Retrospective study evaluating safety, clinical effect, and dosing of dalteparin for the treatment of venous thromboembolism in term neonates.

BACKGROUND: There is an increased risk of venous thromboembolism (VTE) among neonates due to their unique hemostatic system. However, there is lack of approved treatment options for VTE in neonatal population. Importantly, dalteparin, a low molecular weight heparin approved for pediatric VTE in children ≥1 month of age, has also been used for the treatment of neonatal VTE. Based on the request from the Food and Drug Administration, this retrospective study aimed to characterize the safety, clinical effects, and dosing of dalteparin for treatment of VTE among neonates. PROCEDURE: Data from electronic medical records for neonates (born ≥35 weeks of gestation) treated with dalteparin for VTE between January 2010 and December 2021 were collected. The data assessed included bleeding and deterioration in hematological biomarkers among other adverse events, changes in relevant factor antifactor Xa (anti-Xa) levels and VTE status, and dosing of dalteparin and corresponding anti-Xa assay levels. RESULTS: Sixteen neonates from five participating sites in the United Kingdom were included. There were no bleeding events or deaths. Only one serious adverse event of hypoglycemic brain injury (unrelated to dalteparin) was documented in a patient with a history of hyperinsulinism. Median (range) daily dose of dalteparin at initiation was 309 (297-314) IU/kg. Eight of 16 neonates achieved therapeutic anti-Xa level, including two patients who did so after the first dose. CONCLUSIONS: Dalteparin treatment in neonates raised no major safety concerns. Larger cohort studies may help provide further insights on clinical effects of dalteparin for neonatal VTE.

Intense and Mild First Epidemic Wave of Coronavirus Disease, The Gambia.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is evolving differently in Africa than in other regions. Africa has lower SARS-CoV-2 transmission rates and milder clinical manifestations. Detailed SARS-CoV-2 epidemiologic data are needed in Africa. We used publicly available data to calculate SARS-CoV-2 infections per 1,000 persons in The Gambia. We evaluated transmission rates among 1,366 employees of the Medical Research Council Unit The Gambia (MRCG), where systematic surveillance of symptomatic cases and contact tracing were implemented. By September 30, 2020, The Gambia had identified 3,579 SARS-CoV-2 cases, including 115 deaths; 67% of cases were identified in August. Among infections, MRCG staff accounted for 191 cases; all were asymptomatic or mild. The cumulative incidence rate among nonclinical MRCG staff was 124 infections/1,000 persons, which is >80-fold higher than estimates of diagnosed cases among the population. Systematic surveillance and seroepidemiologic surveys are needed to clarify the extent of SARS-CoV-2 transmission in Africa.

Kangaroo mother care: EN-BIRTH multi-country validation study.

BACKGROUND: Kangaroo mother care (KMC) reduces mortality among stable neonates ≤2000 g. Lack of data tracking coverage and quality of KMC in both surveys and routine information systems impedes scale-up. This paper evaluates KMC measurement as part of the Every Newborn Birth Indicators Research Tracking in Hospitals (EN-BIRTH) study. METHODS: The EN-BIRTH observational mixed-methods study was conducted in five hospitals in Bangladesh, Nepal and Tanzania from 2017 to 2018. Clinical observers collected time-stamped data as gold standard for mother-baby pairs in KMC wards/corners. To assess accuracy, we compared routine register-recorded and women's exit survey-reported coverage to observed data, using different recommended denominator options (≤2000 g and ≤ 2499 g). We analysed gaps in quality of provision and experience of KMC. In the Tanzanian hospitals, we assessed daily skin-to-skin duration/dose and feeding frequency. Qualitative data were collected from health workers and data collectors regarding barriers and enablers to routine register design, filling and use. RESULTS: Among 840 mother-baby pairs, compared to observed 100% coverage, both exit-survey reported (99.9%) and register-recorded coverage (92.9%) were highly valid measures with high sensitivity. KMC specific registers outperformed general registers. Enablers to register recording included perceptions of data usefulness, while barriers included duplication of data elements and overburdened health workers. Gaps in KMC quality were identified for position components including wearing a hat. In Temeke Tanzania, 10.6% of babies received daily KMC skin-to-skin duration/dose of ≥20 h and a further 75.3% received 12-19 h. Regular feeding ≥8 times/day was observed for 36.5% babies in Temeke Tanzania and 14.6% in Muhimbili Tanzania. Cup-feeding was the predominant assisted feeding method. Family support during admission was variable, grandmothers co-provided KMC more often in Bangladesh. No facility arrangements for other family members were reported by 45% of women at exit survey. CONCLUSIONS: Routine hospital KMC register data have potential to track coverage from hospital KMC wards/corners. Women accurately reported KMC at exit survey and evaluation for population-based surveys could be considered. Measurement of content, quality and experience of KMC need consensus on definitions. Prioritising further KMC measurement research is important so that high quality data can be used to accelerate scale-up of high impact care for the most vulnerable.

