Maternal exposure to O3 and NO2 may increase the risk of newborn congenital hypothyroidism: a national data-based analysis in China.

Maternal exposure to air pollution during pregnancy is associated with adverse outcomes in the offspring, but limited studies focused on the impacts of gaseous air pollution on newborn congenital hypothyroidism (CH). Therefore, a national data-based analysis was conducted to explore the association between maternal exposure to gaseous air pollution and the incidence of CH in China. Annual average exposure levels of SO2, NO2, CO, and O3 from January 1, 2014, to December 30, 2014, were acquired from the Chinese Air Quality Online Monitoring and Analysis Platform. The annual incidence of newborn CH from October 1, 2014, to September 30, 2015, was collected from the Chinese Maternal and Child Health Surveillance Network. Temperature and toxic metal in wastewater in 2014 were also collected as covariates. Maternal exposure to O3 and NO2 in 1 µg/m3 level increment was positively associated with newborn CH, with an OR of 1.055 (95% CI 1.011, 1.102) and 1.097 (95% CI 1.019, 1.182) after adjusting for covariates completely. Compared with the lowest level of O3, maternal exposure to the 4th quartile of O3 was positively associated with newborn CH (OR 1.393, 95% CI 1.081, 1.794) after adjusting for covariates completely. And the 3rd and 4th quartiles of NO2 were associated positively with CH (OR 1.576, 95% CI 1.025, 2.424, and OR 1.553, 95% CI 0.999, 2.414, respectively) compared with the lowest level of NO2. By fitting the ROC curve, 93.688 µg/m3 in O3 might be used as cutoff to predict the incidence of newborn CH in China.

Unusual cause of congenital hypothyroidism in a term infant.

Both insufficient and excessive maternal iodine consumption can result in congenital hypothyroidism. In East Asian cultures, seaweed is traditionally consumed in high quantities by peripartum women as it is thought to improve lactation. We present a case of transient congenital hypothyroidism due to maternal seaweed consumption at a daily basis during pregnancy and lactation in a Dutch family without Asian background. This case highlights that even in families of non-Asian background, high maternal intake of iodine-rich seaweed occurs and can result in transient or permanent hyperthyrotropinemia in the neonate with risk of impaired neurodevelopmental outcome if untreated.

Maternal exposure to PM2.5 may increase the risk of congenital hypothyroidism in the offspring: a national database based study in China.

BACKGROUND: Maternal exposure to air pollution is related to fetal dysplasia. However, the association between maternal exposure to air pollution and the risk of congenital hypothyroidism (CH) in the offspring is largely unknown. METHODS: We conducted a national database based study in China to explore the association between these two parameters. The incidence of CH was collected from October 1, 2014 to October 1, 2015 from the Chinese Maternal and Child Health Surveillance Network. Considering that total period of pregnancy and consequently the total period of particle exposure is approximately 10 months, average exposure levels of PM2.5, PM10 and Air Quality Index (AQI) were collected from January 1, 2014 to January 1, 2015. Generalized additive model was used to evaluate the association between air pollution and the incidence of CH, and constructing receiver operating characteristic (ROC) curve was used to calculate the cut-off value. RESULTS: The overall incidence of CH was 4.31 per 10,000 screened newborns in China from October 1, 2014 to October 1, 2015. For every increase of 1 µg/m3 in the PM2.5 exposure during gestation could increase the risk of CH (adjusted OR = 1.016 per 1 µg/m3 change, 95% CI, 1.001-1.031). But no significant associations were found with regard to PM10 (adjusted OR = 1.009, 95% CI, 0.996-1.018) or AQI (adjusted OR = 1.012, 95% CI,0.998-1.026) and the risk of CH in the offspring. The cut-off value of prenatal PM2.5 exposure for predicting the risk of CH in the offspring was 61.165 µg/m3. CONCLUSIONS: The present study suggested that maternal exposure to PM2.5 may exhibit a positive association with increased risk of CH in the offspring. We also proposed a cut-off value of PM2.5 exposure that might determine reduction in the risk of CH in the offspring in highly polluted areas.

Maternal iodine excess: an uncommon cause of acquired neonatal hypothyroidism.

