Investigation of the relationship between air pollution and gestational diabetes.

BACKGROUND: Gestational diabetes mellitus (GDM) can have negative effects on both the pregnancy and perinatal outcomes, as well as the long-term health of the mother and the child. It has been suggested that exposure to air pollution may increase the risk of developing GDM. This study investigated the relationship between exposure to air pollutants with gestational diabetes. METHODS: The present study is a retrospective cohort study. We used data from a randomised community trial conducted between September 2016 and January 2019 in Iran. During this period, data on air pollutant levels of five cities investigated in the original study, including 6090 pregnant women, were available. Concentrations of ozone (O3), nitric oxide (NO), nitrogen dioxide (NO2), nitrogen oxides (NOx), sulphur dioxide (SO2), carbon monoxide (CO), particulate matter < 2.5 (PM2.5) or <10 µm (PM10) were obtained from air pollution monitoring stations. Exposure to air pollutants during the three months preceding pregnancy and the first, second and third trimesters of pregnancy for each participant was estimated. The odds ratio was calculated based on logistic regression in three adjusted models considering different confounders. Only results that had a p < .05 were considered statistically significant. RESULTS: None of the logistic regression models showed any statistically significant relationship between the exposure to any of the pollutants and GDM at different time points (before pregnancy, in the first, second and third trimesters of pregnancy and 12 months in total) (p > .05). Also, none of the adjusted logistic regression models showed any significant association between PM10 exposure and GDM risk at all different time points after adjusting for various confounders (p > .05). CONCLUSIONS: This study found no association between GDM risk and exposure to various air pollutants before and during the different trimesters of pregnancy. This result should be interpreted cautiously due to the lack of considering all of the potential confounders.

The health of pregnant women and their children can be impacted by gestational diabetes mellitus (GDM), one of the prevalent pregnancy complications. Some of studies showed that the incidence of gestational diabetes can be influenced by genetic or environmental factors. Air pollution is an environmental stimulus that may predispose pregnant women to GDM. This research explored whether air pollution could increase the risk of developing gestational diabetes. Over 6000 pregnant women in five cities of Iran participated in the study and were screened for gestational diabetes. Their exposure to the various air pollutants during the three months preceding pregnancy and total pregnancy period was measured. In this study, we found no clear association between air pollution and gestational diabetes. However, this finding needs to be interpreted cautiously since all the influential factors were not assessed.

Lack of beneficiary effect of levothyroxine therapy of pregnant women with subclinical hypothyroidism in terms of neurodevelopment of their offspring.

PURPOSE: Despite the beneficial effects of levothyroxine (LT4) therapy on pregnancy outcomes of women with subclinical hypothyroidism (SCH), its impact on the developmental status of offspring remains unclear. We aimed to assess the effects of LT4 therapy on the neurodevelopment of infants of SCH women in the first 3 years of life. METHODS: A follow-up study was conducted on children born to SCH pregnant women who had participated in a single-blind randomized clinical trial (Tehran Thyroid and Pregnancy Study). In this follow-up study, 357 children of SCH mothers were randomly assigned to SCH + LT4 (treated with LT4 after the first prenatal visit and throughout pregnancy) and SCH-LT4 groups. Children born of euthyroid TPOAb-women served as the control group (n = 737). The neurodevelopment status of children was assessed in five domains (communication, gross motor, fine motor, problem-solving, and social-personal domains) using the Ages and Stages Questionnaires (ASQ) at the age of 3 years. RESULTS: Pairwise comparisons of ASQ domains between euthyroid, SCH + LT4, and SCH-LT4 groups show no statistically significant difference between groups in the total score [median 25-75 total score: 265 (240-280); 270 (245-285); and 265 (245-285); P-value = 0.2, respectively]. The reanalyzing data using the TSH cutoff value of 4.0 mIU/L indicated no significant difference between groups in the score of ASQ in each domain or total score with TSH levels < 4.0 mIU/L, however, a statistically significant difference in the median score of the gross motor was observed between those SCH + LT4 with baseline TSH values ≥ 4.0 mIU/L and SCH-LT4 [60 (55-60) vs. 57.5 (50-60); P = 0.01]. CONCLUSIONS: Our study does not support the beneficiary effect of LT4 therapy for SCH pregnant women in terms of the neurological development of their offspring in the first three years of life.

The Relationship between Air Pollution and Infant Mortality Rate.

