New Pt. Richey, Florida

Clinical Investigation of Proton Treatment in Hodgkin Lymphoma Patients - PRO-Hodgkin

ULtrafiltration-Rate Induced CArdiac Strain (ULRICA) - Study

Research plan ULtrafiltration-Rate Induced CArdiac strain (ULRICA) - study Survey of the field: Patients on chronic haemodialysis suffer from an increased risk for morbidity and mortality with the main cause of death being cardiovascular disease. Besides retention of uremic solutes, dialysis patients with poor urine output suffer from water retention. Excessive water retention results in inter dialytic weight gain (IDWG). IDWG is one prominent risk factor for cardiovascular events. With time, the effects of uraemia and dialysis treatment itself cause a cardiac strain leading to an impact on cardiac function. In the course of chronic haemodialysis, a majority of the patients develop heart failure with preserved ejection fraction. Biomarkers for such clinical involvement are i.e., B-type natriuretic peptide (BNP), and Troponin. BNP is one of two natriuretic peptides synthesised in the heart. It is released as a response to stretching of the myocardial wall. BNP is produced as a 108 amino acid long peptide. It is cleaved into two parts, the active 32 amino acid BNP with a molecular weight of 3.5 kDa and the inactive NT-proBNP with a molecular weight of 8.5 kDa. The main effect of BNP in healthy subjects is vasodilatation, natriuresis and diuresis. In addition to their roles in water and electrolyte balance, natriuretic peptides participate in seemingly unrelated processes, such as immune response and lipid metabolism. BNP is cleared by receptor mediated endocytosis and lysosomal degradation and by neutral endopeptidases present in renal tubular cells and cells in the vascular walls. NT-proBNP is thought to be excreted by the kidney and has a half-life of approximately 120 minutes compared to 20 minutes for BNP. The different half-lives and clearance mechanisms explain why the levels in serum of patients are much higher for NT-proBNP than BNP although it is excreted in a 1:1 ratio. Patients with chronic kidney disease (CKD) and especially those on dialysis have increased levels of natriuretic peptides. Both BNP and proBNP have been shown to correlate with increased risk of mortality. In patients with CKD, BNP and proBNP levels have been shown to correlate well with echocardiographic findings such as left ventricular filling pressure, left atrium size and left ventricular mass index, but not with left ventricular ejection fraction. Other studies found no such correlations. The elevated levels of proBNP and BNP in patients on dialysis have been explained not only by cardiac dysfunction/hypertrophy but also with volume overload. To perform haemodialysis, the investigator is dependent on a functioning vascular access. The first choice has for a long time been to create an arteriovenous fistula between A. radialis and V. cephalica in the forearm. According to data from DOPPS (Dialysis Outcomes and Practice Pattern Study) the use of upper arm fistulas is increasing. The increased use of upper arm fistulas is also seen in the Swedish register. The advantage of creating an upper arm fistula comes mainly from the surgical point of view. However, there is a risk of creating a high-output fistula where a large proportion of arterial blood is shunted from the left-sided circulation to the right-sided circulation. The increase in preload can lead to increased cardiac output that over time may lead to cardiac hypertrophy and eventually heart failure. A recent study showed marked changes in left ventricular mass six weeks after fistula creation, especially in those patients with fistula flow >600 ml/min. Purpose and aims: Our aim is to study the effects of haemodialysis on cardiac biomarkers and see if negative effects that haemodialysis can have on the heart can be reduced by changes in haemodialysis prescription. Specifically, in this study, the investigator investigates if cardiac strain caused by dialysis is reduced by lowering the ultrafiltration rate. Method: Study design: prospective multicentre study, cross-over design. Study population: Prevalent hemodialysis (HD) patients. Study sites are dialysis centres at Umeå, Skellefteå, Östersund, Uppsala, Linköping Skövde, Stockholm (Diaverum), Stockholm (Danderyd), Falköping (Diaverum), Malmö, Jönköping, and Örebro. Inclusion criteria: Adult HD patients with an intra-dialytic weight gain (IDWG) ≥2.5% of target weight over the long interval (3 days)26 during the four weeks prior to inclusion. Patients need to be able to understand the study information and be able to give consent. Exclusion criteria: Active systemic inflammatory state such as extensive malignancy or acute septic infection. Uncontrolled hyperphosphatemia decided by the local routine of the physician (due to somewhat decreased efficacy of the LF filter to eliminate phosphate) Study protocol: For each patient, two dialysis sessions are performed in two consecutive weeks. Blood samples, blood pressure and heart rate are taken before HD, at 180 min and after HD. For the dialysis sessions low-flux dialyzers are used. Dialysis 1 is done at usual ultrafiltration rate (UR). Dialysis 2 is done at a reduced or increased UR. Dialysis time is calculated as follows: [hours]=(100 x ultrafiltration need [L])/(0.63 x target weight [kg])28 Treatment with antihypertensives, sodium concentration in dialysate, type of dialysate and target weight should remain unchanged between both dialysis sessions. Such as: If standard dialysis is performed with an increased UR a reduced UR is performed for Dialysis 2; If standard dialysis is performed with a reduced UR Dialysis 2 can be done with an increased UR (while dialysis time can be maintained, if preferred). Blood samples are taken after finalizing of the UR period. Outcome parameters: Difference in pre- and post-dialytic serum troponin and pro-BNP concentrations drawn at the end of the UF-period. Secondary outcomes: Adverse effects related to dialysis (e.g. art. hypotension, muscle cramps), recovery time, filter clotting. Variables: Age, sex, access type (incl. fistula flow), diurnal diuresis, target weight, pre- and post-dialysis weight, height, IDWG, ultrafiltration volume, dialysate flow, blood flow, dialysis time, anticoagulation and blood pressure, heart rate, blood count, urea, CRP, treatment with RAAS-blockade, antihypertensive agents, comorbidities, time on dialysis, ordinary HD modality and dialysis schedule. When available: QRS-time in last ECG, prevalence of atrial fibrillation, volume state in body-composition monitoring. Laboratory samples are drawn predialysis, at 180 minutes and at the end of the ultrafiltration (UR) period. Correction for fluid shift in blood or plasma samples: Results of large molecules, cells and platelets are adjusted for the change in blood volume caused by ultrafiltration according to Schneditz et al 2012. Protection of data privacy: Coding of patient identity with local lists. Analysis and publication of results in anonymized, aggregated form. Power analysis: Assuming an effect size of 0.6, the study would require a sample size of 40 pairs (two consecutive dialysis sessions in a patient) to achieve a power of 95% at a level of significance of 5% (two sided).29 Statistical analysis: paired sampled T-test for the difference of the means.

