Overview
The Canadian Task Force on the Periodic Health
Examination concludes that there is good evidence to recommend screening
for congenital hypothyroidism in newborns between 2 and 6 days of life.
The maneuver consists of the measurement of thyroid-stimulating hormone
(TSH) levels in a dried capillary blood sample, usually taken from the
newborn’s heel. Thyroxine (T4) level is measured if necessary. This recommendation
is unchanged from that made by the Task Force in 1990,<1> except that,
reflecting current thinking regarding test characteristics, TSH is now
considered the primary screening test followed by T4, if necessary (previous
recommendation T4 followed by TSH).
Burden of Suffering
The incidence of congenital hypothyroidism ranges
between 1 per 4,000 to 1 per 3,500 live births<2> and can be as high
as 1 per 141 live births among infants with Down syndrome.<3> Before
screening was available, the age at diagnosis ranged from 1 week to 5 years
or more. The intelligence quotient (IQ) of 65% of patients with congenital
hypothyroidism was below 85 (borderline intellectual functioning or lower),
and in 19% it was below 15 (profound mental retardation).<4> It is estimated
that about 30% of infants with delayed diagnosis would qualify for institutional
care. Children whose mothers ingested iodides, propylthiouracil or radioactive
iodine or had circulating antithyroid antibodies are at high risk for congenital
hypothyroidism.
Maneuver
All industrialized countries now have well organized
screening programs for congenital hypothyroidism. Most screening programs
in Canada and in Europe use a two-step laboratory approach where TSH is
measured first and T4 in borderline cases. However, many programs in the
United States measure T4 first. The recall rate for T4 averages 1.1% with
a positive predictive value of 2.4%.
Blood samples from the heel are collected on filter paper, ideally 3 to 6 days after birth, and tested for TSH concentration. TSH levels after the first 24 hours of life can be as high as 20 mIU/ml, thus increasing the number of false positive results. For this reason, newborns leaving the hospital in their first 24 hours of life are usually not tested.
The cut-off point for hypothyroidism is defined according to the daily standard deviation of test results rather than by a predetermined concentration. Since the laboratory method and the size of the blood spot influence the TSH and T4 levels each program must define its own standards and reference values. If the TSH level falls within normal limits the T4 concentration is measured with another blood spot on the filter paper. The recall rate with TSH testing averages 0.05%. At this rate, two infants are recalled for testing for every case detected. The sensitivity of the combined maneuver is about 95%.
Cases of primary, congenital hypothyroidism or about 5% of all cases of congenital hypothyroidism cannot be identified with the TSH screening approach.<5>
Effectiveness of Screening and
Treatment
The first evidence of the benefits of screening
for congenital hypothyroidism in Canada came with publication of the one-year
follow-up data from the Quebec Screening Program.<6>
The mean IQ of affected infants less than 12 months of age was greater than 100, and did not differ from that of control subjects. Both the Quebec screening program and the New England Congenital Hypothyroidism Collaborative have published five-year follow-up data on children screened at birth.<7,8> The children who had been treated for congenital hypothyroidism were comparable to matched controls on all developmental scales. In the Quebec program, the IQ of the children treated for congenital hypothyroidism was within normal limits for children of their age, though the average IQ was statistically lower than that of the control group (105 vs. 110).<7>
Follow-up data up to 12 years after screening have recently been published.<9> The IQ and developmental scores of the hypothyroid children were still within normal limits. The degree of fetal hypothyroidism at birth influenced the final outcome.
The fact that most hypothyroid infants identified at birth by screening have intellectual and psychomotor development in the normal range, constitutes a dramatic improvement over the outcomes in children previously diagnosed later in life.
Recommendations of Others
Few Canadian organisations have issued recommendations
on screening for thyroid diseases. The U.S. Preventive Services Task Force
has recommended universal screening for congenital hypothyroidism.<10>
Conclusions and Recommendations
The dramatic change in the natural history of
congenital hypothyroidism since the advent of screening warrants a grade
A Recommendation, even in the absence of a randomized controlled trial.
Thus, there is good evidence to recommend routine testing of all neonates.
Screening for congenital hypothyroidism is generally carried out by hospitals and is therefore outside the control of most individual physicians. Nonetheless, primary care physicians should make sure that all infants who are born at home or discharged from hospital within 24 hours after birth are tested for hypothyroidism within 7 days after birth. It is better to obtain a specimen within 24 hours than no specimen at all.
Evidence
Since the last review of the Task Force on thyroid
diseases was published in 1990, a MEDLINE search between 1989 and 1993
was conducted. The search was done using congenital hypothyroidism with
screening and prevention and control. Only original articles were considered.
The search yielded few new articles. Priority was given to the highest
levels of evidence according to the Task Force methodology. This review
was initiated in February 1993 updating a report published in 1990.<1>
Recommendations were finalized by the Task Force in January 1994.
Full Citation
Beaulieu M.D. Screening for congenital hypothyroidism.
In: Canadian Task Force on the Periodic Health Examination. Canadian
Guide to Clinical Preventive Health Care. Ottawa: Health Canada,
1994;190-4.