Neonatal Thyroid-stimulating Hormone Levels Research Articles

Prevalence of high neonatal thyroid stimulating hormone levels as an indicator of iodine deficiency in the province of La Pampa: An epidemiological analysis.

Introduction. Iodine plays a key role in human metabolism, growth, and development. During pregnancy and childhood, the demand for this micronutrient increases notably. Increased neonatal thyroid stimulating hormone (nTSH) levels, defined as nTSH ≥ 5 mIU/L, are a marker of iodine deficiency in a population if its prevalence is higher than 3%. Objective. To establish the prevalence of nTSH ≥ 5 in La Pampa in the 2021-2022 period, analyze its correlation with different variables, and compare it with data from a historical cohort. Population and methods. Cross-sectional, descriptive-analytical study in a population of newborn infants born in the 5 health regions of the province of La Pampa in 2021 and 2022. Results. Of the 5778 assessed newborn infants, 9.6% had nTSH levels ≥ 5 mIU/L. It was reported that 70.4% of these measurements were done after the third day of life. No significant differences were observed in the frequency of high nTSH levels by year of birth, birth weight, or days until sample collection. A higher prevalence was observed among male infants (10.6% versus 8.5%; p = 0.007) and term infants (9.8% versus 6.6%; p = 0.02). The prevalence of high TSH levels was superior to that observed in the 2001-2002 cohort. Conclusions. The prevalence of high nTSH levels in La Pampa during 2021 and 2022 was 9.6%, suggesting the presence of mild iodine deficiency in the population of this province, higher that what had been reported 2 decades ago.

Associations between OGTT results during pregnancy and offspring TSH levels: a birth cohort study

BackgroundLimited evidence exists regarding the association between gestational diabetes mellitus (GDM) and elevated levels of thyroid-stimulating hormone (TSH) in newborns. Therefore, this study aimed to investigate the potential risk of elevated TSH levels in infants exposed to maternal GDM, considering the type and number of abnormal values obtained from the 75-gram oral glucose tolerance test (OGTT).MethodsA population-based, prospective birth cohort study was conducted in Wuhan, China. The study included women who underwent GDM screening using a 75-g OGTT. Neonatal TSH levels were measured via a time-resolved immunofluorescence assay. We estimated and stratified the overall risk (adjusted Risk Ratio [RR]) of elevated TSH levels (defined as TSH > 10 mIU/L or > 20 mIU/L) in offspring based on the type and number of abnormal OGTT values.ResultsOut of 15,236 eligible mother-offspring pairs, 11.5% (1,753) of mothers were diagnosed with GDM. Offspring born to women diagnosed with GDM demonstrated a statistically significant elevation in TSH levels when compared to offspring of non-GDM mothers, with a mean difference of 0.20 [95% CI: 0.04–0.36]. The incidence of elevated TSH levels (TSH > 10 mIU/L) in offspring of non-GDM women was 6.3 per 1,000 live births. Newborns exposed to mothers with three abnormal OGTT values displayed an almost five-fold increased risk of elevated TSH levels (adjusted RR 4.77 [95% CI 1.64–13.96]). Maternal fasting blood glucose was independently and positively correlated with neonatal TSH levels and elevated TSH status (TSH > 20 mIU/L).ConclusionsFor newborns of women with GDM, personalized risk assessment for elevated TSH levels can be predicated on the type and number of abnormal OGTT values. Furthermore, fasting blood glucose emerges as a critical predictive marker for elevated neonatal TSH status.

Relationship between infant hypothyroidism and maternal thyroid disease

Background: Due to the very high complications of neonatal hypothyroidism in the country, neonatal screening program is performed for timely diagnosis and treatment of neonates. The aim of this study to investigate the relationship between infant hypothyroidism and maternal thyroid disease. Methods: This cross-sectional study was done on 195 neonates with a diagnosis of hypothyroidism. Necessary data were collected by a checklist and then analyzed by statistical methods in statistical package for the social sciences (SPSS) version 21 by statistical methods. Results: Of all mothers, 21.0% had a history of thyroid disease. There was no statistically significant relationship between maternal age and infant thyroid stimulating hormone (TSH). There was no significant relationship between the history of maternal hypothyroidism and maternal hypothyroidism (during experiments) with the amount of TSH in the newborn. There was a direct and significant relationship between maternal TSH level and maternal free T4. But there was no statistically significant relationship between infant TSH level and maternal TSH level and free T4. There was no significant difference in neonatal TSH levels with maternal anti-TPO status. There was no significant relationship between the history of maternal diabetes and the history of maternal hypertension with neonatal TSH. There was no significant difference in neonatal TSH levels by maternal thyroid status. Conclusions: In the present study, no significant relationship was found between the incidence of neonatal hypothyroidism and the presence of thyroid disease in mothers. The existence of different genetic and environmental factors and the significant impact of each of these factors can justify this result.

