Infant Prophylaxis Research Articles

In-utero exposure to tenofovir-containing pre-exposure prophylaxis and bone mineral content in HIV-unexposed infants in South Africa.

Tenofovir disoproxil fumarate (TDF) is a common drug of choice for pre-exposure prophylaxis (PrEP) or as a combination HIV treatment for pregnant women. In-utero exposure to TDF was found to be associated with lower bone mineral content (BMC) in HIV-exposed uninfected neonates. Data for infants born to women taking TDF-PrEP are lacking. The CAP016 randomized control trial was conducted in South Africa between September 2017 and August 2021 and pregnant women either initiated TDF/FTC PrEP in pregnancy (Immediate PrEP arm-IP) or at cessation of breastfeeding (Deferred PrEP arm-DP). In a secondary data analysis, we evaluated BMC in HIV-unexposed infants in the CAP016 trial in the first 18 months of life in association with maternal TDF-PrEP use during pregnancy. Infants born to women randomized to the IP arm or DP arm in the CAP016 clinical trial had BMC measurements of the whole body with head (WBH) and lumbar spine (LS) by dual energy X-ray absorptiometry (DXA) at 6, 26, 50 and 74 weeks. Of 481 infants born to women enrolled in the CAP016 clinical trial, 335 (69.6%) infants had a minimum of one DXA scan of the WBH and LS between 6 and 74 weeks of age (168 IP and 167 DP). Women in the IP arm received TDF-FTC PreP for a median of 19 weeks between initiation in pregnancy and delivery. Using a mixed linear regression model and adjusted for gestational age, sex and ever-breastfed, the mean difference (95% CI) for BMC of the WBH between IP and DP arms were -0.74 (-8.69 to 7.20), -1.26 (-10.75 to 8.23), -9.17 (-20.02 to 1.69) and 5.02 (-6.74 to 16.78) g at 6, 26, 50 and 74 weeks (p = 0.283). Mean differences in BMC of the LS were 0.07 (-0.10 to 0.23), 0.02 (-0.18 to 0.22), -0.14 (-0.36 to 0.09) and 0.14 (-0.11 to 0.38) g at 6, 26, 50 and 74 weeks, respectively (p = 0.329). In a randomized controlled trial, there were no differences in BMC of the WBH and LS between infants exposed to in-utero TDF-FTC PrEP and unexposed infants in the first 18 months of life.

The prevalence of vertical transmission of human immunodeficiency virus and associated factors among exposed infants in Eastern Lake zone and Southern Highland of Tanzania: a cross-sectional study

Background Globally, the rate of antiretroviral therapy coverage for pregnant women living with human immunodeficiency virus (HIV) increased by 38% between 2010 and 2015 but only by 2% between 2016 and 2020. Objectives We aimed to determine the prevalence of vertical transmission of HIV among infants from mothers living with HIV and associated factors in the Eastern Lake Zone and Southern Highland of Tanzania from January to December 2022. Methods This retrospective cross-sectional study extracted data from the Open Laboratory Data Repository database collected from January to December 2022 at 93 health facilities. A total of 1,411 infants exposed to HIV from the Mbeya (851), Songwe (304), and Mara regions (256) were enrolled. Results The prevalence for vertical transmission of HIV was 2.48% (35/1411). We observed a non-significant difference in the prevalence of vertical transmission in children whose first test was done below six weeks of life (1.89%) and other age groups (2.52-2.62%) (p < 0.917). Children not given antiretroviral prophylaxis had eleven times higher odds of acquiring infection (AOR 11.39, 95% CI: 3.61–35.97). Mothers who were not on ART during pregnancy had three times the odds of transmitting HIV to their infants (AOR 3.03, 95%CI: 0.91–10.15). Conclusions We found a low prevalence of vertical transmission of HIV compared to previous studies done in Tanzania. The use of ART prophylaxis for infants exposed to HIV is significantly associated with the low rate of HIV transmission.

Updates in the Management of HIV During Pregnancy.

