Correlates of Rotavirus Vaccine Shedding and Seroconversion in a U.S. Cohort of Healthy Infants.

BACKGROUND: Rotavirus is a leading cause of severe pediatric gastroenteritis; two highly effective vaccines are used in the US. We aimed to identify correlates of immune response to rotavirus vaccination in a US cohort. METHODS: PREVAIL is a birth cohort of 245 mother-child pairs enrolled 2017-2018 and followed for 2 years. Infant stool samples and symptom information were collected weekly. Shedding was defined as RT-PCR detection of rotavirus vaccine virus in stools collected 4-28 days after dose one. Seroconversion was defined as a threefold rise in IgA between the six-week and six-month blood draws. Correlates were analyzed using generalized estimating equations and logistic regression. RESULTS: Pre-vaccination IgG (OR=0.84, 95% CI [0.75-0.94] per 100-unit increase) was negatively associated with shedding. Shedding was also less likely among infants with a single-nucleotide polymorphism inactivating FUT2 antigen secretion ("non-secretors") with non-secretor mothers, versus all other combinations (OR 0.37 [0.16-0.83]). Of 141 infants with data, 105 (74%) seroconverted; 78 (77%) had shed vaccine virus following dose one. Pre-vaccination IgG and secretor status were significantly associated with seroconversion. Neither shedding nor seroconversion significantly differed by vaccine product. DISCUSSION: In this US cohort, pre-vaccination IgG and maternal and infant secretor status were associated with rotavirus vaccine response.

Obesity and Prenatal Intention as Predictors of Meeting Breastfeeding Recommendations in an Urban Birth Cohort.

Background and Objectives: Few U.S. women meet the public health recommendations to exclusively breastfeed for 6 months and continue breastfeeding for at least 1-2 years. We compared prenatally collected demographic, health, and breastfeeding support/intention variables to examine how these factors intersect to predict meeting breastfeeding recommendations. Methods: PREVAIL, a CDC-funded birth cohort in Cincinnati, OH, was approved by the IRB at CDC, Cincinnati Children's Hospital, and the hospitals where enrollment (third trimester, 2017-2018) occurred. The prenatal questionnaire captured sociodemographics, pre-pregnancy weight and height, breastfeeding environment, and breastfeeding intention, while health factors were obtained from obstetrical records. Body mass index (BMI) (kg/m2) was categorized as healthy (18.5-24.9), overweight (25-29.9), obesity 1 (30-34.9), and obesity 2+ (≥35). Mothers self-reported date of exclusive and any breastfeeding cessation through quarterly postnatal questionnaires. Random forest was used for variable selection, cross-validated in multivariable logistic models. Results: Analysis included n = 237 mothers with BMI ≥18.5. Random forest identified BMI category, prenatal intention, and insurance type as the most important predictors of meeting breastfeeding recommendations. The resulting logistic models explained >40% of the variance with an area under the curve of ≥0.89 for both recommendations. More than 73% of the risk of not meeting breastfeeding recommendations was attributable to having an elevated BMI or lacking strong breastfeeding intention. Conclusions: In PREVAIL, maternal BMI and prenatal intention explained most risks of not meeting breastfeeding exclusivity and duration recommendations. Our findings suggest efforts to improve breastfeeding exclusivity and duration should focus on strengthening prenatal breastfeeding intention and identifying effective interventions for supporting breastfeeding among mothers with higher BMI.

Factors Associated With Prolonged Respiratory Virus Detection From Polymerase Chain Reaction of Nasal Specimens Collected Longitudinally in Healthy Children in a US Birth Cohort.

