infant

Rationale: Respiratory syncytial virus (RSV) is a highly transmissible pathogen that causes varying degrees of respiratory illness across all age groups. The safety and efficacy profiles of available RSV vaccines, a critical consideration for their integration into public health strategies and clinical practice, remain uncertain.

Objectives: To assess the benefits and harms of RSV vaccines compared to placebo, no intervention, vaccines for other respiratory infections, other RSV vaccines, or monoclonal antibodies (mAbs) across all human populations.

Search methods: We conducted a comprehensive literature search of CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, and the WHO ICTRP following standard systematic review methodology from 2000 to April 2024.

Eligibility criteria: We included both randomised controlled trials (RCTs) and non-randomised studies of interventions (NRSIs) involving all human populations comparing RSV vaccines with placebo, no intervention, vaccines for other respiratory infections, other RSV vaccines, or mAbs. We excluded studies focused on dose-finding schedules and immunogenicity assessment.

Outcomes: Benefits included frequency of RSV illness (both lower and upper respiratory illness) confirmed by laboratory tests (RSV-associated lower respiratory tract illness and RSV-associated acute respiratory illness); hospitalisation due to RSV disease (both lower and upper respiratory illness) confirmed by laboratory tests; mortality from illness caused by RSV (confirmed by laboratory test); all-cause mortality; and admission to an intensive care unit. Harms included serious adverse events (SAEs) related to vaccination, including neurological disorders such as Guillain-Barré syndrome.

Risk of bias: We assessed risk of bias in RCTs using Cochrane's RoB 2 tool.

Synthesis methods: We used standard Cochrane methods.

Included studies: We identified 14 RCTs: five trials (101,825 participants) on older adults; three trials (12,010 participants) on maternal vaccination and effects on infants; one trial (300 participants) on women of childbearing age; and five trials (192 participants) on infants and children. We identified no NRSIs.

Synthesis of results: RSV prefusion vaccine versus placebo in older adults These vaccines reduced RSV-associated lower respiratory tract illness with vaccine efficacy (VE) of 77% (95% confidence interval (CI) 0.70 to 0.83; risk ratio (RR) 0.23, 95% CI 0.17 to 0.30; 4 RCTs, 99,931 participants; high-certainty evidence) and RSV-associated acute respiratory illness with VE of 67% (95% CI 0.60 to 0.73; RR 0.33, 95% CI 0.27 to 0.40; 3 RCTs, 94,339 participants; high-certainty evidence). There may be little to no difference in mortality from illness caused by RSV, all-cause mortality, and SAEs related to vaccination (low-certainty evidence). RSV postfusion F protein-based vaccine versus placebo in older adults There is probably little to no difference in RSV-associated lower respiratory tract illness with VE of -0.37% (95% CI -1.96 to 0.37; RR 1.37, 95% CI 0.63 to 2.96; 1 RCT, 1894 participants; moderate-certainty evidence) and RSV-associated acute respiratory illness with VE of -0.07% (95% CI -1.15 to 0.47; RR 1.07, 95% CI 0.53 to 2.15; 1 RCT, 1894 participants; moderate-certainty evidence). There may be little to no difference in mortality from illness caused by RSV, all-cause mortality, and SAEs related to vaccination (low-certainty evidence). Maternal RSV F protein-based vaccine versus placebo in infants These vaccines reduced medically attended RSV-associated lower respiratory tract illness with VE of 54% (95% CI 0.28 to 0.71; RR 0.46, 95% CI 0.29 to 0.72; 3 RCTs, 12,010 participants; high-certainty evidence), medically attended RSV-associated severe lower respiratory tract illness with VE of 74% (95% CI 0.44 to 0.88; RR 0.26, 95% CI 0.12 to 0.56; 3 RCTs, 12,010 participants; high-certainty evidence), and hospitalisation due to RSV disease with VE of 54% (95% CI 0.27 to 0.71; RR 0.46, 95% CI 0.29 to 0.73; 2 RCTs, 11,502 participants; high-certainty evidence) in infants. There may be little to no difference in mortality from illness caused by RSV, all-cause mortality, and SAEs related to vaccination in mothers and infants (low-certainty evidence). Live-attenuated RSV vaccines versus placebo in infants and children The evidence is very uncertain regarding all-cause medically attended acute respiratory illness (MAARI) with VE of 26% (95% CI -0.01 to 0.46; RR 0.74, 95% CI 0.54 to 1.01; 5 RCTs, 171 participants; very low-certainty evidence) and RSV-associated MAARI with VE of 38% (95% CI -0.24 to 0.69; RR 0.62, 95% CI 0.31 to 1.24; 5 RCTs, 192 participants; very low-certainty evidence). There may be little to no difference in SAEs related to vaccination (low-certainty evidence). RSV recombinant F nanoparticle vaccine versus placebo in women of childbearing age The evidence is very uncertain regarding new RSV infections with VE of 50% (95% CI 0.08 to 0.73; RR 0.50, 95% CI 0.27 to 0.92; 1 RCT, 300 participants; very low-certainty evidence). There may be little to no difference in mortality from illness caused by RSV, all-cause mortality, and SAEs related to vaccination (low-certainty evidence). Phase III trials consistently demonstrated low risk of bias. Whilst phase I and II trials occasionally raised concerns about selection bias in the randomisation process, the overall evidence was deemed robust.

