Autoantibody-positive Women Research Articles

Use of Thyroid Hormones in Hypothyroid and Euthyroid Patients: A THESIS questionnaire survey of members of the Irish Endocrine Society

BackgroundReplacement of thyroid hormones (TH) with Levothyroxine (LT4) is the treatment of choice for hypothyroidism, however, there are aspects of treatment where uncertainties exist and practice varies. Factors influencing initiation and choice of TH replacement may impact patient satisfaction, safety, and health care costs.MethodsThe aim of the study was to examine the attitudes of Irish endocrinologists regarding the treatment of hypothyroid and euthyroid patients with TH. Members of the Irish Endocrine Society (IES) were invited to participate in an online survey.ResultsForty-eight invitations were sent, and 39 (81.3%) participants responded. All respondents favoured LT4 tablet therapy for treatment of hypothyroidism, but 20.5% prescribed combination therapy (LT4 and liothyronine), and 13% regularly used desiccated thyroid extract. A significant proportion (51%) might prescribe TH in euthyroid patients; 41% for thyroid auto-antibody positive women seeking pregnancy, 18% for goitre and 5% for unexplained fatigue. Many (38%) consider combination therapy in patients with persistent symptoms. Respondents reported seeing LT4 treated patients with persistent symptomatology more frequently and perceive psychosocial factors and comorbidities to be the most common reasons for such symptoms.ConclusionLT4 tablets are the treatment of choice for hypothyroidism in Ireland. Approximately a third of Irish endocrinologists either regularly use, or would consider, liothyronine for hypothyroid patients. A significant proportion would give TH to euthyroid individuals in specific circumstances. The prescription of TH amongst Irish endocrinologists was generally in keeping with recommended practice, and areas where practice deviated from guidance were typically where evidence was conflicting or insufficient.

Type 1 diabetes-related autoimmune antibodies in women with gestational diabetes mellitus and the long-term risk for glucose intolerance.

AimsTo characterize women with gestational diabetes mellitus (GDM) positive for type 1 diabetes-related autoimmune antibodies (T1D-related autoantibodies) in pregnancy and to evaluate their risk for long-term glucose intolerance.MethodsIn a multi-centric prospective cohort study with 1843 women receiving universal screening for GDM with a 75 g oral glucose tolerance test (OGTT), autoantibodies were measured in women with GDM: insulin autoantibodies (IAA), islet cell antibodies (ICA), insulinoma-associated protein-2 antibodies (IA-2A) and glutamic acid decarboxylase antibodies (GADA). Long-term follow-up ( ± 4.6 years after delivery) with a 75 g OGTT and re-measurement of autoantibodies was done in women with a history of GDM and autoantibody positivity in pregnancy.ResultsOf all women with GDM (231), 80.5% (186) received autoantibody measurement at a mean of 26.2 weeks in pregnancy, of which 8.1% (15) had one positive antibody (seven with IAA, two with ICA, four with IA-2A and two with GADA). Characteristics in pregnancy were similar but compared to women without autoantibodies, women with autoantibodies had more often gestational hypertension [33.3% (5) vs. 1.7% (3), p<0.001] and more often neonatal hypoglycemia [40.0% (6) vs. 12.5% (19), p=0.012]. Among 14 of the 15 autoantibody positive women with an early postpartum OGTT, two had impaired fasting glucose (IFG). Of the 12 women with long-term follow-up data, four tested again positive for T1D-related autoantibodies (three positive for IA-2A and one positive for ICA and IAA). Five women were glucose intolerant at the long-term follow-up of which two had IA-2A (one had IFG and one had T1D) and three without autoantibodies. There were no significant differences in long-term characteristics between women with and without autoantibodies postpartum.ConclusionsSystematic screening for T1D-related autoantibodies in GDM does not seem warranted since the low positivity rate for autoantibodies in pregnancy and postpartum. At 4.6 years postpartum, five out of 12 women were glucose intolerant but only two still had autoantibodies. In women with clinically significant increased autoantibody levels during pregnancy, postpartum autoantibody re-measurement seems useful since the high risk for further increase of autoantibody levels.

