Diseases In Later Childhood Research Articles

Respiratory infection- and asthma-prone, low vaccine responder children demonstrate distinct mononuclear cell DNA methylation pathways

BackgroundInfants with frequent viral and bacterial respiratory infections exhibit compromised immunity to routine immunizations. They are also more likely to develop chronic respiratory diseases in later childhood. This study investigated the feasibility of epigenetic profiling to reveal endotype-specific molecular pathways with potential for early identification and immuno-modulation. Peripheral blood mononuclear cells from respiratory infection allergy/asthma-prone (IAP) infants and non-infection allergy/asthma prone (NIAP) were retrospectively selected for genome-wide DNA methylation and single nucleotide polymorphism analysis. The IAP infants were enriched for the low vaccine responsiveness (LVR) phenotype (Fisher's exact p-value = 0.02).ResultsAn endotype signature of 813 differentially methylated regions (DMRs) comprising 238 lead CpG associations (FDR < 0.05) emerged, implicating pathways related to asthma, mucin production, antigen presentation and inflammasome activation. Allelic variation explained only a minor portion of this signature. Stimulation of mononuclear cells with monophosphoryl lipid A (MPL), a TLR agonist, partially reversed this signature at a subset of CpGs, suggesting the potential for epigenetic remodeling.ConclusionsThis proof-of-concept study establishes a foundation for precision endotyping of IAP children and highlights the potential for immune modulation strategies using adjuvants for future investigation.

Association of soap use when bathing 18-month-old infants with the prevalence of allergic diseases at age 3 years: TheJapan Environment and Children's Study.

Atopic march is defined as the progression from atopic dermatitis (AD) during early life to other allergic diseases in later childhood. In a nationwide birth cohort study, the Japan Environment and Children's Study, we investigated the association of bathing habits, which are known to affect skin conditions, for infants with their later development of allergic diseases. Pregnant women who lived in 15 designated regional centers throughout Japan were recruited. We obtained information on bathing habits for their 18-month-old infants and the prevalence of allergic diseases when they were aged 3 years. Data for 74,349 children were analyzed. Most 18-month-old infants were bathed or showered almost every day. When they were divided into four groups according to the frequency of soap use during bathing (every time, most of the time, sometimes, and seldom), the risk of AD later at age 3 was shown to increase in association with a decreasing frequency of soap use [most of the time: adjusted odds ratio (aOR) 1.18, 95% confidence interval (CI) 1.05-1.34; sometimes: aOR 1.72, 95% CI 1.46-2.03; seldom: aOR 1.99, 95% CI 1.58-2.50], compared with soap use every time during bathing at 18 months of age. Similar results were obtained for food allergy but not for bronchial asthma. Frequent soap use when bathing 18-month-old infants was associated with a decreased risk of them developing allergic diseases at age 3. Further well-designed clinical studies are warranted to determine an effective bathing regimen for preventing the development of allergic diseases.

The first 1000 days of life, an opportunity that must be taken for the future generations

The “developmental origins of health and disease” (DOHaD) is a concept that has proven the link between the state of maternal health and risk from disease in later childhood and adult life with the environmental conditions of the early life. Hence, the first 1000 days is reported as a critical period of opportunity for interventions to prevent stunting and other associated pathologies at later life.

Infection-exposure in infancy is associated with reduced allergy-related disease in later childhood in a Ugandan cohort.