Trimester-specific associations of maternal exposure to bisphenols with neonatal thyroid stimulating hormone levels: A birth cohort study

BackgroundGrowing evidence suggests that exposure to bisphenol A (BPA) during pregnancy could interfere with neonatal thyroid function. Bisphenol F (BPF) and bisphenol S (BPS) are increasingly used as the substitutes of BPA. However, little is known about the effects of maternal exposure to BPS and BPF on neonatal thyroid function. The current study was aimed to investigate the trimester-specific associations of maternal exposure to BPA, BPS, and BPF with neonatal thyroid stimulating hormone (TSH) levels. MethodsBetween November 2013 and March 2015, a total of 904 mother-newborn pairs were recruited from the Wuhan Healthy Baby Cohort Study, providing maternal urine samples in the first, second, and third trimesters for bisphenol exposure assessment, and neonatal heel prick blood samples for TSH measurement. Multiple informant model and quantile g-computation were used to evaluate the trimester-specific associations of bisphenols individually and mixture with TSH, respectively. ResultsEach doubling concentration increase of maternal urinary BPA in the first trimester was significantly related to a 3.64 % (95% CI: 0.84 %, 6.51 %) increment in neonatal TSH. Each doubling concentration increase of BPS in the first, second and third trimesters were associated with 5.81 % (95 % CI: 2.27 %, 9.46 %), 5.70 % (95 % CI: 1.99 %, 9.55 %), 4.36 % (95 % CI: 0.75 %, 8.11 %) higher neonatal blood TSH, respectively. No significant association between trimester-specific BPF concentration and TSH was observed. The relationships between exposures to BPA/BPS and neonatal TSH were more evident in female infants. Quantile g-computation indicated that maternal co-exposure to bisphenols in the first trimester was significantly associated with neonatal TSH levels in a non-linear fashion. ConclusionMaternal exposure to BPA and BPS were positively associated with neonatal TSH levels. The results indicated the endocrine disrupting effect of prenatal exposure to BPS and BPA, which should be of particular concern.

THE EFFECT OF LEVOTHYROXINE TREATMENT ON MATERNAL AND PERINATAL OUTCOMES IN PREGNANT WOMEN WITH SUBCLINICAL HYPOTHYROIDISM: A 5-YEAR RETROSPECTIVE STUDY AT A TERTIARY CARE HOSPITAL IN TURKEY

Subclinical hypothyroidism is characterized by elevated thyroid stimulating hormone (TSH) levels with normal free thyroxine (fT4) levels. The aim of this study was to compare obstetric and neonatal outcomes in pregnant women with and without treatment for subclinical hypothyroidism. In this study, maternal and perinatal outcomes were evaluated in a total of 270 pregnant women who were diagnosed with subclinical hypothyroidism as a result of screening performed in three trimesters of pregnancy between 2015 and 2020 and followed up in our clinic, 149 of whom received levothyroxine treatment and 121 of whom did not receive treatment. Further, different cutoff values for TSH were compared. The rates of neonatal intensive care unit (NICU) requirement were not different according to the levothyroxine use status of the patients (p=0.73, p>0.05). Miscarriage rates did not differ according to levothyroxine use (p=0,87, p>0,05). TSH, T4 and antithyroid peroxidase levels did not differ according to the maternal use of levothyroxine (p>0,05). Birth weight, gestational week at birth, 1- and 5-minute APGAR scores, neonatal TSH and T4 levels did not differ according to the maternal use of levothyroxine (p>0,05). Among the adverse maternal and perinatal outcomes, the need for NICU admission and the rates of placental abruption, fetal distress, preterm premature rupture of membranes, preeclampsia, preterm labor, and small for gestational age were not significantly different among the TSH cutoff groups (p>0,05). The rate of premature rupture of membranes was higher in the group with TSH levels ≥2.5 mIU/L (p=0.04). Choosing 2.5 mIU/L as the cutoff value for TSH levels allows early diagnosis of subclinical hypothyroidism with a higher rate in pregnant Turkish women and proactive therapeutic management. Our study provides limited evidence for the success of levothyroxine therapy for adverse obstetric and neonatal outcomes.

