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Background Prolonged infection by respiratory viruses has been reported, especially in hospitalized or immunocompromised children. However, little is known of factors contributing to prolonged respiratory viral infection, particularly in asymptomatic and less severe infections. We examined characteristics associated with prolonged viral infection in a community-based birth cohort. Methods The PREVAIL cohort is a CDC-sponsored two-year birth cohort in Cincinnati, Ohio conducted during 4/2017 to 8/2020. Mid-turbinate nasal swabs were collected weekly from children and tested using the Luminex Respiratory Pathogen Panel. The primary outcome was prolonged viral infection, which was defined as a viral nucleic acid detection lasting 4 or more weeks. Proportions of prolonged viral infections were compared using Fisher’s exact test with Holms corrections. Adjusted odds ratios (aOR) and 95% confidence intervals were calculated using a mixed effects logistic regression model while controlling for within-subject clustering, viral species, child age, child sex, symptom status, and coinfection. This analysis was limited to subjects who provided at least 70% of weekly samples. Results Among 101 children, providing 7871 child-weeks of follow-up, we identified 780 viral infections. The median duration of infection across all respiratory viruses was 1 week, except for bocavirus and coronavirus NL63, each with 2 weeks; 40% of bocavirus and >10% of adenovirus, coronavirus NL63, RSV A, human metapneumovirus, and parainfluenza 1 infections were associated with prolonged infection (>4 weeks). No prolonged infections were detected for influenza A or B, coronavirus 229E or HKU1, or parainfluenza 2 or 4 infections. Viral coinfection (aOR=3.1, 95% CI 1.9, 5.0) and female sex (aOR 1.8, 95%CI 1.1, 2.9) were significantly associated with prolonged infection, while symptom status and child age were not. Conclusion In the PREVAIL cohort, detection of respiratory viruses lasting 4 weeks or longer was common for certain respiratory pathogens and was especially prolonged for bocavirus. Biological factors such as the presence of additional viral infections or child sex may affect the likelihood of prolonged infection. Disclosures All Authors: No reported disclosures.

Background Adenoviruses (AdVs) are a common cause of acute respiratory illness (ARI) in children and are often detected with other viruses (coinfection). However, the community incidence of AdV infections is poorly understood due to a lack of prospective studies outside the hospital setting. Here, we aim to characterize respiratory AdV infections and coinfections in a prospective birth cohort of children. Methods The PREVAIL cohort is a CDC-funded, 2-year birth cohort, conducted from 2017–2020 in Cincinnati, OH. ARI was defined as the presence of cough or fever identified with weekly maternal text surveys and medical chart review. Mid-turbinate nasal swabs were collected weekly. Swabs were tested using Luminex Respiratory Pathogen Panel. AdV infection was defined as a swab positive for AdV and included subsequent positives < 30 days apart. Coinfection was defined as detection of any other virus(es) during an AdV infection. Children who submitted at least 70% of weekly samples were included in our analysis. Results 101 children met inclusion criteria, representing 165 child-years. 137 distinct AdV infections were identified (incidence 0.84 infections per child year), with 98 (97%) children having ≥1 AdV infection. Only 40% (n=55) of AdV infections were symptomatic. Of those with symptomatic infections, 51% (n=28) sought medical care, with 42% (n=23) presenting to a primary care provider and 9% (n=5) resulting in an ED visit or hospital admission. Coinfections were detected in 67% (n=92) of AdV infections, with 45% (n=62) coinfected with 1 virus, 19% (n=26) with 2 viruses, and 3% (n=4) with ≥3 viruses. 77% of coinfections (n=71) were rhino/enterovirus. The number of coinfections or the specific coinfection virus was not associated with an increase in symptom prevalence or symptom severity (all p > 0.05). Viral Coinfection Frequency with Adenovirus Infection in the PREVAIL Cohort. Adenovirus Infection and Coinfection in the PREVAIL Cohort. Conclusion In this cohort of healthy children, AdVs were a common cause of respiratory infection. Most infections were asymptomatic or resulted in mild symptoms. Two-thirds of AdV infections involved viral coinfections, but coinfection was not associated with more frequent or severe symptoms. Our findings suggest studies that only include symptomatic or hospitalized patients may overestimate AdVs disease severity. Disclosures All Authors: No reported disclosures.

Cholangiocarcinoma (CCA) is a highly lethal disease because most patients are asymptomatic until they progress to advanced stages. Current CCA diagnosis relies on clinical imaging tests and tissue biopsy, while specific CCA biomarkers are still lacking. This study employed a translational proteomic approach for the discovery, validation, and development of a multiplex CCA biomarker assay. In the discovery phase, label-free proteomic quantitation was performed on nine pooled plasma specimens derived from nine CCA patients, nine disease controls (DC), and nine normal individuals. Seven proteins (S100A9, AACT, AFM, and TAOK3 from proteomic analysis, and NGAL, PSMA3, and AMBP from previous literature) were selected as the biomarker candidates. In the validation phase, enzyme-linked immunosorbent assays (ELISAs) were applied to measure the plasma levels of the seven candidate proteins from 63 participants: 26 CCA patients, 17 DC, and 20 normal individuals. Four proteins, S100A9, AACT, NGAL, and PSMA3, were significantly increased in the CCA group. To generate the multiplex biomarker assays, nine machine learning models were trained on the plasma dynamics of all seven candidates (All-7 panel) or the four significant markers (Sig-4 panel) from 45 of the 63 participants (70%). The best-performing models were tested on the unseen values from the remaining 18 (30%) of the 63 participants. Very strong predictive performances for CCA diagnosis were obtained from the All-7 panel using a support vector machine with linear classification (AUC = 0.96; 95% CI 0.88–1.00) and the Sig-4 panel using partial least square analysis (AUC = 0.94; 95% CI 0.82–1.00). This study supports the use of the composite plasma biomarkers measured by clinically compatible ELISAs coupled with machine learning models to identify individuals at risk of CCA. The All-7 and Sig-4 assays for CCA diagnosis should be further validated in an independent prospective blinded clinical study.

