Risk Factors for Thyroid Dysfunction in Pregnancy: An Individual Participant Data Meta-Analysis.

Background: International guidelines recommend targeted screening to identify gestational thyroid dysfunction. However, currently used risk factors have questionable discriminative ability. We quantified the risk for thyroid function test abnormalities for a subset of risk factors currently used in international guidelines. Methods: We included prospective cohort studies with data on gestational maternal thyroid function and potential risk factors (maternal age, body mass index [BMI], parity, smoking status, pregnancy through in vitro fertilization, twin pregnancy, gestational age, maternal education, and thyroid peroxidase antibody [TPOAb] or thyroglobulin antibody [TgAb] positivity). Exclusion criteria were pre-existing thyroid disease and use of thyroid interfering medication. We analyzed individual participant data using mixed-effects regression models. Primary outcomes were overt and subclinical hypothyroidism and a treatment indication (defined as overt hypothyroidism, subclinical hypothyroidism with thyrotropin >10 mU/L, or subclinical hypothyroidism with TPOAb positivity). Results: The study population comprised 65,559 participants in 25 cohorts. The screening rate in cohorts using risk factors currently recommended (age >30 years, parity ≥2, BMI ≥40) was 58%, with a detection rate for overt and subclinical hypothyroidism of 59%. The absolute risk for overt or subclinical hypothyroidism varied <2% over the full range of age and BMI and for any parity. Receiver operating characteristic curves, fitted using maternal age, BMI, smoking status, parity, and gestational age at blood sampling as explanatory variables, yielded areas under the curve ranging from 0.58 to 0.63 for the primary outcomes. TPOAbs/TgAbs positivity was associated with overt hypothyroidism (approximate risk for antibody negativity 0.1%, isolated TgAb positivity 2.4%, isolated TPOAb positivity 3.8%, combined antibody positivity 7.0%; p < 0.001), subclinical hypothyroidism (risk for antibody negativity 2.2%, isolated TgAb positivity 8.1%, isolated TPOAb positivity 14.2%, combined antibody positivity 20.0%; p < 0.001) and a treatment indication (risk for antibody negativity 0.2%, isolated TgAb positivity 2.2%, isolated TPOAb positivity 3.0%, and combined antibody positivity 5.1%; p < 0.001). Twin pregnancy was associated with a higher risk of overt hyperthyroidism (5.6% vs. 0.7%; p < 0.001). Conclusions: The risk factors assessed in this study had poor predictive ability for detecting thyroid function test abnormalities, questioning their clinical usability for targeted screening. As expected, TPOAb positivity (used as a benchmark) was a relevant risk factor for (subclinical) hypothyroidism. These results provide insights into different risk factors for gestational thyroid dysfunction.

Risk and Benefit of Decreasing Seafood Consumption in Japan-Docosahexaenoic Acid, Methylmercury and Infant IQ.

National statistics show that seafood consumption in Japan is decreasing since the mid-1990s. The risks and benefits of this decreasing seafood consumption was assessed in this study. Intake of docosahexaenoic acid (DHA) and methylmercury (MeHg) of women of childbearing age were estimated by using seafood consumption data of women of age 20-39 in the period 2011-2019 and seafood DHA and MeHg content data to find significantly (p < 0.05) decreasing intake of DHA (2.8 mg/day per year) and MeHg (0.19 µg Hg/day per year) in this period. The effect of the decreasing maternal DHA and MeHg intake on infant IQ was estimated by using the equation developed by the FAO/WHO. Net IQ change (the difference in IQ gain by DHA and IQ loss by MeHg) was constant or even increasing, depending on the assumption, in this period while seafood consumption was significantly decreasing. This was due to the decreasing adverse effect of MeHg, along with saturated DHA-derived benefits on infant IQ, even at the decreased seafood consumption of Japanese women of childbearing age. It was indicated that the recent decreasing trend in seafood consumption in Japan did not have an unfavorable effect on infant IQ.

TSH and FT4 Reference Intervals in Pregnancy: A Systematic Review and Individual Participant Data Meta-Analysis.

