Distinct plasma immune signatures in ME/CFS are present early in the course of illness.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is an unexplained incapacitating illness that may affect up to 4 million people in the United States alone. There are no validated laboratory tests for diagnosis or management despite global efforts to find biomarkers of disease. We considered the possibility that inability to identify such biomarkers reflected variations in diagnostic criteria and laboratory methods as well as the timing of sample collection during the course of the illness. Accordingly, we leveraged two large, multicenter cohort studies of ME/CFS to assess the relationship of immune signatures with diagnosis, illness duration, and other clinical variables. Controls were frequency-matched on key variables known to affect immune status, including season of sampling and geographic site, in addition to age and sex. We report here distinct alterations in plasma immune signatures early in the course of ME/CFS (n = 52) relative to healthy controls (n = 348) that are not present in subjects with longer duration of illness (n = 246). Analyses based on disease duration revealed that early ME/CFS cases had a prominent activation of both pro- and anti-inflammatory cytokines as well as dissociation of intercytokine regulatory networks. We found a stronger correlation of cytokine alterations with illness duration than with measures of illness severity, suggesting that the immunopathology of ME/CFS is not static. These findings have critical implications for discovery of interventional strategies and early diagnosis of ME/CFS.

Association of maternal report of infant and toddler gastrointestinal symptoms with autism: evidence from a prospective birth cohort.

IMPORTANCE: Gastrointestinal (GI) comorbidities are frequently described in association with autism spectrum disorder (ASD). However, the prevalence of GI disturbances and the age at which such problems first appear are unclear, and their specificity for ASD compared with other neurodevelopmental disorders is uncertain. OBJECTIVE: To compare maternal report of GI symptoms during the first 3 years of life in children with ASD, developmental delay (DD), and typical development (TD). DESIGN, SETTING, AND PARTICIPANTS: This large prospective cohort study consists of participants in the Norwegian Mother and Child Cohort Study. During a 10-year period (January 1, 1999, through December 31, 2008), women throughout Norway were recruited at the first prenatal ultrasonographic visit (approximately 18 weeks' gestation). The study enrolled 95,278 mothers, 75,248 fathers, and 114,516 children. Our analyses are based on MoBa data released through October 1, 2013, and NPR diagnoses registered through December 31, 2012, and include children born from January 1, 2002, through December 31, 2008, with completed age 18- and 36-month questionnaires. EXPOSURES: We defined 3 groups of children: children with ASD (n = 195), children with DD and delayed language and/or motor development (n = 4636), and children with TD (n = 40 ,95). MAIN OUTCOMES AND MEASURES: The GI symptoms were based on maternal report of constipation, diarrhea, and food allergy/intolerance. RESULTS: Children with ASD were at significantly increased odds of maternally reported constipation (adjusted odds ratio [aOR], 2.7; 95% CI, 1.9-3.8; P < .001) and food allergy/intolerance (aOR, 1.7; 95% CI, 1.1-2.6; P = .01) in the 6- to 18-month-old age period and diarrhea (aOR, 2.3; 95% CI, 1.5-3.6; P < .001), constipation (aOR, 1.6; 95% CI, 1.2-2.3; P < .01), and food allergy/intolerance (aOR, 2.0; 95% CI, 1.3-3.1; P < .01) in the 18- to 36-month-old age period compared with children with TD. Similar results for these symptom categories were observed in comparisons with children with DD, but ORs were slightly lower. Mothers of children with ASD were significantly more likely to report 1 or more GI symptom in either the 6- to 18-month or the 18- to 36-month-old age period and more than twice as likely to report at least 1 GI symptom in both age periods compared with mothers of children with TD or DD. CONCLUSIONS AND RELEVANCE: In this large prospective cohort, maternally reported GI symptoms are more common and more often persistent during the first 3 years of life in children with ASD than in children with TD or DD.

Respiratory syncytial virus-associated hospitalizations among children less than 24 months of age.

BACKGROUND: Respiratory syncytial virus (RSV) infection is a leading cause of hospitalization among infants. However, estimates of the RSV hospitalization burden have varied, and precision has been limited by the use of age strata grouped in blocks of 6 to ≥ 12 months. METHODS: We analyzed data from a 5-year, prospective, population-based surveillance for young children who were hospitalized with laboratory-confirmed (reverse-transcriptase polymerase chain reaction) RSV acute respiratory illness (ARI) during October through March 2000-2005. The total population at risk was stratified by month of age by birth certificate information to yield hospitalization rates. RESULTS: There were 559 (26%) RSV-infected children among the 2149 enrolled children hospitalized with ARI (85% of all eligible children with ARI). The average RSV hospitalization rate was 5.2 per 1000 children <24 months old. The highest age-specific rate was in infants 1 month old (25.9 per 1000 children). Infants ≤ 2 months of age, who comprised 44% of RSV-hospitalized children, had a hospitalization rate of 17.9 per 1000 children. Most children (79%) were previously healthy. Very preterm infants (<30 weeks' gestation) accounted for only 3% of RSV cases but had RSV hospitalization rates 3 times that of term infants. CONCLUSIONS: Young infants, especially those who were 1 month old, were at greatest risk of RSV hospitalization. Four-fifths of RSV-hospitalized infants were previously healthy. To substantially reduce the burden of RSV hospitalizations, effective general preventive strategies will be required for all young infants, not just those with risk factors.