Study of Perioperative Dostarlimab in Participants With Untreated T4N0 or Stage III dMMR/MSI-H Resectable Colon Cancer

Prognostic and Diagnostic Added Value of Medical Imaging in Gynecological Cancer (PRODIGYN)

This study has a retrospective and a prospective part, where the main aims are to: 1. Retrospectively validate the added value of radiological staging to clinical staging according to the International Federation of Gynecology and Obstetrics (FIGO) tumor classification system, in cervical cancer, endometrial cancer, and epithelial ovarian cancer. 2. Prospectively identify prognostic biomarkers with 18F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose (FDG)-positron emission tomography (PET)/CT and FDG-PET/MRI in cervical cancer, endometrial cancer, and epithelial ovarian cancer 3. Assess the possible effect of PET/MRI on radiotherapy target delineation in cervical cancer 4. Improve non-invasive lymph node staging in endometrial cancer 5. Develop a machine learning decision support tool for characterization of ovarian lesions Material and methods (retrospective): All eligible patients from the multi-disciplinary gynecological tumor conference at Umea University Hospital during 2013-2022, with newly diagnosed cervical, endometrial, or epithelial ovarian cancer, known cFIGO, >18 years old, and no other known current or previous malignancy within the last 10 years, will be included in a retrospective evaluation of radiological stage (rFIGO) based on all pre-operative imaging (MRI, CT and FDG-PET/CT), clinical stage (cFIGO) based on examination under anesthesia (EUA), and histopathological stage (pFIGO) based on available surgical and histopathological findings. The analysis will be carried out in two cohort groups - 2016-01-01-2018-05-31, and 2018-06-01-2022-06-01, before and after the implementation of the 2018 revised FIGO classification, after which the cFIGO may be influenced to larger extent by imaging results. For all epithelial ovarian cancer patients, Ovarian-Reporting and Data System (O-RADS) score will be annotated for each MRI examination. Agreement between rFIGO and cFIGO will be evaluated, and if feasible, compared to pFIGO. The investigators will thus be able to validate rFIGO in cervical cancer with cFIGO up to Ib2, and in endometrial and epithelial ovarian cancer treated with surgery. The added value of rFIGO in terms of metastasis assessment and change of therapy, as well as pattern and incidence of radiotherapy side effects will be evaluated in patients who were considered inoperable. Hypotheses (retrospective): 1. The degree of agreement is high between rFIGO T stage and cFIGO T stage in cervical, endometrial, and epithelial ovarian cancer. 2. There is high sensitivity, specificity, accuracy, and negative and positive predictive values of rFIGO to predict pFIGO in ovarian cancer of epithelial subtype. 3. There is an added value of rFIGO for metastasis assessment and change of patient management in cervical cancer stages >Ib2, and in endometrial and epithelial ovarian cancer patients who are considered inoperable. Material and methods (prospective) All eligible patients with newly diagnosed cervical cancer stage >1a, endometrial cancer type 2 and/or minimum stage 1, or strongly suspected epithelial ovarian cancer, consecutively referred to the gynecological- oncological department of Umea University Hospital, with written informed consent, will be included in a prospective study of the diagnostic and prognostic value of FDG-PET/CT and FDG-PET/MRI at baseline and at therapy response evaluation after 3 months. The subgroup of patients with cervical and endometrial cancer treated with radiotherapy, will undergo one additional stand-alone MRI with dedicated tumor protocol after one week of treatment for early response evaluation. Patient demographics and age of menarche, menopause and parity will be collected to characterize the study population. Furthermore, for epithelial ovarian