Background Excessive iodine exposure is an often overlooked cause of neonatal hypothyroidism. Case presentation We present an infant with iodine-induced hypothyroidism, which was detected at age 15 days by newborn screening. The infant's iodine excess resulted from maternal intake of seaweed soup both during and after pregnancy. Treatment included discontinuation of seaweed soup, temporary interruption of breastfeeding and short-term levothyroxine therapy. By age 4 months, the infant's hypothyroidism had resolved, and her growth and development were normal. Conclusions This case illustrates the importance of considering excess dietary iodine as a possible cause of hypothyroidism in infants.

Iodine-Induced Fetal Hypothyroidism: Diagnosis and Treatment with Intra-Amniotic Levothyroxine.

BACKGROUND: Iodine is necessary for fetal thyroid development. Excess maternal intake of iodine can cause fetal hypothyroidism due to the inability to escape from the Wolff-Chaikoff effect in utero. CASE REPORT: We report a case of fetal hypothyroid goiter secondary to inadvertent excess maternal iodine ingestion from infertility supplements. The fetus was successfully treated with intra-amniotic levothyroxine injections. Serial fetal blood sampling confirmed fetal escape from the Wolff-Chaikoff effect in the mid third trimester. Early hearing test and neurodevelopmental milestones were normal. CONCLUSION: Intra-amniotic treatment of fetal hypothyroidism may decrease the rate of impaired neurodevelopment and sensorineural hearing loss.

Perinatal hypothyroidism increases play behaviors in juvenile rats.

Thyroid hormones play an instrumental role in the development of the central nervous system. During early development, the fetus is dependent on maternal thyroid hormone production due to the dysfunction of its own thyroid gland. Thus, maternal thyroid dysfunction has been shown to elicit significant abnormalities in neural development, neurochemistry, and behavior in offspring. Previous reports have suggested that human maternal hypothyroidism may increase the chances of having children with autism spectrum disorder and attention-deficit/hyperactivity disorder. However, very few studies have evaluated social behaviors in animal models of perinatal hypothyroidism. To evaluate the possibility that hypothyroidism during development influences the expression one of the most commonly observed non-reproductive social behaviors, juvenile play, we used the validated rat model of perinatal hypothyroidism by methimazole administration (MMI; 0.025% in drinking water) from GD12-PD23. Control animals had regular drinking water. During adolescence (PD33-35), we tested subjects for juvenile play behavior by introducing them to a same-sex, unfamiliar (since weaning) littermate for 30min. Play behaviors and other behaviors (sleep, social contact, locomotion) were then scored. MMI-treated subjects played more than twice as much as control animals, and the increase in some behaviors was particularly dramatic in males. Locomotor and other affiliative social behaviors were unaffected. These data suggest that perinatal hypothyroidism may alter the organization of the neural networks regulating play behaviors, but not other social behaviors. Moreover, this implicates perinatal hypothyroidism as a potential etiological factor in the development of neurobehavioral disorders, particularly those characterized by heightened social interactions and impulsivity.

Exposure of Pregnant Mice to Perfluorobutanesulfonate Causes Hypothyroxinemia and Developmental Abnormalities in Female Offspring.

Perfluorobutanesulfonate (PFBS) is widely used in many industrial products. We evaluated the influence of prenatal PFBS exposure on perinatal growth and development, pubertal onset, and reproductive and thyroid endocrine system in female mice. Here, we show that when PFBS (200 and 500 mg/kg/day) was orally administered to pregnant mice (PFBS-dams) on days 1-20 of gestation; their female offspring (PFBS-offspring) exhibited decreased perinatal body weight and delayed eye opening compared with control offspring. Vaginal opening and first estrus were also significantly delayed in PFBS-offspring, and diestrus was prolonged. Ovarian and uterine size, as well as follicle and corpus luteum numbers, were reduced in adult PFBS-offspring. Furthermore, pubertal and adult PFBS-offspring exhibited decreases in serum estrogen (E2) and progesterone (P4) levels with the elevation of luteinizing hormone levels. Notably, decreases in serum total thyroxine (T4) and 3,3', 5-triiodothyronine (T3) levels were observed in fetal, pubertal, and adult PFBS-offspring in conjunction with slight increases in thyroid-stimulating hormone (TSH) and thyrotropin-releasing hormone levels. In addition, PFBS-dams exhibited significant decreases in total T4 and T3 levels and free T4 levels and increases in TSH levels, but no changes in E2 and P4 levels. These results indicate that prenatal PFBS exposure (≥200 mg/kg/day) causes permanent hypothyroxinemia accompanied by deficits in perinatal growth, pubertal onset, and reproductive organ development in female mice.