Authors' conclusions: RSV prefusion vaccines reduced RSV-associated lower respiratory tract illness and acute respiratory illness in older adults. There may be little to no difference in SAEs related to vaccination in older adults. Maternal vaccination with RSV F protein-based vaccines reduced medically attended RSV-associated lower respiratory tract illness and severe cases in infants. There may be little to no difference in SAEs related to vaccination in mothers and infants. The evidence is very uncertain regarding the effects of RSV vaccine on women of childbearing age, and the effects of live-attenuated RSV vaccines on infants and children; there may be little to no difference in SAEs related to vaccination.

Funding: This review was funded by the EU4Health Programme under a service contract with the European Health and Digital Executive Agency (HaDEA).

Registration: The review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42023439128).

Objective: To assist busy primary care providers caring for infants and young children and their families by providing them with the most recent recommendations and supportive evidence included in the 2024 edition of the Rourke Baby Record (RBR).

Quality of evidence: Articles from pediatric preventive care literature (January 2019 to March 2023) were reviewed for relevance and quality of evidence. When available, evidence from systematic reviews, relevant clinical guidelines, and clinical trials were incorporated. In the absence of high-level evidence, observational studies and expert opinion on the topic were included. Primary research studies were reviewed and critically appraised using a modified protocol.

Main message: Notable updates in the 2024 edition of the RBR include the promotion of early relational health for families; identification of targeted support and resources as opposed to labelling of high-risk groups; guidance on culturally safe care; clarification and evidence-based adjustments of the age of achievement of some developmental surveillance milestones; recommendations on plant-based beverages, vegetarian, and vegan diets; screening considerations for iron deficiency; dangers of ingestion of button batteries and cannabis edibles; literacy and socioemotional benefits of reading, singing, and storytelling; the importance of unstructured outdoor play; the environment's effect on children's health; the significance of sentinel injuries; acholic stools; and the normal presence and abnormal persistence of developmental (primitive) reflexes.

Conclusion: Building on its 40-year history, the 2024 RBR provides freely available, evidence-informed recommendations to guide clinicians in providing effective, up-to-date, and comprehensive preventive pediatric care. Despite the challenging and evolving landscape of primary health care delivery, the RBR will continue to support primary care providers.

Objectives. To review the evidence on the association between breastfeeding and infant and child health outcomes, including the extent to which these associations vary by the intensity, duration, mode, and source of breastmilk consumption. In this review, breastfeeding refers to feeding breastmilk whether directly from the breast or other means and includes breastmilk from pasteurized donor milk.

Data sources. Systematic literature searches in MEDLINE, Embase and CINAHL for English-language articles published from 2006 to August 14, 2024. We identified additional studies from reference lists and technical experts.

Review methods. We worked with our sponsor and a panel of technical experts to identify the outcomes of interest for this review. The evidence for more than 20 outcomes was synthesized, including outcomes related to infectious diseases, asthma and allergic conditions, oral health, autoimmune gastrointestinal conditions, endocrine conditions, cardiovascular disease (CVD), childhood cancer, cognitive development, and infant mortality. We relied on existing systematic reviews (ESRs) for all outcomes and conducted bridge searches for newer primary studies since the search date of the most recent and relevant ESR. Studies were evaluated for eligibility and quality, and data were abstracted on study design, demographics, breastfeeding exposures and referents, and outcomes. We synthesized the evidence by outcome, summarizing the results of ESRs alongside those of newer primary studies. No meta-analyses were conducted given the combination of ESR and primary study evidence and heterogeneity in exposures and outcomes; but figures were created to visually display point estimates across studies.

