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Our previous studies have linked gestational methylmercury exposure, originating from seafood, to changes in maternal thyroid hormones and infant birth size in a Swedish birth cohort. Herein we aimed to determine associations between maternal thyroid hormones and infant birth size and elucidate if maternal hormones could mediate the relationship between methylmercury and lower birth size. In 515 women, without known thyroid disease, we assessed metal exposure by erythrocyte mercury concentrations (mainly methylmercury, reflecting exposure over the past months) in early third trimester measured with inductively coupled plasma-mass spectrometry. Plasma concentrations of total and free thyroxine (tT4 and fT4) and triiodothyronine (tT3 and fT3), and thyroid-stimulating hormone (TSH) were measured at an accredited clinical laboratory. In multivariable-adjusted linear regression models, maternal tT3 (per 1 nmol/L increase) was positively associated with birth weight (B: 125 g; 95% CI 36, 214) and length (B: 0.59 cm; 95% CI 0.21, 0.97). Maternal fT4 was inversely associated with birth weight (B: − 33 g; 95% CI − 57, − 9.5), driven by obese women (n = 76). Causal mediation analyses suggested that a doubling of erythrocyte mercury (> 1 µg/kg; n = 374) was associated with a mean tT3-mediated decrease in birth weight of 11 g (95% CI − 25, − 1.6) and in birth length of 0.1 cm (95% CI − 0.12, − 0.01), both equivalent to about 12% of the total effect. To conclude, tT3 was positively associated with infant birth size. Reduced tT3 levels appeared to mediate a minor part of the inverse association between methylmercury exposure and birth size.

Background: Observational studies have indicated that elevated maternal fluoride exposure during pregnancy may impair child neurodevelopment but a potential impact on birth outcomes is understudied. Objectives: To evaluate the impact of gestational fluoride exposure on birth outcomes (birth size and gestational age at birth) and to assess the potential mediating role of maternal thyroid hormones. Methods: We studied 583 mother-child dyads in the NICE cohort in northern Sweden. Maternal fluoride exposure was assessed by measuring urinary concentrations at late pregnancy (median: 29th gestational week) using an ion selective electrode. Plasma levels of free and total thyroxine (fT4, tT4) and triiodothyronine (fT3, tT3), and thyroid stimulating hormone (TSH) were measured with electrochemiluminescence immunoassays. The infant's weight, length, head circumference, and gestational age at birth were extracted from hospital records. Results: Median urinary fluoride concentration was 0.71 mg/L (5th-95th percentile 0.31–1.9 mg/L; specific gravity adjusted). In multivariable-adjusted regression models, every 1 mg/L increase of maternal urinary fluoride was associated with a mean increase in birth weight by 84 g (95%CI: 30, 138), length by 0.41 cm (95%CI: 0.18, 0.65), head circumference by 0.3 cm (95%CI: 0.1, 0.4), and with increased odds of being born large for gestational age (OR = 1.39, 95%CI: 1.03, 1.89). Every 1 mg/L increase of maternal urinary fluoride was also associated with a mean increase of the plasma fT3:fT4 ratio (B = 0.007, 95%CI: 0.000, 0.014), but not with the hormones or TSH. In mediation analyses, the maternal fT3:fT4 ratio did not explain the urinary fluoride-birth size relationships. Discussion: Gestational urinary fluoride concentrations were associated with increased size at birth and even with increased odds of being born large for gestational age. The fluoride-related associations with increased size at birth were not explained by changes in maternal t

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.

