Thyroid hormones in relation to toxic metal exposure in pregnancy, and potential interactions with iodine and selenium

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 \ub5g/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 potential implications for maternal and child health are warranted

Mediation by Thyroid Hormone in the Relationships Between Gestational Exposure to Methylmercury and Birth Size

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\ua0nmol/L increase) was positively associated with birth weight (B: 125\ua0g; 95% CI 36, 214) and length (B: 0.59\ua0cm; 95% CI 0.21, 0.97). Maternal fT4 was inversely associated with birth weight (B: −\ua033\ua0g; 95% CI −\ua057, −\ua09.5), driven by obese women (n = 76). Causal mediation analyses suggested that a doubling of erythrocyte mercury (> 1\ua0\ub5g/kg; n = 374) was associated with a mean tT3-mediated decrease in birth weight of 11\ua0g (95% CI −\ua025, −\ua01.6) and in birth length of 0.1\ua0cm (95% CI −\ua00.12, −\ua00.01), 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

Association of maternal urinary fluoride concentrations during pregnancy with size at birth and the potential mediation effect by maternal thyroid hormones: The Swedish NICE birth cohort

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\u27s 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 thyroid hormone levels

The usefulness of CRP in acute diarrhea syndrome and acute pancreatitis in dogs : A literature review

Uppsatsen bestod i en litteraturöversikt över studier gjorda på CRP:s kliniska betydning och potential som prognostisk markör hos hundar med akut diarré med eller utan kräkning samt hos hundar med akut pankreatit. Uppsatsen föreslog en ny betäckning på det traditionella begreppet ”akut gastroenterit” med att kalla denna presentation av kliniska symptom för ”akut diarrésyndrom”. Då forskning på CRP vid akut diarrésyndrom hos hund är begränsat togs humanstudier på området med i analysen. CRP:s möjligheter att förutse prognos i form av överlevnad och uppstallningslängd hos hundar med akut diarrésyndrom och akut pankreatit undersöktes. CRP visade sig vara användbar inom ett flertal områden hos hundar med denna sjukdomsproblematik och visade potential som prognostisk markör. Dock visade studien också på CRP:s begränsningar som en ospecifik markör för inflammation och bör sammantaget inte användas ensamt för att förutse prognos hos hundar med akut diarrésyndrom eller akut pankreatit.This study consisted of a literature review of the clinical importance of CRP and its potential as a prognostic marker in dogs with acute diarrhea with or without vomiting and in dogs with acute pancreatitis. The study introduced the new term ”acute diarrhea syndrome” to describe dogs with acute diarrhea with or without vomiting who in veterinary medicin traditionally has been called ”acute gastroenteritis”. There has not been a lot of studies done on CRP and dogs with acute diarrhea syndrome so therefore human studies has been implemented as part of the review. The ability of CRP to anticipate prognosis as in survival and time in hospital in dogs with acute diarrhea syndrome and acute pancreatitis were investigated. CRP showed to be valuable in different areas and showed potential as a prognostic marker. The study did illustrate the limitations of CRP as a non specific marker for inflammation and therefore should not be used alone to predict outcome in dogs with acute diarrhea syndrome or acute pancreatitis.Veterinærmedisin - cand.med.vet

CRP och dess användbarhet vid akut diarrésyndrom och akut pankreatit hos hund. En litteraturstudie.

Uppsatsen bestod i en litteraturöversikt över studier gjorda på CRP:s kliniska betydning och potential som prognostisk markör hos hundar med akut diarré med eller utan kräkning samt hos hundar med akut pankreatit. Uppsatsen föreslog en ny betäckning på det traditionella begreppet ”akut gastroenterit” med att kalla denna presentation av kliniska symptom för ”akut diarrésyndrom”. Då forskning på CRP vid akut diarrésyndrom hos hund är begränsat togs humanstudier på området med i analysen. CRP:s möjligheter att förutse prognos i form av överlevnad och uppstallningslängd hos hundar med akut diarrésyndrom och akut pankreatit undersöktes. CRP visade sig vara användbar inom ett flertal områden hos hundar med denna sjukdomsproblematik och visade potential som prognostisk markör. Dock visade studien också på CRP:s begränsningar som en ospecifik markör för inflammation och bör sammantaget inte användas ensamt för att förutse prognos hos hundar med akut diarrésyndrom eller akut pankreatit

