Key Findings

Following are key findings from selected pediatric genetics activities.

Congenital Hypothyroidism (CH)

The rate of primary congenital hypothyroidism (CH) in the United States has almost doubled during the past two decades to approximately 1 in 2,000 live births. Issues involved in this increase include:

Diagnosis and Management of CH

• There is significant variation among clinicians regarding confirmatory serum testing; the use of thyroid imaging; and the process for determining if a newborn with an out-of-range (“positive”) result actually has CH, particularly the preterm newborn.

• The results of diagnostic testing are being reported back to newborn screening laboratory follow-up programs inconsistently.

• National data are lacking on whether the proportion of newborns with an out-of-range (“positive”) result who are being worked up and managed by pediatric endocrinologists compared with those being done by primary care providers has changed over time.

• It is unclear how closely clinicians follow management guidelines.

• With considerable variation in diagnostic and treatment practices, as well as follow-up reporting, CH might be overdiagnosed, contributing to a perceived increasing incidence rate.

Transient Hypothyroidism versus Permanent CH

• There are four recognized causes of transient hypothyroidism: thyrotropin receptor-blocking antibodies, maternal antithyroid drugs, iodine deficiency, and iodine excess.

• Infants and children who are presumed to have CH, but who do not have evidence of hypothyroidism when they are removed from L-thyroxine treatment, often do not fit into one of the four recognized causes of transient hypothyroidism.

• Criteria for infants to be classified as having transient hypothyroidism vary appreciably between newborn screening follow-up programs and clinicians.

• Estimates of the incidence rate of transient hypothyroidism and whether the rate has changed over time are imprecise.

• Transient forms of hypothyroidism can be difficult to differentiate from permanent CH.

• Children with transient hypothyroidism potentially are being included in CH counts, thus inflating the incidence rate for CH.

• Clinicians need to diagnose transient hypothyroidism correctly, treat it with L-thyroxine when appropriate, and perform recommended follow-up testing for the permanence of CH as described in published guidelines.

Newborn Screening Laboratory Practices

• Significant differences exist between state-based newborn screening laboratories in relation to instrumentation, commercial screening kits, and criteria for specifying a test result as out-of-range or "positive".

• Changes in laboratory practices, particularly shifting from radiochemical-based assays to a fluoroimmuno assay or enzyme immunometric assay methods for measuring the thyroxine (T4) concentration, have been associated with an increase in the reported CH incidence rate.

• Clinicians can be confident in their state laboratories’ screening practices, but should remember that any newborn screening test can yield a false-negative result, particularly when the biochemical features of the condition might not manifest during the newborn period.

• Continued vigilance is necessary to recognize CH if symptoms such as poor feeding, failure to thrive, growth retardation, hypotonia, decreased activity, and constipation occur.

Known and Suspected Risk Factors for CH

• Epidemiologic studies have identified a higher rate of CH among newborns with any of the following demographic, birth and family characteristics:

  • Being of Hispanic ethnicity or Asian race;

  • Being female;

  • Having a birthweight less than 2,000 grams (g) or more than 4,500 g;

  • Having a gestational age of less than 37 or more than 40 weeks; or

  • Having a parental history of hypothyroidism.

• The frequency of infants with two of the characteristics associated with a higher rate of CH has increased over time in the birth cohort:

  • The proportion of Hispanic relative to non-Hispanic White and Black or African-American newborns

  • The number of preterm or low birthweight newborns, due to improved survival of these infants

• The CH incidence rate increase cannot be attributed solely to overall changes in the characteristics of the birth cohort because stratified categories in some state-based studies also have shown significant increases in the rate of CH.

Resources

• Articles in the Pediatrics supplement, “The Increasing Incidence of Congenital Hypothyroidism in the United States: Current Trends and Future Directions,” provide more information about the Centers for Disease Control and Prevention (CDC) and Health Resources and Services Administration (HRSA) meeting on CH:

  • Prevalence of Congenital Hypothyroidism-Current Trends and Future Directions: Workshop Summary

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

  • Effect of Laboratory Practices on the Incidence Rate of Congenital Hypothyroidism

  • The Impact of Transient Hypothyroidism on the Increasing Rate of Congenital Hypothyroidism in the United States

  • Future Research Directions to Identify Causes of the Increasing Incidence Rate of Congenital Hypothyroidism in the United States

• AAP clinical report, Update of Newborn Screening and Therapy for Congenital Hypothyroidism.

