Maternal Autoimmunity Research Articles

Thyroid autoantibodies: adverse effects on pregnancy outcomes and child development and its intervention

Thyroid autoantibodies (TAA) in euthyroid women were associated with several adverse pregnancy outcomes,such as miscarriage,preterm birth.Maternal TAA frequently results in transient mild elevation of serum TSH above the normal reference value in women during pregnancy and in infants born in the first month of life,and may affect neuropsychological development of their offspring.The cause is still unclear.Medical interventions on TAA involve levothyroxine or selenium supplementation. The article reviews the effects of maternal thyroid autoantibodies on pregnancy outcomes,as well as on neonatal thyroid status,and neuropsychological development of the fetus and neonate,and summarizes therapeutic strategies used to intervene maternal thyroid autoimmunity. Key words: Thyroid autoantibodies; Autoimmunity; Pregnancy outcomes; Intervention

Maternal Thyroid Autoimmunity During Pregnancy and the Risk of Attention Deficit/Hyperactivity Problems in Children: The Generation R Study

Maternal thyroid status and autoimmunity during pregnancy have been associated with impaired development of the offspring in animal and human studies. Our objective was to examine whether elevated titers of maternal thyroid peroxidase antibodies (TPOAbs) in early pregnancy increased the risk of cognitive impairment and problem behavior in preschool children. Second, we aimed at exploring to what extent any effect on child behavior was mediated by maternal thyroid parameters during pregnancy. In the Generation R Study, a population-based cohort of 3139 children and their mothers, we measured maternal thyroid parameters (thyrotropin [TSH], free Thyroxine, and TPOAbs) at 13.5±1.8 weeks of gestation. Children's verbal and nonverbal cognitive functioning was measured at 2.5 years using the Language Development Survey and the Parent Report of Children Abilities. At 3 years, children's behavior was assessed using the Child Behavior Checklist. Elevated titers of TPOAbs during pregnancy did not predict the verbal and nonverbal cognitive functioning of the children. However, elevated titers of TPOAbs in mothers were associated with externalizing problems in children (odds ratio [OR]=1.64, 95% confidence interval [CI]: 1.17-2.29, p=0.004). In particular, children of TPOAb-positive mothers were at a higher risk of attention deficit/hyperactivity problems (OR=1.77, 95% CI: 1.15-2.72, p=0.01). To explore whether the effect of maternal TPOAbs on child problem behavior was mediated by maternal thyroid parameters, we added maternal TSH to the model. After correcting for TSH, the effect of TPOAbs on externalizing problems was attenuated slightly but remained significant (OR=1.56, 95% CI: 1.14, 2.14, p=0.005). Our findings imply that the elevated titers of TPOAbs during pregnancy impact children's risk of problem behavior, in particular, attention deficit/hyperactivity. The observed effect is only partially explained by maternal TSH levels. These findings may point to a specific mechanism of Attention Deficit/Hyperactivity Disorder in children. Nevertheless, we can only speculate about public health implication of the study, as there is no specific treatment for TPOAb-positive pregnant women with normal thyroid function. Further investigation is needed to explore whether TPOAb-positive pregnant women and their children can benefit from close monitoring and early detection of developmental delay in populations at risk.

Challenges in interpretation of thyroid function tests in pregnant women with autoimmune thyroid disease.

Physiological changes during gestation are important to be aware of in measurement and interpretation of thyroid function tests in women with autoimmune thyroid diseases. Thyroid autoimmune activity is decreasing in pregnancy. Measurement of serum TSH is the first-line screening variable for thyroid dysfunction also in pregnancy. However, using serum TSH for control of treatment of maternal thyroid autoimmunity infers a risk for compromised foetal development. Peripheral thyroid hormone values are highly different among laboratories, and there is a need for laboratory-specific gestational age-related reference ranges. Equally important, the intraindividual variability of the thyroid hormone measurements is much narrower than the interindividual variation (reflecting the reference interval). The best laboratory assessment of thyroid function is a free thyroid hormone estimate combined with TSH. Measurement of antithyroperoxidase and/or TSH receptor antibodies adds to the differential diagnosis of autoimmune and nonautoimmune thyroid diseases.

Thyroid and pregnancy.

Thyroid and pregnancy.

