Comparing the Diagnostic Accuracy of Measures of Maternal Diet During Pregnancy for Offspring Allergy Outcomes: The Healthy Start Study.

BACKGROUND: Allergic diseases in children are increasing. Although maternal diet quality in pregnancy may be protective, it is unclear which measure of maternal diet best predicts offspring diseases. OBJECTIVE: To examine the associations between multiple diet measures and allergy outcomes, and to compare the diagnostic accuracy of the measures for the prediction of allergy outcomes. METHODS: Maternal diet during pregnancy was measured using a validated instrument, and scored using 5 measures: the maternal diet index (MDI), Healthy Eating Index, total diet diversity, healthy diet diversity, and unhealthy diet diversity. Unadjusted and adjusted logistic regression models assessed associations between maternal diet measures and offspring allergy outcomes up to age 4 years. The diagnostic accuracy of the diet measures was compared. RESULTS: There were significant associations between MDI (odds ratio [OR], 0.78; 95% CI, 0.70-0.87), Healthy Eating Index (OR, 0.98; 95% CI, 0.97-0.99), and healthy diet diversity scores (OR, 0.91; 95% CI, 0.85-0.98) during pregnancy and the primary combined outcome "any allergy excluding wheeze" in children up to age 4 years. Neither maternal total diet diversity (OR, 0.99; 95% CI, 0.95-1.03) nor unhealthy diet diversity scores (OR, 1.05; 95% CI, 0.98-1.13) were associated with the "any allergy excluding wheeze" outcome. For all outcomes studied, except for food allergy, there was a significant difference in the diagnostic accuracy between the 5 measures of maternal diet. The area under the curve for MDI was highest for every disease outcome, although not always significantly higher. CONCLUSIONS: Better quality and higher diversity of a woman's diet during pregnancy, measured in various ways, is associated with offspring allergy outcomes, with healthy foods associated with decreased risk, and unhealthy foods associated with a higher risk. The MDI, which appropriately weighted both healthy and unhealthy foods, best predicted childhood allergic disease.

Associations between child filaggrin mutations and maternal diet with the development of allergic diseases in children.

BACKGROUND: Filaggrin (FLG) loss-of-function mutations in children and maternal diet in pregnancy have been implicated in child allergy outcomes. This paper studies the questions: "do FLG mutations modify the effect of maternal diet on the odds of development of allergic diseases?" and "which factor leads to the highest rate of diagnosis allergic diseases over time, maternal diet, or FLG mutations?". METHODS: Exact logistic regressions studied effect modification. Cox proportional hazard models compared the rate of allergic disease development in three groups (N = 624): (1) children with FLG mutation, (2) children without FLG mutation whose mothers did not eat an allergy preventive diet, and (3) children without FLG mutation whose mothers ate an allergy preventive diet. Maternal diet was classified using a validated index. RESULTS: Cox models showed the development of atopic dermatitis, asthma, and wheeze was significantly higher for children in group 1 versus 3 (HR = 2.40 [1.32, 4.37], HR = 2.29 [1.05, 4.97], and HR 2.10 [1.004, 4.38], respectively), but not significantly higher for children in group 1 versus 2 (HR = 1.30 [0.74, 2.29], HR = 1.27 [0.61, 2.63], and HR = 1.29 [0.65, 2.58], respectively). Development of allergic rhinitis was significantly higher for group 1 versus 2 and 3 (1 vs. 2: HR = 2.29 [1.10, 4.76]; 1 vs. 3: HR = 3.21 [1.46, 7.08]). There was no significant effect modification for any outcome. CONCLUSION: Children with FLG mutation had similar risk of atopic dermatitis, asthma, and wheeze as children without an FLG mutation whose mothers did not eat an allergy preventive diet during pregnancy. Child FLG mutation did not modify the effect of maternal diet. The results suggest that maternal diet in pregnancy, a modifiable risk factor, could be a target for preventive interventions.

The maternal diet index in pregnancy is associated with offspring allergic diseases: the Healthy Start study.

BACKGROUND: A systematic review showed limited associations between pregnancy diet and offspring allergy. We developed a maternal diet index during pregnancy that was associated with offspring allergy outcomes. METHODS: Data came from Healthy Start, a Colorado pre-birth cohort of mother/offspring dyads. Food propensity questionnaires were completed during pregnancy. Offspring allergic rhinitis, atopic dermatitis, asthma, wheeze, and food allergy diagnosis up to age four were verified from electronic medical records. Data were randomized into test and replication sets. The index included the weighted combination of variables that best predicted a combined outcome of any allergy in the test set. Index utility was verified in the replication set. Separate adjusted and unadjusted logistic models estimated associations between the index and each offspring allergy diagnosis in the full sample. RESULTS: The index included weighted measures of intake of vegetables, yogurt, fried potatoes, rice/grains, red meats, pure fruit juice, and cold cereals. Vegetables and yogurt were associated with the prevention of any allergy, while other components were associated with increased disease. In adjusted models, a one-unit increase in the index was significantly associated with reduced odds of offspring allergic rhinitis (odds ratio (CI) 0.82 [0.72-0.94]), atopic dermatitis (0.77 [0.69-0.86]), asthma (0.84 [0.74-0.96]), and wheeze (0.80 [0.71-0.90]), but not food allergy (0.84 [0.66-1.08]). CONCLUSIONS: This is the first study that has shown associations between an index of maternal dietary intake during pregnancy and multiple offspring allergic diseases. The results give hope for prevention of allergic diseases in utero.

