Gestational Thyroid Dysfunction Research Articles

Defining Gestational Thyroid Dysfunction Through Modified Nonpregnancy Reference Intervals: An Individual Participant Meta-analysis.

Establishing local trimester-specific reference intervals for gestational TSH and free T4 (FT4) is often not feasible, necessitating alternative strategies. We aimed to systematically quantify the diagnostic performance of standardized modifications of center-specific nonpregnancy reference intervals as compared to trimester-specific reference intervals. We included prospective cohorts participating in the Consortium on Thyroid and Pregnancy. After relevant exclusions, reference intervals were calculated per cohort in thyroperoxidase antibody-negative women. Modifications to the nonpregnancy reference intervals included an absolute modification (per .1 mU/L TSH or 1 pmol/L free T4), relative modification (in steps of 5%) and fixed limits (upper TSH limit between 3.0 and 4.5 mU/L and lower FT4 limit 5-15 pmol/L). We compared (sub)clinical hypothyroidism prevalence, sensitivity, and positive predictive value (PPV) of these methodologies with population-based trimester-specific reference intervals. The final study population comprised 52 496 participants in 18 cohorts. Optimal modifications of standard reference intervals to diagnose gestational overt hypothyroidism were -5% for the upper limit of TSH and +5% for the lower limit of FT4 (sensitivity, .70, CI, 0.47-0.86; PPV, 0.64, CI, 0.54-0.74). For subclinical hypothyroidism, these were -20% for the upper limit of TSH and -15% for the lower limit of FT4 (sensitivity, 0.91; CI, 0.67-0.98; PPV, 0.71, CI, 0.58-0.80). Absolute and fixed modifications yielded similar results. CIs were wide, limiting generalizability. We could not identify modifications of nonpregnancy TSH and FT4 reference intervals that would enable centers to adequately approximate trimester-specific reference intervals. Future efforts should be turned toward studying the meaningfulness of trimester-specific reference intervals and risk-based decision limits.

A Nomogram Prediction Model for Persistent Pulmonary Hypertension of the Newborn in Neonates Hospitalized for the First Time After Birth.

Persistent pulmonary hypertension of the newborn (PPHN) is one of the critical neonatal diseases associated with high morbidity and mortality. This study attempted to conduct a nomogram prediction model for performing early identification of PPHN and providing effective information for clinical practice. A total of 456 newborns who first admitted to the hospital after birth were included in the analysis, including 138 newborns with PPHN and 318 newborns without PPHN (as controls). The optimal predictive variables selection was performed based on LASSO (least absolute shrinkage and selection operator) regression and multivariate logistic regression. Using the selected variables, a nomogram prediction model was developed. To validate the model, the model was assessed using the receiver operating characteristic curve, calibration plot, and clinical impact curve. Six predictors, namely, gestational age, neonatal respiratory distress syndrome, the levels of hemoglobin and creatine kinase-MB, gestational thyroid dysfunction, and Pa o2 , were identified by LASSO and multivariate logistic regression analysis from the original 30 variables studied. The constructed model, using these predictors, exhibited favorable predictive ability for PPHN, with an area under the receiver operating characteristic of 0.897 (sensitivity = 0.876, specificity = 0.785) in the training set and 0.871 (sensitivity = 0.902, specificity = 0.695) in the validation set, and was well calibrated, as indicated by the PHosmer-Lemeshow test values of 0.233 and 0.876 for the training and validation sets, respectively. The model included gestational age, neonatal respiratory distress syndrome, the levels of hemoglobin and creatine kinase-MB, gestational thyroid dysfunction, and Pa o2 had good prediction performance for predicting PPHN among newborns first admitted to the hospital after birth.

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.

Prevalence and Pattern of Gestational Thyroid Dysfunction in a Population of South-East Nigerian Women.