Thyroid function abnormalities among first‐degree relatives of Iranian congenital hypothyroidism neonates

Congenital hypothyroidism (CH) is a relatively common metabolic disease in neonates. Until recent years the disorder was usually regarded as occurring in a sporadic manner. Over the past few years, however, a considerable proportion of familial cases have been identified, and possible roles of autoimmune factors suggested. The aim of the present study was to evaluate abnormality of thyroid function tests in first-degree relatives of CH neonates and compared this to the normal population. From 2002 until 2007 thyroid function tests (T4 and thyroid-stimulating hormone [TSH]) were done in randomly selected CH and normal neonates (n= 194 and n= 350, respectively) and their first-degree relatives. Most mothers of the CH neonates and control groups were also evaluated for thyroid peroxidase antibody (TPOAb). Thyroid function test in first-degree relative of neonates with CH (361 parents, 136 siblings) were compared with those in control groups (665 parents, 478 siblings). Abnormal thyroid function tests were found in 85 patients in the CH group versus 96 patients in the control group; hypothyroidism was found in 75 (15.1%) and 57 subjects (5%) person in the CH and control groups, respectively (P < 0.05). Positive TPO antibody was found in 22 mothers (17.3%) of CH neonates in comparison with 65 mothers (32.5%) of control groups (P < 0.05). Frequency of hyperthyroidism in parents of control group had trend to be higher than parents of CH neonates (P= 0.05) Familial and genetic components play a role in inheritance of CH, but maternal thyroid autoimmunity may not play an important role in the development of CH in Iran.

Maternal Thyroid Autoantibodies Predict Poor Perinatal Outcomes

Endocrinology| July 01 2009 Maternal Thyroid Autoantibodies Predict Poor Perinatal Outcomes AAP Grand Rounds (2009) 22 (1): 5. https://doi.org/10.1542/gr.22-1-5 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter LinkedIn Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Maternal Thyroid Autoantibodies Predict Poor Perinatal Outcomes. AAP Grand Rounds July 2009; 22 (1): 5. https://doi.org/10.1542/gr.22-1-5 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search toolbar search search input Search input auto suggest filter your search All PublicationsAll JournalsAAP Grand RoundsPediatricsHospital PediatricsPediatrics In ReviewNeoReviewsAAP NewsAll AAP Sites Search Advanced Search Topics: perinatal period, thyroid autoantibodies, thyroid diseases, antibodies Source: Männistö T, Vääräsmäki M, Pouta A, et al. Perinatal outcome of children born to mothers with thyroid dysfunction or antibodies: a prospective population-based cohort study. J Clin Endocrinol Metab. 2009;94(3):772–779; doi:10.1210/jc.2008-1520 Investigators from Finland and the UK prospectively evaluated the effect of maternal thyroid dysfunction and autoimmunity on perinatal outcomes. Data on 9,247 pregnant Finnish women and their singleton births from the Northern Finland Birth Cohort were analyzed. Blood samples from a subset of mothers during the first trimester were analyzed for serum free T4 (fT4), thyroid stimulating hormone (TSH), thyroid-peroxidase antibody (TPO-Ab), and thyroglobulin antibody (TG-Ab). The study participants were divided into four groups based on thyroid studies: 1) clinical hypothyroidism (high TSH, low fT4); 2) subclinical hypothyroidism (high TSH, normal fT4); 3) subclinical hyperthyroidism (low TSH, normal fT4); and 4) clinical hyperthyroidism (low TSH, high fT4). Blood samples were available from 5,805 mothers. Approximately 1% (n=54) had clinical hypothyroidism, 4% (n=224) subclinical hypothyroidism, 4% (n=204) subclinical hyperthyroidism, and 1.5% (n=77) clinical hyperthyroidism. Approximately 5% had TPO-Ab or TG-Ab positivity. Infants born to clinically hyperthyroid mothers were more likely to be large for gestational age (6.6% vs 2.5%) although this effect disappeared after correction for maternal age and parity. Infants born to TPO-Ab positive but not TG-Ab positive mothers were more likely to have low birth weight or be large for gestational age. The adjusted odds ratio of perinatal death among children born to TPO-Ab positive mothers was 3.2 (95% CI, 1.4–7.1) and 2.5 (95% CI, 1.1–5.9) for children born to TG-Ab positive mothers. More than half the deaths among children born to thyroid autoantibody positive mothers occurred in infants born at less than 28 weeks gestation. The authors conclude that positive maternal thyroid autoantibody but not thyroid hormone status is a risk factor for perinatal death. Dr Varma has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device. This large Finnish study sheds new light on the relationship of maternal thyroid disease and perinatal outcomes, an issue that has been addressed in previous studies.1,–3 Prior investigations suggested that thyroid dysfunction is associated with spontaneous abortions, fetal death, premature births, microcephaly, low birth weight, and impaired psychological development.4,5 The strengths of this current study are its large size and relatively complete collection of data on this cohort. The data support the authors’ conclusion that maternal thyroid autoantibodies detected during the first trimester are independently associated with risk for perinatal mortality, most likely through a higher incidence of pre-term delivery. However, the authors also acknowledge that, even with this large cohort, perinatal mortality was a rare event and thus the actual risk may be different from that seen in this study. In addition, because the Finnish population is 99% Caucasian the study needs to be replicated in more ethnic groups before its results are applied to a diverse populace such as that of... You do not currently have access to this content.