Long-term pituitary downregulation before frozen embryo transfer improves clinical outcomes in women positive for serum autoantibodies

ObjectiveAutoantibodies are associated with worse outcomes in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI), including increasing miscarriage rate, lowering pregnancy rate, and lowering delivery rate. However, little is known about improving IVF/ICSI outcomes for autoantibody-positive women, especially in frozen-thawed embryo transfer (FET) cycles. This study aimed to investigate whether pituitary suppression before FET improves the clinical pregnancy rate (CPR) and live birth rate (LBR) for IVF/ICSI women positive for serum autoantibodies. Study designA total of 181 infertile women positive for serum autoantibodies were recruited, including 65 women receiving GnRHa and hormone replacement therapy protocols (G-HRT group) and 116 women using modified natural cycles (MNC)/mild stimulated cycles (MSC) as FET protocols (MNC/MSC group). The outcomes were compared between two groups, including CPR, implantation rate (IR), miscarriage rate (MR), ongoing pregnancy rate (OPR), LBR, and gestational age (GA). The primary outcome of the study was CPR. ResultsCPR, OPR, and LBR per embryo transferred in the G-HRT groups were significantly higher than those in the MNC/MSC group. No statistically significant differences were observed in the IR and MR. The CPR, IR, MR, OPR, and LBR was 72.23%, 64.00%, 12.77%, 63.07%, and 63.07% in the G-HRT group, respectively, while that was 56.90%, 53.07%, 10.60%, 50.00%, and 50.00% in the MNC/MSC group, respectively. After adjusting for partial potential confounding factors using multiple logistic regression, the type of endometrial preparation is the factor independently associated with enhanced CPR (OR = 0.48, 95%CI: 0.24–0.96, P = 0.039). ConclusionsThe current study showed that prior long-term GnRHa suppression could benefit patients with high serum autoantibody levels during IVF/ICSI FET cycles.

Subclinical hypothyroidism in pregnancy.

Subclinical hypothyroidism (SCH) is a common diagnosis among women of reproductive age. The importance of sufficient maternal thyroid supply during pregnancy is well known. Nevertheless, the effects of SCH during pregnancy and the efficacy of its treatment on maternofetal outcomes are not well established. This review discusses the recent evidence on SCH in pregnancy and how this evidence is reflected in current clinical care. Recent observational studies have found a positive association between SCH during pregnancy and adverse maternal, neonatal and offspring outcomes, mainly in thyroid peroxidase autoantibody positive women. Although interventional studies have shown a benefit of levothyroxine (LT4) treatment on selected pregnancy outcomes, there was no effect on offspring neurodevelopment. Current evidence strengthens the association between SCH with both maternofetal and offspring adverse outcomes. An earlier and more individualized diagnostic assessment taking into consideration predictors of thyroid dysfunction and major risk factors for complications could result in better management of SCH during pregnancy. The effectiveness of LT4 on improving maternofetal and long-term offspring outcomes is still not fully elucidated.

Comorbidity and long-term outcome in patients with congenital heart block and their siblings exposed to Ro/SSA autoantibodies in utero

ObjectiveCongenital heart block (CHB) may develop in fetuses of Ro/SSA autoantibody-positive women. Given the rarity of CHB, information on comorbidity and complications later in life is difficult to systematically collect...

The prevalence and predictive value of the SLC30A8 R325W polymorphism and zinc transporter 8 autoantibodies in the development of GDM and postpartum type 1 diabetes.

The objectives were to evaluate possible associations between the SLC30A8 R325W polymorphism and gestational diabetes mellitus (GDM) as well as postpartum development of type 2 diabetes. Furthermore, we wanted to confirm the prevalence of zinc transporter 8 autoantibodies (ZnT8A), as previously reported, in a larger population and study its predictive value in relation to other βcell specific autoantibodies in postpartum development of type 1 diabetes. Women diagnosed with GDM (n=776) and women without diabetes (n=511) were included in the study. Autoantibodies were analyzed in all women using enzyme-linked immunosorbent assay. DNA was extracted when possible from women with GDM (n=536) and all of the controls. R325W was detected through polymerase chain reaction and specific restriction digestion. The R325W C-allele were more frequent in women with GDM compared to in controls (OR 1.47, 95% CI 1.16-1.88, p=0.0018) but not significantly increased in women with GDM and postpartum development of type 2 diabetes. Autoantibodies were found in 6.8% (53/776) of the women with GDM and approximately 3.2% (25/776) were ZnT8A positive. Approximately 19% (10/53) of the autoantibody positive women with GDM developed postpartum type 1 diabetes. In conclusion, this is the first study to report a significant association between the R325W C-allele and increased risk of developing GDM. All of the autoantibody positive women with GDM who developed postpartum type 1 diabetes were positive for autoantibodies against glutamic acid decarboxylase (GADA). Thus ZnT8A did not have any additional predictive value in postpartum development of type 1 diabetes.

