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Relationship between anti-thyroid peroxidase antibody positivity and pregnancy-related and fetal outcomes in Euthyroid women: a single-center cohort study.

ABSTRACT: BACKGROUND:Thyroid autoimmunity (TAI) and subclinical hypothyroidism (SCH) have been associated with poor pregnancy and fetal outcomes. However, whether euthyroid women with anti-thyroid peroxidase antibody (TPOAb) positivity have a higher risk of poor pregnancy and fetal outcomes is debatable. Therefore, this study aimed to investigate the association between TPOAb positivity and pregnancy-related and fetal outcomes in euthyroid women. METHODS:In total, 938 pregnant women participated in this prospective cohort study. The euthyroid group included 837 pregnant women and the TPOAb-positive group included 101 euthyroid pregnant women. Serum TPOAb, thyroglobulin antibody (TGAb), thyroid-stimulating hormone (TSH), and free thyroxine (FT4) levels were assessed. Pregnancy and fetal outcomes included gestational diabetes mellitus, spontaneous abortion, premature rupture of membranes, hypertensive disorders of pregnancy, preterm birth, fetal distress, low birth weight, fetal macrosomia, and small for gestational age infant. RESULTS:Logistic regression analysis showed TPOAb positivity was not associated with an increased risk of poor pregnancy or fetal outcomes in euthyroid women. However, TPOAb-positive euthyroid women pregnant with a female fetus were independently associated with preterm births (OR: 4.511, 95% CI: 1.075-18.926) after adjustment for potential confounding factors. CONCLUSIONS:TPOAb positivity was not found to be associated with poor pregnancy-related or fetal outcomes in euthyroid women. However, in euthyroid women with a female fetus, TPOAb positivity was strongly associated with preterm births. The risk of preterm birth in the euthyroid women with TPOAb positivity should be emphasized in clinical practice. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT02966405 . Registered on October 24th 2016 - Retrospectively registered.

SUBMITTER: Yuan N

PROVIDER: S-EPMC7449005 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Relationship between anti-thyroid peroxidase antibody positivity and pregnancy-related and fetal outcomes in Euthyroid women: a single-center cohort study.

Yuan Ning N Sun Jianbin J Li Zhi Z Chai Sanbao S Zhang Xiaomei X Ji Linong L

BMC pregnancy and childbirth 20200826 1

<h4>Background</h4>Thyroid autoimmunity (TAI) and subclinical hypothyroidism (SCH) have been associated with poor pregnancy and fetal outcomes. However, whether euthyroid women with anti-thyroid peroxidase antibody (TPOAb) positivity have a higher risk of poor pregnancy and fetal outcomes is debatable. Therefore, this study aimed to investigate the association between TPOAb positivity and pregnancy-related and fetal outcomes in euthyroid women.<h4>Methods</h4>In total, 938 pregnant women partici ...[more]

PMID: 32847542

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Project description:BACKGROUND:Thyroid autoimmunity (TAI) - the presence of anti-thyroid peroxidase and/or anti-thyroglobulin antibodies - affects 8-14% of reproductively-aged women. It is hotly debated whether TAI adversely affects IVF/ICSI outcomes. This systematic review and meta-analysis evaluated the relationship between thyroid autoimmunity (TAI) and IVF/ICSI outcomes, both overall and amongst euthyroid women of known age using strict criteria for grouping pregnancy outcomes. METHODS:The review was registered with PROSPERO: CRD42019120947. Searches were undertaken in MEDLINE, EMBASE, Web of Science and Cochrane Database from Inception-March 2020. Primary outcomes were clinical pregnancy rate, clinical miscarriage rate, biochemical pregnancy loss, livebirth rate per-cycle and live birth rate per clinical pregnancy (CP). RESULTS:14 studies were included in the meta-analysis. Compared with women who tested negative for thyroid autoantibodies (TAI-), there was no significant difference in clinical pregnancy rate overall (OR 0.86; 95%CI [0.70, 1.05]; P?=?0.14; 11 studies; I2 =?29.0%), or in euthyroid women (OR 0.88; 95%CI [0.69, 1.12]; P?=?0.29; 10 studies; I2 =?32.0%). There was also no significant difference in clinical miscarriage rate overall (OR 1.04; 95%CI [0.52, 2.07]; P?=?0.908; 8 studies; I2 =?53%), or in euthyroid women (OR 1.18; 95%CI [0.52, 2.64]; P?=?0.69; 7 studies; I2 =?54%). There was no significant difference in biochemical pregnancy loss (OR 1.14; 95%CI [0.48, 2.72]; P?=?0.769; 4 studies; I2?=?0.0%), live birth rate per cycle (OR 0.84; 95%CI [0.67, 1.06]; P?=?0.145; I2 =?1.7%), live birth rate per clinical pregnancy (OR 0.67; 95%CI [0.28, 1.60]; P?=?0.369; I2 =?69.2%), both overall and in euthyroid women as all studies included consisted of euthyroid women only. There was also no significant difference in number of embryos transferred, number of oocytes retrieved, mean maternal age or TSH levels overall or in euthyroid women. CONCLUSION:The findings of the present study suggest that thyroid autoimmunity has no effect on pregnancy outcomes in euthyroid women alone, or in euthyroid women and women with subclinical hypothyroidism.

