Excessive inflammation during pregnancy alters homeostatic mechanisms of the developing fetus and has been linked to adverse pregnancy outcomes. An anti-inflammatory diet could be a promising avenue to combat the pro-inflammatory state of pregnancy, particularly in obese women, but we lack mechanistic data linking this dietary pattern during pregnancy to inflammation and birth outcomes. In an ethnically diverse cohort of 1057 mother-child pairs, we estimated the relationships between dietary inflammatory potential [measured via the energy-adjusted dietary inflammatory index (E-DII™)] and birth outcomes overall, as well as by offspring sex and maternal pre-pregnancy body mass index (BMI). In a subset of women, we also explored associations between E-DII, circulating cytokines (n = 105), and offspring methylation (n = 338) as potential modulators of these relationships using linear regression. Adjusted regression models revealed that women with pro-inflammatory diets had elevated rates of preterm birth among female offspring [β = -0.22, standard error (SE) = 0.07, P<0.01], but not male offspring (β=0.09, SE = 0.06, P<0.12) (P = 0.003). Similarly, we observed pro-inflammatory diets were associated with higher rates of caesarean delivery among obese women (β = 0.17, SE = 0.08, P = 0.03), but not among women with BMI <25 kg/m (P = 0.02). We observed consistent inverse associations between maternal inflammatory cytokine concentrations (IL-12, IL-17, IL-4, IL-6, and TNFα) and lower methylation at the MEG3 regulatory sequence (P<0.05); however, results did not support the link between maternal E-DII and circulating cytokines. We replicate work by others on the association between maternal inflammatory diet and adverse pregnancy outcomes and provide the first empirical evidence supporting the inverse association between circulating cytokine concentrations and offspring methylation.

Background In the US, norovirus is the leading cause of healthcare-associated gastroenteritis outbreaks. To inform prevention efforts, we describe the epidemiology of norovirus outbreaks in long-term care facilities (LTCFs). Methods CDC collects epidemiologic and laboratory data on norovirus outbreaks from U.S. health departments through the National Outbreak Reporting System (NORS) and CaliciNet. Reports from both systems were merged, and norovirus outbreaks in nursing homes, assisted living, and other LTCFs occurring in 2009–2018 were analyzed. Data from the Centers for Medicare and Medicaid Services and the National Center for Health Statistics were used to estimate state LTCF counts. Results During 2009–2018, 50 states, Washington D.C., and Puerto Rico reported 13,092 norovirus outbreaks and 416,284 outbreak-associated cases in LTCFs. Participation in NORS and CaliciNet increased from 2009-2014 and median reporting of LTCF norovirus outbreaks stabilized at 4.1 outbreaks per 100 LTCFs (IQR: 1.0-7.1) annually since 2014. Most outbreaks were spread via person-to-person transmission (90.4%) and 75% occurred during December-March. Genogroup was reported for 7,292 outbreaks with 862 (11.8%) positive for GI and 6,370 (87.3%) for GII. Among 4,425 GII outbreaks with typing data, 3,618 (81.8%) were GII.4. LTCF residents had higher attack rates than staff (median 29.0% versus 10.9%; p&lt;0.001). For every 1,000 cases, there were 21.6 hospitalizations and 2.3 deaths. Conclusions LTCFs have a high burden of norovirus outbreaks. Most LTCF norovirus outbreaks occurred during winter months and were spread person-to-person. Outbreak surveillance can inform development of interventions for this vulnerable population, such as vaccines targeting GII.4 norovirus strains.

I n the United States, the incidence of acute gastroenteritis (AGE) is high. AGE is estimated to cause 179 million illnesses annually (1,2). Precise data are limited on the occurrence and characteristics of sporadic AGE, particularly because the illnesses are generally mild and usually do not require medical care; may not have had diagnostic testing even if care was sought; and, depending on the pathogen, may not be reportable through public health surveillance systems. Previous US publications, using data from the US Foodborne Diseases Active Surveillance Network (FoodNet), have reported AGE prevalence ranging from 7.7 to 11%, equivalent to roughly 0.7-1.4 illnesses/person/year, depending on the recall period (i.e., 7 or 28 days) and symptom profile (i.e., diarrheal illness alone or with the presence of additional symptoms) (1,3-5). These studies have been essential in establishing estimates of AGE incidence in the community and highlighting the substantial burden of disease. However, differences in AGE case definitions have complicated efforts to compare findings across studies and time periods, and robust estimates of occurrence across the age spectrum remain limited. Consequently, there is a need to obtain all-age, population-based estimates of AGE within the United States.Even assuming the lowest reported AGE prevalence of 7.7%, there is potential for substantial disease burden on the local healthcare systems and on society, such as through lost productivity (6). Among persons with AGE, 12%-20% have reported visiting a healthcare provider to manage their symptoms, and AGE has been estimated to contribute to 2-3 million ambulatory visits and 900,000 hospitalizations per year in the United States (1,3,4,7-10). However, these data have relied on samples of persons within a geographic area who may differentially seek care depending on if they have medical insurance or access to an affordable care source. As a result, these studies may not accurately estimate the true potential burden on a healthcare system.Clarifying the etiology of AGE illness within communities and healthcare systems can help to effectively target prevention efforts. Sporadic cases of AGE are largely attributable to viral pathogens; norovirus is the most common cause of AGE across the age spectrum. Evidence in the literature suggests that intensity of viral shedding among those with asymptomatic norovirus infections is similar to that of symptomatic infections (2,8,11); however, according to transmission modeling of a healthcare-

Background The National Outbreak Reporting System (NORS) captures data on foodborne, waterborne, and enteric illness outbreaks in the United States. The aim of this study is to describe enteric illness outbreaks reported during 11 years of surveillance. Methods We extracted finalized reports from NORS for outbreaks occurring during 2009–2019. Outbreaks were included if they were caused by an enteric etiology or if any patients reported diarrhea, vomiting, bloody stools, or unspecified acute gastroenteritis. Results A total of 38,395 outbreaks met inclusion criteria, increasing from 1,932 in 2009 to 3,889 in 2019. Outbreaks were most commonly transmitted through person-to-person contact (n=23,812, 62%) and contaminated food (n=9,234, 24%). Norovirus was the most commonly reported etiology, reported in 22,820 (59%) outbreaks, followed by Salmonella (n=2,449, 6%) and Shigella (n=1,171, 3%). Norovirus outbreaks were significantly larger, with a median of 22 illnesses per outbreak, than outbreaks caused by the other most common outbreak etiologies (p&lt;0.0001, all comparisons). Hospitalization rates were higher in outbreaks caused by Salmonella and E. coli outbreaks (20.9% and 22.8%, respectively) than those caused by norovirus (2%). The case fatality rate was highest in E. coli outbreaks (0.5%) and lowest in Shigella and Campylobacter outbreaks (0.02%). Conclusions Norovirus caused the most outbreaks and outbreak-associated illness, hospitalizations, and deaths. However, persons in E. coli and Salmonella outbreaks were more likely to be hospitalized or die. Outbreak surveillance through NORS provides the relative contributions of each mode of transmission and etiology for reported enteric illness outbreaks, which can guide targeted interventions.