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Despite the high vaccination coverage, potential COVID‐19 vaccine‐induced adverse effects, especially in pregnant women, have not been fully characterized. We examined the association between COVID‐19 vaccination before conception and maternal thyroid function during early pregnancy. We conducted a retrospective cohort study in Shanghai, China. A total of 6979 pregnant women were included. Vaccine administration was obtained from electronic vaccination records. Serum levels of thyroid hormone were measured by fluorescence and chemiluminescence immunoassays. Among the 6979 included pregnant women, 3470 (49.7%) received at least two doses of an inactivated vaccine. COVID‐19 vaccination had a statistically significant association with both maternal serum levels of free thyroxine (FT4) and thyroid stimulating hormone (TSH). Compared with unvaccinated pregnant women, the mean FT4 levels were lower in pregnant women who had been vaccinated within 3 months before the date of conception by 0.27 pmol/L (β = −0.27, 95% confidence interval [CI], −0.42, −0.12), and the mean TSH levels were higher by 0.08 mIU/L (β = 0.08, 95% CI, 0.00, 0.15). However, when the interval from vaccination to conception was prolonged to more than 3 months, COVID‐19 vaccination was not associated with serum FT4 or TSH levels. Moreover, we found that COVID‐19 vaccination did not significantly associate with maternal hypothyroidism. Our study suggested that vaccination with inactivated COVID‐19 vaccines before conception might result in a small change in maternal thyroid function, but this did not reach clinically significant levels. [ABSTRACT FROM AUTHOR]

Objective: Preterm delivery (PTD) is the primary cause of mortality in infants. Mounting evidence indicates that thyroid dysfunction might be associated with an increased risk of PTD, but the dose-dependent association between the continuous spectrum maternal free thyroxine (FT4) and PTD is still not well-defined. This study aimed to further investigate this relationship using a machine learning-based model. Methods: A hospital-based cohort study was conducted from January 2014 to December 2018 in Shanghai, China. Pregnant women who delivered singleton live births and had first-trimester thyroid function data available were included. The generalized additive models with penalized cubic regression spline were applied to explore the non-linear association between maternal FT4 and risk of PTD and also subtypes of PTD. The time-to-event method and multivariable Cox proportional hazard model were further applied to analyze the association of abnormally high and low maternal FT4 concentrations with the timing of PTD. Results: A total of 65,565 singleton pregnancies with completed medical records and no known thyroid disease before pregnancy were included for final analyses. There was a U-shaped dose-dependent relationship between maternal FT4 in the first trimester and PTD (p < 0.001). Compared with the normal range of maternal FT4, increased risk of PTD was identified in both low maternal FT4 (<11.7 pmol/L; adjusted hazard ratio [HR] 1.34, 95% CI [1.13–1.59]) and high maternal FT4 (>19.7 pmol/L; HR 1.41, 95% CI [1.13–1.76]). The association between isolated hypothyroxinemia and PTD was mainly associated with spontaneous PTD (HR 1.33, 95% CI [1.11–1.59]) while overt hyperthyroidism may be attributable to iatrogenic PTD (HR 1.51, 95% CI [1.18–1.92]) when compared with euthyroid women. Additionally, mediation analysis identified that an estimated 11.80% of the association between overt hyperthyroidism and iatrogenic PTD risk was mediated via the occurrence of hypertensive disorders in pregnancy (p < 0.001). Conclusions: We revealed a U-shaped association between maternal FT4 and PTD for the first time, exceeding the clinical definition of maternal thyroid function test abnormalities. Our findings provide insights towards the need to establish optimal range of maternal FT4 concentrations for preventing adverse outcomes in pregnancy. [ABSTRACT FROM AUTHOR]