Advanced glycation end product intake during pregnancy and offspring allergy outcomes: A Prospective cohort study.

BACKGROUND: Associations have been shown between concurrent assessment of dietary intake of advanced glycation end products (AGEs) and childhood allergic outcomes. We examined the association between maternal AGEs intake and development of offspring asthma, wheeze, atopic dermatitis, allergic rhinitis and food allergies, and sought to determine whether the intake of AGEs was associated with cord sera cytokines/chemokines. METHODS: Pregnant women ≥16 years were recruited in the Healthy Start study, a prospective pre-birth cohort from Colorado (N = 1410). The analysis included 962 dyads with adequate diet (≥2 recalls) and allergy outcome details. AGEs intake was estimated for each mother by matching intakes reported using 24-h dietary recalls during pregnancy to a reference database of commonly consumed foods' AGEs values. Child diagnoses of asthma and allergies up to 8 years were obtained from electronic medical records. Cord sera cytokines and chemokines were analysed in a subset (N = 462) of children. RESULTS: The median [IQR] AGEs intake for the overall sample was 11,919 kU/day [8293, 16,573]. Unadjusted analysis showed a positive association between maternal AGEs intake in pregnancy and rhinitis up to 8 years of age (HR = 1.03; 95% CI: 1.01, 1.06), but the association was attenuated and no longer significant in adjusted models (HR = 1.01; 95% CI: 0.98, 1.04). Both adjusted and unadjusted models showed no associations between AGEs intake in pregnancy and any of the other outcomes (p > .05). There were no significant associations between any cytokine or chemokine measured and AGEs intake or any of the outcomes studied (p > .05). CONCLUSION: The study showed that maternal AGEs intake was not associated with offspring asthma and allergy outcomes. AGEs exposure during pregnancy may not have the same impact on child development as postnatal exposure.

Incidence and timing of offspring asthma, wheeze, allergic rhinitis, atopic dermatitis, and food allergy and association with maternal history of asthma and allergic rhinitis.

BACKGROUND: Studying the developmental precursors of allergy may help explain the mechanisms (or etiology) of allergic disease. We studied childhood respiratory and allergic diseases in a pre-birth cohort from the United States. OBJECTIVE: We assessed the associations between maternal history of asthma and the development of respiratory and allergic diseases in offspring. We also assessed associations with maternal history of allergic rhinitis. METHODS: Maternal history of asthma and allergic rhinitis was self-reported during early pregnancy. Offspring respiratory and allergy information was obtained from electronic medical records. Adjusted Cox proportional hazard models assessed the associations between maternal history of asthma and development of respiratory and allergic diseases in the offspring up to 8 years. A similar approach was used for maternal history of allergic rhinitis. RESULTS: Children born to women with a history of asthma had a 77% greater risk of developing asthma, a 45% greater risk of atopic dermatitis/eczema, and a 65% greater risk of wheeze (all p < 0.01), but no significantly increased risk of allergic rhinitis or food allergies, compared to children born to women with no history of asthma. Maternal history of allergic rhinitis was not associated with any child allergy outcome, and maternal history of both asthma and allergic rhinitis was associated with child atopic dermatitis/eczema only. CONCLUSIONS: Maternal history of asthma was significantly associated with offspring respiratory and allergic diagnoses. The association between maternal history of asthma and offspring asthma and atopic dermatitis is a novel finding. Our findings may guide physicians who counsel families with a history of maternal asthma and allergic rhinitis about their child's risk of developing respiratory and allergic diseases.

Examining Associations Between Dietary Inflammatory Index in Pregnancy, Pro-inflammatory Cytokine and Chemokine Levels at Birth, and Offspring Asthma and/or Wheeze by Age 4 Years.