cancer, levels of tumor markers cancer antigen (CA)-125 and CA-19-9 as well as risk of malignancy index will be collected. The FDG-PET/CT will be performed according to clinical routine with intravenous injection of FDG 3 megabecquerel (MBq)/kg, 60 minutes post-injection (with the addition of Sharp Inversion Recovery (IR) reconstruction to be used for comparison with the FDG-PET/MRI), but without intravenous iodine contrast agent, since the FDG-PET/MRI will be performed 120 minutes after the same FDG-injection and will be prioritized for administration of gadolinium-based contrast agent. The FDG-PET/MRI will be designed according to standard clinical MRI protocol, dedicated for each cancer type as described in detail below, with preparatory administration of 2 ml Buscopan 20 mg/ml and gadolinium-based contrast agent Dotarem 279.3 mg/ml, 0.2 ml/kg body weight (maximum 20 ml). If renal function is moderately impaired (relative GFR 45-59 ml/min/1.73 m2), the dose will be reduced to 0.1 ml/kg. If relative GFR is <45 ml/min/1.73 m2 the examination will be performed without iv contrast agent. The total examination time is estimated to approximately 40 minutes. Cervical cancer: T2-weighted (T2W) (sagittal, axial, coronal oblique, axial oblique), T1 Dixon all (axial), diffusion-weighted imaging (DWI) (b 100, 800, axial), optional Gd+ T1 Dixon (axial). Endometrial cancer: T2W (sagittal, axial, axial oblique), T1Dixon all (axial oblique), DWI (b 100, 800, axial oblique), Gd+T1 Dixon (axial oblique, sagittal oblique). Ovarian cancer: T2W (sagittal, axial, coronal), T1 Dixon all (axial), DWI (b 100, 800, axial), Gd+T1Dixon (axial, sagittal). Clinical evaluation will take place at 3 months, 6 months, 1 year and 5 years after start of treatment with collection of clinical data progression-free survival (PFS, defined as the time from start of treatment to progression or specific cancer-related death), overall survival (OS, defined as the time from start of treatment to death from any cause), and pattern and incidence of any radiotherapy side effects. In FDG-PET/CT, pathological uptake of the suspected primary tumor will be visually categorized into 1 = uptake < mediastinal background, 2 = uptake > mediastinal background and < liver background, 3 = moderate uptake > liver background, or 4 = intense uptake > liver background. From the PET/CT and PET/MRI examinations, primary tumor PET parameters will also be quantified in maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), functional tumor volume (FTV) and total lesion glycolysis (TLG). In addition, the categorical parameters tumor heterogeneity, suspected radiological lymph node metastases (present or not, N1 or N0) will be reported for both, and distant metastases (M1 or M0) will be reported for PET/CT. CT and MRI parameters volume, delineation, contrast enhancement and diffusion restriction, as well as tumor heterogeneity will also be assessed. Interpretation of rFIGO will be reported for both PET/MRI and PET/CT. At the 3 months´evaluation, the same imaging parameters will be evaluated and absolute differences in continuous parameters as well as up-grading or down-grading of categorical parameters will be analyzed. The patients treated with radiotherapy or chemotherapy will be categorized into responders, defined as complete or partial metabolic response, and non-responders, defined as stable metabolic disease or progressive metabolic disease, according to PERCIST criteria (see References). The feasibility of FDG-PET/MRI for radiotherapy dose planning guidance will be compared to standard imaging-based guidance regarding target delineation of gross tumor volume (GTV), and the prognostic difference between the group of early responders (any perceptible response) at one week´s stand-alone MRI evaluation, compared to non-responders (stable or progressive disease), will be assessed. In the histopathological analysis, prognostic factors will be recorded and if