Lack of early infection-exposure has been associated with increased allergy-related disease (ARD) susceptibility. In tropical Africa, little is known about which infections contribute to development of ARDs, and at which time. We used latent class analysis to characterise the early infection-exposure of participants in a Ugandan birth cohort and assessed ARDs in later childhood. Of 2345 live births, 2115 children (90%) had data on infections within the first year of life while 1179 (50%) had outcome data at 9 years. We identified two latent classes of children based on first-year infection-exposure. Class 1 (32% membership), characterised by higher probabilities for malaria (80%), diarrhoea (76%), and lower respiratory tract infections (LRTI) (22%), was associated with lower prevalence of wheeze, eczema, rhinitis, and Dermatophagoides skin prick test (SPT) positivity at 9 years. Based on 5-year cumulative infection experience, class 1 (31% membership), characterised by higher probabilities for helminths (92%), malaria (79%), and LRTI (45%), was associated with lower probabilities of SPT positivity at 9 years. In this Ugandan birth cohort, early childhood infection-exposure, notably to malaria, helminths, LRTI, and diarrhoea, is associated with lower prevalence of atopy and ARDs in later childhood. This work was supported by several funding sources. The Entebbe Mother and Baby Study (EMaBS) was supported by the Wellcome Trust, UK, senior fellowships for AME (grant numbers 064693, 079110, 95778) with additional support from the UK Medical Research Council. LL is supported by a PhD fellowship through the DELTAS Africa Initiative SSACAB (grant number 107754). ELW received funding from MRC Grant Reference MR/K012126/1. SAL was supported by the PANDORA-ID-NET Consortium (EDCTP Reg/Grant RIA2016E-1609). HM was supported by the Wellcome's Institutional Strategic Support Fund (grant number 204928/Z/16/Z).

Pollen exposure at birth and adolescent lung function, and modification by residential greenness.

Exposure to high levels of pollen in infancy is a risk factor for allergic respiratory diseases in later childhood, but effects on lung function are not fully understood. We aim to examine associations between grass pollen exposure in the first months of life and lung function at 12 and 18years, and explore potential modification. Using the Melbourne Atopy Cohort Study, a birth cohort of children with a family history of allergic diseases, we modeled the association between cumulative grass pollen exposure up to 3months after birth, on FEV1 , FVC, and FEV1 /FVC ratio at 12 and 18years. We also assessed modifying effects of residential greenness levels (derived from satellite imagery), asthma, and early life sensitization to ryegrass. Grass pollen exposure in the first 7days was associated with a reduction in FEV1 (-15.5mL; 95% CI: -27.6, -3.3 per doubling of pollen count) and FVC (-20.8mL; -35.4, -6.1) at 12years, but not at 18years. Increase in cumulative grass pollen exposure up to 3months was negatively associated with FVC at 12 and 18. Exposure to high residential greenness modified the association at 18 years. Early exposure to grass pollen was associated with decreased lung function in children and adolescents. Targeted interventions for pollen avoidance strategies that take into account local topography could be implemented alongside other clinical interventions such as immunotherapy.

Sex-specific association between prenatal life stress exposure and infant pro-inflammatory cytokine levels during acute respiratory infection

BackgroundPrenatal life stress exposure is linked to dysregulated immune function and chronic inflammatory disease in offspring, but we know little about its effects on infant immune response during viral infection. MethodTo address this issue, we examined associations between prenatal life stress exposure and infant upper-airway inflammatory markers during acute respiratory infection (ARI) using data from a prospective, population-based birth-cohort study (N = 180). Infant inflammation was measured as a continuous latent factor within a structural equation modeling framework using nasal wash concentrations of interleukin-1β, interleukin-6, and tumor necrosis factor-α. We hypothesized that infants exposed to prenatal life stress would have greater levels of nasal inflammation during ARI and increased risk for ARI-related morbidity in early childhood. ResultsOur findings contradicted these hypotheses and provided evidence of sexually dimorphic effects of prenatal stress exposure on infant immune functioning during ARI. Among boys, but not girls, prenatal stress was negatively associated with nasal inflammation and indirectly associated with both lower ARI severity and reduced likelihood of subsequent ARI-related hospitalization in the 2nd and 3rd years of life. ConclusionThese data suggest that prenatal stress exposure may be beneficial for infant boys in the context of respiratory viral infections; however, it will be critical to determine if these benefits are offset by increased risk for chronic inflammatory diseases in later childhood. As the participants in this cohort are being followed longitudinally through age 8, we will be able to evaluate long-term health outcomes in future studies.