Human immunodeficiency virus in pregnant people remains a significant public health issue worldwide. The rate of perinatal transmission is 15% to 40% but can be decreased to less than 1% with appropriate antenatal management. Previous recommendations included a protease inhibitor-based antiretroviral therapy, infant prophylaxis, performance of cesarean section for uncontrolled viremia, and the use of formula for infant feeding. However, recent updates include first line of integrase inhibitor-based regimens and supporting parental choices for safe lactation. In this review, we summarize and provide updated recommendations for the care of people living with human immunodeficiency virus during pregnancy.

HIV in pregnant woman and children: Mother-to-child transmission of HIV in the Brazilian land border from 2010 to 2021.

The aim of the present study was to analyze the profile and trends of HIV mother-to-child transmission (MTCT) in the Brazilian land border strip (LBS). This was a quantitative, ecological, and cross-sectional study using secondary data available in the information systems of the Brazilian Ministry of Health. All cases reported in the Notifiable Diseases Information System between 2010 and 2021 were studied. Between 2010 and 2021, 275 children were born infected through MTCT, and 6076 pregnant women were living with HIV in the Brazilian LBS. HIV detection rates in pregnant women increased in all border arcs. The northern arc experienced the highest increase (19.6%), followed by the central arc (11.4%), and the southern arc (6.1%). Despite historically high detection rates, the southern arc exhibited the smallest increase. While MTCT rate decreased by 37.7% in the border area, the central arc showed no statistically significant reduction. In 2021, the average age of pregnant women was 26.2 years, 25.7% had up to 8 years of schooling, and 55.8% identified as non-white. The majority (92.8%) received antenatal care, and 59.7% were diagnosed with HIV before prenatal care. The use of prophylactic antiretroviral therapy during prenatal care occurred in 69.6% of pregnant women, and infant prophylaxis was provided within first 24 h to 43.6% of live births. The results indicate progress in reducing MTCT cases in Brazilian LBS. Disparities in HIV detection rates may be influenced by differences in testing uptake, despite mandatory testing for all babies. It is crucial to continue implementing strategies to reach these women and ensure equitable access to healthcare services for MTCT prevention.

Use of Different Iron Preparations for Prophylaxis and Effects on Iron Status in Infancy.

Aim: To evaluate using different iron preparations for iron deficiency and/or iron deficiency anemia prophylaxis in infants and their iron status. Methods: In this study, we retrospectively evaluated the electronic patient records of 651 healthy children aged 9 to 13 months who met the inclusion criteria and who were followed up in pediatric follow-up outpatient clinics between January 2023 and June 2023. Results: A total of 651 children with a mean age of 11.2 ± 1.4 months, 54.7% of whom were boys, who met the inclusion criteria were included in the study; 56.5% of the children were using Fe + 3 salt and the others were using Fe + 2 salt, microencapsulated iron, or sucrosomial iron drops. After the fifth month of prophylaxis, when the effects of the iron preparations used on the mean laboratory values were evaluated, it was found that hemoglobin, serum iron, and ferritin levels were lower in sucrosomial iron and microencapsulated iron users compared to other preparations (p = 0.001). When statistically pairwise comparisons were made between the groups, hemoglobin and serum iron values were found to be lower in the group using sucrosomial iron compared to the groups using Fe + 2 and Fe + 3 salts (p < 0.0001). Hemoglobin and ferritin levels were higher in the group using Fe + 2 salt compared to both sucrosomial iron and microencapsulated iron groups (p < 0.0001). When the infants were evaluated according to iron status, it was found that 208 (31.9%) had iron deficiency. Iron deficiency was found to be less in infants of families who defined their economic status as rich and in infants who used iron regularly (p-values 0.044 and 0.001, respectively). Iron deficiency/iron deficiency anemia was observed at a higher rate in the group using sucrosomial iron and microencapsulated iron prophylaxis (p = 0.001). Conclusions: To prevent iron deficiency, it is very important to use appropriate iron preparations for prophylaxis and to feed foods with high iron content. Although we found that families were willing to use different iron preparations other than iron salts for their infants, the results presented herein indicate that the rate of iron deficiency was lower in patients using iron salts. However, randomized controlled studies are needed to determine whether these preparations are effective in iron prophylaxis in infants.

