scholarly journals Association between Sleep Duration and Subclinical Thyroid Dysfunction Based on Nationally Representative Data

2019 ◽  
Vol 8 (11) ◽  
pp. 2010 ◽  
Author(s):  
Woojun Kim ◽  
Jeongmin Lee ◽  
Jeonghoon Ha ◽  
Kwanghoon Jo ◽  
Dong-Jun Lim ◽  
...  
Keyword(s):  
Sleep Duration ◽  
Thyroid Function ◽  
Subclinical Hypothyroidism ◽  
Thyroid Dysfunction ◽  
Multiple Logistic Regression Analysis ◽  
Subclinical Hyperthyroidism ◽  
Free T4 ◽  
Representative Data ◽  
Increased Risk ◽  
The Impact

Background: Sleep duration is an identified risk factor for adverse health outcomes. As the endocrine system is closely intertwined with sleep duration and quality, the association between endocrine dysfunction and sleep has been evaluated. Thyroid function, particularly that related to thyrotropin (TSH), is also known to be influenced by the sleep/awake status and circadian rhythm. Additionally, a link between sleep duration and autoimmunity, which is a common cause of thyroid dysfunction, has been suggested; however, depending on the sleep deprivation method used in studies, the effects of sleep on thyroid function vary. The relationship between subclinical thyroid dysfunction and sleep duration is poorly documented. Thus, to elucidate the impact of sleep on thyroid function, we investigated the association of subclinical thyroid dysfunction with sleep duration using representative data from the sixth Korea National Health and Nutrition Examination Survey, conducted from 2013 to 2015. Methods: In all, 4945 participants (2543 male and 2402 female) were included after excluding subjects using the following criteria: <19 years of age, free T4 level outside the normal range, history of thyroid disease, or incomplete data. The population was classified into three groups: short sleeper (<7 h/day), normal sleeper (7–8 h/day), and long sleeper (>8 h/day). The odds ratio (OR) for subclinical hypothyroidism or hyperthyroidism according to sleep duration was evaluated. Results: The short, normal, and long sleeper groups consisted of 2097, 2514, and 334 subjects, respectively. On multiple logistic regression analysis, compared to normal sleepers, short sleepers showed a significantly increased risk of subclinical hyperthyroidism (OR 1.37, 95% confidential interval (CI) 1.02–1.84, p = 0.036), while the risk of subclinical hypothyroidism in short sleepers was not elevated. Comparing long sleepers to normal sleepers, the OR for subclinical hyperthyroidism and hypothyroidism was 1.79 (95% CI 1.12–2.86, p = 0.015) and 1.91 (95% CI 1.03–3.53, p = 0.039), respectively. Conclusions: Both shorter and longer sleep durations were associated with an increase in the risk of subclinical thyroid dysfunction compared to the optimal sleep duration. This analysis of representative population data shows that sleep duration could intertwine with thyroid function resulting in increased risk of subclinical thyroid dysfunction.

Association between systemic lupus erythematosus and thyroid dysfunction: a meta-analysis

Lupus ◽  
2018 ◽  
Vol 27 (13) ◽  
pp. 2120-2128 ◽  
Author(s):  
W Luo ◽  
P Mao ◽  
L Zhang ◽  
Z Yang
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Subclinical Hypothyroidism ◽  
Thyroid Dysfunction ◽  
Meta Analysis ◽  
Healthy Controls ◽  
Subclinical Hyperthyroidism ◽  
Systemic Lupus ◽  
Increased Risk ◽  
Chronic Autoimmune Disease

