BACKGROUND:We aimed to investigate associations between newborn metabolite concentrations and the development of early-life wheezing and asthma. Our goal was to advance understanding of pathways involved in childhood asthma pathogenesis and identify potential targets for disease prevention. METHODS:Our study populations included children enrolled in two Environmental influences on Child Health Outcomes (ECHO) cohorts (INSPIRE, discovery; Healthy Start, replication) with linked newborn screening metabolic and outcome data (4-year recurrent wheeze and 5-year current asthma). We used elastic net penalized regression, followed by multivariable logistic regression, to determine metabolite-wheeze and metabolite-asthma associations. We secondarily assessed whether metabolite-asthma associations differed by asthma phenotype in the discovery cohort. RESULTS:Among 1554 INSPIRE children, the prevalence of recurrent wheeze and current asthma is 11% and 18%, respectively. Newborn concentrations of butyrylcarnitine + isobutyrylcarnitine (C4) and decenoylcarnitine (C10:1) are associated with recurrent wheeze (C4: aOR 0.75 [95% CI 0.59, 0.95]; C10:1: aOR 1.42 [95% CI 1.13, 1.78]), while linoleoylcarnitine (C18:2) and citrulline (CIT) are associated with current asthma (C18:2: aOR 1.20 [95% CI 1.02, 1.41]; CIT: aOR 0.74 [95% CI 0.58, 0.93]). The effect size and directionality of the association between C18:2 and childhood asthma is similar in Healthy Start (n = 518), although the relationship is not statistically significant. C18:2 is additionally associated with increased odds of non-allergic asthma compared to no asthma in INSPIRE. CONCLUSIONS:These findings suggest biologic pathways that may be involved in childhood asthma pathogenesis and support investigation of the mechanisms underlying these relationships given the potential for targeted prevention strategies.

Background: Infant respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) is associated with subsequent childhood wheeze and asthma (wheeze/asthma), with accumulating evidence supporting a causal relationship, but the attributable burden in the United States is uncertain. Methods: We developed a population-based model integrating national surveillance and epidemiologic data to estimate the population attributable fraction of childhood wheeze/asthma at age 6 associated with medically attended RSV LRTI during infancy. As a secondary analysis, RSV LRTI incidence was modeled under a national nirsevimab program at 50% coverage, reflecting contemporary RSV protection levels. The RSV LRTI-wheeze/asthma association was derived from a systematic review and meta-analysis. Results: We estimated 379,659 (95% uncertainty interval [UI] 207,061–542,490) medically attended RSV LRTI episodes in a US birth cohort during infancy. Overall, 11.1% (95% UI 1.9–23.2) of childhood wheeze/asthma at age 6 was attributable to RSV LRTI, corresponding to 35,800 (95% UI 6,052–74,980) cases. A national nirsevimab program at 50% coverage reduced RSV-attributable wheeze/asthma burden by 27.4% (95% UI 20.1–37.2), corresponding to 9,823 (95% UI 1,761–22,326) fewer cases. Conclusion: Nearly 1 in 9 (11.1%) cases of childhood wheeze/asthma may be attributable to RSV LRTI during infancy, and a national nirsevimab program reduced RSV-attributable wheeze/asthma burden by 27.4% in our model. These findings suggest that infant RSV LRTI may account for a substantial burden of childhood wheeze/asthma in the United States. Failure to account for RSV-attributable wheeze/asthma may underestimate the burden of RSV disease and the potential benefits of RSV prevention.