applicable, immunohistochemical stainings for P53, Ki-67, ER, D240 and CD31, as well as molecular analysis of microsatellite instability (MSI), breast cancer susceptibility gene (BRCA)-, and polymerase-epsilon (POLE)-mutations and possible additional genes of emerging interest will be performed. For the study participants with endometrial cancer scheduled for surgery with sentinel node algorithm, imaging characteristics of suspected lymph nodes will be described in terms of visually quantified pathological FDG-PET uptake according to the four previously mentioned categories, and PET parameters SUVmax, SUVmean, FTV, TLG and tumor heterogeneity. CT and MRI parameters size, shape, delineation, contrast enhancement, diffusion restriction and tumor heterogeneity will also be assessed. The lymph node with the highest metabolic activity (SUVmax) will be selected for each affected lymph node region: external iliac, internal iliac, common iliac, obturator and infrarenal paraaortic regions. In addition, the same parameters will be analyzed for the primary tumor to evaluate its predictive value of lymph node metastases. Regarding histopathology in this sub-study, as a starting point morphological patterns detected on hematoxylin-eosin stained glass will be recorded. These patterns will then guide further immunohistochemical and molecular analyses to highlight the changes that have occurred in the metastatic lymph nodes. For the ovarian cancer dataset, the investigators will develop a machine learning method for diagnostic decision support and prognostic prediction. The modeling data set will consist of the various MRI data from different MRI scanners and protocols, annotated with O-RADS (MRI), from ovarian cancer patients from the previous retrospective part of the PRODIGYN study. The matching dataset of controls will be acquired from the non-ovarian (cervical and endometrial) cancer patient cohort from the above-mentioned retrospective study. After training, validation and testing, the investigators will apply the machine learning method for O-RADS (MRI) risk categorization on the prospective study dataset and compare the diagnostic performance of the machine learning method with two radiologists, by area under the receiver operating characteristic curve (AUC-ROC) analysis, with ground truth histopathology. The prognostic predictive performance will be assessed using O-RADS 4 and 5 lesion labeling as markers of poor prognostic outcome, with ground truth PFS and OS. Hypotheses (prospective): 1. FDG-PET/CT and FDG-PET/MRI biomarkers can predict PFS and OS in cervical, endometrial, and epithelial ovarian cancer 2. FDG-PET/CT and FDG-PET/MRI metrics at follow-up of therapy response have higher prognostic impact than baseline 3. Early tumor response on MRI after radiotherapy predicts better prognosis 4. Early response patterns in organs at risk may predict serious adverse events 5. Target delineation of GTV in cervical cancer is significantly different with FDG-PET/MRI compared to local standard MRI 6. Degree of agreement, sensitivity, specificity and accuracy of FDG-PET/CT and FDG-PET/MRI are high for lymph node metastases on regional and on patient basis in endometrial cancer 7. Primary tumor FDG-PET/CT and FDG-PET/MRI imaging characteristics can predict aggressive histological type II, MSI phenotype and presence of lymph node metastases in endometrial cancer 8. FDG-PET/MRI can be used to distinguish BRCA-mutated from non-BRCA-mutated ovarian cancer by differences in growth pattern and metabolic activity 9. The histopathological immune response in sentinel nodes can predict prognosis and correlate with FDG-PET/CT and FDG-PET/MRI biomarkers in endometrial cancer 10. There is an added value of FDG-PET/CT and FDG-PET/MRI to the sentinel node algorithm, for detection of para-aortic lymph node metastases in endometrial cancer 11. The machine learning method performs similarly to radiologists in O-RADS 1-4 but is inferior in O-RADS 5