Assessment of effectiveness and impact of universal prophylaxis with nirsevimab for prevention of hospitalizations due to respiratory syncytial virus in infants. The NIRSE-GAL study protocol

ABSTRACT Nirsevimab has been recently licensed for universal RSV prophylaxis in infants. NIRSE-GAL is a three-year population-based study initiated in Galicia in September 2023. It aims to evaluate nirsevimab effectiveness against RSV-related hospitalizations lower respiratory tract infections (LRTI), severe RSV, all-cause LRTI, and all-cause hospitalization. NIRSE-GAL also aims to estimate nirsevimab impact on primary healthcare use in the short and mid-term, children’s wheezing and asthma, and medical prescriptions for RSV. The immunization campaigns will be scheduled based on the expected start week for the RSV season and will last the whole season. Immunization will be offered to: i) infants born during the campaign (seasonal), ii) infants < 6 months at the start of the campaign (catch-up), and iii) infants with high-risk factors, aged 6–24 months at the start of the campaign (high-risk). The follow-up period will start: i) the immunization date for all immunized infants, ii) the start of the campaign, for the non-immunized catch-up or high-risk groups, or iii) the birthdate for the non-immunized seasonal group. Infants will be followed up until outcome occurrence, death, or end of study. Nirsevimab effectiveness will be estimated using Poisson and Cox regression models. Sensitivity and stratified analyses will be undertaken. The number of averted cases and the number needed to immunize will be estimated. Immunization failure and nirsevimab safety will be monitored. NIRSE-GAL was approved by the ethics committee of Galicia (CEIC 2023–377) and registered in ClinicalTrials.gov (ID: NCT06180993). Findings will be mainly shared via peer-reviewed publications and scientific conferences.

Effectiveness and impact of universal prophylaxis with nirsevimab in infants against hospitalisation for respiratory syncytial virus in Galicia, Spain: initial results of a population-based longitudinal study

Galicia (Spain) was one of the first regions worldwide to incorporate nirsevimab for universal respiratory syncytial virus (RSV) prophylaxis in infants into its immunisation programme. The NIRSE-GAL longitudinal population-based study aimed to assess nirsevimab effectiveness in preventing hospitalisations (ie, admittance to hospital). The 2023-24 immunisation campaign with nirsevimab in Galicia began on Sept 25, 2023, and concluded on March 31, 2024. The campaign targeted three groups: infants born during the campaign (seasonal group), infants younger than 6 months at the start of the campaign (catch-up group), and infants aged 6-24 months with high-risk factors at the start of the campaign (high-risk group). Infants in the seasonal group were offered immunisation on the first day of life before discharge from hospital. Infants in the catch-up and high-risk groups received electronic appointments to attend a public hospital or health-care centre for nirsevimab administration. For this interim analysis, we used data collected from Sept 25 to Dec 31, 2023, from children born up to Dec 15, 2023. Data were retrieved from public health registries. Nirsevimab effectiveness in preventing RSV-associated lower respiratory tract infection (LRTI) hospitalisations; severe RSV-related LRTI requiring intensive care unit admission, mechanical ventilation, or oxygen support; all-cause LRTI hospitalisations; and all-cause hospitalisations was estimated using adjusted Poisson regression models. Data from five past RSV seasons (2016-17, 2017-18, 2018-19, 2019-20, and 2022-23), excluding the COVID-19 pandemic period, were used to estimate the number of RSV-related LRTI hospitalisations averted along with its IQR. The number needed to immunise to avoid one case in the 2023-24 season was then estimated from the averted cases. Nirsevimab safety was routinely monitored. The NIRSE-GAL study protocol was registered on ClinicalTrials.gov (NCT06180993), and follow-up of participants is ongoing. 9408 (91·7%) of 10 259 eligible infants in the seasonal and catch-up groups received nirsevimab, including 6220 (89·9%) of 6919 in the catch-up group and 3188 (95·4%) of 3340 in the seasonal group. 360 in the high-risk group were offered nirsevimab, 348 (97%) of whom received it. Only infants in the seasonal and catch-up groups were included in analyses to estimate nirsevimab effectiveness and impact because there were too few events in the high-risk group. In the catch-up and seasonal groups combined, 30 (0·3%) of 9408 infants who received nirsevimab and 16 (1·9%) of 851 who did not receive nirsevimab were hospitalised for RSV-related LRTI, corresponding to an effectiveness of 82·0% (95% CI 65·6-90·2). Effectiveness was 86·9% (69·1-94·2) against severe RSV-related LRTI requiring oxygen support, 69·2% (55·9-78·0) against all-cause LRTI hospitalisations, and 66·2% (56·0-73·7) against all-cause hospitalisations. Nirsevimab effectiveness against other endpoints of severe RSV-related LRTI could not be estimated because of too few events. RSV-related LRTI hospitalisations were reduced by 89·8% (IQR 87·5-90·3), and the number needed to immunise to avoid one RSV-related LRTI hospitalisation was 25 (IQR 24-32). No severe adverse events related to nirsevimab were registered. Nirsevimab substantially reduced infant hospitalisations for RSV-associated LRTI, severe RSV-associated LRTI requiring oxygen, and all-cause LRTI when given in real-world conditions. These findings offer policy makers and health authorities robust, real-world, population-based evidence to guide the development of strategies for RSV prevention. Sanofi and AstraZeneca. For the Spanish translation of the abstract see Supplementary Materials section.