INTRODUCTION:The airway epithelial barrier continues to develop during the first year of life, representing a critical time window of susceptibility to the effects of respiratory viruses that may contribute to the development of childhood asthma. This study specifically aimed to assess the impact of respiratory syncytial virus (RSV) infection on the longitudinal development of the airway epithelium, airway metabolism, DNA methylation and subsequent childhood asthma. METHODS AND ANALYSIS:The Wheezing, Asthma and Viral effects on the Epithelial Structure and function (WAVES) birth cohort study is a prospective, observational birth cohort that is enrolling mother-child dyads beginning in pregnancy and following children through age 5 years. It is designed as a quasi-natural randomisation of RSV infection in infancy, capturing the first RSV infection event during infancy and longitudinal nasal sampling from birth through age 5 years for multi-omic assays and assessment of clinical outcomes. The WAVES study protocol will enrol 250 pregnant women and their offspring (200 at high-risk for asthma and 50 at general-risk for asthma). The primary outcomes are pathways through which RSV infection intersects with airway epithelial development leading to asthma by age 5 years. We will employ a longitudinal systems biology approach to investigate the development of the airway epithelium following infant RSV infection in those who do and do not develop asthma. This approach will integrate single-cell and bulk RNA-sequencing gene expression, metabolomic and epigenetic data at the resolution of epithelial cell subsets. ETHICS AND DISSEMINATION:This study has been approved by the Vanderbilt University Medical Center IRB (#222277), and study results will be communicated in peer-reviewed publications and to the study participants and lay community. By analysing these longitudinal multi-omic datasets, we aim to uncover key mechanisms driving airway epithelial development and identify how these processes are altered by early-life RSV infection and contribute to the development of early-life respiratory morbidity and asthma.

Animal and in vitro studies suggest that leukotriene-modifying agents (LMAs) may decrease susceptibility to influenza illness. We estimated the effect of LMAs on severe human influenza illness in a retrospective cohort using three analytic approaches: (1) a marginal structural model, (2) a proportional hazards model, and (3) a case-time-control design. Study populations included individuals with asthma and/or allergic rhinitis for whom LMAs are approved and who were enrolled in Tennessee Medicaid (TennCare) or Department of Defense Military Health System (DoD MHS) from 1995 to 2019. Exposed periods were defined by LMA prescription start dates plus days' supply. Severe influenza illness was defined using previously validated International Classification of Diseases criteria. Montelukast accounted for 99% of LMA prescription fills. Adjusted incidence rate ratios from the marginal structural model and adjusted hazard ratios from the proportional hazards model were 1.26 (95% confidence interval [CI], 0.99-1.59) and 1.14 (95% CI, 0.92-1.41) for TennCare and 1.01 (95% CI, 0.84-1.21) and 0.97 (95% CI, 0.82-1.16) for DoD MHS, respectively. Adjusted odds ratios from the case-time-control were 1.11 (95% CI, 0.74-1.65) for TennCare and 1.91 (95% CI, 1.29-2.84) for DoD MHS. Findings in different populations and designs do not support the use of LMAs for chemoprophylaxis of severe influenza illness. Conclusions regarding LMAs other than montelukast were not possible.

Investigation of in utero, tissue-specific molecular pathways contributing to prenatal programming of childhood-onset asthma is needed to develop effective, targeted prevention strategies. We aimed to examine the relationship between predicted gene expression in placenta and childhood-onset asthma and to compare relationships between childhood- and adult-onset asthma. Asthma genome-wide association study published summary statistics were obtained from the UK Biobank and published placental gene expression quantitative trait loci were obtained from the Rhode Island Child Health Study. We used S-PrediXcan to evaluate and compare associations between placental predicted gene expression and childhood- and adult-onset asthma and to determine whether signals were placenta-specific. Among 8,038 tested placental predicted expression-asthma associations, we identified 56 (0.7%) genes only significantly associated with childhood-onset asthma, 12 (0.1%) genes only significantly associated with adult-onset asthma, and 18 (0.2%) shared genes. Predicted expression of several genes (ACTL9, AMN, C9orf38, C11orf30, CTSE, EFCAB13, EIF4E1B, FN1, GLS2, IL6, IVL, LZIC, MAN2A2, MEGT1, RACGAP1, SMAD6, SPATA5, TMEM25, VTI1B, WDR19) was not significantly associated with childhood- or adult-onset asthma in any non-placental tissue, suggesting that the associations may be placenta-specific. This study identified alterations in predicted expression of placental genes associated with transcriptional pathways critical to the development of asthma. We identified unique and shared pathways, particularly related to immune regulation, associated with childhood- and adult-onset. This expands our understanding of the fetal origins of asthma, highlights the placenta as an informative tissue in understanding asthma pathogenesis, and identifies target genes to prioritize for future functional studies.