Background: Prospective birth cohorts are essential for identifying associations between exposures and outcomes. However, voluntary participation introduces a potential bias due to self selection since the persons that chose to participate may differ in background characteristics and behaviors. Objectives: To investigate potential bias due to self-selection in the Nutritional impact onImmunological maturation duringChildhood in relation to theEnvironment (NICE) birth cohort in northern Sweden. Methods: Women in the NICE birth cohort (N = 621) were compared to nonparticipating pregnant women in Norrbotten County in northern Sweden who were eligible for participation (N = 4976) regarding maternal characteristics and lifestyle. Maternal characteristics and pregnancy outcomes were compared between the groups and associations between exposures (smoking, folic acid, BMI, parity, education) and pregnancy outcomes (birth weight and gestational age) were analyzed by linear regression analyses, examining any interaction with the group. Results: NICE participants were more highly educated, older and more likely to cohabit than the non-participants. They more often took folic acid and multivitamin supplements and less often smoked during early pregnancy. Pregnancy outcomes (mode of delivery, gestational age at delivery, birth weight and APGAR score) did, however, not differ significantly between participants and non-participants. Smoking, BMI, education and parity affected gestational age and birth weight, but the associations were of similar magnitude in participants and non-participants, with no significant effect on the group. Conclusion: Self-selection to the NICE study was evident in some factors related to lifestyle and socioeconomic characteristics but did not appear to skew pregnancy outcomes or alter well-known effects of certain lifestyle parameters on pregnancy outcomes.

Atopic eczema, the most common atopic disease in infants, may pave the way for sensitization and allergy later in childhood. Fatty acids have immune-regulating properties and may regulate skin permeability. Here we examine whether the proportions of fatty acids among the infant and maternal plasma phospholipids at birth were associated with maternal dietary intake during pregnancy and development of atopic eczema during the first year of age in the Nutritional impact on Immunological maturation during Childhood in relation to the Environment (NICE) birth cohort. Dietary data were collected with a semi-quantitative food frequency questionnaire, fatty acids were measured with GC-MS and atopic eczema was diagnosed by a pediatric allergologist at 12 months of age. We found that higher proportions of n-6 PUFAs (including arachidonic acid) but lower proportions of n-3 PUFAs (including DPA) in the infant’s phospholipids at birth were associated with an increased risk of atopic eczema at 12 months of age. The n-6 and n-3 PUFAs were related to maternal intake of meat and fish, respectively. Our results suggest that prenatal exposure to unsaturated fatty acids is associated with eczema development in the infant. Maternal diet during pregnancy may partly explain the fatty acid profiles in utero.

Background: Several endocrine-disrupting metals may affect thyroid function, but the few available studies of exposure during pregnancy and thyroid hormones are inconclusive. Objective: To explore if environmental exposure to cadmium (Cd), lead (Pb), and methylmercury (MeHg) impacts thyroid function in pregnancy, and interacts with iodine and selenium status. Methods: Women in a Swedish birth cohort provided blood and urine samples in early third trimester. Concentrations of erythrocyte Cd, Pb, and Hg (n = 544), urinary Cd and iodine (n = 542) and plasma selenium (n = 548) were measured using inductively coupled plasma-mass spectrometry. Free and total thyroxine (fT4, tT4) and triiodothyronine (fT3, tT3), and thyroid stimulating hormone (TSH), were measured in plasma (n = 548) with electrochemiluminescence immunoassays. Metal-hormone associations were assessed in regression models, and metal mixture effects and metal-nutrient interactions were explored in Bayesian kernel machine regression (BKMR). Results: In multivariable-adjusted regression models, a doubling of urinary Cd was associated with a mean increase in tT4 of 2.7 nmol/L (95% CI: 0.78, 4.6), and in fT3 and tT3 of 0.06 pmol/L (0.02, 0.10) and 0.09 nmol/L (0.05, 0.13), respectively. A doubling of urinary Cd was associated with a −0.002 (−0.003, −0.001) and −0.03 (−0.05, −0.02) decrease in the fT4:tT4 and fT3:tT3 ratio, respectively. A doubling of erythrocyte Hg (>1 µg/kg) was associated with a decrease in fT3 and tT3 by −0.11 pmol/L (−0.16, −0.05) and −0.11 nmol/L (−0.16, −0.06), respectively, and a −0.013 (−0.02, −0.01) decrease in the fT3:fT4 ratio. BKMR did not indicate any mixture effect of toxic metals or interactions between metals and iodine or selenium in relation to the hormones. Conclusion: Our findings suggest that exposure to Cd and Hg, at levels globally prevalent through the diet, may affect thyroid function during pregnancy, independently of iodine and selenium levels. Further studies on po