Background: We aimed to investigate the relationship between air pollution and the Infant mortality rate (IMR) during nearly ten years in Tehran, Iran. Methods: This study is a retrospective cohort case using time series analysis. Air pollution monitoring data during the study period (2009-2018) were collected from the information of 23 Air Quality Control Centers in different areas of Tehran. For this purpose, the daily measures of PM10, PM2.5, O3, CO, SO2, NO2 were obtained. Data on infant mortality was obtained from the National Statistics Office of Iran and mortality registered in Tehran's main cemetery during the study period. Distributed lag linear and non-linear models were used. Results: A total of 23,206 infant deaths were reported during the study period. Following an increase of 10 ug/m3 in PM10 in an early day of exposure, the risk of mortality increased significantly (RR=1.003, 95%CI:1.001-1.005). There is a pick on lag 5-10 that shows a very strong and immediate effect of cold temperature which means that cold temperatures increase the risk of mortality at an early time. At cold temperate, (var=0 and lag 0) risk of infant mortality was significantly higher than reference temperature (19°C) (RR=1.1295, %CI: 1.01-1.25). Conclusion: The results show the adverse effects of PM10 exposure on infant mortality in Tehran, Iran. Accordingly, a steady decline in PM10 levels in Tehran may have greater benefits in reducing the Infant mortality rate.

A Bayesian model to estimate the cutoff value of TSH for management of preterm birth.

BACKGROUND: Determining a thyroid hormone cutoff value in pregnancy is challenging issue and several approaches have been introduced to optimize a utility function. We aimed to estimate the cutoff value of TSH using Bayesian method for prediction of preterm-birth. METHODS: This study was a secondary-analysis of the population-based data collected prospectively within the framework of the Tehran Thyroid and Pregnancy Study. A total of 1,538 pregnant women attending prenatal clinics. RESULTS: Using Bayesian method resulted a TSH-cutoff of (3.97mIU/L,95%CI:3.95-4.00) for distinguishing pregnant women at risk of preterm-birth. The cutoff was associated with acceptable positive predictive and negative predictive values (0.84,95% CI:0.80-0.88) and 0.92 (95%CI: 0.91-0.94), respectively). In women who were negative for thyroid peroxides antibody (TPOAb) with sufficient urinary iodine concentration (UIC), the TSH cutoff of 3.92 mIU/L(95%CI:3.70-4) had the highest predictive value; whereas in TPOAb positive women with insufficient UIC, the cutoff of 4.0 mIU/L(95%:CI 3.94-4) could better predict preterm birth. Cutoffs estimated in this study are close to the revised TSH value of 4.0mIU/L which is currently recommended by the American Thyroid Association. CONCLUSION: Regardless of TPOAb status or iodine insufficiency, risk of preterm labor is increased in pregnant women with TSH value of > 3.92 mIU/L; these women may benefit from Levothyroxine (LT4) therapy for preventing preterm birth.

Prediction of preterm delivery based on thyroid peroxidase antibody levels and other identified risk factors.

OBJECTIVE: Thyroid dysfunction and TPOAb positivity during pregnancy are associated with adverse pregnancy outcomes such as preterm delivery. The aim of this study was to predict preterm delivery based on identified risk factors, especially TPOAb levels. STUDY DESIGN: A secondary analysis was run on data collected in the Tehran Thyroid and Pregnancy study (TTPs). We used the data of 1515 pregnant women with singletons. The association between risk factors and preterm birth (delivery before 37 completed weeks of gestation) was investigated in univariate analysis. Multivariate logistic regression analysis was performed to identify independent risk factors, and a stepwise backward elimination method was used to determine the helpful combination of risk factors. The nomogram was developed based on a multivariate logistic regression model. The performance of the nomogram was evaluated using a concordance index and calibration plots with bootstrap samples. Statistical analysis was performed using STATA software package; the significance level was set at P < 0.05. RESULTS: Based on multivariate logistic regression analysis, a combination of previous preterm delivery [OR: 5.25; 95 %CI: (2.13-12.90), p < 0.01], TPOAb [OR: 1.01; 95 %CI: (1.01-1.02), and T4 [OR: 0.90; 95 %CI: (0.83-0.97); p = 0.04] as independent risk factors that most precisely predicted preterm birth. The area under the curve (AUC) was 0.66 (95% CI: 0.61-0.72). The calibration plot suggests that the fit of the nomogram is reasonable. CONCLUSION: A combination of T4, TPOAb, and previous preterm delivery was identified as independent risk factors that accurately predicted preterm delivery. The total score obtained based on the nomogram designed based on risk factors can predict the risk of preterm delivery.