"We All Join Hands": Perceptions of the Kangaroo Method Among Female Relatives of Newborns in The Gambia.

Family support is essential for kangaroo mother care (KMC), but there is limited research regarding perceptions of female relatives, and none published from West African contexts. In-depth interviews were conducted from July to August 2017 with a purposive sample of 11 female relatives of preterm neonates admitted to The Gambia's referral hospital. Data were coded in NVivo 11, and thematic analysis was conducted applying an inductive framework. Female relatives were willing to support mothers by providing KMC and assisting with domestic chores and agricultural labor. Three themes were identified: (a) collective family responsibility for newborn care, with elder relatives being key decision makers, (b) balance between maintaining traditional practices and acceptance of KMC as a medical innovation, and (c) gendered expectations of women's responsibilities postnatally. Female relatives are influential stakeholders and could play important roles in KMC programs, encourage community ownership, and contribute to improved outcomes for vulnerable newborns.

Taking ethical photos of children for medical and research purposes in low-resource settings: an exploratory qualitative study.

BACKGROUND: Photographs are commonly taken of children in medical and research contexts. With the increased availability of photographs through the internet, it is increasingly important to consider their potential for negative consequences and the nature of any consent obtained. In this research we explore the issues around photography in low-resource settings, in particular concentrating on the challenges in gaining informed consent. METHODS: Exploratory qualitative study using focus group discussions involving medical doctors and researchers who are currently working or have recently worked in low-resource settings with children. RESULTS: Photographs are a valuable resource but photographers need to be mindful of how they are taken and used. Informed consent is needed when taking photographs but there were a number of problems in doing this, such as different concepts of consent, language and literacy barriers and the ability to understand the information. There was no consensus as to the form that the consent should take. Participants thought that while written consent was preferable, the mode of consent should depend on the situation. CONCLUSIONS: Photographs are a valuable but potentially harmful resource, thus informed consent is required but its form may vary by context. We suggest applying a hierarchy of dissemination to gauge how detailed the informed consent should be. Care should be taken not to cause harm, with the rights of the child being the paramount consideration.

Acquisition and carriage of genetically diverse multi-drug resistant gram-negative bacilli in hospitalised newborns in The Gambia.

BACKGROUND: This detailed genomic study characterised multi-drug resistant-Gram negative bacilli (MDR-GNB) carriage in neonates < 2 kg and paired mothers at a low-resource African hospital. METHODS: This cross-sectional cohort study was conducted at the neonatal referral unit in The Gambia with weekly neonatal skin and peri-anal sampling and paired maternal recto-vaginal swabs. Prospective bacteriological culture used MacConkey agar with species identification by API20E and API20NE. All GNB isolates underwent whole genome sequencing on Illumina Miseq platform. Multi-Locus Sequence Typing and SNP-distance analysis identified strain type and relatedness. RESULTS: 135 swabs from 34 neonates and 21 paired mothers, yielded 137 GNB isolates, of which 112 are high quality de novo assemblies. Neonatal MDR-GNB carriage prevalence is 41% (14/34) at admission with 85% (11/13) new acquisition by 7d. Multiple MDR and ESBL-GNB species are carried at different timepoints, most frequently K. pneumoniae and E. coli, with heterogeneous strain diversity and no evidence of clonality. 111 distinct antibiotic resistance genes are mostly beta lactamases (Bla-AMPH, Bla-PBP, CTX-M-15, Bla-TEM-105). 76% (16/21) and 62% (13/21) of mothers have recto-vaginal carriage of ≥1 MDR-GNB and ESBL-GNB respectively, mostly MDR-E. coli (76%, 16/21) and MDR-K. pneumoniae (24%, 5/21). Of 21 newborn-mother dyads, only one have genetically identical isolates (E. coli ST131 and K. pneumoniae ST3476). CONCLUSIONS: Gambian hospitalised neonates exhibit high MDR and ESBL-GNB carriage prevalence with acquisition between birth and 7d with limited evidence supporting mother to neonate transmission. Genomic studies in similar settings are required to further understand transmission and inform targeted surveillance and infection prevention policies.

