Risk Factors for Thyroid Dysfunction in Pregnancy: An Individual Participant Data Meta-Analysis.

Background: International guidelines recommend targeted screening to identify gestational thyroid dysfunction. However, currently used risk factors have questionable discriminative ability. We quantified the risk for thyroid function test abnormalities for a subset of risk factors currently used in international guidelines. Methods: We included prospective cohort studies with data on gestational maternal thyroid function and potential risk factors (maternal age, body mass index [BMI], parity, smoking status, pregnancy through in vitro fertilization, twin pregnancy, gestational age, maternal education, and thyroid peroxidase antibody [TPOAb] or thyroglobulin antibody [TgAb] positivity). Exclusion criteria were pre-existing thyroid disease and use of thyroid interfering medication. We analyzed individual participant data using mixed-effects regression models. Primary outcomes were overt and subclinical hypothyroidism and a treatment indication (defined as overt hypothyroidism, subclinical hypothyroidism with thyrotropin >10 mU/L, or subclinical hypothyroidism with TPOAb positivity). Results: The study population comprised 65,559 participants in 25 cohorts. The screening rate in cohorts using risk factors currently recommended (age >30 years, parity ≥2, BMI ≥40) was 58%, with a detection rate for overt and subclinical hypothyroidism of 59%. The absolute risk for overt or subclinical hypothyroidism varied <2% over the full range of age and BMI and for any parity. Receiver operating characteristic curves, fitted using maternal age, BMI, smoking status, parity, and gestational age at blood sampling as explanatory variables, yielded areas under the curve ranging from 0.58 to 0.63 for the primary outcomes. TPOAbs/TgAbs positivity was associated with overt hypothyroidism (approximate risk for antibody negativity 0.1%, isolated TgAb positivity 2.4%, isolated TPOAb positivity 3.8%, combined antibody positivity 7.0%; p < 0.001), subclinical hypothyroidism (risk for antibody negativity 2.2%, isolated TgAb positivity 8.1%, isolated TPOAb positivity 14.2%, combined antibody positivity 20.0%; p < 0.001) and a treatment indication (risk for antibody negativity 0.2%, isolated TgAb positivity 2.2%, isolated TPOAb positivity 3.0%, and combined antibody positivity 5.1%; p < 0.001). Twin pregnancy was associated with a higher risk of overt hyperthyroidism (5.6% vs. 0.7%; p < 0.001). Conclusions: The risk factors assessed in this study had poor predictive ability for detecting thyroid function test abnormalities, questioning their clinical usability for targeted screening. As expected, TPOAb positivity (used as a benchmark) was a relevant risk factor for (subclinical) hypothyroidism. These results provide insights into different risk factors for gestational thyroid dysfunction.

Gestation-suppressed serum TSH levels during early pregnancy are not associated with altered maternal and neonatal outcomes.

Objective: The aim of the study was to investigate the impact of suppressed serum TSH levels (sTSH) during early pregnancy on maternal and neonatal outcomes. Methods: In this single-centre, retrospective cohort study 1081 women were screened at 11.8 ± 2.4 weeks of pregnancy for TSH, free T4 (FT4) and TPOAb. Exclusion criteria were twin- and assisted- reproduction pregnancies, women with TSH levels >3.74 mIU/L, severe hyperthyroidism, treated for thyroid dysfunction before or after screening and gestational blood sampling <6 or >16 weeks of pregnancy. The prevalence of adverse pregnancy outcomes was compared between the study group sTSH (TSH: < 0.06 mIU/L; n = 36) and euthyroid controls (TSH: 0.06-3.74 mIU/L; n = 1045), and the impact of sTSH on pregnancy outcomes verified in logistic regression analyses. Results: Median (IQR) serum TSH level in women with sTSH was 0.03 (0.03-0.03) vs 1.25 (0.81-1.82) mIU/L in controls and FT4 levels 18.0 (14.4-20.3) vs 14.2 (12.9-15.4) pmol/L; both P < 0.001. None of the women with sTSH had thyrotropin receptor antibodies. Compared with controls, the prevalence of TPOAb positivity (TAI) was comparable between groups (5.6% vs 6.6%; P = 0.803). The prevalence of maternal and neonatal pregnancy outcomes was comparable between the study and control group. The logistic regression analyses with corrections for TAI, FT4 and demographic parameters confirmed the absence of an association between sTSH, and the following outcomes: iron deficient anaemia (aORs (95% CI)): 1.41 (0.64-2.99); P = 0.385, gestational diabetes: 1.19 (0.44-2.88); P = 0.713, preterm birth: 1.57 (0.23-6.22);P = 0.574 and low Apgar-1' score: 0.71 (0.11-2.67); P = 0.657. Conclusions: Suppressed serum TSH levels during the first to early second trimester of pregnancy were not associated with altered maternal or neonatal outcomes.

