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Respiratory syncytial virus (RSV) is a leading cause of illness in infants (1). Previous epidemiologic studies of RSV infection during infancy have focused on symptomatic illness, predominantly lower respiratory tract [...]

BACKGROUND: Childhood wheeze, asthma, and allergic rhinitis are common and likely have prenatal origins. Oxidative stress is associated with respiratory disease, but the association of oxidative stress during the prenatal period with development of respiratory and atopic disease in childhood, particularly beyond the infancy period, is unknown. This study aims to investigate associations between prenatal oxidative stress, measured by maternal urinary F2-isoprostanes, and child respiratory outcomes, including effect modification by maternal race. METHODS: We prospectively studied Black (n = 717) and White (n = 363) mother-child dyads. We measured F2-isoprostanes in 2nd-trimester urine (ng/mg-creatinine). At approximately age 4, we obtained parent report of provider-diagnosed asthma (ever), current wheeze, current asthma (diagnosis, symptoms and/or medication), and current allergic rhinitis (current defined as previous 12 months). We used multivariable logistic regression to estimate adjusted odds ratios (aOR) and 95% confidence intervals (95%CI) per interquartile range (IQR) increase in F2-isoprostane concentration, controlling for confounders. We examined modification by maternal race using interaction terms. RESULTS: The prevalence of provider-diagnosed asthma and current wheeze, asthma and allergic rhinitis was 14%, 19%, 15%, and 24%, respectively. Median (IQR) F2-isoprostane levels were 2.1 (1.6, 2.9) ng/mg-creatinine. Associations between prenatal F2-isoprostanes and provider-diagnosed asthma, current wheeze, and current asthma were modified by maternal race. Results were strongest for current wheeze (aOR [95%CI]: 1.55 [1.16, 2.06] for White; 0.98 [0.78, 1.22] for Black; p-interaction = 0.01). We observed no association between F2-isoprostanes and allergic rhinitis. CONCLUSION: Prenatal urinary F2-isoprostanes may be a marker associated with childhood wheeze/asthma in certain populations. Research is needed to understand underlying mechanisms and racial differences.

BACKGROUND: Postnatal exposures, including breastfeeding, may influence asthma development. OBJECTIVE: To investigate the association between breastfeeding duration and child asthma. METHODS: We studied 2021 mother-child dyads in the ECHO PATHWAYS consortium of prospective pregnancy cohorts (GAPPS, CANDLE, TIDES). Women reported the duration of any and exclusive breastfeeding and child asthma outcomes during follow-up at child age 4 to 6 years. Outcomes included current wheeze (previous 12 months), ever asthma, current asthma (having ≥2 of current wheeze, ever asthma, medication use in past 12-24 months), and strict current asthma (ever asthma with either or both current wheeze and medication use in past 12-24 months). We used multivariable logistic regression to assess associations (odds ratios and 95% confidence intervals) between breastfeeding and asthma outcomes adjusting for potential confounders. We assessed effect modification by mode of delivery, infant sex, and maternal asthma. RESULTS: Among women, 33%, 13%, 9%, and 45% reported 0 to less than 2, 2 to 4, 5 to 6, and more than 6 months of any breastfeeding, respectively. The duration of any breastfeeding had a protective linear trend with ever asthma but no other outcomes. There was a duration-dependent protective association of exclusive breastfeeding and child asthma outcomes (eg, current asthma adjusted odds ratio [95% confidence interval], 0.64 [0.41-1.02], 0.61 [0.38-0.98], and 0.52 (0.31-0.87) for 2to 4 months, 5 to 6 months, and more than 6 months, respectively, compared with

BackgroundChildhood asthma is a common chronic disease that likely has prenatal origins. Gestational diabetes alters maternal physiology and may influence fetal risk for childhood-onset disease. However, the association between gestational diabetes and child asthma is not well characterized.ObjectiveTo investigate the association between gestational diabetes and wheeze/asthma at approximately 4 years of age in a racially diverse US cohort.MethodsWe studied mother-child dyads enrolled prenatally in the Conditions Affecting Neurocognitive Development and Learning in Early Childhood study. Gestational diabetes was determined by medical chart review. At approximately 4 years of age, we assessed child respiratory outcomes including parent report of physician-diagnosed asthma (ever), current wheeze (symptoms within the past 12 months), and current asthma (physician diagnosis and/or medication or symptoms within the past 12 months). We used the modified Poisson regression to assess associations between gestational diabetes and child respiratory outcomes, adjusting for maternal age, race, prenatal smoking, pre-pregnancy body mass index, parity, asthma history, socioeconomic status, and infant sex.ResultsAmong 1107 women, 66% were African American/Black. Six percent (n = 62) had gestational diabetes documented during pregnancy. Gestational diabetes was associated with increased risk of physician-diagnosed asthma (adjusted risk ratio (RR) [95% Confidence Interval]: 2.13 [1.35, 3.38]; prevalence: 14%), current wheeze (RR: 1.85 [1.23, 2.78]; prevalence: 19%), and current asthma (RR: 2.01 [1.30, 3.10]; prevalence: 16%).ConclusionsGestational diabetes was associated with increased risk of asthma and wheeze outcomes. Additional studies are needed to elucidate modifiable pathways underlying this association.