Thyroid Autoimmunity in Schoolchildren in an Area with Long-Standing Iodine Sufficiency: Correlation with Gender, Pubertal Stage, and Maternal Thyroid Autoimmunity

A strong genetic background and gender are believed to be involved in thyroid autoimmunity (TA). The age these factors become manifest is less clear, however. The objective of the present study was to determine the prevalence of TA in children and adolescents and to determine if there are relationships between the period of onset of TA and gender and between TA and maternal autoimmunity. Antithyroperoxidase antibodies (anti-TPO Ab), antithyroglobulin antibodies (anti-Tg Ab), thyrotropin, thyroxine, triiodothyronine, and urinary iodine were determined in 440 healthy schoolchildren (200 boys and 240 girls), aged 5-18 years, and in 123 mothers living in an iodine-replete region. The prevalence of positive anti-TPO and anti-Tg Ab was 4.6% and 4.3%, respectively. In girls, the prevalence of positive anti-TPO Ab was higher in Tanner stage II-V compared to Tanner stage I (8.2% vs. 2.2%; p < 0.05). No difference was detected with regard to anti-Tg Ab. In girls, positive anti-TPO and anti-Tg Ab levels were associated with significantly greater thyroid volume. Hypoechogenicity was detected in 52.6% and 36.8% of the children with positive anti-TPO or anti-Tg Ab, respectively (p = 0.0005). The prevalence of autoimmune thyroiditis, as defined by positive serum anti-TPO and/or anti-Tg and an echographic pattern of the thyroid gland having diffuse or irregular hypoechogenicity, was 2.5%. Mothers of anti-TPO Ab positive children had positive anti-TPO Ab more frequently compared to mothers of anti-TPO Ab negative children (82% vs. 18%; p = 0.0005). Mothers of anti-Tg Ab positive children had positive anti-Tg Ab more frequently compared to mothers of anti-Tg Ab negative children (75% vs. 25%; p = 0.0005). These findings demonstrate that thyroid antibody positivity in children was significantly associated with maternal autoimmunity and their development in girls emerges at puberty. Since heredity, female gender, and puberty are strongly associated with TA, girls in families with TA should be examined at the onset of puberty.

Chondrodysplasia Punctata and Maternal Autoimmune Disease: A New Case and Review of the Literature

Classic rhizomelic chondrodysplasia punctata is a rare, autosomal, recessively inherited disorder that is characterized by proximal shortening of the limbs, punctuate calcifications of the epiphyses, cataracts, developmental delay, and early lethality. A distinctive biochemical profile is characteristic for each of the several defects of peroxisomal metabolism. Recently, cases have been described that were not associated with peroxisomal dysfunction. These cases were found to be secondary to teratogen exposure or maternal conditions. Since 1993, there have been 9 reported cases of neonates with rhizomelic chondrodysplasia punctata who were born to mothers with connective tissue disease. We followed a newborn boy with features suggestive of rhizomelic chondrodysplasia punctata whose biochemical studies failed to demonstrate a defect in either plasmalogen or cholesterol biosynthesis. His mother developed systemic lupus erythematosus 8 months after delivery. This case is compared with the previously reported 9 cases from the literature and is instructive in demonstrating a lesser known effect of maternal autoantibodies on the fetus.