Perinatal Maternal Stress and Susceptibility to Infectious Diseases in Later Childhood: An Early Life Programming Perspective

There is evidence of transmission of stress-related dysregulation from parents to offspring during early developmental stages, leading to adverse health outcomes. This study investigates whether perinatal stress is linked to the risk of infectious diseases in children aged 7–11 years. We hypothesize that stress exposure during pregnancy and the first 6 months after birth independently predict common infectious diseases. Data are obtained from ELSPAC-CZ, a prospective birth cohort. Maternal stress, operationalized as the number of life events, is examined for pregnancy and the first 6 months postpartum. Children’s diseases include eye infection, ear infection, bronchitis/lung infection, laryngitis, strep throat, cold sores, and flu/flu-like infection. More prenatal and postnatal life events are both independently linked to a higher number of infectious diseases between the ages of 7–11 years. The effect is larger for postnatal vs. prenatal events, and the effect of prenatal events is attenuated after maternal health in pregnancy is controlled. The results suggest that perinatal stress is linked to susceptibility to infectious diseases in school-age children. Interventions to address stress in pregnant and postpartum women may benefit long-term children’s health.

P68: THE LINK BETWEEN INFANT INTESTINAL MICROBIOTA DIVERSITY AND ATOPIC DISEASE: A SYSTEMATIC REVIEW WITH META‐ANALYSIS

The rapid rise of atopic diseases in recent decades has increasingly turned attention to potential environmental variables that modulate allergic phenotype expression. Recent discoveries regarding the human microbiome’s complex signaling with our immune system are driving research to comprehend how altered infant microflora may result in persistently impaired immunomodulation. This systematic review and meta-analysis of published data between 2005 and 2016 seeks to clarify the evidence for a relationship between infant microbiota diversity and the development of atopic disease in later childhood. Studies were selected that analyzed the nature of the infant intestinal microbiota and the relationship to childhood atopy. Focus was directed towards studies assessing microbiota diversity although this was frequently not the primary focus of the individual papers. Selection of studies required diversity analysis calculated by non-culture methods. Exclusion of studies occurred if the assessment of children’s microflora occurred after 12 months of age, where a clinical intervention was uncontrolled or if there was a lack of clear diagnosis by laboratory or clinical methods. Twelve studies met the criteria for final inclusion with eleven used within the meta-analysis. Within the 11 studies, there are 24 effect sizes. There is a spectrum of infant ages and allergic disease within the studies including atopic dermatitis, asthma/wheeze, and food sensitisation. Infants in the control group had higher diversity scores than infants in the atopic group, d = 0.4217, 95%CI = 0.1874 to 0.6559, P = .0004. There is a significant trend within the data for early infancy as the most influential time for decreased microbiome diversity and an association with later atopy. Public health implications thus arising include reduction of unnecessary antimicrobial interventions, environmental modifications that improve healthy diversity exposure, and further research into appropriate microbial signaling to foster balanced immune responses in utero and early infancy.

Influence of antibiotic use in early childhood on asthma and allergic diseases at age 5

BackgroundIn the past few decades, the prevalence of allergic diseases has increased rapidly worldwide. At the same time, the overuse of antibiotics has been observed, especially in Japan. ObjectiveTo elucidate the association of early childhood antibiotic use with allergic diseases in later childhood at 5 years of age. MethodsRelevant data were extracted from the hospital-based birth cohort study, the Tokyo Children's Health, Illness and Development Study. To identify signs of asthma and allergic diseases in children, the International Study of Asthma and Allergies in Childhood questionnaire was used. Logistic regression models were applied to estimate the effect of antibiotic use on outcomes in later life. ResultsAntibiotic exposure in children within the first 2 years of life was associated with current asthma (adjusted odds ratio [aOR] 1.72, 95% confidence interval [CI] 1.10–2.70), current atopic dermatitis (aOR 1.40, 95% CI 1.01–1.94), and current allergic rhinitis (aOR 1.65, 95% CI 1. 05–2.58) at 5 years of age. Analysis of the associations by type of antibiotics showed that cephem was associated with current asthma (aOR 1.97, 95% CI 1.23–3.16) and current rhinitis (aOR 1.82, 95% CI 1.12–2.93), and macrolide was associated with current atopic dermatitis (aOR 1.58, 95% CI 1.07–2.33). ConclusionOur findings suggest that antibiotic use within the first 2 years of life was a risk factor for current asthma, current atopic dermatitis, and current allergic rhinitis in 5-year-old children.