[Iodinated contrast in pregnant women and neonatal thyroid function]. / Injection de produit de contraste iodé en cours de grossesse et fonction thyroïdienne néonatale.

OBJECTIVES: There is a theoretical risk for neonatal hypothyroidism after prenatal exposure to iodinated contrast media. Current recommendations are in favour of neonatal thyroid function assessment. Our aim was to check if recommendations were observed, and if neonatal evaluation demonstrated anomalies. METHODS: Over the period from 01/01/2010 to 01/08/2015, maternal and newborn records were retrospectively reviewed. All pregnant women who underwent a computed tomography and their newborns were included. We collected thyroid-stimulating hormone (TSH), thyroxine (T4) and tri-iodothyronine (T3) levels. RESULTS: A total of 101 maternal and newborn records were reviewed. Mean gestational age at CT scan was 29.3±7.2 weeks. The mean dose of total iodine administered was 82.6±19.1mL. Only 21 newborns had a biological analysis (20.8%). All newborns had normal TSH and T4 levels at birth. Only 7 newborns had a T3 level above the upper threshold value, but according to expert opinion none have been considered pathological. CONCLUSION: Our study revealed that recommendations for neonatal thyroid function assessment after prenatal exposure to iodinated contrast media were not observed. This exposure seemed unlikely to have an important effect on thyroid function at birth.

The Effect of Congenital and Postnatal Hypothyroidism on Depression-Like Behaviors in Juvenile Rats.

OBJECTIVE: The aim of this study was to investigate depression-like behaviors of juvenile rats with congenital and postnatal hypothyroidism. METHODS: Twenty-seven newborn rat pups were used. First, 6-month-old Wistar Albino female rats were impregnated. Methimazole (0.025% wt/vol) was given to dam rats from the first day of pregnancy until postnatal 21 days (P21) to generate pups with congenital hypothyroidism (n=8), whereas in the postnatal hypothyroidism group (n=10), methimazole was given from P0 to P21. In the control group (n=9), dam rats were fed ad libitum and normal tap water. Offspring were fed with breast milk from their mothers. The behavioral parameters were measured with the juvenile forced swimming test (JFST). The procedure of JFST consisted of two sessions in two consecutive days: the 15-minute pre-test on day 1 and the 5-minute test on day 2. RESULTS: Increased immobility and decreased climbing duration were observed in both congenital and postnatal hypothyroidism groups. Decreased swimming duration was detected in the postnatal hypothyroidism group. Both hypothyroidism groups had a lower body weight gain compared with the control group, while the congenital hypothyroidism group had the lowest body weight. CONCLUSION: Our results showed that hypothyroidism had negative effects on depression-like behavior as well as on growth and development. Both congenital and postnatal hypothyroidism caused an increase in immobility time in JFST. New studies are required to understand the differing results on depression-like behavior between congenital and postnatal hypothyroidism.

Effect of Fetal Hypothyroidism on Cardiac Myosin Heavy Chain Expression in Male Rats / O Efeito de Hipotireoidismo Fetal na Expressão da Miosina Cardíaca de Cadeia Pesada em Ratos Macho

Abstract Background: Thyroid hormone deficiency during fetal life could affect the cardiac function in later life. The mechanism underlying this action in fetal hypothyroidism (FH) in rats has not been elucidated thus far. Objective: The aim of this study is to evaluation the effect of FH on cardiac function in male rats and to determine the contribution of α-myosin heavy chain (MHC) and β-MHC isoforms. Methods: Six pregnant female rats were randomly divided into two groups: The hypothyroid group received water containing 6-propyl-2-thiouracil during gestation and the controls consumed tap water. The offspring of the rats were tested in adulthood. Hearts from the FH and control rats were isolated and perfused with langendroff setup for measuring hemodynamic parameters; also, the heart mRNA expressions of α- MHC and β-MHC were measured by qPCR. Results: Baseline LVDP (74.0 ± 3.1 vs. 92.5 ± 3.2 mmHg, p < 0.05) and heart rate (217 ± 11 vs. 273 ± 6 beat/min, p < 0.05) were lower in the FH rats than controls. Also, these results showed the same significance in ±dp/dt. In the FH rats, β-MHC expression was higher (201%) and α- MHC expression was lower (47%) than control. Conclusion: Thyroid hormone deficiency during fetal life could attenuate normal cardiac functions in adult rats, an effect at least in part due to the increased expression of β-MHC to α- MHC ratio in the heart.

