Tygerberg Children’s Hospital

IntroductionSuccessful programmes for prevention of vertical HIV transmission have reduced the risk of infant HIV infection in South Africa from 8% in 2008 to below 1% in 2018/2019, resulting in an increasing population of children exposed to HIV perinatally but who are uninfected (HEU). However, the long-term effects of HIV and antiretroviral treatment (ART) exposure on the developing brain are not well understood. Whereas children who are HEU perform better than their HIV-infected counterparts, they demonstrate greater neurodevelopmental delay than children who are HIV unexposed and uninfected (HUU), especially in resource-poor settings. Here we investigate subcortical volumetric differences related to HIV and ART exposure in neonates.MethodsWe included 120 infants (59 girls; 79 HEU) born to healthy women with and without HIV infection in Cape Town, South Africa, where HIV sero-prevalence approaches 30%. Of the 79 HEU infants, 40 were exposed to ART throughout gestation (i.e., mothers initiated ART pre conception; HEU-pre), and 39 were exposed to ART for part of gestation (i.e., mothers initiated ART post conception; HEU-post). Post-conception mothers had a mean (± SD) gestational age (GA) of 15.4 (± 5.7) weeks at ART initiation. Mothers with HIV received standard care fixed drug combination ART (Tenofovir/Efavirenz/Emtricitabine). Infants were imaged unsedated on a 3T Skyra (Siemens, Erlangen, Germany) at mean GA equivalent of 41.5 (± 1.0) weeks. Selected regions (caudate, putamen, pallidum, thalamus, cerebellar hemispheres and vermis, and corpus callosum) were manually traced on T1-weighted images using Freeview.ResultsHEU neonates had smaller left putamen volumes than HUU [β (SE) = −90.3 (45.3), p = 0.05] and caudate volume reductions that depended on ART exposure duration in utero. While the HEU-pre group demonstrated no caudate volume reductions compared to HUU, the HEU-post group had smaller caudate volumes bilaterally [β (SE) = −145.5 (45.1), p = 0.002, and −135.7 (49.7), p = 0.008 for left and right caudate, respectively].DiscussionThese findings from the first postnatal month suggest that maternal ART throughout gestation is protective to the caudate nuclei. In contrast, left putamens were smaller across all HEU newborns, despite maternal ART.

BackgroundElectrical biosensing technology (EBT) is an umbrella term for non-invasive technology utilizing the body’s fluctuating resistance to electrical current flow to estimate cardiac output. Monitoring cardiac output in neonates may allow for timely recognition of hemodynamic compromise and allow for prompt therapy, thereby mitigating adverse outcomes. For a new technology to be safely used in the clinical environment for therapeutic decisions, it must be proven to be accurate, precise and be able to track temporal changes. The aim of this systematic review was to identify and analyze studies that describe the accuracy, precision, and trending ability of EBT to non-invasively monitor Left ventricular cardiac output and/or stroke volume in neonates.MethodsA qualitative systematic review was performed. Studies were identified from PubMed NCBI, SCOPUS, and EBSCOHost up to November 2021, where EBT technologies were analyzed in neonates, in comparison to a reference technology. Outcome measures were bias, limits of agreement, percentage error for agreement studies and data from 4-quadrant and polar plots for trending studies. Effect direction plots were used to present results.ResultsFifteen neonatal studies were identified, 14 for agreement and 1 for trending analysis. Only thoracic electrical biosensing technology (TEBT), with transthoracic echocardiography (TTE) as the comparator, studies were available for analyzes. High heterogeneity existed between studies. An equal number of studies showed over- and underestimation of left ventricular output parameters. All studies showed small bias, wide limits of agreement, with most studies having a percentage error >30%. Sub-analyses for respiratory support mode, cardiac anomalies and type of technology showed similar results. The single trending study showed poor concordance, high angular bias, and poor angular concordance.DiscussionOverall, TEBT shows reasonable accuracy, poor precision, and non-interchangeability with TTE. However, high heterogeneity hampered proper analysis. TEBT should be used with caution in the neonatal population for monitoring and determining therapeutic interventions. The use of TEBT trend monitoring has not been sufficiently studied and requires further evaluation in future trials.

Studies investigating the associations between histories of childhood maltreatment (CM) in parent-child dyads have primarily involved samples from high-income countries; however, CM rates are higher in low- and middle-income countries. The present study aimed to examine the (a) association between maltreatment in parents and maltreatment of their children through risk (i.e., parent depression) and protective (i.e., parent-child connectedness) factors and (b) associations between CM in children with aggression through posttraumatic stress symptoms (PTSS) and peer/sibling victimization. Participants were 227 parent-child dyads from Burundi, Africa, a low-income country. Parents were 18 years of age or older, and children were 12-18 years (M = 14.76, SD = 1.88, 57.7% female). Among parents, 20.7%-69.5% of participants reported a history of physical and emotional abuse and neglect; among children, the rates of sexual, physical, and emotional abuse ranged from 14.5% to 89.4%. A history of CM in parents was associated with CM in children, B = 0.19, p < .01, and CM in parents was indirectly associated with CM in children through parent-child connectedness, β = .04, 95% CI [.01, .10], and parental depression, β = .08, 95% CI [.03, .15]. In children, maltreatment was positively associated with peer/sibling victimization, and CM was associated with aggression, β = .07, 95% CI [.04, 0.11], through PTSS but not via peer/sibling victimization. Continued efforts to improve CM-related preventive strategies and the accessibility of prevention services are needed to reduce CM in low-income countries such as Burundi.