Influence of early childhood antibiotics use on asthma and allergic diseases at the age of five years

Introduction: In these decades, we have been facing with rapid increase in prevalence of allergic diseases world-widely. At the same time, overuse of antibiotics have been pointed out especially in Japan. The aim of this study is to elucidate the association of early childhood antibiotics use with signs of asthma and allergic diseases in later childhood. Methods: Relevant data were extracted from a hospital based birth cohort study named as Tokyo-Children’s Health, Illness and Development Study (T-CHILD), of which questionnaire surveys were conducted during pregnancy and yearly after delivery. To identify signs of asthma and allergic diseases in the children, the questionnaire of the International Study of Asthma and Allergies in Childhood (ISAAC) was used. Logistic regression models were applied to estimate the effect of antibiotic use on outcomes in later life and adjustments were made for maternal history of allergy, maternal age at pregnancy, maternal smoking during pregnancy, mode of delivery, gestational age at delivery, daycare attendance, number of previous live births, bronchitis, and gender of child. Results: Antibiotics exposure of children under 3 years of age was associated with current asthma (adjusted odds ratio [aOR], 1.72; 95% confidence interval [CI], 1.10-2.69), current atopic dermatitis (aOR, 1.39; 95% CI, 1.001-1.92), and current rhinitis (aOR, 1.64; 95% CI, 1. 05-2.58) at their five years of age. Conclusions: Our findings suggest that antibiotics use under 3 years of age was a risk factor of asthma, atopic dermatitis and rhinitis in 5 years old children.

Prenatal maternal bereavement and risk of eating disorders in infants and toddlers: a population-based cohort study.

BackgroundPrenatal stress has been associated to a number of neuropsychiatric diseases but its role on the development of eating disorders (ED) remains unknown. Infants and toddlers with feeding or eating disorders are also at an increased risk of such diseases in later childhood and adolescence. We aimed to examine whether prenatal stress following maternal bereavement is associated with ED in infants and toddlers.MethodsThis population-based cohort study included children born from 1977 to 2008 in Denmark (N = 2,127,126) and from 1977 to 2006 in Sweden (N = 2,974,908). Children were categorized as exposed if they were born to mothers who lost a close relative one year prior to or during pregnancy and were categorized as unexposed otherwise. They were followed until the age of 3 for a first diagnosis of ED. Poisson regression models were used to examine incidence rate ratio (IRR) between the exposed and the unexposed cohort.ResultsA total of 9,403 ED cases were identified and 179 of whom were in the exposed cohort. Offspring born to mothers bereaved by loss of a core family member (older child or spouse) within the six months before pregnancy had a higher risk of ED than the unexposed offspring (IRR: 1.63, 95 % confidence intervals (CI): 1.07–2.47). In stratified analyses, bereavement during the six months before pregnancy was associated with an increased risk of ED in boys (IRR: 2.21, 95 % CI: 1.28–3.82), but not in girls (IRR: 1.18, 95 % CI: 0.61–2.27).DiscussionThis is the first population-based study to explore the association between prenatal stress and the risk of ED in infants and toddlers within two Nordic countries. This study added new evidence of early life stress for etiology of ED while the potential mechanism still needs further studies.ConclusionsPrenatal stress following maternal bereavement by loss of a core family member is associated with an increased risk of ED among infants and toddlers. The six months before conception may be a susceptible time window, especially for boys.