Bacteria that are resistant to multiple antibiotics are an important cause of infection and death of newborns in low-resource countries, especially small or premature babies born in hospital settings. How these resistant bacteria are acquired on the skin and in the gut of newborns is not known, particularly whether they are commonly transferred from mothers. We studied the bacteria present in small Gambian newborns and their mothers to understand the type of bacteria, amount of antibiotic resistance, number of newborns and mothers affected and similarity of these bacteria between newborns and their mothers. We found that despite many newborns carrying these bacteria, they are different from those present in mothers. This suggests that the bacteria are acquired from the hospital environment. Our study highlights the importance of developing strategies to identify and reduce the presence of such bacteria in hospitals to reduce their acquisition by vulnerable hospitalised newborns.

Barriers and enablers to kangaroo mother care prior to stability from perspectives of Gambian health workers: A qualitative study.

Aims: Kangaroo mother care (KMC) is an evidence-based intervention recommended for stable newborns <2,000 g. Recent trials have investigated survival benefits of earlier initiation of KMC, including prior to stability, with WHO's iKMC trial showing 25% relative risk reduction for mortality of neonates 1-1.8 kg at tertiary Indian and African neonatal units (NNU). However, evidence is lacking about how to safely deliver this intervention to the most vulnerable neonates in resource limited settings (RLS). Our study aimed to understand barriers and enablers for early KMC prior to stability from perspectives of neonatal health care workers (HCW) in a high neonatal mortality RLS. Methods: This qualitative study was conducted at Edward Francis Small Teaching Hospital (EFSTH), the main neonatal referral unit in The Gambia. It was ancillary study to the eKMC clinical trial. Ten semi-structured interviews were conducted with all neonatal HCW cadres (4 nurses; 1 nurse attendant; 5 doctors; all Gambian). Study participants were purposively selected, and saturation was reached. Thematic analysis was conducted using Atun's conceptual framework for evaluation of new health interventions with methods to ensure data reliability and trustworthiness. Results: HCW's perceptions of early KMC prior to stability included recognition of potential benefits as well as uncertainty about effectiveness and safety. Barriers included: Unavailability of mothers during early neonatal unit admission; safety concerns with concomitant intravenous fluids and impact on infection prevention control; insufficient beds, space, WASH facilities and staffing; and lack of privacy and respectful care. Enablers included: Education of HCW with knowledge transfer to KMC providers; paternal and community sensitization and peer-to-peer support. Conclusions: Addressing health systems limitations for delivery of KMC prior to stability is foundational with linkage to comprehensive HCW and KMC provider education about effectiveness, safe delivery and monitoring. Further context specific research into safe and respectful implementation is required from varied settings and should include perceptions of all stakeholders, especially if there is a shift in global policy toward KMC for all small vulnerable newborns.

The Impact of Interventions to Prevent Neonatal Healthcare-associated Infections in Low- and Middle-income Countries: A Systematic Review.

BACKGROUND: Clinically suspected and laboratory-confirmed bloodstream infections are frequent causes of morbidity and mortality during neonatal care. The most effective infection prevention and control interventions for neonates in low- and middle-income countries (LMIC) are unknown. AIM: To identify effective interventions in the prevention of hospital-acquired bloodstream infections in LMIC neonatal units. METHODS: Medline, PUBMED, the Cochrane Database of Systematic Reviews, EMBASE and PsychInfo (January 2003 to October 2020) were searched to identify studies reporting single or bundled interventions for prevention of bloodstream infections in LMIC neonatal units. RESULTS: Our initial search identified 5206 articles; following application of filters, 27 publications met the inclusion and Integrated Quality Criteria for the Review of Multiple Study Designs assessment criteria and were summarized in the final analysis. No studies were carried out in low-income countries, only 1 in Sub-Saharan Africa and just 2 in multiple countries. Of the 18 single-intervention studies, most targeted skin (n = 4) and gastrointestinal mucosal integrity (n = 5). Whereas emollient therapy and lactoferrin achieved significant reductions in proven neonatal infection, glutamine and mixed probiotics showed no benefit. Chlorhexidine gluconate for cord care and kangaroo mother care reduced infection in individual single-center studies. Of the 9 studies evaluating bundles, most focused on prevention of device-associated infections and achieved significant reductions in catheter- and ventilator-associated infections. CONCLUSIONS: There is a limited evidence base for the effectiveness of infection prevention and control interventions in LMIC neonatal units; bundled interventions targeting device-associated infections were most effective. More multisite studies with robust study designs are needed to inform infection prevention and control intervention strategies in low-resource neonatal units.