Impact of thyroid hormone treatment on maternal pregnancy outcomes in women with subclinical hypothyroidism without TPOAb: a retrospective cross-sectional study.

BACKGROUND: Evidence on the impact of thyroid hormone treatment (LT4) on maternal pregnancy outcomes in women with subclinical hypothyroidism (SCH) without thyroid peroxidase antibodies (TPOAb) positivity is scarce. METHODS: Single centre, cross-sectional study in 1460 women screened for TSH, free T4 and TPOAb at median 13 (11-17) weeks of gestation during the period 2013-2014. Exclusion criteria were twin- and assisted reproduction pregnancies, TPO positivity, overt thyroid dysfunction, and treatment with LT4 before screening. The impact of LT4 on maternal pregnancy outcomes was investigated in a group of 53 women with SCH (TSH > 3.74 mIU/L) in which LT4 was initiated at median 13 (10-22) weeks (treated group). The control group included 18 women with SCH (TSH > 3.74 mIU/L). The prevalence of pregnancy complications in these two groups was compared with that in a euthyroid reference (REF) group of 1389 women (TSH ≤ 3.74 mIU/L). RESULTS: The prevalence of pre-eclampsia and gestational diabetes (GDM) was higher in the control group vs the REF group (16.7% vs 5.0% and 27.8% vs 18.9%; p = 0.017 and p = 0.016, respectively), but comparable in the treated group vs the REF group (7.6% vs 5.0% and 22.6% vs 18.9%; p = 0.918 and 0.676, respectively). The prevalence of iron-deficiency anaemia was lower in the treated vs the REF group (17.0% vs 32.5%; p = 0.017). CONCLUSION: Pregnant women with untreated SCH and without TPOAb positivity had a higher prevalence of pre-eclampsia and GDM compared with euthyroid women, while this was not the case in women with treated SCH, even when it was initiated after the first trimester.

Obstructive sleep apnea is not associated with diabetic retinopathy in diabetes: a prospective case-control study.

PURPOSE: Diabetic retinopathy (DR) is the most common ocular complication of type 2 diabetes mellitus (T2D) and is associated with diabetes duration, glycemic control, and hypertension (HTN). Obstructive sleep apnea (OSA) is frequent in T2D and is associated with poor glycemic control. However, it is unclear if there is an association between OSA and DR. This study aimed to assess whether or not the presence of OSA in patients with T2D was associated with DR. METHODS: In this prospective case-control study, consecutive patients with DM attending the ophthalmology clinics were recruited to include patients with DR (cases) and without DR (controls). OSA was diagnosed by attended polysomnography (PSG). Blood pressure and a fasting morning blood sample, including glycosylated hemoglobin (HbA1c), were recorded. Patients were matched for age, body mass index (BMI), gender, and T2D duration. RESULTS: Thirty diabetic patients with DR were matched with 30 controls. In all patients, the prevalence of moderate-to-severe OSA was 57%. In the logistic regression analysis, DR was associated with increased HbA1c (OR 2.63, 95% CI 1.35-5.16, p = 0.004) but not with any PSG parameter. In the DR group, PSG parameters were not associated with the severity of ocular disease (non-proliferative, proliferative, presence/absence of macular edema). The proliferative aspect of DR was correlated with age (p = 0.017). DR occurred more frequently in uncontrolled diabetes compared to well-controlled diabetes (80% vs 38%, p = 0.029). CONCLUSIONS: In patients with T2D, the presence of DR is not associated with OSA, but with poorly controlled T2D.