Nirsevimab: Expansion of Respiratory Syncytial Virus Prevention Options in Neonates, Infants, and At-Risk Young Children.

Review available data from clinical trials of nirsevimab for efficacy and safety in the setting of respiratory syncytial virus (RSV) prophylaxis in infants and children, while exploring nirsevimab's role in clinical practice and highlighting continuing questions. A literature search of PubMed was conducted utilizing the phrases "nirsevimab" and "medi8897." Additional references were identified through found references. Organizational guidelines, medication labeling, and regulatory organization presentations were utilized. Relevant clinical trials investigating nirsevimab in infants and children were included as well as other references on pharmacology, pharmacokinetics, and pharmacoeconomics. Nirsevimab, a once-a-season monoclonal antibody, demonstrated a 79.5% (95% CI, 65.9-87.7; P < 0.00001) lower incidence of RSV-associated medically attended lower respiratory tract infections (MA RSV-associated LRTI) and 77.3% (95% CI, 50.3-89.7; P = 0.0002) reduction in hospitalizations for RSV-associated MA-LRTI across 2 placebo-controlled studies. Nirsevimab demonstrated comparable safety to placebo with minor dermatologic reactions being the most common adverse event (0.9% vs 0.6%). Nirsevimab was approved by the US Food and Drug Administration, and recommended by the Advisory Committee on Immunization Practices and American Academy of Pediatrics for broad administration to infants entering their first RSV season and at risk patients during their second RSV season. Questions remain over efficacy in infants born < 29-week gestation and other economical considerations. Nirsevimab demonstrated clinical efficacy in reducing RSV-associated MA-LRTI and RSV-associated hospitalizations in infants and was well tolerated.

Comparative Efficacy of Ferrous, Ferric and Liposomal Iron Preparations for Prophylaxis in Infants

Comparative Efficacy of Ferrous, Ferric and Liposomal Iron Preparations for Prophylaxis in Infants

Urinary stone in infants; should vitamin D prophylaxis be stopped?

BackgroundThis study investigated the effect of the discontinuation of vitamin D supplementation on kidney stone formation in children under 2 years of age. MethodsThis study involved a retrospective analysis of two patient groups. The first group comprised postoperative patients who were stone-free, while the second group consisted of asymptomatic patients with kidney stones. The patients who discontinued vitamin D supplementation and those who continued were compared in terms of stone formation and stone size progression. The data collected included patient characteristics, stone size measurements, and laboratory results. ResultsThe findings showed that the discontinuation of vitamin D supplementation was not associated with kidney stone formation or the progression of stone size in either group. For patients who were stone-free on ultrasonography 1 month after the operation, according to the 12-month ultrasonography evaluation, in the group that discontinued vitamin D, 42 (78%) patients had no stones, 6 (11%) patients had stones larger than 3 mm, and 6 (11%) patients had microlithiasis. However, in the group that continued vitamin D, 49 (72%) patients were stone-free, 10 (15%) patients had stones larger than 3 mm, and 9 (13%) patients had microlithiasis. There was no difference between the groups in terms of stone status at 12 months (p=0.76). For patients with asymptomatic kidney stones, the initial stone sizes were similar between the groups (p=0.74). During the 6th month of ultrasound, the changes in stone size were 1.76±1.81 mm and 1.79±1.75 mm for the two groups, respectively (p=0.9). During the 12-month ultrasound measurement, the changes in stone size were 1.98±2.93 mm and 2.60±2.48 mm for the two groups, respectively (p=0.09). ConclusionsWe believe that more research is needed to make definitive recommendations regarding vitamin D prophylaxis in infants with kidney stones. Although the first objective of our study is not conclusively proven with the current findings, we recommend continued vitamin D prophylaxis in infants with urolithiasis.

