Prematurity (HR 2.82 [95% CI 2.28-3.49]), delayed infant vaccinations (1.43 [1.12-1.82]), or raised maternal HIV viral load in HEU infants were risk factors; breastfeeding was protective (0.69 [0.53-0.90]). Conclusion: Children in SSA continue to experience high rates of hospitalisation in early life. Infectious causes, especially RSV-LRTI, underly most hospital admissions. HEU children are at particular risk in infancy. Available strategies such as promoting breastfeeding, timely vaccination, and optimising antenatal maternal HIV care should be strengthened. New interventions to prevent RSV may have a large additional impact in reducing hospitalisation.

Influence of Maternal Childhood Trauma on Perinatal Depression, Observed Mother-Infant Interactions, and Child Growth.

INTRODUCTION: Mothers who have experienced childhood trauma may be at increased risk for disruptions in caregiving behavior, with potential consequences for early child development. However, assessments of caregiving behavior tend to be self-reported, which may bias results, and have been limited in lower-resource settings. METHODS: In an overall sample of 256 South African mothers followed across the perinatal period, this longitudinal study used structural equation modeling to test pathways of association between maternal childhood trauma and depressive symptoms on observed mother-infant interactions at 3.5 months and subsequent child growth outcomes at 1 year. RESULTS: On average, mothers with childhood trauma histories tended to show lower rated overall interactions with their infants (B = - 0.16, p = .013), which in turn was associated with reduced child growth at 1 year (B = 0.17, p = .046). When this model was adjusted for maternal age and relative socioeconomic status (SES), maternal SES strongly explained child growth (B = 0.31, p < .001) such that the direct effect of mother-infant interactions was no longer significant. DISCUSSION: For child growth in a lower-resource setting, quality of mother-infant interactions could be a relevant predictor but more strongly explained by maternal SES factors, suggesting a need for broader approaches that not only improve dyadic relationships but also address maternal ecological resources.

Systematic review of the global epidemiology of viral-induced acute liver failure.

OBJECTIVES: The aetiology and burden of viral-induced acute liver failure remains unclear globally. It is important to understand the epidemiology of viral-induced ALF to plan for clinical case management and case prevention. PARTICIPANTS: This systematic review was conducted to synthesize data on the relative contribution of different viruses to the aetiology of viral-induced acute liver failure in an attempt to compile evidence that is currently missing in the field. EBSCOhost, PubMed, ScienceDirect, Scopus and Web of Science were searched for relevant literature published from 2009 to 2019. The initial search was run on 9 April 2019 and updated via PubMed on 30 September 2019 with no new eligible studies to include. Twenty-five eligible studies were included in the results of this review. RESULTS: This systematic review estimated the burden of acute liver failure after infection with hepatitis B virus, hepatitis A virus, hepatitis C virus, hepatitis E virus, herpes simplex virus/human herpesvirus, cytomegalovirus, Epstein-Barr virus and parvovirus B19. Data were largely missing for acute liver failure after infection with varicella-zostervirus, human parainfluenza viruses, yellow fever virus, coxsackievirus and/or adenovirus. The prevalence of hepatitis A-induced acute liver failur was markedly lower in countries with routine hepatitis A immunisation versus no routine hepatitis A immunisation. Hepatitis E virus was the most common aetiological cause of viral-induced acute liver failure reported in this review. In addition, viral-induced acute liver failure had poor outcomes as indicated by high fatality rates, which appear to increase with poor economic status of the studied countries. CONCLUSIONS: Immunisation against hepatitis A and hepatitis B should be prioritised in low-income and middle-income countries to prevent high viral-induced acute liver failure mortality rates, especially in settings where resources for managing acute liver failure are lacking. The expanded use of hepatitis E immunisation should be explored as hepatitis E virus was the most common cause of acute liver failure. REGISTRATION: PROSPERO registration number: CRD42017079730.

The global epidemiology of viral-induced acute liver failure: a systematic review protocol.

INTRODUCTION: The burden of viral-induced acute liver failure (ALF) around the world still remains unclear, with little to no data collected regarding the disease incidence in general and synthesised data on the relative contribution of different viruses to the aetiology of ALF is missing in the field. The aim of this review is to estimate the burden (prevalence, incidence, mortality, hospitalisation) of ALF following infection HAV, HBV, HCV, HDV, HEV, EBV), HSV1, HSV2, VZV, parvo-virus B19, HPIVs, YFV, HVV-6, CMV, CA16 and/or HAdVs. Establishing the common aetiologies of viral-induced ALF, which vary geographically, is important so that: (1) treatment can be initiated quickly, (2) contraindications to liver transplant can be identified, (3) prognoses can be deterined more accurately, and most importantly, (4) vaccination against viral ALF aetiologies can be prioritised especially in under-resourced regions with public health risks associated with the relevant attributable diseases. METHODS AND ANALYSIS: EBSCOhost, PubMed, ScienceDirect, Scopus and Web of Science databases will be searched for relevant literature published and grey literature from 2009 up to 2019. Published cross-sectional and cohort studies will be eligible for inclusion in this review. Qualifying studies will be formally assessed for quality and risk of bias using a standardised scoring tool. Following standardised data extraction, meta-analyses will be carried out using STATA. Depending on characteristics of included studies, subgroup analyses and meta-regression analyses will be performed. This review will be reported according to Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. ETHICS AND DISSEMINATION: No ethics approval is required as the systematic review will use only published data already in the public domain. Findings will be disseminated through publication in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42018110309.

Infections among pediatric transplant candidates: An approach to decision-making.

INTRODUCTION: The presence of infections in the immediate pretransplant period poses challenges in decision-making. Delaying transplantation because of these infections may be required, but is associated with a risk to the potential recipient. The aim of this project was to develop a structured framework based on expert opinion to guide decision-making regarding the safety of transplantation for candidates with infection immediately before transplant, and to show how this framework can be applied to clinical scenarios. METHODS: Categories were created as follows: Category A: no delay; Category B: brief delay (≤1 week); Category C: intermediate delay (>1 week); and Category D: more prolonged or indefinite delay. A survey containing 59 clinical scenarios was sent to members of the IPTA ID CARE committee. Answers were reviewed, and the level of agreement was characterized as follows: Level 1: ≥75% agreement; Level 2:51%-74% agreement; and Level 3: ≤50% agreement. 95% CIs were calculated for the mean overall agreement across 59 scenarios. RESULTS: Among the panel, the agreement level ranged from 33% to 92% with the mean overall agreement across the 59 scenarios being 61%. For 7/59 scenarios, the lower bound of 95% CI was greater than 50%, indicating a difference at the 5% level of significance between the observed proportion and the chance level of 0.5. SUMMARY: The document provides expert opinion regarding the need to delay transplantation in the setting of different infections. The most important points in the decision to proceed to SOT included the urgency of transplantation and the severity of infection.