Introduction/Rationale: Respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) is a common cause of hospitalization in young children. Newly licensed preventive interventions, including maternal vaccines and extended half-life RSV monoclonal antibodies (mAb), are recommended to prevent RSV-LRTI during the first year of life. Early childhood RSV-LRTI is associated with the subsequent development of recurrent wheezing illness and asthma (wheeze/asthma) although this relationship may be confounded in part by genetic predisposition. We modeled the potential impact of RSV-LRTI disease and prevention on pediatric wheeze/asthma in the United States. Methods: We adapted a national birth cohort model with 12 monthly cohorts which integrated demographics, RSV-LRTI incidence, prevention efficacy from clinical trials, and vaccine coverage to estimate health outcomes averted during the first year of life by RSV-LRTI mAb programs. We expanded the model to incorporate the asthma prevalence at 6 years (8.8%) from the National Health Interview Survey, and the relative risk (2.45) of developing wheeze/asthma given RSV-LRTI during the first year of life, as calculated by a 2020 systematic review. We projected RSV-LRTI and wheeze/asthma outcomes under three scenarios: 1) no preventive interventions, 2) pre-seasonal RSV-LRTI mAb immunoprophylaxis (mAb), and 3) a counterfactual scenario assuming no RSV-LRTI events (no RSV-LRTI). Results: In the simulated birth cohort (n=3645942), the frequencies of RSV-LRTI events during the first year of life was 534,895 (no intervention scenario) and 448,964 (mAb scenario), and 0 (no RSV-LRTI scenario). The estimated prevalence per 10,000 children of all-cause wheeze/asthma at age six was 880 (no intervention scenario), 855 (mAb scenario), and 726 (no RSV-LRTI scenario). At the same age, the prevalence per 10,000 children of RSV-LRTI-attributable wheeze/asthma was 154 (no intervention scenario) and 129 (mAb scenario), and 0 (no RSV-LRTI scenario). We estimate that RSV-LRTI mAb programs can decrease all-cause wheeze/asthma prevalence at 6 years by 2.8% and RSV-LRTI-attributable wheeze/asthma at 6 years by 16.1%. We estimate that 17.5% of all wheeze/asthma at 6 years of age was attributable to RSV-LRTI. Conclusion: While RSV-LRTI immunoprophylaxis programs in the United States will substantially decrease severe respiratory infections in young children, they may also meaningfully decrease wheeze/asthma prevalence. We estimate RSV-LRTI prevention programs may reduce nearly 9,000 cases of pediatric wheeze/asthma annually. Future analyses will incorporate uncertainty into our estimates. Our modeling of all-cause wheeze/asthma attributable to RSV-LRTI suggests that improvements in RSV-LRTI prevention coverage, effectiveness, and duration of protection can lead to even greater impacts.

BACKGROUND:There is growing interest in understanding the link between early life exposures to ambient air pollution and childhood blood pressure; however, existing findings, largely from single site/cohort studies, are inconclusive. METHODS:We examined the association between exposures to fine particulate matter (PM2.5) and nitrogen dioxide (NO2) and blood pressure measured at age 5-12 years in 4863 U.S. children from 20 pregnancy cohorts of the NIH ECHO cohort. Point-based residential exposures were derived from spatiotemporal models with a biweekly resolution and averaged over each trimester, the whole pregnancy, and child age 0-2 years. We converted systolic (SBP) and diastolic blood pressure (DBP) to age-, sex-, and height-specific percentiles and classified children with SBP and/or DBP ≥ 90th percentile as high blood pressure (HBP). Associations of PM2.5 (per 5-μ g/m3) or NO2 (per 10-ppb) exposures with blood pressure outcomes were estimated using linear and Poisson regressions adjusted for sociodemographic, lifestyle, temporal, and spatial confounders. RESULTS:Across windows, mean PM2.5 ranged from 7.6 to 7.9 μ g/m3, and mean NO2 ranged was 8.1-8.8 ppb. We found positive associations of PM2.5 in the first trimester with SBP percentile (β: 1.92, 95 %CI: 0.02, 3.83) and risk of HBP (RR: 1.16, 95 %CI: 1.02, 1.33). Higher PM2.5 exposures averaged over pregnancy and age 0-2 years were also related to elevated SBP percentiles and a higher risk of HBP, but with lower precision. Contrary to our hypotheses, inverse associations of pregnancy average NO2 with both SBP (β: -2.42, 95 %CI: -4.70, -0.14) and DBP (β: -1.94, 95 %CI: -3.81, -0.08) percentiles were suggested. CONCLUSION:Results reinforce the detrimental effects of PM2.5 on childhood cardiometabolic health, even at low exposure levels. Such findings can inform regulatory policy on acceptable air pollution levels and appropriate controls. The inverse association between prenatal NO2 and blood pressure was counterintuitive and warrants further investigation.

