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Women who have had repeated miscarriages often have uncertainties about the cause, the likelihood of recurrence, the investigations they need, and the treatments that might help. Health-care policy makers and providers have uncertainties about the optimal ways to organise and provide care. For this Series paper, we have developed recommendations for practice from literature reviews, appraisal of guidelines, and a UK-wide consensus conference that was held in December, 2019. Caregivers should individualise care according to the clinical needs and preferences of women and their partners. We define a minimum set of investigations and treatments to be offered to couples who have had recurrent miscarriages, and urge health-care policy makers and providers to make them universally available. The essential investigations include measurements of lupus anticoagulant, anticardiolipin antibodies, thyroid function, and a transvaginal pelvic ultrasound scan. The key treatments to consider are first trimester progesterone administration, levothyroxine in women with subclinical hypothyroidism, and the combination of aspirin and heparin in women with antiphospholipid antibodies. Appropriate screening and care for mental health issues and future obstetric risks, particularly preterm birth, fetal growth restriction, and stillbirth, will need to be incorporated into the care pathway for couples with a history of recurrent miscarriage. We suggest health-care services structure care using a graded model in which women are offered online health-care advice and support, care in a nurse or midwifery-led clinic, and care in a medical consultant-led clinic, according to clinical needs.

There is a need for consensus on the recommendations for follow-up of children and adolescents with celiac disease. Objectives: To gather the current evidence and to offer recommendations for follow-up and management. Methods: The Special Interest Group on Celiac Diseases of the European Society of Paediatric Gastroenterology Hepatology and Nutrition formulated ten questions considered to be essential for follow-up care. A literature search (January 2010-March 2020) was performed in PubMed or Medline. Relevant publications were identified and potentially eligible studies were assessed. Statements and recommendations were developed and discussed by all coauthors. Recommendations were voted upon: joint agreement was set as at least 85%. Results: Publications (n = 2775) were identified and 164 were included. Using evidence or expert opinion, 37 recommendations were formulated on: The need to perform follow-up, its frequency and what should be assessed, how to assess adherence to the gluten-free diet, when to expect catch-up growth, how to treat anemia, how to approach persistent high serum levels of antibodies against tissue-transglutaminase, the indication to perform biopsies, assessment of quality of life, management of children with unclear diagnosis for which a gluten-challenge is indicated, children with associated type 1 diabetes or IgA deficiency, cases of potential celiac disease, which professionals should perform follow-up, how to improve the communication to patients and their parents/caregivers and transition from pediatric to adult health care. Conclusions: We offer recommendations to improve follow-up of children and adolescents with celiac disease and highlight gaps that should be investigated to further improve management.

Objective: To assess a possible relationship between maternal cognitive dysfunction during pregnancy and hypothyroxinemia, adjusted for major confounders.Background: Thyroid dysfunction in general is associated with cognitive dysfunction. Cognitive dysfunction is common during pregnancy.Design: Prospective follow‐up study from 12 to 32 weeks of pregnancy.Participants: 2082 healthy pregnant women.Measurements:Cognitive function, depression and sleeping problems were as‐sessed by self‐report questionnaires at 12, 22 and 32 weeks of gestation, higher scores reflecting more symptoms. FT4, TSH and TPO‐Ab were assessed at 12 weeks of gestation.Definitions: healthy (euthyroxinemia) control group: FT4 within 10‐90th percen‐tiles, without elevated TPO‐Ab titres and TSH within first trimester‐specific refer‐ence range (0.23‐4.0 mU/L). Hypothyroxinemia: FT4 1 SD > mean on the cognitive function scale.Results: A total of 54 women showed hypothyroxinemia and 1476 women had eu‐thyroxinemia. At 12 weeks, multiple logistic regression showed that poor cognitive function was independently related to hypothyroxinemia: OR: 2.9 (95% CI: 1.6‐5.4), adjusted for depression (OR: 3.1; 95% CI: 2.7‐4.6) and sleeping problems (OR: 2.8, 95% CI: 1.9‐3.9). TPO‐Ab + women with hypothyroxinemia had the highest levels of cognitive dysfunction. Other cut‐offs of hypothyroxinemia (Conclusions: Women with hypothyroxinemia during early gestation are at risk for poor cognitive function throughout gestation, adjusted for depression and sleeping problems.