Resumo Fundamento: Deficiência de hormônio da tireoide durante vida fetal pode afetar a função cardíaca no futuro. O mecanismo subjacente dessa ação em hipotireoidismo fetal (HF) em ratos ainda não tem explicação. Objetivo: O objetivo desse estudo é avaliar o efeito de HF na função cardíaca em ratos macho e determinar a contribuição da α-miosina de cadeia pesada (α-MCP) e de isoformas β-MCP. Métodos: Seis ratos fêmea gestantes foram aleatoriamente divididas em dois grupos. O grupo do hipotireoidismo recebeu água contendo 6-propil-2-tiouracil durante a gestação, e os ratos no grupo de controle receberam água de torneira. Os filhotes dos ratos foram testados quando atingiram idade adulta. O coração dos ratos HF e controle foram isolados e submetidos a perfusão pelo método de Langendorff para medição de parâmetros hemodinâmicos. Também foram medidas as expressões de mRNA do coração de α-MCP e β-MCP por qPCR. Resultados: PVED de base (74,0 ± 3,1 vs. 92,5 ± 3,2 mmHg, p < 0,05) e pressão arterial (217 ± 11 vs. 273 ± 6 batidas/min, p < 0,05) mostraram-se mais baixas em ratos HF do que em ratos controle. Além disso, esses resultados mostraram a mesma significância em ±dp/dt. Em ratos HF, a expressão de β-MCP foi mais alta (201%) e a de α-MCP foi mais baixa (47%) do que em ratos controle. Conclusão: Deficiência de hormônio da tireoide durante a vida fetal pode enfraquecer funções cardíacas normais em ratos adultos, efeito devido em parte à expressão aumentada de β-MCP em relação a α-MCP no coração.

Effect of Fetal Hypothyroidism on Cardiac Myosin Heavy Chain Expression in Male Rats.

BACKGROUND: Thyroid hormone deficiency during fetal life could affect the cardiac function in later life. The mechanism underlying this action in fetal hypothyroidism (FH) in rats has not been elucidated thus far. OBJECTIVE: The aim of this study is to evaluation the effect of FH on cardiac function in male rats and to determine the contribution of α-myosin heavy chain (MHC) and ß-MHC isoforms. METHODS: Six pregnant female rats were randomly divided into two groups: The hypothyroid group received water containing 6-propyl-2-thiouracil during gestation and the controls consumed tap water. The offspring of the rats were tested in adulthood. Hearts from the FH and control rats were isolated and perfused with langendroff setup for measuring hemodynamic parameters; also, the heart mRNA expressions of α- MHC and ß-MHC were measured by qPCR. RESULTS: Baseline LVDP (74.0 ± 3.1 vs. 92.5 ± 3.2 mmHg, p < 0.05) and heart rate (217 ± 11 vs. 273 ± 6 beat/min, p < 0.05) were lower in the FH rats than controls. Also, these results showed the same significance in ±dp/dt. In the FH rats, ß-MHC expression was higher (201%) and α- MHC expression was lower (47%) than control. CONCLUSION: Thyroid hormone deficiency during fetal life could attenuate normal cardiac functions in adult rats, an effect at least in part due to the increased expression of ß-MHC to α- MHC ratio in the heart.

Perfluoroalkyl substances in serum from South Korean infants with congenital hypothyroidism and healthy infants--Its relationship with thyroid hormones.

Exposure to perfluoroalkyl substances (PFASs) may disrupt thyroid systems, though the specific effects of PFASs are still being elucidated. Since research regarding exposure in infants is highly limited, our goal was to investigate exposure levels of PFASs in infant serum and correlate these levels with thyroid hormones (THs). This was accomplished by analyzing 16 PFASs in sera from a case group of infants with congenital hypothyroidism and a control group. Total PFAS exposure level was 2.63-44.7ng/mL in the case group and 2.44-22.4ng/mL in the control group. Concentrations of serum perfluorooctanoic acid (PFOA, p<0.01), perfluorononanoic acid (PFNA, p<0.001), perfluorooctanoic acid (PFDA, p<0.005), and perfluoroundecanoic acid (PFUnDA, p<0.005) were significantly higher in the case group than the control group. Levels of certain PFASs (PFOA, perfluorotridecanoic acid [PFTrDA], and perfluorohexane sulfonate [PFHxS]) showed a moderate to weak correlation with relevant antibodies.