Introduction Systemic lupus erythematosus (SLE) is a chronic autoimmune disease, the pathogenesis of which remains elusive. The deficiency or excess of thyroid hormone is defined as thyroid dysfunction, including (subclinical) hypothyroidism and (subclinical) hyperthyroidism. Autoimmune factors are likely to be relevant to the development of SLE and thyroid dysfunction. Recently, many studies have indicated that the prevalence of thyroid dysfunction is higher in SLE patients than in the general population. The objective of our study was to perform a systematic review and meta-analysis to find out the relationship between SLE and thyroid dysfunction. Methods Literature databases were searched, including PubMed, Embase, Web of science, Cochrane, CNKI, CHINESE WANFANG, China Science and Technology Database (VIP). Studies comparing presence of thyroid dysfunction in SLE patients to healthy controls were extracted. All the statistical analyses were performed with STATA 12.0 software. Results Ten studies with 10,500 SLE patients and 44,170 healthy controls were included in this study. The meta-analysis results showed that the prevalence of (subclinical) hypothyroidism in SLE patients was higher than in the healthy controls (hypothyroidism: OR = 2.93, 95% CI = 1.81–4.75; subclinical hypothyroidism: OR = 5.67, 95% CI = 3.50–9.18). No statistical difference of (subclinical) hyperthyroidism was found between SLE patients and controls. Conclusion Our meta-analysis suggests that SLE is significantly associated with increased risk of (subclinical) hypothyroidism, but it has little influence on (subclinical) hyperthyroidism.

scholarly journals Frequency of subclinical thyroid dysfunction and risk factors for cardiovascular disease among women at a workplace

2010 ◽  
Vol 128 (1) ◽  
pp. 18-23 ◽  
Author(s):  
Rodrigo Diaz-Olmos ◽  
Antônio-Carlos Nogueira ◽  
Daniele Queirós Fucciolo Penalva ◽  
Paulo Andrade Lotufo ◽  
Isabela Martins Benseñor
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Thyroid Function ◽  
Subclinical Hypothyroidism ◽  
Thyroid Disease ◽  
Thyroid Dysfunction ◽  
Free T4 ◽  
Cross Sectional

CONTEXT AND OBJECTIVE: Subclinical thyroid dysfunction is very common in clinical practice and there is some evidence that it may be associated with cardiovascular disease. The aim here was to evaluate the frequencies of subclinical thyroid disease and risk factors for cardiovascular disease among women at a workplace, and to evaluate the association between subclinical thyroid disease and cardiovascular risk factors among them. DESIGN AND SETTING: Cross-sectional study on 314 women aged 40 years or over who were working at Universidade de São Paulo (USP). METHODS: All the women answered a questionnaire on sociodemographic characteristics and risk factors for cardiovascular disease and the Rose angina questionnaire. Anthropometric variables were measured and blood samples were analyzed for blood glucose, total cholesterol and fractions, high-sensitivity C-reactive protein, thyroid-stimulating hormone (TSH), free thyroxine (free-T4) and anti-thyroperoxidase antibodies (anti-TPO). RESULTS: The frequencies of subclinical hypothyroidism and hyperthyroidism were, respectively, 7.3% and 5.1%. Women with subclinical thyroid disease presented higher levels of anti-TPO than did women with normal thyroid function (P = 0.01). There were no differences in sociodemographic factors and cardiovascular risk factors according to thyroid function status, except for greater sedentarism among the women with subclinical hypothyroidism. Restricting the comparison to women with subclinical hypothyroidism (TSH > 10 mIU/l) did not change the results. CONCLUSION: In this sample of women, there was no association between poor profile of cardiovascular risk factors and presence of subclinical thyroid disease that would justify screening at the workplace.

scholarly journals Morphological and Functional Assessment of Thyroid in Individuals with Down Syndrome

2021 ◽  
Author(s):  
Celia Neder Kalil Mangabeira ◽  
Rafael Kalil Mangabeira ◽  
Luis Jesuino de Oliveira Andrade
Keyword(s):  
Down Syndrome ◽  
Thyroid Function ◽  
Autoimmune Thyroiditis ◽  
Thyroid Dysfunction ◽  
Cross Sectional Study ◽  
Free T4 ◽  
Cross Sectional ◽  
Key Words Down Syndrome ◽  
Normal Thyroid Function ◽  
Increased Risk

