Incidence and associated risk factors of congenital hypothyroidism among newborns in Hainan, China: a retrospective study.

OBJECTIVES: This study aims to investigate the incidence and risk factors of congenital hypothyroidism (CH) in newborns in Hainan Province, China, to provide a reference for early and effective prevention strategies. METHODS: Newborns born in Hainan Province from 2017 to 2021 were the subjects of this study. Time-resolved immunofluorescence was used for initial screening and chemiluminescence for confirmatory diagnosis. Based on the diagnosis, newborns were classified into CH and non-CH groups. Statistical analysis was conducted on the initial screening and confirmed CH cases in newborns in Hainan Province, and potential risk factors for CH were explored. RESULTS: From 2017 to 2021, a total of 585,886 newborns were screened, revealing 6,856 initial positive results, 614 positive rescreens, and 420 confirmed CH cases, yielding an incidence rate of 1/1,395 (420/585,886). The annual initial positive screening rate of newborns in Hainan Province showed a rising trend from 2017 to 2021 (p=0.000). No significant differences were found regarding gender (p=0.400) and ethnicity (p=0.836). Multivariate logistic regression analysis indicated that residing in coastal areas, especially those with salt fields (OR=2.151, 95 % CI: 1.364-3.390), was risk factors for the development of CH in newborns. CONCLUSIONS: The incidence of CH in newborns showed a year-on-year increase in Hainan Province from 2017 to 2021. Residing in coastal areas, particularly those with salt fields, was identified as a risk factor for the development of CH.

Neonatal screening for congenital hypothyroidism in Sweden 1980-2013: effects of lowering the thyroid-stimulating hormone threshold.

OBJECTIVE: This study aims to evaluate the neonatal screening for congenital hypothyroidism (CH) and the diagnosis CH in the national health registers and to study the effects of lowering screening thyroid-stimulating hormone (TSH) threshold on the incidence of CH and birth characteristics of screening positive and negative CH children. DESIGN: This is a nationwide register-study of all children (n = 3 427 240) in the Swedish Medical Birth Register (MBR) and national cohort for screening positive infants (n = 1577) in 1980-2013. METHODS: The study population was further linked to several other Swedish health registers. Evaluation of the CH screening and CH diagnosis was performed with levothyroxine use in the first year of life as reference. The incidence of CH was estimated by the Clopper-Pearson method. Regression models were used to study associations between CH and birth characteristics. RESULTS: The neonatal CH screening had high efficacy, but 50% of all children with a CH diagnosis were screening negative. The incidence of screening positive CH increased (1/3375 to 1/2222), and the incidence of screening negative CH decreased (1/2563 to 1/7841) after lowering the TSH screening threshold in 2009. Screening negative CH was associated with female sex, twinning, prematurity, low birth weight, birth defects, and need of neonatal intensive care, and 42% had transient disease. CONCLUSIONS: Despite high efficacy of the CH screening, 50% of children diagnosed as CH was screening negative. Although other factors influencing the incidence of the CH diagnosis cannot be ruled out, the incidence of screening negative CH decreased with lowering of the TSH threshold. Birth characteristics differed between screening positive and negative CH.

Medical Management of Dental Abnormalities Related to Congenital Hypothyroidism in a Cat.

A 5-month-old intact male domestic shorthair cat presenting for routine vaccinations was diagnosed with congenital hypothyroidism. His primary presenting symptom was incomplete dentition with delayed dental eruption. Congenital hypothyroidism was confirmed by baseline thyroxine (T4), free T4, and thyroid-stimulating hormone testing. The cat was treated with oral thyroid hormone supplementation and 16 weeks after initiation of therapy the cat was clinically normal with age-appropriate dentition. No surgical intervention was necessary to achieve normal dental eruption.

Comparison of developmental outcomes in children with permanent and transient congenital hypothyroidism.