Maternal paraben exposure and intra-pair thyroid-stimulating hormone difference in twin neonates

Thyroid hormones are essential for fetal growth and neurodevelopment. The recent frequent use of parabens has raised concerns about their endocrine-disrupting potential. However, the effects of maternal paraben exposure on neonatal thyroid hormone levels are still largely unknown. In our study, a co-twin control design was employed to analyze the relationships between maternal paraben exposure and neonatal thyroid-stimulating hormone (TSH) difference. We collected information from 252 mother-twin pairs from a twin birth cohort in Wuhan, China. Concentrations of six parabens were measured in maternal urine samples collected at < 16, 16–28, and > 28 weeks of gestation. Data of neonatal TSH levels were retrieved from medical records. Multiple informant models were applied to explore the time-specific relationships between paraben exposure and intra-twin TSH difference and to determine the susceptible window of exposure. We found that maternal urinary methyl paraben (MeP) during early pregnancy was positively associated with intra-twin TSH difference (%change = 5.96 %; 95 % confidant interval (CI): 0.04 %, 12.2 %). However, no significant differences were observed for exposure to ethyl paraben (EtP) and propyl paraben (PrP), and the associations between parabens and intra-twin TSH difference did not differ materially across pregnancy. Further, a stratified analysis based on twin zygosity and chorionicity and sex types indicated that the positive association between early pregnancy MeP exposure and intra-twin TSH difference was significant in monochorionic diamniotic (MCDA) twins of female-female fetuses and dichorionic diamniotic (DCDA) twins of opposite-sex. The prospective twin study provides first evidence that MeP exposure in early pregnancy was associated with an increased TSH difference in twin neonates, especially in female fetuses.

Prenatal exposure to perfluorooctane sulfonate alternatives and associations with neonatal thyroid stimulating hormone concentration: A birth cohort study

BackgroundChlorinated polyfluorinated ether sulfonic acids (Cl-PFESA) and perfluorobutane sulfonate (PFBS), used as perfluorooctanesulfonate (PFOS) alternatives, were indicated as thyroid hormone disruptive toxicants in experimental studies. However, it is unclear whether prenatal exposure to Cl-PFESA and PFBS affects neonatal thyroid stimulating hormone (TSH) in human. ObjectiveTo disclose the relationships between prenatal Cl-PFESAs and PFBS exposure and neonatal thyroid-stimulating hormone (TSH) levels based on a perspective cohort study. MethodsA total of 1015 pairs of mother and newborn were included from an ongoing birth cohort study in Wuhan, China, between 2013 and 2014. Six PFASs in cord blood sera and TSH concentration in neonatal postpartum heel sticks blood were quantified. Mixed linear and weighted quantile sum (WQS) regression models were applied to assess the individual and combination effects of PFASs exposure on neonatal TSH levels with multiple covariates adjustments. ResultsAfter adjusting for potential confounders and other five PFASs, for each 1-ng/mL increase of PFBS or 8:2 Cl-PFESA, was negatively associated with 25.90% (95%CI: 37.37%, −12.32%; P < 0.001) and 27.19% (95%CI: 46.15%, −1.55%; P = 0.033) change in TSH in male but not female infants, respectively. No significant association was found between other PFASs exposure and neonatal TSH. Higher PFAS mixture in cord blood was significantly associated with decrease TSH concentration in all newborns (β = −0.36; 95%CI: 0.58, −0.13; P = 0.001) identified by WQS regression model. PFBS, PFOS and 6:2 Cl-PFESA were the major contributors to the neonatal TSH decrement with the weights of 56.50%, 18.71%, 12.81% among PFAS mixture, respectively.Conclusions: our prospective cohort study suggested a negative association of cord serum PFBS and 8:2 CI-PFESA with TSH concentration in newborns, especially for boys. Additional studies are required to elaborate on the underlying biological mechanisms, especially for PFBS.

Higher maternal thyroid resistance indices were associated with increased neonatal thyroid-stimulating hormone- analyses based on the Huizhou mother-infant cohort.