Hypoplastic Left Heart Syndrome

See related article, pages 1363–1370 Hypoplastic left heart syndrome (HLHS) is one of the most severe congenital heart defects, accounting for 20% to 25% of mortality in infants born with congenital heart disease. In the United States, ≈2000 infants are born each year with HLHS.1 To date, there is a paucity of studies that define the underlying genetic, molecular and cellular mechanisms of HLHS.2–4 Most cases of HLHS are thought to arise secondarily because of decreased flow into the developing embryonic left ventricle, although in some cases, abnormal left ventricular growth could be the primary defect. There is strong evidence for a genetic etiology for HLHS, although very little is understood about the genetic mechanisms underlying HLHS. Nineteen percent of first degree relatives of infants with HLHS have a congenital heart defect.5 In addition, there are several chromosomal disorders that are associated with HLHS. For example, 10% of all infants born with a terminal 11q deletion (Jacobsen syndrome) have HLHS.6 Mutations in at least one gene, the cardiac transcription factor NKX2.5, have been identified in patients with HLHS.7,8 Similar to many of the most severe congenital heart defects, treatment strategies for HLHS have evolved and are still changing. The two current surgical strategies include the three-stage Norwood/Fontan procedure, or, alternatively, cardiac transplantation. The Norwood procedure, which is performed optimally in the neonatal period to avoid the development of pulmonary vascular disease, entails reconstructing the aortic arch, transecting the pulmonary artery, anastamosing the pulmonary artery root to the reconstructed aorta, and placing a systemic to pulmonary artery shunt (either from aorta or more recently, from the right ventricle). Although there has been significant progress in outcomes, neither surgical approach is curative and long-term outcomes are uncertain. Consequently, there has been an ongoing effort to develop …

Environmental factors in the development of Type 1 diabetes

Environmental factors appear to play an important role in the pathogenesis of childhood-onset type 1 diabetes (T1D). The most important factors are thought to be infectious, dietary, perinatal, and psychosocial. Enteroviruses (especially Coxsackie B virus), breastfeeding, the early presence or lack of certain foods, birth weight, childhood over-nutrition, maternal islet autoimmunity, and negative stress events have been shown to be related to the prevalence of T1D. However, clear conclusions to date are limited because most studies lacked power to detect exposure/disease associations, were not prospective or long-term, did not start in infancy, had imprecise or infrequent exposure estimates, had confounding exposures, and failed to account for genetic susceptibility. In addition to the identification of specific antigenic triggers, several more general hypotheses, including the accelerator and hygiene hypotheses, are testable approaches worth pursuing.

Evidence for immunological priming and increased frequency of CD4+ CD25+ cord blood T cells in children born to mothers with type 1 diabetes

Maternal transmission of islet autoantibodies to children born to mothers with type 1 diabetes (T1D) has been shown to protect from autoantibodies and diabetes development later in life. However, the factors conferring disease protection are poorly understood. The aim of this study was to evaluate comparatively proinflammatory cytokines, autoantibodies and lymphocyte subsets in cord blood (CB) of children born to mothers with either T1D (n = 13), gestational diabetes (GDM) (n = 32) or healthy mothers (n = 81) in relation to transplacental passage of autoantibodies. The results are consistent with early priming of the fetal immune system only in children born to mothers with T1D. Levels of interleukin (IL)-1beta (P = 0.022), tumour necrosis factor (TNF)-alpha (P = 0.002) and IL-8 (P = 0.0012), as well as the frequency of CD4(+) CD25(+) T cells (P < 0.01) were significantly increased, and the increased levels correlated positively with anti-GAD65 autoantibody (GADA) levels. Moreover, CD4(+) CD25(+) T cells of children born to T1D mothers exhibited a more pronounced memory phenotype with increased CCR4 expression and down-regulation of CD62L. These data suggest that early activation of the fetal immune system as a consequence of maternal autoimmunity and transplacental passage of GADA may influence the generation and expansion of fetal regulatory T cells. This might induce an early antigen-specific immunological tolerance that could protect against T1D later in life.

The changing maternal “self” hypothesis: A mechanism for maternal tolerance of the fetus

Recent advances in placental biology and immunology lead us to propose a novel hypothesis for maternal tolerance of the semi-allogeneic fetus and amelioration of rheumatoid arthritis (RA) during pregnancy. The initial event in this hypothesis is extrusion of placental apoptotic syncytiotrophoblast debris recently identified to contain intracellular fetal HLA Class II molecules, into maternal blood. The second event is uptake of apoptotic syncytiotrophoblast by immature maternal dendritic cells and presentation of fetal HLA class II peptides. In addition to presenting foreign antigens, HLA molecules also present HLA self-peptides. In the setting of the non-inflammatory environment of pregnancy, this process is expected to induce peripheral tolerance of fetal antigens through T cell death, anergy or induction of regulatory T cells in the lymph nodes. This hypothesis suggests a mechanism by which the simultaneous presentation of fetal and (RA-associated) HLA peptides by tolerogenic dendritic cells during pregnancy may explain the observed amelioration of RA as a secondary benefit of fetal tolerance. After delivery, apoptotic syncytiotrophoblast debris disappears from maternal blood, autoimmunity returns and RA recurs. Thus, during pregnancy maternal immunologic self includes fetal HLA Class II as a result of apoptotic syncytiotrophoblast uptake by maternal tolerogenic dendritic cells.