Prospective birth cohort studies have identified important factors associated with the development and occurrence of early life conditions and facilitated exploration of causal mechanisms. We discuss the strengths, importance, and biases of birth cohort data for causal inference and predictive modeling, using childhood asthma and allergic disease research as an illustrative example. State-of-the-art study design and statistical methodologies are considered and recommended to mitigate bias and infer causality, as well as using cohort assembly for increased power, sample size, and generalizability. These include effective control for confounding, limiting loss to follow-up, and leveraging risk factors for precision. While logistical and methodologic challenges exist for establishing, maintaining, and analyzing birth cohorts and their respective data, this prospective study design offers numerous benefits for inferring causality over other observational designs, and it is often the only alternative for assessing critical research questions. With long-term follow-up and extensive data collection, birth cohort studies represent powerful tools for studying disease etiology and have been integral to developing effective treatment and prevention strategies.

Rationale: Complete blood count (CBC)-derived inflammation indices have recently been associated with asthma and asthma morbidity. These indices are novel, calculated from a routine lab test, and have primarily been assessed in adult populations. Biomarkers for childhood asthma phenotypes are needed, especially for non-allergic asthma, which remains an understudied phenotype. We aimed to assess associations of CBC-derived inflammation indices with allergic and non-allergic childhood asthma phenotypes. Methods: In a birth cohort of participants who were enrolled as healthy term infants to study asthma development (INSPIRE), asthma was ascertained at the 6-year follow-up visit. Children with an available CBC with differential were included, and inflammation indices were calculated. Allergic and non-allergic asthma phenotypes were defined by asthma at age 6 years (physician diagnosis and symptoms, systemic corticosteroid use, or asthma healthcare utilization in prior 12 months) and specific IgE and/or allergen skin testing at age 3 years. Multinomial logistic regression models were performed to assess associations between each log-transformed CBC-derived inflammation index and allergic and non-allergic asthma phenotypes (referent: no asthma), adjusted for sex, infant race and ethnicity, maternal asthma, and month CBC was obtained. Results: Among 418 children with asthma phenotype and CBC data (36% of 6-year cohort), 11% (48/418) had allergic asthma, 9% (37/418) had non-allergic asthma, and 80% (333/418) had no asthma. The median age at time of CBC collection was 6.30 years (interquartile range 6.11-6.62). In cross-sectional analyses, a higher eosinophil-to-lymphocyte ratio was associated with allergic asthma (adjusted odds ratio [aOR] 2.20, 95% confidence interval [CI] 1.42-3.41) but not with non-allergic asthma (aOR 0.96, 95%CI 0.61-1.50). Conversely, the association with platelet-to-lymphocyte ratio was nominally significant and may suggest that platelet-to-lymphocyte ratio is associated with non-allergic asthma (aOR 0.31, 95%CI 0.09-1.02) but not with allergic asthma (aOR 1.16, 95%CI 0.40-3.38). Associations with other CBC-derived inflammation indices (neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, systemic immune-inflammation index, and systemic inflammatory response index) were not statistically significant. Conclusions: The CBC, a readily attainable lab test, and its derived inflammation indices may provide clinical utility as a biomarker for childhood asthma phenotypes. The association with eosinophil-to-lymphocyte ratio and allergic asthma is consistent with T2-high and eosinophilic inflammation. Platelet-to-lymphocyte ratio may be a biomarker for the non-allergic asthma phenotype in children and may provide insight into understanding non-allergic inflammation in childhood asthma. Further studies are needed to determine the contribution of CBC-derived inflammation indices in predicting asthma phenotypes and severity in children.