OBJECTIVES: Congenital hypothyroidism (CH) is still one of the most common causes of preventable cognitive impairment in children, and its early detection and treatment prevent irreversible neurodevelopmental delay. Depending on the underlying cause, cases with CH may be transient or permanent. This study aimed to compare the developmental evaluation results of transient and permanent CH patients and to reveal any differences. METHODS: A total of 118 patients with CH, who were followed up jointly in pediatric endocrinology and developmental pediatrics clinics, were included. The patients' progress was evaluated per the International Guide for Monitoring Child Development (GMCD). RESULTS: Of the cases, 52 (44.1%) were female, and 66 (55.9%) were male. While 20 (16.9%) cases were diagnosed with permanent CH, 98 (83.1%) were diagnosed with transient CH. According to the results of the developmental evaluation made with GMCD, the development of 101 (85.6%) children was compatible with their age, while 17 (14.4%) children had delays in at least one developmental area. All 17 patients had a delay in expressive language. Developmental delay was detected in 13 (13.3%) of those with transient CH and 4 (20%) with permanent CH. CONCLUSIONS: There is difficulty in expressive language in all cases of CH with developmental delay. No significant difference was found between the developmental evaluations of permanent and transient CH cases. The results revealed the importance of developmental follow-up, early diagnosis and interventions in those children. GMCD is thought to be an important guide to help monitoring the development of patients with CH.

Incidence of primary congenital hypothyroidism over 24 years in Finland.

BACKGROUND: A rise in the incidence of congenital hypothyroidism (CH) has been reported worldwide. This nationwide study aimed to describe the secular trends and current incidence of CH in Finland. METHODS: Two independent study cohorts, a national and a regional, were collected from national registers and patient records. The national cohort represents all CH cases born in Finland between 1994 and 2017. Birth data, results of the screening test, and the incidence of CH were reviewed. RESULTS: Between 1994 and 2017, 1,400,028 children were born in Finland. Of these children, 503 were diagnosed with primary CH (incidence 1:2783). Male-to-female sex ratio was 1:2.0. The nationwide incidence was 33 cases per 100,000 live births between 1994 and 1999, 38 cases per 100,000 live births between 2000 and 2005, 40 cases per 100,000 live births between 2006 and 2011, and 33 cases per 100,000 live births between 2012 and 2017. In the regional cohort (n = 139), the incidence of transient CH was 3.6%. The incidence of mild, moderate, and severe CH remained constant. CONCLUSIONS: In Finland, the incidence of CH has not changed during the 24-year study period. IMPACT: As opposed to recent reports worldwide, the incidence of congenital hypothyroidism has not changed between 1994 and 2017 in Finland. The proportions of mild, moderate, and severe congenital hypothyroidism did not change significantly over the study period. Lowering the TSH cut-off limit or increasing immigration did not affect the incidence rate of primary congenital hypothyroidism in Finland.

Risk Factors of Congenital Hypothyroidism in Israel.

BACKGROUND: Congenital hypothyroidism (CH) is the most common preventable cause of mental retardation and delayed growth in children. Several prenatal and environmental factors might be associated with the disease. OBJECTIVES: To determine the prevalence and risk factors of permanent CH and transient congenital hypothyroidism (TCH) in Israel. METHODS: We conducted a retrospective analysis of the Israeli national newborn screening program database from 2011 to 2015. Chi-square and logistic regression were used to assess the association of the demographic and gestational factors with the CH and TCH. RESULTS: Of the 889,033 live births screened between 2011 and 2015, 860 were diagnosed with CH (9.76 per 10,000 live births) and 298 with TCH (3.35 per 10,000 live births). In multivariate analyses, CH was positively associated with female sex, gestational ages < 38 or > 39 weeks, birth weight < 3000 grams, and winter birth. A decreased risk of TCH was detected in Arabs and neonates from high socioeconomic areas. An increased risk was independently associated with gestational ages < 38 weeks, low birth weight, and winter birth. CONCLUSIONS: Several demographic, gestational, and geographical factors are associated with the development of CH and TCH. Future studies are needed to further investigate the pathogenesis in Israel.

Iatrogenic hyperthyroidism in primary congenital hypothyroidism: prevalence and predictive factors.