Introduction: It is unknown whether bioreactance (BR) can accurately track cardiac output (CO) changes in preterm neonates. Methods: A prospective observational longitudinal study was performed in stable preterm infants (<37 weeks) during the first 72 h of life. Stroke volume (SV) and CO, as measured by BR and transthoracic echocardiography, were compared. Results: The mean gestational age (GA) was 31.3 weeks and mean birth weight (BW) was 1,563 g. Overall, 690 measurements were analysed for trending ability by 4-quadrant and polar plots. For non-weight-indexed measurements, 377 (54.6%) lay outside the 5% exclusion zone, the concordance rate was poor (77.2%) with a high mean angular bias (28.6°), wide limits of agreement and a poor angular concordance rate (17.4%). Neither GA, BW nor respiratory support mode affected trending data. Patent ductus arteriosus, postnatal age, and CO level had variable effects on trending data. Trending data for 5 and 10% exclusion zones were also compared. Conclusion: The ability of BR to track changes in CO is not interchangeable with CO changes as measured by echocardiography. BR, as a trend monitor for changes in CO or SV to determine clinical decisions around interventions in neonatology, should be used with caution.

There is a growing number of perinatally HIV-1-infected children worldwide who must maintain life-long ART. In early life, HIV-1 infection is established in an immunologically inexperienced environment in which maternal ART and immune dynamics during pregnancy play a role in reservoir establishment. Children that initiated early antiretroviral therapy (ART) and maintained long-term suppression of viremia have smaller and less diverse HIV reservoirs than adults, although their proviral landscape during ART is reported to be similar to that of adults. The ability of these early infected cells to persist long-term through clonal expansion poses a major barrier to finding a cure. Furthermore, the effects of life-long HIV persistence and ART are yet to be understood, but growing evidence suggests that these individuals are at an increased risk for developing non-AIDS-related comorbidities, which underscores the need for an HIV cure.

IntroductionThere is limited data in children on whether persistence of HIV‐1 infected cells is affected by age at initiating antiretroviral therapy (ART), its duration or any subsequent ART interruption. We therefore investigated the effects of both age of ART initiation and duration of ART interruption on HIV‐1 DNA decay in children.MethodsWe investigated HIV‐1 DNA decay in three groups of children on ART: Group‐1 (n = 7) started uninterrupted ART within eight days of life; Group‐2 (n = 8) started uninterrupted ART at a median of five months of age; and Group‐3 (n = 23) started ART at a median age of 1.8 months for either 40 or 96 weeks, then interrupted ART (median of seven months), and restarted ART based on CD4 count and clinical criteria. Total HIV‐1 DNA was assayed using a sensitive HIV‐1 subtype C‐adapted quantitative PCR for integrase. The duration of ART was square root transformed to fit the observed slowing of HIV‐1 DNA decay rate. For each group, point estimates for decay rates were determined after six months of continuous suppressive ART in groups 1 and 2 or six months after restarting ART in Group‐3. Groups‐2 and 3 were combined using a mixed effect regression model to investigate covariates of HIV‐1 DNA decay rate.Results and DiscussionAt six months of continuous suppressive ART, the HIV‐1 DNA t½ (95% CI) was shorter in Group‐1 (n = 7): 2.7 months (2.1 to 3.8), than 9.2 months (7.4 to 12.1) in Group‐2 (n = 8); and 9.6 months (7.6 to 12.6) in Group‐3 (n = 23) (p < 0.01). In multivariable analyses, HIV‐1 DNA before treatment (p < 0.001) and the change in HIV‐1 DNA during interruption (p < 0.01) were independent predictors of slower HIV‐1 DNA decay.ConclusionsThese data suggest that ART initiation within the first week of life can reduce the persistence of long‐lived infected cells. Delaying ART is associated with slower decay of infected cells.

The rate of central-line-associated bloodstream infection (CLABSI) in South African (SA) public sector neonatal intensive care units (NICUs) is unknown. Tygerberg Children's Hospital (TCH), Cape Town, introduced a neonatal CLABSI surveillance and prevention programme in August 2012. To describe CLABSI events and identify risk factors for development of CLABSI in a resource-limited NICU. A retrospective case-control study was conducted using prospectively collected NICU CLABSI events matched to four randomly selected controls, sampled from the NICU registry between 9 August 2012 and 31 July 2014. Clinical data and laboratory records were reviewed to identify possible risk factors, using stepwise forward logistic regression analysis. A total of 706 central lines were inserted in 530 neonates during the study period. Nineteen CLABSI events were identified, with a CLABSI rate of 5.9/1 000 line days. CLABSI patients were of lower gestational age (28 v. 34 weeks; p=0.003), lower median birth weight (1 170 g v. 1 975 g; p=0.014), had longer catheter dwell times (&gt;4 days) (odds ratio (OR) 5.1 (95% confidence interval (CI) 1.0 - 25.4);p=0.04) and were more likely to have had surgery during their NICU stay (OR 3.5 (95% CI 1.26 - 10); p=0.01). Significant risk factors for CLABSI were length of stay &gt;30 days (OR 20.7 (95% CI 2.1 - 203.2); p=0.009) and central-line insertion in the operating theatre (OR 8.1 (95% CI 1.2 - 54.7); p=0.03). Gram-negative pathogens predominated (12/22; 54%), with most isolates (10/12; 83%) exhibiting multidrug resistance. The TCH NICU CLABSI rate is similar to that reported from resource-limited settings, but exceeds that of high-income countries. Prolonged NICU stay and central-line insertion in the operating theatre were important risk factors for CLABSI development. Intensified neonatal staff training regarding CLABSI maintenance bundle elements and hand hygiene are key to reducing CLABSI rates.