BACKGROUND:It is unknown whether nasal corticosteroid (NCS) or inhaled corticosteroid (ICS) use impacts the susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. OBJECTIVES:We sought to examine the associations of NCS and ICS use with the risk of SARS-CoV-2 infection among individuals with allergic rhinitis or asthma. METHODS:This is a prospective, multicenter, SARS-CoV-2 surveillance study of households with children. Nasal swabs were obtained from participants every 2 weeks with additional collections based on coronavirus disease 2019-related symptoms. In our primary adjusted models, we examined the association of NCS or ICS use at study entry (in participants with allergic rhinitis or asthma, respectively) with the time to the first SARS-CoV-2-positive quantitative PCR testing using Cox proportional hazard regression. RESULTS:There were 2211 participants in the 1113 households included. The associations of NCS and ICS use with the risk of SARS-CoV-2 infection were modified by age (P for both interactions <.05). NCS and ICS use were individually associated with higher risks of SARS-CoV-2 infection among adults (adjusted hazard ratio [aHR] = 1.88, 95% CI: 1.14-3.12, P = .01, and aHR = 2.15, 95% CI: 1.003-4.63, P = .049, respectively). The association of NCS use with the risk of SARS-CoV-2 infection in adults was consistent in a series of sensitivity analyses. There was no association of NCS or ICS use with the risk of SARS-CoV-2 infection in children. CONCLUSION:Our findings suggest that the risk of SARS-CoV-2 infection is increased in adults who use NCS but not in children. Similar, albeit less consistent, age-dependent findings were observed for ICS use. While the results of this observational study should be interpreted with caution, they emphasize the need to conduct studies to understand potential mechanisms that could explain these findings.

Importance:Inorganic arsenic is associated with adverse birth outcomes, but evidence is limited for public water concentrations (modifiable by federal regulatory action) in US populations. Objective:To evaluate the association between prenatal public water arsenic exposure below the federal regulatory standard of 10 μg/L and birth outcomes in the US. Design, Setting, and Participants:This cohort study analyzed observational pregnancy cohort data from the Environmental Influences on Child Health Outcomes (ECHO) Cohort for birthing parent-infant dyads from 35 pregnancy cohort sites. Infants were born between 2005 and 2020. The data were analyzed between 2024 and 2025. Exposure:Individual, time-weighted, mean prenatal public water arsenic exposures were estimated by joining Zip Code Tabulation Area-level public water arsenic concentrations with monthly residential history data during pregnancy. Main Outcome and Measure:Adjusted risk ratios (RRs) of preterm birth, low birth weight, and small for gestational age were evaluated. Adjusted RRs, mean differences in birth weight-for-gestational age z score and birth weight, and the geometric mean ratio of gestational age at birth were calculated via cubic splines, per 1 μg/L higher prenatal water arsenic, and across policy-relevant categories of exposure. Results:The cohort comprised 13 998 birthing parents (mean [SD] age, 30.8 [5.6] years) of whom 4.5% were of American Indian, Alaska Native, Native Hawaiian, or Pacific Islander; 7.2% Asian; 12.4% Black; 56.1% White; 4.2% multiple races; and 8.5% another race and 28.1% were of Hispanic/Latino and 70.4% non-Hispanic/Latino ethnicity. Prenatal public water arsenic ranged from less than 0.35 to 37.28 μg/L. In spline models, prenatal public water arsenic was associated with a higher risk of low birth weight, lower birth weight, and lower birth weight-for-gestational age z score, although effect estimates lacked precision. The RR of low birth weight per 1 μg/L higher prenatal water arsenic was higher among Black (1.02; 95% CI, 1.01-1.03), Hispanic/Latino (1.07; 95% CI 1.02-l.12), and White (1.04; 95% CI, 102-1.06) birthing parents, and the RR for preterm birth was higher among Hispanic/Latino birthing parents (1.05; 95% CI, 1.01-1.09). The mean difference of birth weight and birth weight-for-gestational age z score per 1 μg/L higher prenatal water arsenic was more pronounced among White birthing parents (-10 g [95% CI, -17 to -3 g]; -0.02 SDs [95% CI -0.03 to -0.01 SDs]). No evidence that prenatal public water arsenic mediated the association between birthing parent race and ethnicity and adverse birth outcomes was observed. Conclusions and Relevance:In this cohort study of birthing parent-infant dyads across the US, arsenic measured in public water systems was associated with birth outcomes at levels below the current US Environmental Protection Agency's maximum contaminant level. The findings suggest that further reducing the maximum contaminant level for arsenic may decrease the number of infants with low birth weight in the US.