OBJECTIVES: Primary congenital hypothyroidism (CH) is a preventable cause of mental retardation. Iatrogenic hyperthyroidism has occasionally been reported using the recommended LT4 dosage. Currently, information regarding iatrogenic hyperthyroidism and predictive factors for permanent hypothyroidism (P-CH) among Thai patients is lacking. The aim of this study is to determine the prevalence and factors for predicting iatrogenic hyperthyroidism at one month after LT4 initiation and for predicting P-CH in primary CH infants. METHODS: This retrospective cohort study involved 87 infants with primary CH. Patients were classified by thyroid status at one month after LT4 initiation. At 3 years, patients were reevaluated after LT4 cessation and assigned as P-CH or transient CH (T-CH). Differences between groups were analyzed. RESULTS: One month after LT4 initiation, 35.6% of patients were classified as having iatrogenic hyperthyroidism. An initial LT4 dose of 10.2 µg/kg/day (sensitivity 64.5%, specificity 71.4%) was a suitable cutoff value for predicting iatrogenic hyperthyroidism, wherein 55.6 and 21.6% of patients were treated with initial doses of ≥10.2 and <10.2 µg/kg/day, respectively (p=0.004). Initial LT4 dose was the only predictive factor for thyroid status after initial treatment. At reevaluation, 47.4% of patients were diagnosed with P-CH. LT4 dosage at 3 years of age was significantly higher in patients with P-CH (3.3 vs. 2.85 µg/kg/day, p=0.02) and the only relevant factor for predicting P-CH. CONCLUSIONS: Iatrogenic hyperthyroidism is common among infants with primary CH when treated with the recommended LT4 dosage. LT4 dose was the only factor for predicting iatrogenic hyperthyroidism after LT4 initiation and the diagnosis of P-CH.

Incidence tendency, etiological classification and outcome of congenital hypothyroidism in Guangzhou, China: an 11-year retrospective population-based study.

OBJECTIVES: An increased incidence of congenital hypothyroidism (CH) has been described worldwide over the years. In this study, we aimed to investigate the epidemiologic characteristics of CH, the iodine status in Guangzhou, China and to investigate which factors might influence the CH incidence during the period 2010-2020. METHODS: We retrospectively reviewed all cases of CH detected by newborn screening during the period 2010-2020. CH was classified as either suspected thyroid dyshormonogenesis (SDH) or thyroid dysgenesis (TD) based on thyroid ultrasound at first diagnosis. Patients were re-evaluated after 4 weeks of L-thyroxine withdrawal at age of 2-3 years to confirm the diagnosis of permanent CH (PCH) or transient CH (TCH). RESULTS: From 2010 to 2020, 1,655 patients with CH were confirmed from 2,400,383 newborns (1:1,450). The CH incidence increased from 1:2,584 in period [2010-2014] to 1:1,086 in period [2015-2020]. Among the 1,337 patients with thyroid ultrasound, 84.29% were SDH whereas 15.71% had TD. Further analysis revealed that more SDH (78.32%) were TCH whereas more TD (87.12%) turned to be PCH. The proportion of blood spot thyrotropin values >5 mIU/L ranged from 8.03 to 20.46%, indicating iodine deficiency. The prevalence of preterm infants increased from 5.50% in period [2010-2014] to 7.06% in period [2015-2020] (p<0.001). CONCLUSIONS: In the past decade, the CH incidence has increased progressively. SDH was the majority of CH, most of which were TCH, while most patients with TD were PCH. The increased incidence might be mainly due to iodine deficiency and increased rates of preterm infants in our study.

[Prevention of iodine deficiency diseases: focus on regional targeted programs].

The strategy for the elimination of diseases associated with iodine deficiency throughout the Russian Federation is based on the adoption of a federal law providing for the use of iodized salt as a means of mass (population) iodine prophylaxis. Chronic iodine deficiency that exists in Russia leads to dramatic consequences: the development of mental and physical retardation in children, cretinism, thyroid diseases, and infertility. Under conditions of iodine deficiency, the risk of radiation-induced thyroid cancer in children in the event of nuclear disasters increases hundreds of times. By definition, all iodine deficiency diseases (IDDs) can be prevented, while changes caused by iodine deficiency during fetal development and in early childhood are irreversible and practically defy treatment and rehabilitation. The actual average consumption of iodine by a resident of Russia is only 40-80 mcg per day, which is 3 times less than the established norm (150-250 mcg). Every year, more than 1.5 million adults and 650 thousand children with various thyroid diseases turn to medical institutions. The cause of 65% of cases of thyroid disease in adults and 95% in children is insufficient intake of iodine from the diet. At the stage of preparing the relevant legislative act, the development and implementation of regional programs for the prevention of IDD is of utmost importance. A typical draft of such a program is proposed in this article for its adaptation and use at the regional level.