Project description:Background: Women with hypothyroidism before pregnancy often require an increase in their levothyroxine dosage to maintain a euthyroid state during pregnancy. The objectives of this study were to investigate: (i) the frequency and distribution of thyrotropin (TSH) testing and levothyroxine dosage adjustment by gestational age, (ii) the magnitude of levothyroxine increase by the underlying etiology of hypothyroidism, and (iii) the relationship of overtreatment or undertreatment during pregnancy with adverse pregnancy outcomes among women using thyroid replacement before pregnancy. Methods: A retrospective cohort study of pregnancies in women on thyroid replacement before pregnancy in Alberta, Canada, was performed. Women using thyroid replacement anytime during the two years before pregnancy who delivered between October 2014 and September 2017 were included. Delivery records, physician billing, and laboratory and pharmacy administrative data were linked. Outcomes included characteristics of TSH testing, levothyroxine dosing, and pregnancy outcomes. The frequency and gestational timing of TSH testing and levothyroxine adjustments were calculated. Multiple logistic regression was used to test whether pregnancies with TSH <0.10 mIU/L (overtreatment) or TSH ≥10.00 mIU/L (undertreatment) compared with control pregnancies (TSH 0.10-4.00 mIU/L) were associated with adverse pregnancy and neonatal outcomes. Results: Of the 10,680 deliveries, 8774 (82.2%) underwent TSH testing at least once during pregnancy, at a median gestational age of six weeks. An adjustment of levothyroxine dosage was made for 4321 (43.7%) during pregnancy. TSH in pregnancy below 0.10 mIU/L increased the odds of preterm delivery when compared with control pregnancies (adjusted odds ratio, 2.14 [95% confidence interval 1.51-2.78]). TSH ≥10.00 mIU/L during pregnancy was not associated with any adverse pregnancy or neonatal outcomes in the multivariable analysis. Conclusions: Although most women on thyroid replacement before conception had TSH measured at some point during pregnancy, it is concerning that 17.8% did not. Levothyroxine overtreatment in pregnancy was associated with preterm delivery. These findings suggest that clinicians should be careful to avoid overtreatment with levothyroxine in pregnancy.

Project description:Objective: The objective of this study was to evaluate whether evolution of bone mineral density (BMD) is associated with the thyroid hormone profile in a cohort of euthyroid women with no other known diseases within 1 year. Methods: This was a prospective cohort study conducted at the University of Campinas, Brazil. We used a database with 52 women aged 20-39 who were followed for 1 year in a family planning outpatient clinic. The inclusion criteria were body mass index (BMI) <30 kg/m2, no known diseases/medication use, fasting glucose <100 mg/dl, and 2 h glucose after a 75 g oral glucose load <140 mg/dl. The women were divided into groups of normal weight (n = 30) and overweight (n = 22). The main outcomes were BMD measured by dual-energy x-ray absorptiometry (DXA) and thyroid hormone profile (thyrotropin TSH, free triiodothyronine FT3, free thyroxine FT4, and T3/T4 ratio); other variables were body composition (DXA), calcium metabolism markers, and life habits. We used a repeated measures analysis of variance (ANOVA) and multiple regression analyses to evaluate associations. Results: At the baseline data collection, overweight women showed a higher T3/T4 ratio, leptin, calcium, BMD in the lumbar spine and total femur, total mass, mass, and percentage of fat mass than normal weight women. At 12 months, both groups had increased FT4, calcium, ALP, femoral neck BMD, and total mass by time effect. The normal weight group presented a decrease of vitamin D when compared to the baseline. Increased BMD of the femoral neck was associated with moderate coffee intake, and as such, there were no associations found between this increase and the thyroid hormone profile. Leptin and ALP were associated with total mass variation, while leptin and PTH were associated with fat mass variation. The normal BMI was inversely associated with the variation of total mass, mass, and percentage of fat mass, and engaging in regular physical activity was inversely associated with fat mass variation. Conclusions: In this sample of euthyroid healthy women who were both normal weight and overweight, the thyroid hormone profile was not associated with variations in bone mineral density and body composition after a 1 year follow-up.