Lower Insulin Sensitivity Through 36 Months of Life With in Utero HIV and Antiretroviral Exposure in Botswana: Results From the Tshilo Dikotla Study.

There are little data on changes in insulin sensitivity during the first few years of life following in utero human immunodeficiency virus (HIV) and antiretroviral (ARV) exposure. The Tshilo Dikotla study enrolled pregnant persons with HIV (PWH) (receiving tenofovir/emtricitabine or lamivudine plus dolutegravir or efavirenz) and pregnant individuals without HIV, as well as their liveborn children. Newborns were randomized to receive either zidovudine (AZT) or nevirapine (NVP) postnatal prophylaxis. Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) was assessed at birth and 1, 18, 24, and 36 months of life. We fit linear mixed-effects models to evaluate the association between in utero HIV/ARV exposure and average HOMA-IR from birth through 36 months of life, adjusting for confounders. A total of 419 children were included (287 with in utero HIV/ARV exposure and uninfected [CHEU] and 132 without in utero HIV/ARV exposure [CHUU]). CHEU were born to older women (29.6 vs 25.3 years of age) with higher gravidity (3 vs 1). HOMA-IR was persistently higher in CHEU versus CHUU in adjusted analyses (mean difference of 0.07 in log10 HOMA-IR, P = .02) from birth through 36 months of life. Among CHEU, no differences in HOMA-IR were observed from birth through 36 months by in utero ARV exposure status or between AZT and NVP infant prophylaxis arms. In utero HIV/ARV exposure was associated with lower insulin sensitivity throughout the first 36 months of life, indicating persistent early life metabolic disturbances which may raise concern for poorer metabolic health later in life.

Effectiveness of telemedicine for the prevention of mother-to-child transmission of HIV in low-income and middle-income countries: a systematic review and meta-analysis

ObjectivesWe aimed to estimate the effectiveness of telemedicine for the prevention of mother-to-child transmission (PMTCT) program of HIV in low- and middle-income countries (LMICs). MethodsWe did a systematic literature search of 15 databases for articles published from database inception to October 26, 2022, and performed meta-analyses to estimate the pooled risk ratio of intervention effect (RR) and its 95% confidence interval (CI). We used subgroup analyses and meta-regressions to explore variation in the RRs. Funnel plots and Egger regression tests were also performed to assess publication bias. ResultsSeventeen studies were included in the systematic review, with a total sample size of 9118 participants. We found that telemedicine was beneficial for early infant diagnosis (EID) in the sixth week (RR 1.04 [95% CI 1.00-1.09]), exclusive breastfeeding (RR 1.12 [95% CI 1.01-1.24]) and PMTCT retention (RR 1.34 [95% CI 1.16-1.55]). However, we did not find a significant effect of telemedicine on infant prophylaxis, HIV transmission, and ART adherence. Besides, the heterogeneity of ART adherence was associated with enrollment time, while retention was related to ART initiation. ConclusionsOur meta-analysis demonstrated the benefits of telemedicine in improving PMTCT, especially for EID, exclusive breastfeeding, and PMTCT retention.

Hepatitis B prophylaxis of infants born to mothers with no antenatal care: Understanding the nuances in Canada.

Hepatitis B prophylaxis of infants born to mothers with no antenatal care: Understanding the nuances in Canada.