[Ectopic thyroid gland: clinical features and diagnostics in children].

BACKGROUND: The frequency of ectopia of thyroid gland among all types of dysgenesis varies from 30 to 70%, its most common localization is the root of the tongue. Otorhinolaryngologists, oncologists, pediatricians can take lingual ectopia for hypertrophy of the lingual tonsil or fibroma of the tongue root, which leads to unreasonable surgical treatment. Thyroid scintigraphy plays a key role in the diagnosis of ectopia. AIM: To assess the etiological structure of congenital hypothyroidism (CH) and demonstrate the clinical course in patients with ectopic thyroid tissue in the root of the tongue. MATERIALS AND METHODS: A group of patients with CH was examined. All patients underwent neck ultrasound and radionuclide imaging. The examination was carried out against the background of the abolition of hormone replacement therapy for 14 days or before its initiation. Patients with ectopia in the root of the tongue underwent videofibrolaryngoscopy. Some patients underwent a genetic study with using genes panel of a panel of candidate genes responsible for the development of CH using the NGS method. The molecular genetic study was conducted to some patients, next-generation sequencing with the genes panel. RESULTS: The study included 73 patients with primary CH aged from 2 weeks to 17.3 years: 69 children were diagnosed based on the results of neonatal screening, 4 children with thyroid ectopia were first examined older than 6 years. The median age of patients at the time of the examination was 6.9 years [4.8; 10.0]. By data of ultrasound aplasia was diagnosed in 47.9% of patients, one child had hemiagenesis and ectopic thyroid tissue of various localization was detected in 26.0% of  children. In 24.7% of children thyroid tissue was found in a typical location. Scintigraphy confirmed thyroid aplasia in 65.7% of children. Examination revealed various variants of ectopically located thyroid tissue in 31 children (42.4%): thyroid ectopia in the root of the tongue in 25 children (80.6%), ectopia in the sublingual region in 5 children (16.2%), double ectopia was detected in 1 child. The median level of TSH in newborns with ectopic thyroid gland was 124 IU/ml and was significantly lower than in children with aplasia - 219 IU/ml, p<0.05. On the other side the level of TG in children with ectopia was significantly higher than in children with aplasia - 37.12 ng/ml versus 0.82 ng/ml, p><0.05. CONCLUSION: Combination of two methods is the best diagnostic approach to determine the etiology of CH - ultrasound and scintigraphy studies compensates deficiencies of each other. Our study demonstrates the importance of scintigraphy in children with CH and patients with the formation of the root of the tongue and the anterior surface of the neck in order to avoid unnecessary removal of the thyroid gland. In case of confirmation of thyroid ectopia in the root of the tongue and in the absence of symptoms of obstruction or bleeding, it is recommended to refer the patient to an endocrinologist for conservative treatment. ><0.05. On the other side the level of TG in children with ectopia was significantly higher than in children with aplasia - 37.12 ng/ml versus 0.82 ng/ml, p< 0.05. CONCLUSION: Combination of two methods is the best diagnostic approach to determine the etiology of CH - ultrasound and scintigraphy studies compensates deficiencies of each other. Our study demonstrates the importance of scintigraphy in children with CH and patients with the formation of the root of the tongue and the anterior surface of the neck in order to avoid unnecessary removal of the thyroid gland. In case of confirmation of thyroid ectopia in the root of the tongue and in the absence of symptoms of obstruction or bleeding, it is recommended to refer the patient to an endocrinologist for conservative treatment.

[Perinatal risk factors for congenital hypothyroidism in very preterm infants: a multicenter prospective study].

