Objective Congenital hypothyroidism (CHT) is a common cause of preventable mental retardation, and the quantification of intellectual disability due to CHT is needed to assess the public health benefit of newborn screening. Design Review of published studies conducted among children born prior to the introduction of newborn screening for CHT and reporting cognitive test scores. Setting Population-based studies. Patients Children with clinically diagnosed CHT. Interventions Thyroid hormone substitution. Main outcome measures Intelligence quotient (IQ) (mean and distribution). Results The prevalence of recognised CHT rose from one in 6500 prior to screening to approximately one in 3000 with screening. In four population-based studies in high-income countries, among children with clinically diagnosed CHT 8–28% were classified as having intellectual disability (defined as an IQ Conclusions Although the prevalence of overt disability among children with CHT in the absence of screening may be less than previously estimated, the preventable burden of intellectual disability due to CHT is substantial and justifies newborn screening. However, changes in existing newborn screening protocols to capture more cases are unlikely to prevent overt cases of disability and should therefore be justified instead by the documentation of other benefits of early detection.

https://adc.bmj.com/content/archdischild/96/4/374.full.pdf

Prevention of intellectual disability through screening for congenital hypothyroidism: how much and at what level?

Primary congenital hypothyroidism (CH) is a common and preventable cause of intellectual disability. The incidence rate of CH has been reported to be increasing in the United States, but the factors behind the observed rate increase are not known. We summarize here the data presented at a workshop on CH, at which factors potentially related to the CH-incidence-rate increase (namely, race, ethnicity, sex, and birth outcomes) were evaluated. Data sources for the analyses included a national data set of newborn-screening results and state-specific data from newborn-screening programs in California, Massachusetts, New York, and Texas. The incidence rate of CH increased in the United States by 3% per year; however, an increase did not occur in all states, at a constant rate, or even at the same rate. Analysis of US data (1991-2000) showed a CH-incidence-rate increase only among white newborns. More recently, in California (2000-2007), the rate was constant in non-Hispanic newborns, but it increased among Hispanic newborns. In the national data, the CH-incidence rate increased similarly among boys and girls, whereas in Texas (1992-2006), the rate among boys increased significantly more than among girls and varied according to race and ethnicity. In Massachusetts (1995-2007), low birth weight newborns or newborns who had a delayed rise in thyrotropin concentration accounted for the majority of the recent rate increase. Race, ethnicity, sex, and pregnancy outcomes have affected the observed increasing incidence rate of CH, although there have been some inconsistencies and regional differences. The association with preterm birth or low birth weight could reflect the misclassification of some cases of transient hypothyroxinemia as true CH. Future studies of risk factors should focus on correct initial identification and reporting of demographic characteristics and pregnancy outcomes for cases of CH. In addition, long-term follow-up data of presumed cases of CH should be ascertained to differentiate true cases of CH from cases of transient hypothyroidism.

https://pediatrics.aappublications.org/content/pediatrics/125/Supplement_2/S37.full.pdf

Trends in Incidence Rates of Congenital Hypothyroidism Related to Select Demographic Factors: Data From the United States, California, Massachusetts, New York, and Texas

Infants of diabetic mothers.

Background/Aims: Over the years a rise in the incidence of congenital hypothyroidism (CH) has been described worldwide. The aim of our study was to investigate trends in the incidence of CH in Italy over the period 1987-2008, and to investigate which factors may have influenced the CH incidence in our country. Methods: Data were derived from the Italian National Registry of Infants with Congenital Hypothyroidism. Since 1998 the laboratory procedures related to neonatal screening for CH have changed drastically. Accordingly, we estimated the CH incidence during the period 1987-1998 (period 1) and the period 1999-2008 (period 2). Results: The incidence of CH confirmed at birth (including transient hypothyroidism) has increased from 1:3,000 liveborn infants in period 1 to 1:1,940 in period 2 (+54%), whereas the incidence of purely permanent CH increased from 1:3,200 to 1:2,320 (+38%). Lowering of the TSH cutoff was the most important factor contributing to the increase of CH incidence in Italy. Moreover, an increment of 58% of preterm babies with permanent CH was found in period 2 compared with period 1. Conclusion: Our results suggest that more than one cause is responsible for the rise in the increasing CH incidence, with lowering of the screening TSH cutoff and an increased survival rate of a growing number of preterm babies both playing an important role.