Cost-effectiveness of intervention combinations towards the elimination of vertical transmission of HIV in limited-resource settings: a mathematical modelling study

Since 2000, there has been a substantial global reduction in the vertical transmission of HIV. Despite effective interventions, gaps still remain in progress towards elimination in many low-income and middle-income countries. We developed a mathematical model to determine the most cost-effective combinations of interventions to prevent vertical transmission. We developed a 12-month Markov model to follow a cohort of women of childbearing age (aged 15-49 years) in Zambia (n=1 107 255) who were either pregnant, in delivery, or breastfeeding; the population included in the model reflects the estimated number of pregnant women in Zambia from the 2018 Zambia Demographic and Health Survey. The model incorporated nine interventions: infant prophylaxis; three different HIV retesting schedule options; oral pre-exposure prophylaxis; maternal peer-support groups; regimen shift; tracing of loss to follow-up; and point-of-care viral load testing. We analysed incident HIV infections among mothers and infants, intervention costs, and evaluated 190 scenarios of different combinations of inventions to calculate the incremental cost-effectiveness ratios (ICERs) over 1 year. Three interventions with the greatest reduction in vertical transmission, individually, were support groups for 80% of those in need (35% reduction in infant infections), HIV retesting schedules (6·5% reduction), and infant prophylaxis (4·5% reduction). Of all 190 scenarios evaluated, eight were on the cost-effectiveness frontier (ie, were considered to be cost-effective); all eight included increasing infant prophylaxis, regimen shift, and use of support groups. Excluding the highest-cost scenarios, for a 1-22% increase in total budget, 23-43% of infant infections could be prevented, producing ICERs between US$244 and $16 242. Using the interventions modelled, it is possible to reduce vertical transmission and to cost-effectively prevent up to 1734 infant HIV infections (43% reduction) in Zambia over a period of 1 year. To optimise their effect, these interventions must be scaled with fidelity. Future work is needed to incorporate evidence on additional innovative interventions and HIV risk factors, and to apply the model to other country contexts to support targeted implementation and resource use. The ELMA Foundation.

Continuous Antibiotic Prophylaxis in Infants with Grade III, IV, or V Vesicoureteral Reflux

Continuous Antibiotic Prophylaxis in Infants with Grade III, IV, or V Vesicoureteral Reflux

Fall 2023 ACIP Update on Meningococcal, RSV, COVID-19, and Other Pediatric Vaccines.

The Advisory Committee on Immunization Practices (ACIP), a group of medical and public health experts that provides advice to the Centers for Disease Control and Prevention, normally meets 3 times per year to develop US vaccine recommendations. The ACIP met October 25 to 26, 2023, to discuss meningococcal vaccines, mpox vaccines, respiratory syncytial virus (RSV) vaccines, influenza vaccines, coronavirus disease 2019 (COVID-19) vaccines, and the combined pediatric and adult immunization schedules for 2024. The ACIP also held special meetings on September 12 and September 22 to discuss COVID-19 2023-2024 vaccine recommendations and RSV immunization in pregnant women. This update summarizes the proceedings of these meetings that are most relevant to the pediatric population. Major updates for pediatric clinicians include recommendations for XBB monovalent COVID-19 immunization for the 2023-2024 respiratory season, the recently licensed pentavalent meningococcal conjugate vaccine and mpox vaccination in high-risk young adults, and discussion regarding the parallel strategies of protection against RSV disease in infants via maternal immunization during pregnancy or direct prophylaxis of infants with nirsevimab.

Emicizumab prophylaxis in infants: Single-centre experience.

The hallmark of haemophilia A (HA) therapy is prophylaxis, aimed at spontaneous bleeding prevention. Emicizumab provides a viable alternative to intravenous factor replacement therapy. However, data on its use in infants are limited. This single-centre open arm prospective study reports on emicizumab prophylaxis in infants. We included severe HA patients under 1 year who started emicizumab prophylaxis since 2018, with longitudinal follow-up. The study collected data on demographics, clinical and laboratory variables, the occurrence of bleeding events, surgeries and treatment outcomes. Of the 27 enrolled infants, whose median age at prophylaxis initiation was 7 months, 24 primarily choose to start emicizumab therapy (3/27 switched from FVIII prophylaxis due to development of FVIII inhibitors). The median age for prophylaxis initiation decreased to 3 months in 2023. Following emicizumab initiation, the median calculated ABR decreased, and no intracranial haemorrhages were observed. Thrombin generation showed a significant improvement in peak height and endogenous thrombin potential at steady state after a loading period. Our study highlights a shift towards early prophylaxis in the era of non-replacement therapies. It underscores the need for continuous evaluation and refinement of treatment approaches, emphasizing personalized care and diligent monitoring in the evolving field of paediatric haemophilia care.