CONTEXT: Interpretation of thyroid function tests during pregnancy is limited by the generalizability of reference intervals between cohorts due to inconsistent methodology. OBJECTIVE: (1) To provide an overview of published reference intervals for thyrotropin (TSH) and free thyroxine (FT4) in pregnancy, (2) to assess the consequences of common methodological between-study differences by combining raw data from different cohorts. METHODS: (1) Ovid MEDLINE, EMBASE, and Web of Science were searched until December 12, 2021. Studies were assessed in duplicate. (2) The individual participant data (IPD) meta-analysis was performed in participating cohorts in the Consortium on Thyroid and Pregnancy. RESULTS: (1) Large between-study methodological differences were identified, 11 of 102 included studies were in accordance with current guidelines; (2) 22 cohorts involving 63 198 participants were included in the meta-analysis. Not excluding thyroid peroxidase antibody-positive participants led to a rise in the upper limits of TSH in all cohorts, especially in the first (mean +17.4%; range +1.6 to +30.3%) and second trimester (mean +9.8%; range +0.6 to +32.3%). The use of the 95th percentile led to considerable changes in upper limits, varying from -10.8% to -21.8% for TSH and -1.2% to -13.2% for FT4. All other additional exclusion criteria changed reference interval cut-offs by a maximum of 3.5%. Applying these findings to the 102 studies included in the systematic review, 48 studies could be used in a clinical setting. CONCLUSION: We provide an overview of clinically relevant reference intervals for TSH and FT4 in pregnancy. The results of the meta-analysis indicate that future studies can adopt a simplified study setup without additional exclusion criteria.

Association between maternal thyroid function and risk of gestational hypertension and pre-eclampsia: a systematic review and individual-participant data meta-analysis.

BACKGROUND: Adequate maternal thyroid function is important for an uncomplicated pregnancy. Although multiple observational studies have evaluated the association between thyroid dysfunction and hypertensive disorders of pregnancy, the methods and definitions of abnormalities in thyroid function tests were heterogeneous, and the results were conflicting. We aimed to examine the association between abnormalities in thyroid function tests and risk of gestational hypertension and pre-eclampsia. METHODS: In this systematic review and meta-analysis of individual-participant data, we searched MEDLINE (Ovid), Embase, Scopus, and the Cochrane Database of Systematic Reviews from date of inception to Dec 27, 2019, for prospective cohort studies with data on maternal concentrations of thyroid-stimulating hormone (TSH), free thyroxine (FT4), thyroid peroxidase (TPO) antibodies, individually or in combination, as well as on gestational hypertension, pre-eclampsia, or both. We issued open invitations to study authors to participate in the Consortium on Thyroid and Pregnancy and to share the individual-participant data. We excluded participants who had pre-existing thyroid disease or multifetal pregnancy, or were taking medications that affect thyroid function. The primary outcomes were documented gestational hypertension and pre-eclampsia. Individual-participant data were analysed using logistic mixed-effects regression models adjusting for maternal age, BMI, smoking, parity, ethnicity, and gestational age at blood sampling. The study protocol was registered with PROSPERO, CRD42019128585. FINDINGS: We identified 1539 published studies, of which 33 cohorts met the inclusion criteria and 19 cohorts were included after the authors agreed to participate. Our study population comprised 46 528 pregnant women, of whom 39 826 (85·6%) women had sufficient data (TSH and FT4 concentrations and TPO antibody status) to be classified according to their thyroid function status. Of these women, 1275 (3·2%) had subclinical hypothyroidism, 933 (2·3%) had isolated hypothyroxinaemia, 619 (1·6%) had subclinical hyperthyroidism, and 337 (0·8%) had overt hyperthyroidism. Compared with euthyroidism, subclinical hypothyroidism was associated with a higher risk of pre-eclampsia (2·1% vs 3·6%; OR 1·53 [95% CI 1·09-2·15]). Subclinical hyperthyroidism, isolated hypothyroxinaemia, or TPO antibody positivity were not associated with gestational hypertension or pre-eclampsia. In continuous analyses, both a higher and a lower TSH concentration were associated with a higher risk of pre-eclampsia (p=0·0001). FT4 concentrations were not associated with the outcomes measured. INTERPRETATION: Compared with euthyroidism, subclinical hypothyroidism during pregnancy was associated with a higher risk of pre-eclampsia. There was a U-shaped association of TSH with pre-eclampsia. These results quantify the risks of gestational hypertension or pre-eclampsia in women with thyroid function test abnormalities, adding to the total body of evidence on the risk of adverse maternal and fetal outcomes of thyroid dysfunction during pregnancy. These findings have potential implications for defining the optimal treatment target in women treated with levothyroxine during pregnancy, which needs to be assessed in future interventional studies. FUNDING: Arkansas Biosciences Institute and Netherlands Organization for Scientific Research.

