Blood spot thyroid stimulating hormone or thyroxine, or both can be used for congenital hypothyroidism newborn screening. Learn more about testing strategies around the world
About 71% of babies worldwide are born in a location without an established newborn screening program for congenital hypothyroidism.
Since the 1970s, newborn screening for congenital hypothyroidism has been performed using thyroid stimulating hormone (TSH), thyroxine (T4), or both. Neonatal screening for this disorder has largely eliminated the intellectual disability associated with it in the world.
Newborn screening for congenital hypothyroidism (CH) is one of the major achievements in preventive medicine. However, only 30% of births worldwide were screened in the 2010s. Here is some useful information on successful testing strategies.
For each strategy, its strengths and weaknesses
Primary TSH
Most screening programs use primary thyroid stimulating hormone measurements. It is the most specific for newborn screening for primary congenital hypothyroidism. Cut-off values generally range from 20 to 25 mIU/L. Nevertheless, this approach misses in identifying rarer forms of CH, e.g. thyroid-binding globulin (TBG) deficiency, central hypothyroidism or hypothyroxinemia. It may miss delayed TSH raise, as in low-birth weight neonates [1, 2].
Elevated TSH samples often undergo a thyroxine assay for confirmation.
Primary T4
Primary thyroxine test is used in the Netherlands and in some American states. It succeeds in screening all forms of CH. Even the rarest. However, higher false-positive/negative rates may be observed compared to primary thyroid stimulating hormone. Birth weight and prematurity greatly influence the assay results. Cut-off values are often based on a daily percentile – i.e. 5th or 10th percentile – but absolute cut-off values also work [1, 2]. They are dependent on birth weight and on the baby’s age at sample collection.
TSH of low T4 samples is often assessed for confirmation.
TSH and T4 together
This is the ideal approach for newborn screening for congenital hypothyroidism. It combines the advantages of both methods. But one must remain aware of each assay potential limitations. Unfortunately, it is the less cost-effective approach [1, 2].
Newborn screening for congenital hypothyroidism worldwide
Neonates’ coverage is total in North America and Oceania. Almost complete in Europe. In Asia and Latin America, newborn screening for congenital hypothyroidism is uneven. The proportion of population screened range from 0% to 100% depending on the country. In Africa, no screening is done except in Egypt and South Africa [3].
In total, approximately 71% of the world's births are therefore not covered by a screening program for congenital hypothyroidism.
Yet, CH screening in neonates’ population is essential. The disease incidence continues to increase. From an incidence of 1 in 3,000-4,000 in the 1990s to an incidence of 1 in 2,000 in the 2000s with ethnic disparities [3]:
- Non-hispanic white: 1:3,533
- Non-hispanic black: 1:11,000
- Asian (Chinese & Vietnamese): 1:2,380
- Hispanic: 1:1,600
- Asian Idian: 1:1,200
Future challenges
Increase in global newborn screening
It is estimated that approximatively 30,000 babies with CH are born each year. This represents 30 billion US dollars at a lifetime cost [3]. Establishing screening programs in as many countries as possible would reduce these costs.
Reduction of false negatives
Any CH screening program may still miss approximately 5% of positive cases. The reasons could be failure of sample collection, unsatisfactory samples or results misinterpretation. Here are some suggestions to improve the outcome of CH screening
Blood sampling
The ideal sampling time is 3-5 days after birth. It minimizes the false positive results for TSH concentration determination. It stabilizes the T4 concentrations [2].
Consider the impact of seasonal changes
Seasons affect measured thyroxine and thyroid stimulating hormone values. TSH concentration increases during summer while T4 concentration decreases. This rises the false-negative risk [4].
Adjusting the cut-off value
The cut-off value must be adjusted to the child's age at the time of sampling for TSH and also to birth weight for T4. This reduces both the risk of false positives and false negatives [2, 3].
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Sources:
[1] Pediatrics, A.A. of et al. (2006) ‘Update of Newborn Screening and Therapy for Congenital Hypothyroidism’, Pediatrics, 117(6), pp. 2290–2303.
[2] Büyükgebiz, A. (2013) ‘Newborn Screening for Congenital Hypothyroidism’, Journal of Clinical Research in Pediatric Endocrinology, 5(Suppl 1), pp. 8–12.
[3] Ford, G. and LaFranchi, S.H. (2014) ‘Screening for congenital hypothyroidism: a worldwide view of strategies’, Best Practice & Research. Clinical Endocrinology & Metabolism, 28(2), pp. 175–187.
[4] McMahon, R. et al. (2021) ‘The Impact of Seasonal Changes on Thyroxine and Thyroid-Stimulating Hormone in Newborns’, International Journal of Neonatal Screening, 7(1), p. 8.
Source : Madeleine Boulanger, PhD