Neighbourhood socio-economic environment (SEE) is associated with obesity in older children and adults, but little is known about this relationship in younger children. Breastfeeding is an important preventative of adiposity in childhood, but its relationship with neighbourhood SEE is unknown.We assessed differences in adiposity and obesity in children before age two by neighbourhood SEE, controlling for family socio-demographics and breastfeeding duration.Family socio-demographics, child body mass index z scores (BMIz), and breastfeeding duration were collected at periodic study visits from participants in PREVAIL (n = 245), a birth cohort in Cincinnati, OH. Addresses were assigned a Deprivation Index score, a validated measure of SEE, and dichotomized into highest SEE (least deprived quartile of scores) and not highest SEE (remaining quartiles). Longitudinal and Poisson models assessed differences in BMIz by SEE over the second year of life and obesity risk at age two, respectively (highest SEE, reference), while attenuation of obesity risk by breastfeeding duration was tested in mediation models.Residing outside of the highest SEE neighbourhoods was associated with an increased BMIz of 0.04 (95%CI 0.02, 0.06) per month of life and increased obesity risk at age two (aRR: 3.7, 95%CI 1.2, 16.2), controlling for family socio-demographics. Breastfeeding duration attenuated9% of the obesity risk attributable to SEE (mediated RR: 3.4, 95%CI 1.1, 14.8).In the PREVAIL Cohort, residing outside of the highest SEE neighbourhoods predicted a significant increase in BMIz and obesity risk in children before age two, a relationship that was partially mediated by breastfeeding duration.Breastfeeding support may play an important role in reducing obesity rates in children in lower SEE neighbourhoods.

Maternal antibiotic (ABx) exposure can significantly perturb the transfer of microbiota from mother to offspring, resulting in dysbiosis of potential relevance to neurodevelopmental disorders such as autism spectrum disorder (ASD). Studies in rodent models have found long-term neurobehavioral effects in offspring of ABx-treated dams, but ASD-relevant behavior during the early preweaning period has thus far been neglected. Here, we exposed C57BL/6J mouse dams to ABx (5 mg/ml neomycin, 1.25 μg/ml pimaricin, .075% v/v acetic acid) dissolved in drinking water from gestational day 12 through offspring postnatal day 14. A number of ASD-relevant behaviors were assayed in offspring, including ultrasonic vocalization (USV) production during maternal separation, group huddling in response to cold challenge, and olfactory-guided home orientation. In addition, we obtained measures of thermoregulatory competence in pups during and following behavioral testing. We found a number of behavioral differences in offspring of ABx-treated dams (e.g., modulation of USVs by pup weight, activity while huddling) and provide evidence that some of these behavioral effects can be related to thermoregulatory deficiencies, particularly at younger ages. Our results suggest not only that ABx can disrupt microbiomes, thermoregulation, and behavior, but that metabolic effects may confound the interpretation of behavioral differences observed after early-life ABx exposure.

Background Reducing infant mortality is a major public health goal. The potential impact of breastfeeding on infant deaths is not well studied in the United States (US). Methods We analyzed linked birth−death certificates for 3,230,500 US births that occurred in 2017, including 6,969 post-perinatal deaths from 7−364 days of age as the primary outcome, further specified as late-neonatal (7−27 days) or post-neonatal (28−364 days) deaths. The primary exposure was ‘ever breastfed' obtained from birth certificates. Multiple logistic regression examined associations of ever breastfeeding with post-perinatal deaths and specific causes of deaths, controlling for maternal and infant factors. Findings We observed an adjusted reduced odds ratio (AOR)=0·74 with 95% confidence intervals (CI)=0·70–0·79 for the association of breastfeeding initiation with overall infant deaths (7−364 days), AOR=0·60 (0·54–0·67) for late-neonatal deaths, and AOR=0·81 (0·76–0·87) for post-neonatal deaths. In race/ethnicity-stratified analysis, significant associations of breastfeeding initiation with reduced odds of overall infant deaths were observed for Hispanics [AOR=0·64 (0·55−0·74)], non-Hispanic Whites [AOR=0·75 (0·69−0·81)], non-Hispanic Blacks [AOR=0·83 (0·75−0·91)], and non-Hispanic Asians [AOR=0·51 (0·36−0·72)]. Across racial/ethnic groups, effect sizes for late-neonatal deaths were consistently larger than those for post-neonatal deaths. Significant effects of breastfeeding initiation were observed for deaths due to infection [AOR=0·81(0·69–0·94)], Sudden Unexpected Infant Death [AOR=0·85 (0·78–0·92)], and necrotizing enterocolitis [AOR=0·67 (0·49−0·90)]. Interpretation Breastfeeding initiation is significantly associated with reduced odds of post-perinatal infant deaths in multiple racial and ethnic groups within the US population. These findings support efforts to improve breastfeeding in infant mortality reduction initiatives.

A major polymorphism in the fucosyltransferase2 (FUT2) gene influences risk of multiple gut diseases, but its impact on the microbiome of breastfed infants was unknown. In individuals with an active FUT2 enzyme (“secretors”), the intestinal mucosa is abundantly fucosylated, providing mutualist bacteria with a rich endogenous source of fucose. Non-secretors comprise approximately one-fifth of the population, and they lack the ability to create this enzyme. Similarly, maternal secretor status influences the abundance of a breastfeeding mother’s fucosylated milk oligosaccharides. We compared the impact of maternal secretor status, measured by FUT2 genotype, and infant secretor status, measured by FUT2 genotype and phenotype, on early infant fecal microbiome samples collected from 2-month-old exclusively breastfed infants (n = 59). Infant secretor status (19% non-secretor, 25% low-secretor, and 56% full-secretor) was more strongly associated with the infant microbiome than it was with the maternal FUT2 genotype. Alpha diversity was greater in the full-secretors than in the low- or non-secretor infants (p = 0.049). Three distinct microbial enterotypes corresponded to infant secretor phenotype (p = 0.022) and to the dominance of Bifidobacterium breve, B. longum, or neither (p < 0.001). Infant secretor status was also associated with microbial metabolic capacity, specifically, bioenergetics pathways. We concluded that in exclusively breastfed infants, infant—but not maternal—secretor status is associated with infant microbial colonization and metabolic capacity.