Pregnancy serves as a physiological stress test for the thyroid which often leads to dysfunction in women with limited thyroid reserves. The occurrence of gestational thyroid dysfunction is linked to unfavourable obstetric and foetal outcomes. Globally, iodine deficiency is a prominent causative factor for thyroid dysfunction. The study aimed to determine the prevalence and pattern of thyroid dysfunction among pregnant women in Enugu, South-east Nigeria. This hospital-based descriptive cross-sectional and observational study was conducted over six months on selected participants from pregnant women attending antenatal clinics at the study sites. Maternal clinical and demographic risk factors for thyroid dysfunction were evaluated in a cohort of 318 pregnant women. An analysis of variance (ANOVA) was performed to compare participants' thyroid status across different trimesters of pregnancy, and different thyroid and nutritional iodine states. The prevalence of thyroid dysfunction in the study population is 6.6%. Hypothyroidism was detected in 5.3% of the participants, consisting of 3.8% sub-clinical hypothyroidism and 1.6% overt hypothyroidism. Sub-clinical hyperthyroidism accounted for 1.3% of all participants; no overt hyperthyroidism was detected in this study. There is a relatively high prevalence of gestational thyroid dysfunction in the study population with hypothyroidism being the predominant disorder. This highlights the need for region-specific considerations in antenatal care to facilitate early detection and effective management of gestational thyroid dysfunction, thereby mitigating potential adverse maternal and foetal outcomes.

THU237 A Case Of Primary Hypothyroidism, Dysglycemia And Epilepsy With PAX8 And SETD1A Mutation

Abstract Disclosure: S.K. Singh: None. KEYWORDS: PAX8, SETD1A, DYSGLYCEMIA INTRODUCTION: Hypothyroidism is associated with dysglycemia linked with insulin resistance and shared common genetic determinants.PAX 8 gene regulates the development of thyroid gland as well as the expression of TG,TPO and NIS genes.It impacts glucose homeostasis by favoring beta-cell survival and through thyroid hormones.Epilepsy in hypothyroid patients can be idiopathic or due to Hashimoto’s Encephalopathy (HE). Thyroid hormones can impact epileptogenesis through mitochondrial dysfunction, oxidative-stress and GABAergic transmission. THE INDEX PATIENT: A 13 year old female(weight and height age 1.5 years below her chronological age by Indian growth chart and a further lag of 18 months and 6 months, respectively by CDC chart)was diagnosed as a case of thyroprivic hypothyroidism with TSH - 100 mIU/L and positive anti-TPO antibody. She was euthyroid on 112 ug/d L-T4.She is on anticonvulsant since 12 years of age for tonic-clonic epilepsy. The MRI of brain showed focal gliosis with few small encephalomalacic streaks in right occipital lobe. On evaluation at 12.5 years of age, her fasting plasma glucose was 80 mg/dl and her HbA1c was 4.8% but 2-h post glucose was 233 mg/dl with another value of 270 mg/dl. Her father has T2DM and Hypothyroidism. Her mother is Hypothyroid. Her genetic study showed SETDIA and PAX8(-) mutations. DISCUSSION: PAX8 regulates development of thyroid gland and biosynthesis of thyroid hormones. It can impact glucose homeostasis by enhancing beta-cell survival by inhibiting apoptosis, immunomodulation, maintaining local anti-inflammatory milieu in pancreas, ensuring systemic levels of thyroid hormone to stimulate insulin secretion and protect beta-cells from environmental stressors.PAX8 mutation in a family has been shown to be associated with a spectrum of disorders encompassing Gestational Thyroid Dysfunction(GTD),Gestational Diabetes Mellitus(GDM) and T2DM.[1] Although mutation analysis was done only in the index patient, Hypothyroidism and Dysglycemia (post- glucose&amp;gt;200 mg/dl)in the patient and family history of Hypothyroidism and T2DM could be linked with PAX8 mutation.SETD1A mutation has been linked with early-onset epilepsy with or without developmental delay. The mutation study can aid in deciding appropriate therapy including steroids for HE. CONCLUSION: This case highlights the significance of evaluation for PAX8 mutation in hypothyroid patients, even if anti-TPO positive, particularly when there is family history of thyroid dysfunction, GDM, T2DM. It also underlies the importance of SETD1A mutation analysis in hypothyroid patients with epilepsy. Presentation: Thursday, June 15, 2023

TSH and FT4 Reference Interval Recommendations and Prevalence of Gestational Thyroid Dysfunction: Quantification of Current Diagnostic Approaches.

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. 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. 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. 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.

Analysis of Risk Factors and Screening Results of Neonatal Congenital Hypothyroidism in a Tertiary Care Center of Southern China.