Anti-Ro/SSA autoantibody-positive women's experience of information given on the risk of congenital heart block.

Congenital heart block (CHB) may develop in fetuses of women with anti-Ro/SSA autoantibodies, and carries substantial morbidity and mortality. The aim was to evaluate how information on CHB is imparted and identify areas of improvement. A questionnaire was distributed to anti-Ro/SSA antibody-positive women who had either participated in a surveillance programme but whose expected child did not develop CHB (n = 100, denoted Doppler-Assessed Pregnancies (DAP) group) or given birth to a child with CHB (n = 88, denoted CHB-Affected Pregnancies (CAP) group). The response rate was 83% (157/188). Most women received the information on CHB when they were already pregnant (DAP group 60%, CAP group 83%). However, a majority of them would have wanted the information before pregnancy (DAP group 52%, CAP group 56%), and most stated that it would not have influenced their decision to have a child (DAP group 77%, CAP group 58%). The ability to both understand the information and to perceive the information as sufficient were significantly higher when someone trained in paediatric cardiology gave the information. Our findings indicate that information on CHB should be given to women before pregnancy. The data further highlight the importance of having specific knowledge for giving relevant and understandable, yet sufficient information.

Ro/SSA autoantibody-positive pregnancy: reactions to serial fetal Doppler echocardiographic surveillance.

The risk for congenital heart block (CHB) associated with maternal Ro/SSA autoantibodies is low, but the possibility of treating early stages of disease has seen the introduction of Doppler echocardiographic surveillance programs with serial examinations during the CHB susceptibility weeks of pregnancy. The aim of the present study was to understand how Ro/SSA autoantibody-positive women having undergone Doppler echocardiographic surveillance programs and giving birth to children without CHB experienced their pregnancy and frequent ultrasound examinations. A validated questionnaire based on data from an interview-study was distributed to Ro/SSA-positive women supervised with Doppler examinations during their pregnancy (n = 100). The response rate was 79%. The majority of the women (61%) reported that the increased number of ultrasound examinations influenced their pregnancy, but in a positive way, with qualified information and additional support from health care personnel in conjunction with the examinations. Further, the visits to the clinic provided opportunities to see the ultrasound picture of the expected infant. However, one-third of the women also reported stress in relation to the examinations. Fetal echocardiographic surveillance holds many and predominantly positive effects for Ro/SSA-positive women during pregnancy in addition to the medical advantages.

Examination of peripheral blood lymphocytes in thyroid autoantibody-positive women with infertility or pregnancy loss

Examination of peripheral blood lymphocytes in thyroid autoantibody-positive women with infertility or pregnancy loss

SP0084 Reproductive Health and Arthritis: What to Expect

A number of studies have shown that the symptoms of rheumatoid arthritis (RA) or inflammatory polyarthritis (IP) ameliorate during pregnancy, especially pregnant women who are rheumatoid factor (RF) negative and...

Ro52 autoantibody-positive women's experience of being pregnant and giving birth to a child with congenital heart block

Background and objectiveCongenital heart block may develop in the fetus of women with Ro/SSA autoantibodies.The aim of this study was to investigate how women expecting a child with congenital heart...

Ro52 autoantibody-positive women's experience of being pregnant and giving birth to a child with congenital heart block