Arsenolipids in salmon are partly converted to thioxo analogs during cooking.

BACKGROUND: Arsenic hydrocarbons, major arsenolipids occurring naturally in marine fish, have substantial cytotoxicity leading to human health-related studies of their distribution and abundance in foods. These studies have all investigated fresh foods; because most fish are cooked before being consumed, it is both food- and health-relevant to determine the arsenolipids present in cooked fish. METHODS: We used HPLC/mass spectrometry to investigate the arsenolipids present in salmon (Salmo salar) before and after cooking by either baking or steaming. RESULTS: In raw salmon (total As 2.74 mg kg-1 dry mass, of which 6% was lipid-soluble), major arsenolipids were three arsenic hydrocarbons (oxo-AsHC 332, oxo-AsHC 360, and oxo-AsHC 404, ca 55% of total arsenolipids) and a band of unidentified less-polar arsenolipids (ca 40%), trace amounts of another four arsenic hydrocarbons and two thioxo analogs were also detected. During the cooking process, 28% of the oxo-AsHCs were converted to their thioxo analogs. CONCLUSION: Our study shows that arsenic hydrocarbons naturally present in fresh fish are partly converted to their thioxo analogs during cooking by either baking or steaming. The greater lipophilicity of the thioxo analogs could alter the mode of toxicity of arsenic hydrocarbons, and hence future food regulations for arsenic should consider the influence of cooking on the precise type of arsenolipid in fish.

Carbon and nitrogen stable isotope ratios of diet of the Japanese and diet-hair offset values.

The stable isotope ratios of carbon and nitrogen (δ13C and δ15N) were measured in composite samples of Japanese food and hair. Three hundred eighty-nine foodstuffs were collected in Tokyo and Gunma Prefecture, Japan, in 2020. The foodstuffs were classified into 15 food categories, prepared as usually consumed, and mixed to make 15 composite samples representing each of the food categories. Similarly prepared samples for foodstuffs collected in 2011 and 2015 were also examined. Composite hair samples were collected from a barber shop in Tokyo and a beauty salon in Gunma in 2019. The δ13C and δ15N values of the food and hair composites were measured by elemental analyzer/isotope ratio mass spectrometry after defatting. The δ13C and δ15N values of the food composite varied from composite to composite and according to year of collection. The whole-diet δ13C values were -21.1, -22.0, and -21.5 ‰ for the 2011, 2015, and 2020 samples, respectively; the δ15N values were 5.0, 4.4, and 4.4 ‰, respectively. Diet-hair offset values of δ13C and δ15N were calculated to be 1.9 and 4.3 ‰ for δ13C and δ15N, respectively. These offset values will be important for dietary analysis and nutritional research using hair isotope ratios.

Telomere length and urinary 8-hydroxy-2'-deoxyguanosine and essential trace element concentrations in female Japanese university students.

Telomere length is thought to be a biomarker of biological aging. This study examined whether telomere length was associated with urinary concentrations of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of oxidative stress, and antioxidative trace elements in 73 female Japanese university students (age: 19.2 ± 0.7 years). We quantified 8-OHdG and selenium in urine by liquid chromatography-mass spectrometry and inductively coupled plasma-mass spectrometry, respectively. Telomere length and urinary concentrations of other essential trace elements (molybdenum, cobalt, and chromium) that were previously measured in the same study participants, were used in this study. We used multiple linear regression analysis to examine the associations of telomere length with urinary 8-OHdG and essential trace element concentrations (covariates: urinary cotinine concentration, age, BMI, and drinking status). The geometric means (geometric standard deviation) of 8-OHdG and selenium were 3.4 (1.5) and 31 (1.3) µg/g creatinine, respectively. Telomere length was not associated with urinary 8-OHdG concentration, but was negatively associated with urinary selenium concentration. In conclusion, telomere length was not associated with urinary 8-OHdG concentration in the young women in this study. Longitudinal studies should be conducted to clarify the association between telomere shortening rate and oxidative stress level.