Long-Term Follow-Up (LTFU) of Subjects Dosed With NTLA-2001

Treatment and Mapping of Impostor Phenomenon

The investigators have noticed that these conditions are common among patients attending the clinic. The investigators therefore want to do mapping of the occurrence and make an intervention to be able to change and evaluate handling of these patients. The hypothesis is that there is a connection between these conditions and that they are all part of the patients´ disease. The study will be done by using validated questionnaires which are answered anonymously using a code, that is known only by the participant, and with exercises/interventions for five or ten weeks. The questionnaires and interventions are formerly used in several international studies and by the investigators in populations of healthy persons with different professions. Examples of diseases is localised provoked vulvodynia (former vulvar vestibulitis) a state of pain that mainly affects young women. The symptoms are localized to the vulvar vestibulum and provoked by touch and experienced by the patient as pain or burning. The aetiology is not clearly known but probably due to both physical and psychological factors. Treatment is due to several strategies like treating the pain, rehabilitation of the perineum, and psychosocial support. Persons with this type of pain will also answer a short questionnaire regarding their symptoms. Another example is hyperhidrosis is excessive sweating without known cause. Hyperhidrosis may be primary focal or multifocal with debut in childhood. Secondary hyperhidrosis is often due to another disease. Hyperhidrosis often means big stress on mental health but may also affect physical functions. Persons with hyperhidrosis estimate their quality of life equal with those affected by severe acne or psoriasis. The investigators´ ongoing research with mapping of these different traits of character shows that the occurrence is increasing, but no treatment has so far been available in Sweden. The investigators therefore want to evaluate whether treatment by intervention with one or two exercises each week may diminish the occurrence of impostor phenomenon and to be able to influence the disease. The questionnaires that will be used are "Self-Compassion scale short version" (SCS-SF), "Clance Impostor Phenomenon scale" (CIPS), "Perceived Stress scale 4" (PSS-4), "Generalized Anxiety Disorder-2" (GAD-2), and "Clinical Perfectionism Questionnaire short form" (CPQ-SF). These questionnaires are validated by other investigators and used in several international research studies. The questionnaires have already been translated from English to Swedish, except CIPS that has been translated and back-translated. There will also be questions on gender, age, and term. The software for statistical analyses is Statistical Package for the Social Sciences (SPSS) version 27 from International Business Machines Corporation (IBM). Before starting treatment, the participants will get a web-based survey including twenty questions about impostor phenomenon (CIPS), six questions about stress and anxiety (PSS-4 and GAD-2), twelve questions about self-compassion (SCS-SF) and six questions about perfectionism (CPQ-SF). The questionnaires are repeated week twelve and 24 after intervention. After inclusion and answering the first questionnaire the persons are asked to participate in a series of one or two interventions, 30 minutes each, every week for ten or five weeks respectively.