Objective: An association between hypothyroidism (HT) and oral lichen planus (OLP) has been reported. However, the mechanisms that could explain this association remain unresolved. This study aimed to evaluate the expression of thyroid-stimulating hormone (TSH) and thyroid-stimulating hormone receptor (TSHR) in healthy oral mucosa and in OLP lesions of individuals with and without HT. Material and methods: Immunohistochemical expression of TSH and TSHR was studied in oral mucosal biopsies obtained from 14 OLP patients with HT, 14 OLP patients without HT and 10 healthy controls without oral mucosal lesions. Gene expression of TSHR was investigated by using three different PCR techniques in oral mucosal samples from 7 OLP patients with HT, 3 OLP patients without HT, 9 healthy controls and in cultured human oral epithelial cells. Gene expression of TSH was examined by employing 2 PCR techniques in oral mucosal samples from 2 OLP patients with HT, 2 OLP patients without HT and 4 healthy controls. Results: TSH and TSHR stainings were negative in the studied oral mucosal specimens. Gene quantification assays demonstrated negative gene expression of TSH and TSHR in clinical and in vitro samples. Conclusions: These results suggest that TSH and TSHR may not be commonly involved in the pathogenetic mechanism that could explain the association between OLP and hypothyroidism.

Background: Pregnancy is characterized by many biological and psychosocial changes. Adequate maternal thyroid function is important for the developing fetus throughout gestation. Latent class analyses (LCA) (including three consecutive trimester assessments) recently showed new insights into changes of thyroid function in relation to obstetric outcome. Furthermore, maternal distress during pregnancy (anxiety and depression) negatively affects obstetric outcome. Pregnancy distress in turn may be affected by personality traits and attachment styles. Moreover, during pregnancy, substantial social changes occur in the partner relationship and work experience. The aim of the Brabant Study is to investigate the association between thyroid function trajectories and obstetric outcomes. Moreover, within the Brabant Study, we will investigate how different trajectories of pregnancy distress are related to obstetric outcome, and the role of personality in this association. We will evaluate the possible role of maternal distress and attachment style on maternal-fetal bonding. Finally, we will study social changes in the perinatal period regarding partner relationship and well-being and performance at work. Methods and analysis: The Brabant Study is a longitudinal, prospective cohort study of an anticipated 4000 pregnant women. Women will be recruited at 8-10 weeks gestation among community midwife practices in South-East Brabant in the Netherlands. Thyroid hormone levels (TSH and fT4), TPO-Ab and hCG will be assessed at 12, 20 and 28 weeks gestation. Moreover, at these three time points women will fill out questionnaires assessing demographic and obstetric features, life style habits and psychological and social variables, such as depressive symptoms, personality, partner relationship quality and burnout. Data from the obstetric records will also be collected. Ethics and dissemination: The study has been approved by the Medical Ethical Committee of the Máxima Medical Center Veldhoven. Results will be submitted to peer reviewed journals in the relevant fields and presented on national and international conferences. Strengths and limitations of this study•Prospective design with three measurements of both biological and psychological variables during pregnancy which enables the use of Latent Class Analysis;•A multi-factorial approach;•A large sample size;•Use of self-report with validated questionnaires instead of interviews.