ObjectivesThis study aimed to explore the relationship of maternal thyroid function and thyroid resistance parameters with neonatal thyroid-stimulating hormone (TSH).MethodsThis work was a longitudinal study. Singleton pregnant women without a history of thyroid disorders were recruited in their first prenatal visit from October 2018 to June 2020. Maternal thyroid markers including TSH, free triiodothyronine (FT3), free thyroxine (FT4), and neonatal TSH were tested in the clinical laboratory of the hospital by electrochemiluminescence immunoassay. Thyroid resistance indices including Thyroid Feedback Quantile-based Index (TFQI), TSH index (TSHI), and thyrotroph T4 resistance index (TT4RI) were estimated in accordance with maternal FT4 and TSH levels. Multivariable linear and logistic regression was applied to explore the associations of maternal thyroid indices with infantile TSH level.ResultsA total of 3,210 mothers and 2,991 newborns with valid TSH data were included for analysis. Multivariable linear regression indicated that maternal thyroid variables were significantly and positively associated with neonatal TSH levels with standardized coefficients of 0.085 for TSH, 0.102 for FT3, 0.100 for FT4, 0.076 for TSHI, 0.087 for TFQI, and 0.089 for TT4RI (all P < 0.001). Compared with the lowest quartile, the highest quartile of TSHI [odds ratio (OR) = 1.590, 95% CI: 0.928–2.724; Ptrend = 0.025], TFQI (OR = 1.746, 95% CI: 1.005–3.034; Ptrend = 0.016), and TT4RI (OR = 1.730, 95% CI: 1.021–2.934; Ptrend = 0.030) were significantly associated with an increased risk of elevated neonatal TSH (>5 mIU/L) in a dose–response manner.ConclusionThe longitudinal data demonstrated that maternal thyroid resistance indices and thyroid hormones in the first half of gestation were positively associated with neonatal TSH levels. The findings offered an additionally practical recommendation to improve the current screening algorithms for congenital hypothyroidism.

Effect of Maternal Triclosan Exposure on Neonatal Thyroid-Stimulating Hormone Levels: A Cross-Sectional Study.

Objective This study is aimed at assessing the relationship between maternal urinary triclosan (uTCS) exposure and the thyroid-stimulating hormone (TSH) level of infant cord blood. Methods This cross-sectional study was carried out in 2019-2020 in Isfahan, Iran, and 99 pregnant women participated in the study. Urine samples were collected after the 28th week of pregnancy, and the concentration of TCS was measured using GC/MS. The cord blood levels of TSH (CBL-TSH) were measured. The association between uTCS and CBL-TSH was examined based on the general linear model. Results TCS was detected (≥0.01 ng/mL) in 100% of the urine samples, with the interquartile range (25%-75%) of uTCS levels 0.6-6.23 μg/g Cr. uTCS was not associated with CBL-TSH after adjustment for covariates. A significant relationship was observed between CBL-TSH of neonates born to mothers who had given birth only once compared to mothers who had given birth twice or more times. Conclusions Maternal exposure to TCS did not affect the infant CBL-TSH. However, the high concentrations of TCS in maternal urinary samples indicate the necessity of more precise regulations to decrease the use of this chemical in the industry and increase public awareness about using TCS-free compounds.

Increased maternal leptin levels may be an indicator of subclinical hypothyroidism in a newborn.

BackgroundSeveral factors may influence newborn thyroid-stimulating hormone (TSH) concentrations and cause subclinical hypothyroidism in a newborn. A sufficient level of leptin signalling is needed for the normal production of TSH and thyroid hormones by the thyroid gland. Our study aimed to investigate the correlation between maternal serum leptin concentration during the third trimester of pregnancy and newborn screening-TSH levels.MethodsThis prospective cross-sectional study was conducted in obstetrics and gynaecology clinics of a state hospital between June and August 2013. Maternal venous blood samples were collected from 270 healthy pregnant women in the third trimester just before delivery. Measurements of maternal fT3, fT4, TSH, anti-thyroid peroxidase (TPO), and anti-thyroglobulin (anti-Tg) antibodies from serum samples were performed by chemiluminescence immunoassay. Maternal serum leptin levels were determined by ELISA. Dried capillary blood spots were used to measure newborn TSH levels.ResultsSubjects were divided into two groups according to the neonatal TSH levels using a cut-point of 5.5 mIU/L. Median maternal serum leptin levels were significantly higher in newborns whose TSH levels were higher than >5.5 mIU/L [13.2 μg/L (1.3 - 46.5) vs 19.7 μg/L (2.4 - 48.5), p<0.05]. Serum leptin levels showed a negative correlation with maternal fT4 (r=0.32, p<0.05), fT3 (r=0.23, p<0.05), and a positive correlation with BMI (r=0.30, p<0.05).ConclusionsOur results suggest that high leptin levels in the third trimester of pregnancy influence maternal thyroid functions and might cause an increase in newborn TSH levels. Detection of high maternal serum leptin levels may be a reason for subclinical hypothyroidism.

