Results

Table 1 gives information on the number of live births and Guthrie tests performed from 1979 to 1993. The excess of tests over births is explained by some infants being tested more than once. Between 1 August 1979 and 31 December 1993, 344 children were found to have raised TSH values and all but one of these was positive on the Guthrie screening programme, the only exception being a girl who was diagnosed clinically as hypothyroid at 42 days, no Guthrie card having been submitted previously. There were three other manifest errors during the study period, with late Guthrie card submission (at 35 and 49 days) in two children and in a third child where Guthrie test had been performed on day 7 but the raised TSH had been missed on the printout, and she was diagnosed clinically at 13 days.

Only one possible false negative case was reported. This was a girl who had a negative Guthrie test on day 9 but presented at 4 years with delayed speech and was manifestly hypothyroid at 7 years. Isotope scanning showed no functioning thyroid tissue and autoantibodies were negative.

ASSIGNMENT TO DIAGNOSTIC CATEGORIES

Table 2 shows the number of children in each of the four diagnostic categories: definite and probable congenital hypothyroidism, uncertain status, and transient TSH elevation. Eighty eight children were found to have transient TSH elevation. Of these, 22 were given thyroxine initially, but were subsequently found to have normal thyroid function when treatment was withdrawn. As expected, there was a female preponderance of approximately 2 to 1 in the definite and probable groups, but not in the transient group. The number of premature and/or ‘sick’ infants was much greater in the transient group.

In the 224 children with definite hypothyroidism, 96 had a thyroid isotope scan and this was of diagnostic value in 91. A specific cause, based on information from family history, clinical examination, thyroid scan, maternal thyroid autoantibody status, necropsy findings (three patients), or various combinations of these was established in 108 children. These were: thyroid ectopia (32), athyreosis (35) and hypoplasia (17), dyshormonogenesis (20), isoimmune thyroiditis (3), and pseudohypoparathyroidism (1). Of the remaining 115 children in whom no cause was established (usually because no thyroid scan had been performed) the diagnosis of definite hypothyroidism was based on TSH elevation of greater than 10 mU/l after the first year in 56, and/or an initial venous T4 of less than 60 nmol/l and a TSH of greater than 50 mU/l in the absence of prematurity or ‘sickness’ in 84.

INCIDENCE OF CONGENITAL HYPOTHYROIDISM

The annual incidence of true congenital hypothyroidism in Scotland (taking the definite and probable groups together, but excluding the groups where thyroid status was uncertain or the rise in TSH transient) varied between 1 in 2900 and 1 in 7300 live births, with an average incidence of 1 in 4400 (table 1).

EFFICIENCY OF CONGENITAL HYPOTHYROID SCREENING PROGRAMME

Figures 2, 3, and 4 show the age at Guthrie collection, notification, and treatment for the cohort of children between 1979 and 1993 in box plot form, where the bottom of the box is at the lower quartile, the top at the upper quartile, and the median is drawn across the box. Vertical lines represent upper and lower limits with outliers represented as single dots. In figs 3 and 4 the transient/uncertain groups are excluded.

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Figure 2

Box and whiskers plot of age at Guthrie collection in infants with raised thyroid stimulating hormone (TSH) in the Scottish hypothyroid screening programme, 1979–93. Median values are represented by the line across the box, outliers by dots.

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Figure 3

Box and whiskers plot of age at notification in 234 infants with definite/probable congenital hypothyroidism diagnosed in Scotland, 1979–93. Median values are represented by the line across the box, outliers by dots.

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Figure 4

Box and whiskers plot of age at start of treatment in 234 infants with definite/probable congenital hypothyroidism diagnosed in Scotland, 1979–93. Median values are represented by the line across the box, outliers by dots.

Age at Guthrie collection

Median ages of Guthrie collection were consistently 6-7 days in the definite/probable groups from 1983 onwards but more variable in the uncertain/transient groups, at between 5 and 14 days. Of the 344 infants in the cohort 36 (10.5%) had their first Guthrie test after 10 days of birth—11 from the definite group, five from the uncertain group, and 20 from the transient group.

Age at notification

Of the 235 infants with definite/probable congenital hypothyroidism, only 18 (7.7%) had been clinically detected and treated by the time of notification, which in this group was consistently between 10 and 12 days from 1983 onwards. Again the uncertain/transient groups showed more variation (11–21.5 days), consistent with a combination of later initial sampling and time taken for recall samples.