Abstract Background Molecular polymerase chain reaction (PCR) based assays are increasingly used to diagnose viral respiratory infections and conduct epidemiology studies. Molecular assays have generally been evaluated by comparing them to conventional direct fluorescent antibody (DFA) or viral culture techniques, with few published direct comparisons between molecular methods or between institutions. We sought to perform a real-world comparison of two molecular respiratory viral diagnostic methods between two experienced respiratory virus research laboratories. Methods We tested nasal and throat swab specimens obtained from 225 infants with respiratory illness for 11 common respiratory viruses using both a multiplex assay (Respiratory MultiCode-PLx Assay [RMA]) and individual real-time RT-PCR (RT-rtPCR). Results Both assays detected viruses in more than 70% of specimens, but there was discordance. The RMA assay detected significantly more human metapneumovirus (HMPV) and respiratory syncytial virus (RSV), while RT-rtPCR detected significantly more influenza A. We speculated that primer differences accounted for these discrepancies and redesigned the primers and probes for influenza A in the RMA assay, and for HMPV and RSV in the RT-rtPCR assay. The tests were then repeated and again compared. The new primers led to improved detection of HMPV and RSV by RT-rtPCR assay, but the RMA assay remained similar in terms of influenza detection. Conclusions Given the absence of a gold standard, clinical and research laboratories should regularly correlate the results of molecular assays with other PCR based assays, other laboratories, and with standard virologic methods to ensure consistency and accuracy.

Abstract Background Diabetes is a common disease with self-management a key aspect of care. Large prospective trials have shown that maintaining glycated hemoglobin less than 7% greatly reduces complications but translating this level of control into everyday clinical practice can be difficult. Intensive improvement programs are successful in attaining control in patients with type 2 diabetes, however, many patients experience glycemic relapse once returned to routine care. This early relapse is, in part, due to decreased adherence in self-management behaviors. Objective This paper describes the design of the Glycemic Relapse Prevention study. The purpose of this study is to determine the optimal frequency of maintenance intervention needed to prevent glycemic relapse. The primary endpoint is glycemic relapse, which is defined as glycated hemoglobin greater than 8% and an increase of 1% from baseline. Methods The intervention consists of telephonic contact by a nurse practitioner with a referral to a dietitian if indicated. This intervention was designed to provide early identification of self-care problems, understanding the rationale behind the self-care lapse and problem solve to find a negotiated solution. A total of 164 patients were randomized to routine care (least intensive), routine care with phone contact every three months (moderate intensity) or routine care with phone contact every month (most intensive). Conclusion The baseline patient characteristics are similar across the treatment arms. Intervention fidelity analysis showed excellent reproducibility. This study will provide insight into the important but poorly understood area of glycemic relapse prevention.

BackgroundAtopic dermatitis is a common childhood disease, potentially influenced by prenatal nutritional exposures such as polyunsaturated fatty acids (PUFAs).ObjectiveIn a racially diverse cohort, we hypothesized that childhood atopic dermatitis would be associated with higher prenatal omega-6 (n-6) and lower omega-3 (n-3) PUFAs.MethodsWe included mother-child dyads, births 2006 to 2011, enrolled in the University of Tennessee Health Sciences Center Conditions Affecting Neurocognitive Development in Early Childhood cohort. Primary exposures included second trimester plasma n-3 and n-6 PUFA status and the ratio of the two (n-6:n-3). We assessed child current atopic dermatitis symptoms in the previous 12 months at age approximately 4 to 6 years. We investigated the association between PUFA exposures and atopic dermatitis using multivariable logistic regression, adjusting for potential confounders. We assessed for effect modification by maternal prenatal smoking, atopic disease history, and child sex.ResultsAmong 1131 women, 67% were African American and 42% had an atopic disease history; 17% of children had atopic dermatitis. Higher prenatal n-6 PUFAs were associated with increased relative odds of child atopic dermatitis (adjusted odds ratio: 1.25; confidence interval: 1.01-1.54 per interquartile range difference), and interaction models demonstrated that this association was seen in dyads in which the women had a history of atopic disease. Neither prenatal n-3 PUFAs nor n-6:n-3 were associated with child atopic dermatitis.ConclusionIn this racially diverse cohort, higher second trimester n-6 PUFAs were associated with atopic dermatitis in children of women with atopy. PUFAs may represent a modifiable risk factor for atopic dermatitis, particularly in individuals with a familial predisposition.