The Changing Maternal “Self” Hypothesis: A Mechanism for Maternal Tolerance of the Fetus

Recent advances in placental biology and immunology lead us to propose a novel hypothesis for maternal tolerance of the semi-allogeneic fetus and amelioration of rheumatoid arthritis (RA) during pregnancy. The initial event in this hypothesis is extrusion of placental apoptotic syncytiotrophoblast debris recently identified to contain intracellular fetal HLA Class II molecules, into maternal blood. The second event is uptake of apoptotic syncytiotrophoblast by immature maternal dendritic cells and presentation of fetal HLA class II peptides. In addition to presenting foreign antigens, HLA molecules also present HLA self-peptides. In the setting of the non-inflammatory environment of pregnancy, this process is expected to induce peripheral tolerance of fetal antigens through T cell death, anergy or induction of regulatory T cells in the lymph nodes. This hypothesis suggests a mechanism by which the simultaneous presentation of fetal and self (RA-associated) HLA peptides by tolerogenic dendritic cells during pregnancy may explain the observed amelioration of RA as a secondary benefit of fetal tolerance. After delivery, apoptotic syncytiotrophoblast debris disappears from maternal blood, autoimmunity returns and RA recurs. Thus, during pregnancy maternal immunologic “self” includes fetal HLA Class II as a result of apoptotic syncytiotrophoblast uptake by maternal tolerogenic dendritic cells.

Effects of Maternal Autoimmune Diseases on Fetus and Neonates

Effects of Maternal Autoimmune Diseases on Fetus and Neonates

Neonatal Hemochromatosis: Is It an Alloimmune Disease?

Neonatal hemochromatosis (NH) has been defined clinically as severe neonatal liver disease in association with extrahepatic siderosis in a distribution similar to that seen in HFE-associated hereditary hemochromatosis (1). Though it is generally considered a rare disease, it is one of the most commonly recognized causes of liver failure in the neonate and a frequent indication for liver transplantation in the first 3 months of life (2–4). Its etiology and pathogenesis are as yet unknown. Indeed, it has been considered to be a syndrome in which a number of primary etiologies, such as infection, genetic-metabolic disease and toxic insult, lead to a common phenotype. We have hypothesized that much, if not all, NH is a consequence of gestational alloimmune disease. This review presents the clinical evidence leading to this hypothesis, the data we have collected in its support, and the direction our investigations are taking to ultimately prove or disprove it.

Maternal Autoimmune Diseases, Asthma and Allergies, and Childhood Autism Spectrum Disorders

To investigate the association between physician-documented diagnoses of maternal autoimmune diseases, allergies, and asthma around the time of pregnancy and subsequent diagnoses of autism in children. A case-control study nested within a cohort of infants born between January 1995 and June 1999. Northern California Kaiser Permanente Medical Care Program. Cases (n = 420) were children with at least 1 diagnosis of an autism spectrum disorder (ASD) recorded in Kaiser Permanente outpatient clinical databases. Controls (n = 2100) were children without an ASD diagnosis who were frequency matched to cases on sex, birth year, and hospital of birth. Frequencies of maternal immunologic disorders were compared between cases and controls with a chi2 statistic, and relative risks were estimated by crude and adjusted odds ratios and 95% confidence intervals using logistic regression. The final study population included 407 cases and 2095 controls. A similar proportion of case and control mothers had a diagnosis of any autoimmune disease in the 4-year period surrounding pregnancy (10.3% vs 8.2%, P = .15). After adjustment for maternal factors, only 1 autoimmune condition, psoriasis, was significantly associated with ASDs (adjusted odds ratio, 2.7; 95% confidence interval, 1.3-5.8). A greater than 2-fold elevated risk of ASD was observed for maternal asthma and allergy diagnoses recorded during the second trimester of pregnancy. These findings suggest that maternal autoimmune disorders present in women around the time of pregnancy are unlikely to contribute significantly to autism risk. Further etiologic investigations are needed to confirm these results and should include objective documentation of diagnoses and consider a larger set of maternal immune-related conditions, including asthma and allergies.