Background The impact of COVID-19 on physical and mental health and employment after hospitalisation with acute disease is not well understood. The aim of this study was to determine the effects of COVID-19-related hospitalisation on health and employment, to identify factors associated with recovery, and to describe recovery phenotypes. Methods The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a multicentre, long-term follow-up study of adults (aged ≥18 years) discharged from hospital in the UK with a clinical diagnosis of COVID-19, involving an assessment between 2 and 7 months after discharge, including detailed recording of symptoms, and physiological and biochemical testing. Multivariable logistic regression was done for the primary outcome of patient-perceived recovery, with age, sex, ethnicity, body-mass index, comorbidities, and severity of acute illness as covariates. A post-hoc cluster analysis of outcomes for breathlessness, fatigue, mental health, cognitive impairment, and physical performance was done using the clustering large applications k-medoids approach. The study is registered on the ISRCTN Registry (ISRCTN10980107). Findings We report findings for 1077 patients discharged from hospital between March 5 and Nov 30, 2020, who underwent assessment at a median of 5·9 months (IQR 4·9–6·5) after discharge. Participants had a mean age of 58 years (SD 13); 384 (36%) were female, 710 (69%) were of white ethnicity, 288 (27%) had received mechanical ventilation, and 540 (50%) had at least two comorbidities. At follow-up, only 239 (29%) of 830 participants felt fully recovered, 158 (20%) of 806 had a new disability (assessed by the Washington Group Short Set on Functioning), and 124 (19%) of 641 experienced a health-related change in occupation. Factors associated with not recovering were female sex, middle age (40–59 years), two or more comorbidities, and more severe acute illness. The magnitude of the persistent health burden was substantial but only weakly associated with the severity of acute illness. Four clusters were identified with different severities of mental and physical health impairment (n=767): very severe (131 patients, 17%), severe (159, 21%), moderate along with cognitive impairment (127, 17%), and mild (350, 46%). Of the outcomes used in the cluster analysis, all were closely related except for cognitive impairment. Three (3%) of 113 patients in the very severe cluster, nine (7%) of 129 in the severe cluster, 36 (36%) of 99 in the moderate cluster, and 114 (43%) of 267 in the mild cluster reported feeling fully recovered. Persistently elevated serum C-reactive protein was positively associated with cluster severity. Interpretation We identified factors related to not recovering after hospital admission with COVID-19 at 6 months after discharge (eg, female sex, middle age, two or more comorbidities, and more acute severe illness), and four different recovery phenotypes. The severity of physical and mental health impairments were closely related, whereas cognitive health impairments were independent. In clinical care, a proactive approach is needed across the acute severity spectrum, with interdisciplinary working, wide access to COVID-19 holistic clinical services, and the potential to stratify care. Funding UK Research and Innovation and National Institute for Health Research.

The interaction of SARS-CoV-2 infection with extracellular vesicles (EVs) is of particular interest at the moment. Studying SARS-CoV-2 contaminated-EV isolates in instruments located outside of the biosafety level-3 (BSL-3) environment requires knowing how viral inactivation methods affect the structure and function of extracellular vesicles (EVs). Therefore, three common viral inactivation methods, ultraviolet-C (UVC; 1350 mJ/cm

OBJECTIVES: The first USDA Dietary Guidelines for Americans for children under 2 were released in December, 2020, and recommend a diverse diet rich in fruits and vegetables (FV), whole grains and lean protein and avoidance of sugar-sweetened beverages (SSB). We analyzed data for children 12–24 months enrolled in the CDC-funded PREVAIL Cohort in Cincinnati, OH to assess adherence to FV and SSB recommendations by the socioeconomic position (SEP) of their neighborhoods. METHODS: Diet was assessed using a validated food frequency questionnaire and daily servings of FV and SSB were calculated. Home addresses were geocoded and merged with the Deprivation Index, a validated measure of census tract-level SEP, with residence then classified as being High SEP (least deprived), Low SEP (most deprived) or the middle quartiles of deprivation score. Comparisons of FV and SSB intake were made using logistic or Poisson regression and generalized estimating equations (GEE). RESULTS: Dietary data was available for N = 207 children from research visits at 12 (n = 155), 18 (n = 196), and 24 (n = 171) months. Residents in High SEP neighborhoods were 86% white with a median household income of ≥$50,000; residents of Low SEP neighborhoods were 86% Black with a median income of ≤$25,000. Children in High SEP consumed the most and those in Low SEP the least FV per day (mos. 12, 18, 24: High: 3.8, 3.8, 4.5; Low: 2.1, 2.7, 3.2; all P

Background: Black mothers in the United States have shorter breastfeeding (BF) durations and less exclusive breastfeeding (EBF) than others. The factors underlying these disparities require investigation. Methods: Using longitudinal data from a CDC-sponsored birth cohort in Cincinnati, Ohio, we analyzed the factors mediating racial disparity in BF outcomes. Study mothers were enrolled in prenatal clinics associated with two large birth hospitals. Analysis was restricted to racial groups with sufficient numbers in the cohort, non-Hispanic Black (n = 92) and White (n = 113) mothers, followed to at least 6 months postpartum. Results: Black mothers were 25 times more likely to reside in socioeconomically deprived neighborhoods and 20 times more likely to have an annual household income

Nationally representative data from mother–child dyads that capture human milk composition (HMC) and associated health outcomes are important for advancing the evidence to inform federal nutrition and related health programs, policies, and consumer information across the governments in the United States and Canada as well as in nongovernment sectors. In response to identified gaps in knowledge, the National Institute of Diabetes and Digestive and Kidney Diseases of the NIH sponsored the “Workshop on Human Milk Composition—Biological, Environmental, Nutritional, and Methodological Considerations” held 16–17 November 2017 in Bethesda, Maryland. Through presentations and discussions, the workshop aimed to 1) share knowledge on the scientific need for data on HMC; 2) explore the current understanding of factors affecting HMC; 3) identify methodological challenges in human milk (HM) collection, storage, and analysis; and 4) develop a vision for a research program to develop an HMC data repository and database. The 4 workshop sessions included 1) perspectives from both federal agencies and nonfederal academic experts, articulating scientific needs for data on HMC that could lead to new research findings and programmatic advances to support public health; 2) information about the factors that influence lactation and/or HMC; 3) considerations for data quality, including addressing sampling strategies and the complexities in standardizing collection, storage, and analyses of HM; and 4) insights on how existing research programs and databases can inform potential visions for HMC initiatives. The general consensus from the workshop is that the limited scope of HM research initiatives has led to a lack of robust estimates of the composition and volume of HM consumed and, consequently, missed opportunities to improve maternal and infant health.

Background: Breastfeeding promotion and support are not universally accepted in the United States as a strategy to reduce infant mortality. We investigated associations between breastfeedi...

The consumption of human milk by a breastfeeding infant is associated with positive health outcomes, including lower risk of diarrheal disease, respiratory disease, otitis media, and in later life, less risk of chronic disease. These benefits may be mediated by antibodies, glycoproteins, glycolipids, oligosaccharides, and leukocytes. More recently, human milk extracellular vesicles (hMEVs) have been identified. HMEVs contain functional cargos, i.e., miRNAs and proteins, that may transmit information from the mother to promote infant growth and development. Maternal health conditions can influence hMEV composition. This review summarizes hMEV biogenesis and functional contents, reviews the functional evidence of hMEVs in the maternal–infant health relationship, and discusses challenges and opportunities in hMEV research.