• The American College of Medical Genetics’ newborn screening ACTion (ACT) sheets describe actions to be taken in the follow-up of infants with out-of-range results for CH.

Enhancing Current Surveillance Systems To Capture Long-Term Outcomes for Children with Confirmed Newborn Screening (NBS) Conditions

CDC is funding pilot projects in states to standardize data collection on long-term follow-up (LTFU) of children with confirmed newborn screening conditions. LTFU benefits children by ensuring that they receive the full benefits of early identification through newborn screening. Tracking these children is also important for public health.

Goals

• Build capacity for state health departments:

  • Promote novel methods of data collection for NBS.

  • Expand existing data systems.

• Document characteristics of infants entering into LTFU for conditions detected through NBS and describe contacts with health care system.

• Demonstrate feasibility of an aggregated LTFU data system using a variety of data collection methods.

Initial Objectives for State Programs

• Screen for 19 metabolic conditions detected by tandem mass spectrometry.

• Collect data that is de-identified, on an individual level, and population-based.

• Demonstrate feasibility of assembling a combined interstate core dataset for the 2006–2007 birth cohort.

Funded State Programs and Data Collection Methods

• California

  • Adapt and enhance existing web-based Screening Information System to collect LTFU data elements compatible with emerging national standards.

  • Improve the quality of LTFU data entry by engaging metabolic center staff in the process of data collection, developing data definitions, creating a data entry manual, and training metabolic center staff.

• Utah and Iowa

  • Integrate newborn screening data into established birth defects monitoring systems.

  • Use expanded existing authority for active surveillance of congenital and inherited disorders in accordance with public health legislation and regulations.

• New York

  • Merge newborn screening cases into birth defects surveillance system.

  • Link infants identified through newborn screening with vital records, hospital discharge files, and early intervention programs.

Data Elements - General Categories Collected on Children with Confirmed NBS Conditions:

• Demographics

• Basic diagnostic information

• Morbidity and mortality

• Service encounters

• Treatments

• Hospitalizations

• Developmental assessments

Maternal and Neonatal Vitamin B₁₂ Deficiency Detected Through Expanded Newborn Screening—United States, 2003–2007

The incidence of neonatal vitamin B₁₂ (cobalamin) deficiency because of maternal deficiency was determined by surveying state newborn screening programs. Thirty-two infants with nutritional vitamin B₁₂ deficiency were identified (0.88/100 000 newborns). Pregnant women should be assessed for their risk of inadequate intake or malabsorption of vitamin B₁₂.

• The causes of maternal vitamin B₁₂ deficiency include adherence to a diet that excludes or has limited amounts of animal products, pernicious anemia, and previous gastric bypass surgery.

• Unrecognized neonatal vitamin B₁₂ deficiency worsens if an infant is breastfed without vitamin B₁₂ supplementation.

• Clinical presentation of vitamin B₁₂ deficiency among infants often is nonspecific (e.g., developmental delay and failure to thrive), which can lead to a delay in diagnosis and treatment and can result in irreversible neurologic damage.

• Newborn screening using tandem mass spectrometry has the potential to identify vitamin B₁₂ deficiency.

• The incidence of neonatal vitamin B₁₂ (cobalamin) deficiency due to maternal deficiency was determined by surveying state newborn screening programs: 32 infants with nutritional vitamin B₁₂ deficiency were identified (0.88/100,000 newborns).

• Health care providers should ask pregnant and lactating women about their diet and medical history to identify those at risk for an inadequate intake or malabsorption of vitamin B₁₂.

• Providers should not rely solely on measurement of serum vitamin B₁₂ levels, but should measure plasma methylmalonic acid and total homocysteine to diagnose vitamin B₁₂ deficiency among women at risk for a B₁₂ deficiency.

• Both the mother and the infant should be evaluated promptly for vitamin B₁₂ deficiency if a deficiency is suspected.

Learn more about Vitamin B₁₂ deficiency »

Resources

• The Journal of Pediatrics article, “Maternal and Neonatal Vitamin B₁₂ Deficiency Detected through Expanded Newborn Screening-United States, 2003-2007”.