Individuals with Down syndrome (DS) present increased risk for thyroid dysfunction, especially hypothyroidism, due in increased expression of the DYRK1A gene. Objective: The aim of this study was to make a morphological functional thyroid assessment in individuals with DS. Materials and Methods: This is a descriptive cross-sectional study, consisting of 29 individuals with DS, with a mean age of 12,3 (0.66 / 36.00) years, 16 women (55.2%) and 13 men (44.8%), with a morphological/functional thyroid assessment being made comprising hormonal dose (Free T4, TSH), antithyroid antibody (TPOAb and TgAb) and ultrasonography of the thyroid. Results: Twenty-three (79.3%) individuals presented normal thyroid function while 6 (20.7%) presented with thyroid dysfunction, 4 with hypothyroidism and 2 with hyperthyroidism. Autoimmune thyroiditis and goiter were present in 27.6% of the individuals. Conclusion: Thyroid function should be assessed periodically in individuals with DS, in view of the high prevalence of thyroid dysfunction, especially autoimmune thyroiditis with consequent hypothyroidism. Key Words: Down Syndrome, thyroid, ultrasonography, thyroid dysfunction.

scholarly journals Guidelines for diagnosis and monitoring of thyroid disease: nonthyroidal illness

1996 ◽  
Vol 42 (1) ◽  
pp. 188-192 ◽  
Author(s):  
J R Stockigt
Keyword(s):  
Positive Predictive Value ◽  
Clinical Features ◽  
Thyroid Function ◽  
Predictive Value ◽  
Thyroid Disease ◽  
Thyroid Dysfunction ◽  
Reference Intervals ◽  
Free T4 ◽  
Prognostic Information ◽  
Increased Risk

Abstract On the basis of low specificity, poor positive predictive value, and cost, there is at present no basis for routine assessment of thyroid function in acutely hospitalized patients, unless clinical features suggest the possibility of thyroid dysfunction, or a patient's background increases the likelihood of thyroid dysfunction. When used in severely ill patients, estimates of both thyroxine (T4) and thyrotropin (TSH) show a high prevalence of abnormal results, but lack specificity and have poor positive predictive value for true thyroid disease. When thyroid function is tested in the critically ill, the positive predictive value for true thyroid disease of both free T4 and TSH measurements could be improved by using wider reference intervals than for unselected populations. The knowledge of nonspecific disease-related abnormalities of triiodothyronine, T4, and TSH is not currently likely to yield useful prognostic information or to alter management for individual patients. Thyroid testing should be readily available for any acutely ill patient with any clinical features that suggest thyroid dysfunction, and for groups at increased risk of thyroid dysfunction. An initial abnormal result for either TSH or free T4 estimate should be followed by combined analysis of free T4 and TSH with the best available methodology. Diagnosis of thyroid dysfunction should be based on the T4-TSH relation rather than either value alone. Persistence of an apparent diagnostic abnormality should be confirmed before therapy is commenced.

Thyroid Dysfunction States and Incident Cardiovascular Events: The Tehran Thyroid Study

2017 ◽  
Vol 50 (01) ◽  
pp. 37-43 ◽  
Author(s):  
Maryam Tohidi ◽  
Arash Derakhshan ◽  
Samaneh Akbarpour ◽  
Atieh Amouzegar ◽  
Ladan Mehran ◽  
...  
Keyword(s):  
Thyroid Function ◽  
Subclinical Hypothyroidism ◽  
Thyroid Dysfunction ◽  
Middle Eastern ◽  
Thyroid Stimulating Hormone ◽  
Overt Hypothyroidism ◽  
Subclinical Hyperthyroidism ◽  
Significant Difference ◽  
Middle Eastern Population

AbstractThe objective of the study was to investigate the relation of different thyroid function states with the incidence of cardiovascular disease (CVD)/coronary heart disease (CHD) among a Middle-Eastern population with a high incidence of CVD/CHD. A total of 3975 participants entered the study (43.6% men). According to their thyroid stimulating hormone (TSH) and free thyroxin (FT4) levels, the participants were categorized into 5 groups: euthyroid, subclinical hypothyroidism, overt hypothyroidism, subclinical hyperthyroidism, and overt hyperthyroidism. Multivariable Cox proportional hazard models were used to assess the relation of different thyroid function states with incident CVD/CHD, with euthyroid state as reference. The mean age (SD) of the participants was 46.5 (12.0) years. At baseline, no significant difference was observed in the frequency of prevalent CVD cases (n=201) between all groups. No significant interaction was found between prevalent CVD and different thyroid function states with outcomes, hence, we did not exclude participants with prevalent CVD from data analysis. A total of 400 CVD events (358 CHD cases) during a median follow-up of 11.2 years (inter-quartile range: 1.96) occurred. During the follow-up, even in the age and sex adjusted model, no association was observed between different states of thyroid dysfunction and incidence of CVD/CHD. The multivariable hazard ratios (95% CI) of subclinical hypothyroidism, hypothyroidism, subclinical hyperthyroidism, and hyperthyroidism for CVD events were 1.21 (0.77–1.88), 0.76 (0.33–1.69), 0.81 (0.46–1.41) and 1.48 (0.70–3.16), respectively. Both at baseline and during follow-up, no relation was observed between different states of thyroid function with prevalence and incidence of CVD/CHD.