Evaluation of pregnancy outcomes in mothers with COVID-19 infection: a systematic review and meta-analysis.

Pregnant women are one of the endangered groups who need special attention in the COVID-19 epidemic. We conducted a systematic review and summarised the studies that reported adverse pregnancy outcomes in pregnant women with COVID-19 infection. A literature search was performed in PubMed and Scopus up to 1 September 2022, for retrieving original articles published in the English language assessing the association between COVID-19 infection and adverse pregnancy outcomes. Finally, in this review study, of 1790 articles obtained in the initial search, 141 eligible studies including 1,843,278 pregnant women were reviewed. We also performed a meta-analysis of a total of 74 cohort and case-control studies. In this meta-analysis, both fixed and random effect models were used. Publication bias was also assessed by Egger's test and the trim and fill method was conducted in case of a significant result, to adjust the bias. The result of the meta-analysis showed that the pooled prevalence of preterm delivery, maternal mortality, NICU admission and neonatal death in the group with COVID-19 infection was significantly more than those without COVID-19 infection (p<.01). A meta-regression was conducted using the income level of countries. COVID-19 infection during pregnancy may cause adverse pregnancy outcomes including of preterm delivery, maternal mortality, NICU admission and neonatal death. Pregnancy loss and SARS-CoV2 positive neonates in Lower middle income are higher than in High income. Vertical transmission from mother to foetus may occur, but its immediate and long-term effects on the newborn are unclear.

Maternal Subclinical Hyperthyroidism and Adverse Pregnancy Outcomes: A Systematic Review and Meta-analysis of Observational Studies.

Context: Findings from studies evaluating adverse pregnancy outcomes in pregnant women with subclinical hyperthyroidism are conflicting and inconclusive. Objectives: In this systematic review and meta-analysis, our aim was to evaluate the pooled odds ratio (OR) of adverse pregnancy outcomes in women with subclinical hyperthyroidism, compared to euthyroid women. Data Sources: Scopus, PubMed (including Medline), and Web of Science databases were systemically searched for regaining published studies to January 2022 examining adverse pregnancy outcomes in women with subclinical hyperthyroidism. Study Selection: Outcomes of interest were classified into seven composite outcomes, including hypertensive disorders, preterm delivery, macrosomia/large for gestational age (LGA), pregnancy loss, adverse maternal outcomes, adverse neonatal outcomes, and adverse fetal outcomes. Data Extraction: In this meta-analysis, both fixed and random effect models were used. Publication bias was also evaluated by Egger test and the funnel plot, and the trim and fill method was conducted in case of a significant result, to adjust the bias. Results: Of 202 records retrieved through searching databases, 11 studies were selected for the final analyses. There were no significant differences in pooled ORs of hypertensive disorders, preterm delivery, macrosomia/LGA, and pregnancy loss in pregnant women with subclinical hyperthyroidism, compared to the euthyroid controls. The pooled OR of adverse maternal, neonatal, and fetal outcomes in pregnant women with subclinical hyperthyroidism was not statistically significantly different from that of the euthyroid control group. Conclusions: The current meta-analysis demonstrated that subclinical hyperthyroidism in pregnancy is not related with adverse maternal and fetal outcomes. Therefore, clinicians should be avoided unnecessary treatments for pregnant women with subclinical hyperthyroidism.

Maternal subclinical hyperthyroidism and adverse pregnancy outcomes considering the iodine status: Tehran thyroid and pregnancy study.