Objective: To investigate the incidence and perinatal risk factors of congenital hypothyroidism (CH) in very preterm infants. Methods: This prospective, multicenter observational cohort study was conducted at 33 neonatal intensive care units based on the data from Sina-northern Neonatal Network (SNN). Perinatal information and thyroid function of 3 179 very preterm infants with gestational age <32 weeks who were born from January 2019 to June 2021 was collected. According to the occurrence of CH during hospitalization, all the infants were assigned into CH group and non-CH group. Chi square test, Fisher exact probability method, rank sum test and multivariate Logistic regression model were tested to detect the perinatal risk factors for CH. Results: A total of 3 179 very preterm infants were enrolled with 56.4% (1 793/3 179) male. The incidence of CH was 6.9% (220/3 179), in which the incidence for extremely low birth weight infant (ELBWI) and extremely preterm infants (EPI) of gestational age <28 weeks were 13.5% (64/475) and 13.9% (66/475), respectively. On Logistic regression analysis, maternal hypertensive disorders of pregnancy (OR=1.59, 95%CI 1.14-2.23, P=0.007) and multiple birth (OR=1.60, 95%CI 1.18-2.17, P=0.003) were both significant perinatal risk factors of CH. In addition, gestational age (OR=0.81, 95%CI 0.71-0.93, P=0.002), birth weight (OR=0.99, 95%CI: 0.98-0.99, P<0.001) and 1 min Apgar score (OR=0.92, 95%CI 0.86-0.98, P=0.008) were protective factors. Conclusions: The incidence of CH is high in very preterm infants which increased with the decreased birth weight and gestational age. For very premature infants with perinatal high risk factors such as hypertensive disorders of pregnancy, attention should be paid to assess thyroid function status dynamically.

Congenital Hypothyroidism in Preterm Newborns - The Challenges of Diagnostics and Treatment: A Review.

Preterm newborns are forced to adapt to harsh extrauterine conditions and endure numerous adversities despite their incomplete growth and maturity. The inadequate thyroid hormones secretion as well as the impaired regulation of hypothalamus-pituitary-thyroid axis may lead to hypothyroxinemia. Two first weeks after birth are pivotal for brain neurons development, synaptogenesis and gliogenesis. The decreased level of thyroxine regardless of cause may lead to delayed mental development. Congenital hypothyroidism (CH) is a disorder highly prevalent in premature neonates and it originates from maternal factors, perinatal and labor complications, genetic abnormalities, thyroid malformations as well as side effects of medications and therapeutic actions. Because of that, the prevention is not fully attainable. CH manifests clinically in a few distinctive forms: primary, permanent or transient, and secondary. Their etiologies and implications bear little resemblance. Therefore, the exact diagnosis and differentiation between the subtypes of CH are crucial in order to plan an effective treatment. Hypothyroxinemia of prematurity indicates dynamic changes in thyroid hormone levels dependent on neonatal postmenstrual age, which directly affects patient's maintenance and wellbeing. The basis of a successful treatment relies on an early and accurate diagnosis. Neonatal screening is a recommended method of detecting CH in preterm newborns. The preferred approach involves testing serum TSH and fT4 concentrations and assessing their levels according to the cut-off values. The possible benefits also include the evaluation of CH subtype. Nevertheless, the reference range of thyroid hormones varies all around the world and impedes the introduction of universal testing recommendations. Unification of the methodology in neonatal screening would be advantageous for prevention and management of CH. Current guidelines recommend levothyroxine treatment of CH in preterm infants only when the diagnose is confirmed. Moreover, they underline the importance of the re-evaluation among preterm born infants due to the frequency of transient forms of hypothyroidism. However, results from multiple clinical trials are mixed and depend on the newborn's gestational age at birth. Some benefits of treatment are seen especially in the preterm infants born <29 weeks' gestation. The discrepancies among trials and guidelines create an urgent need to conduct more large sample size studies that could provide further analyses and consensus. This review summarizes the current state of knowledge on congenital hypothyroidism in preterm infants. We discuss screening and treatment options and demonstrate present challenges and controversies.

Family history of thyroid disease and risk of congenital hypothyroidism in neonates with Down síndrome.

