Biomarker candidates of habitual food intake in a Swedish cohort of pregnant and lactating women and their infants

Circulating food metabolites could improve dietary assessments by complementing traditional methods. Here, biomarker candidates of food intake were identified in plasma samples from pregnancy (gestational week 29, N = 579), delivery (mothers, N = 532; infants, N = 348), and four months postpartum (mothers, N = 477; breastfed infants, N = 193) and associated to food intake assessed with semi-quantitative food frequency questionnaires. Families from the Swedish birth cohort Nutritional impact on Immunological maturation during Childhood in relation to the Environment (NICE) were included. Samples were analyzed using untargeted liquid chromatography–mass spectrometry (LC-MS)-based metabolomics. Both exposure and outcome were standardized, and relationships were investigated using a linear regression analysis. The intake of fruits and berries and fruit juice were both positively related to proline betaine levels during pregnancy (fruits and berries, β = 0.23, FDR < 0.001; fruit juice, β = 0.27, FDR < 0.001), at delivery (fruit juice, infants: β = 0.19, FDR = 0.028), and postpartum (fruits and berries, mothers: β = 0.27, FDR < 0.001, infants: β = 0.29, FDR < 0.001; fruit juice, mothers: β = 0.37, FDR < 0.001). Lutein levels were positively related to vegetable intake during pregnancy (β = 0.23, FDR < 0.001) and delivery (mothers: β = 0.24, FDR < 0.001; newborns: β = 0.18, FDR = 0.014) and CMPF with fatty fish intake postpartum (mothers: β = 0.20, FDR < 0.001). No clear relationships were observed with the expected food sources of the remaining metabolites (acetylcarnitine, choline, indole-3-lactic acid, pipecolic acid). Our study suggests that plasma lutein could be useful as a more general food group intake biomarker for vegetables and fruits during pregnancy and delivery. Also, our results suggest the application of proline betaine as an intake biomarker of citrus fruit during gestation and lactation

Food and Nutrient Intake during Pregnancy in Relation to Maternal Characteristics : Results from the NICE Birth Cohort in Northern Sweden

Linkages between diet and other lifestyle factors may confound observational studies. We used cluster analysis to analyze how the intake of food and nutrients during pregnancy co-varies with lifestyle, clinical and demographic factors in 567 women who participated in the NICE (nutritional impact on immunological maturation during childhood in relation to the environment) birth-cohort in northern Sweden. A food frequency questionnaire, Meal-Q, was administered in pregnancy Week 34, and the reported food and nutrient intakes were related to maternal characteristics such as age, education, rural/town residence, parity, pre-pregnancy smoking, first-trimester BMI, allergy and hyperemesis. Two lifestyle-diet clusters were identified: (1) High level of education and higher age were related to one another, and associated with a diet rich in fruits, vegetables, whole grains and fish, and (2) smoking before pregnancy and higher BMI in early pregnancy were related to one another and associated with a diet that contained white bread, French fries, pizza, meat, soft drinks, candy and snacks. More than half of the women had lower-than-recommended daily intake levels of vitamin D, folate, selenium, and iodine. Complex lifestyle-diet interactions should be considered in observational studies that link diet and pregnancy outcome

Infant Iodine and Selenium Status in Relation to Maternal Status and Diet During Pregnancy and Lactation

Iodine and selenium are essential trace elements. Recent studies indicate that pregnant and lactating women often have insufficient intake of iodine and selenium, but the impact on fetal and infant status is unclear. Here, we assessed iodine and selenium status of infants in relation to maternal intake and status of these trace elements in the birth cohort NICE, conducted in northern Sweden (n = 604). Iodine was measured in urine (UIC) in gestational week 29, and in breast milk and infant urine 4 months postpartum, while selenium was measured in maternal plasma and erythrocytes in gestational week 29, and in breast milk and infant erythrocytes 4 months postpartum, in both cases using ICP-MS. Maternal intake was assessed with semi-quantitative food frequency questionnaires in gestational week 34 and at 4 months postpartum. The median intake of iodine and selenium during pregnancy (98 and 40 μg/d, respectively) and lactation (108 and 39 μg/d, respectively) was below recommended intakes, reflected in insufficient status (median UIC of 113 μg/L, median plasma selenium of 65 μg/L). Also, breast milk concentrations (median iodine 77 μg/L, median selenium 9 μg/L) were unlikely to meet infant requirements. Median UIC of the infants was 114 μg/L and median erythrocyte selenium 96 μg/kg, both similar to the maternal concentrations. Infant UIC correlated strongly with breast milk levels (rho = 0.64, p < 0.001). Their erythrocyte selenium correlated with maternal erythrocyte selenium in pregnancy (rho = 0.38, p < 0.001), but not with breast milk selenium, suggesting formation of prenatal reserves. Our results indicate that the transport of iodine and selenium to the fetus and infant is prioritized. Still, it is uncertain whether most infants had sufficient intakes. Further, the results might indicate an involvement of iodine in asthma development during the first year of life, which is essential to follow up. The low maternal and infant dietary intake of both iodine and selenium, especially when the mothers did not use supplements or iodized table salt, suggest a need for a general screening of women and young children

