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Research on health effects and potential harms of electronic cigarette (EC) use during pregnancy is limited. We sought to determine the risks of pregnancy EC use on pregnancy-related adverse birth outcomes and assess whether quitting ECs reduces the risks. Women with singleton live births who participated in the US Pregnancy Risk Assessment Monitoring System (PRAMS) survey study 2016-2020 were classified into four mutually exclusive groups, by their use of ECs and combustible cigarettes (CCs) during pregnancy: non-use, EC only use, CC only use, and dual use. We determined the risk of preterm birth, low birth weight, and small-for-gestational-age (SGA) by comparing cigarette users to non-users with a modified Poisson regression model adjusting for covariates. In a subset of women who all used ECs prior to pregnancy, we determined whether quitting EC use reduces the risk of preterm birth, low birth weight, and SGA by comparing to those who continued its use. All analyses were weighted to account for the PRAMS survey design and non-response rate. Of the 190,707 women (weighted N = 10,202,413) included, 92.1% reported cigarette non-use, 0.5% EC only use, 6.7% CC only use, and 0.7% dual use during pregnancy. Compared with non-use, EC only use was associated with a significantly increased risk of preterm birth (adjusted risk ratio [aRR]: 1.29, 95% confidence interval [CI]: 1.00, 1.65) and low birth weight (aRR: 1.38, 95%CI: 1.09, 1.75), but not SGA (aRR: 1.04, 95%CI: 0.76, 1.44). Among 7,877 (weighted N = 422,533) women EC users, quitting use was associated with a significantly reduced risk of low birth weight (aRR: 0.76, 95%CI: 0.62, 0.94) and SGA (aRR: 0.77, 95%CI: 0.62, 0.94) compared to those who continued to use ECs during pregnancy. Pregnancy EC use, by itself or dual use with CC, is associated with preterm birth and low birth weight. Quitting use reduces that risk. ECs should not be considered as a safe alternative nor a viable gestational smoking cessation strategy.

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.

IntroductionThe 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 analysisThe 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 disseminationThis 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.

Newborn metabolite perturbations may identify potential biomarkers or mechanisms underlying adverse, smoking-related childhood health outcomes. We assessed associations between third-trimester smoking and newborn metabolite concentrations using the Tennessee Pregnancy Risk Assessment Monitoring System (PRAMS, 2009–2019) as the discovery cohort and INSPIRE (2012–2014) as the replication cohort. Children were linked to newborn screening metabolic data (33 metabolites). Third-trimester smoking was ascertained from birth certificates (PRAMS) and questionnaires (INSPIRE). Among 8600 and 1918 mother–child dyads in PRAMS and INSPIRE cohorts, 14% and 13% of women reported third-trimester smoking, respectively. Third-trimester smoking was associated with higher median concentrations of free carnitine (C0), glycine (GLY), and leucine (LEU) at birth (PRAMS: C0: adjusted fold change 1.11 [95% confidence interval (CI) 1.08, 1.14], GLY: 1.03 [95% CI 1.01, 1.04], LEU: 1.04 [95% CI 1.03, 1.06]; INSPIRE: C0: 1.08 [95% CI 1.02, 1.14], GLY: 1.05 [95% CI 1.01, 1.09], LEU: 1.05 [95% CI 1.01, 1.09]). Smoking cessation (vs. continued smoking) during pregnancy was associated with lower median metabolite concentrations, approaching levels observed in infants of non-smoking women. Findings suggest potential pathways underlying fetal metabolic programming due to in utero smoke exposure and a potential reversible relationship of cessation.

OBJECTIVES/GOALS: Children with Down syndrome are at increased risk of respiratory diseases including asthma. Prenatal antibiotic exposure has been shown to be associated with the development of childhood asthma. We aim to estimate the association between prenatal antibiotic exposure and childhood asthma among children with Down syndrome. METHODS/STUDY POPULATION: We conducted a retrospective cohort study of mother-child dyads of children with Down syndrome who were born 1995-2013. Both children and mothers were continuously enrolled in the Tennessee Medicaid Program (TennCare). Prenatal antibiotic exposure was measured using mother’s prescription fill records. Childhood asthma was defined between age 4.5-6 years by asthma-related healthcare encounters and asthma-specific medication fills. We assessed the association between prenatal antibiotic exposure and childhood asthma among children with Down syndrome using modified Poisson regression adjusting for maternal age, race, residence, education, marital status, smoking during pregnancy, maternal asthma status, delivery method, number of siblings, and children’s sex. RESULTS/ANTICIPATED RESULTS: Among 346 mother-child dyads of children with Down syndrome, 273 (78.9%) children were exposed prenatally to antibiotics and 104 (30.0%) had asthma by age 4.5-6 years. Among those who were exposed to at least one course, the median antibiotic course equaled 2 (interquartile range: 1-4). Prenatal antibiotic exposure was associated with a 20% increase in risk of childhood asthma in the unadjusted analysis (risk ratio [RR] 1.20, 95% confidence interval [CI] 0.78, 1.83) and a 26% increase in risk after adjustment (adjusted RR 1.26, 95% CI 0.79, 2.01). DISCUSSION/SIGNIFICANCE: In our study population, the majority of children with Down syndrome were exposed to antibiotics prenatally and the prevalence of asthma was high. Prenatal antibiotic exposure was associated with an increased risk of childhood asthma among children with Down syndrome; however, this increase was not statistically significant.