Mild Thyroid Hormone Insufficiency During Development Compromises Activity-Dependent Neuroplasticity in the Hippocampus of Adult Male Rats.

Severe thyroid hormone (TH) deficiency during critical phases of brain development results in irreversible neurological and cognitive impairments. The mechanisms accounting for this are likely multifactorial, and are not fully understood. Here we pursue the possibility that one important element is that TH affects basal and activity-dependent neurotrophin expression in brain regions important for neural processing. Graded exposure to propylthiouracil (PTU) during development produced dose-dependent reductions in mRNA expression of nerve growth factor (Ngf) in whole hippocampus of neonates. These changes in basal expression persisted to adulthood despite the return to euthyroid conditions in blood. In contrast to small PTU-induced reductions in basal expression of several genes, developmental PTU treatment dramatically reduced the activity-dependent expression of neurotrophins and related genes (Bdnft, Bdnfiv, Arc, and Klf9) in adulthood and was accompanied by deficits in hippocampal-based learning. These data demonstrate that mild TH insufficiency during development not only reduces expression of important neurotrophins that persists into adulthood but also severely restricts the activity-dependent induction of these genes. Considering the importance of these neurotrophins for sculpting the structural and functional synaptic architecture in the developing and the mature brain, it is likely that TH-mediated deficits in these plasticity mechanisms contribute to the cognitive deficiencies that accompany developmental TH compromise.

Protective effects of GM-CSF in experimental neonatal hypothyroidism.

Hypothyroidism induced by methimazole (MMI), has a negative impact on the postnatal development. Neonatal Granulocyte Macrophage-Colony Stimulating Factor [GM-CSF; 50µg/kg, intramuscular injection at postnatal day (PND) 17] had been tested to ameliorate the effects of MMI [0.05%, (weight per volume; w/v), intraperitoneal injection at PND 15]-induced hypothyroidism in Wistar rats. The hypothyroid conditions due to the administration of MMI produced inhibitory effects on neonatal serum thyroxine (T4), 3,5,3'-triiodothyronine (T3), neutrophil count in bone marrow and blood, cerebellar glutathione (GSH) and acetylcholinesterase (AchE), although it induced stimulatory actions on serum thyrotropin (TSH), growth hormone (GH), insulin growth factor-II (IGF-II), tumor necrosis factor alpha (TNF-α), and cerebellar malondialdehyde (MDA) at PND 19. The treatment with GM-CSF could reverse the depressing and stimulating effects of MMI on these markers except for cerebellar AchE where its enhancement was non-significant (P>0.05) at tested PND. Thus, neonatal GM-CSF may be responsible for suppressing autoimmune responses and preventing hypothyroidism.

Undiagnosed congenital hypothyroidism in a newborn treated with dopamine infusion.

Medications administered during the neonatal period may mask the diagnosis of congenital hypothyroidism. Herein, we report a case of undiagnosed congenital hypothyroidism while the infant was on treatment with dopamine. Given the inhibitory effect of dopamine on thyroid-stimulating hormone, a high index of suspicion for potential congenital hypothyroidism is needed in such neonates.

MiR-124 effect in neurons apoptosis in newborn rat with thyroid hypofunction.

Congenital thyroid hypofunction can cause a variety of developmental disorders. Hippocampus is an important structure participating in the cognitive activities. Neural function damage is able to induce hippocampal neuron apoptosis. As a miRNA expressed specifically and abundantly in brain tissue, miR-124 has protective effect to neuron apoptosis caused by cerebral apoplexy. However, its role in neuron apoptosis caused by thyroid hypofunction is still unclear. The rats were divided into four groups including normal group, thyroid hypofunction group, miR-124 negative control group, and miR-124 mimics group. Propylthiouracil (50 mg/d) was injected to the stomach to the rats with 15 d pregnancy till the newborn rats were born. Inducing the thyroid hypofunction rat model and then injecting miR-124 mimics to ventricle. Serum TSH, FT3 and FT4 were detected to confirm the model. Immunohistochemistry was carried out to calculate neuron number. Tunel assay was used to detect neuron apoptosis. Western blot was applied to detect apoptosis related protein Caspase-3, Bcl-2 and Bax expression. After brain injection miR-124 mimics, hippocampal neuron number and morphology both improved in 15 d newborn mice compared with thyroid hypofunction group. Tunel staining found positive neurons reduced, which indicated that miR-124 can inhibit hippocampal neuron apoptosis in thyroid hypofunction rats. Further Western blot results revealed that apoptosis inhibition might be related to down-regulating activated Caspase-3 and Bax levels, and up-regulating tumor-suppressor gene Bcl-2 expression. MiR-124 can protect neuron apoptosis in thyroid hypofunction rat.