Interfant-21 Treatment Protocol for Infants Under 1 Year with KMT2A-rearranged ALL or Mixed Phenotype Acute Leukemia

All infants that are eligible for this study and for whom the parents/legal representatives give informed consent will be enrolled in this study. All patients will receive one cycle of blinatumomab on top of the standard treatment backbone after induction therapy. Medium risk patients, that respond well to the 1st cycle will be treated with a 2nd cycle of blinatumomab replacing one chemo course after consolidation therapy. If they do not respond well enough they will be treated according to the current treatment standard. Minimal residual disease will be used to determine the response to blinatumomab. High risk patients will be eligible for allogeneic stem cell transplantation after the first blinatumomab cycle if they are Minimal Residual Disease (MRD) negative (defined as < 0.01%). Also medium risk patients with insufficient MRD response after induction or after the 1st cycle of blinatumomab will be allocated to high risk treatment and will be eligible for allogeneic stem cell transplantation.

Study to Continue Treatment With Darolutamide in Patients Who Have Been Participating in Previous Darolutamide Studies Supported by Bayer

Loop Ileostomy Closure:Stapled or Hand-sewn Anastomoses? Suture or Mesh Closure of the Stoma Site?

Postoperative complications after closure of a temporary loop ileostomy after rectal cancer surgery are common. In this study the investigators propose the hypothesis that a stapled anastomotic technique will decrease postoperative small bowel obstruction and a mesh closure of the stoma site in the abdominal wall will decrease hernia formation. All patients will be randomized to stapled or hand-sewn anastomosis. The randomization to mesh or suture closure of the abdominal wall is optional. The stapled anastomotic technique is performed by the use of a linear staple device and the hand-sewn technique with a running seromuscular monofilament suture. The stoma site has two options and will be closed either by the use of mesh (lightweight), positioned under the muscle (retromuscular), or just by long-lasting suture. The anterior fascia of the rectus as well as the skin are closed by the use of running monofilament longlasting sutures, the latter in a pursestring procedure.