Objectivecongenital heart block may develop in the fetus of women with Ro/SSA autoantibodies. The aim of this study was to investigate how women expecting a child with congenital heart block (CHB) experienced their pregnancy and post-partum period. Design, setting and participantswomen giving birth to a child with CHB in Sweden during 2000–2009 were identified in a population-based manner and individually interviewed post-pregnancy using a semi-structured interview guide. The interviews (n=21) were audiotaped, transcribed verbatim and analysed by qualitative content analysis. Findingsthree categories emerged from the responses: learning, suspense and facing.Learning contained both learning about the child's heart block, but frequently also about autoantibody-positivity and a potential rheumatic diagnosis in the mother (16/21). The medical procedures and information differed considerably depending on the area of residence and who was encountered in the health-care system. In many cases, ignorance about this rare condition caused a delay in treatment and surveillance. Suspense described the women's struggle to cope with the feeling of guilt and that the child had a serious heart condition and might not survive the pregnancy. Facing included the post-partum period, leaving the hospital and adjusting to everyday life. The women had tended to put their pregnancies ‘on hold’, and some described that they needed prolonged time to bond with their newborn child. Conclusionincreased awareness and knowledge of CHB are needed to provide adequate care. Offering psychological support by a health-care professional to facilitate early bonding with the child should be considered. Implications for practicethere is a need for structured programs for surveillance of the pregnancies. Such programme should implement guidelines for the involved personnel in the chain of care and make relevant information accessible for the women and families.

HLA-DRB1*04 is a novel fetal susceptibility allele in congenital heart block

ObjectiveCongenital heart block may develop in the fetus of Ro52 autoantibody positive women. The reported recurrence rate for autoantibody associated congenital heart block is however only 10–25%, indicating that other...

The experiences of pregnancy in women with SSA/Ro52 autoantibodies

Congenital heart block may develop in the foetus during pregnancy in SSA/Ro52 autoantibody-positive women. The aim of this study was to investigate how women with SSA/Ro52 autoantibodies experience their pregnancy in terms of the risk of developing foetal heart block, and in undergoing serial ultrasound Doppler echocardiography to detect early signs of congenital heart block. Data were collected through individual semi-structured interviews with SSA/Ro52-positive women post-pregnancy (n = 14). The interviews were audio-taped, transcribed verbatim and analysed according to qualitative content analysis. Three categories emerged from the responses: information, emotional response and support. The information received prior to and during early pregnancy was focused on the need for attending a specialized antenatal clinic, and information on the risk for congenital heart block was scarce or missing. During gestational weeks 18-24, when the ultrasound/Doppler examinations were performed, all women described increased stress. However, the interaction with the caregivers made the women feel more safe and secure. Several women also said that they did not emotionally acknowledge the pregnancy until after gestational week 24. None had been offered psychological support. There is a need for structured information and organized programmes for the surveillance of women who are SSA/Ro52 positive during their pregnancy. Further, offering psychological support to the women and their families to manage the stress and to facilitate the early attachment to the child should be considered.

Women with rheumatoid arthritis negative for anti-cyclic citrullinated peptide and rheumatoid factor are more likely to improve during pregnancy, whereas in autoantibody-positive women autoantibody levels are not influenced by pregnancy

Objectives:To determine whether changes in levels of anti-cyclic citrullinated peptide (anti-CCP) and rheumatoid factor (RF) are associated with the spontaneous improvement of rheumatoid arthritis (RA) during pregnancy and with the...

Prevalence of post-partum thyroiditis in Liguria (Italy): An observational study

Post-partum thyroiditis (PPT) is an autoimmune disorder occurring within the first year following delivery. A variable prevalence has been reported in different surveys. We prospectively evaluated PPT prevalence and outcome in a cohort of pregnant women living in a well-defined geographic area. A subset from a group of healthy women consecutively evaluated for thyroid function and thyroid autoimmunity during pregnancy, referring to the same obstetric unit, were followed up at 4-6 months and 1 yr after delivery. Follow-up for PPT was performed in 258 pregnant women. Control data were obtained in a comparable group of healthy non-pregnant women. Free T3 (fT3), free T4 (fT4), TSH thyroglobulin/thyroid peroxidase autoantibodies (TgAb/TPOAb), and urinary iodine excretion were measured. Autoantibody positivity was observed in 9.3% of pregnant, similar to control women. Forty-three out of 59 autoantibody-positive women were followed up; 23 showed PPT at the first control, 18 had hypothyroidism at 1 yr (5 had not shown PPT at the first control). Among 215 out of 584 autoantibody-negative women followed up, 27 developed PPT (15 of them without thyroid autoantibodies); 16 developed thyroid autoantibodies without PPT. After 1 yr, 9 women had hypothyroidism: only 1 of them was autoantibody-negative at the former control. Urinary iodine was increased in several pregnant women. An overall PPT prevalence of about 18% may be estimated. PPT was also observed in autoantibody- negative women. Differences with other surveys may be related to both study protocol and characteristics of the population studied.