Acetaminophen and/or antibiotic use in early life and the development of childhood allergic diseases

Our understanding of whether the use of acetaminophen and/or antibiotics in early life can cause allergic diseases in later childhood remains inconclusive. The objective of this study was to investigate the temporal relationship between exposure to acetaminophen and/or antibiotics in early life and the development of allergic diseases in later childhood, using two independent birth cohorts derived from the National Health Insurance Research Database (NHIRD) in Taiwan. The authors conducted a prospective birth cohort study of 263 620 children born in 1998 and 9910 children born in 2003, separately, from the NHIRD. Exposure status of acetaminophen and/or antibiotics and potential confounding factors were included in the analyses. Cox proportional hazards models were applied to determine the temporal relationship between acetaminophen and/or antibiotic exposure and the development of allergic diseases. We observed a positive relationship between acetaminophen and/or antibiotic exposure during the 1st year of life and the subsequent development of the three examined allergic diseases (atopic dermatitis, asthma and allergic rhinitis) in the 1998 birth cohort, but the observed relationship of drug exposure in the 2003 cohort, especially for atopic dermatitis and asthma, was lower than for those in the 1998 cohort and was not statistically significant. Our findings provide suggestive evidence that the temporal effect of exposure to acetaminophen and/or antibiotics influences the development of common allergic diseases in later childhood. Further functional studies and/or animal studies are needed to better understand the underlying regulatory mechanisms driving this important clinical and public health issue.

Atopic dermatitis in a high-risk cohort: natural history, associated allergic outcomes, and risk factors

BackgroundAtopic dermatitis (AD) is commonly associated with asthma and other atopic disorders in childhood. ObjectiveTo evaluate the natural history of AD and its association with other allergic outcomes in a high-risk cohort through the age of 7 years. MethodsA total of 373 high-risk infants, who had undergone a randomized controlled trial with intervention measures for primary prevention of asthma applied during the first year of life, were assessed for asthma, AD, and allergic sensitization at 1, 2, and 7 years. ResultsThe multifaceted intervention program did not reduce AD despite reducing the prevalence of asthma significantly. Sixty-two children (16.6%) had AD during the first 2 years (early-onset AD); of these, 26 continue to have AD at the age of 7 years (persistent), whereas 36 no longer had the disease (nonpersistent) at the age of 7 years. Twenty-three children (6.2%) developed AD only after the age of 2 years (late-onset AD). Early-onset AD, persistent or nonpersistent, was associated with increased risk of allergic sensitization to food allergens within the first 2 years of life and asthma diagnosis at year 7. However, only persistent AD was associated with an increased risk of other atopic diseases and allergic sensitization to food and aeroallergens at year 7. Late-onset AD was not associated with atopic diseases or allergic sensitization at year 7 with the exception of Alternaria alternans. ConclusionIn this cohort of infants at high risk of asthma, early-onset persistent AD, which was highly associated with atopic sensitization, increased the risk of atopic diseases in later childhood and thus appears to be part of the atopic march.

Childhood morbidity and health in early adulthood: Life course linkages in a high morbidity context

This paper examines whether morbidity in early and later childhood is associated with health later in life. I investigate the relationship between five types of childhood morbidity and risk factors for cardiovascular disease among Guatemalan adults who experienced high levels of morbidity in childhood. The analysis is based on the Human Capital Study (2002-2004), a recent follow-up of the INCAP Longitudinal Study conducted between 1969 and 1977. I find that most types of childhood morbidity are associated with poorer adult health, independent of family background, adult socioeconomic status, and health behaviors. Higher levels of infections in childhood were associated with a low level of high density lipoprotein (HDL), and higher level of triglycerides, plasma glucose, waist circumference, and obesity (but not hypertension). These results are consistent with the literature that finds that childhood morbidity is associated with increased morbidity and mortality at older ages. However, diarrheal disease in later childhood was associated with lower levels of some risk factors, as measured by triglycerides and plasma glucose, suggesting that exposure to bacteria after infancy may be beneficial for some measures of adult health.