The development of targeted treatment options for precision medicine is hampered by a slow and costly process of drug screening. While small molecule docking simulations are often applied in conjunction with cheminformatic methods to reduce the number of candidate molecules to be tested experimentally, the current approaches suffer from high false positive rates and are computationally expensive. Here, we present a novel in silico approach for drug discovery and repurposing, dubbed connectivity enhanced Structure Activity Relationship (ceSAR) that improves on current methods by combining docking and virtual screening approaches with pharmacogenomics and transcriptional signature connectivity analysis. ceSAR builds on the landmark LINCS library of transcriptional signatures of over 20,000 drug-like molecules and ~5,000 gene knock-downs (KDs) to connect small molecules and their potential targets. For a set of candidate molecules and specific target gene, candidate molecules are first ranked by chemical similarity to their ‘concordant’ LINCS analogs that share signature similarity with a knock-down of the target gene. An efficient method for chemical similarity search, optimized for sparse binary fingerprints of chemical moieties, is used to enable fast searches for large libraries of small molecules. A small subset of candidate compounds identified in the first step is then re-scored by combining signature connectivity with docking simulations. On a set of 20 DUD-E benchmark targets with LINCS KDs, the consensus approach reduces significantly false positive rates, improving the median precision 3-fold over docking methods at the extreme library reduction. We conclude that signature connectivity and docking provide complementary signals, offering an avenue to improve the accuracy of virtual screening while reducing run times by multiple orders of magnitude.

Background and Objectives: Feeding of human milk is associated with improved health outcomes in preterm infants. Mothers of preterm infants have difficulty establishing and maintaining an adequate ...

Bifidobacterium species are beneficial and dominant members of the breastfed infant gut microbiome; however, their health benefits are partially species-dependent. Here, we characterize the species and subspecies of Bifidobacterium in breastfed infants around the world to consider the potential impact of a historic dietary shift on the disappearance of B. longum subsp. infantis in some populations. Across populations, three distinct patterns of Bifidobacterium colonization emerged: (1) The dominance of Bifidobacterium longum subspecies infantis, (2) prevalent Bifidobacterium of multiple species, and (3) the frequent absence of any Bifidobacterium. These patterns appear related to a country’s history of breastfeeding, with infants in countries with historically high rates of long-duration breastfeeding more likely to be colonized by B. longum subspecies infantis compared with infants in countries with histories of shorter-duration breastfeeding. In addition, the timing of infant colonization with B. longum subsp. infantis is consistent with horizontal transmission of this subspecies, rather than the vertical transmission previously reported for other Bifidobacterium species. These findings highlight the need to consider historical and cultural influences on the prevalence of gut commensals and the need to understand epidemiological transmission patterns of Bifidobacterium and other major commensals.

Coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has become a global health crisis with more than four million deaths worldwide. A substantial number of COVID-19 survivors continue suffering from long-COVID syndrome, a long-term complication exhibiting chronic inflammation and gut dysbiosis. Much effort is being expended to improve therapeutic outcomes. Human milk oligosaccharides (hMOS) are non-digestible carbohydrates known to exert health benefits in breastfed infants by preventing infection, maintaining immune homeostasis and nurturing healthy gut microbiota. These beneficial effects suggest the hypothesis that hMOS might have applications in COVID-19 as receptor decoys, immunomodulators, mucosal signaling agents, and prebiotics. This review summarizes hMOS biogenesis and classification, describes the possible mechanisms of action of hMOS upon different phases of SARS-CoV-2 infection, and discusses the challenges and opportunities of hMOS research for clinical applications in COVID-19.

Blood type purportedly influences susceptibility to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, but whether it affects severity of coronavirus disease 2019 (COVID-19) is unclear. Therefore, we examined the association of blood type and rhesus with hospitalization and disease severity among 428 COVID-19 patients diagnosed at the University of Cincinnati health system. In the sample, 50.2% of participants had the blood type O, 38.7% had the blood type A, 17.5% had the blood type B, and 3.5% had the blood type AB. In analysis adjusted for sociodemographic characteristics and comorbidities, the blood types A (OR: 0.90, 95% CI: 0.54, 1.50), B (OR: 0.93, 95% CI: 0.51, 1.69), AB (OR: 0.69, 95% CI: 0.20, 2.41), and O (OR: 1.18, 95%: 0.74, 1.98) were not associated with hospitalization for COVID-19. Similarly, the blood types A (OR: 0.93, 95% CI: 0.52, 1.65), B (OR: 0.92, 95% CI: 0.46, 1.84), AB (OR: 0.30, 95% CI: 0.04, 2.44), and O (OR: 1.25, 95%: 0.73, 2.14) were not associated with admission to intensive care unit or death in COVID-19. In conclusion, blood type is not associated with hospitalization or disease severity in COVID-19; therefore, it may not be useful marker for identifying patients at risk for severe COVID-19.

To assess whether titers of anti-rotavirus immunoglobulin G persist during the post–rotavirus vaccine era, the Pediatric Respiratory and Enteric Virus Acquisition and Immunogenesis Longitudinal (PREVAIL) Cohort analyzed serum samples collected from Cincinnati-area mothers and young infants in 2017–2018. Rotavirus-specific antibodies continue to be transferred from US mothers to their offspring in the post–rotavirus vaccine era, despite dramatic decreases in childhood rotavirus gastroenteritis.

BackgroundThe coronavirus disease (COVID-19) first identified in Wuhan in December 2019 became a pandemic within a few months of its discovery. The impact of COVID-19 is due to both its rapid spread and its severity, but the determinants of severity have not been fully delineated.ObjectiveIdentify factors associated with hospitalization and disease severity in a racially and ethnically diverse cohort of COVID-19 patients.MethodsWe analyzed data from COVID-19 patients diagnosed at the University of Cincinnati health system from March 13, 2020 to May 31, 2020. Severe COVID-19 was defined as admission to intensive care unit or death. Logistic regression modeling adjusted for covariates was used to identify the factors associated with hospitalization and severe COVID-19.ResultsAmong the 689 COVID-19 patients included in our study, 29.2% were non-Hispanic White, 25.5% were non-Hispanic Black, 32.5% were Hispanic, and 12.8% were of ‘Other’ race/ethnicity. About 31.3% of patients were hospitalized and 13.2% had severe disease. In adjusted analyses, the sociodemographic factors associated with hospitalization and/or disease severity included older age, non-Hispanic Black or Hispanic race/ethnicity (compared non-Hispanic White), and smoking. The following comorbidities: diabetes, hypercholesterolemia, asthma, chronic obstructive pulmonary disease (COPD), chronic kidney disease, cardiovascular diseases, osteoarthritis, and vitamin D deficiency, were associated with hospitalization and/or disease severity. Hematological disorders such as anemia, coagulation disorders, and thrombocytopenia were associated with higher odds of both hospitalization and disease severity.ConclusionThis study confirms race and ethnicity as predictors of severe COVID-19 and identifies clinical risk factors not previously reported such a vitamin D deficiency, hypercholesterolemia, osteoarthritis, and anemia.