Dietary intake and urinary excretion of methylated arsenicals of Japanese adults consuming marine foods and rice.

Dietary intake and urinary excretion of monomethylarsonic acid (MMA), dimethylarsinic acid (DMA) and arsenobetaine (AsB) were measured in 150 adult Japanese subjects. Duplicate diet (DD) samples and first void of urine on the next morning of DD sampling day were collected and analysed for arsenic species with liquid chromatography-ICP mass spectrometry. Median (min-max) intakes of MMA, DMA and AsB were <2.3 (<2.3-<2.3), 4.57 (<2.3-24.3), and 13.6 (<2.4-231) µg As/day, respectively, and median urinary concentrations were 1.90 (<0.37-26.), 21.9 (<0.27-141) and 19.6 (<0.37-1063) ng As/mg creatinine, respectively. Interrelationships between intake levels and urinary concentrations were mostly significant with positive coefficients indicating mutual association due to co-exposure, metabolism and/or dietary habit. Urinary concentrations and intake levels of AsB were also positively correlated confirming the applicability of urine analysis as biomarker of exposure. The present descriptive results provide with essential piece of information in assessing health risk of methylated arsenicals for population who consume marine products and rice.

Association between nutrient intake and telomere length in Japanese female university students.

OBJECTIVE: Telomere length can be a biomarker of cumulative oxidative stress and inflammation indicating biological aging. Previous studies examined association of nutrient intake with telomere length targeting middle-aged and elderly individuals. This study examined whether dietary macro- and micronutrient intake was associated with telomere length in young females. METHODS: Seventy-four Japanese young females (median (interquartile range) age was 19 (19 - 20) years) participated. We estimated their intake of nutrients (energy, protein, fat, carbohydrate, essential elements, vitamins, fatty acids, and dietary fibre) using a semi-quantitative food frequency questionnaire and measured telomere length (T/S ratio, the ratio of telomere repeat copy number (T) to single-copy gene number (S)) of DNA extracted from blood by qPCR. The association between telomere length and tertiles of nutrient intake were analysed. RESULTS: The median (interquartile range) of telomere length was 0.70 (0.52 - 0.98). Vitamin A intake was positively associated with telomere length (tertile 1 vs. 2, coefficient [95% confidence interval] = 0.42 [0.12, 0.71]; tertile 1 vs. 3, coefficient [95% confidence interval] = 0.33 [0.04, 0.62]) after adjusting for covariates (age, BMI, passive smoking, and drinking). CONCLUSIONS: Our findings suggest that variation in vitamin A intake might influence telomere attrition in healthy individuals.

Source Identification Analysis of Lead in the Blood of Japanese Children by Stable Isotope Analysis.

Considering the negative effect of lead (Pb) on children's neurodevelopment, Pb exposure should be minimized to the lowest extent possible, though the blood Pb (BPb) concentrations in Japanese children are among the lowest in the world. To identify the sources of Pb in blood, isotope ratios (IRs: 207Pb/206Pb and 208Pb/206Pb) of Pb (PbIR) in whole blood from eight Japanese children were measured by multi-collector ICP mass spectrometry. Further, samples of house dust, soil, duplicate diet, and tobacco, collected from home environments, were also measured and were compared with PbIR of blood case by case. The relative contribution of Pb in the home environment to BPb were estimated by linear programming (finding an optimal solution which satisfy the combination of IRs and intakes from various sources) when appropriate. Source apportionment for three children could be estimated, and contributions of diet, soil, and house dust were 19-34%, 0-55%, and 20-76%, respectively. PbIR for the remaining five children also suggested that non-dietary sources also contributed to Pb exposure, though quantitative contributions could not be estimated. Non-dietary sources such as soil, house dust, and passive tobacco smoke are also important contributors to Pb exposure for Japanese children based on PbIR results.