Lung Function Testing in Infants

The neonatal period and the first year of life are times in which a significant amount of disease is caused by lung disorders related to a number of age-related factors. These include the lack of lung development due to preterm birth, the effects of intensive care treatment on the immature lung and early life infections with highly pathogenic agents including respiratory syncytial virus. Prenatal factors such as impaired foetal growth and maternal smoking in pregnancy can also have significant effects on lung function both in the immediate neonatal period but also throughout the first year of life and beyond. It has become increasingly recognised that lung pathology in infancy and early childhood is an important predisposing factor in the aetiology of long-term lung diseases in later childhood and possibly into adult life. The measurement of lung function in the neonatal period and during infancy has required the development of equipment specially adapted to the physical size of the patient and the unique physiology of breathing throughout this early phase of life. During the latter part of the 20th century specific tests to measure respiratory mechanics and to enable forced expiratory manoeuvres using the forced expiratory technique were developed. In more recent times forced inspiration to maximal lung capacity has also been developed. Some lung function tests can be performed reliably and reproducibly in unsedated preterm neonates. An important factor in measuring lung function after this period and especially during the first year of life is the need to sedate the patient in order to obtain cooperation during the specific respiratory manoeuvres mentioned above. Currently, chloral hydrate is the most frequently used agent. It has been shown to be safe and effective and also not to affect the results obtained as compared to unsedated infants. Standardisation of techniques and the establishment of normal values has been another major area of work in this field. The establishment several years ago of a joint European Respiratory Society/American Thoracic Society (ERS/ATS) task force on infant lung function has been responsible for many publications in this field and also the setting of standards for manufacturers of lung function equipment for this age group. Anatomical aspects are also important in this age group. During infancy, nasal breathing is predominant and can account for as much as 50% of total airway resistance, this may be especially important if measuring lung function 3–4 weeks after an upper respiratory tract infection. Another important anatomical aspect in infancy is that the chest wall is much more compliant than in later life. This means that during normal passive expiration the inward pull of the intrinsic elastic properties of the lung parenchyma will result in a lower level of overall lung capacity as compared to that of older children and adults. The result of this is that in some infants small airway closure occurs very close to the end of normal tidal breathing.

The Immune System in Human Milk and the Developing Infant

The concept of the immune system in human milk emerged in the 1970s from clinical and laboratory observations made between the late 18th through the mid-20th centuries. The discovery of living leukocytes in human milk in 1970 was the final link to the chain of evidence that culminated in the concept. The concept was later expanded to include not only antimicrobial but also anti-inflammatory and immunoregulatory agents. These agents evolved to compensate for developmental delays in the immune system during infancy. Indeed, that explains the defense by human milk against common infectious diseases in infancy, necrotizing enterocolitis in preterm infants, and immune-mediated disorders such as Crohn's disease in later childhood. These diverse evolutionary outcomes underscore the superiority of human milk for the nutrition of human infants. Finally, other components of the immune system in human milk and their fate and functions in the developing infant may well be discovered in the near future.

Allergens and allergic diseases in children.

The prevalence of allergic diseases is increasing gradually. Exposure to allergens is one of the trigger factors for symptoms in sensitized individuals. House dust mites and cockroach are the two most common indoor aeroallergens in Taiwan. There are wide differences in the numbers in different locations and in different seasons of these allergens. Sensitization to food allergens is prominent in young infants and can predict further aeroallergen sensitization. However, whether early exposure to allergens might develop or prevent allergic diseases in later childhood requires further research. Up to the present, allergen avoidance has demonstrated no prominent clinical efficacy in the improvement of allergic symptoms, although it is able to reduce allergen load in the environment. In a clinical regard, allergen avoidance should still be included as a part of treatment plans and be well explained to patients.

