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Context: Guidelines recommend use of population- and trimester-specific thyroid-stimulating hormone (TSH) and free thyroxine (FT4) reference intervals (RIs) in pregnancy. Since these are often unavailable, clinicians frequently rely on alternative diagnostic strategies. We sought to quantify the diagnostic consequences of current recommendations. Methods: We included cohorts participating in the Consortium on Thyroid and Pregnancy. Different approaches were used to define RIs: a TSH fixed upper limit of 4.0 mU/L (fixed limit approach), a fixed subtraction from the upper limit for TSH of 0.5 mU/L (subtraction approach) and using nonpregnancy RIs. Outcome measures were sensitivity and false discovery rate (FDR) of women for whom levothyroxine treatment was indicated and those for whom treatment would be considered according to international guidelines. Results: The study population comprised 52 496 participants from 18 cohorts. Compared with the use of trimester-specific RIs, alternative approaches had a low sensitivity (0.63-0.82) and high FDR (0.11-0.35) to detect women with a treatment indication or consideration. Sensitivity and FDR to detect a treatment indication in the first trimester were similar between the fixed limit, subtraction, and nonpregnancy approach (0.77-0.11 vs 0.74-0.16 vs 0.60-0.11). The diagnostic performance to detect overt hypothyroidism, isolated hypothyroxinemia, and (sub)clinical hyperthyroidism mainly varied between FT4 RI approaches, while the diagnostic performance to detect subclinical hypothyroidism varied between the applied TSH RI approaches. Conclusion: Alternative approaches to define RIs for TSH and FT4 in pregnancy result in considerable overdiagnosis and underdiagnosis compared with population- and trimester-specific RIs. Additional strategies need to be explored to optimize identification of thyroid dysfunction during pregnancy., SCOPUS: re.j, info:eu-repo/semantics/published

Context: Guidelines recommend use of population- and trimester-specific thyroid-stimulating hormone (TSH) and free thyroxine (FT4) reference intervals (RIs) in pregnancy. Since these are often unavailable, clinicians frequently rely on alternative diagnostic strategies. We sought to quantify the diagnostic consequences of current recommendations. Methods: We included cohorts participating in the Consortium on Thyroid and Pregnancy. Different approaches were used to define RIs: a TSH fixed upper limit of 4.0 mU/L (fixed limit approach), a fixed subtraction from the upper limit for TSH of 0.5 mU/L (subtraction approach) and using nonpregnancy RIs. Outcome measures were sensitivity and false discovery rate (FDR) of women for whom levothyroxine treatment was indicated and those for whom treatment would be considered according to international guidelines. Results: The study population comprised 52 496 participants from 18 cohorts. Compared with the use of trimester-specific RIs, alternative approaches had a low sensitivity (0.63-0.82) and high FDR (0.11-0.35) to detect women with a treatment indication or consideration. Sensitivity and FDR to detect a treatment indication in the first trimester were similar between the fixed limit, subtraction, and nonpregnancy approach (0.77-0.11 vs 0.74-0.16 vs 0.60-0.11). The diagnostic performance to detect overt hypothyroidism, isolated hypothyroxinemia, and (sub)clinical hyperthyroidism mainly varied between FT4 RI approaches, while the diagnostic performance to detect subclinical hypothyroidism varied between the applied TSH RI approaches. Conclusion: Alternative approaches to define RIs for TSH and FT4 in pregnancy result in considerable overdiagnosis and underdiagnosis compared with population- and trimester-specific RIs. Additional strategies need to be explored to optimize identification of thyroid dysfunction during pregnancy.

CONTEXT: Guidelines recommend use of population- and trimester-specific thyroid-stimulating hormone (TSH) and free thyroxine (FT4) reference intervals (RIs) in pregnancy. Since these are often unavailable, clinicians frequently rely on alternative diagnostic strategies. We sought to quantify the diagnostic consequences of current recommendations.METHODS: We included cohorts participating in the Consortium on Thyroid and Pregnancy. Different approaches were used to define RIs: a TSH fixed upper limit of 4.0 mU/L (fixed limit approach), a fixed subtraction from the upper limit for TSH of 0.5 mU/L (subtraction approach) and using nonpregnancy RIs. Outcome measures were sensitivity and false discovery rate (FDR) of women for whom levothyroxine treatment was indicated and those for whom treatment would be considered according to international guidelines.RESULTS: The study population comprised 52 496 participants from 18 cohorts. Compared with the use of trimester-specific RIs, alternative approaches had a low sensitivity (0.63-0.82) and high FDR (0.11-0.35) to detect women with a treatment indication or consideration. Sensitivity and FDR to detect a treatment indication in the first trimester were similar between the fixed limit, subtraction, and nonpregnancy approach (0.77-0.11 vs 0.74-0.16 vs 0.60-0.11). The diagnostic performance to detect overt hypothyroidism, isolated hypothyroxinemia, and (sub)clinical hyperthyroidism mainly varied between FT4 RI approaches, while the diagnostic performance to detect subclinical hypothyroidism varied between the applied TSH RI approaches.CONCLUSION: Alternative approaches to define RIs for TSH and FT4 in pregnancy result in considerable overdiagnosis and underdiagnosis compared with population- and trimester-specific RIs. Additional strategies need to be explored to optimize identification of thyroid dysfunction during pregnancy.