Project description:Background:It is well documented that overt hypothyroidism is associated with adverse pregnancy outcomes, but studies of subclinical hypothyroidism have demonstrated conflicting results. Objective:Thyroid hormones are known to regulate mitochondrial function, and the aim of this study was to examine the possible relationship of subclinical hypothyroidism and mitochondrial dysfunction to adverse pregnancy outcomes in pregnant women. Methods:Women in their third trimester of pregnancy (n = 113) who did not receive thyroid medication were included in this cross-sectional study. All participants were interviewed, and their thyroid status was determined. All participants had concentrations of thyroid hormones (fT4 and tT3) within the reference range. In addition to thyroid status, mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) were measured by flow cytometry. To establish a reference range of MMP and ROS, a group of euthyroid, nonpregnant women were used as euthyroid controls. Adverse pregnancy outcome was defined as preterm delivery, preeclampsia, placental abruption, Apgar score <7 points 1 minute after birth, or postpartum hemorrhage. Results:The prevalence of subclinical hypothyroidism among pregnant women was 17% (n = 19), and the number of overall adverse pregnancy outcomes was increased (p = 0.02) compared with that in euthyroid pregnant women. Preeclampsia, poor Apgar score, and postpartum hemorrhage were more frequent in the subclinical hypothyroidism group than in the euthyroid group (p = 0.04, p = 0.001 and p = 0.03, respectively), and more women showed prolonged gestation and gave birth later than 41 weeks of gestation than in the euthyroid group (p = 0.04). Compared with euthyroid, nonpregnant controls, a physiological upregulation of mitochondrial function was observed in euthyroid pregnant women. This was impaired in pregnant women with subclinical hypothyroidism. Compared with euthyroid, nonpregnant controls, pregnant women had increased ROS regardless of their thyroid status. Conclusion:We speculate that the unfavorable effects on mitochondrial function in women with subclinical hypothyroidism may be associated with higher prevalence of adverse pregnancy outcomes.

Project description:BackgroundSubjects at risk for major mood disorders have a higher risk to develop autoimmune thyroid disease (AITD) and vice-versa, implying a shared pathogenesis. In mood disorder patients, an abnormal profile of hematopoietic/neuronal growth factors is observed, suggesting that growth/differentiation abnormalities of these cell lineages may predispose to mood disorders. The first objective of our study was to investigate whether an aberrant profile of these hematopoietic/neuronal growth factors is also detectable in subjects at risk for AITD. A second objective was to study the inter relationship of these factors with previously determined and published growth factors/cytokines in the same subjects.MethodsWe studied 64 TPO-Ab-negative females with at least 1 first- or second-degree relative with AITD, 32 of whom did and 32 who did not seroconvert to TPO-Ab positivity in 5-year follow-up. Subjects were compared with 32 healthy controls (HCs). We measured serum levels of brain-derived neurotrophic factor (BDNF), Stem Cell Factor (SCF), Insulin-like Growth Factor-Binding Protein 2 (IGFBP-2), Epidermal Growth Factor (EGF) and IL-7 at baseline.ResultsBDNF was significantly lower (8.2 vs 18.9 ng/ml, P<0.001), while EGF (506.9 vs 307.6 pg/ml, P = 0.003) and IGFBP-2 (388.3 vs 188.5 ng/ml, P = 0.028) were significantly higher in relatives than in HCs. Relatives who seroconverted in the next 5 years had significantly higher levels of SCF than non-seroconverters (26.5 vs 16.7 pg/ml, P = 0.017). In a cluster analysis with the previously published growth factors/cytokines SCF clustered together with IL-1?, IL-6 and CCL-3, of which high levels also preceded seroconversion.ConclusionRelatives of AITD patients show aberrant serum levels of 4 hematopoietic/neuronal growth factors similar to the aberrancies found in mood disorder patients, suggesting that shared growth and differentiation defects in both the hematopoietic and neuronal system may underlie thyroid autoimmunity and mood disorders. A distinct pattern of four inter correlating immune factors in the relatives preceded TPO-Ab seroconversion in the next 5 years.

Dataset Information

Relationship between anti-thyroid peroxidase antibody positivity and pregnancy-related and fetal outcomes in Euthyroid women: a single-center cohort study.

Publications

Relationship between anti-thyroid peroxidase antibody positivity and pregnancy-related and fetal outcomes in Euthyroid women: a single-center cohort study.

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