Results. A total of 29 ESRs and 145 primary studies were included. The cumulative number of studies included for each outcome varied from only 4 studies examining the relationship between breastfeeding and type 2 diabetes to more than 180 studies reporting on the relationship between breastfeeding and obesity-related outcomes. We rated the strength of evidence as “Low” or “Moderate” for most outcomes, given limitations of the underlying evidence base, along with concerns related to heterogeneity of the study designs, and the consistency and precision of results. An association indicating a reduced risk from “more” versus “less” breastfeeding was most apparent for otitis media, asthma, obesity in childhood, and childhood leukemia. A protective association of breastfeeding was also found for severe respiratory and gastrointestinal infections in younger children, allergic rhinitis, malocclusion, inflammatory bowel disease, type 1 diabetes, rapid weight gain and growth, systolic blood pressure, and infant mortality, including sudden unexpected infant death, although our confidence in these findings was lower. There was no apparent association for the outcomes of atopic dermatitis, celiac disease, and cognitive ability. An association indicating an increased risk of dental caries was noted for breastfeeding 12 months or longer. There was insufficient evidence to draw conclusions about the relationship with food allergies and type 2 diabetes and no data on coronavirus disease 2019 (COVID-19) or CVD endpoint outcomes (i.e., events or mortality). While nearly all outcomes had evidence on ever (versus never) breastfeeding, exclusive (versus nonexclusive or no) breastfeeding, and longer durations (versus shorter or no) of any or exclusive breastfeeding, the exposure comparisons and categorizations reported in the ESRs and primary evidence made it extremely difficult to examine the nuances of these relationships. There was no clear “threshold” of breastfeeding that appeared to be most beneficial for any outcome. Furthermore, there were little data on how the relationships varied by mode of breastfeeding or source of breastmilk.

Conclusions. Breastfeeding is associated with beneficial effects for several infant and child outcomes, although there are limitations to the data that preclude high certainty in the findings. Further research that addresses the limitations of existing studies is needed to continue to inform national guidelines and initiatives.

BACKGROUND
Food allergies are common and are associated with substantial morbidity; the only approved treatment is oral immunotherapy for peanut allergy.
METHODS
In this trial, we assessed whether omalizumab, a monoclonal anti-IgE antibody, would be effective and safe as monotherapy in patients with multiple food allergies. Persons 1 to 55 years of age who were allergic to peanuts and at least two other trial-specified foods (cashew, milk, egg, walnut, wheat, and hazelnut) were screened. Inclusion required a reaction to a food challenge of 100 mg or less of peanut protein and 300 mg or less of the two other foods. Participants were randomly assigned, in a 2:1 ratio, to receive omalizumab or placebo administered subcutaneously (with the dose based on weight and IgE levels) every 2 to 4 weeks for 16 to 20 weeks, after which the challenges were repeated. The primary end point was ingestion of peanut protein in a single dose of 600 mg or more without dose-limiting symptoms. The three key secondary end points were the consumption of cashew, of milk, and of egg in single doses of at least 1000 mg each without dose-limiting symptoms. The first 60 participants (59 of whom were children or adolescents) who completed this first stage were enrolled in a 24-week open-label extension.

RESULTS
Of the 462 persons who were screened, 180 underwent randomization. The analysis population consisted of the 177 children and adolescents (1 to 17 years of age). A total of 79 of the 118 participants (67%) receiving omalizumab met the primary end-point criteria, as compared with 4 of the 59 participants (7%) receiving placebo (P<0.001). Results for the key secondary end points were consistent with those of the primary end point (cashew, 41% vs. 3%; milk, 66% vs. 10%; egg, 67% vs. 0%; P<0.001 for all comparisons). Safety end points did not differ between the groups, aside from more injection-site reactions in the omalizumab group.
CONCLUSIONS
In persons as young as 1 year of age with multiple food allergies, omalizumab treatment for 16 weeks was superior to placebo in increasing the reaction threshold for peanut and other common food allergens. (Funded by the National Institute of Allergy and Infectious Diseases and others; ClinicalTrials.gov number, NCT03881696.)