Multiple Factors Influencing the Incidence of Congenital Hypothyroidism Detected by Neonatal Screening

The reported incidence rate of primary congenital hypothyroidism (CH) has been increasing in the United States over the past 2 decades. We have considered the possibility that the inclusion of cases of transient hypothyroidism has inflated the reported incidence rate of CH. Assessing the effects of cases of transient hypothyroidism on the incidence rate is problematic, because the definitions, diagnostic criteria, and differentiation from transient hyperthyrotropinemia vary widely among state newborn screening programs. Among the 4 etiologies for transient hypothyroidism (maternal thyrotropin receptor-blocking antibodies, exposure to maternal antithyroid medications, iodine deficiency, and iodine excess), there is little evidence of increases in the incidence rate from thyrotropin receptor-blocking antibodies. Exposure to antithyroid drugs could contribute significantly to the incidence rate of transient CH, given the high estimated incidence of active maternal hyperthyroidism. Iodine deficiency or excess in the United States seems unlikely to have contributed significantly to the incidence rate of CH, because the secular trend toward lower iodine intake among women of reproductive age in the 1980s and 1990s seems to have plateaued, and perinatal iodine exposure has presumably declined as a result of recommendations to discontinue using iodine-containing disinfectants. Although the female-to-male sex ratio among newborns with thyroid agenesis or dysgenesis (the most common causes of CH) is typically 2:1, analysis of the sex ratio of newborns diagnosed with presumed CH in the United States suggests that a substantial proportion might have transient hypothyroidism or hyperthyrotropinemia, because the sex ratio has been well below the expected 2:1 ratio. Combined ultrasonography and (123)I scintigraphy of the thyroid gland are effective tools for identifying cases of thyroid agenesis and dysgenesis and can help to differentiate cases of transient hypothyroidism from true CH. Imaging is also a vital component in evaluating children who, at 3 years of age, undergo a trial of discontinuation of levothyroxine treatment to test for persistence of hypothyroidism. Ultimately, thyroid gland imaging, in conjunction with long-term follow-up studies that appropriately assess and report whether there was permanence of hypothyroidism, will be necessary to address the true incidence rate of CH and any contribution to the observed rate by transient cases of hypothyroidism or hyperthyrotropinemia.

https://pediatrics.aappublications.org/content/pediatrics/125/Supplement_2/S54.full.pdf

The impact of transient hypothyroidism on the increasing rate of congenital hypothyroidism in the United States.

Objective: To identify risk factors for permanent and transient congenital hypothyroidism (CH). Design: A population-based case-control study was carried out by using the network created in Italy for the National Register of Infants with CH. Methods: Four controls were enrolled for each new CH infant; 173 cases and 690 controls were enrolled in 4 years. In order to distinguish among risk factors for permanent and transient CH, diagnosis was re-evaluated 3 years after enrolment when there was a suspicion of transient CH being present. Familial, maternal, neonatal and environmental influences were investigated. Results: An increased risk for permanent CH was detected in twins by a multivariate analysis (odds ratio (OR) ¼ 12.2, 95% confidence interval (CI): 2.4‐62.3). A statistically significant association with additional birth defects, female gender and gestational age .40 weeks was also confirmed. Although not significant, an increased risk of CH was observed among infants with a family history of thyroid diseases among parents (OR ¼ 1.9, 95% CI: 0.7‐5.2). Maternal diabetes was also found to be slightly associated with permanent CH (OR ¼ 15.7, 95% CI: 0.9‐523) in infants who were large for gestational age. With regard to transient CH, intrauterine growth retardation and preterm delivery were independent risk factors for this form of CH. Conclusion: This study showed that many risk factors contribute to the aetiology of CH. In particular, our results suggested a multifactorial origin of CH in which genetic and environmental factors play a role in the development of the disease.

/pdf/risk-factors-for-congenital-hypothyroidism-results-of-a-1xonk8nh3e.pdf

Severo Pagliardini

Papers

Risk factors for congenital hypothyroidism: results of a population case-control study (1997-2003).