Prenatal exposure to polycyclic aromatic hydrocarbons and effects on neonatal anthropometric indices and thyroid-stimulating hormone in a Middle Eastern population

Prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) evokes extensive concerns regarding public health. Monitoring the pregnant women's exposure can be considered a suitable alternative to assess the fetus's exposure. This study aimed to monitor pregnant women's exposure (n = 126) to PAHs using a biomonitoring approach to evaluate effects on anthropometric indices and neonatal thyroid-stimulating hormone (TSH) in Shiraz, Iran. PAHs priority compounds were measured by gas chromatography-mass spectrometry (GC-MS) after separating blood serum and liquid-liquid extraction (LLE) method. Information on anthropometric indices, neonatal TSH levels, and data from the respondents was obtained from medical records and questionnaires. The mean PAHs concentrations ranged from 0.29 to 327.91 ng/g lipid. There was no significant difference between the measured PAHs in maternal serum at the seventh month and pregnancy termination except for ACY (p-Value<0.05). Regression analysis results showed a significant correlation (p-value<0.05) between exposure to passive smoke and total PAHs concentrations. There was no significant relationship between exposure to PAHs and weight, height, head circumference, and Apgar score of newborns. The results showed TSH decreased by 0.99 units as ACE increased per unit (β = -0.001). This study is the first to evaluate relationships between prenatal exposure to PAHs and effects on newborn health indicators, including TSH levels in a Middle Eastern population. Future studies are suggested to perform detailed assessments of PAHs intake sources, especially in vulnerable populations such as pregnant women and children.

Prenatal exposure to organophosphate esters and neonatal thyroid-stimulating hormone levels: A birth cohort study in Wuhan, China.

Increasing animal studies have indicated that organophosphate esters (OPEs) have endocrine-disruptive potential. However, human epidemiological evidence is limited, especially in susceptible populations, such as pregnant women and neonates. The purpose of this present study was to examine the trimester-specific relationships of prenatal exposure to OPEs with neonatal thyroid-stimulating hormone (TSH). A total of 102 mother-newborn pairs were recruited from a birth cohort study between April 2015 and September 2016 in Wuhan, China. Eight OPE metabolites were detectable in urine samples from pregnant women across the different three trimesters. Neonatal TSH levels were measured using time-resolved immunofluorescence assay. The associations between maternal urinary OPE metabolites and neonatal TSH and the critical exposure windows of fetal vulnerability were estimated using multiple informant models. Seven OPE metabolites with detection frequency>50% (52.9%-98.0%) were detected in repeated urine samples from different three trimesters, and the urinary OPE metabolites across pregnancy was of high variability (ICCs: 0.09-0.26). After adjusted for confounders (e.g., maternal age, prepregnancy BMI, passive smoking during pregnancy), some suggestive associations were observed between maternal urinary OPE metabolites and neonatal TSH in different trimesters. A doubling of second trimester di-o-cresyl phosphate & di-p-cresyl phosphate (DoCP & DpCP) was associated with a 7.82% increase in neonatal TSH level (95% CI: -0.70%, 17.06%, p-value=0.07), a doubling of third trimester diphenyl phosphate (DPHP) was associated with a 4.71% decrease in neonatal TSH level (95% CI: -9.80%, 0.67%, p-value=0.09), and a doubling of third trimester bis(2-butoxyethyl) phosphate (BBOEP) was associated with a 6.38% increase in neonatal TSH level (95% CI: -0.12%, 13.31%, p=0.05). However, such associations did not differ materially across trimesters. When performing stratified analysis by infant sex, the associations were statistically significant and were sex-dependent.In females, maternal urinary DoCP & DpCP concentrations in each trimester were associated with increased neonatal TSH levels, and urinary DPHP concentration in the third trimester was associated with decreased neonatal TSH level. In males, maternal urinary BBOEP concentration in the first trimester was positively related to neonatal TSH level. This prospective study demonstrated that prenatal exposure to OPEs can lead to a sex-dependent change in neonatal TSH levels. Although the sex-selective effect was differed among various urinary OPE metabolites, more evidence was supported that OPE exposure was related to increased TSH levels for both males and females.

The association of lactating mothers' urinary and breast milk iodine levels with iodine nutrition status and thyroid hormone levels of newborns.