BACKGROUND: Unlike overt thyroid diseases, the impacts of subclinical thyroid dysfunction, especially subclinical hyperthyroidism (SH), on adverse pregnancy outcomes are inconclusive. OBJECTIVE: We aimed to investigate the effect of maternal SH on adverse maternal and neonatal outcomes based on urinary iodine concentration (UIC). METHODS: A secondary analysis was run on data collected in the Tehran Thyroid and Pregnancy study (TTPs). We used the data of 131 women with SH and 1650 cases of euthyroid. Serum levels of thyroid-stimulating hormone (TSH), thyroxine (T4), free thyroxine index (FT4I), and thyroid peroxidase antibody (TPOAb) were assessed at the first prenatal visit. A generalized linear regression model was applied to identify the effect of SH on the pregnancy outcomes based on UIC, and the effects were estimated with a 95% confidence interval. RESULTS: Preterm delivery was observed in 12.3% of women with SH and 6.7% of those with euthyroid (P = 0.03). Women with TSH< 0.3 mIU/L had a higher odds of preterm delivery than those with TSH≥ 0.3 regardless of urine iodine cut-off [OR= 2.27; 95% CI: (1.15, 4.48), p = 0.02]. Among those with UIC levels≥ 150 µg/L, the odds ratio of preterm delivery was 4.61 folds higher in the SH group compared to those with euthyroid [95%CI: (1.36, 15.71), p = 0.01)]. No significant difference between these two study groups was found in Neonatal Intensive Care Unit admission. Moreover, the results revealed no statistically significant difference in the means of neonatal anthropometric parameters in the SH and euthyroid groups in none of the subgroups of UIC (<150 or ≥150 µg/l). CONCLUSIONS: According to our results, maternal SH appears to be a risk factor for preterm delivery. This effect is more pronounced in women with higher UIC than those with lower UIC.

Effects of isolated maternal hypothyroxinemia on adverse pregnancy outcomes.

PURPOSE: There are conflicting results about the effects of maternal hypothyroidism (IMH) on adverse pregnancy outcomes. This study aimed to investigate the relationship between IMH identified in the first trimester of gestation and adverse pregnancy outcomes. METHODS: In this prospective cohort study, we used data from the Tehran Thyroid and Pregnancy study (TTPs). To diagnose IMH, we considered a threshold of 2.04 for FTI, which was based on the 10th percentile of this marker identified in the 1st trimesters. A generalized linear regression (GLM) model adjusted for the gravidity, urine iodine, and TPOAb status was applied to assess the effects of IMH on adverse pregnancy outcomes, compared to the controls group. RESULTS: Penalized logistic regression analysis indicated that the adjusted odds ratio (aOR) of Preterm premature rupture of the membranes (PPROM) in women with IMH was 5.43-folder higher than euthyroid group [aOR 5.43, 95% CI (1.40, 21.1), p = 0.01]. Besides, the adjusted odds ratio of low birth weight (LBW) in the IMH group was 2.53-folder higher than the healthy group [aOR 2.53, 95% CI (1.01, 6.33), p = 0.047]. Furthermore, the results of the GLM adjusted model revealed that the mean of neonatal head circumference and weight in the IMH group was around 0.43 cm (95% CI - 0.80, - 0.07, p = 0.02) and 145.4 g (95% CI - 242.6, - 48.1, p = 0.003) lower than euthyroid group, respectively. CONCLUSIONS: This study demonstrated that women with IMH identified in early pregnancy have a higher odds ratio for developing some adverse pregnancy outcomes, including PPROM and LBW compared to their euthyroid counterparts. Also, the neonatal head circumference and weight in the IMH group were lower than in the euthyroid group.

Delivery factors and neonatal thyroid hormone levels: a systematic review.

Postnatal thyroid hormone changes enable the neonate to be adapted for postnatal life. Several factors can affect this adaption. In this review, we summarized the studies that reported the association among the delivery factors and neonatal thyroid hormones and thyroid stimulating hormone. A comprehensive literature search was performed in PubMed, Web of Science, and Scopus up to March 2020, to identify the studies investigating the relationship between delivery factors, especially the mode of delivery and labor pain, and neonatal thyroid hormones and TSH. Finally, in this review study, of 157 articles obtained in the initial search, 25 eligible studies were reviewed. Various maternal, fetal/neonatal, and obstetric factors affected neonatal TSH and thyroid hormones. Among various influencing factors, mode of delivery, labor pains, and duration of labor have a strong relationship with neonatal thyroid hormones and need to be considered for interpretation of neonatal thyroid status. The majority of the studies revealed that vaginal deliveries (instrumental or natural) lead to higher levels of cord TSH compared to elective cesarean section. This can be explained by the increased secretion of catecholamine during labor. It has been suggested that blood TSH and thyroid hormone levels are affected by perinatal stress events such as maternal anxiety, labor pains, fetal distress, and other stimulants of the catecholamine response. These changes may act as the trigger to increase thyroid hormone levels for adapting of neonates in the first hours after birth. This assumption needs to be re-evaluated by performing comprehensive and well-designed studies.