A Simplified Questionnaire for the Assessment of Inorganic Arsenic Intake in a Japanese Population.

A simplified questionnaire was developed to assess inorganic arsenic (iAs) intake level in a Japanese population. The two page questionnaire included photographs of single serving sizes of rice and cooked hijiki (Hizikia fusiforme: brown algae), and asked subjects about the number of servings of rice and cooked hijiki, two predominant dietary sources of iAs in Japan, they consume in a day. Daily intake of iAs was estimated for 72 Japanese subjects using the questionnaire together with data of iAs content in rice and hijiki seaweed, and the estimated intakes were compared with actual iAs intakes of the subjects as measured for a duplicate diet using liquid chromatography-inductively coupled plasma mass spectrometry. A highly significant correlation was found between the estimated and measured intakes (r = 0.65, p < 0.001); however, the slope of regression indicated a systematic error in the intake estimation. Possible sources of error are discussed herein. It was concluded that this approach is promising if minor improvements are made to the questionnaire.

Association of dietary intake and urinary excretion of inorganic arsenic in the Japanese subjects.

Quantitative relationship between intake of inorganic arsenic (iAs) and urinary excretion of iAs and its metabolite, methylarsonic acid (MMA), was investigated for 150 adult Japanese subjects. Duplicate diet was used for the determination of intake and first void of urine on the next day of duplicate diet sampling was used for urinary iAs + MMA determination. Speciation analysis of arsenic in diet and urine was carried out with liquid chromatography-inductively coupled plasma mass spectrometry. Geometric mean iAs intake of the subjects was 0.349 µg/kg/day and that of urinary iAs + MMA concentration was 5.20 ng As/mL (specific gravity (SG) corrected) or 4.05 ng As/mg creatinine (Cre). There was a significant positive correlation between iAs intake and urinary iAs + MMA concentration: the correlation coefficient between intake and Cre-corrected urinary concentration (r = 0.544) was greater than that between intake and SG-corrected concentration (r = 0.458). The regression equation of intake-excretion was: log10[dailyintake]=0.451×log10[creatininecorrectedurinaryiAs+MMA]+0.814. This equation has a practical value for converting urinary As levels, measured as a biomarker of exposure in epidemiologic study, to dietary intake levels in the future risk assessment.

Hg isotopic composition and total Hg mass fraction in NIES Certified Reference Material No. 28 Urban Aerosols.

An interlaboratory study on the National Institute for Environmental Studies (NIES) certified reference material (CRM) No. 28 Urban Aerosols, collected on the filters of a central ventilating system in a building in Beijing city center, was performed to obtain informative values of Hg isotopic composition and total Hg (THg) mass fraction. The THg mass fraction was determined by four organizations using atomic absorption spectrometry; it resulted in the mean value of 1.19 ± 0.12 mg/kg (2SD, n = 24). The Hg isotopic composition of the CRM was measured and intercompared at two different institutions by cold vapor generation system coupled to multicollector inductively coupled plasma mass spectrometry. Subsequently, a conventional dissolution method that uses a mixture of HNO3/HCl/H2O2 in Hotblock® and two different dissolution methods that use a mixture of HNO3/HCl with a microwave and a digestion bomb were applied. The Hg isotopic compositions were δ202Hg = - 1.26 ± 0.17‰, Δ199Hg = - 0.23 ± 0.06‰, Δ200Hg = 0.01 ± 0.07‰, and Δ201Hg = - 0.22 ± 0.09‰ (2SD, n = 18) for the conventional method, which agree well with those obtained using microwave and bomb digestion. Our results indicate that, for the quality control of particulate matter analyses, this CRM is appropriate for use in environmental and geochemical studies. Graphical abstract.

Association of maternal thyroid function with birthweight: a systematic review and individual-participant data meta-analysis.