Importance Limited access to healthy foods, resulting from residence in neighborhoods with low food access, is a public health concern. The contribution of this exposure in early life to child obesity remains uncertain. Objective To examine associations of neighborhood food access during pregnancy or early childhood with child body mass index (BMI) and obesity risk. Design, Setting, and Participants Data from cohorts participating in the US nationwide Environmental Influences on Child Health Outcomes consortium between January 1, 1994, and March 31, 2023, were used. Participant inclusion required a geocoded residential address in pregnancy (mean 32.4 gestational weeks) or early childhood (mean 4.3 years) and information on child BMI. ExposuresResidence in low-income, low-food access neighborhoods, defined as low-income neighborhoods where the nearest supermarket is more than 0.5 miles for urban areas or more than 10 miles for rural areas. Main Outcomes and MeasuresBMI z score, obesity (age- and sex-specific BMI >= 95th percentile), and severe obesity (age- and sex-specific BMI >= 120% of the 95th percentile) from age 0 to 15 years. Results Of 28 359 children (55 cohorts; 14 657 [51.7%] male and 13 702 [48.3%] female; 590 [2.2%] American Indian, Alaska Native, Native Hawaiian, or Other Pacific Islander; 1430 [5.4%] Asian; 4034 [15.3%] Black; 17 730 [67.2%] White; and 2592 [9.8%] other [unspecified] or more than 1 race; 5754 [20.9%] Hispanic and 21 838 [79.1%] non-Hispanic) with neighborhood food access data, 23.2% resided in low-income, low-food access neighborhoods in pregnancy and 24.4% in early childhood. After adjusting for individual sociodemographic characteristics, residence in low-income, low-food access (vs non-low-income, low-food access) neighborhoods in pregnancy was associated with higher BMI z scores at ages 5 years (beta, 0.07; 95% CI, 0.03-0.11), 10 years (beta, 0.11; 95% CI, 0.06-0.17), and 15 years (beta, 0.16; 95% CI, 0.07-0.24); higher obesity risk at 5 years (risk ratio [RR], 1.37; 95% CI, 1.21-1.55), 10 years (RR, 1.71; 95% CI, 1.37-2.12), and 15 years (RR, 2.08; 95% CI, 1.53-2.83); and higher severe obesity risk at 5 years (RR, 1.21; 95% CI, 0.95-1.53), 10 years (RR, 1.54; 95% CI, 1.20-1.99), and 15 years (RR, 1.92; 95% CI, 1.32-2.80). Findings were similar for residence in low-income, low-food access neighborhoods in early childhood. These associations were robust to alternative definitions of low income and low food access and additional adjustment for prenatal characteristics associated with child obesity. Conclusions Residence in low-income, low-food access neighborhoods in early life was associated with higher subsequent child BMI and higher risk of obesity and severe obesity. We encourage future studies to examine whether investments in neighborhood resources to improve food access in early life would prevent child obesity.

Background:Currently, there are no available tools to identify infants at the highest risk of significant morbidity and mortality from respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) who would benefit most from RSV prevention products. The objective was to develop and internally validate a personalized risk prediction tool for use among all newborns that uses readily available birth/postnatal data to predict RSV LRTI requiring intensive care unit (ICU) admission.Methods:We conducted a population-based birth cohort study of infants born from 1995 to 2007, insured by the Tennessee Medicaid Program, and who did not receive RSV immunoprophylaxis during the first year of life. The primary outcome was severe RSV LRTI requiring ICU admission during the first year of life. We built a multivariable logistic regression model including demographic and clinical variables available at or shortly after birth to predict the primary outcome.Results:In a population-based sample of 429 365 infants, 713 (0.2%) had severe RSV LRTI requiring ICU admission. The median age of admission was 66 days (interquartile range, 37-120). Our tool, including 19 variables, demonstrated good predictive accuracy (area under the curve, 0.78; 95% confidence interval, 0.77-0.80) and identified infants who did not qualify for palivizumab, based on American Academy of Pediatrics guidelines, but had higher predicted risk levels than infants who qualified (27% of noneligible infants with >0.16% predicted probabilities [lower quartile for eligible infants]).Conclusions:We developed a personalized tool that identified infants at increased risk for severe RSV LRTI requiring ICU admission, expected to benefit most from immunoprophylaxis.