We aimed first to assess associations between maternal health characteristics and newborn metabolite concentrations and second to assess associations between metabolites associated with maternal health characteristics and child body mass index (BMI). This study included 3492 infants enrolled in three birth cohorts with linked newborn screening metabolic data. Maternal health characteristics were ascertained from questionnaires, birth certificates, and medical records. Child BMI was ascertained from medical records and study visits. We used multivariate analysis of variance, followed by multivariable linear/proportional odds regression, to determine maternal health characteristic-newborn metabolite associations. Significant associations were found in discovery and replication cohorts of higher pre-pregnancy BMI with increased C0 and higher maternal age at delivery with increased C2 (C0: discovery: aβ 0.05 [95% CI 0.03, 0.07]; replication: aβ 0.04 [95% CI 0.006, 0.06]; C2: discovery: aβ 0.04 [95% CI 0.003, 0.08]; replication: aβ 0.04 [95% CI 0.02, 0.07]). Social Vulnerability Index, insurance, and residence were also associated with metabolite concentrations in a discovery cohort. Associations between metabolites associated with maternal health characteristics and child BMI were modified from 1–3 years (interaction: p < 0.05). These findings may provide insights on potential biologic pathways through which maternal health characteristics may impact fetal metabolic programming and child growth patterns.

Women with singleton live births who participated in the US Pregnancy Risk Assessment Monitoring System (PRAMS) survey study 2016-2020 were classified into four mutually exclusive groups, by their use of ECs and combustible cigarettes (CCs) during pregnancy: non-use, EC only use, CC only use, and dual use. We determined the risk of preterm birth, low birth weight, and small-for-gestational-age (SGA) by comparing cigarette users to non-users with a modified Poisson regression model adjusting for covariates. In a subset of women who all used ECs prior to pregnancy, we determined whether quitting EC use reduces the risk of preterm birth, low birth weight, and SGA by comparing to those who continued its use. All analyses were weighted to account for the PRAMS survey design and non-response rate. Of the 190,707 women (weighted N = 10,202,413) included, 92.1% reported cigarette non-use, 0.5% EC only use, 6.7% CC only use, and 0.7% dual use during pregnancy. Compared with non-use, EC only use was associated with a significantly increased risk of preterm birth (adjusted risk ratio [aRR]: 1.29, 95% confidence interval [CI]: 1.00, 1.65) and low birth weight (aRR: 1.38, 95%CI: 1.09, 1.75), but not SGA (aRR: 1.04, 95%CI: 0.76, 1.44). Among 7,877 (weighted N = 422,533) women EC users, quitting use was associated with a significantly reduced risk of low birth weight (aRR: 0.76, 95%CI: 0.62, 0.94) and SGA (aRR: 0.77, 95%CI: 0.62, 0.94) compared to those who continued to use ECs during pregnancy. Pregnancy EC use, by itself or dual use with CC, is associated with preterm birth and low birth weight. Quitting use reduces that risk. ECs should not be considered as a safe alternative nor a viable gestational smoking cessation strategy.

Abstract 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. Timely identification of infants at highest risk of respiratory syncytial virus–related morbidity is key to prevention. We developed a personalized risk prediction tool using birth/postnatal data that may have applications in promoting immunoprophylaxis to prevent the most severe infant respiratory syncytial virus infections.

In this cohort study of hospitalized patients with linked medical record data, we developed International Classification of Diseases (ICD) criteria that accurately identified laboratory‐confirmed, severe influenza hospitalizations (positive predictive value [PPV] 80%, 95% confidence interval [CI] 71–87%), which we validated through medical record documentation. These criteria identify patients with clinically important influenza illness outcomes to inform evaluation of preventive and therapeutic interventions and public health policy recommendations.

OBJECTIVES/GOALS: Nearly half of mothers who report electronic (e)-cigarette use during pregnancy believe e-cigarettes are less harmful than traditional cigarettes. We aim to determine the association of quitting e-cigarette use in pregnancy with the risk of preterm birth and low birth weight. METHODS/STUDY POPULATION: We conducted a cross-sectional study of women participating in the Pregnancy Risk Assessment Monitoring System and with live singleton birth during 2016-2019. Women were classified based on their e-cigarette use: before pregnancy only (quitters), last three months of pregnancy only (initiators), at both times (sustained users), and neither time (non-users). We used a modified Poisson regression to determine the association between quitting e-cigarette use and preterm birth (<37 weeks) and low birth weight (<2,500 grams) adjusting for demographic, social-economic, and behavior-related risk factors. Analyses were weighted to account for the survey design and non-response. RESULTS/ANTICIPATED RESULTS: Based on 150,950 women who responded to the survey, there were estimated 2.9% quitters, 0.2% initiators, 1.0% sustained users, and 95.9% non-users in the U.S. Compared to sustained e-cigarette users, quitters had a similar risk in preterm birth (adjusted risk ratio [ARR]: 0.84, 95% confidence interval [CI]: 0.65, 1.08) and a significantly reduced risk in low birth weight (ARR: 0.77, 95%CI: 0.61, 0.97) adjusting for traditional cigarette use, age, race/ethnicity, education, marital status, family income, prior preterm birth, prior live births, BMI prior to pregnancy, pregnancy weight gain, kotelchuck index, multivitamin use, drinking prior to pregnancy, year of birth, and residential state. DISCUSSION/SIGNIFICANCE: As FDA authorizes the sales of certain e-cigarettes, women smokers may switch to e-cigarettes, believing they are reducing harm. Our study shows that quitting e-cigarette use is associated with a reduction of low birth weight. Clear messaging is needed to help women cease e-cigarette use in pregnancy.