This review focuses on the current evidence that maternal dietary and gut bacterial exposures during pregnancy influence the developing fetal immune system and subsequent offspring asthma. Part 1 addresses exposure to a farm environment, antibiotics, and prebiotic and probiotic supplementation that together indicate the importance of bacterial experience in immune programming and offspring asthma. Part 2 outlines proposed mechanisms to explain these associations including bacterial exposure of the fetoplacental unit; immunoglobulin-related transplacental transport of gut bacterial components; cytokine signaling producing fetomaternal immune alignment; and immune programming via metabolites produced by gut bacteria. Part 3 focuses on the interplay between diet, gut bacteria, and bacterial metabolites. Maternal diet influences fecal bacterial composition, with dietary microbiota-accessible carbohydrates (MACs) selecting short-chain fatty acid (SCFA)-producing bacteria. Current evidence from mouse models indicates an association between increased maternal dietary MACs, SCFA exposure during pregnancy, and reduced offspring asthma that is, at least in part, mediated by the induction of regulatory T lymphocytes in the fetal lung. Part 4 discusses considerations for future studies investigating maternal diet-by-microbiome determinants of offspring asthma including the challenge of measuring dietary MAC intake; limitations of the existing measures of the gut microbiome composition and metabolic activity; measures of SCFA exposure; and the complexities of childhood respiratory health assessment.

Institute*, the BIS Investigator Group* In mice, the maternal microbiome influences fetal immune development and postnatal allergic outcomes. Westernized populations have high rates of allergic disease and low rates of gastrointestinal carriage of Prevotella, a commensal bacterial genus that produces short chain fatty acids and endotoxins, each of which may promote the development of fetal immune tolerance. In this study, we use a prebirth cohort (n = 1064 mothers) to conduct a nested case-cohort study comparing 58 mothers of babies with clinically proven food IgE mediated food allergy with 258 randomly selected mothers. Analysis of the V4 region of the 16S rRNA gene in fecal samples shows maternal carriage of Prevotella copri during pregnancy strongly predicts the absence of food allergy in the offspring. This association was confirmed using targeted qPCR and was independent of infant carriage of P. copri. Larger household size, which is a well-established protective factor for allergic disease, strongly predicts maternal carriage of P. copri.

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Background:In previous studies, deficits in regulatory T-cell (Treg) number and function at birth have been linked with subsequent allergic disease. However, longitudinal studies that account for relevant perinatal factors are required. The aim of this study was to investigate the relationship between perinatal factors, naïve Treg (nTreg) over the first postnatal year and development of food allergy. Methods:In a birth cohort (n = 1074), the proportion of nTreg in the CD4 + T-cell compartment was measured by flow cytometry at birth (n = 463), 6 (n = 600) and 12 (n = 675) months. IgE-mediated food allergy was determined by food challenge at 1 year. Associations between perinatal factors (gestation, labour, sex, birth size), nTreg at each time point and food allergy at 1 year were examined by linear regression. Results:A higher proportion of nTreg at birth, larger birth size and male sex was each associated with higher nTreg in infancy. Exposure to labour, as compared to delivery by prelabour Caesarean section, was associated with a transient decrease nTreg.Infants that developed food allergy had decreased nTreg at birth, and the labour-associated decrease in nTreg at birth was more evident among infants with subsequent food allergy. Mode of birth was not associated with risk of food allergy, and there was no evidence that nTreg at either 6 or 12 months were related to food allergy. Conclusion:The proportion of nTreg at birth is a major determinant of the proportion present throughout infancy, highlighting the importance of prenatal immune development. Exposure to the inflammatory stimulus of labour appears to reveal differences in immune function among infants at risk of food allergy. K E Y W O R D S food allergy, naïve regulatory T cells, perinatal factors | 1761 COLLIER Et aL. S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section at the end of the article. How to cite this article: Collier F, Ponsonby A-L, O'Hely M, et al. Naïve regulatory T cells in infancy: Associations with perinatal factors and development of food allergy. Allergy.