TSH and FT4 Reference Intervals in Pregnancy: A Systematic Review and Individual Participant Data Meta-Analysis.

CONTEXT: Interpretation of thyroid function tests during pregnancy is limited by the generalizability of reference intervals between cohorts due to inconsistent methodology. OBJECTIVE: (1) To provide an overview of published reference intervals for thyrotropin (TSH) and free thyroxine (FT4) in pregnancy, (2) to assess the consequences of common methodological between-study differences by combining raw data from different cohorts. METHODS: (1) Ovid MEDLINE, EMBASE, and Web of Science were searched until December 12, 2021. Studies were assessed in duplicate. (2) The individual participant data (IPD) meta-analysis was performed in participating cohorts in the Consortium on Thyroid and Pregnancy. RESULTS: (1) Large between-study methodological differences were identified, 11 of 102 included studies were in accordance with current guidelines; (2) 22 cohorts involving 63 198 participants were included in the meta-analysis. Not excluding thyroid peroxidase antibody-positive participants led to a rise in the upper limits of TSH in all cohorts, especially in the first (mean +17.4%; range +1.6 to +30.3%) and second trimester (mean +9.8%; range +0.6 to +32.3%). The use of the 95th percentile led to considerable changes in upper limits, varying from -10.8% to -21.8% for TSH and -1.2% to -13.2% for FT4. All other additional exclusion criteria changed reference interval cut-offs by a maximum of 3.5%. Applying these findings to the 102 studies included in the systematic review, 48 studies could be used in a clinical setting. CONCLUSION: We provide an overview of clinically relevant reference intervals for TSH and FT4 in pregnancy. The results of the meta-analysis indicate that future studies can adopt a simplified study setup without additional exclusion criteria.

Association between thyroid autoimmunity and gestational diabetes mellitus in euthyroid women.

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.

Does foetal gender influence maternal thyroid parameters in pregnancy?

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.

Thyroid Disorders and In Vitro Outcomes of Assisted Reproductive Technology: An Unfortunate Combination?

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.

The Impact of Thyroid Disorders on Clinical Pregnancy Outcomes in a Real-World Study Setting.

Background: Subclinical hypothyroidism (SCH) and thyroid autoimmunity (TAI) have been associated with poor clinical pregnancy outcomes. However, these outcomes also depend on a number of demographic and obstetric variables. Therefore, the aim of this study was to investigate the impact of thyroid disorders on these outcomes, after adjustment for associated demographic and obstetrical parameters. Methods: This is cross-sectional study including 1521 pregnant women who underwent work-up and follow-up in the Centre Hospitalier Universitaire (CHU) Saint-Pierre, Brussels, and had ongoing pregnancies. Thyroid function (thyrotropin [TSH], free thyroxine [fT4]) and TAI (thyroid peroxidase antibodies) was determined at median (Q1-Q3) 13 (11-17) weeks. Baseline parameters and the prevalence of poor clinical pregnancy outcomes were compared between controls (no TAI and TSH <2.51 mIU/L) and three study groups (isolated TAI [TSH <2.51 mIU/L], SCH1 [TSH 2.51-3.7 mIU/L], SCH2 [TSH >3.7 mIU/L]). The impact of the different thyroid groups and demographic/obstetric independent variables on six poor clinical pregnancy outcomes (preeclampsia, intrauterine growth restriction [IUGR], preterm birth, neonatal intensive care unit [NICU] admission, low birth weight, and macrosomia) was investigated in a logistic regression model. Treatment with thyroid hormone before and during pregnancy and assisted and multiple pregnancies were exclusion criteria. Results: In total, 79 preeclampsias (5.2%), 40 IUGRs (2.6%), 79 preterm births (5.2%), 10 admissions to NICU (0.66%), 74 low birth weights (4.9%), and 94 babies with macrosomia (6.2%) were documented. TAI was independently associated with NICU admission (adjusted odds ratio [aOR] 16.92 confidence interval [CI 3.36-85.29]; p < 0.001) and TSH, as a continuous variable in the whole range, with preeclampsia (aOR 1.97 [CI 1.18-3.31]; p = 0.010). Trends were present for an association between SCH2 and preeclampsia (aOR 16.73 [CI 1.43-196.42]; p = 0.025), and for SCH1with NICU admission and low birth weight (aOR 19.36 [CI 1.18-316.97]; p = 0.038 and 21.38 [CI 1.29-353.39]; p = 0.032, respectively). Conclusions: Pregnant women with TAI had a significantly higher risk of an admission of the baby to the NICU, and SCH tended to be associated with a higher risk of preeclampsia and low birth weight. Other poor clinical pregnancy outcomes were not associated with thyroid disorders, but with demographic and obstetric parameters.