Presence of GAD Antibodies During Gestational Diabetes Mellitus Predicts Type 1 Diabetes

We sought to study the frequency of beta-cell-specific autoantibody markers in women with gestational diabetes mellitus (GDM) and to follow these women to estimate the risk of later development of type 1 diabetes. Of 385 pregnant women with GDM during 1995-2005 in the district of Lund, 24 (6%) women were found positive for at least one of the following: islet cell antibody (ICA), GAD antibody (GADA), or tyrosine phosphatase antibody (IA-2A). The women were followed and autoantibodies reanalyzed. Those who had not developed diabetes did an oral glucose tolerance test. The frequencies of known risk factors for GDM were compared in women with GDM with and without pancreatic autoantibodies. Among the autoantibody-positive women, 50% had developed type 1 diabetes compared with none among the GDM control subjects (P = 0.001), 21% had impaired fasting glucose or impaired glucose tolerance compared with 12.5% among control subjects (P = 0.3), and none had developed type 2 diabetes compared with 12.5% among control subjects (P = 0.1). Autoantibody screening in pregnant women with GDM and follow-up after delivery should be considered for early recognition of type 1 diabetes.

Predictors of Postpartum Diabetes in Women With Gestational Diabetes Mellitus

The aim of this study was to stratify risk for postpartum diabetes in women who have gestational diabetes. Women with gestational diabetes were recruited between 1989 and 1999, and 302 were followed with oral glucose tolerance tests at 9 months and 2, 5, 8, and 11 years postpregnancy. The 8-year postpartum diabetes risk was 52.7% (130 diabetic cases). Risk was increased in women with autoantibodies to GAD and/or insulinoma antigen-2 (adjusted hazard ratio 4.1; P < 0.0001), women who required insulin during pregnancy (4.7; P < 0.0001), women with BMI >30 kg/m2 (1.5; P = 0.04), and women with more than two prior pregnancies (2.5; P = 0.02). Women without these risk factors had a postpartum diabetes risk of 14% by 8 years, and risk rose incrementally to 96% by 8 years in autoantibody-positive women. Parity status, C-reactive protein concentration, a diabetes family history, maternal age, weeks of gestation, and the child's birth weight did not significantly affect risk in multivariate analysis. Prospective diabetes assessment is indicated and intervention should be considered in women with gestational diabetes who are autoantibody positive, require insulin treatment during pregnancy, or are obese.

Efficacy of Low Dose ASA Administration in Autoantibody-Negative Women With a History of Recurrent Pregnancy Loss

Efficacy of Low Dose ASA Administration in Autoantibody-Negative Women With a History of Recurrent Pregnancy Loss

Clinical characteristics and outcome of pregnancy in women with gestational hyperglycaemia with and without antibodies to beta-cell antigens.

To evaluate the prevalence of beta-cell autoantibodies in women with gestational diabetes and impaired glucose tolerance, and identify clinical characteristics differentiating hyperglycaemic patients with and without autoantibodies. One hundred and twenty-three pregnant patients with gestational diabetes, 84 with impaired glucose tolerance and 290 with normoglycaemia were evaluated for anti-islet cell antibodies, glutamic acid decarboxylase (GAD) autoantibodies, and the components of the metabolic syndrome. Autoantibody positivity was 8.9%, 17.9% and 0.3% in patients with diabetes, impaired tolerance and normoglycaemia, respectively. Hyperglycaemic patients with autoantibodies had lower body mass index, waist, weight gain at the time of the screening test and a lower percentage of previous pregnancies than those without autoantibodies. In addition, their fasting insulin values were significantly lower and inversely related to the presence of autoantibodies (odds ratio (OR) = 0.64; 95% confidence interval (CI) 0.42-0.96), the lowest values being found in anti-GAD+ patients. Autoantibody-positive women with diabetes were more frequently treated with insulin than negative patients (OR = 7.21; 95% CI 1.85-28.08). Autoantibody-positive women with gestational hyperglycaemia displayed fewer features of insulin resistance and required more frequent insulin therapy than negative women and presumably had presymptomatic Type 1 diabetes. If this conclusion is corroborated by the follow-up of larger series, clinical and immunological distinction of types of gestational hyperglycaemia would be useful.