scholarly journals Effect of Contrast Media used in Coronary Angiography on Thyroid Function

2019 ◽  
pp. 339-344
Author(s):  
Khaled S. El-Hadidy ◽  
Rania E. Sheir ◽  
M.N. Salem ◽  
Ahmed M. EL-Dien ◽  
Yasser A. Abd El-Hady
Keyword(s):  
Coronary Angiography ◽  
Contrast Media ◽  
Thyroid Function ◽  
Subclinical Hypothyroidism ◽  
Thyroid Dysfunction ◽  
Thyroid Stimulating Hormone ◽  
P Value ◽  
Free T4 ◽  
Iodinated Contrast ◽  
Significant Difference

Radiocontrast-induced thyroid dysfunction prevalence has not been assessed accurately. It is greater among patients with pre-existing thyroid disease. Aim of this work to investigate effect of iodinated radiographic contrast media used in coronary angiography on the thyroid function in euthyroid patients. This study was conducted on 85 patients underwent elective coronary angiography. Baseline assessment of Free Thyroxine (FT4) and Thyroid-stimulating hormone (TSH) for the patients and three months later after Coronary Angiography. We observed that there was a statistically significant increase of TSH levels from baseline till 3 months following administration of contrast media (P-value=0.007). However, there was no statistical significant difference of Free T4 level from baseline till 3 (P-value=0.765). The incidence of increased TSH above normal range was 2.4% after 3 months ( 2 subclinical hypothyroidism cases). We noticed that there were no effect of age, gender, hypertension, diabetes, type of contrast, creatinine level or GFR on increased the level of TSH above normal value after 3 months. So, administration of Iodinated Contrast Media (ICM) associated with thyroid dysfunction mainly subclinical hypothyroidism so we should closely monitor patients after receiving ICM especially who have thyroid dysfunction.

scholarly journals The kidney, subclinical thyroid disease and cardiovascular outcomes in older patients

2020 ◽  
Vol 9 (1) ◽  
pp. 55-62
Author(s):  
L E Zijlstra ◽  
D M van Velzen ◽  
S Simsek ◽  
S P Mooijaart ◽  
M van Buren ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Thyroid Hormones ◽  
Kidney Function ◽  
Thyroid Function ◽  
Primary Endpoint ◽  
Subclinical Hypothyroidism ◽  
Thyroid Disease ◽  
Older Patients ◽  
Thyroid Dysfunction ◽  
Subclinical Hyperthyroidism

Objective Thyroid hormones have been implicated to play a role in cardiovascular disease, along with studies linking thyroid hormone to kidney function. The aim of this study is to investigate whether kidney function modifies the association of subclinical thyroid dysfunction and the risk of cardiovascular outcomes. Methods In total, 5804 patients were included in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). For the current analysis, 426 were excluded because of overt thyroid disease at baseline or 6 months, 266 because of inconsistent thyroid function at baseline and 6 months, 294 because of medication use that could influence thyroid function, and 16 because of missing kidney or thyroid values. Participants with normal fT4 were classified, based on TSH both at inclusion and 6 months, into three groups: subclinical hypothyroidism (TSH >4.5 mIU/L); euthyroidism (TSH = 0.45–4.5 mIU/L); and subclinical hyperthyroidism (TSH <0.45 mIU/L). Strata of kidney function were made based on estimated glomerular filtration rate into three clinically relevant groups: <45, 45–60, and >60 mL/min/1.73 m2. The primary endpoint consists of death from coronary heart disease, non-fatal myocardial infarction and (non)fatal stroke. Results Mean age was 75.3 years, and 49.0% patients were male. Mean follow-up was 3.2 years. Of all participants, 109 subjects (2.2%) had subclinical hypothyroidism, 4573 (94.0%) had euthyroidism, and 182 (3.7%) subclinical hyperthyroidism. For patients with subclinical hypothyroidism, euthyroidism, and subclinical hyperthyroidism, primary outcome occurred in 9 (8.3%), 712 (15.6%), and 23 (12.6%) patients, respectively. No statistically significant relationship was found between subclinical thyroid dysfunction and primary endpoint with adjusted hazard ratios of 0.51 (0.24–1.07) comparing subclinical hyperthyroidism and 0.90 (0.58–1.39) comparing subclinical hypothyroidism with euthyroidism. Neither was this relationship present in any of the strata of kidney function, nor did kidney function interact with subclinical thyroid dysfunction in the association with primary endpoint (P interaction = 0.602 for subclinical hyperthyroidism and 0.388 for subclinical hypothyroidism). Conclusions In this secondary analysis from PROSPER, we found no evidence that the potential association between thyroid hormones and cardiovascular disease is modified by kidney function in older patients with subclinical thyroid dysfunction.