Isolated maternal hypothyroxinemia and adverse pregnancy outcomes: A systematic review.

Maternal thyroid hormones are vital for a normal pregnancy and the development of fetus and childhood; inadequate availability of thyroid hormones during pregnancy is associated with adverse pregnancy outcomes. Isolated maternal hypothyroxinemia (IMH) is defined as a low maternal T4 in the absence of TSH elevation. This systematic review aimed to investigate the association between IMH and adverse pregnancy outcomes. PubMed, Scopus and Web of science were searched for retrieving observational studies published up to September 2020, investigating the association of IMH with adverse pregnancy outcomes. From a total of 308 articles, 17 met our eligibility criteria and were used for the purpose of the present study. Definition of IMH varied in different studies. While some studies reported no adverse pregnancy outcomes for IMH, other studies found a positive association between first trimester IMH and feto-maternal outcomes including gestational hypertension, gestational diabetes, preterm delivery, fetal distress, small for gestational age, musculoskeletal malformations, spontaneous abortion, placental abruption and macrosomia. IMH, identified in the second trimester was associated with an increase in the risk of gestational diabetes, and hypertensive disorders of pregnancy in one study. There is no consensus on the adverse effects of IMH on pregnancy outcomes. Further comprehensive cohort studies using one standard definition for IMH, with large sample size and control of important confounders such as iodine status and maternal Thyroid peroxidase antibody (TPOAb) are needed for precise assessment of this association.

Maternal Urinary Iodine Concentration and Pregnancy Outcomes: Tehran Thyroid and Pregnancy Study.

Iodine is essential for the production of thyroid hormones, and its deficiency during pregnancy may be associated with poor obstetric outcomes. The aim of this study was to investigate the relationship between maternal iodine statuses with pregnancy outcomes among pregnant Iranian women, considering their baseline thyrotropin (TSH) status. We used data from the Tehran Thyroid and Pregnancy Study (TTPS), a two-phase population-based study carried out among pregnant women receiving prenatal care. By excluding participants with overt thyroid dysfunction and those receiving levothyroxine, the remaining participants (n = 1286) were categorized into four groups, according to their urine iodine status: group 1, urine iodine concentration (UIC) < 100 µg/L; group 2, UIC between 100 and 150 µg/L; group 3, UIC between 150 and 250 µg/L; and group 4, UIC ≥ 250 µg/L. Primary outcome was preterm delivery. Preterm delivery occurred in 29 (9%), 19 (7%), 15 (5%), and 8 (4%) women, and neonatal admission was documented in 22 (7%), 30 (12%), 28 (11%), and 6 (3%) women of groups 1, 2, 3, and 4, respectively. Generalized linear regression model (GLM) demonstrated that the odds ratio of preterm delivery was significantly higher in women with urinary iodine < 100 µg/L and TSH ≥ 4 µIU/mL than those with similar urinary iodine with TSH < 4 µIU/mL (OR 2.5 [95% CI 1.1, 10], p = 0.024). Adverse pregnancy outcomes are increased among women with UIC < 100 µg/L, with serum TSH concentrations ≥ 4 µIU/mL.

Maternal Urinary Iodine Concentration and Pregnancy Outcomes in Euthyroid Pregnant Women: a Systematic Review and Meta-analysis.