OBJECTIVES: Diet quality in childhood predicts diet quality and obesity in adulthood. Breastfeeding (BF) history and neighborhood socio-economic position (SEP) are associated with diet quality in school-age children, but little is known about the effect of neighborhood on the developing diet in infancy. We analyzed data from PREVAIL, a birth cohort in Cincinnati, OH, to examine residence in a low-SEP neighborhood as a predictor of diet quality in infants. METHODS: PREVAIL subjects (n = 153) with a completed a food frequency questionnaire (FFQ) at 12 months of age were included for analysis. The FFQ estimated infant daily intake of tubers, fruits, vegetables, nuts/legumes, meats and grains. BF initiation and duration, and household confounding factors were determined via periodic questionnaires throughout infancy. Diet quality was measured in terms of BF history, daily portions of fruits & vegetables (F&V) and sugar sweetened beverages, and a calculated dietary diversity score. Subject residence was geocoded and assigned a Deprivation Index (DI) score, a composite of US census-derived factors describing community-level SEP. Diet quality measures were analyzed in relation to the infant's Deprivation Index quartile (DIQ), with quartiles ranked from the least (Q1) to most (Q4) deprived neighborhoods. RESULTS: DIQ was inversely associated with diet quality measured by median daily F&V intake (Q1 3.1, Q2 3.4, Q3 3.5, Q4 1.7, P

Rotaviruses bind to enterocytes in a genotype-specific manner via histo-blood group antigens (HBGAs), which are also detectable in saliva. We evaluated antirotavirus immunoglobulin A seroconversion ('vaccine take") among 166 Ghanaian infants after 2-3 doses of G1P[8] rotavirus vaccine during a vaccine trial, by HBGA status from saliva collected at age 4.1 years. Only secretor status was associated with seroconversion: 41% seroconversion for secretors vs 13% for nonsecretors; relative risk, 3.2 (95% confidence interval, 1.2-8.1; P = .016). Neither Lewis antigen nor salivary antigen blood type was associated with seroconversion. Likelihood of "take" for any particular rotavirus vaccine may differ across populations based on HBGAs.

BACKGROUND Human milk feeding is encouraged for all infants; however, the mammary gland depends on maternal dietary intake of vitamins A, B1, B2, B6, B12, D, docosahexaenoic acid (DHA), choline, and iodine. Nutrition support team knowledge of maternal feeding guidelines for these nutrient sources can therefore impact infant intake. We hypothesized that these key nutrients for lactation in the mother's diet would be less than the dietary guidelines in the United States. METHODS This was a secondary analysis of nutrition data collected during a randomized, controlled trial. Dietary records were analyzed from 16 mothers (13 with singleton and 3 with multiple births) completing the study. Mean dietary intakes of selected nutrients were calculated and compared with the current dietary reference intakes. RESULTS Mean maternal dietary intake for singletons was significantly (P < .05) lower than the dietary reference intakes for (vitamin A (58%), vitamin D (44%), and choline (58%);) DHA comprised only 5% of the current expert recommendation. Based on singleton recommendations, mothers to twins consumed an adequate intake except for DHA. CONCLUSIONS Women providing breast milk for singleton preterm infants did not consume dietary reference intakes for key nutrients. Twin mothers' diets were adequate except for DHA, but these guidelines are based on singleton pregnancies and remain poorly understood for twin needs. The nutrition support team can have a unique role in maternal dietary education to impact human milk nutrient delivery to the infant.

Objective Obesity in adults is associated with inflammation and oxidative stress. Whether or not this phenotype is reflected in human milk (HM) composition, or may impact infant growth remains unknown. We investigated whether HM from overweight/obese (OW/Ob) mothers exhibited higher concentrations of inflammatory cytokines and markers of oxidative stress. We also correlated these bioactive components with infant growth patterns. Methods This was an observational cohort of 56 breastfeeding mothers and their infants [33 normal weight (NW) and 23 OW/Ob]. Infants were followed until 6 months of age and HM collected at 2-weeks and 4-months. Results Markers of oxidative stress, 8-hydroxy-deoxyguanosine (8OHdG) and 4-hydroxynonenol (HNE), decreased in HM over time (p

Histo-blood group antigens (HBGAs) expressed on enterocytes are proposed receptors for rotaviruses and can be measured in saliva. Among 181 Pakistani infants in a G1P[8] rotavirus vaccine trial who were seronegative at baseline, anti-rotavirus immunoglobulin A seroconversion rates after 3 vaccine doses differed significantly by salivary HBGA phenotype, with the lowest rate (19%) among infants who were nonsecretors (ie, who did not express the carbohydrate synthesized by FUT2), an intermediate rate (30%) among secretors with non-blood group O, and the highest rate (51%) among secretors with O blood group. Differences in HBGA expression may be responsible for some of the discrepancy in the level of protection detected for the current rotavirus vaccines in low-income versus high-income settings.

Objective: To evaluate the effectiveness of a dietary intervention to increase target vegetable intake in overweight, postpartum mothers; and their children. Methods: Overweight mothers attending their six-week postpartum follow-up visit and their infants (n = 104 pairs) were randomized to intervention or usual care groups during the time period 2008-2011. Mothers received four 60 minute education sessions with a nutrition professional and eight monthly follow-up phone calls. Counseling began at the obstetrician office and continued at the regularly scheduled pediatric visits. The primary study outcome was the change in maternal target vegetable intake. Secondary outcomes included child target vegetable intake and whether child vegetable intake was modified by exposure to breastfeeding. Mother/child energy intake and weight indices were also assessed. Outcomes were measured at baseline (6-weeks postpartum), 6, 12 (post-intervention), and 18 (follow-up) months. Mixed-effects models were used to estimate the impact of the dietary intervention on study outcomes relative to usual care. Results: Mothers randomized to the intervention had greater consumption of target vegetables at 6, 12 and 18 months (P < 0.01, P < 0.01 and P = 0.03, respectively). There were no differences between groups in maternal energy intake, body mass index, or child target vegetable or energy intake. The child’s target vegetable intake at 12 months was related to the mother’s intake at 6 months (P = 0.03), however, this relationship was not modified by exposure to breastfeeding. Conclusion: A dietary intervention targeting the diet of the mother/child dyad resulted in improved maternal vegetable intake.