Iodine-induced hypothyroidism in full-term infants with congenital heart disease: more common than currently appreciated?

CONTEXT: Iodine is a micronutrient essential for thyroid hormone synthesis. Thyroid hormone is critical for normal neurocognitive development in young infants, and even transient hypothyroidism can cause adverse neurodevelopmental outcomes. Both iodine deficiency and excess can cause hypothyroidism. Although iodine-induced hypothyroidism is well recognized in premature infants, full-term neonates have received less attention. Infants with congenital heart disease (CHD) are commonly exposed to excess iodine from administration of iodinated contrast agents during cardiac catheterization as well as topical application of iodine-containing antiseptics and dressings; hence, this is a vulnerable population. OBJECTIVE: We report three cases of iodine-induced hypothyroidism in full-term neonates with CHD after cardiac angiography and topical application of iodine-containing antiseptics and dressings in the operative setting. RESULTS: Three neonates with CHD and normal thyroid function at birth developed hypothyroidism after exposure to excess iodine. Two of these infants had transient hypothyroidism, and one had severe hypothyroidism requiring ongoing thyroid replacement therapy. All infants were asymptomatic, with hypothyroidism detected incidentally in the inpatient setting due to repeat newborn screening mandated by the long duration of hospitalization in these infants. CONCLUSIONS: Iodine-induced hypothyroidism may be under-recognized in infants with CHD exposed to excess iodine. Systematic monitoring of thyroid function should be considered to avoid potential long-term adverse neurodevelopmental effects of even transient thyroid dysfunction in this susceptible population.

Reproductive toxicity and thyroid effects in Sprague Dawley rats exposed to low doses of ethylenethiourea.

Ethylenethiourea (ETU) is the common metabolite of the widely used ethylenebisdithiocarbamate fungicides. It is identified as Endocrine Disruptor given its ability to interfere with thyroid hormone biosynthesis by inhibiting thyroid peroxidase activity. As far as we know, no studies have been performed to assess potential effects of ETU exposure at low dose levels, i.e. below the established LOAEL and NOAEL, during critical phases of development. Therefore, the aim of the present study was to verify the short- and long-term effects on thyroid function, reproduction and development of oral exposure to ETU levels comparable to and lower than LOAEL/NOAEL in rats. Sixty dams were treated daily by gavage during pregnancy and lactation with 0, 0.1, 0.3, 1.0 mg/kg bw per day of ETU. F1 generation was similarly treated from weaning to sexual maturity. Thyroid biomarkers were analyzed in dams and in offspring. Reproductive biomarkers were analyzed in F1 rats. For the first time this study has demonstrated reproductive toxicity and hypothyroidism at a lower than LOAEL dose exposure in pregnant dams and F1 generation. Our data suggest that even low doses of ETU can interfere with thyroid homeostasis and reproductive hormone profile if exposure starts in critical stages of development.

Brain derived neurotrophic factor and oxidative stress index in pups with developmental hypothyroidism: neuroprotective effects of selenium.

Thyroid hormones (THs) are crucial for growth and development and particularly brain development. The present study was carried out to investigate the brain derived neurotrophic factor (BDNF) and Oxidative stress index (OSI) in the brain of pups born to dams with methimazole (MMI) induced hypothyroidism. Also, to elucidate the effectiveness of selenium (Se) in ameliorating the brain damaging effects induced by maternal hypothyroidism. Our results reveled that plasma free T3 (FT3), free T4 (FT4), growth hormone (GH) were significantly decreased while plasma thyroid stimulating hormone (TSH) was significantly increased in the pups. BDNF level significantly decreased while OSI significantly increased in both the hippocampus and cerebellum in pups born to hypothyroid dams. Se supplementation significantly alleviated the levels of these parameters. The biochemical modifications were confirmed histologically with the abnormal development of the hippocampus and cerebellum and partial reversal of these effects with Se supplementation. We concluded that reduced hippocampal and cerebellar BDNF levels and increment of oxidative stress during early development may contribute to the adverse neurodevelopmental effects of hypothyroidism during pregnancy. Also, Se is an important neuroprotective element that may be used as a dietary supplement against brain damage induced by hypothyroidism.