INTRODUCTION: Family history of thyroid disease (FHTD) constitutes a possible risk factor for congenital hypothyroidism (CH) in the general population; however, FHTD possible relationship with CH in subjects with Down syndrome (DS) has not yet been explored. OBJECTIVE: To determine whether FHTD is associated with an increased incidence of CH in neonates with DS. METHOD: Hospital-based case-control study in 220 neonates with DS. Thyroid function tests of 37 infants with DS and positive FHTD (cases) were compared with those of 183 newborns with DS without FHTD (control group). Data were analyzed using multivariate logistic regression analysis and adjusted odds ratios (aORs) with their respective 95 % confidence intervals (CI) were calculated. RESULTS: Nine newborns with DS in our sample had CH (4.1 %). In the multivariate analysis, FHTD showed an association with CH in neonates with DS (aOR = 8.3, 95 % CI: 2.0-34.3), particularly in males (aOR = 9.0, 95 % CI: 1.6-49.6). In contrast, newborns with DS without FHTD were less likely to suffer from CH (aOR = 0.4, 95 % CI: 0.1-0.8). CONCLUSIONS: Newborns with DS and FHTD have an eight-fold higher risk for CH, particularly when the index case is male. FHTD detailed evaluation can be an easy and accessible strategy to identify those newborns with DS at higher risk for CH.

INTRODUCCIÓN: La historia familiar de enfermedad tiroidea (HFET) como factor de riesgo para hipotiroidismo congénito (HC), en síndrome de Down (SD) aún no ha sido explorada. OBJETIVO: Determinar si la HFET está asociada a mayor riesgo de HC en neonatos con SD. MÉTODO: Estudio de casos y controles en 220 neonatos con SD. Se compararon las pruebas de función tiroidea (PFT) de 37 con SD e HFET (casos), frente a las PFT de 183 recién nacidos con SD sin HFET (grupo de referencia). Se realizó análisis de regresión logística multivariante y se calculó la razón de momios (RM) y sus respectivos intervalos de confianza del 95 % (IC 95 %). RESULTADOS: Nueve casos HC (4.1 %). El HC mostró asociación con la HFET (RMa = 8.3, IC 95 %: 2.0-34.3), particularmente en los varones (RMa = 9.0, IC 95 %: 1.6-49.6). La ausencia de HFET tuvo una RM de protección para HC (RMa = 0.4, IC 95 %: 0.1-0.8). CONCLUSIONES: La HFET puede es una estrategia fácil y accesible para identificar pacientes con SD con mayor riesgo de HC.

Case Report: Neonatal Diabetes Mellitus Caused by a Novel GLIS3 Mutation in Twins.

Background: Mutations in GLIS3 cause a rare syndrome characterized by neonatal diabetes mellitus (NDM), congenital hypothyroidism, congenital glaucoma and cystic kidneys. To date, 14 mutations in GLIS3 have been reported, inherited in an autosomal recessive manner. GLIS3 is a key transcription factor involved in ß-cell development, insulin expression, and development of the thyroid, eyes, liver and kidneys. Cases: We describe non-identical twins born to consanguineous parents presenting with NDM, congenital hypothyroidism, congenital glaucoma, hepatic cholestasis, cystic kidney and delayed psychomotor development. Sequence analysis of GLIS3 identified a novel homozygous nonsense mutation, c.2392C>T, p.Gln798Ter (p.Q798*), which results in an early stop codon. The diabetes was treated with a continuous subcutaneous insulin infusion pump and continuous glucose monitoring. Fluctuating blood glucose and intermittent hypoglycemia were observed on follow-up. Conclusions: This report highlights the importance of early molecular diagnosis for appropriate management of NDM. We describe a novel nonsense mutation of GLIS3 causing NDM, extend the phenotype, and discuss the challenges in clinical management. Our findings provide new areas for further investigation into the roles of GLIS3 in the pathophysiology of diabetes mellitus.

[Risk factors for neonatal congenital hypothyroidism: a Meta analysis].

