A mixed-methods study to investigate feasibility and acceptability of an early warning score for preterm infants in neonatal units in Kenya: results of the NEWS-K study

Preterm birth (\u3c 37 weeks gestation) complications are the leading cause of neonatal mortality. Early-warning scores (EWS) are charts where vital signs (e.g., temperature, heart rate, respiratory rate) are recorded, triggering action. To evaluate whether a neonatal EWS improves clinical outcomes in low-middle income countries, a randomised trial is needed. Determining whether the use of a neonatal EWS is feasible and acceptable in newborn units, is a prerequisite to conducting a trial. We implemented a neonatal EWS in three newborn units in Kenya. Staff were asked to record infants’ vital signs on the EWS during the study, triggering additional interventions as per existing local guidelines. No other aspects of care were altered. Feasibility criteria were pre-specified. We also interviewed health professionals (n = 28) and parents/family members (n = 42) to hear their opinions of the EWS. Data were collected on 465 preterm and/or low birthweight (\u3c 2.5 kg) infants. In addition to qualitative study participants, 45 health professionals in participating hospitals also completed an online survey to share their views on the EWS. 94% of infants had the EWS completed at least once during their newborn unit admission. EWS completion was highest on the day of admission (93%). Completion rates were similar across shifts. 15% of vital signs triggered escalation to a more senior member of staff. Health professionals reported liking the EWS, though recognised the biggest barrier to implementation was poor staffing. Newborn unit infant to staff ratios varied between 10 and 53 staff per 1 infant, depending upon time of shift and staff type. A randomised trial of neonatal EWS in Kenya is possible and acceptable, though adaptations are required to the form before implementation

A mixed-methods study to investigate feasibility and acceptability of an early warning score for preterm infants in neonatal units in Kenya: results of the NEWS-K study

Preterm birth (< 37 weeks gestation) complications are the leading cause of neonatal mortality. Early-warning scores (EWS) are charts where vital signs (e.g., temperature, heart rate, respiratory rate) are recorded, triggering action. To evaluate whether a neonatal EWS improves clinical outcomes in low-middle income countries, a randomised trial is needed. Determining whether the use of a neonatal EWS is feasible and acceptable in newborn units, is a prerequisite to conducting a trial. We implemented a neonatal EWS in three newborn units in Kenya. Staff were asked to record infants’ vital signs on the EWS during the study, triggering additional interventions as per existing local guidelines. No other aspects of care were altered. Feasibility criteria were pre-specified. We also interviewed health professionals (n = 28) and parents/family members (n = 42) to hear their opinions of the EWS. Data were collected on 465 preterm and/or low birthweight (< 2.5 kg) infants. In addition to qualitative study participants, 45 health professionals in participating hospitals also completed an online survey to share their views on the EWS. 94% of infants had the EWS completed at least once during their newborn unit admission. EWS completion was highest on the day of admission (93%). Completion rates were similar across shifts. 15% of vital signs triggered escalation to a more senior member of staff. Health professionals reported liking the EWS, though recognised the biggest barrier to implementation was poor staffing. Newborn unit infant to staff ratios varied between 10 and 53 staff per 1 infant, depending upon time of shift and staff type. A randomised trial of neonatal EWS in Kenya is possible and acceptable, though adaptations are required to the form before implementation

Breast Milk Virome and Bacterial Microbiome Resilience in Kenyan Women Living with HIV

ABSTRACT Breast milk is nutritionally and immunologically beneficial in early life but is also a potential source of infection. Little is known about breast milk microbiota of women living with HIV (WLHIV), the impact of severe immunosuppression, and the contribution to mortality of HIV-exposed infants. Here, we performed metagenomic sequencing to characterize the bacterial microbiome and DNA virome of breast milk samples at 1 month postpartum from Kenyan WLHIV who were not receiving combination antiretroviral therapy (cART), 23 women with CD4 counts of 500; and additionally, 19 WLHIV with infants that lived and 26 WLHIV with infants that died during the first 2 years of life were included. We found that breast milk bacterial microbiomes in this study population were highly diverse but shared a core community composed of the Streptococcaceae, Staphylococcaceae, Moraxellaceae, and Eubacteriaceae families. The breast milk virome was dominated by human cytomegalovirus (CMV) and included the bacteriophage families Myoviridae, Siphoviridae, and Podoviridae. Bacterial microbiome and virome profiles and diversity were not significantly altered by HIV immunosuppression, as defined by a CD4 of <250. CMV viral load was not associated with maternal CD4 counts or infant mortality. In conclusion, we show that the core bacterial and viral communities are resilient in breast milk despite immunosuppression in WLHIV. IMPORTANCE Breastfeeding plays an important role in seeding the infant gut microbiome and mammary health. Although most studies focus on the diverse breast milk bacterial communities, little is known about the viral communities harbored in breast milk. We performed the first breast milk virome study of an HIV population. In this study cohort of Kenyan women living with HIV from the pre-antiretroviral therapy era, we found that breast milk harbors a core bacterial microbiome and a virome dominated by human cytomegalovirus. The virome and bacterial microbiome were not substantially altered by immunosuppression or associated with infant mortality. Together, these findings indicate resilience of the microbial community in breast milk compartmentalization. These findings advance out fundamental understanding of the breast milk core microbiome and virome interactions in the context of HIV disease

HIV and SARS-CoV-2 infection in postpartum Kenyan women and their infants.