Iodine is an essential macronutrient for feto-maternal growth and development. Emerging evidence suggests that maternal iodine deficiency during pregnancy is potentially associated with both maternal and fetal adverse outcomes. The aim of this systematic review and meta-analysis was to investigate the association between maternal iodine status in euthyroid pregnant women and adverse pregnancy outcomes. A comprehensive literature search was performed in PubMed, Web of Science and Scopus up to October 2019 for retrieving related published articles in English. World Health Organization maternal median urinary iodine concentration (UIC) classification was used as follows: median UIC of less than 100, 100-149, 150-249, and more than 250 µg/L, for moderate-to-severe iodine deficiency, mild iodine deficiency, iodine adequate and more than adequate-to-excessive iodine, respectively. The primary outcomes of interest in this meta-analysis were the pooled prevalence and pooled odds ratio of the preterm birth, low birth weight (LBW), and one composite outcome of hypertensive disorders of pregnancy comprising pregnancy hypertension and preeclampsia. The secondary outcome was pooled mean of neonatal characteristics including birth weight, head circumference, Apgar score, and gestational age at birth. A total of 6 studies involving 7698 participants were included in this meta-analysis. The pooled prevalence of preterm birth, LBW, and hypertensive disorders of pregnancy were not statistically significantly different in the four groups of UIC levels. The pooled prevalence of preterm birth was 0.05, 0.04, 0.04, and 0.03 in UIC < 100, 100-149, 150-249, and > 250 µg/L, respectively. No evidence of an association was observed among the odds of preterm birth, LBW, and hypertensive disorders of pregnancy in euthyroid pregnant women with UIC between 100 and 149, 150-249, and > 250 µg/L compared with UCI < 100 µg/L. Likewise, there were not any statistical significant differences between the neonatal characteristics in different UIC groups. The results remained unchanged after subgroup analysis based on UIC less than 150 µg/L as abnormal UIC level. The present meta-analysis showed that the UIC of euthyroid pregnant women is not generally associated with the pregnancy outcomes and it per se is an insufficient indicator for prediction of pregnancy complications. The results of this study are important for reproductive healthcare providers and policymakers in providing appropriate healthcare service for pregnant women. However, further studies are needed to confirm these findings.

Levothyroxine treatment and pregnancy outcomes in women with subclinical hypothyroidism: a systematic review and meta-analysis.

PURPOSE: To evaluate the benefits of LT4 treatment on pregnancy outcomes in SCH women. STUDY DESIGN: PubMed [including Medline], Web of Science, Wiley, Google Scholar, Science direct and Scopus were searched for identifying and retrieving all English articles published up to May 2018 on the effects of levothyroxine treatment on pregnancy outcomes in pregnant women with SCH compared to untreated or healthy controls. In this systematic review and meta-analysis, both fixed and random effect models were applied to estimate the pooled effect size. Heterogeneity and publication bias were evaluated using the I-squared (I2) and Begg's statistics, respectively. We also explored heterogeneity sources using meta-regression models and sensitivity analysis. RESULTS: Data of 13 cohort studies and randomized controlled trials with a total of 11,503 participants were analyzed. This meta-analysis showed that pregnant women with SCH treated with levothyroxine had lower chances of pregnancy loss (OR 0.78, 95% CI 0.66-0.94; I2 = 0%) and higher chances for live birth rates (OR 2.72, 95% CI 1.44-5.11; I2 = 25%) than the placebo group. Compared to euthyroid women, SCH patients treated with levothyroxine had higher odds ratio for preterm labor (OR 1.82, 95% CI 1.14-2.91; I2 = 0%). CONCLUSIONS: Results of this study showed that the effects of treatment with levothyroxine in SCH pregnant women are not the same for all pregnancy outcomes. Levothyroxine treatment in these patients can reduce pregnancy loss. Considering the limited number of studies available, further studies are warranted to document more precise data on other consequences.

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.

BACKGROUND: Despite 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/DESIGN: This 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). DISCUSSION: The 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 REGISTRATION: Iranian Registry of Clinical Trials, IRCT2017090314849N5 . Registered on 11 September 2017. Iranian Registry of Clinical Trials, IRCT2017090414849N6 . Registered on 14 October 2017.

Reproductive Assessment: Findings from 20 Years of the Tehran Lipid and Glucose Study.

CONTEXT: Reproductive domains of the Tehran lipid and glucose study (TLGS) are unique in that they provide reliable information on reproduction of an urban population of West Asia. The aim of this review is to present the most important reproductive findings of TLGS. EVIDENCE ACQUISITION: This review is summarizing all articles published in the context of reproductive aspects of TLGS results over the 20-year follow-up. A comprehensive databases search was conducted in PubMed (including Medline), Web of Science and Scopus for retrieving articles on the reproductive histories in context of the TLGS. RESULTS: The mean (SD) age at menarche and menopause was 13 (1.2) and 49.6 (4.5) years respectively. While pills were the most commonly used modern methods at the initiation of TLGS, the prevalence of condoms rose sharply and significantly over the follow up duration. Among women with history of gestational diabetes, the risk of diabetes and dyslipidemia progression were 2.44 and 1.2 fold higher than others. Prevalences of PCOS and idiopathic hirsutism among reproductive age participants of TLGS were 8.5% (95% CI: 6.8% - 10.2%) and 13.0% (95% CI: 10.9% - 15.1%), respectively. Trend of cardio-metabolic risk factors among women with PCOS showed that there were no statistically significant differences between mean changes of each cardio metabolic variables between PCOS and healthy women; PCOS status also significantly associated with increased hazard of diabetes and prediabetes among women aged younger than 40 years (HR: 4.9; 95% CI: 2.5 - 9.3, P value < 0.001)) and (HR: 1.7; 95% CI: 1.1 - 2.6), P value < 0.005), respectively. CONCLUSIONS: The population based nature of TLGS provides a unique opportunity for valid assessment of reproductive issues, the results of which could provide new information for modification of existing guidelines.