OBJECTIVE: To investigate the risk factors for congenital hypothyroidism (CH) in neonates, and to provide a reference for the prevention of CH. METHODS: The databases including China Biomedical Literature Service System, China National Knowledge Infrastructure, Wanfang Data, and Weipu Periodical Database, PubMed, Web of Science, Embase, SpringerLink, and Elsevier/ScienceDirect were searched for studies on the risk factors for CH in neonates published up to August 1, 2020. R 3.6.2 and RevMan 5.3 software were used to perform a Meta analysis. RESULTS: A total of 20 studies were included, with 13 case-control studies and 7 cross-sectional studies. There were 11 564 neonates in total, with 3 579 neonates in the case group and 7 985 neonates in the control group. The Meta analysis showed that advanced maternal age (OR=2.111, 95%CI: 1.275-3.493), thyroid disease during pregnancy (OR=3.365, 95%CI: 1.743-6.500), gestational diabetes mellitus (OR=2.158, 95%CI: 1.545-3.015), anxiety (OR=3.375, 95%CI: 2.133-5.340), medication during pregnancy (OR=2.774, 95%CI: 1.344-5.725), radiation exposure during pregnancy (OR=3.262, 95%CI: 1.950-5.455), family history of thyroid disease (OR=8.706, 95%CI: 5.991-12.653), low birth weight (OR=2.674, 95%CI: 1.895-3.772), fetal macrosomia (OR=1.657, 95%CI: 1.187-2.315), preterm birth (OR=2.567, 95%CI: 2.070-3.183), post-term birth (OR=2.083, 95%CI: 1.404-3.091), twin pregnancy or multiple birth (OR=3.455, 95%CI: 1.958-6.096), and birth defects (OR=6.038, 95%CI: 3.827-9.525) were risk factors for CH in neonates. CONCLUSIONS: Advanced maternal age, gestational thyroid disease, gestational diabetes mellitus, anxiety, medication during pregnancy, radiation exposure during pregnancy, family history of thyroid disease, low birth weight, fetal macrosomia, preterm birth, post-term birth, twin pregnancy or multiple pregnancy, and birth defects may increase the risk of CH in neonates.

Historia familiar de enfermedad tiroidea y riesgo de hipotiroidismo congénito en neonatos con síndrome de Down / Family history of thyroid disease and risk of congenital hypothyroidism in neonates with Down syndrome

Resumen Introducción: La historia familiar de enfermedad tiroidea (HFET) como factor de riesgo para hipotiroidismo congénito (HC), en síndrome de Down (SD) aún no ha sido explorada. Objetivo: Determinar si la HFET está asociada a mayor riesgo de HC en neonatos con SD. Método: Estudio de casos y controles en 220 neonatos con SD. Se compararon las pruebas de función tiroidea (PFT) de 37 con SD e HFET (casos), frente a las PFT de 183 recién nacidos con SD sin HFET (grupo de referencia). Se realizó análisis de regresión logística multivariante y se calculó la razón de momios (RM) y sus respectivos intervalos de confianza del 95 % (IC 95 %). Resultados: Nueve casos HC (4.1 %). El HC mostró asociación con la HFET (RMa = 8.3, IC 95 %: 2.0-34.3), particularmente en los varones (RMa = 9.0, IC 95 %: 1.6-49.6). La ausencia de HFET tuvo una RM de protección para HC (RMa = 0.4, IC 95 %: 0.1-0.8). Conclusiones: La HFET puede es una estrategia fácil y accesible para identificar pacientes con SD con mayor riesgo de HC.

Abstract Introduction: Family history of thyroid disease (FHTD) as risk factor for congenital hypothyroidism (CH) in patients with Down syndrome (DS) has not yet been explored. Objective: To determine whether FHTD is associated with an increased risk for CH in DS. Method: Case-control study in 220 neonates with DS. Thyroid function tests of 37 infants with DS and FHTD (cases) were compared with those of 183 DS newborns without FHTD (reference group). Data were analyzed using multivariate logistic regression analysis and adjusted odds ratios (aORs) with their respective 95 % confidence intervals (CI) were calculated. Results: Nine newborns with DS in our sample had CH (4.1 %). FHTD showed an association with CH in neonates with DS (aOR = 8.3, 95 % CI: 2.0-34.3), particularly in males (aOR = 9.0, 95 % CI: 1.6-49.6). In contrast, newborns with DS without FHTD were less likely to suffer from CH (aOR = 0.4, 95 % CI: 0.1-0.8). Conclusions: FHTD detailed evaluation can be an easy and accessible strategy to identify those newborns with DS at higher risk for CH.