Screening for Thyroid Dysfunction in Pregnancy With Targeted High-Risk Case Finding: Can It Be Improved?

CONTEXT AND OBJECTIVE: Targeted screening is proposed for the detection of thyroid dysfunction in pregnant women rather than universal screening (US). We aimed to determine the detection rate of subclinical hypothyroidism (SCH) and overt hypothyroidism (OH) based on American Thyroid Association guidelines (ATA-GL) and whether it could be improved. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study of 1832 pregnant women in a single center. Thyroid function (TSH and free T4) and iron status were determined. The high-risk group (HRG) included women with one or more ATA-GL risk factors and the low-risk group (LRG) included women without. Participants with other risk factors [body mass index (BMI) 30 to 39.9 kg/m2, Caucasian background] were classified as HRG+ and those with iron deficiency as HRG++. RESULTS: The HRG included 64% of women and the LRG included 36% (P < 0.001). Of all participants, 4.5% had SCH and 0.5% OH. The detection rate of SCH and OH was comparable between the LRG and HRG (46% vs 54% and 25% vs 75%; P = 0.560 and 0.157, respectively). In the HRG, the detection rate of SCH was lower than that of US (54% vs 100%; P < 0.001), but that of OH was comparable (75%; P = 0.596). The detection rate of SCH in the HRG+ and HRG++ was comparable to that in the US group (81% and 88% vs 100%; P = 0.220 and 0.439, respectively). CONCLUSIONS: Targeted high-risk case finding screening was not effective for the detection of SCH but performed better for OH. When obesity in the range BMI 30 to 39.9 kg/m2 and a Caucasian background were included as risk factors, the detection rate of SCH became comparable with that of US.

Prevalence of newly established thyroid disorders in patients with moderate-to-severe obstructive sleep apnea syndrome.

BACKGROUND: Hypothyroidism can directly cause obstructive sleep apnea (OSA) but may also contribute to it through its impact on the metabolic syndrome. The purpose of this study was to establish the prevalence of known and newly diagnosed overt and subclinical hypothyroidism (SCH) among patients with OSA. METHODS: We prospectively included all consecutive moderate or severe OSA patients referred for CPAP therapy. A fasting blood sample was collected to determine thyroid-stimulating hormone (TSH) and free T4 (FT4) levels. RESULTS: A total of 280 patients were included (70% male). Mean ± SD body mass index (BMI) and apnea-hypopnea index (AHI) were 33 ± 7 kg/m2 and 49 ± 25, respectively. Median (range) serum TSH levels and mean ± SD FT4 levels were comparable between severe and moderate OSA (1.7 (1.3-2.6) vs 2.1 (1.2-2.8); p = 0.378 and 15.3 ± 2.3 vs 15.3 ± 2.3; p = 0.981). TSH and FT4 levels were not correlated with AHI (p = 0.297 and p = 0.370, respectively), but TSH was correlated with BMI (p = 0.049).Of all patients, 8.9% had increased serum TSH levels (severe and moderate OSA patients had similar levels (p = 0.711)) and 8.2% were newly diagnosed patients (no differences were observed between severe and moderate OSA (p = 0.450)). A total of 16.4% of patients had some type of thyroid disorder. Thyroid function parameters were associated with BMI but not with the severity of OSA. CONCLUSION: In our population of moderate or severe OSA, 16% of patients had a thyroid problem and 8% of these were newly diagnosed with SCH.