Background: Human chorionic gonadotropin (hCG) is a marker of placental function, which also stimulates the maternal thyroid gland. Maternal thyroid function can be associated with the pathophysiology of gestational diabetes mellitus (GDM). We aimed to study whether there is an association of hCG concentrations in early pregnancy with GDM and whether it is mediated through maternal thyroid hormones. Methods: This study included 18,683 pregnant women presenting at a tertiary hospital in Shanghai, China, between January 2015 and December 2016. GDM was diagnosed using a 2-hour, 75-g, oral glucose tolerance test (OGTT) according to the American Diabetes Association guidelines. Multivariable logistic or linear regression models were used to identify associations, adjusting for maternal age, education level, family history of diabetes, parity, fetal sex, thyroperoxidase antibody (TPOAb) status, and prepregnancy body–mass index. Results: Higher hCG concentrations were associated with a lower plasma glucose level during the OGTT, but not with fasting plasma glucose or hemoglobin A1c concentrations tested during early pregnancy. hCG in early pregnancy was negatively associated with GDM risk (p = 0.027). Mediation analysis identified that an estimated 21.4% of the association of hCG-associated GDM risk was mediated through changes in free thyroxine (fT4) concentrations (p < 0.05). In the sensitivity analysis restricted to TPOAb-positive women, hCG was not associated with GDM (p = 0.452). Conclusions: Higher hCG levels in early pregnancy are associated with a lower risk of GDM. Maternal fT4 may act as an important mediator in this association. [ABSTRACT FROM AUTHOR]

Purpose: Although overt thyroid dysfunction has been found to influence the level of glycated albumin (GA), the associations between thyroid hormones and GA in individuals with euthyroidism and subclinical hypothyroidism (SHypo) are still unknown. The present study aimed to investigate whether thyroid hormones were related to GA in euthyroid and SHypo individuals. Methods: We recruited 685 euthyroid and 103 SHypo subjects with normal weight from communities in Shanghai. Electrochemiluminescence immunoassay was used to detect the serum levels of free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone. GA was detected by the enzymatic method. Glycated hemoglobin (HbA1c) was detected by high-performance liquid chromatography. Results: Among the 788 subjects (age range 31– 81 years old), 307 were men and 481 were women. In the Spearman correlation analysis and multiple stepwise regression analysis, FT3 was negatively correlated with both GA and GA/HbA1c in euthyroid subjects (all P < 0.05). The values of GA and GA/HbA1c were reduced by approximately 0.30 and 0.05, respectively, for each 0.50 pmol/L increment in FT3. In SHypo subjects, FT4 was negatively associated with both GA and GA/HbA1c (all P < 0.05). The values of GA and GA/HbA1c were reduced by approximately 0.23 and 0.03, respectively, for each 1.00 pmol/L increment in FT4. Conclusion: In euthyroid and SHypo subjects, more attention should be paid to the potential effects of individual differences in thyroid hormones on GA. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study was to estimate the combined effect of serum ferritin (SF) concentration and free thyroxine (fT4) levels on the risk of gestational diabetes mellitus (GDM).Methods: Women presented for antenatal care at a tertiary hospital in Shanghai, China were included in this study from December 2012 to March 2014. Women were divided into six groups according to the SF and fT4 level. Multiple logistical regression model was used to estimate odds ratio (OR) among different groups. Relative excess risk of interaction (RERI), the attributable proportion (AP) of the interaction and the synergy index (SI) were applied to evaluate the additive interaction of SF concentration and fT4 level.Results: A total of 6542 qualifying pregnant women were included in this study. We observed that a high SF concentration in early pregnancy was related to an increased risk of GDM (OR = 1.21, 95%CI: 1.02-1.43); while a low fT4 level was not (OR = 1.18, 95%CI: 0.89-1.58). There is no addictive interaction between SF and fT4 level on the presence of GDM.Conclusions: The study suggests that only high serum ferritin concentration is associated with an increased risk of GDM in early pregnancy. The level of fT4 in early pregnancy might have no effect on the association between high SF and risk of GDM. [ABSTRACT FROM AUTHOR]