To explore the iodine status of lactating mother-newborn pairs, and whether neonatal serum thyroid-stimulating hormone (TSH) can be used for estimation of iodine status of the population. A total of 334 mothers and their healthy neonates were included. Urine, serum, and breast milk samples were obtained at 4th and 6th days of delivery. Urinary iodine concentration (UIC) was measured in urine samples of mothers and their neonates, as well as breast milk iodine concentration (BMIC) and serum thyroid hormone levels of neonates, were measured from the samples taken between the 4th and 6th days after birth. Median age of the mothers was 27 years (23-30). The median UIC of mothers and their newborns were 125 μg/L and 142 μg/L, respectively. The median BMIC was 138,0 μg/L. There was a significant positive correlation between the BMIC and UIC of neonates (r=0.276, p<0.001). The prevalence of neonatal serum TSH >10 mIU/L, which is suggestive of mild iodine deficiency (i.e. 3.0-19.9%), was 19.0%. However, there were no participants with iodine deficiency in lactating mothers and neonates according to UIC. By previous reports, Aydın is iodine sufficient. Although 19% of the neonates had serum TSH levels >10 mU/L, which is suggestive of a mild iodine deficiency, iodine deficiency was observed in none of the neonates and their mothers. Therefore, it will be appropriate to investigate the role of neonatal TSH levels in a larger sample to assess the iodine status of the population.

Evidence for differential thyroid sensitivity from prenatal exposure to polychlorinated biphenyl chemicals in children with autism

Background/Aim: Prenatal exposure to polychlorinated biphenyls (PCBs), persistent organic pollutants, is linked to altered thyroid function and adverse neurodevelopmental outcomes, including autism spectrum disorder (ASD). We examined whether neonatal thyroid-stimulating hormone (TSH) mediates the relationship between prenatal PCB exposure and risk of ASD. Methods: We analyzed data from the Early Markers for Autism (EMA) Study, a case-control study of children born during 2000-2003 in Southern California. Children diagnosed with ASD (n=523), Intellectual disability (ID; n=147), and general population controls (n=405) were identified from birth and Department of Developmental Services records. Eleven PCB congeners were measured above the limit of detection in maternal serum collected during the second trimester and modeled as quartiles. Neonatal TSH levels were obtained from state newborn screening records and ln-transformed. We assessed relationships between PCBs and neonatal TSH in models stratified by neurodevelopmental outcome and TSH mediation of the significant relationships we previously observed in EMA between several PCBs and ASD. Results: In the full sample, correlations between PCB concentrations and neonatal TSH were weak and not significant (ranging from 0 to 0.06). However, among children with ASD, we observed significant increases in neonatal TSH associated with an interquartile increase in prenatal levels of four PCBs, including PCB153 (adj-β: 0.21, 95%CI: 0.02-0.39) and PCB138/158 (adj-β: 0.19, 95%CI: 0.01-0.37). We did not observe associations between neonatal TSH and PCBs among children with ID only or controls. Mediation analyses did not suggest that relationships between these PCBs and ASD were mediated by neonatal TSH. Conclusions: Prenatal exposure to PCBs, particularly congeners previously found to be associated with ASD in EMA, were positively associated with neonatal TSH, but only among children subsequently diagnosed with ASD. These findings, needing replication in larger cohorts, may indicate differential fetal sensitivity to thyroid-disrupting chemicals among individuals born, and later-diagnosed, with ASD.

Exposure to organophosphate ester flame retardants and plasticizers during pregnancy: Thyroid endocrine disruption and mediation role of oxidative stress

Organophosphate esters (OPEs) are widely used as flame retardants and plasticizers in consumer and industrial products. Human exposure to OPEs raises concerns due to their endocrine disruptive potentials. Till now, the effects of OPEs on thyroid hormones (THs) and the mediating role of oxidative stress in pregnant women have not been studied. In this study, prenatal urinary concentrations of OPE metabolites (mOPEs), levels of free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), and oxidative stress levels of 8-hydroxy-2-deoxy guanosine (8-OHdG) and malondialdehyde (MDA) were measured in pregnant women (n = 360) from a coastal urbanized region and moderate socioeconomic status. Neonatal TSH in heel blood was also measured in newborns (n = 309). Dibutyl phosphate (DBP) and diphenyl phosphate (DPHP) were extensively detected with a median creatinine-adjusted level of 0.19 μg/g and 0.66 μg/g, respectively, and the median of ∑mOPEs was 1.82 μg/g. DBP and DPHP were included in the analysis. The concentrations of DBP and DPHP were positively associated with either maternal or neonatal TSH levels, while not for maternal FT3 and FT4 levels. Positive associations for maternal and neonatal TSH were particularly observed in girls as stratified by newborn sex suggesting a sex-selective difference. Furthermore, 8-OHdG, the biomarker of DNA damage, was found to be a major mediator (>60%) for the association between neonatal TSH and DPHP, suggesting that DNA damage is involved in fetal thyroid function disruption. On the other hand, MDA showed a partially suppressing effect (<40%) for the associations between mOPEs and neonatal TSH, which needs further clarification. For maternal TSH, both 8-OHdG and MDA showed moderate mediating effects while the direct effects of mOPEs on maternal TSH also contributed. These results suggest thyroid disrupting effects of OPE exposure on mothers and fetuses during pregnancy and the potential influence mediated by the oxidative stresses of DNA damage and lipid peroxidation.