To explore the risk factors for neonatal congenital hypothyroidism (CH) and the influencing factors of false-positive results in CH screening. In this study, 255 neonatal patients with CH who completed the screening and further diagnosis and 366 neonates with positive CH screening results and normal thyroid function were selected as the case group. 246 healthy neonates with normal thyroid function were selected as the control group. Gestational age, birth-weight, maternal age, small for gestational age (SGA), perinatal factors (gestational thyroid dysfunction, gestational diabetes mellitus, etc.) were used as influencing factors, using χ 2 tests were performed for comparison. The statistically significant variables were analyzed with Logistic multiple regression models, and the difference was considered statistically significant (P<0.05). There were statistical differences in the SGA, maternal gestational diabetes mellitus, thyroid disease, and the proportion using assisted reproduction technology among the case group, false-positive screening group, and control group (χ 2 was 11.943, 6.857, 6.999, 9.732, respectively, P < 0.05). The results of multivariate logistic regression analysis showed that the gestational thyroid disease (OR = 8.452, 95% CI:1.051-67.982), gestational diabetes mellitus (OR = 2.654, 95% CI:1.051-6.706), and assisted reproduction (OR = 0.194, 95% CI:0.041-0.911) were the influencing factors for neonatal CH, and the difference was statistically significant (P < 0.05). The SGA (OR = 2.556, 95% CI:1.027-6.361), gestational thyroid disease (OR = 7.801, 95% CI:1.03-59.057), gestational diabetes mellitus (OR = 2.731, 95% CI:1.18-6.322), and assisted reproduction (OR = 0.28, 95% CI:0.102-0.765) were the influencing factors of the false-positive screening results of neonatal CH. The difference was statistically significant (P < 0.05). Neonatal CH and positive screening results are influenced by assisted reproduction, gestational thyroid dysfunction, gestational diabetes mellitus, and SGA.

Maternal Thyroid Dysfunction and Neuropsychological Development in Children.

Thyroid hormones are essential for fetal brain development. The potential effects of maternal gestational thyroid dysfunction on offspring neuropsychological development remain inconclusive. This work aimed to estimate effects of maternal thyroid dysfunction during pregnancy on offspring neuropsychological development in the first 2 years. We prospectively examined 1903 mothers and their children from the Shanghai Birth Cohort. Thyroid hormones were assessed at about 12 gestational weeks. Maternal thyroid function was classified into 7 categories: euthyroid, overt/subclinical hyperthyroidism, overt/subclinical hypothyroidism, hyperthyroxinemia, and hypothyroxinemia. Neuropsychological development was assessed by the Ages and Stages Questionnaire at age 6 months, and Bayley Scales at age 24 months. Compared with children of euthyroid mothers, maternal overt hypothyroidism was associated with 7.0 points (95% CI, 1.7-12.4) lower scores in personal-social domain in girls aged 6 months, 7.3 points (95% CI, 2.0-12.6) lower in motor domain, and 7.7 points (95% CI, 1.1-14.2) lower social-emotional scores in boys at age 24 months; maternal subclinical hypothyroidism was associated with 6.5 points (95% CI, 1.0-12.1) poorer social-emotional domain in boys at age 6 months, and 7.4 points (95% CI, 0.1-14.8) poorer adaptive behavior domain in boys at age 24 months; maternal hypothyroxinemia was associated with 9.3 points (95% CI, 3.5-15.1) lower motor scores in boys at age 24 months; and maternal subclinical hyperthyroidism was associated with 6.9 points (95% CI, 0.1-13.7) lower language scores in girls at age 24 months. Maternal overt hypothyroidism, subclinical hypothyroidism/hyperthyroidism, and hypothyroxinemia during early pregnancy were associated with weakened neuropsychological development in infancy, and some effects may be sex specific.

Reference values and the effect of clinical parameters on thyroid hormone levels during early pregnancy.