To determine the prevalence of autoimmune diseases and autoantibodies in relatives of Caucasian patients with systemic lupus erythematosus (SLE) we questioned 118 patients for the prevalence of autoimmune diseases in their relatives. Multicase SLE families were selected for further investigation: assessment of the presence of antinuclear antibodies (ANA), thyroid antibodies and IgM rheumatoid factor (IgM-RF). Thirty-three patients reported the presence of 50 autoimmune diseases in 43 relatives. Twenty-two diagnoses could be either confirmed (n=14) or refuted (n=8). SLE clustered significantly within families of SLE patients. Multiple sclerosis and rheumatoid arthritis also seemed to cluster within families of lupus patients. The prevalence of ANA (24%) and thyroid antibodies (44%) in 29 relatives of multicase SLE families was raised (P

To determine the prevalence of autoimmune diseases and autoantibodies in relatives of Caucasian patients with systemic lupus erythematosus (SLE) we questioned 118 patients for the prevalence of autoimmune diseases in their relatives. Multicase SLE families were selected for further investigation: assessment of the presence of antinuclear antibodies (ANA), thyroid antibodies and IgM rheumatoid factor (IgM-RF). Thirty-three patients reported the presence of 50 autoimmune diseases in 43 relatives. Twenty-two diagnoses could be either confirmed (n = 14) or refuted (n = 8). SLE clustered significantly within families of SLE patients. Multiple sclerosis and rheumatoid arthritis also seemed to cluster within families of lupus patients. The prevalence of ANA (24%) and thyroid antibodies (44%) in 29 relatives of multicase SLE families was raised (P

Hypothyroxinaemia early in pregnancy may impair fetal brain development. Increased body weight has been associated with low thyroxine concentrations in non‐pregnant women. In pregnant women, morbid maternal obesity is a risk factor for thyroid dysfunction. But whether lesser degrees of overweight that are much more common could be a risk factor for hypothyroxinaemia in pregnancy is unclear. The objective of this study was to investigate if overweight increases risk for thyroid dysfunction, and specifically hypothyroxinaemia, in iodine‐deficient pregnant women. We performed a cross‐sectional study at first hospital visit among healthy Thai pregnant women. We measured weight and height, urinary iodine concentration (UIC), serum thyroid hormones and thyroglobulin. Pre‐pregnancy weight and relevant dietary factors were determined by questionnaire, and body mass index (BMI) was used to classify weight status. Among 514 women (mean gestational age, 11 weeks) with a median UIC of 111 μg dL(–1), indicating mild iodine deficiency, 12% had low free thyroxine (fT4) concentrations: 3% had overt hypothyroidism; 7% had subclinical hypothyroidism; and 8% had isolated hypothyroxinaemia. Based on pre‐pregnancy BMI, 26% of women were overweight or obese. In a multiple regression model, BMI was a negative predictor of fT4 (β = −0.20, P

Objectives There is a clinical impression of dissatisfaction with treatment for hypothyroidism among some patients. Psychometric properties of the new ThyTSQ questionnaire are evaluated. The questionnaire, measuring patients' satisfaction with their treatment for hypothyroidism, has two parts: the seven-item ThyTSQ-Present and four-item ThyTSQ-Past, measuring satisfaction with present and past treatment, respectively, on scales from 6 (very satisfied) to 0 (very dissatisfied). Methods The questionnaire was completed once by 103 adults with hypothyroidism, age (mean [SD]) 55.2 [14.4], range 23–84 years (all treated with thyroxine). Results Completion rates were very high. Internal consistency reliability was excellent for both ThyTSQ-Present and ThyTSQ-Past (Cronbach's alpha=0.91 and 0.90, respectively [N = 102 and 103]). Principal components analyses indicated that the seven items of the ThyTSQ-Present and the four items of the ThyTSQ-Past could be summed into separate Present Satisfaction and Past Satisfaction total scores. Mean Present Satisfaction was 32.5 (7.8), maximum range 0–42, and mean Past Satisfaction was 17.5 (6.1), maximum range 0–24, indicating considerable room for improvement. Patients were least satisfied with their present understanding of their condition, mean 4.2 (1.7) (maximum range 0–6), and with information provided about hypothyroidism around the time of diagnosis, mean 3.9 (1.8) (maximum range 0–6). Conclusions The ThyTSQ is highly acceptable to patients with hypothyroidism (excellent completion rates), and has established internal consistency reliability. It will assist health professionals in considering psychological outcomes when treating people with hypothyroidism, and is suitable for clinical trials and routine clinical monitoring.