The acutely unwell and shocked neonate is an important clinical challenge for paediatricians. In general, management involves concurrent resuscitation and investigation of the underlying cause. Although the most common causes of shock in the neonatal period are sepsis and dehydration, there are a wide range of other diagnostic possibilities that should be considered. 1 Here, we present the case of a neonate who presented with shock, hyponatraemia and hyperkalaemia. The diagnostic journey was challenging and instructive. Case StudyA 14-day-old, ex-38/40 male boy born by normal vaginal delivery presented to the emergency department of our hospital with a 3day history of poor feeding and reduced wet nappies.On examination, he looked unwell, with a mottled grey-bronze colouration, cool peripheries and delayed capillary refill time. His heart rate was 140 and regular, respiratory rate 100 and rectal temperature 33.5°C, and on cardiovascular examination, he was noted to have a gallop rhythm and a 2/6 systolic murmur. On abdominal examination, he was noted to have hepatomegaly. The femoral pulses were palpable bilaterally. His scrotum appeared well pigmented (Fig. 1). His genitalia were of normal appearance with both testes present. His weight had increased from a birth weight of 3050 to 3560 g.

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Aim The burden of wheezing illnesses in Australian infants has not been documented since the success of initiatives to reduce maternal cigarette smoking. We aimed to determine the incidence of wheeze and related health‐care utilisation during the first year of life among a contemporary Australian birth cohort. Methods A birth cohort of 1074 infants was assembled between 2010 and 2013. Parents completed questionnaires periodically. Several non‐exclusive infant respiratory disease phenotypes were defined, including any wheeze, wheeze with shortness of breath and recurrent wheeze. Skin prick testing was performed to determine atopic wheeze. Health‐care utilisation for respiratory disease was determined from questionnaires and hospital medical records. Results Retention to 1 year was 840/1074 (83%). The incidence of any wheeze was 51.8% (95% confidence interval (CI) 48.3–55.2%), wheeze with shortness of breath 20.6% (95% CI 17.9–23.5), recurrent wheeze 19.4% (95% CI 16.8–22.2) and atopic wheeze 6% (95% CI 4.6–7.8). Respiratory illness resulted in primary health‐care utilisation in 82.2% (95% CI 79.3–84.8) of participants and hospital presentation in 8.8% (95% CI 7.2–10.6). Maternal smoking during pregnancy was uncommon (15.7%) and was not associated with wheeze or health resource utilisation. Male gender, familial atopy and asthma and smaller household size were associated with a higher incidence of wheeze. Conclusions The incidence of wheezing illness among Australian infants remains high despite relatively low rates of maternal smoking during pregnancy. The majority of the health‐care burden is borne by primary health‐care services. Further research is required to inform novel prevention strategies.

Background: A few studies have investigated the antecedents and outcomes of infants who demonstrate IgE sensitization to foods that they clinically tolerate. Improved understanding of this sensitized-tolerant phenotype may inform strategies for the prevention of food allergy. Methods:In an Australian birth cohort (n = 1074), assembled using an unselected antenatal sampling frame, participants were categorized as nonsensitized (NS), sensitizedtolerant (ST), or food allergic (FA) based on skin prick testing and food challenge at 12 months of age. Environmental exposures were recorded throughout. Cord blood regulatory T-cell populations were measured at birth. Subsequent childhood allergic disease was assessed by parent report, clinical examination, and repeat skin prick testing. Results:The covariates of interest varied between NS (n = 698), ST (n = 27), and FA (n = 61) groups as follows, suggesting that across these measures, the ST group was more similar to the NS than the FA group: family history of eczema NS 44.6%, ST. 44.6%, FA 65.6%; pet ownership at 12 months: NS 71.5%, ST 81.5%, FA 45.8%; eczema during the first 12 months: NS 19%, ST 32%, FA 64%; and aeroallergen sensitization at 4 years: NS 19.1%, ST 28.6%, FA 44.4%. At birth, a higher proportion of activated regulatory T cells was associated with ST (OR = 2.89, 95% CI 1.03-8.16, P = .045). Conclusion:Food-sensitized-tolerance in infancy appears to be associated with a similar pattern of exposures, immunity, and outcomes to nonsensitized infants. In addition, we found some evidence that an elevated proportion of activated regulatory T cells at birth was specific to the sensitized-tolerant infants, which may be relevant to suppression of clinical disease. K E Y W O R D Sallergy, food allergy, immune programing, regulatory T cell, sensitized tolerant | 1405 GRAY et Al.