Objective: Thyroid dysfunction is a common endocrine problem during pregnancy; correct diagnosis and appropriate treatments are essential to avoid adverse pregnancy outcomes. Besides, it is vital to identify and quantify the major risk factors for gestational thyroid dysfunction, including thyroid autoimmunity, human chorionic gonadotropin (HCG) concentration, body mass index (BMI) and parity. The study objective was to establish reference ranges during early pregnancy and to explore the relationship between risk factors and thyroid stimulating hormone (TSH), free thyroxine (FT4) and free triiodothyroxine (FT3).Design, patients and measurements: To establish the reference ranges of thyroid hormone during early pregnancy in China and to identify the risk factors for thyroid dysfunction, woman in the first trimester of pregnancy (4–12 weeks gestation) were recruited. After excluding thyroid peroxidase antibody (TPO-Ab) positive and/or thyroglobulin antibody (TG-Ab) positive women, previous thyroid disease, a lack of iodine intake, reference values were calculated by 2.5th to 97.5th percentiles.Results: After exclusion of TPO-Ab and/or TG-Ab positive women, reference values were as follows: TSH, 0.11–3.67 mIU/l; FT3, 3.19–5.91 pmol/l; FT4 10.95–16.79 pmol/l. Higher BMI was associated with lower FT4 concentrations (P=0.005). In multiple regression analysis, TSH was significantly and positively associated with TG (P=0.03). Maternal parity and maternal age may be risk factors for the abnormal thyroidal response to hCG concentrations.Conclusions: Our study defined first trimester-specific reference ranges for serum TSH, FT4, FT3 in a Chinese population, and demonstrated that BMI ≥23kg/m2, maternal parity ≥3 and maternal age ≥30 years may increase the risk of thyroid dysfunction.

Diagnosis, treatment, and management of gestational hypothyroidism. The TIROGEST study

IntroductionThere is no agreement on the procedures to be used for diagnosis and treatment of gestational thyroid dysfunction. Controversy still exists on the normal range of thyroid-stimulating hormone (TSH) levels and use of gestational hypothyroidism (GH) screening. The aim of this study was to assess diagnosis and treatment of thyroid dysfunction during pregnancy in a group of Spanish hospitals. Study designThis was a retrospective, multicenter study in pregnant females with GH attending Spanish healthcare centers from March 2013 to July 2014. Variables analyzed included diagnosis criteria for GH (availability of universal screening for gestational thyroid disorders and TSH reference values (RVs) by trimester of pregnancy): risk factors for GH, iodine intake from food or supplementation, gestational age (at diagnosis/treatment) and l-thyroxine treatment. ResultsFourteen centers participated in the study. Universal screening was performed in only half of the centers, and only 14% had their own TSH RVs. Overall, 257 pregnant women were enrolled, 53.7% with hypothyroidism (HT) diagnosed before pregnancy (pre-GH) and 46.3% with HT diagnosed during pregnancy (intra-GH). A comparison of intra-GH and pre-GH women showed that intra-GH women made their first visit later (59.7% vs. 75.4% respectively before week 12, p=0.007) and had more frequently high TSH levels (>2.5μIU/ml) during the first trimester (94.4% vs. 67.0% respectively, p<0.001). ConclusionsOur results suggest that GH may be underdiagnosed or inadequately diagnosed in most healthcare centers. These findings suggest the need of improving the current practice in Spain.

Diagnosis, treatment, and management of gestational hypothyroidism. The TIROGEST study

IntroductionThere is no agreement on the procedures to be used for diagnosis and treatment of gestational thyroid dysfunction. Controversy still exists on the normal range of thyroid-stimulating hormone (TSH) levels and use of gestational hypothyroidism (GH) screening. The aim of this study was to assess diagnosis and treatment of thyroid dysfunction during pregnancy in a group of Spanish hospitals. Study designThis was a retrospective, multicenter study in pregnant females with GH attending Spanish healthcare centers from March 2013 to July 2014. Variables analyzed included diagnosis criteria for GH (availability of universal screening for gestational thyroid disorders and TSH reference values (RVs) by trimester of pregnancy): risk factors for GH, iodine intake from food or supplementation, gestational age (at diagnosis/treatment) and l-thyroxine treatment. ResultsFourteen centers participated in the study. Universal screening was performed in only half of the centers, and only 14% had their own TSH RVs. Overall, 257 pregnant women were enrolled, 53.7% with hypothyroidism (HT) diagnosed before pregnancy (pre-GH) and 46.3% with HT diagnosed during pregnancy (intra-GH). A comparison of intra-GH and pre-GH women showed that intra-GH women made their first visit later (59.7% vs. 75.4% respectively before week 12, p=0.007) and had more frequently high TSH levels (>2.5μIU/ml) during the first trimester (94.4% vs. 67.0% respectively, p<0.001). ConclusionsOur results suggest that GH may be underdiagnosed or inadequately diagnosed in most healthcare centers. These findings suggest the need of improving the current practice in Spain.