The increased risk for ischemic heart disease (IHD) associated with subclinical hypothyroidism (SH) has been partly attributed to dyslipidemia. There is limited information on the effect of SH on lipoprotein (a) [Lp(a)], which is considered a significant predictor of IHD. Serum Lp(a) levels are predominantly regulated by apolipoprotein [apo(a)] gene polymorphisms. The aim of our study was to evaluate the Lp(a) levels and apo(a) phenotypes in patients with SH compared to healthy controls as well as the influence of levothyroxine substitution therapy on Lp(a) values in relation to the apo(a) isoform size. Lp(a) levels were measured in 69 patients with SH before and after restoration of a euthyroid state and in 83 age- and gender-matched healthy controls. Apo(a) isoform size was determined by sodium dodecyl sulfate (SDS) agarose gel electrophoresis followed by immunoblotting and development via chemiluminescence. Patients with SH exhibited increased Lp(a) levels compared to controls (median value 10.6 mg/dL vs. 6.0 mg/dL, p = 0.003]), but this was not because of differences in the frequencies of apo(a) phenotypes. There was no association between thyrotropin (TSH) and Lp(a) levels in patients with SH. In subjects with either low (LMW; 25 patients and 28 controls) or high (HMW; 44 patients and 55 controls) molecular weight apo(a) isoforms, Lp(a) concentrations were higher in patients than in the control group (median values 26.9 mg/dL vs. 21.8 mg/dL, p = 0.02 for LMW, and 6.0 mg/dL versus 3.3 mg/dL, p < 0.001 for HMW). Levothyroxine treatment resulted in an overall reduction of Lp(a) levels (10.6 mg/dL baseline vs. 8.9 mg/dL posttreatment, p = 0.0081). This effect was mainly evident in patients with LMW apo(a) isoforms associated with high baseline Lp(a) concentrations (median values 26.9 mg/dL vs. 23.2 mg/dL pretreatment and posttreatment, respectively; p = 0.03). In conclusion, even though a causal effect of thyroid dysfunction on Lp(a) was not clearly demonstrated in patients with SH, levothyroxine treatment is beneficial, especially in patients with increased baseline Lp(a) levels and LMW apo(a) isoforms. Thyroid

The majority of human autoimmune diseases are characterized by female predominance. Although sex hormone influences have been suggested to explain this phenomenon, the mechanism remains unclear. In contrast to the role of hormones, it has been suggested, based on pilot data in primary biliary cirrhosis, that there is an elevation of monosomy X in autoimmune disease. Using peripheral white blood cells from women with systemic sclerosis (SSc), autoimmune thyroid disease (AITD), or healthy age-matched control women, we studied the presence of monosomy X rates using fluorescence in situ hybridization. We also performed dual-color fluorescence in situ hybridization analysis with a chromosome Y α-satellite probe to determine the presence of the Y chromosome in the monosomic cells. In subsets of patients and controls, we determined X monosomy rates in white blood cell subpopulations. The rates of monosomy X increased with age in all three populations. However, the rate of monosomy X was significantly higher in patients with SSc and AITD when compared with healthy women (6.2 ± 0.3% and 4.3 ± 0.3%, respectively, vs 2.9 ± 0.2% in healthy women, p < 0.0001 in both comparisons). Importantly, X monosomy rate was more frequent in peripheral T and B lymphocytes than in the other blood cell populations, and there was no evidence for the presence of male fetal microchimerism. These data highlight the thesis that chromosome instability is common to women with SSc and AITD and that haploinsufficiency for X-linked genes may be a critical factor for the female predominance of autoimmune diseases.