Stress Ulcer Prophylaxis Versus Placebo-A Blinded Pilot Randomized Controlled Trial to Evaluate the Safety of Two Strategies in Critically Ill Infants With Congenital Heart Disease.

The routine use of stress ulcer prophylaxis (SUP) in infants with congenital heart disease (CHD) in the cardiac ICU (CICU) is controversial. We aimed to conduct a pilot study to explore the feasibility of performing a subsequent larger trial to assess the safety and efficacy of withholding SUP in this population (NCT03667703). Single-center, prospective, double-blinded, parallel group (SUP vs. placebo), pilot randomized controlled pilot trial (RCT) in infants with CHD admitted to the CICU and anticipated to require respiratory support for greater than 24 hours. Patients were randomized 1:1 (stratified by age and admission type) to receive a histamine-2 receptor antagonist or placebo until respiratory support was discontinued, up to 14 days, or transfer from the CICU, if earlier. Feasibility was defined a priori by thresholds of screening rate, consent rate, timely drug allocation, and protocol adherence. The safety outcome was the rate of clinically significant upper gastrointestinal (UGI) bleeding. We screened 1,426 patients from February 2019 to March 2022; of 132 eligible patients, we gained informed consent in 70 (53%). Two patients did not require CICU admission after obtaining consent, and the remaining 68 patients were randomized to SUP (n = 34) or placebo (n = 34). Ten patients were withdrawn early, because of a change in eligibility (n = 3) or open-label SUP use (n = 7, 10%). Study procedures were completed in 58 patients (89% protocol adherence). All feasibility criteria were met. There were no clinically significant episodes of UGI bleeding during the pilot RCT. The percentage of patients with other nonserious adverse events did not differ between groups. Withholding of SUP in infants with CHD admitted to the CICU was feasible. A larger multicenter RCT designed to confirm the safety of this intervention and its impact on incidence of UGI bleeding, gastrointestinal microbiome, and other clinical outcomes is warranted.

Respiratory Syncytial Virus-Associated Deaths among Children under Five before and during the COVID-19 Pandemic in Bangladesh.

Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory infections in young children worldwide. RSV-associated deaths in children are underreported in Bangladesh. We analyzed hospital-based surveillance data on severe acute respiratory infections (SARIs) in under-five children before (August 2009-February 2020) and during the COVID-19 pandemic (March 2020-March 2022). Using the World Health Organization definition, we identified SARI cases in 14 tertiary-level hospitals. Nasopharyngeal and oropharyngeal swabs were collected for real-time reverse-transcriptase-polymerase chain reaction (rRT-PCR) testing of six respiratory viruses, including RSV. SARI deaths during the pandemic (2.6%, 66) were higher than pre-pandemic (1.8%, 159; p < 0.001). Nearly half of pandemic deaths (47%) had underlying respiratory viruses, similar to the pre-pandemic rate (45%). RSV detection in deaths was consistent pre-pandemic (13%, 20/159) and during the pandemic (12%, 8/66). Children aged < 6 months constituted 57% (16) of RSV-related deaths. Evaluating interventions like maternal vaccination and infant monoclonal antibody prophylaxis is crucial to address RSV, a major contributor to under-five SARI deaths.

Breastfeeding in the United States Among Women With HIV: Con Viewpoint.

To breast feed or not has long been a difficult question for women with human immunodeficiency virus (HIV) in high-income countries, as undetectable HIV in maternal plasma does not translate to zero risk of transmission while breastfeeding, and clean water and formula are readily available. Recent, and more permissive, changes in US and other high-income-country guidelines regarding breastfeeding underscore this issue and acknowledge the information gaps that are essential for informed maternal choice and provider management. These include lack of guidance as to routine monitoring of mothers during lactation, type and length of prophylaxis for infants, and lack of data on factors associated with increased breast-milk viral load and risk of transmission. Ancillary to data are the education and staffing needs for providers participating in the management of breastfeeding individuals. Future studies of breast-milk transmission will need to evaluate these gaps so that we can move transmission to zero.