Evaluation of the impact of levothyroxine treatment on the psychomotor developmental status of three-year-old children born to mothers with mild thyroid impairment; Tehran Thyroid and pregnancy study: study protocol for a randomized clinical trial

BackgroundDespite the known adverse effects of maternal overt hypothyroidism on the neurocognitive development of children, there is uncertainty regarding the impact of gestational thyroid dysfunction or autoimmune thyroiditis on infant/child neurological development. This study aims to evaluate the impact of levothyroxine (LT4) treatment on the psychomotor developmental status of three-year-old children born to mothers with mild thyroid impairment (subclinical hypothyroidismwith/without autoimmune thyroiditis).Methods/DesignThis is a follow-up study of the Tehran Thyroid and Pregnancy Study, a randomized trial in which subclinical hypothyroid pregnant women were assigned to an intervention group (treated with levothyroxine) or a control group (received no treatment). The primary outcome for the purpose of the present study is the developmental status of the children, aged three years, in five domains (communication, gross motor, fine motor, problem-solving, and social–personal domains) using the Ages and Stages Questionnaire (ASQ).DiscussionThe study is designed to assess the developmental status of children born to mothers with mild thyroid impairment (subclinical hypothyroidism with/without autoimmune thyroiditis). This study is one of the limited studies available in this field and has the potential to facilitate much-needed information for related public health policies.Trial registrationIranian Registry of Clinical Trials, IRCT2017090314849N5. Registered on 11 September 2017. Iranian Registry of Clinical Trials, IRCT2017090414849N6. Registered on 14 October 2017.

Transient PAX8 Expression in Islets During Pregnancy Correlates With β-Cell Survival, Revealing a Novel Candidate Gene in Gestational Diabetes Mellitus.

Transient Pax8 expression was reported in mouse islets during gestation, whereas a genome-wide linkage and admixture mapping study highlighted PAX8 as a candidate gene for diabetes mellitus (DM). We sought the significance of PAX8 expression in mouse and human islet biology. PAX8 was induced in gestating mouse islets and in human islets treated with recombinant prolactin. Global gene expression profiling of human and mouse islets overexpressing the corresponding species-specific PAX8 revealed the modulation of distinct genetic pathways that converge on cell survival. Accordingly, apoptosis was reduced in PAX8-overexpressing islets. These findings support that PAX8 could be a candidate gene for the study of gestational DM (GDM). PAX8 was genotyped in patients with GDM and gestational thyroid dysfunction (GTD), a pathology commonly found in patients with mutations on PAX8 A novel missense PAX8 mutation (p.T356M, c.1067C>T) was identified in a female diagnosed with GDM and GTD as well as in her father with type 2 DM but was absent in control patients. The p.T356M variant did not alter protein stability or cellular localization, whereas its transactivation activity was hindered. In parallel, a retrospective clinical analysis uncovered that a pregnant female harboring a second PAX8 mutation (p.P25R, c.74C>G) previously reported to cause congenital hypothyroidism also developed GDM. These data indicate that increased expression of PAX8 affects islet viability and that PAX8 could be considered as a candidate gene for the study of GDM.

Influence of thyroid peroxidase antibodies on TSH levels of pregnant women and maternal–fetal complications

IntroductionDuring pregnancy, thyroid peroxidase (TPO) antibodies may increase the risk of developing subclinical hypothyroidism (SCH). Both conditions appear to be associated to maternal–fetal complications. The objectives of this study were to analyze if a relationship exists between TSH and TPO levels during pregnancy and the potential effects on gestational and perinatal complications, and to assess whether detectable, but not positive, TPO levels have an impact on development of gestational SCH. MethodsA prospective study was conducted at the Leon Health Area (CAULE), where universal screening for gestational thyroid dysfunction is performed between weeks 7–13 of pregnancy. Data on TSH and TPO levels and gestational and perinatal complications were collected for all 2016 deliveries. Positive TPO antibodies were defined as values≥35IU/ml. In a previous study, a TSH level>3.72mU/l was established as the cut-off value for gestational SCH. ResultsRecords corresponding to 1980 deliveries at CAULE, 21 abortions, and 18 deliveries outside the hospital were analyzed. Of the 1670 pregnant women screened (84.34%), 142 (8.50%) had positive TPO antibodies and their presence was associated to diagnosis of SCH (p<0.01) and to significantly higher mean TSH levels (3.51mU/l versus 2.46mU/l, p=0.03). There were no significant differences in gestational or neonatal complications. In the group with undetectable TPO antibodies (<10lU/ml), the mean TSH levels was slightly lower than in the group with TPO values ranging from 10 to 35IU/ml, but the difference was not significant (p=0.89). ConclusionPresence of positive TPO antibodies is associated to higher TSH levels and higher risk of gestational SCH, but does not increase the rate of maternal–fetal complications.