Age at starting treatment

Median ages fell from 17.5–21 days before 1983 to 11–15 days thereafter in the definite/probable groups, with much later median treatment times for the minority (37%) of infants in the uncertain/transient groups who actually received treatment. This was attributable to a combination of later notification and clinical uncertainty as to whether treatment was appropriate. During the study period, 45 infants (13% of the cohort) started treatment after 20 days—27 from the definite group, five from the uncertain group, and 13 from the transient group.

PATTERN OF TRANSIENT TSH ELEVATION DURING THE STUDY PERIOD

An unusually large number of infants was found to have transient TSH elevation in 1985 and 1986 (table 1), with only four from each year actually receiving treatment. This coincided with a change in radiolabel in the screening laboratory. In 1988 there was a similar peak of transient TSH elevation, with 10 cases reported but only two treated. A further peak in 1990 was associated with a particularly high incidence of prematurity and sickness.

EDUCATIONAL STATUS

One hundred and forty nine children were of school age in 1994, and information was available on 139 (93%). Two children (1.4%) were attending special schools, one of whom had mild dyshormonogenesis with raised TSH but normal thyroxine off treatment. Sixteen children (11.5%) were receiving some sort of extra help in mainstream education—12 of 104 in primary school and four of 35 in secondary school. Four children (2.9%) had had a Record of Needs taken out by the Education Department, of whom two were the children attending special school.

Discussion

This audit has shown a favourable uptake of neonatal screening and, in those infants with definite/probable hypothyroidism, reasonable median ages of Guthrie sample collection (7 days). However, it is of concern that some infants are still sampled late, particularly those with uncertain classification or transient TSH elevation, in whom there is a much higher incidence of prematurity and sickness (see table2).9 A common reason for late Guthrie card sampling is the belief that the child must be receiving milk for the phenylketonuria test to be valid. However, an infant not receiving milk beyond 5 days of age is likely to be catabolic so that phenylketonuria is unlikely to be missed. Moreover, it is perfectly feasible to submit a Guthrie card on all newborns on day 5 irrespective of gestation or sickness, sending a second sample for repeat phenylalanine estimation once the infant is receiving milk.

The median ages of notification before 1983 (17.5–21 days) are consistent with other reports from that time in the United Kingdom10 and North America,11 while the current age of notification (10–11 days) and start of treatment (11–15 days) compares favourably with more recent reports from Europe.12

Numerous studies have shown small differences in IQ between healthy controls and hypothyroid children detected by neonatal screening.13-17 Of particular relevance to our study is the large and detailed psychometric evaluation carried out by Fuggleet al who showed a 7 point difference in IQ between 344 hypothyroid children and 112 controls at 5 years of age.17This group went on to demonstrate a discontinuous relation between IQ and plasma thyroxine concentration at diagnosis, with an apparent threshold at 43 nmol/l.6

In this study we have simply audited the number of children attending special school, and mainstream education with special help. While these indices are extremely crude, it is nevertheless of value, when counselling the parents of newly diagnosed infants, to translate the prognosis for intellectual outcome in terms of their child’s likely educational requirement. In this study, data were available on 139 children of whom only two were receiving special education. One of these is known to have mild hypothyroidism and his placement is more due to social and emotional problems than to academic difficulties. Sixteen children (11.5%) were receiving learning support in mainstream education, of whom two had had a Record of Needs made out by the Education Department, together with the two children at special schools, bringing the total to four (2.9%). These data are comparable with information from the Scottish Office on special educational needs in Scottish primary and secondary school pupils. In 1993, 1.3% of Scottish children were attending special schools and a Record of Needs had been taken out on 1.2% of children; 6.4% of children were classified as having learning difficulties.18 In the Scottish low birthweight study, Hall et al obtained two age matched controls for each index child in a study of very low birth weight Scottish children aged 8 years.8 These investigators found that 18% of 500 controls and 17% of another group of 90 controls were receiving learning support; 1% of the first group and none of the second had had a Record of Needs taken out. No children in either control group were at special schools.

We conclude that the Scottish hypothyroid screening programme is working reasonably well, and our data indicate that the educational needs of affected children are not different from those of the general population. However, efficiency could be increased by earlier and more reliable Guthrie collection.19 To rectify this the screening laboratory in Glasgow has recently introduced a quality assurance programme, employing a clinical liaison nurse to monitor the adequacy and timing of blood samples as well as the quality of demographic information provided.