BACKGROUND An understudied component of the diet, branched-chain fatty acids (BCFAs) are distinctive saturated fatty acids that may have an important influence on health. Human-milk fatty acid composition is known to differ worldwide, but comparative data are lacking on BCFAs. OBJECTIVE We tested the hypotheses that concentrations of BCFAs in human milk differ between populations and are associated with maternal diet. DESIGN We surveyed the BCFA composition of samples collected as part of a standardized, prospective study of human-milk composition. Mothers were enrolled from 3 urban populations with differing diets: Cincinnati, Ohio; Shanghai, China; and Mexico City, Mexico. Enrollment was limited to healthy mothers of term singleton infants. We undertook a cross-sectional analysis of milk from all women with samples at postpartum week 4 (n = 359; ∼120 women/site). Fatty acids were extracted from milk by using a modified Bligh-Dyer technique and analyzed by gas chromatography. Statistical analysis was performed by ANOVA and Tobit regression. For Cincinnati mothers, 24-h diet recalls were analyzed in relation to the individual BCFA concentrations measured in milk samples. RESULTS Total BCFAs in milk differed by site, with the highest concentration in Cincinnati followed by Mexico City and Shanghai (mean ± SE: 7.90 ± 0.41, 6.10 ± 0.36, and 4.27 ± 0.25 mg/100 mL, respectively; P < 0.001). Site differences persisted after delivery mode, maternal age, and body mass index were controlled for. The individual concentrations of iso-14:0, iso-16:0, iso-18:0, anteiso-15:0, and anteiso-17:0 also differed between sites. Milk concentrations of iso-14:0 and anteiso-15:0 were associated with maternal intake of dairy; iso-16:0 was associated with maternal intakes of dairy and beef. CONCLUSIONS BCFA concentrations in milk at 4 wk postpartum differed between mothers from Cincinnati, Shanghai, and Mexico City. Variations in human-milk BCFAs are influenced by diet. The impact of BCFAs on infant health warrants investigation.

OBJECTIVES: Lack of microbiota accessible carbohydrates (MAC) can drive gut commensal extinctions. Infant formula lacks the MAC found in breastmilk, human milk oligosaccharides (HMOs). As a result, a switch from breastmilk feeding (high MAC) to formula (low MAC) may drive extinctions of infant gut commensals. METHODS: The prevalence of Bifidobacterium longum subsp. infantis, a bacterium that efficiently consumes HMOs, was compared in cohorts from Austria, Bangladesh, Finland, Gambia, Germany, Switzerland, and United States. Scientific literature reports that both Bangladesh and Gambia have long duration breastfeeding without a history of prevalent formula use; Bangladesh has a mean duration of breastfeeding of 31.9 months and Gambia has a median duration of breastfeeding >18 months. This contrasts with European countries and the US, who all have median duration of breastfeeding 50% relative abundance Bifidobacterium) despite the low frequency of colonization with B. infantis. The R0 of B. infantis transmission varied by country. CONCLUSIONS: The prevalence of infant colonization with B. infantis may be sensitive to breastfeeding duration in populations. Our data supports the concept that lack of MAC drives commensal extinctions, and suggests that deliberate intervention may be needed to restore B. infantis, a bacteria that benefits infant health. More studies are needed, particularly to determine whether species of Bifidobacterium other than B. infantis are sensitive to breastfeeding duration, and to understand the impact of different types of Bifidobacterium on infant health. FUNDING SOURCES: NIH awards F32HD093185 (DHT), AT007079 (DAM), and AT008759 (DAM).

OBJECTIVES: Infant formulas typically lack prebiotic human milk oligosaccharides (HMO) that promote the growth of beneficial gut flora. Supplementation of infant formulas with a variety of non-HMO prebiotics has attempted to replicate this effect, but study sizes have been small and results have been inconclusive. This meta-analysis summarized the results of the published studies of Bifidobacteria abundance in infants fed standard and non-HMO prebiotic-supplemented formulas compared to that of exclusively breastfed infants. METHODS: A literature search was conducted of PubMed and EMBASE for randomized controlled trials of Bifidobacteria abundance in healthy, term, pre-weaning human infants given a non-HMO prebiotic-supplemented infant formula (PF) or a control formula (CF) compared to an exclusively breastfed (EBF) reference group. The prebiotics tested were fructo-oligosaccharide (FOS), galacto-oligosaccharide (GOS), polydextrose (PDX), and inulin; CF were identical to corresponding PF excepting the addition of prebiotics. Results were pooled and post-intervention standardized mean difference in Bifidobacteria absolute abundance was calculated for CF and PF groups compared to an EBF reference group and to each group's own baseline value. Network meta-analysis summarized the data for each group. Significance was set at P

Maternal supplementation with 1000 mg/day docosahexaenoic acid (DHA) provides third trimester DHA accretion levels in breast milk for the preterm infant. We hypothesized that DHA supplementation to mothers providing breastmilk for extremely preterm infants would result in decreased inflammatory markers, in the infant. Mother/infant dyads (n = 27) were enrolled at birth and mothers were assigned to receive 200 or 1000 mg/day of DHA. Milk and plasma samples were analyzed for fatty acids and inflammatory markers. Decreases in inflammation were observed in both maternal and infant plasma and correlated with red blood cell (RBC) DHA levels. The fact that maternal DHA supplementation decreases infant markers of inflammation implies that DHA, delivered through breastmilk, has the potential to decrease inflammation in the infant.

Human milk administration in the early peritransplant period would lower intestinal inflammation after bone marrow transplant (BMT).Children 0-5 years undergoing BMT received either a ready-to-feed human milk preparation designed for these children (Prolacta Bioscience, Duarte, CA) or standard formula. Babies breastfeeding at the time of BMT were also enrolled on the human milk arm. Human milk was administered from day -3 until day +14 after BMT. Metagenomic shotgun sequencing and metabolomics of stool, plasma cytokines, and regenerating islet-derived 3α (REG3α) levels were measured at enrollment and day +14. Human leukocyte antigen-DR isotype (HLA-DR), CD38, and CD69 expression on T cells were evaluated at day +21.Forty-six children were enrolled, 32 received human milk (donor milk n = 23, breastfeeding babies n = 9), and 14 were controls who received standard feeds supervised by a BMT dietician. Twenty-four patients received at least 60% of goal human milk and were evaluable. Plasma interleukin (IL)-8 (p = 0.04), IL-10 (p = 0.02), and REG3α (p = 0.03) were decreased in the human milk cohort. Peripheral blood CD69Administration of human milk resulted in decreased markers of intestinal inflammation and could be a valuable adjunct for patients after BMT.