BACKGROUND: Respiratory viral shedding is incompletely characterized by existing studies due to the lack of longitudinal nasal sampling and limited inclusion of healthy/asymptomatic children. We describe characteristics associated with prolonged virus detection by polymerase chain reaction (PCR) in a community-based birth cohort. METHODS: Children were followed from birth to 2 years of age in the PREVAIL cohort. Weekly nasal swabs were collected and tested using the Luminex Respiratory Pathogen Panel. Weekly text surveys were administered to ascertain the presence of acute respiratory illnesses defined as fever and/or cough. Maternal reports and medical chart abstractions identified healthcare utilization. Prolonged virus detection was defined as a persistently positive test lasting ≥4 weeks. Factors associated with prolonged virus detection were assessed using mixed effects multivariable logistic regression. RESULTS: From a sub-cohort of 101 children with ≥70% weekly swabs collected, a total of 1489 viral infections were detected. Prolonged virus detection was found in 23.4% of viral infections overall, 39% of bocavirus infections, 33% of rhinovirus/enterovirus infections, 14% of respiratory syncytial virus (RSV) A infections, and 7% of RSV B infections. No prolonged detection was found for influenza virus A or B, coronavirus 229E or HKU1, and parainfluenza virus 2 or 4 infections. First-lifetime infection with each virus, and co-detection of another respiratory virus were significantly associated with prolonged detection, while symptom status, child sex, and child age were not. CONCLUSIONS: Prolonged virus detection was observed in 1 in 4 viral infections in this cohort of healthy children and varied by pathogen, occurring most often for bocavirus and rhinovirus/enterovirus. Evaluating the immunological basis of how viral co-detections and recurrent viral infections impact duration of virus detection by PCR is needed to better understand the dynamics of prolonged viral shedding.

Endemic Coronavirus Infections are Associated with Strong Homotypic Immunity in a US Cohort of Children from Birth to 4 Years.

BACKGROUND: The endemic coronaviruses OC43, HKU1, NL63, and 229E cause cold-like symptoms and are related to SARS-CoV-2, but their natural histories are poorly understood. In a cohort of children followed from birth to 4 years, we documented all coronavirus infections, including SARS-CoV-2, to understand protection against subsequent infections with the same virus (homotypic immunity) or a different coronavirus (heterotypic immunity). METHODS: Mother-child pairs were enrolled in metropolitan Cincinnati during the third trimester of pregnancy in 2017-2018. Mothers reported their child's sociodemographics, risk factors, and weekly symptoms. Mid-turbinate nasal swabs were collected weekly. Blood was collected at 6 weeks, 6, 12, 18, 24 months, and annually thereafter. Infections were detected by testing nasal swabs by an RT-PCR multi-pathogen panel and by serum IgG responses. Health care visits were documented from pediatric records. Analysis was limited to 116 children with high sample adherence. Reconsent for monitoring SARS-CoV-2 infections from June 2020 through November 2021 was obtained for 74 (64%) children. RESULTS: We detected 345 endemic coronavirus infections (1.1 infections/child-year) and 21 SARS-CoV-2 infections (0.3 infections/child-year). Endemic coronavirus and SARS-CoV-2 infections were asymptomatic or mild. Significant protective homotypic immunity occurred after a single infection with OC43 (77%) and HKU1 (84%) and after two infections with NL63 (73%). No heterotypic protection against endemic coronaviruses or SARS-CoV-2 was identified. CONCLUSIONS: Natural coronavirus infections were common and resulted in strong homotypic immunity but not heterotypic immunity against other coronaviruses, including SARS-CoV-2. Endemic coronavirus and SARS-CoV-2 infections in this US cohort were typically asymptomatic or mild.

Comparison of neighborhood deprivation index and food desert status as environmental predictors of early childhood obesity.

Nearly 14% of American children aged 2-5 have obesity, with higher rates in children from lower-income and Black families. While evidence connects neighborhood socioeconomic environment (SEE) and obesity in adults and adolescents, little is known of this relationship in young children. We compared measures of SEE and family-level socio-demographic factors as predictors of obesity at age two. METHODS: Family-level data from the PREVAIL Cohort, a CDC-funded birth cohort in Cincinnati, Ohio, were collected prenatally from the mothers. Residential addresses were geocoded and assigned validated measures of census tract-level SEE, including USDA food desert indicators and the Deprivation Index. Family-level and ecological SEE were compared as predictors of obesity (BMIz ≥1.65) at age two in terms of proportional differences, relative risk, and model fit statistics. RESULTS: Residing outside of Deprivation Index High SEE neighborhoods was significantly associated with higher proportion (20.0% vs 5.9%; χ2 = 4.36, p = 0.037) and increased risk of obesity in univariable (RR = 3.4, 95%CI: 1.26-13.86) and multivariable models (RR = 3.5, 95%CI: 1.06-11.71). There were no differences in proportion or risk of obesity by USDA food desert indicators or family-level factors. Models using categorical Deprivation Index performed better than the family-level and the USDA food desert variables in terms of model fit. CONCLUSION: In the PREVAIL Cohort, only category of Deprivation Index was a significant predictor of obesity in two-year-old children. Future studies are needed to evaluate the Deprivation Index as a generalizable tool to identify neighborhoods at higher risk for obesity.