An Epidemiology Study On The Impact Of Maternal Thyroid Autoimmune During Pregnancy On Neuropsychological Development Of Their Offspring

·英文论著摘要一·An Prospective Study on the Impact of Maternal Thyroid Peroxidase Antibodies Positive During the First Trimester on Neuropsychological Development of Their OffspringObjectivesIt was noticed that maternal with elevated titres of thyroid peroxidase antibodies (TPOAb) during the third trimester may impact cognitive function in their offspring. The aim of the study was to investigate the effects of maternal with elevated titers of TPOAb during the first trimester on neuropsychological development of their offspring at 20-30 months.MethodsEpidemiological investigation was performed in ten hospitals in north-east China, from February 2006 to November 2006.1761 pregnant women were investigated and received blood tests for thyrotropin, free thyroxine and anti-thyroperoxidase antibody. Forty-nine pregnant women with TPOAb>50 IU/mL were selected and studied. Pregnant women with TPOAb elevated were divided into two subgroups:group TPOAb-A1 (50 IU/mL300 IU/mL,30 cases). Thirty euthyroid and TPOAb-negative women, matched for gestational age from the same cohort were selected as controls. Intellectual and motor development score evaluations were performed on the children from the pregnancy associated with the thyroid function test at 20-30 months of age.ResultsChildren of women in TPOAb-A1 and TPOAb-A2 subgroups'got mean intelligence scores of 2.27 and 6.67 points, respectively, which were lower than those of the control groups (P= 0.329 and 0.002 respectively); mean motor scores were 1.78 and 7.00 points lower than those of the controls (P= 0.430 and 0.009 respectively). One-way ANOVA analysis in TPOAb-A1, TPOAb-A2 and control group revealed that differences of TPOAb affect intelligence and motor scores (F= 4.150, P=0.008 and F = 3.258, P= 0.024 respectively).In addition, Ordinal logistic regression revealed that Odds ratios (ORs) of maternal serum TPOAb>300IU/mL, compared with controls, were associated with decreased MDI and PDI scores ORs 3.77 and 6.32 (95% CI 1.426～9.95 P=0.007,95% CI 2.31～17.287 P=0.000). Intelligence scores and motor scores negatively correlated with TPOAb levels (r=-0.380, P= 0.001 and r=-0.410, P<0.001 respectively).ConclusionIntellectual and motor development of children at 20-30 months of age is associated with maternal elevated titres of TPOAb during first trimester and with the titer of TPOAb elevated the effect of Intellectual and motor development of children is difference. Maternal elevated titres of TPOAb were statistically significant predictors of lower motor and intellectual development at 20-30 months. ·英文论著摘要二·Abnormalities of maternal thyroid function during pregnancy affect neuropsychological development of their children at 25-30 monthsObjectivesTo examine the relationship between specific thyroid abnormalities (subclinical hypothyroidism, hypothyroxinaemia or elevated thyroid peroxidase antibody titres) in women during pregnancy and the subsequent neuropsychological development of their offspringMethodsSerum was collected from 1268 women at 16-20 weeks of gestation and thyroid stimulating hormone (TSH), total thyroxine TT4, free thyroxine FT4, and Thyroid peroxidase antibodies (TPOAb) levels were measured. Thyroid function reference ranges specific for pregnancy were used to screen for thyroid abnormalities. Patients with isolated subclinical hypothyroidism (18 cases), hypothyroxinaemia (19 cases), and those who were euthyroid patients with elevated titres of TPOAb (34 cases) were identified. One hundred and forty two euthyroid and TPOAb-negative women matched for gestational age from the same cohort were selected as controls. Measurements: Intellectual and motor development score evaluations were performed on the children from the pregnancies at 25-30 months of age.ResultsChildren of women with subclinical hypothyroidism, hypothyroxinemia and elevated TPOAb titres had mean intelligence scores 8.88,9.30 and 10.56 points lower than those of the control group (P=0.008 P=0.004 and P=0.001 respectively); mean motor scores were 9.98,7.57 and 9.03 points lower than those of the controls (P<0.001 P=0.007 and P<0.001 respectively (t-test)). Unconditional multivariate