Fatty acids (FAs) and fat-soluble vitamins are vital components of the human milk lipid fraction. About two-thirds of the human milk FA fraction consist of oleic, linoleic, and palmitic FAs, but the precise composition depends on maternal geography, diet, and genetics. Mothers with high fish consumption have more docosahexaenoic acid (DHA) and other ω-3 FAs in their milk, while mothers with high dairy consumption have more branched-chain FAs in their milk. Vitamins A and E are the most common fat-soluble vitamins, but milk concentrations vary, depending on maternal diet and body stores. Vitamin D is typically low or undetectable in mother's milk and typically fails to meet the infant needs. However, trial data indicate that high maternal supplementation (6,400 IU/day) safely provides nutritionally adequate amounts of vitamin D in her milk. FA and fat-soluble vitamin levels in mother's milk can significantly influence infant health; for example, in preterm infants, low endogenous stores of DHA paired with low levels in maternal milk may influence the risk of chronic lung disease and other inflammatory conditions. Greater attention is warranted to the variation in FA and fat-soluble vitamin content of human milk in relation to infant health.

Fatty acids (FAs) and fat-soluble vitamins are vital components of the human milk lipid fraction. About two-thirds of the human milk FA fraction consist of oleic, linoleic, and palmitic FAs, but the precise composition depends on maternal geography, diet, and genetics. Mothers with high fish consumption have more docosahexaenoic acid (DHA) and other ω-3 FAs in their milk, while mothers with high dairy consumption have more branched-chain FAs in their milk. Vitamins A and E are the most common fat-soluble vitamins, but milk concentrations vary, depending on maternal diet and body stores. Vitamin D is typically low or undetectable in mother's milk and typically fails to meet the infant needs. However, trial data indicate that high maternal supplementation (6,400 IU/day) safely provides nutritionally adequate amounts of vitamin D in her milk. FA and fat-soluble vitamin levels in mother's milk can significantly influence infant health; for example, in preterm infants, low endogenous stores of DHA paired with low levels in maternal milk may influence the risk of chronic lung disease and other inflammatory conditions. Greater attention is warranted to the variation in FA and fat-soluble vitamin content of human milk in relation to infant health.

We identify the significance and typical requirements of developmental analyses of the microbiome-gut-brain (MGB) in parents, offspring, and parent-offspring relations, which have particular importance for neurobehavioral outcomes in mammalian species, including humans. We call for a focus on behavioral measures of social-emotional function. Methodological approaches to interpreting relations between the microbiota and behavior are discussed.

Background Acute gastroenteritis (AGE) and acute respiratory infections (ARIs) cause significant pediatric morbidity and mortality. Developing childhood vaccines against major enteric and respiratory pathogens should be guided by the natural history of infection and acquired immunity. The United States currently lacks contemporary birth cohort data to guide vaccine development. Objective The PREVAIL (Pediatric Respiratory and Enteric Virus Acquisition and Immunogenesis Longitudinal) Cohort study was undertaken to define the natural history of infection and immune response to major pathogens causing AGE and ARI in US children. Methods Mothers in Cincinnati, Ohio, were enrolled in their third trimester of pregnancy, with intensive child follow-up to 2 years. Blood samples were obtained from children at birth (cord), 6 weeks, and 6, 12, 18, and 24 months. Whole stool specimens and midturbinate nasal swabs were collected weekly and tested by multipathogen molecular assays. Saliva, meconium, maternal blood, and milk samples were also collected. AGE (≥3 loose or watery stools or ≥1 vomiting episode within 24 hours) and ARI (cough or fever) cases were documented by weekly cell phone surveys to mothers via automated SMS text messaging and review of medical records. Immunization records were obtained from registries and providers. follow-up ended in October 2020. Pathogen-specific infections are defined by a PCR-positive sample or rise in serum antibody. Results Of the 245 enrolled mother–child pairs, 51.8% (n=127) were White, 43.3% (n=106) Black, 55.9% (n=137) publicly insured, and 86.5% (n=212) initiated breastfeeding. Blood collection was 100.0% for mothers (n=245) and 85.7% for umbilical cord (n=210). A total of 194/245 (79.2%) mother–child pairs were compliant based on participation in at least 70% (≥71/102 study weeks) of child-weeks and providing 70% or more of weekly samples during that time, or blood samples at 18 or 24 months. Compliant participants (n=194) had 71.0% median nasal swab collection (IQR 30.0%-90.5%), with 98.5% (191/194) providing either an 18- or 24-month blood sample; median response to weekly SMS text message surveys was 95.1% (IQR 76.5%-100%). Compliant mothers reported 2.0 AGE and 4.5 ARI cases per child-year, of which 25.5% (160/627) and 38.06% (486/1277) of cases, respectively, were medically attended; 0.5% of AGE (3/627) and 0.55% of ARI (7/1277) cases were hospitalized. Conclusions The PREVAIL Cohort demonstrates intensive follow-up to document the natural history of enteric and respiratory infections and immunity in children 0-2 years of age in the United States and will contribute unique data to guide vaccine recommendations. Testing for pathogens and antibodies is ongoing. International Registered Report Identifier (IRRID) RR1-10.2196/22222

The human gut microbiome is involved in vital biological functions, such as maintenance of immune homeostasis and modulation of intestinal development and enhanced metabolic capabilities. Disturbances of the intestinal microbiota have been associated with development and progression of inflammatory conditions, including graft-versus-host disease (GVHD). The fucosyltransferase 2 (FUT2) gene produces an enzyme that is responsible for the synthesis of the H antigen in body fluids and on the intestinal mucosa. FUT2 genotype has been shown to modify the gut microbiome. We hypothesized that FUT2 genotype influences risk of GVHD and bacterial translocation after allogeneic hematopoietic stem cell transplantation (HSCT). FUT2 genotype was determined in 150 consecutive patients receiving allogeneic HSCT at our center. We abstracted clinical characteristics and outcomes from the transplantation database. Cumulative risk of any acute GVHD varied by FUT2 genotype, with decreased risk in those with A/A genotype and increased risk in those with G/G genotype. In contrast, the cumulative incidence of bacteremia was increased in those with A/A genotype. We conclude that the FUT2 genotype influences risk of acute GVHD and bacteremia after HSCT. We hypothesize that the mechanisms involve altered intestinal surface glycosylation and microbial composition but this requires additional study.