Variables Contributing to Thyroid (Dys)Function in Pregnant Women: More than Thyroid Antibodies?

Variability in thyroid function in pregnant women is the result of 2 main determinants, each accounting for approximately half of it. The first is the genetically determined part of which the knowledge increases fast, but most remains to be discovered. The second determinant is caused by an ensemble of variables of which thyroid autoimmunity is the best known, but also by others such as parity, smoking, age, and BMI. More recently, new candidate variables have been proposed, such as iron, endocrine disruptors, and the ethnicity of the pregnant women. In the future, the diagnosis and treatment of thyroid (dys)function may be optimized by the use of each individual's pituitary-thyroid set point, corrected with a factor taking into account the impact of nongenetically determined variables.

'Does levothyroxine improve pregnancy outcomes in euthyroid women with thyroid autoimmunity undergoing assisted reproductive technology?'

Evidence on the treatment of euthyroid infertile women and thyroid autoimmunity with thyroid hormone is scare, and therefore the recent study by Wang et al. is a welcome addition to it. Based on their results, thyroid hormone seems not to be indicated to decrease the miscarriage rate in that particular group of infertile women. This comment is meant to put the study results into perspective with the available evidence and the current guidelines, and to highlight its strengths and weaknesses.

Thyroid autoimmunity and intracytoplasmic sperm injection outcome: a systematic review and meta-analysis.

BACKGROUND: Since 2010, three meta-analyses have been published on the impact of thyroid autoimmunity (TAI) on pregnancy outcomes in infertile women treated with assisted reproductive technology (ART). The initially observed high risk of miscarriage became very low in the most recent meta-analysis published in 2016. OBJECTIVE: To investigate whether the lower risk of miscarriage in the latest meta-analysis was associated with the increased use of intracytoplasmic sperm injection (ICSI) in recent studies. DATA SOURCE: MEDLINE was searched from January, 1990, to May, 2017. STUDY SELECTION: Data from case-control and cohort studies, on ART (IVF/ICSI) pregnancy outcomes in women with and without TAI. Only studies were included in which women were treated with ICSI. DATA EXTRACTION AND SYNTHESIS: Four studies were retained including 1855 ICSI cycles (290 with and 1565 without TAI). In women with a clinical pregnancy (114 ICSI cycles with TAI and 651 without), there was no difference in miscarriage or live birth rates: respective combined OR 0.95 (95% CI, 0.48 to 1.87) and 1.12 (95% CI, 0.62 to 2.03). There was no difference in age in women with and without TAI: combined mean difference of 0.13 years (95% CI, -0.51 to 0.76), but serum TSH was higher in women with TAI: combined mean difference of 0.20 mIU/L (95% CI, 0.07 to 0.33). CONCLUSION: Infertile women with TAI treated with ICSI had no increased risk of a first trimester miscarriage compared with women without TAI.

Pregnancy outcomes are not altered by variation in thyroid function within the normal range in women free of thyroid disease.