Circulation of respiratory viruses during the COVID-19 pandemic in The Gambia.

Background: In many countries, non-pharmaceutical interventions to limit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission resulted in significant reductions in other respiratory viruses. However, similar data from Africa are limited. We explored the extent to which viruses such as influenza and rhinovirus co-circulated with SARS-CoV-2 in The Gambia during the COVID-19 pandemic.  Methods: Between April 2020 and March 2022, respiratory viruses were detected using RT-PCR in nasopharyngeal swabs from 1397 participants with influenza-like illness. An assay to detect SARS-CoV-2 and a viral multiplex RT-PCR assay was used as previously described  to detect influenza A and B, respiratory syncytial virus (RSV) A and B, parainfluenza viruses 1-4, human metapneumovirus (HMPV), adenovirus, seasonal coronaviruses (229E, OC43, NL63) and human rhinovirus. Results: Overall virus positivity was 44.2%, with prevalence higher in children <5 years (80%) compared to children aged 5-17 years (53.1%), adults aged 18-50 (39.5%) and >50 years (39.9%), p<0.0001. After SARS-CoV-2 (18.3%), rhinoviruses (10.5%) and influenza viruses (5.5%) were the most prevalent. SARS-CoV-2 positivity was lower in children <5 (4.3%) and 5-17 years (12.7%) than in adults aged 18-50 (19.3%) and >50 years (24.3%), p<0.0001. In contrast, rhinoviruses were most prevalent in children <5 years (28.7%), followed by children aged 5-17 (15.8%), adults aged 18-50 (8.3%) and >50 years (6.3%), p<0.0001. Four SARS-CoV-2 waves occurred, with 36.1%-52.4% SARS-CoV-2 positivity during peak months. Influenza infections were observed in both 2020 and 2021 during the rainy season as expected (peak positivity 16.4%-23.5%). Peaks of rhinovirus were asynchronous to the months when SARS-CoV-2 and influenza peaked. Conclusion: Our data show that many respiratory viruses continued to circulate during the COVID-19 pandemic in The Gambia, including human rhinoviruses, despite the presence of NPIs during the early stages of the pandemic, and influenza peaks during expected months.

Impact of early kangaroo mother care versus standard care on survival of mild-moderately unstable neonates <2000 grams: A randomised controlled trial.

BACKGROUND: Understanding the effect of early kangaroo mother care on survival of mild-moderately unstable neonates <2000 g is a high-priority evidence gap for small and sick newborn care. METHODS: This non-blinded pragmatic randomised clinical trial was conducted at the only teaching hospital in The Gambia. Eligibility criteria included weight <2000g and age 1-24 h with exclusion if stable or severely unstable. Neonates were randomly assigned to receive either standard care, including KMC once stable at >24 h after admission (control) versus KMC initiated <24 h after admission (intervention). Randomisation was stratified by weight with twins in the same arm. The primary outcome was all-cause mortality at 28 postnatal days, assessed by intention to treat analysis. Secondary outcomes included: time to death; hypothermia and stability at 24 h; breastfeeding at discharge; infections; weight gain at 28d and admission duration. The trial was prospectively registered at www.clinicaltrials.gov (NCT03555981). FINDINGS: Recruitment occurred from 23rd May 2018 to 19th March 2020. Among 1,107 neonates screened for participation 279 were randomly assigned, 139 (42% male [n = 59]) to standard care and 138 (43% male [n = 59]) to the intervention with two participants lost to follow up and no withdrawals. The proportion dying within 28d was 24% (34/139, control) vs. 21% (29/138, intervention) (risk ratio 0·84, 95% CI 0·55 - 1·29, p = 0·423). There were no between-arm differences for secondary outcomes or serious adverse events (28/139 (20%) for control and 30/139 (22%) for intervention, none related). One-third of intervention neonates reverted to standard care for clinical reasons. INTERPRETATION: The trial had low power due to halving of baseline neonatal mortality, highlighting the importance of implementing existing small and sick newborn care interventions. Further mortality effect and safety data are needed from varying low and middle-income neonatal unit contexts before changing global guidelines.