Objective: Pregnant women with autoimmune (subclinical) hypothyroidism have an increased risk of developing gestational diabetes mellitus (GDM). However, this association remains controversial in euthyroid women with thyroid autoimmunity (TAI). Therefore, the aim of the study was to determine the association between TAI and GDM in euthyroid women in a logistic regression analysis with adjustments for baseline/ demographic parameters. Methods: Cross-sectional study in 1447 euthyroid women who performed their entire clinical/biological workup and oral glucose tolerance test (OGTT) in our center. At median 13 (11–17) weeks of gestation, thyroid-stimulating hormone, free T4, and thyroid peroxidase antibodies (TPOAb) were measured, baseline characteristics were recorded, and an OGTT was performed between 24 and 28 weeks of pregnancy. Exclusion criteria were pre-pregnancy diabetes, assisted pregnancies, and women with (treated) thyroid dysfunction before or after screening. The diagnosis of GDM was based on 2013 World Health Organization criteria, and TAI was defined as TPOAb levels ≥60 kIU/L. Results: Two hundred eighty women were diagnosed with GDM (19.4%), 26.1% in women with TAI, and 18.9% in women without TAI (P = 0.096). In the logistic regression analysis, TAI was associated with GDM in women older than 30 years (adjusted odds ratio 1.68 (95% CI, 1.01–2.78); P = 0.048). Maternal age >30 years, pre-pregnancy BMI ≥30 kg/m2, and other than Caucasian background were also associated with GDM; aOR 1.93 (95% CI, 1.46–2.56); P < 0.001, 2.03 (95% CI, 1.46–2.81); P < 0.001 and 1.46 (95% CI, 1.03–2.06); P = 0.034, respectively. Conclusions: In older pregnant women, the presence of TAI in euthyroid women was associated with GDM. In line with the literature data, (higher) age and BMI were strongly associated with GDM. Future investigations should focus on treatments that might prevent the development of GDM in euthyroid women with TAI., SCOPUS: ar.j, info:eu-repo/semantics/published

Objective: It is unknown if foetal gender influences maternal thyroid function during pregnancy. We therefore investigated the prevalence of thyroid disorders and determined first-trimester TSH reference ranges according to gender. Methods: A cross-sectional study involving 1663 women with an ongoing pregnancy was conducted. Twin and assisted pregnancies and l-thyroxine or antithyroid treatment before pregnancy were exclusion criteria. Serum TSH, free T4 (FT4) and thyroid peroxidase antibodies (TPOAb) were measured at median (interquartile range; IQR) 13 (11–17) weeks of gestation. Subclinical hypothyroidism (SCH) was present when serum TSH levels were >3.74 mIU/L with normal FT4 levels (10.29–18.02 pmol/L), and thyroid autoimmunity (TAI) was present when TPOAb were ≥60 kIU/L. Results: Eight hundred and forty-seven women were pregnant with a female foetus (FF) and 816 with a male foetus (MF). In women without TAI and during the gestational age period between 9 and 13 weeks (with presumed high-serum hCG levels), median (IQR range) serum TSH in the FF group was lower than that in the MF group: 1.13 (0.72–1.74) vs 1.24 (0.71–1.98) mIU/L; P = 0.021. First-trimester gender-specific TSH reference range was 0.03–3.53 mIU/L in the FF group and 0.03–3.89 mIU/L in the MF group. The prevalence of SCH and TAI was comparable between the FF and MF group: 4.4% vs 5.4%; P = 0.345 and 4.9% vs 7.5%; P = 0.079, respectively. Conclusions: Women pregnant with an MF have slightly but significantly higher TSH levels and a higher upper limit of the first-trimester TSH reference range, compared with pregnancies with a FF. We hypothesise that this difference may be related to higher hCG levels in women pregnant with a FF, although we were unable to measure hCG in this study. Further studies are required to investigate if this difference has any clinical relevance., SCOPUS: ar.j, info:eu-repo/semantics/published

Background: The impact of thyroid disorders on in vitro outcomes of assisted reproductive technology (ART) remains controversial. Therefore, the aim of our study was to investigate whether thyroid peroxidase antibodies (TPO-Abs)/thyroid autoimmunity (TAI) or thyroid function (serum thyrotropin [TSH])/subclinical hypothyroidism are associated with an altered number of oocyte retrieval (NOR), fertilization rate (FR), and embryo quality (EQ). Methods: Cross-sectional study in 279 women in a single center, comprising 297 cycles and 1168 embryos. In vitro data (NOR, FR, and EQ) were documented in two groups; one according to thyroid function in women without TAI (TSH ≤2.5 and >2.5 mIU/L) and one according to the presence/absence of TAI (determined by TPO-Abs). EQ was evaluated according to international criteria and classified as excellent/good and poor. Women treated with levothyroxine (LT4) were excluded. Furthermore, the impact of thyroid parameters on outcomes, normal NOR (>6 or 8) and high FR (>60%), was verified in a multivariable logistic regression model. Results: In women without TAI, 27% had TSH levels >2.5 mIU/L, the prevalence of TAI was 8%, and overall, 6% of women had TSH levels >4.2 mIU/L. NOR, FR, and EQ were comparable between study groups. In the regression analysis, women aged ≥30 years and receiving a high ovarian stimulation dosage (>2300 IU/cycle) had lower rates of normal NOR (odds ratio [OR] 0.18 [95% confidence interval, CI 0.04-0.72]; p = 0.016 and OR 0.17 [CI 0.06-0.48]; p < 0.001, respectively). Conclusions: Our results do not suggest an impact of thyroid antibodies/autoimmunity and (dys)function on ART in vitro outcomes., SCOPUS: ar.j, info:eu-repo/semantics/published