Validation of Billewicz Scoring System for Detection of Overt Hypothyroidism During Pregnancy.

BACKGROUND: Currently, various clinical and laboratory diagnostic methods are used to detect overt hypothyroidism during pregnancy. The Billewicz scoring index, as a clinical scale for detection of hypothyroidism, has been applied in general populations; however, its application during pregnancy remains a controversial subject of ongoing research. OBJECTIVES: The purpose of this study was to evaluate the diagnostic value of Billewicz scoring index for overt hypothyroidism in a general population of Iranian pregnant women. METHODS: This study was conducted on 1843 pregnant women. A comprehensive questionnaire, including Billewicz scoring items, was completed, and relevant clinical examinations were performed. The participants underwent serum measurements of thyroxine (T4), thyroid hormone uptake, thyroid-stimulating hormone (TSH), and thyroid peroxidase antibody (TPOAb). Using the receiver operating characteristic (ROC) curve analysis, the optimal sensitivity and specificity were determined as values with maximum yields on the Youden and Rsquo's Index (sensitivity + specificity-1). RESULTS: The prevalence of overt hypothyroidism and subclinical hypothyroidism was 3.3% and 28.6%, respectively. Overall, 3.6%, 18.9%, and 50% of euthyroid, subclinical hypothyroid, and overt hypothyroid women were TPOAb-positive, respectively. The mean Billewicz scores of euthyroid, overt hypothyroid, and subclinical hypothyroid women were -41.16 (11.16), -17.11 (13.63), and -40.1 (11.2), respectively. Based on the Billewicz scale, at least one sign of hypothyroidism was reported in 38.84% (n, 491) of euthyroid women. Scores ≤ -26.5 (sensitivity, 100%; specificity, 90.82%) were considered as the optimal scores for predicting overt hypothyroidism (Ldquo, Norisk, and Rsquo). CONCLUSIONS: The Billewicz clinical scoring system, as a reliable and inexpensive clinical tool, used along with laboratory measurements, can help screen overt hypothyroidism during pregnancy, primarily in low-resource settings.

Establishment of trimester-specific reference range for thyroid hormones during pregnancy.

OBJECTIVE: Physiological gestational changes are associated with alterations in thyroid function which require different biochemical interpretation from that of non-pregnant women and necessitate established pregnancy-specific reference ranges. We aimed to identify the trimester-specific ranges of thyroid markers in a healthy population of pregnant Iranian women. METHODS: In this self-sequential study, data were extracted from The Tehran Thyroid and Pregnancy Study; a total of 314 women were tested during the 1st, 2nd and 3rd trimesters for serum levels of thyrotropin (TSH), thyroxine (T4), free thyroxine index (FT4I) and thyroid peroxidase antibody (TPOAb). Trimester-specific reference intervals for TSH, T4 and FT4I and first trimester reference range for TPOAb were estimated. The normal and modulus exponential-normal models were fitted by maximum likelihood using STATA software. The 2.5th and 97.5th percentiles of thyroid parameters were determined and used as reference intervals. RESULTS: Mean±SD age of participants was 26.8±5.2years. Estimated reference intervals for TSH, T4 and FT4I in the 1st, 2nd and 3rd trimesters corresponding to the 2.5th and 97.5th percentiles were 0.14-6.14, 0.43-4.64, 0.63-3.9µIU/ml; 78.01-215.19, 93.23-243.87, 89.61-211.37nmol/L; and 1.73-4.53, 1.96-5.64, 1.72-4.30, respectively. Reference interval for TPOAb in the 1st trimester was 1.40-38.02IU/mL. Median of TSH was low in the 1st trimester, and gradually increased until 2nd trimester, followed by a slight decrease onward. A decreasing trend in TSH levels was observed in higher centiles with advancing gestational age. CONCLUSION: This study provides trimester-specific reference ranges for some common thyroid markers among healthy Iranian women in an iodine sufficient area, to prevent biochemical misinterpretations during pregnancy.