BACKGROUND: The contribution of prenatal anthropometric measures to the development of specific fi c childhood asthma phenotypes is not known. OBJECTIVE: We aimed to evaluate associations between prepregnancy body mass index (BMI) and gestational weight gain (GWG) with allergic and nonallergic asthma phenotypes in childhood. METHODS: Our study population included term, healthy infants in the middle Tennessee region of the United States. Prepregnancy BMI and GWG were ascertained from questionnaires administered during early infancy and categorized based on World Health Organization and Institute of Medicine recommendations, respectively. Allergic asthma was defined fi ned as 5-year current asthma and a positive skin test or specific fi c IgE to aeroallergen(s). We used multivariable logistic regression models for asthma and multinomial logistic regression models for nonasthma, allergic asthma, and nonallergic asthma. RESULTS: A total of 1266 children were included. At the 5-year follow-up, 194 (15.3%) had asthma; among them, 102 (52.6%) had allergic asthma. Both inadequate and excessive GWG, compared with adequate GWG, were associated with increased odds of asthma (inadequate: adjusted odds ratio [aOR]: 1.76 [95% confidence fi dence interval (CI): 1.03-2.98]; excessive: aOR: 1.70 [95% CI: 1.12-2.57]) and increased odds of allergic asthma compared with no asthma (inadequate: aOR: 3.49 [95% CI: 1.66-7.32]; excessive: aOR: 2.55 [95% CI: 1.34-4.85]). Pre- pregnancy BMI was not associated with asthma nor with asthma phenotypes. CONCLUSIONS: Both inadequate and excessive GWG were associated with allergic asthma risk. These results support the benefits fi ts of optimal GWG during pregnancy on child health outcomes.(c) 2024 The Authors. Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology. This is an open access article under the CC BY- NC-ND license (http://creativecommons.org/licenses/by-nc-nd/ 4.0/). (J Allergy Clin Immunol Pract 2024;12:2719-29)

INTRODUCTION:Health agencies have called for research evaluating e-cigarette (EC) use in supporting prenatal smoking cessation. This study aimed to describe (1) the characteristics of smokers who begin using electronic cigarettes (ECs) during pregnancy, (2) how frequently smokers reduce or eliminate pre- and post-natal combustible cigarette (CC) use, and (3) the risk for neonatal health complications among smokers who initiate ECs during pregnancy. AIMS AND METHODS:Pregnant women using CCs exclusively during prepregnancy, who participated in a U.S. surveillance study, were classified by their reported late-pregnancy smoking behavior as CC-exclusive users, EC initiators, or quitters. EC initiators were further subclassified as dual users (used both ECs and CCs) or EC replacers (used ECs exclusively). RESULTS:Of 29 505 pregnant smokers, 1.5% reported using ECs during the last three pregnancy months. Among them, 29.7% became EC-exclusive users. EC initiators were disproportionately non-Hispanic White. Relative to quitters, EC initiators had lower income, were less likely to be married, have intended pregnancies, receive first-trimester prenatal care, and participate in a federal assistance program. Compared to CC-exclusive users, EC initiators overall, and dual users specifically, were more likely to reduce pre- and post-natal CC usage relative to prepregnancy levels. EC initiators' risk for neonatal health complications fell between quitters and CC-exclusive users, though the differences were not statistically significant. CONCLUSIONS:Although EC initiators reduced CC use more than CC-exclusive users, only 29.7% reported complete CC cessation, and there was insufficient evidence of reduction in neonatal health complications relative to CC-exclusive users. Currently, ECs should not be considered a viable gestational smoking cessation strategy. IMPLICATIONS:Health agencies have identified a critical need for research evaluating the use of e-cigarettes in supporting prenatal smoking cessation. Using the U.S. Pregnancy Risk Assessment Monitoring System surveillance study data, we provide real-world evidence that prenatal e-cigarette initiation as a smoking cessation tool is used infrequently among pregnant CCs smokers. Most using e-cigarettes in the last 3 months of pregnancy also used CCs.