BACKGROUND: Few studies have demonstrated associations between maternal dietary inflammatory index (DII) during pregnancy and offspring asthma and/or wheeze. OBJECTIVE: The study aimed to assess associations between maternal DII during pregnancy and 1) offspring cord sera pro-inflammatory cytokines (interleukin [IL]-1ß, IL-4, IL-6, IL-10, tumor necrosis factor-α) and chemokines (IL-8, monocyte chemoattractant protein-1) at birth and 2) offspring asthma and/or wheeze at age 4 years. DESIGN: The Healthy Start study is a prospective prebirth longitudinal study that recruited pregnant women in Denver, Colorado and tracked their offspring. PARTICIPANTS AND SETTING: This study used data from 1228 mother-child dyads enrolled in the Healthy Start study. Pregnant women were recruited in Denver, Colorado, between 2009 and 2014, and offspring tracked until age 4 years. MAIN OUTCOME MEASURES: Cord sera cytokines and chemokines were analyzed with multiplex panel immunoassays. Offspring diagnosis of asthma and/or wheeze by age 4 years was extracted from electronic medical records. STATISTICAL ANALYSES PERFORMED: Unadjusted and adjusted linear and logistic regression models were used to assess associations. Covariates included factors such as nulliparity, race/ethnicity, gestational smoking, and maternal history of asthma. RESULTS: Unadjusted analysis showed that increasing maternal DII scores were associated with increased odds of child asthma and/or wheeze by 4 years (odds ratio = 1.17; 95% CI: 1.07-1.27), but the association was attenuated and no longer statistically significant in the adjusted model (odds ratio = 1.15; 95% CI: 0.99-1.33). There were no significant associations between DII scores and cord sera cytokine or chemokine levels. CONCLUSIONS: The study showed that the inflammatory profile of the maternal diet was not associated with cytokines and chemokine levels at birth. The results suggested that a more inflammatory maternal diet was associated with increased odds of offspring asthma and/or wheeze by age 4 years, which could be considered of clinical relevance but the finding was not statistically significant at the .05 level.

Fat Mass Accretion from Birth to 5 Years and Metabolic Homeostasis in Childhood: the Healthy Start Study.

CONTEXT: It is unclear how fat mass accretion in early life is related to glucose-insulin homeostasis. OBJECTIVE: Examine associations of fat and fat-free mass accretion from birth to early childhood with glucose-insulin homeostasis in early childhood in a multi-ethnic cohort. METHODS: Observational Healthy Start study with data collection from 2010 to 2020. Air displacement plethysmography at birth and 4.8 (SD 0.7) years estimated fat mass percent (FMP, %), fat mass index (FMI, kg/m2), and fat-free mass index (FFMI, kg/m2). General population recruited from academic obstetrics clinics in Denver, Colorado, consisting of 419 mother/offspring dyads. The main outcome measures were fasting glucose, insulin, homeostasis model assessment-2 insulin resistance (HOMA2-IR), and beta-cell function (HOMA2-B) at 4.8 years. RESULTS: Greater fat mass accretion from birth to early childhood was associated with higher fasting glucose (ΔFMP ß = 0.20 [95% CI 0.06-0.34], ΔFMI ß = 0.90 [0.30-1.50]) in participants of Hispanic, Black, and Other races/ethnicities, while greater fat-free mass accretion was associated with higher fasting glucose in non-Hispanic White participants (ΔFFMI ß = 0.76 [0.21-1.32]). Overall, greater fat, but not fat-free, mass accretion was also associated with higher insulin (ΔFMP ß = 0.14 [0.09-0.18], ΔFMI 0.71 [0.51-0.92]), HOMA2-IR (FMP ß = 0.02 [0.01-0.02], ΔFMI ß = 0.09 [0.06-0.12]), and HOMA2-B (ΔFMP ß = 0.92 [0.18-1.36], ΔFMI ß = 4.76 [2.79-6.73]). CONCLUSION: Greater fat mass accretion in infancy and childhood is associated with shifts in fasting glucose in children of Hispanic, Black, and Other races/ethnicities at 5 years of age. Body composition beginning in early life is relevant for metabolic health, and precise assessments of adiposity in pediatric research are needed.

Effects of adolescent caffeine consumption on cocaine self-administration and reinstatement of cocaine seeking.

BACKGROUND:: Caffeine consumption by children and adolescents has risen dramatically in recent years, yet the lasting effects of caffeine consumption during adolescence remain poorly understood. AIM:: These experiments explore the effects of adolescent caffeine consumption on cocaine self-administration and seeking using a rodent model. METHODS:: Sprague-Dawley rats consumed caffeine for 28 days during the adolescent period. Following the caffeine consumption period, the caffeine solution was replaced with water for the remainder of the experiment. Age-matched control rats received water for the duration of the study. Behavioral testing in a cocaine self-administration procedure occurred during adulthood (postnatal days 62-82) to evaluate how adolescent caffeine exposure influenced the reinforcing properties of cocaine. Cocaine seeking was also tested during extinction training and reinstatement tests following cocaine self-administration. RESULTS:: Adolescent caffeine consumption increased the acquisition of cocaine self-administration and increased performance on different schedules of reinforcement. Consumption of caffeine in adult rats did not produce similar enhancements in cocaine self-administration. Adolescent caffeine consumption also produced an upward shift in the U-shaped dose response curve on cocaine self-administration maintained on a within-session dose-response procedure. Adolescent caffeine consumption had no effect on cocaine seeking during extinction training or reinstatement of cocaine seeking by cues or cocaine. CONCLUSIONS:: These findings suggest that caffeine consumption during adolescence may enhance the reinforcing properties of cocaine, leading to enhanced acquisition that may contribute to increased addiction vulnerability.