Background The ACIP recommends influenza and Tdap vaccination during pregnancy to reduce the risk of influenza and pertussis in the mother and her infant. We assessed influenza and Tdap vaccination coverage and associated factors among pregnant women enrolled in PREVAIL, a prospective birth cohort study in Cincinnati, OH. We assessed sensitivity and specificity of self report for both vaccines against state registry, maternal healthcare provider, and work-place records. Methods We enrolled and interviewed 265 pregnant women regarding self-reported receipt of influenza and Tdap vaccines, and obtained vaccine records from registry, electronic medical record, provider, employer, or pharmacy. We grouped subjects by documented vaccination status and analyzed demographic variables and vaccine attitudes regarding efficacy, safety, and hesitancy using unadjusted Fisher exact tests. We analyzed sensitivity and specificity of maternal recall. Results We identified documentation of influenza and Tdap vaccine receipt during pregnancy in 172/265 (64.9%) and 238/265 (89.8%) of women, respectively (Figure 1); by self report, 177/265 (66.8%) reported receiving influenza and 221/265 (83.4%) Tdap vaccine. The two most common primary reasons cited for receiving influenza vaccine were “to protect my baby” (36.7%) and “to protect myself” (26%; Figure 2). Pregnant women were more likely to get Tdap vaccine if a healthcare worker recommended it (OR 5.4). Subjects were more likely to get influenza vaccine if they believed it was effective in preventing influenza in themselves (OR 9.0) or their babies (OR 8.1). While positive recall had a high concordance (95.2% and 93.4% for influenza and Tdap, respectively), 12.5% and 32.1% of mothers incorrectly recalled not receiving an influenza or Tdap vaccine, respectively, that was documented as received in the records (Figure 3). Conclusion We found high concordance between maternal recall and verification for both influenza and Tdap vaccines. In this single-site cohort of 265 women, self report was a reliable measure of vaccination status among pregnant women. Provider communication to pregnant women regarding effectiveness of influenza and Tdap vaccinations for themselves and their infants may lead to higher maternal vaccination rates. Disclosures All authors: No reported disclosures.

OBJECTIVES: We examined the impact of prenatal exposure to maternal antibiotics on risk of necrotizing enterocolitis (NEC), late onset sepsis (LOS), and death in preterm infants. STUDY DESIGN: Secondary data analysis was conducted using an extant cohort of 580 infants born 5 days) duration. RESULTS: Two-thirds of mothers received antibiotics within 72 hours prior to delivery, of whom 59.8% received more than one antibiotic. Ampicillin (37.6%) and azithromycin (26.4%) were the most common antibiotics given. NEC occurred in 7.5%, LOS in 11.1%, death in 9.6%, and the combined outcome of NEC, LOS, or death in 21.3% of study infants. In multiple logistic regression models adjusted for gestational age, postnatal empiric antibiotic exposure, and other factors, prenatal antibiotic exposure was associated with reduced risk of NEC (odds ratio [OR; CI=0.28; 0.14–0.56], P < .001), death ([OR; CI = 0.29; 0.14–0.60], p=0.001), but not LOS ([OR; CI=1.59; 0.84–2.99], p=0.15), though protection was significant for the combined outcome (OR=0.52, p

Breastfeeding reduces infant morbidity and mortality caused by many diseases. The impact of breastfeeding may due in large measure to the human milk oligosaccharides (HMOs). Many HMOs are analogs to histo-blood group antigens on the mucosal surface that some pathogens use for binding and infection and can thus serve as pathogen-binding inhibitors. HMOs also shift microbial community composition and function and influence host immune response. Due to breakthroughs in biosynthesis, testing HMOs as therapeutic agents is now imaginable. Synthesized, bioidentical HMOs could be developed and tested for prevention or treatment of many conditions, for which oral intake is ensured, particularly those that involve GI infection or microbial dysbiosis and inflammation and, in some way, GI glycosylation (fucosylation or sialylation). Patient populations that should have high priority for testing HMOs include preterm infants and inflammatory bowel disease patients, as well as individuals with intestinal failure and immunocompromised patients.

Qualitative polymerase chain reaction (PCR) was used to determine the prevalence of fecal excretion of BK virus, JC virus, and simian virus 40 in 1-year-old infants. Overall, 17.8% of 321 specimens from 64.1% of 39 infants were polyomavirus positive. These data suggest that the gastrointestinal tract may be a site of polyomavirus persistence in humans.

Background:Factors associated with successful provision of mother’s own milk (MOM) for premature infants in a Japanese neonatal intensive care unit (NICU) context are not well known.Objective:We determined the independent risk factors for low milk volume at day 4 postpartum and formula feeding at the time of NICU discharge.Methods:We reviewed the medical records of mothers who delivered at < 32 weeks’ gestation. We determined maternal, premature infant, and milk expression variables predictive of (1) day 4 postpartum milk volume being less than the cohort median and (2) formula feeding at the time of NICU discharge, reported as adjusted odds ratios (95% confidence interval).Results:Among 85 dyads, median (quartile range) milk volume on day 4 postpartum was 153 (34-255) mL. The rate of formula feeding at discharge was 42%. Mothers delivering by cesarean (vs vaginal) delivery had 4.3-fold (1.5-12.4) greater odds of day 4 milk volume < median ( P < .01). Pregnancy-induced hypertension, delayed milk expression initiation, and low pumping frequency were strongly associated with cesarean delivery. Subsequently, mothers with day 4 milk volume < median (vs ≥ median) had 7.1-fold (2.6-19.5) greater odds of formula feeding at discharge ( P < .01).Conclusion:Cesarean delivery is associated with lower milk volume on day 4 but may represent a composite of underlying risk factors for low milk volume in the early postpartum period. Further, low milk volume on day 4 is a strong correlate of lack of exclusive breast milk feeding at NICU discharge.

Our aim was to review the use of high-dimensional biology techniques, specifically transcriptomics, proteomics, and metabolomics, in amniotic fluid to elucidate the mechanisms behind preterm birth or assessment of fetal development. We performed a comprehensive MEDLINE literature search on the use of transcriptomic, proteomic, and metabolomic technologies for amniotic fluid analysis. All abstracts were reviewed for pertinence to preterm birth or fetal maturation in human subjects. Nineteen articles qualified for inclusion. Most articles described the discovery of biomarker candidates, but few larger, multicenter replication or validation studies have been done. We conclude that the use of high-dimensional systems biology techniques to analyze amniotic fluid has significant potential to elucidate the mechanisms of preterm birth and fetal maturation. However, further multicenter collaborative efforts are needed to replicate and validate candidate biomarkers before they can become useful tools for clinical practice. Ideally, amniotic fluid biomarkers should be translated to a noninvasive test performed in maternal serum or urine.