The Association of Maternal Thyroid Autoimmunity During Pregnancy With Child IQ.

Thyroperoxidase antibody (TPOAb) positivity is a major risk factor for gestational thyroid dysfunction. During the first 18 to 20 weeks of pregnancy, high concentrations of human chorionic gonadotropin (hCG) stimulate the thyroid to ensure adequate thyroid hormone availability for the developing fetus. However, TPOAb-positive women have an impaired thyroidal response to hCG stimulation. To study the association of maternal TPOAb positivity during pregnancy with child IQ. This study was embedded in two prospective birth cohorts: Generation R (Rotterdam, the Netherlands) and Avon Longitudinal Study of Parents and Children (ALSPAC; United Kingdom). Mother-child pairs with available data on early pregnancy TPOAb (≤18 weeks of gestation) and offspring IQ were included (n = 3637 for Generation R and n = 2396 for ALSPAC). Child IQ at 5 to 10 years of age. In Generation R, TPOAb positivity was associated with a 2.0 ± 0.9-point lower mean child IQ (P = 0.03). Sensitivity analyses showed negative effect estimates already from TPOAb concentrations considerably lower than currently used manufacturer cutoffs. In ALSPAC, neither TPOAb positivity nor TPOAb concentrations below manufacturer cutoffs were associated with child IQ (TPOAb positivity: 0.7 ± 1.0; P = 0.45). Adjustment for maternal TSH or free T4 concentrations or urinary iodine/creatinine ratio did not change the results. TPOAb positivity during pregnancy was associated with lower child IQ in Generation R but not in ALSPAC. Further studies are needed to elucidate whether differences between the study populations, such as maternal iodine status, could be the underlying cause for these differences.

Influencia de los anticuerpos antiperoxidasa tiroidea en los valores de TSH de gestantes y en las complicaciones materno-fetales

IntroductionDuring pregnancy, thyroid peroxidase (TPO) antibodies may increase the risk of developing subclinical hypothyroidism (SCH). Both conditions appear to be associated to maternal-fetal complications. The objectives of this study were to analyze if a relationship exists between TSH and TPO levels during pregnancy and the potential effects on gestational and perinatal complications, and to assess whether detectable, but not positive, TPO levels have an impact on development of gestational SCH. MethodsA prospective study was conducted at the Leon Health Area (CAULE), where universal screening for gestational thyroid dysfunction is performed between weeks 7-13 of pregnancy. Data on TSH and TPO levels and gestational and perinatal complications were collected for all 2016 deliveries. Positive TPO antibodies were defined as values≥35IU/mL. In a previous study, a TSH level>3.72mU/L was established as the cut-off value for gestational SCH. ResultsRecords corresponding to 1,980 deliveries at CAULE, 21 abortions, and 18 deliveries outside the hospital were analyzed. Of the 1,670 pregnant women screened (84.34%), 142 (8.50%) had positive TPO antibodies and their presence was associated to diagnosis of SCH (P<0.01) and to significantly higher mean TSH levels (3.51mU/L vs. 2.46mU/L, P=0.03). There were no significant differences in gestational or neonatal complications. In the group with undetectable TPO antibodies (<10lU/mL), the mean TSH levels was slightly lower than in the group with TPO values ranging from 10-35 IU/mL, but the difference was not significant (P=0.89). ConclusionPresence of positive TPO antibodies is associated to higher TSH levels and higher risk of gestational SCH, but does not increase the rate of maternal-fetal complications.