307 Disturbed Cardiac Functional Parameters and Blood Flow Parameters of Peripheral Arteries in Premature Sga Neonates

Top of pageAbstract Problem: Small for gestational age preterm neonates (SGA) are at higher risk for early postnatal morbidity and cardiovascular and metabolic diseases in later childhood. The aim of the prospective study was to determine the cardiac adaptation and the organ blood flow in growth retarded neonates after intrauterine hemodynamic disturbances in comparison to appropriate for gestational age preterm infants (AGA). Patients and methods: 25 AGA neonates (29.1 ± 1.4 wks, 1420 ± 243 g) and 25 small for gestational age neonates (30.1 ± 1.2 wks, 985 ± 167 g) were examined during the first five days. By Doppler sonographic measurements the cardiac left ventricular systolic time intervals, peak systolic velocities, end diastolic velocities and pulsatility indices of anterior cerebral artery (ACA), superior mesenteric artery (SMA) and renal artery (RA) were investigated. Results: Significantly increased left ventricular pre ejection period was observed in SGA neonates. Systolic peak velocities and end diastolic velocities of ACA, SMA and RA were significantly decreased in SGA neonates in relationship to AGA neonates. The pulsatility indices were significantly increased in SGA neonates during the first five days. Conclusions: Disturbed left ventricular time intervals were observed as a sign of myocardial dysfunction in SGA neonates. In relationship to the diminished myocardial contractility there were demonstrated pathologically diminished blood flow parameters of peripheral vessels and an increased pulsatility caused by a vasoconstriction in the regional vascular bed. For that reason it seems possible, that the disturbed intrauterine perfusion persists into the postnatal life and could cause later cardiac and metabolic problems.

Antioxidant Intake in Pregnancy in Relation to Wheeze and Eczema in the First Two Years of Life

Two thousand women were recruited for a prospective investigation of the influence of maternal antioxidant intake in pregnancy on the development of asthma and eczema in children. A food frequency questionnaire was used to characterize diet during pregnancy and blood antioxidant levels were measured. Postal questionnaires were used to follow up the 1,924 singleton children born to the cohort at 6, 12, and 24 months of age. There were no associations between maternal antioxidant intake and wheezing symptoms and eczema in the children's first year. In the children's second year, maternal vitamin E intake during pregnancy was negatively associated with wheeze in the absence of a "cold" (p for trend 0.010) and, in children whose mothers were atopic, there was a negative association between maternal vitamin E intake and childhood eczema (p for trend 0.024). Maternal vitamin C intake during pregnancy was positively associated with "ever wheeze" and eczema during the children's second year. This study suggests that maternal dietary antioxidant intakes during pregnancy may modify the risks of developing wheeze and eczema during early childhood. Further follow up of the cohort will determine whether maternal diet during pregnancy is associated with asthma and atopic disease in later childhood.

The epidemiology of the atopic child: Who is at risk for what?

In the past few decades, a number of epidemiologic studies have identified risk factors for the development of allergic disease. Although both maternal and paternal history of allergy are associated with an increased risk of atopy, maternal history of asthma confers the greater risk for childhood asthma, which suggests that environmental factors such as the in utero immunologic environment may confer additional susceptibility. Cytokine profiles at birth may also indicate a predisposition to allergic disease in later childhood. Specifically, low interferon-γ appears to be associated with an increased risk for later development of allergic symptoms and atopic disease. Allergen exposure may also increase the risk of atopic consequences, but the outcome is highly dependent on dose of the allergen, timing of exposure, and, most interestingly, the nature of the allergen in question. Endotoxin exposure during infancy has been associated with increased wheezing during the first years of life, but several studies indicate that early exposure may confer some protection against allergy later in life. Clearly, all these factors should be evaluated in identifying the appropriate prevention measures and treatment for the child who is at risk for allergic disease.