Is Age a Risk Factor for Hypothyroidism in Pregnancy? An Analysis of 5223 Pregnant Women

CONTEXT: The guidelines of American Thyroid Association from 2011 include age over 30 as one of the risk factors for hypothyroidism in pregnancy. OBJECTIVE: Our objective was to verify whether age increases the risk of autoimmune thyroid disease in pregnancy. DESIGN: We performed a cross-sectional study in 2006-2008 with laboratory assessment in a single center using primary care gynecological ambulances in cooperation with a referral center. PATIENTS: The study included 5223 consecutive pregnant women in gestational wk 9-12. MAIN OUTCOME MEASURE: We assessed the occurrence of pathological serum concentrations of TSH and/or antibodies against thyroperoxidase (TPOAb) with regard to age. Reference interval for TSH was 0.06-3.67 mU/liter; the upper cutoff value for TPOAb was 143 kU/liter. RESULTS: Overall, 857 women (16.4%) were positively screened. Of these, 294 (5.63%) had TSH elevation, 146 (2.79%) had TSH suppression, 561 (10.74%) were TPOAb positive, and 417 (7.98%) were euthyroid and TPOAb positive. The average age of women was 31.1 yr. The prevalence of hypothyroidism was 5.5 and 5.8% in women aged 30 or older and those under 30 yr, respectively (P value nonsignificant). Using a logistic regression model, we didn't find any significant association between age and serum TSH suppression, TSH elevation, or TPOAb positivity (P = 0.553, P = 0.680, and P = 0.056, respectively) or between age and TSH elevation with TPOAb positivity (P = 0.967). In a subgroup analysis of risk factors for hypothyroidism in 132 hypothyroid women, addition of age 30 or older increased the proportion of women identified in a case-finding screening strategy from 55.3 to 85.6%. CONCLUSIONS: Prevalence of autoimmune thyroid disease does not increase with age in pregnant women; however, addition of age 30 or over to the case-finding screening strategy may substantially improve its efficiency due to a larger number of women screened

Association between low levels of Mannan-binding lectin and markers of autoimmune thyroid disease in pregnancy.

Functional deficiency of mannan-binding lectin (MBL) has been associated with adverse pregnancy outcome. Adverse events during pregnancy have also been described in women with autoimmune thyroid diseases (AITD), and thyroid hormones have been shown to influence serum levels of MBL. Therefore, the aim of this study was to analyse the impact of MBL-deficiency on the outcome of pregnancy in relation to the presence of AITD. Almost one year after delivery, we assessed serum MBL levels and MBL2-genotypes in 212 women positively screened for AITD in pregnancy. In 103 of these women, we could also measure MBL levels in frozen serum samples from the 9-12(th) gestational week, obtaining 96 pairs of MBL values (pregnancy vs. follow-up). As controls, 80 sera of pregnant women screened negatively for AITD were used. MBL2-genotyping was performed using multiplex PCR. Women with thyroid dysfunction and/or thyroid peroxidase antibodies (TPOAb) had lower MBL levels during pregnancy than controls, (3275 vs. 5000 ng/ml, p<0.05). The lowest levels were found in women with elevated thyroid-stimulating hormone (TSH) levels in the absence of TPOAb (2207 ng/ml; p<0.01 as compared to controls). MBL2 genotype distribution did not differ between subgroups. At a median follow-up period of 17 months (range: 3-78 months) after delivery, median MBL level had decreased further to 1923 ng/ml (p<0.0001) without significant changes in TSH. In an explorative survey, functional MBL-deficiency was neither linked to a history of spontaneous abortion, nor other obstetric complications, severe infections throughout life/pregnancy or antibiotics use in pregnancy. In conclusion, hypothyroidism during pregnancy is associated with decreased MBL levels, and the levels decreased further after delivery

The production of mannan-binding lectin is dependent upon thyroid hormones regardless of the genotype : a cohort study of 95 patients with autoimmune thyroid disorders

Complement mannan-binding lectin (MBL) deficiency is associated with increased susceptibility to infections and autoimmune diseases. Previous studies suggested that the production of MBL is stimulated by thyroid hormones. The aim of our study was to investigate this association in patients with autoimmune thyroid diseases (AITD). Serum levels of MBL and parameters of the thyroid function were determined in 62 patients with Hashimoto's thyroiditis, 33 with Graves' disease and 47 blood donors. Follow-up measurements were performed after 6 to 24 months. MBL2 genotypes were determined using multiplex PCR and compared to 359 healthy Czech individuals. Serum levels of MBL tightly correlated with thyroid hormones, leading to strongly increased MBL levels in hyperthyroidism and decreased levels in hypothyroidism. With normalization of the thyroid function during follow-up, MBL levels decreased or increased respectively. The observed correlations were not due to MBL polymorphisms since the frequency of MBL2 polymorphisms in AITD patients was not different from the general population. We conclude that AITD are not associated with MBL polymorphisms. However, the MBL production is strongly dependent on thyroid function, regardless of the genotype

Prevalence of atopy, asthma and allergy with regard to MBL status.

<p>–1000 ng/ml; high: >1000 ng/ml. MBL2 genotypes represent the allelic variations associated with low, intermediate or high MBL levels. Statistical analysis was performed using the Chi-square test. Serum MBL levels are regarded as low if they are <100 ng/ml; intermediate: 100</p

MBL levels in pregnant women with and without autoimmune thyroid disorders.

<p>Overall, 103 women tested positively in a screening for AITD performed between the 9^th and 12^th gestational weeks (grouped together in the left column). They were found to be positive for TPOAb in 86 cases (of these, 12 had TSH elevation, 6 had TSH suppression; the rest was euthyroid). Of the 17 TPOAb-negative ones, 10 had TSH elevation and 7 had TSH suppression. Eighty women were negative for both parameters (right column). Horizontal bars represent median values of serum MBL.</p

Clinical characteristics of the study group.

<p> AITD: autoimmune thyroid disorders. TPOAb: antibodies against thyroperoxidase. The data were obtained from questionnaires filled by the participating women.</p

Serum MBL levels in pregnant women screened for AITD.

<p>–1000 ng/ml and high: >1000 ng/ml. Low serum MBL levels: <100 ng/ml; intermediate: 100</p

Serum levels of MBL and thyroid parameters in pregnant women screened for autoimmune thyroid disorders in the 9-12^th gestational wks.

<p>^*(p<0.05), ^**(p<0.01), ^***(p<0.001) (Mann Whitney test). Positivity in screening: TSH<0.06 or >3.67 mIU/l and/or TPOAb>143 kU/l. TSH: thyroid stimulating hormone; FT4: free thyroxine; TPOAb: antibodies against thyroperoxidase. All 212 women included provided a blood sample for MBL analysis after delivery. In 103women, MBL could also be measured in a sample frozen at screening in pregnancy, which summed up to 96 pairs (pregnancy vs. follow-up). Statistical significances of comparison between values in positively vs. negatively screened women are marked by </p