Association of elevated neonatal thyroid-stimulating hormone levels with school performance and stimulant prescription for attention deficit hyperactivity disorder in childhood.

Untreated severe newborn thyroid deficiency causes neurocognitive impairment; however, the impact of mild thyroid deficiency is not known. This study aimed to examine whether mildly elevated neonatal thyroid-stimulating hormone (TSH) levels are associated with poor school performance or stimulant prescription for attention deficit hyperactivity disorder (ADHD). This record-linkage study included 232,790 term-born infants in Australia with a TSH level below newborn screening threshold (< 15mIU/L). Among our cohort, as TSH levels increased, the proportion of infants born low birthweight via caesarean section and with disadvantaged socioeconomic status increased. Multivariable logistic regression analysis showed that, compared with infants with 'normal' neonatal TSH level (< 5mIU/L), those with neonatal TSH 10-15mIU/L had an increased risk of being exempt from school testing (aOR 1.63 (95% CI 1.06-2.69)) or prescribed a stimulant for ADHD (aOR 1.57 (95% CI 1.10-2.24)), adjusted for perinatal and sociodemographic factors. Among a nested analysis of 460 sibling pairs, siblings with 'mildly elevated' TSH levels were more likely to be exempt from school tests compared with siblings with normal TSH levels (aOR 2.53, 95% CI 1.01-6.33).Conclusion: In this population cohort and sibling analysis, mildly elevated neonatal TSH levels were associated with being exempt from school testing due to significant or complex disability. What is Known: • Newborn screening for severe thyroid hormone deficiency has virtually eliminated congenital hypothyroidism-associated intellectual disability in developed countries. • The impact of mild thyroid hormone deficiency in infants is unclear. What is New: • Children with a mildly elevated neonatal TSH level below current newborn screening cut-offs have an increased likelihood of being exempt from school testing due to significant or complex disability compared with siblings and peers. This study includes a population-based and nested sibling analysis.

Identifying a critical window of maternal metal exposure for maternal and neonatal thyroid function in China: A cohort study

BackgroundChina, a developing country, has a particularly serious problem with metal pollution. We evaluated the association of metal exposure during pregnancy with maternal and neonatal thyroid function, and identified the critical window for maternal metal exposure effects on maternal and neonatal thyroid functions. MethodsThe maternal urinary concentrations of mercury (Hg), cadmium (Cd), arsenic (As) and cesium (Cs) were determined in pregnant women during their first (n = 389) or third (n = 257) trimesters in a prospective cohort from 2014 to 2015 in Nanjing, China, using an inductively coupled plasma mass spectrometry (ICP-MS) instrument. Maternal serum-free thyroxine (FT4) and thyroid-stimulating hormone (TSH) were measured by electrochemiluminescent microparticle immunoassays in the second and third trimesters. Neonatal TSH levels were detected 72 h after birth. ResultsHg (>0.162 µg/L), Cd (>0.084 µg/L), As (>0.348 µg/L) and Cs (>0.093 µg/L) were detectable in 76.9%, 90.1%, 100% and 100% of maternal urine samples from women in the first trimester of pregnancy. In the multiple adjusted linear regression models, maternal exposures to Hg and Cd in the first trimester were positively associated with maternal TSH levels in the second trimester (P < 0.01, P = 0.02). Moreover, maternal exposures to Cd and Cs in the first trimester were positively associated with neonatal TSH levels (P = 0.04, P = 0.02). In the Bayesian kernel machine regression (BKMR) model, the results were stable and consistent with the linear regression model. ConclusionsMaternal exposure to Hg, Cd and Cs in the first trimester was related to TSH levels in mothers and newborns. Efforts to identify maternal and neonatal thyroid disruptors should carefully consider the effects of exposure to these metals.

Neonatal Thyroid Stimulating Hormone and Subsequent Diagnosis of Autism Spectrum Disorders and Intellectual Disability.