BackgroundHIV may increase SARS-CoV-2 infection risk and COVID-19 severity generally, but data are limited about its impact on postpartum women and their infants. As such, we characterized SARS-CoV-2 infection among mother-infant pairs in Nairobi, Kenya.MethodsWe conducted a nested study of 62 HIV-uninfected and 64 healthy women living with HIV, as well as their HIV-exposed uninfected (N = 61) and HIV-unexposed (N = 64) infants, participating in a prospective cohort. SARS-CoV-2 serology was performed on plasma collected between May 1, 2020-February 1, 2022 to determine the incidence, risk factors, and symptoms of infection. SARS-CoV-2 RNA PCR and sequencing was also performed on available stool samples from seropositive participants.ResultsSARS-CoV-2 seropositivity was found in 66% of the 126 mothers and in 44% of the 125 infants. There was no significant association between SARS-CoV-2 infection and maternal HIV (Hazard Ratio [HR] = 0.810, 95% CI: 0.517-1.27) or infant HIV exposure (HR = 1.47, 95% CI: 0.859-2.53). Maternal SARS-CoV-2 was associated with a two-fold increased risk of infant infection (HR = 2.31, 95% CI: 1.08-4.94). Few participants (13% mothers, 33% infants) had symptoms; no participant experienced severe COVID-19 or death. Seroreversion occurred in about half of mothers and infants. SARS-CoV-2 sequences obtained from stool were related to contemporaneously circulating variants.ConclusionsThese data indicate that postpartum Kenyan women and their infants were at high risk for SARS-CoV-2 infection and that antibody responses waned over an average of 8-10 months. However, most cases were asymptomatic and healthy women living with HIV did not have a substantially increased risk of infection or severe COVID-19

Detailed methods for stool viral RNA extraction, RT-PCR, and sequencing.

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SARS-CoV-2 serology and stool viral RNA results over calendar time.

Results of SARS-CoV-2 serology and quantitative real-time PCR testing of stool samples from Linda Kizazi participants that first tested seropositive and had ≥1 available stool sample collected between May 1-December 31, 2020. Anonymized ID numbers on y-axis for mothers (M) and infants (B). Grey circles indicate date of last seronegative serology test and orange circles indicate date of first seropositive sample. White triangles represent SARS-CoV-2 RNA-negative and red triangles represent RNA-positive stool samples. Calendar time is on the x-axis.</p

SARS-CoV-2 antibody levels over time in mother-infant Pairs.

OD ratios show SARS-CoV-2 antibody levels over time in pairs where both mother and infant were first SARS-CoV-2 positive at the same visit and had ≥1 sample available after initial antibody detection. Increased levels of antibody denoted by darker purple shading as shown in key. Positive antibody levels denoted by filled circle, equivocal levels by X, and levels below the limit of detection by empty circles. Mother-infant pairs in which the mother was living with HIV are shown on top with bold red IDs; HIV-uninfected and -unexposed pairs are shown below with black IDs. (TIF)</p

SARS-CoV-2 genomes sequenced from Kenyan stool samples.

Complete SARS-CoV-2 genomes were sequenced from six RNA-positive stool samples. (A) Phylogenetic analyses of 500 randomly selected SARS-CoV-2 global sequences, the Wuhan1 reference, and the two Kenyan stool-derived genomes (indicated in red) are shown. Clade labels are shown. (B) Next-generation sequencing data statistics of the six Kenyan stool samples. (TIF)</p

Detection of SARS-CoV-2 antibody among mothers and infants over time.

(A) SARS-CoV-2 antibody levels over time relative to the first seropositive time point (0 months). Individual patterns in infants (top) and mothers (bottom) are shown in grey. Grouped by maternal HIV status, running means are shown for HIV-uninfected women or HIV-unexposed infants in black and women living with HIV or HIV-exposed infants in red. Limit of detection denoted by dashed vertical line. (B) and (C) are Kaplan-Meier hazard functions for participants’ estimated time to loss of detectable antibodies stratified by maternal HIV status and infant HIV exposure, respectively. HEU = HIV-exposed uninfected, HUU = HIV-unexposed uninfected. The risk period for loss of detectable antibody begins at the participant’s first positive serology test and ends either at the time of loss of detectable antibodies (estimated as the midpoint between the last positive test and first negative test after a positive test) or at the time of the most recent positive test.</p

Incidence of SARS-CoV-2 infection in postpartum Kenyan women and their infants from May 1, 2020 to February 1, 2022.

Incidence of SARS-CoV-2 infection in postpartum Kenyan women and their infants from May 1, 2020 to February 1, 2022.</p