scholarly journals The Relation Between Thyroid Function and Anemia: A Pooled Analysis of Individual Participant Data

2018 ◽  
Vol 103 (10) ◽  
pp. 3658-3667 ◽  
Author(s):  
Daisy M Wopereis ◽  
Robert S Du Puy ◽  
Diana van Heemst ◽  
John P Walsh ◽  
Alexandra Bremner ◽  
...  
Keyword(s):  
Thyroid Function ◽  
Subclinical Hypothyroidism ◽  
Sensitivity Analyses ◽  
Overt Hypothyroidism ◽  
Individual Participant Data ◽  
Subclinical Hyperthyroidism ◽  
Thyroid Status ◽  
Increased Risk ◽  
Individual Participant ◽  
Overt Hyperthyroidism

Abstract Context Anemia and thyroid dysfunction often co-occur, and both increase with age. Human data on relationships between thyroid disease and anemia are scarce. Objective To investigate the cross-sectional and longitudinal associations between clinical thyroid status and anemia. Design Individual participant data meta-analysis. Setting Sixteen cohorts participating in the Thyroid Studies Collaboration (n = 42,162). Main Outcome Measures Primary outcome measure was anemia (hemoglobin &lt;130 g/L in men and &lt;120 g/L in women). Results Cross-sectionally, participants with abnormal thyroid status had an increased risk of having anemia compared with euthyroid participants [overt hypothyroidism, pooled OR 1.84 (95% CI 1.35 to 2.50), subclinical hypothyroidism 1.21 (1.02 to 1.43), subclinical hyperthyroidism 1.27 (1.03 to 1.57), and overt hyperthyroidism 1.69 (1.00 to 2.87)]. Hemoglobin levels were lower in all groups compared with participants with euthyroidism. In the longitudinal analyses (n = 25,466 from 14 cohorts), the pooled hazard ratio for the risk of development of anemia was 1.38 (95% CI 0.86 to 2.20) for overt hypothyroidism, 1.18 (1.00 to 1.38) for subclinical hypothyroidism, 1.15 (0.94 to 1.42) for subclinical hyperthyroidism, and 1.47 (0.91 to 2.38) for overt hyperthyroidism. Sensitivity analyses excluding thyroid medication or high levels of C-reactive protein yielded similar results. No differences in mean annual change in hemoglobin levels were observed between the thyroid hormone status groups. Conclusion Higher odds of having anemia were observed in participants with both hypothyroid function and hyperthyroid function. In addition, reduced thyroid function at baseline showed a trend of increased risk of developing anemia during follow-up. It remains to be assessed in a randomized controlled trial whether treatment is effective in reducing anemia.

scholarly journals Relationship between Subclinical Thyroid Dysfunction and the Risk of Cardiovascular Outcomes: A Systematic Review and Meta-Analysis of Prospective Cohort Studies

