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.

Allergy is one of the most common diseases among young children yet all factors that affect development of allergy remain unclear. In a small cohort of 65 children living in the same rural area of south-west Sweden, we have previously found that maternal factors, including prenatal diet, affect childhood allergy risk, suggesting that in utero conditions may be important for allergy development. Here, we studied if metabolites in the umbilical cord blood of newborns may be related to development of childhood allergy, accounting for key perinatal factors such as mode of delivery, birth order and sex. Available umbilical cord blood plasma samples from 44 of the participants were analysed using gas chromatography-mass spectrometry metabolomics; allergy was diagnosed by specialised paediatricians at ages 18 months, 3 years and 8 years and included eczema, asthma, food allergy and allergic rhinoconjunctivitis. Nineteen cord blood metabolites were related to future allergy diagnosis though there was no clear pattern of up- or downregulation of metabolic pathways. In contrast, perinatal factors birth order, sex and mode of delivery affected several energy and biosynthetic pathways, including glutamate and aspartic acid—histidine metabolism (p = 0.004) and the tricarboxylic acid cycle (p = 0.006) for birth order; branched chain amino acid metabolism (p = 0.0009) and vitamin B6 metabolism (p = 0.01) for sex; and glyoxylate and dicarboxylic acid metabolism (p = 0.005) for mode of delivery. Maternal diet was also related to some of the metabolites associated with allergy. In conclusion, the cord blood metabolome includes individual metabolites that reflect lifestyle, microbial and other factors that may be associated with future allergy diagnosis, and also reflects temporally close events/factors. Larger studies are required to confirm these associations, and perinatal factors such as birth order or siblings must be considered in future cord-blood metabolome studies.

Allergic diseases are the most common chronic diseases in childrenin the Western world, but little is know about what factors influence immune maturation and allergy development. We therefore aimed to associate infant and maternal metabolomes to T- and B-cell subpopulations and allergy diagnosis. We performed liquid chromatography-mass spectrometry based untargeted metabolomics on blood plasma from mothers (third trimester, n = 605; delivery, n = 558) and from the umbilical cord (n = 366). The measured metabolomes were associated to T- and B-cell subpopulations up to 4 months after delivery and to doctor´s diagnosed eczema, food allergy and asthma at one year of age using random forest analysis. Maternal and cord plasma at delivery could predict the number of CD24+CD38low memory B-cells (p = 0.033, n = 26 and p = 0.009, n = 22), but future allergy status could not be distinguished from any of the three measured metabolomes. Replication of previous literature findings showed hypoxanthine to be upregulated in the umbilical cord of children with subsequent asthma. This exploratory study suggests foetal immune programming occuring during pregnancy as the metabolomic profiles of mothers and infants at delivery related to infants’ B-cell maturation.

Umbilical cord blood is frequently used in health monitoring of the neonate. Results may be affected by the proportion of arterial and venous cord blood, the venous blood coming from the mother to supply oxygen and nutrients to the infant, and the arterial carrying waste products from the fetus. Here, we sampled arterial and venous umbilical cords separately from 48 newly delivered infants and examined plasma metabolomes using GC-MS/MS metabolomics. We investigated differences in metabolomes between arterial and venous blood and their associations with gestational length, birth weight, sex, and whether the baby was the first born or not, as well as maternal age and BMI. Using multilevel random forest analysis, a classification rate of 79% was achieved for arteriovenous differences (p = 0.004). Several monosaccharides had higher concentrations in the arterial cord plasma while amino acids were higher in venous plasma, suggesting that the main differences in the measured arterial and venous plasma metabolomes are related to amino acid and energy metabolism. Venous cord plasma metabolites related to energy metabolism were positively associated with parity (77% classification rate, p = 0.004) while arterial cord plasma metabolites were not. This underlines the importance of defining cord blood type for metabolomic studies.

Introduction: Allergies and other immune-mediated diseases are thought to result from incomplete maturation of the immune system early in life. We previously showed that infants’ metabolites at birth were associated with immune cell subtypes during infancy. The placenta supplies the fetus with nutrients but may also provide immune maturation signals. Objectives: To examine the relationship between metabolites in placental villous tissue and immune maturation during the first year of life and infant and maternal characteristics (gestational length, birth weight, sex, parity, maternal age, and BMI). Methods: Untargeted metabolomics was measured using a Liquid Chromatography-Mass Spectrophotometer and subpopulations of T and B cells using flow cytometry at birth, 48 hours, one, four, and 12 months. Random forest modeling showed modest associations (Q2 = 0.2–0.3) between the placental metabolome and kappa-deleting recombination excision circles (KREC) at birth and naïve B cells and memory T cells at 12 months. Results: Weak associations were observed between the placental metabolome and sex and parity. Still, most metabolite features of interest were of low intensity compared to associations previously found in cord blood, suggesting that underlying metabolites were not of placental origin. Conclusions: Our results indicate that metabolomic measurements of the placenta may not effectively recognize metabolites important for immune maturation.