These fads are here to stay—clinicopathological patterns of food allergic diseases

These fads are here to stay—clinicopathological patterns of food allergic diseases

Autoantibodies in Mothers of Children with Neonatal Liver Disease

ABSTRACTObjectivesNeonatal lupus erythematosus (NLE) is associated with maternal anti‐Ro/La autoantibodies. It is characterized by heart block and/or cutaneous skin lesions, and occasionally liver disease. This study was performed to determine whether idiopathic neonatal cholestasis (INC) represents NLE without its cardiac or cutaneous findings.MethodsSera were obtained for autoantibody analysis from mothers of children with INC (N = 11), biliary atresia (N = 25), other liver disease excluding viral hepatitis (liver disease control subjects, N = 14), and healthy children (normal control subjects [NC], N = 22).ResultsThe characteristic serologic findings of NLE, high titer antibodies to Ro and/or La, were absent in mothers from all groups. An unexpected finding was the prevalence of autoantibodies in mothers of infants with liver disease of any type. The frequency of maternal antinuclear antibodies at ≥ 1:120 dilution was greater than the estimated frequency in the general population (22% vs. 9%, P = 0.044). The frequency of maternal low titer autoantibodies to 52 kD Ro detected by ELISA was significantly greater than in the NC group (31% vs. 5%, P = 0.014).ConclusionsThe majority of cases of INC do not represent NLE. The frequent presence of autoantibodies in mothers of infants in all neonatal liver disease groups raises the possibility that maternal serologic autoimmunity is associated with neonatal liver disease.

Autoantibodies in mothers of children with neonatal liver disease.

Neonatal lupus erythematosus (NLE) is associated with maternal anti-Ro/La autoantibodies. It is characterized by heart block and/or cutaneous skin lesions, and occasionally liver disease. This study was performed to determine whether idiopathic neonatal cholestasis (INC) represents NLE without its cardiac or cutaneous findings. Sera were obtained for autoantibody analysis from mothers of children with INC (N = 11), biliary atresia (N = 25), other liver disease excluding viral hepatitis (liver disease control subjects, N = 14), and healthy children (normal control subjects [NC], N = 22). The characteristic serologic findings of NLE, high titer antibodies to Ro and/or La, were absent in mothers from all groups. An unexpected finding was the prevalence of autoantibodies in mothers of infants with liver disease of any type. The frequency of maternal antinuclear antibodies at > or = 1:120 dilution was greater than the estimated frequency in the general population (22% vs. 9%, P = 0.044). The frequency of maternal low titer autoantibodies to 52 kD Ro detected by ELISA was significantly greater than in the NC group (31% vs. 5%, P = 0.014). The majority of cases of INC do not represent NLE. The frequent presence of autoantibodies in mothers of infants in all neonatal liver disease groups raises the possibility that maternal serologic autoimmunity is associated with neonatal liver disease.

Transient Congenital Hypothyroidism due to maternal autoimmune thyroid disease

The neonatal screening program for congenital hypothyroidism (CH) in Greece shows an overall incidence of the disease of 1:2321. The cases with permanent CH have an incidence of 1:2542, whereas the transient forms of CH account for 8.7% of all cases diagnosed as CH. Transplacental passage of maternal thyrotropin receptor-blocking antibodies is a rare cause of transient CH. In our program, a retrospective analysis of 508,358 screened newborns revealed 6 infants with transient CH caused by maternal thyroid autoimmunity, representing 2.7% of all cases of CH. All the newborns with transient CH, due to maternal autoimmune thyroid disease, had high serum TSH concentration (ranging from 98 to 689 mU/L), whereas serum thyroxine (T4) values were low normal to normal in 3 of them. Replacement therapy with L-thyroxine was initiated at a mean age of 6.5 days. The newborns with transient CH belonged to 4 families, one of which had 4 and another 2 children with the same pathology. Thyrotropin-receptor antibodies (TSH-R Abs), present at the initial examination in newborns' serum, had disappeared from the infants' circulation by the third month of life. One mother carried the Abs for at least 8 years during which period she delivered four babies. The diagnosis of transient CH should be suspected if the mother has autoimmune thyroid disease, if there are siblings with transient CH or if there is no need for an increase in L-thyroxine dose with advancing age. The diagnosis is very important for genetic counseling, early treatment initiation of subsequent offspring and adequate control of the mother's thyroid function during subsequent pregnancies so that any neurodevelopmental abnormality of the fetus could be avoided.