OBJECTIVE: In the recently revised guidelines on the management of thyroid dysfunction during pregnancy, treatment with thyroid hormone (LT4) is not recommended in women without thyroid autoimmunity (TAI) and TSH levels in the range 2.5-4.0 mIU/L, and in a recent study in that particular group of pregnant women, more complications were observed when a treatment with LT4 was given. The objective of the study was therefore to investigate whether variation in thyroid function within the normal (non-pregnant) range in women free of thyroid disease was associated with altered pregnancy outcomes? DESIGN: Cross-sectional data analysis of 1321 pregnant women nested within an ongoing prospective collection of pregnant women's data in a single centre in Brussels, Belgium. METHODS: Thyroid peroxidase antibodies (TPO-abs), thyroid-stimulating hormone (TSH), free T4 (FT4) and ferritin levels were measured and baseline characteristics were recorded. Women taking LT4, with TAI and thyroid function outside the normal non-pregnant range were excluded. Pregnancy outcomes and baseline characteristics were correlated with all TSH and FT4 levels within the normal range and compared between two groups (TSH cut-off < and ≥2.5 mIU/L). RESULTS: Tobacco use was associated with higher serum TSH levels (OR: 1.38; CI 95%: 1.08-1.74); P = 0.009. FT4 levels were inversely correlated with age and BMI (rho = -0.096 and -0.089; P < 0.001 and 0.001 respectively) and positively correlated with ferritin levels (rho = 0.097; P < 0.001). Postpartum haemorrhage (>500 mL) was inversely associated with serum FT4 levels (OR: 0.35; CI 95%: 0.13-0.96); P = 0.040. Also 10% of women free of thyroid disease had serum TSH levels ≥2.5 mIU/L. CONCLUSIONS: Variation in thyroid function during the first trimester within the normal (non-pregnant) range in women free of thyroid disease was not associated with altered pregnancy outcomes. These results add evidence to the recommendation against LT4 treatment in pregnant women with high normal TSH levels and without TPO antibodies.

Maternal thyroid parameters in pregnant women with different ethnic backgrounds: Do ethnicity-specific reference ranges improve the diagnosis of subclinical hypothyroidism?

OBJECTIVE: Guidelines on the management of thyroid dysfunction during pregnancy have recently been updated and, for the diagnosis of subclinical hypothyroidism (SCH), a thyroid-stimulating hormone (TSH) upper reference limit (cut-off) of 4.0 mIU/L has been proposed when no institutional values are available. It is also suggested that serum TSH and thyroid autoimmunity (TAI) may be different according to the ethnic background of the women. We therefore determined the prevalence of TAI and SCH in pregnant women with different ethnic backgrounds and, to define SCH, we used different first trimester TSH upper reference cut-offs (institutional, ethnicity-specific, 2.5 mIU/L [Endocrine Society] and 4.0 mIU/L [American Thyroid Association]). DESIGN: Cross-sectional data analysis of 1683 pregnant women nested within an ongoing prospective database of pregnant women. METHOD: The study was performed in a single centre in Brussels, Belgium. During the first antenatal visit, thyroid peroxidase antibodies (TPO-abs), TSH and free T4 (FT4) were measured and baseline characteristics recorded. Data from 481 women with sub-Saharan (SaBg; 28.6%), 754 North African (NaBg; 44.8%) and 448 Caucasian (CaBg; 26.6%) backgrounds were analysed. For the calculation of TSH reference ranges, women with TAI, outliers, twin and assisted pregnancies were excluded. RESULTS: The prevalence of TAI was significantly lower in the SaBg group than in NaBg and CaBg groups (3.3% vs 8.6% and 11.1%; P<.001, respectively). Median TSH was significantly lower in SaBg and NaBg groups as compared with the CaBg group (1.3 and 1.4 vs 1.5 mIU/L; P=.006 and .014, respectively). The prevalence of women with SCH was comparable between all groups when 2.5 mIU/L was used as cut-off, but when 4.0 mIU/L or the institutional cut-off (3.74 mIU/L) was used, it was significantly higher in the CaBg group vs the NaBg group (5.4% vs 2.1% and 7.1% vs 3.3%, P=.008 and .013, respectively). The use of ethnicity-specific cut-offs did not change the prevalence of SCH as compared to the use of institutional cut-offs. However, when these cut-offs were used, the prevalence of SCH reduced by >70% (4.5% instead of 16.7%; P<.001) relative to the 2.5 mIU/L cut-off. CONCLUSIONS: Pregnant women with a sub-Saharan African background had a lower prevalence of TAI and TSH levels as compared with women from other backgrounds. The use of ethnicity-specific TSH cut-offs in early pregnancy was not more specific for the diagnosis of SCH as compared to the use of the institutional cut-off.