Swedish Iodine in Pregnancy and Development in Children (SWIDDICH) Study

AIMS - To determine if children exposed to deficient micronutrition including mild iodine deficiency (ID) during fetal life achieve worse cognitive development compared to children exposed to normal iodine status reached by maternal iodine supplementation. - To investigate the interaction between iodine, selenium and iron, as components of the intervention. - To compare urinary iodine concentration (UIC), thyroglobulin (Tg), free tetraiodothyronine (FT4) and thyroid stimulating hormone (TSH) in pregnant women on daily tablet with vitamins and minerals, including 150 µg iodine or placebo - To compare milk iodine concentration (MIC) in colostrum, and TSH in the first 200 newborn children to pregnant women receiving daily tablet with vitamins and minerals, including 150 µg iodine or placebo BACKGROUND Iodine deficiency increases the risk for hypothyroidism and goiter and during the pregnancy for abortion or cognitive and other abnormalities of the baby. According to the WHO recommendations, UIC during pregnancy should be 150-249 ug/L. In 2007 a national study showed iodine sufficiency in Swedish general population. It is debated whether or not iodine shall be given to pregnant women in iodine sufficient populations. The research group started this randomized iodine intervention in pregnant women in 2012. The first hypothesis was that daily supplementation with a tablet with vitamins and minerals including 150 µg iodine is needed during pregnancy in Sweden in order to ensure normal iodine and thyroid hormone status in mothers and newborn children and that pregnant women in Sweden suffer from mild iodine deficiency (ID). There is a substantial gap of knowledge with regards to whether mild ID during fetal life entails negative consequences on cognition. Two large observational studies have shown association between mild ID during pregnancy and lower IQ or educational performance in school-children. The only two randomized placebo-controlled trials (RCTs) studying mild ID in pregnancy were either too small for safe conclusions to be drawn ( Brucker-Davis et al, n=86), or did not manage to separate groups based on iodine levels (the MITCH study, Melse-Boonstra et al, n=839). The need for a RCT with sufficient sample size remains. This led the research team to form a second hypothesis within the trial: children exposed to deficient micronutrition including mild ID during fetal life have lower cognitive development compared to children to mothers taking a daily tablet with vitamins and minerals including150 ug iodine during pregnancy. The decision to expand the trial was made and the target number of participants to be recruited increased from 200 to 1275 in order to reach enough power to follow-up the childrens' cognitive development. METHODS Design This is a prospective placebo-controlled trial of children whose mothers got iodine supplement 150 µg/day (a tablet with vitamins and minerals) or placebo (a multivitamin preparation without minerals) during pregnancy (week 10±2 until delivery). The target number participants during pregnancy is 1275 to enable sufficient power in the children follow-up (n=788). The main outcome is intelligence quotient (IQ) at 3.5 year of age. Cognitive development in children will be also assessed at 18 months, 7, and 14 years. Pregnancy part Pregnant women from more than ten maternity care centers in Sweden are randomized to daily receive a multivitamin tablet with minerals, including 150 µg iodine or placebo (multivitamin without iodine). The intervention starts at pregnancy week 8-12 and ends directly post-partum for the first 200 women and at pregnancy week 36±2weeks for the remaining participants. This time point may be adjusted to local circumstances, depending on when during the third trimester the routine visit at maternity care center takes place. Participants are included after the first visit by a midwife. Urine sample for UIC and U-creatinine, and blood sample for thyroid hormones, thyroid stimulating hormone (TSH), thyroglobuline (Tg) and thyroperoxidase antibodies (TPO-ab) are collected and a simple questionnaire is filled in at week 10±2 weeks of pregnancy and placebo/intervention is started. Selenium and iron are also measured. The same measurements are collected in week 25±1 week and week 36±2 weeks. Directly after delivery (within 5 days), MIC and UIC in the first 200 mother as well as UIC and TSH in their newborn child were collected and a simple questionnaire is filled in. Weight, length and APGAR in the child and pregnancy complications are registered. Blood is also frozen for future analyses and access to medical files is accepted. In parallel 90 healthy female controls from Skaraborg area stratified for age and smoking habits are collected from a randomized sample attained by the Swedish Tax Agency. UIC, u-creatinine, FT4, TSH, Tg, TPO-ab, and samples to be frozen are collected and a questionnaire is filled in. Selenium and iron will be analyzed in blood sample from the first 200 pregnant women and from controls. The primary purpose for having a control population is to ascertain that the normal population in the area of Skaraborg is iodine sufficient. Children follow-up At 18 months ± 1 month psychomotor development is assessed by means of ASQ (Ages and Stages Questionnaire). At 3,5 years ± 2 months the IQ is measured (WPPSI-IV), behavior is assessed (CBCL questionnaire) and urine is collected for UIC measurement. At 7 years ± 3 months the following are assessed: IQ (WISC IV), motor development (Movement ABC), behavior (CBCL), symptoms related to attention deficit and hyperactivity disorder (ADHD, 5-15 Nordic questionnaire). Additionally, at 7 years ± 3 months urine is collected for UIC measurement, blood sample is taken for thyreoglobulin (Tg), thyroid hormones and deiodinases, and MRI of the brain is performed in a subsample. At 14 years ± 6 months all these, except for the Movement ABC, are repeated. On all occasions information on socio-economic status and other possible confounders are collected by means of questionnaires filled by parents and by children (14 years).