BackgroundFindings on prenatal polyunsaturated fatty acid (PUFA) intake and child wheeze and asthma have been inconsistent.ObjectiveWe sought to examine associations between prenatal PUFA status and child wheeze/asthma and modifying effects of maternal asthma/atopy, child sex, and maternal race.MethodsAnalyses included 1019 mother-child dyads with omega-3 (n-3) and omega-3 (n-6) PUFAs measured in second-trimester plasma; n-6/n-3 ratios were calculated. Child wheeze/asthma outcomes ascertained at age 4 to 6 years included ever physician-diagnosed asthma, current wheeze (symptoms past 12 months), current asthma (diagnosis and medication and/or symptoms past 12 months), and current diagnosed asthma. Each PUFA indicator and outcome was analyzed in separate models using modified Poisson regression with interaction terms.ResultsIn quartile (Q) analyses, higher n-6 PUFAs were associated with increased risk of ever (risk ratio [RR] high vs low [RR Q4 vs Q1], 1.70; 95% CI, 1.07-2.71) and current (RR Q4 vs Q1, 1.70; 95% CI, 1.07-2.71) diagnosed asthma, whereas n-3 PUFAs were associated with lower risk (RR Q4 vs Q1, 0.59; 95% CI, 0.33-1.03) of current diagnosed asthma (Ptrend < .05 for all). Higher n-6 PUFAs were associated with a higher risk of all respiratory outcomes among children born to women with asthma (Pinteraction < .05 for all outcomes). A significant 3-way interaction between child sex, maternal asthma, and n-6/n-3 PUFA indicated that male children born to women with asthma and a higher ratio had the highest risk across wheeze/asthma outcomes (Pinteraction < .05).ConclusionsAssociations between prenatal PUFA status and childhood wheeze/asthma were modified by maternal history of asthma and child sex.

The Human Epidemiology and Response to SARS-CoV-2 (HEROS) Study is a prospective, multicity, 6-month incidence study conducted from May 2020 to February 2021. The objectives were to identify risk factors for SARS-CoV-2 infection and household transmission among children and people with asthma and allergic diseases, and to use the host nasal transcriptome sampled longitudinally to understand infection risk and sequelae at the molecular level. To overcome challenges of clinical study implementation due to the coronavirus pandemic, this surveillance study used direct-to-participant methods to remotely enroll and prospectively follow eligible children who are participants in other National Institutes of Health–funded pediatric research studies and their household members. Households participated in weekly surveys and biweekly nasal sampling regardless of symptoms. The aim of this report is to widely share the methods and study instruments and to describe the rationale, design, execution, logistics, and characteristics of a large, observational, household-based, remote cohort study of SARS-CoV-2 infection and transmission in households with children. The study enrolled a total of 5598 individuals, including 1913 principal participants (children), 1913 primary caregivers, 729 secondary caregivers, and 1043 other household children. This study was successfully implemented without necessitating any in-person research visits and provides an approach for rapid execution of clinical research. Trial registration: ClinicalTrials.gov. Identifier: NCT04375761 [ABSTRACT FROM AUTHOR]

Objective: We aimed to develop an algorithm that accurately identifies children with Down syndrome (DS) using administrative data. Methods: We identified a cohort of children born between 2000 and 2017, enrolled in the Tennessee Medicaid Program (TennCare), who either had DS coded on their birth certificate or had a diagnosis listed using an International Classification of Diseases (ICD) code (suspected DS), and who received care at Vanderbilt University Medical Center, a comprehensive academic medical center, in the United States. Children with suspected DS were defined as having DS if they had (a) karyotype-confirmed DS indicated on their birth certificate; (b) karyotype-pending DS indicated on their birth certificate (or just DS if test type was not specified) and at least two healthcare encounters for DS during the first 6 years of life; or (c) at least three healthcare encounters for DS, with the first and last encounter separated by at least 30 days, during the first six years of life. The positive predictive value (PPV) of the algorithm and 95% confidence interval (CI) were reported. Results: Of the 411 children with suspected DS, 354 (86.1%) were defined as having DS by the algorithm. According to medical chart review, the algorithm correctly identified 347 children with DS (PPV = 98%, 95%CI: 96.0–99.0%). Of the 57 children the algorithm defined as not having DS, 50 (97.7%, 95%CI: 76.8–93.9%) were confirmed as not having DS by medical chart review. Conclusions: An algorithm that accurately identifies individuals with DS using birth certificate data and/or ICD codes provides a valuable tool to study DS using administrative data. [ABSTRACT FROM AUTHOR]