Prevalence of thyroid dysfunction and autoimmunity in the older population and implications of age-specific reference ranges.

OBJECTIVE: To investigate the prevalence of thyroid dysfunction and autoimmunity (TAI) and to determine age-specific reference ranges in individuals <60 and ≥60-year-old. Furthermore we investigated the impact of the age-specific reference ranges on the prevalence of thyroid dysfunction. DESIGN: Retrospective analysis of laboratory data collected over six months in 2015, mainly from individuals consulting the outpatient clinic. METHOD: Data from 676 individuals were withheld, after having applied strict exclusion criteria to avoid confounders. After exclusion of individuals with TAI (TPO-abs >60kIU/L) and/or outliers, data of 547 individuals were used to determine age-specific reference ranges. The prevalence of subclinical hypothyroidism (SCH) and subclinical hyperthyroidism (sch) was determined according to the reference ranges from the commercial assay and also according to the calculated age-specific reference ranges. From our study population. RESULTS: From the 676 individuals included, 559 (83%) were <60year-old and 117 (17%) ≥60year-old. The prevalence of sch and TAI was comparable between both groups (8.6% vs. 13.7% and 15.4% vs. 20.5% respectively). The prevalence of SCH was significantly higher in individuals ≥60years, compared to that in individuals <60years (14.5% vs. 5.4%; p<0.001). The calculated 2.5 and 97.5 percentile for the age-specific TSH range was 0.24 and 4.4 mIU/L in individuals <60years and 0.15 and 8.2mIU/L in individuals ≥60years. When these the prevalence of sch and SCH was then determined on the basis of the age-specific reference ranges, the prevalence of SCH significantly decreased in individuals ≥60years (14.5% to 5%; p=0.027) and it then became comparable with that in individuals <60years (5% vs. 3%). CONCLUSIONS: The prevalence of SCH was higher in individuals ≥60years, compared to that in individuals <60years, but when age-specific TSH reference ranges were used, it was comparable between both study groups. In order to avoid misclassification in older individuals, it is important to use age-specific reference ranges in daily clinical practice.

Prevalence of thyroid autoimmunity and dysfunction in women with iron deficiency during early pregnancy: is it altered?

OBJECTIVE: Thyroid disorders and iron deficiency (ID) are associated with obstetrical and fetal complications. Iron is essential for the normal functioning of thyroid peroxidase (TPO-abs) and ID is frequent during pregnancy. The aim of this study was to compare the prevalence of thyroid autoimmunity (TAI) and dysfunction during the first trimester of pregnancy in women with and without ID. DESIGN: Cross-sectional data analysis of 1900 pregnant women nested within an ongoing prospective collection of pregnant women's data. METHOD: The study was performed in a single, tertiary referral center. During the first antenatal visit, ferritin, TPO-abs, thyroid-stimulating hormone (TSH) and free T4 (FT4) were measured and age and BMI were recorded. ID was defined as ferritin <15µg/L, TAI when TPO-abs was >60kIU/L, and subclinical hypothyroidism (SCH) when TSH was >2.5mIU/L. RESULTS: ID was present in 35% of women. Age and BMI were comparable between both groups. In the ID group, the prevalence of TAI and SCH was significantly higher, compared with that in the non-ID group (10% vs 6% and 20% vs 16%; P=0.011 and 0.049 respectively). Ferritin was inversely correlated with serum TSH (ρ=-0.076; P=0.001) and positive with FT4 levels (ρ=0.112; P<0.001). In the logistic regression model, ID remained associated with TAI after correction for confounding factors (P=0.017). The association with SCH was absent after correction for the confounders in the logistic regression model (P=0.082), but remained present in the linear regression model (P=0.035). CONCLUSIONS: ID was frequent during the first trimester of pregnancy and was associated with a higher prevalence of TAI, higher serum TSH, and lower FT4 levels.