Assessment of Joint Impact of Iodine, Selenium, and Zinc Status on Women's Third-Trimester Plasma Thyroid Hormone Concentrations

Background: Iodine is essential for synthesizing thyroid hormones, but other micronutrients are also required for optimal thyroid function. However, there is a lack of data on combined micronutrient status in relation to thyroid hormones in pregnancy. Objectives: We aimed to assess the joint associations of iodine, selenium, and zinc status with plasma concentrations of thyroid hormones and thyroid-stimulating hormone (TSH) in pregnancy. Methods: We included 531 pregnant women (aged 22-40 y) participating in a Swedish birth cohort who provided blood and spot urine samples in gestational weeks 27-33 (mean: 29). Associations of urinary iodine concentration (UIC), plasma selenium concentration, and plasma zinc concentration (measured by inductively coupled plasma mass spectrometry) with plasma hormone concentrations [total and free thyroxine (tT4, fT4), total and free triiodothyronine (tT3, fT3), and TSH] were explored with Bayesian kernel machine regression (BKMR; n = 516; outliers excluded) and multivariable-adjusted linear regression (n = 531; splined for nonlinear associations). Results: Median (IQR) micronutrient concentrations were 112 μg/L (80-156 μg/L) for UIC, 67 μg/L (58-76 μg/L) for plasma selenium, and 973 μg/L (842-1127 μg/L) for plasma zinc; the former 2 median values were below recommended concentrations (150 μg/L and 70 μg/L, respectively). Mean ± SD TSH concentration was 1.7 ± 0.87 mIU/L, with 98% < 4 mIU/L. BKMR showed a positive trend of joint micronutrient concentrations in relation to TSH. Plasma zinc was most influential for all hormones but tT3, for which plasma selenium was most influential. In adjusted linear regression models, zinc was positively associated with tT4, tT3, and TSH, and <1200 μg/L also with fT4 and fT3. Selenium was inversely associated with fT3, and <85 μg/L with tT3. Conclusions: Pregnant women's plasma TSH concentrations in the early third trimester increased with increasing joint status of iodine, selenium, and zinc. Zinc and selenium were more influential than iodine for the hormone concentrations. Multiple micronutrients need consideration in future studies of thyroid hormone status

Low-level maternal exposure to cadmium, lead, and mercury and birth outcomes in a Swedish prospective birth-cohort

Observational studies have indicated that low-to-moderate exposure to cadmium (Cd), lead (Pb), and mercury (Hg) adversely affects birth anthropometry, but results are inconclusive. The aim of this study was to elucidate potential impact on birth anthropometry of exposure to Cd, Pb, and Hg in pregnant women, and to identify the main dietary sources. In the NICE (Nutritional impact on Immunological maturation during Childhood in relation to the Environment) birth-cohort in northern Sweden, blood and urine were collected from pregnant women in early third trimester. Cd, Pb and Hg were measured in erythrocytes (n = 584), and Cd also in urine (n = 581), by inductively coupled plasma mass spectrometry. Dietary data were collected through a semi-quantitative food frequency questionnaire administered in mid-third trimester. Birth anthropometry data were extracted from hospital records. In multivariable-adjusted spline regression models, a doubling of maternal erythrocyte Cd (median: 0.29 mu g/kg) above the spline knot of 0.50 mu g/kg was associated with reduced birth weight (B: -191 g; 95% CI: -315, -68) and length (-0.67 cm; -1.2, -0.14). The association with birth weight remained when the analysis was restricted to never-smokers. Likewise, a doubling of erythrocyte Hg (median 1.5 mu g/kg, mainly MeHg) above 1.0 mu g/kg, was associated with decreased birth weight (-59 g; -115, -3.0), and length (-0.29 cm; -0.54, -0.047). Maternal Pb (median 11 mu g/kg) was unrelated to birth weight and length. Erythrocyte Cd was primarily associated with intake of plant derived foods, Pb with game meat, tea and coffee, and Hg with fish. The results indicated that low-level maternal Cd and Hg exposure were associated with poorer birth anthropometry. Further prospective studies in low-level exposed populations are warranted

Maternal characteristics and pregnancy outcomes in the NICE birth cohort: an assessment of self-selection bias

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