logistic regression analysis showed that increased maternal serum TSH, decreased maternal serum TT4, and elevated maternal TPOAb titres were separately associated with lower intelligence scores (ORs 15.63,12.98, and 6.69 respectively) and poorer motor scores (ORs 9.23,5.52, and 8.25, respectively).ConclusionIntellectual and motor development of children at 25-30 months of age is separately associated with abnormalities of maternal thyroid at 16-20 weeks gestation. Maternal subclinical hypothyroidism, hypothyroxinaemia or euthyroidism with elevated TPOAb titres were all statistically significant predictors of lower motor and intellectual development at 25-30 months. ·英文论著摘要三·A novel animal model of Graves disease in Lewis rats immunized by thyroglobulinObjectivesGraves'disease (GD) and Hashimoto's thyroiditis (HT) are autoimmune thyroid diseases (AITD) that occur as a result of an immune response directed against the thyroid gland. Patients with Graves' disease produce autoantibodies against Tg and TPO and it is characterized by development of IgG class autoantibodies to the generation of autoantibodiesm against the TSH receptor (TSHR) causes continuous stimulation of the thyroid gland and hyperthyroidism. In contrast, HT is also characterized by serum autoantibodies against thyroglobulin (Tg) and thyroid peroxidase (TPO), and histologically by diffuse enlargement of the thyroid gland, lymphocytic infiltration. Experimental autoimmune thyroiditis (EAT) in mice as a model for Hashimoto's thyroiditis has been induced using mouse thyroglobulin (mTg) combined with complete Freund's adjuvant(CFA) or bacterial lipopolysaccharide. However, we found serum free T3 and free T4 levels were significantly higher than the control during producing experimental autoimmune thyroiditis in Lewis rat by immunizing with Tg, and recently two researcher also found this during immunizing mice with Tg, So we have produced Graves'disease.model in Lewis rat by immunizing them with Tg in order to researching the resean of hyperthyroidism and the mechanism of Graves'disease.MethodsAll rat were 8 weeks old at the beginning of the experiments. Saline was emulsified with the same volume of complete Freund's adjuvant (Sigma-Aldrich Chemical).The first time complete Freund's adjuvant 0.25ml+0.2mgTg/rat. (0.5ml emulsion)was injected into the soleus muscle and two weeks later from the second time using incomplete Freund's adjuvant 0.25ml+0.2mgTg/mouse(0.5ml emulsion) was injected into the soleus muscle once every 1 weeks. Booster immunization was 8 times (total 8 weeks). Thyroid function and antibody were estimated by measuring serum total T4 T3, TPOAb and TgAb at the Booster immunization 2,4,6,8 weeks. And at Booster immunization 4 or 8 weeks, rat were weighed and anesthetize, thyroid tissues were removed and the raletive thyroid weight were measured, the severity of lymphocytic infiltration in thyroids was observed using HE-stained thyroid sections.Thyroid 131I uptake rate were measured And stimulating TSHRAb activity was measured using rTSHR-transfected CHO cells.ResultsEight weeks after the booster immunization, we examined their thyroid functions, histology of the glands, and presence of autoantibodies in the sera and the rate of thyroid iodide uptake.The results showed that the mean serum total T3 and total T4 levels of the immunized rat were significantly (P<0.001) higher than those of the controls. And the mean serum TPOAb and TgAb levels of the immunized rat were significantly elevated. Thyroid glands of the rat immunized with thyroglobulin (Tg) are diffusely enlarged and having high iodide uptake activity compared with those of the Freund's adjuvant-injected mice. Microscopic examination of the tissues revealed that the height of the epithelial cells in the immunized rat was significantly taller than the control.Lewis rat shown immunized with Tg had high 131I uptake activity of the thyroid, and positive thyroid-stimulating antibody activity.ConclusionDiffuse goiter, thyrotoxicosis, high iodide uptake activity, and positive thyroid-stimulating antibody are the characteristics of Graves' disease.These results suggest that immunization with Tg induces Graves'-like disease in mice and that our methods will provide a new animal model of Graves' disease...