Background: We investigated the individual and interaction effects of maternal plasma 훂‐ and ϒ‐tocopherol levels (vitamin E isomers) on child asthma and wheeze at age 8–9. Methods: Mother–child dyads were enrolled between 2006 and 2011 into the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) prenatal cohort. Maternal second‐trimester samples were analyzed for tocopherol and lipid concentrations. We assessed child asthma/wheeze using the International Study of Asthma and Allergies in Childhood (ISAAC) and other self‐reported Ent wheeze. In multivariable logistic regression analyses, we assessed associations between vitamin E isomers and child asthma/wheeze outcomes (n = 847 mother–child dyads) and tested for prespecified interaction terms. Results: Median cholesterol‐corrected tocopherol levels (interquartile range (IQR)) were 5.0 (4.3–5.7) and 0.8 (0.7–0.9) (umol/mmol) for 훂‐ and ϒ‐tocopherol, respectively. Associations between 훂‐tocopherol and asthma outcome variables were inverse but not statistically significant. In contrast, for ϒ‐tocopherol, associations were in the positive direction, but also nonsignificant. Interactions analysis between tocopherols did not reach statistical significance for any outcome. Among children of women with a history of asthma, the likelihood of ever asthma in the child appears to be decreasing with increasing maternal 훂‐tocopherol levels, whereas this trend was not observed among those without a history of asthma (p‐interaction =.05). Conclusion: We observed no associations for prenatal 훂‐ or ϒ‐tocopherol concentrations with child asthma/wheeze. We detected some evidence of effect modification by maternal asthma history in associations between 훂‐tocopherol and child asthma. [ABSTRACT FROM AUTHOR]

Objectives Viral bronchiolitis is the most common cause of infant hospitalization. Folic acid supplementation is important during the periconceptional period to prevent neural tube defects. An area of investigation is whether higher prenatal folate is a risk factor for childhood respiratory illnesses. We investigated the association between maternal 2nd trimester plasma folate levels and infant bronchiolitis. Methods We conducted a retrospective cohort analysis in a subset of mother-infant dyads (n = 676) enrolled in the Conditions Affecting Neurocognitive Development and Learning in Early Childhood study and Tennessee Medicaid. Maternal folate status was determined using 2nd trimester (16-28 weeks) plasma samples. Bronchiolitis diagnosis in the first year of life was ascertained using International Classification of Diagnosis-9 codes from Medicaid administrative data. We used multivariable logistic regression to assess the adjusted association of prenatal folate levels and infant bronchiolitis outcome. Results Half of the women in this lower-income and predominately African-American (84%) study population had high levels of folate (median 2nd trimester level 19.2 ng/mL) and 21% of infants had at least one bronchiolitis healthcare visit. A relationship initially positive then reversing between maternal plasma folate and infant bronchiolitis was observed that did not reach statistical significance (p.sub.overall = .112, p.sub.nonlinear effect = .088). Additional adjustment for dietary methyl donor intake did not significantly alter the association. Conclusions for Practice Results did not confirm a statistically significant association between maternal 2nd trimester plasma folate levels and infant bronchiolitis. Further work is needed to investigate the role of folate, particularly higher levels, in association with early childhood respiratory illnesses., Author(s): Shanda Vereen [sup.1] [sup.4] [sup.5] , Tebeb Gebretsadik [sup.2] [sup.5] , Nia Johnson [sup.6] , Terryl J. Hartman [sup.7] , Sreenivas P. Veeranki [sup.1] [sup.4] [sup.5] , Chandrika Piyathilake [...]

Adults with type 2 diabetes (T2DM) and low socioeconomic status (SES) have high rates of medication nonadherence, and, in turn, suboptimal glycemic control (hemoglobin A1c [HbA1c]). We tested the initial efficacy of a short message service (SMS) text messaging and interactive voice response (IVR) intervention to promote adherence among this high-risk group. Eighty low SES, diverse adults with T2DM used the MEssaging for Diabetes (MED) SMS/IVR intervention for 3 months. We used a pre-post single group design to explore adherence changes over 3 months, and a quasi-experimental design to test the impact of MED on HbA1c among the intervention group relative to a matched, archival control group. Compared to baseline, adherence improved at one (AOR 3.88, 95 % CI 1.79, 10.86) and at 2 months (AOR 3.76, 95 % CI 1.75, 17.44), but not at 3 months. HbA1c remained stable, with no differences at 3 months between the intervention group and the control group. MED had a positive, short-term impact on adherence, which did not translate to improvements in HbA1c. Future research should explore the longer-term impact of SMS/IVR interventions on the medication adherence of high risk adults with T2DM., Author(s): Lyndsay A. Nelson[sup.1] [sup.2] , Shelagh A. Mulvaney[sup.3] [sup.4] [sup.5] [sup.6] , Tebeb Gebretsadik[sup.7] , Kevin B. Johnson[sup.5] , Chandra Y. Osborn[sup.1] [sup.2] [sup.4] [sup.5] Author Affiliations: (1) Department [...]