Assessment of normal range of thyroid function tests in healthy Egyptian pregnant women

Background: Gestational thyroid dysfunction has been associated with a variety of adverse pregnancy outcomes. This study aimed to determine trimester-specific reference intervals of thyroid function tests for normal pregnant Egyptian women. Subjects and Methods: A cross-sectional study was conducted at the Obstetric Clinic, Ain Shams University Hospitals. The total enrolled pregnant women were 360, who were divided into the following three groups according to gestational age: Group 1 included 120 participants in the first trimester; Group 2 included 120 participants in the second trimester; and Group 3 included 120 participants in the third trimester. All women were healthy with uncomplicated single intrauterine gestations. A detailed obstetric history, clinical examination, estimation of thyroid-stimulating hormone (TSH), free tetraiodothyronine (FT4), free triiodothyronine (FT3), antithyroid peroxidase antibodies, and thyroglobulin antibodies were done for all participated women. Results: TSH value increased with advancing pregnancy from 1.43 ± 1.16 μIU/mL in the first trimester to 1.78 ± 1.19 μIU/mL in the third trimester, and the difference between each trimester was statistically significant. The FT4 level decreased from 1.16 ± 0.23 ng/dL in the first trimester to 0.98 ± 0.17 ng/dL in the third trimester, and the difference was statistically significant. The FT3 level decreased from 3.18 ± 0.52 pg/ml in the first trimester to 2.79 ± 0.38 pg/ml in the third trimester, and the difference was statistically significant. Conclusion: There were significant changes of thyroid function test during each trimester of pregnancy, the reference ranges in this study are different from previous studies outside Egypt. Accordingly, it is necessary to use trimester specific reference range for every population.

Incidence and Prevalence of Pregnant Women with Gestational Diabetes Mellitus, Thyroid Disorders and Eclampsia in Khammam Region, Telangana State

Objective: The aim of this study was to estimate the incidence and prevalence of Gestational Diabetes Mellitus (GDM), Thyroid dysfunction and Eclampsia in pregnant women prior to delivery. Methods: An observational retrospective study was conducted between December 2016 and June 2017 in a District Headquarters Hospital and two other tertiary antenatal care centers on pregnant women who delivered between 37 and 42 weeks of gestational age. The study participants data was collected prior delivery who were diagnosed as GDM with Random Blood Sugar levels ≥ 140mg/dl, hyperthyroidism with ≤1.1 µIU/ml and hypothyroidism with ≥ 5.5 µIU/ml and Eclampsia in women who had a grand mal seizure with features of preeclampsia. Results: A total of 265 pregnant women was included whose information was sampled. A prevalence of 10.5% (n = 28) was identified with GDM, 77.7% (n = 206) was identified with Thyroid Disorders and 11.6% (n = 31) with Eclampsia who were categorized into rural and urban communities based on age groups. Conclusion: Ignorance regarding antenatal check-up, lack of transport and lack of early communication with a tertiary hospital play an important role for high incidence and prevalence of complications in pregnancy in Khammam region, Telangana State.

MECHANISMS IN ENDOCRINOLOGY: Maternal thyroid dysfunction during pregnancy and behavioural and psychiatric disorders of children: a systematic review.

Maternal thyroid dysfunction during pregnancy may lead to persistent neurodevelopmental disorders in the offspring appearing in later life. This study aimed to review the available evidence concerning the relationship between maternal thyroid status during pregnancy and offspring behavioural and psychiatric disorders. Systematic electronic database searches were conducted using PubMed, Embase, PsycNET, Scopus, Google Scholar and Cochrane library. Studies including gestational thyroid dysfunction as the exposure and offspring behavioural and psychiatric disorders as the outcome were included. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed and, after thorough screening by two independent reviewers, 13 articles remained eligible for inclusion in this study. Indicators of maternal thyroid dysfunction, including low and high thyroid hormone level and autoimmune thyroiditis, during early pregnancy, were found to be associated with several offspring behavioural and psychiatric disorders such as attention deficit hyperactivity disorder (ADHD), autism, pervasive developmental problems, externalising behaviour, in addition to epilepsy and seizure. The majority of associations were found with low maternal thyroid hormone level. Maternal thyroid function during pregnancy, particularly hypothyroidism, is associated with behavioural and psychiatric disorders in children. Further studies are needed with a capacity to adjust for a fuller range of confounding factors.

LETTER: Women with Gestational Thyroid Dysfunction May Be at Higher Risk for Thyroid Disease Developing Postpartum

LETTER: Women with Gestational Thyroid Dysfunction May Be at Higher Risk for Thyroid Disease Developing Postpartum