Associations of gestational and early-life exposure to toxic metals and fluoride with a diagnosis of food allergy or atopic eczema at 1 year of age

Studies have indicated that early-life exposure to toxic metals and fluoride affects the immune system, but evidence regarding their role in allergic disease development is scarce. We aimed to evaluate the relations of exposure to such compounds in 482 pregnant women and their infants (4 months of age) with food allergy and atopic eczema diagnosed by a paediatric allergologist at 1 year of age within the Swedish birth-cohort NICE (Nutritional impact on Immunological maturation during Childhood in relation to the Environment). Urinary cadmium and erythrocyte cadmium, lead, and mercury concentrations were measured by inductively coupled plasma mass spectrometry (ICP-MS), urinary inorganic arsenic metabolites by ICP-MS after separation by ion exchange chromatography, and urinary fluoride by an ion-selective electrode. The prevalence of food allergy and atopic eczema was 8 and 7%, respectively. Gestational urinary cadmium, reflecting chronic exposure, was associated with increased odds of infant food allergy (OR [95% CI]: 1.34 [1.09, 1.66] per IQR [0.08 μg/L]). Both gestational and infant urinary fluoride were associated, albeit at a statistically non-significant level, with increased atopic eczema odds (1.48 [0.98, 2.25], 1.36 [0.95, 1.95], per doubling, respectively). By contrast, gestational and infant erythrocyte lead was associated with decreased odds of atopic eczema (0.48 [0.26, 0.87] per IQR [6.6 μg/kg] and 0.38 [0.16, 0.91] per IQR [5.94 μg/kg], respectively), and infant lead with decreased odds of food allergy (0.39 [0.16, 0.93] per IQR [5.94 μg/kg]). Multivariable adjustment had marginal impact on the estimates above. After additional adjustment for fish intake biomarkers, the methylmercury associated atopic-eczema odds were considerably increased (1.29 [0.80, 2.06] per IQR [1.36 μg/kg]). In conclusion, our results indicate that gestational cadmium exposure might be associated with food allergy at 1 year of age and, possibly, early-life exposure to fluoride with atopic eczema. Further prospective and mechanistic studies are needed to establish causality

Short-chain fatty acids (SCFA) in infants’ plasma and corresponding mother’s milk and plasma in relation to subsequent sensitisation and atopic diseaseResearch in context

Summary: Background: Short-chain fatty acids (SCFAs) in intestinal contents may influence immune function, while less is known about SCFAs in blood plasma. The aims were to investigate the relation between infants’ and maternal plasma SCFAs, as well as SCFAs in mother’s milk, and relate SCFA concentrations in infant plasma to subsequent sensitisation and atopic disease. Methods: Infant plasma (N = 148) and corresponding mother’s milk and plasma were collected four months postpartum. Nine SCFA (formic, acetic, propionic, isobutyric, butyric, succinic, valeric, isovaleric, and caproic acid) were analysed by UPLC-MS. At 12 months of age, atopic disease was diagnosed by a pediatric allergologist, and sensitisation was measured by skin prick test. All families participated in the Swedish birth cohort NICE (Nutritional impact on Immunological maturation during Childhood in relation to the Environment). Findings: Infants with sensitisation, atopic eczema, or food allergy had significantly lower concentrations of five, three, and two SCFAs, respectively, in plasma at four months. Logistic regressions models showed significant negative associations between formic, succinic, and caproic acid and sensitisation [ORadj (95% CI) per SD: 0.41 (0.19–0.91); 0.19 (0.05–0.75); 0.25 (0.09–0.66)], and between acetic acid and atopic eczema [0.42 (0.18–0.95)], after adjusting for maternal allergy. Infants’ and maternal plasma SCFA concentrations correlated strongly, while milk SCFA concentrations were unrelated to both. Butyric and caproic acid concentrations were enriched around 100-fold, and iso-butyric and valeric acid around 3-5-fold in mother’s milk, while other SCFAs were less prevalent in milk than in plasma. Interpretation: Butyric and caproic acid might be actively transported into breast milk to meet the needs of the infant, although mechanistic studies are needed to confirm this. The negative associations between certain SCFAs on sensitisation and atopic disease adds to prior evidence regarding their immunoregulatory potential. Funding: Swedish Research Council (Nr. 2013-3145 and 2019-0137 to A-S.S.), Swedish Research Council for Health, Working Life and Welfare FORTE, Nr 2018-00485 to A.W.), The Swedish Asthma and Allergy Association's Research Fund (2020-0020 to A.S.)