Effects of Levothyroxine on Pregnant Women With Subclinical Hypothyroidism, Negative for Thyroid Peroxidase Antibodies.

Context: Currently, there is no consensus on universal thyroid screening and levothyroxine (LT4) treatment of pregnant women with subclinical hypothyroidism (SCH) who are negative for thyroid peroxidase antibody (TPOAb-). Objective: We aimed to evaluate the benefits of LT4 treatment on pregnancy outcomes in SCH-TPOAb- women. Design: This study was conducted within the framework of the Tehran Thyroid and Pregnancy Study. A single-blind randomized clinical trial was undertaken in pregnant women who were SCH-TPOAb-. Setting: Prenatal care centers of the Shahid Beheshti University of Medical Sciences. Patients: Using the thyrotropin (TSH) cut point of 2.5 mIU/L, 366 SCH-TPOAb- and 1092 euthyroid TPOAb- women were recruited. Intervention: SCH-TPOAb- women were randomly assigned to two groups: group A (n = 183) who were treated with LT4 and group B (n = 183) who received no treatment. A total of 1,028 euthyroid TPOAb- women served as the control group (group C). Main Outcome Measure: The primary outcome was the rate of preterm delivery. Results: Using the TSH cutoff of 2.5 mIU/L, no significant difference in preterm delivery was observed between groups A and B [relative risk (RR): 0.86; 95% confidence interval (CI): 0.47 to 1.55; P = 0.61]. However, log-binomial model analysis based on a cut point of 4.0 mIU/L demonstrated a significantly lower rate of preterm delivery in LT4-treated women compared with those who received no treatment (RR: 0.38; 95% CI: 0.15 to 0.98; P = 0.04). Conclusions: Despite no beneficial effect of LT4 therapy in reducing preterm delivery in SCH-TPOAb- women with a TSH cut point of 2.5 to 4 mIU/L, LT4 could precisely decrease this complication using the newly recommended cutoff ≥4.0 mIU/L.

Effects of levothyroxine treatment on pregnancy outcomes in pregnant women with autoimmune thyroid disease.

BACKGROUND: Despite some studies indicating that thyroid antibody positivity during pregnancy has been associated with adverse pregnancy outcomes, evidence regarding the effects of levothyroxine (LT4) treatment of euthyroid/subclinical hypothyroid pregnant women with autoimmune thyroid disease on pregnancy outcome is limited. We aimed to assess whether pregnant women with autoimmune thyroid disease, but without overt thyroid dysfunction are affected by higher rates of adverse pregnancy outcomes. In addition, we aimed to explore whether LT4 treatment improves the pregnancy outcome of affected women. METHODS: A prospective study was carried out on pregnant women from the first trimester to delivery. The study was conducted among pregnant women receiving prenatal care in centers under coverage of Shahid Beheshti University of Medical Sciences. Of a total of 1746 pregnant women, screened for thyroid dysfunction, 1028 euthyroid TPOAb-negative (TPOAb-) and 131 thyroid peroxidase antibody-positive (TPOAb+) women without overt thyroid dysfunction entered the second phase of the study. TPOAb+ women were randomly divided into two groups: group A (n = 65), treated with LT4 and group B (n = 66), received no treatment. The 1028 TPOAb- women (group C) served as a normal population control group. Primary outcomes were preterm delivery and miscarriage and secondary outcomes included placenta abruption, still birth, neonatal admission and neonatal TSH levels. RESULTS: Groups A and C displayed a lower rate of preterm deliveries compared with group B (RR = 0.30, 95% CI: 0.1-0.85, P = 0.0229) and (RR = 0.23, 95% CI: 0.14-0.40, P < 0.001) respectively. There was no statistically significant difference in the rates of preterm labor between groups A and C (RR = 0.79, 95% CI: 0.30-2.09, P = 0.64). The number needed to treat (NNT) for preterm birth was 5.9 (95% CI: 3.33­25.16). CONCLUSIONS: Treatment with LT4 decreases the risk of preterm delivery in women who are positive for TPOAb.