Hypothyroid conditions in early life, if left untreated, are associated with adverse neurodevelopmental outcomes, including intellectual disability (ID). However, evidence addressing the role of neonatal thyroid hormone insufficiencies in the altered neurobiology underlying autism spectrum disorders (ASD), particularly among its subphenotypes, is limited. We conducted a population-based, case-control study among a sample of children born during 2000-2003 in Southern California. We examined neonatal thyroid-stimulating hormone (TSH) measured during routine newborn screening among children later diagnosed with ASD (n = 518) or ID (n = 145) and general population (GP) controls (n = 399). TSH was further analyzed in relation to ASD subgroups of intellectual ability and onset type (early-onset ASD vs. ASD with regression) ascertained by expert review of developmental services records. Odds ratios (ORs) of the differences in TSH between groups were obtained from multivariate logistic regression. We examined neonatal TSH as continuous (ln-transformed) and as quartiles. We found no association between continuous neonatal TSH levels and ASD (adj-OR: 1.00, 95% CI: 0.79-1.26) nor ID (adj-OR = 1.01, 95% CI: 0.73-1.40). Among ASD subphenotypes, we observed a suggestive inverse trend between ASD with regression and TSH, though the association only reached statistical significance in the highest TSH quartile (adj-OR: 0.50, 95% CI: 0.26-0.98). While there was little evidence that neonatal TSH is related to overall ASD risk, more work is needed to understand the influence of thyroid hormones on ASD subphenotypes. Autism Res 2020, 13: 444-455. © 2019 International Society for Autism Research,Wiley Periodicals, Inc. LAY SUMMARY: Low levels of thyroid hormone at birth can negatively impact brain development. We studied whether newborn levels of thyroid stimulating hormone (TSH) were associated with autism spectrum disorder (ASD) and its subtypes in a sample of children born in California. Newborn TSH was not related to the overall risk of ASD or intellectual disability. However, the relationships of thyroid hormone levels at birth and specific subtypes of ASD, particularly ASD with developmental regression, may need more research.

Prenatal exposure of rare earth elements cerium and ytterbium and neonatal thyroid stimulating hormone levels: Findings from a birth cohort study

BackgroundPrior studies have suggested exposure to heavy metals and endocrine disrupting chemicals could disturb the homeostasis of thyroid stimulating hormone (TSH), but no epidemiology study concerning the influence of rare earth elements (REE) exposure during pregnancy on neonatal TSH levels. The present study aimed to investigate the relationships between prenatal REE exposure and neonatal TSH levels. MethodsA total of 7367 pregnant women were recruited from Wuhan Children’s Hospital between September 2012 and October 2014 in Wuhan, China. Urinary concentrations of cerium (Ce), and ytterbium (Yb) were measured by inductively coupled plasma mass spectrometry (ICP-MS). Immunofluorescence assay was used to detect neonatal TSH levels. The associations between REE exposure and neonatal TSH levels were evaluated using multivariate linear regression models. ResultsThe geometric means of maternal urinary Ce and Yb concentrations were 0.060 μg/g creatinine and 0.025 μg/g creatinine, respectively. The results showed that per doubling of maternal urinary Ce and Yb were associated with 4.07% (95% CI: −5.80%, −2.31%), 5.13% (95% CI: −6.93%, −3.30%) decreased neonatal TSH levels respectively in the adjusted model. Sex stratified analysis demonstrated that the decreased neonatal TSH levels were observed both in male infants and female infants, and the decrease was greater in male infants in urinary Ce. There were no significant interactions between maternal urinary Ce, Yb and infant sex (Ce: P for interaction = 0.173, Yb: P for interaction = 0.967). ConclusionsOur findings demonstrated that increased maternal urinary Ce and Yb were associated with decreased neonatal TSH levels. Further researches from different populations are warranted to verify the association and to explore the mechanisms.

Association Between Neonatal Thyroid Stimulating Hormone Status and Maternal Urinary Iodine Status

Maternal urinary iodine concentration (MUIC) and percentage of neonates with Thyroid stimulating hormone (TSH) >5 mIU/L are amongst the parameters suggested for assessing adequate iodine status. To assess the correlation between MUIC and neonatal TSH levels. Cross-sectional. Tertiary care center in Delhi, India, between November 2015 to November 2016. Postnatal mother-neonate dyads. TSH levels assessed among neonatal samples were stratified as below and above 5 mIU/L. MUIC was measured in 544 mothers, 400 mother-neonate dyads with neonatal TSH levels >5 mIU/L (cases) and 144 mother-neonate newborn mother dyads with neonatal TSH <5 mIU/L (controls). Results: The percentage of mothers with iodine insufficiency (9.8% vs 5.6%) as well as iodine excess (54.3% vs 41.7%) were significant higher in cases than controls. Mean TSH was also higher (P=0.0002) in both the iodine deficient and iodine excess group. There was no correlation between neonatal TSH values and MUIC. Lack of correlation between neonatal TSH and MUIC is due to iodine excess together with iodine deficiency.