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Jing Sun ◽  
Liang Yao ◽  
Yuan Fang ◽  
Ruifei Yang ◽  
Yaolong Chen ◽  
...  
Keyword(s):  
Cardiovascular Mortality ◽  
Subclinical Hypothyroidism ◽  
Thyroid Dysfunction ◽  
Meta Analysis ◽  
Total Mortality ◽  
Cardiovascular Outcomes ◽  
Cochrane Library ◽  
Subclinical Hyperthyroidism ◽  
Estimation Risk ◽  
Increased Risk

Background. Evidence on the association between subclinical thyroid dysfunction and the risk of cardiovascular outcomes are conflicting. Methods and Results. PubMed, EMbase, Web of Science, Cochrane Library, and China Biology Medicine (CBM) databases were searched from inception to July 10, 2016. A total of 16 studies were included for meta-analysis. We found that subclinical hypothyroidism was not correlated with coronary heart disease (CHD) (RR = 1.17; 95% CI, 0.91–1.52), total mortality (RR = 1.02; 95% CI, 0.93–1.13), cardiovascular mortality (RR = 1.06; 95% CI, 0.77–1.45), heart failure (RR = 1.17; 95% CI, 0.87–1.57), and atrial fibrillation (RR = 1.05; 95% CI, 0.91–1.21), except CHD mortality (RR = 1.37; 95% CI, 1.03–1.84). Subgroup analysis indicated a higher estimation risk in CHD (RR = 1.54; 95% CI, 1.00–2.39), cardiovascular mortality (RR = 2.14; 95% CI, 1.43–3.22), and CHD mortality (RR = 1.54; 95% CI, 1.11–2.15) among participants < 65 years. Furthermore, subclinical hyperthyroidism was found to be associated with CHD (RR = 1.20; 95% CI, 1.02–1.42), total mortality (RR = 1.27; 95% CI, 1.07–1.51), and CHD mortality (RR = 1.45; 95% CI, 1.12–1.86). Conclusions. Subclinical hypothyroidism is likely associated with an increased risk of CHD mortality, and subclinical hyperthyroidism is likely associated with increased risk of CHD, CHD mortality, and total mortality.

scholarly journals Retrospective analysis of the effects induced by maternal thyroid dysfunction on obstetrical complications and outcomes

2020 ◽  
Author(s):  
Manna Sun ◽  
Xinghe Wang ◽  
Yunyong Fang ◽  
Jiwu Lou ◽  
Chenning Liu ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Thyroid Function ◽  
Subclinical Hypothyroidism ◽  
Pregnancy Outcomes ◽  
Pregnancy Complications ◽  
Thyroid Dysfunction ◽  
Subclinical Hyperthyroidism ◽  
Obstetrical Complications ◽  
Significant Difference ◽  
Maternal Thyroid

Abstract Background: Abnormal concentrations of maternal thyroid hormones are risk factors for some obstetrical complications. However, the influence induced by different types of maternal thyroid dysfunction on obstetrical complications and outcomes is still controversial.Methods: A total of 17219 pregnant women were drawn for a thyroid function test, including TSH and fT4. All participants were divided into 7 groups, on the basis of their blood tested results, and their pregnancy outcomes were followed up. The isolated hypothyroxinemia group was further divided into 2 cohorts, according to whether they receive levothyroxine. Pregnant complications and outcomes in two cohorts were observed and analyzed.Results: A total of 2621 (15.22%)were identified to have abnormal thyroid function, including 1150 with subclinical hypothyroidism, 526 with gestational transient thyrotoxicosis (GTT), 419 with subclinical hyperthyroidism, 336 with isolated hypothyroxinemia, 78 with hyperthyroidism and 76 with hypothyroidism. Compare to control group, subclinical hypothyroidism, subclinical hyperthyroidism, isolated hypothyroxinemia and hypothyroidism groups presented higher incidence in one or more complications of pregnancy, while, GTT and drug-controlled hyperthyroidism had little significant effect on pregnancy complications. In isolated hypothyroxinemia group, there were no significant difference outcomes between cohorts using levothyroxine and not treatment.Conclusions: Our results showed a high incidence rate of thyroid dysfunction in pregnant women, and subclinical hypothyroidism is most common, followed by GTT. In general, pregnant women with thyroid dysfunction presented high risk of pregnancy complications. Isolated hypothyroxinemia in pregnant women is a matter of concern and treatment with levothyroxine couldn’t improve pregnancy outcomes and obstetrical complications.

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