BACKGROUND: Adequate transplacental passage of maternal thyroid hormone is important for normal fetal growth and development. Maternal overt hypothyroidism and hyperthyroidism are associated with low birthweight, but important knowledge gaps remain regarding the effect of subclinical thyroid function test abnormalities on birthweight-both in general and during the late second and third trimester of pregnancy. The aim of this study was to examine associations of maternal thyroid function with birthweight. METHODS: In this systematic review and individual-participant data meta-analysis, we searched MEDLINE (Ovid), Embase, Web of Science, the Cochrane Central Register of Controlled Trials, and Google Scholar from inception to Oct 15, 2019, for prospective cohort studies with data on maternal thyroid function during pregnancy and birthweight, and we issued open invitations to identify study authors to join the Consortium on Thyroid and Pregnancy. We excluded participants with multiple pregnancies, in-vitro fertilisation, pre-existing thyroid disease or thyroid medication usage, miscarriages, and stillbirths. The main outcomes assessed were small for gestational age (SGA) neonates, large for gestational age neonates, and newborn birthweight. We analysed individual-participant data using mixed-effects regression models adjusting for maternal age, BMI, ethnicity, smoking, parity, gestational age at blood sampling, fetal sex, and gestational age at birth. The study protocol was pre-registered at the International Prospective Register of Systematic Reviews, CRD42016043496. FINDINGS: We identified 2526 published reports, from which 36 cohorts met the inclusion criteria. The study authors for 15 of these cohorts agreed to participate, and five more unpublished datasets were added, giving a study population of 48 145 mother-child pairs after exclusions, of whom 1275 (3·1%) had subclinical hypothyroidism (increased thyroid stimulating hormone [TSH] with normal free thyroxine [FT4]) and 929 (2·2%) had isolated hypothyroxinaemia (decreased FT4 with normal TSH). Maternal subclinical hypothyroidism was associated with a higher risk of SGA than was euthyroidism (11·8% vs 10·0%; adjusted risk difference 2·43%, 95% CI 0·43 to 4·81; odds ratio [OR] 1·24, 1·04 to 1·48; p=0·015) and lower mean birthweight (mean difference -38 g, -61 to -15; p=0·0015), with a higher effect estimate for measurement in the third trimester than in the first or second. Isolated hypothyroxinaemia was associated with a lower risk of SGA than was euthyroidism (7·3% vs 10·0%, adjusted risk difference -2·91, -4·49 to -0·88; OR 0·70, 0·55 to 0·91; p=0·0073) and higher mean birthweight (mean difference 45 g, 18 to 73; p=0·0012). Each 1 SD increase in maternal TSH concentration was associated with a 6 g lower birthweight (-10 to -2; p=0·0030), with higher effect estimates in women who were thyroid peroxidase antibody positive than for women who were negative (pinteraction=0·10). Each 1 SD increase in FT4 concentration was associated with a 21 g lower birthweight (-25 to -17; p<0·0001), with a higher effect estimate for measurement in the third trimester than the first or second. INTERPRETATION: Maternal subclinical hypothyroidism in pregnancy is associated with a higher risk of SGA and lower birthweight, whereas isolated hypothyroxinaemia is associated with lower risk of SGA and higher birthweight. There was an inverse, dose-response association of maternal TSH and FT4 (even within the normal range) with birthweight. These results advance our understanding of the complex relationships between maternal thyroid function and fetal outcomes, and they should prompt careful consideration of potential risks and benefits of levothyroxine therapy during pregnancy. FUNDING: Netherlands Organization for Scientific Research (grant 401.16.020).

Development of Human Hair Reference Material Supporting the Biomonitoring of Methylmercury.

A certified reference material, NIMD-01, was developed for the analysis of mercury speciation in human hair. We collected the hair of Vietnamese males from a barbershop in Hanoi in 2016 and prepared 1200 bottles containing 3 g of sieved and blended hair powder. The certified value was given on a dry-mass basis, with the moisture content obtained by drying at 85°C for 4 h. Certified values with the expanded uncertainties (coverage factor, k = 2) were as follows: methylmercury, 0.634 ± 0.071 mg kg-1 as mercury; total mercury, 0.794 ± 0.050 mg kg-1; copper, 12.8 ± 1.4 mg kg-1; zinc, 234 ± 29 mg kg-1; selenium, 1.52 ± 0.29 mg kg-1. An indicative arsenic concentration of 0.17 ± 0.03 mg kg-1 was measured. Extended uncertainties were estimated by sample homogeneity, long- and short-term stabilities, and a characterization from measurements made by collaborating laboratories.