Impact of maternal thyroid disease on neonatal thyroid status.

OBJECTIVES: Prevalence of Maternal and congenital hypothyroidism is on the rise. To present the thyroid stimulating hormone screening results in babies born to hypothyroid mothers and assess the burden, aetiology of hypothyroidism in these babies. METHODS: All antenatal mothers attending our hospital during the study period were enrolled into the study. Group I includes 249 term babies born to hypothyroid mothers and group II comprises 2154 newborns born to mothers who are euthyroid. Heel prick thyroid stimulating hormone was done for all newborns on day 3 for both groups. Confirmatory venous testing was done for all for babies in group I and screen positives belonging to group II. Evaluation and therapy done as per standard guidelines. RESULTS: Thyroid stimulating hormone values in the two groups are presented. There was significant correlation between peak maternal thyroid stimulating hormone and neonatal day 3 heel prick in group I (r=0.7, P<0.05). The prevalence of positive screening test in groups I and II was 3.8 and 1.03% (p<0.05) whereas corresponding values for confirmed disease was 4.3 and 0.6%, respectively (p<0.05). Aetiological evaluation revealed both transient hypothyroidism (33.3%) and permanent hypothyroidism (66.6%). CONCLUSION: 4.3% of babies born to hypothyroid mothers develop congenital hypothyroidism; aetiology being both transient and permanent. A venous test by 3 weeks is helpful in these babies to improve case identification.

Sonography of the distal femoral epiphysis in the etiological diagnosis of congenital hypothyroidism.

The etiology of congenital hypothyroidism (CH) is often difficult to identify, owing mainly to limitations in currently available diagnostic tests. Characteristics of the distal femoral epiphyseal (DFE) ossification center may provide important information and help identify some causes of CH. We analyzed the contribution of DFE ultrasonography in the investigation of 11 young infants with positive screening for CH. DFE ultrasonography emerged as a simple test that helped indicate the period of onset of CH and, when associated with clinical history, hormone levels, and thyroid ultrasonography, contributed to suggest the etiology of CH.

Thyroxine Treatment During the Perinatal Stage Prevents the Alterations in the ObRb-STAT3 Leptin Signaling Pathway Caused by Congenital Hypothyroidism.

Thyroid hormone deficiency during crucial stages of development causes congenital hypothyroidism. This syndrome alters hypothalamic pathways involved in long-term bodyweight regulation as ObRb-STAT3 leptin signaling pathway, which is associated with metabolic syndrome. This study aimed to determine if thyroxine treatment during pregnancy and lactation in hypothyroid mothers avoids, in the congenital hypothyroid offspring, the alterations in metabolic programming related to metabolic syndrome and the ObRb-STAT3 leptin signaling pathway in hypothalamus. Twenty-four virgin female Wistar rats were divided into euthyroid, hypothyroid, and hypothyroid with thyroxine treatment (20 µg/kg/day T4 since pregnancy until lactation). The bodyweight and energy intake, insulin resistance, glucose tolerance, metabolic and hormonal parameters were determined in offspring at 28 weeks after birth. Then, the rats were euthanized to obtain adipose tissue reserves and hypothalamus to measure the expression of ObRb, STAT3, pSTAT3, and SOCS3. Congenital hypothyroidism presented metabolic syndrome such as insulin resistance, glucose tolerance, dyslipidemias, an increase in cardiovascular risk (Castelli I males:166.67%, females: 173.56%; Castelli II males: 375.51%, females: 546.67%), and hypothalamic leptin resistance (SOCS3, Males: 10.96%, females: 25.85%). Meanwhile, the thyroxine treatment in the mothers during pregnancy and lactation prevents the metabolic disturbance. In conclusion, thyroxine treatment during the critical perinatal stage for metabolic programming prevents congenital hypothyroidism-caused metabolic syndrome and hypothalamic leptin resistance.