Variation in arsenolipid concentrations in seafood consumed in Japan.

Variation in arsenolipid concentrations was assessed in 18 seafood samples including fish, shellfish, and crustaceans purchased in Japan. Analyses were performed by high performance liquid chromatography-inductively coupled plasma mass spectrometry/electrospray ionization tandem mass spectrometry. Stable isotope ratios for nitrogen and carbon were also measured in the samples for obtaining trophic level information of the species. Arsenic-containing hydrocarbons (AsHCs) and arsenic-containing fatty acids (AsFAs) were detected in the seafood samples; the toxic AsHCs were found in all of the seafood samples with large variation in the concentrations (83 ±â€¯73 ng As/g fw, coefficient of variation = 88%). Our previous point estimate of health risk of AsHCs intake via seafood consumption in Japan, based on average AsHC concentration in seafood, suggested insignificant risk, and the present study supports our previous estimate. AsHC concentrations significantly correlated with lipid content of the seafood samples (r = 0.67, p < 0.01), a result expected because of the fat solubility of the compounds. The AsHCs concentrations, however, were not significantly correlated with nitrogen stable isotope ratios suggesting that AsHCs do not biomagnify. The source of the observed large variation in AsHC concentrations will be the subject of further investigation.

Association of Thyroid Function Test Abnormalities and Thyroid Autoimmunity With Preterm Birth: A Systematic Review and Meta-analysis.

Importance: Maternal hypothyroidism and hyperthyroidism are risk factors for preterm birth. Milder thyroid function test abnormalities and thyroid autoimmunity are more prevalent, but it remains controversial if these are associated with preterm birth. Objective: To study if maternal thyroid function test abnormalities and thyroid autoimmunity are risk factors for preterm birth. Data Sources and Study Selection: Studies were identified through a search of the Ovid MEDLINE, EMBASE, Web of Science, the Cochrane Central Register of Controlled Trials, and Google Scholar databases from inception to March 18, 2018, and by publishing open invitations in relevant journals. Data sets from published and unpublished prospective cohort studies with data on thyroid function tests (thyrotropin [often referred to as thyroid-stimulating hormone or TSH] and free thyroxine [FT4] concentrations) or thyroid peroxidase (TPO) antibody measurements and gestational age at birth were screened for eligibility by 2 independent reviewers. Studies in which participants received treatment based on abnormal thyroid function tests were excluded. Data Extraction and Synthesis: The primary authors provided individual participant data that were analyzed using mixed-effects models. Main Outcomes and Measures: The primary outcome was preterm birth (<37 weeks' gestational age). Results: From 2526 published reports, 35 cohorts were invited to participate. After the addition of 5 unpublished data sets, a total of 19 cohorts were included. The study population included 47 045 pregnant women (mean age, 29 years; median gestational age at blood sampling, 12.9 weeks), of whom 1234 (3.1%) had subclinical hypothyroidism (increased thyrotropin concentration with normal FT4 concentration), 904 (2.2%) had isolated hypothyroxinemia (decreased FT4 concentration with normal thyrotropin concentration), and 3043 (7.5%) were TPO antibody positive; 2357 (5.0%) had a preterm birth. The risk of preterm birth was higher for women with subclinical hypothyroidism than euthyroid women (6.1% vs 5.0%, respectively; absolute risk difference, 1.4% [95% CI, 0%-3.2%]; odds ratio [OR], 1.29 [95% CI, 1.01-1.64]). Among women with isolated hypothyroxinemia, the risk of preterm birth was 7.1% vs 5.0% in euthyroid women (absolute risk difference, 2.3% [95% CI, 0.6%-4.5%]; OR, 1.46 [95% CI, 1.12-1.90]). In continuous analyses, each 1-SD higher maternal thyrotropin concentration was associated with a higher risk of preterm birth (absolute risk difference, 0.2% [95% CI, 0%-0.4%] per 1 SD; OR, 1.04 [95% CI, 1.00-1.09] per 1 SD). Thyroid peroxidase antibody-positive women had a higher risk of preterm birth vs TPO antibody-negative women (6.6% vs 4.9%, respectively; absolute risk difference, 1.6% [95% CI, 0.7%-2.8%]; OR, 1.33 [95% CI, 1.15-1.56]). Conclusions and Relevance: Among pregnant women without overt thyroid disease, subclinical hypothyroidism, isolated hypothyroxinemia, and TPO antibody positivity were significantly associated with higher risk of preterm birth. These results provide insights toward optimizing clinical decision-making strategies that should consider the potential harms and benefits of screening programs and levothyroxine treatment during pregnancy.

Speciation and isotopic characterization of mercury detected at high concentration in Pakistani hair samples.

Speciation and isotopic analyses of mercury (Hg) detected at high concentration (11-107 mg total Hg/kg) in the hair samples of Pakistani subjects were carried out to analyze whether the source of Hg was the skin cream or the soap they used. Liquid chromatography-ICP mass spectrometric speciation analysis revealed that the Hg in the hair was primarily inorganic. This result supported our assumption that skin care products were the source of the high concentration of Hg in hair, which was based on the statistical association found in our previous study because it is known that inorganic Hg compounds are added to some skin care products sold in some countries. Stable isotope ratios of the Hg in the hair samples of 6 subjects and 3 skin cream samples, which were reported to be used by the subjects, were measured by multi-collector ICP mass spectrometry after acid digestion. A comparison of the isotopic compositions of Hg in hair and skin cream in two subjects revealed that the composition in both samples matched in one subject, hence confirming that the products were the source of high Hg concentration in hair. However, the isotopic compositions of Hg in hair and skin cream did not match in the other subject demonstrating the presence of other exposure source(s).

Cadmium Exposure and Blood Telomere Length in Female University Students in Japan.

Cadmium is a toxic metal found ubiquitously throughout the world. Our study evaluated whether cadmium exposure was associated with telomere length in 73 female university students. Determination of telomere length was performed by quantitative polymerase chain reaction using DNA in blood. Urinary cadmium concentration was measured by inductively coupled plasma mass spectrometry. The students' physiological attributes and lifestyle were surveyed by means of a self-administered questionnaire. The geometric mean of urinary cadmium concentration was 0.312 µg/g creatinine, which was lower than the levels previously reported for Japan. Urinary cadmium concentration was not significantly associated with telomere length, though the exposure level of the present subjects was similar to that of previous study subjects which found significantly negative associations. It is possible that other factors affected telomere length in this study population.

Urinary 8-Hydroxy-2'-deoxyguanosine (8-OHdG) Concentrations and Menstrual Cycle Characteristics in Female University Students.

Higher concentrations of oxidative stress biomarkers are found in women with polycystic ovary syndrome (PCOS) and endometriosis, conditions linked to irregular menstrual cycles and menstrual pain. The aim of the present study was to test whether women with higher oxidative stress are more likely to show irregular menstrual cycles and severe menstrual pain compared with women with lower oxidative stress. A cross-sectional study was conducted targeting female university students with a mean (SD) age of 20.5 (1.8) years (n = 188). Participants completed a questionnaire on reproductive characteristics and anthropometry and kept a menstrual cycle diary for 5 consecutive months. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), cotinine, and creatinine concentrations were measured once during the study period. The mean (SD) value of the urinary 8-OHdG concentration was 4.7 (2.0) µg/g of creatinine. A total of 1021 menstrual cycles were recorded. The participants were categorized as either having regular (68%) or irregular (18%) cycles or oligomenorrhea (13%) or polymenorrhea (1%). The urinary 8-OHdG concentration did not significantly differ across menstrual cycle regularity or pain categories. Even after adjusting for age, body mass index (BMI), and urinary cotinine concentrations, having irregular cycles or more severe menstrual pain was not associated with urinary 8-OHdG concentration.