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Neonatal screening for congenital hypothyroidism in Estonia
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20 J Med Screen 1998;5:20–21
Neonatal screening for congenital hypothyroidism
in Estonia
Ruth V Mikelsaar, R Zordania, M Viikmaa, G Kudrjavtseva
Abstract The screening was carried out in three
Screening for congenital hypothyroidism stages: (a) TSH concentration was measured
was carried out by measuring thyroid on the first dried blood spots in the institute
stimulating hormone (TSH) on dried laboratory; (b) when the TSH concentration
blood spots (mean + 2SD cut oV value 12 was above the cut oV value the infants were
µU/ml) by fluoroimmunoassay using recalled and TSH measurement repeated on a
DELFIA kits. A total of 20 021 infants were second filter paper; (c) if the TSH concentra-
screened, and seven cases with congenital tion when retested was still over the cut oV
hypothyroidism were detected, giving an value TSH, thyroxine (T4), and triiodothyro-
incidence of congenital hypothyroidism of nine (T3) concentrations were measured in the
1:2860 (female:male ratio 6:1). In four of serum to confirm the diagnosis. The diagnostic
seven infants with congenital hypothyr- criteria for congenital hypothyroidism were:
oidism (57%) the mother also had thyroid (a) a TSH concentration above the cut oV
disease, supporting the importance of value (12 µU/ml) on the first and second blood
genetic factors as a cause of congenital spot analysis; (b) a TSH concentration in
hypothyroidism. Transient hyperthyro- serum above normal (more than 15 µU/ml) but
tropinaemia occurred in 654 infants (re- T4 and T3 concentrations below the normal
call rate 3.3%). There was a significant value in serum; (c) the existence of clinical fea-
association of transient hyperthyrotropi- tures of congenital hypothyroidism and an
naemia only with cardiac failure at birth abnormal thyroid scan.
or caesarean section (p<0.01). Family When screening was positive, additional data
studies showed no predisposition to thyr- on the clinical status of the newborns and the
oid diseases associated with a transient health of the parents, pregnancy and delivery,
increase of TSH. and the family history of thyroid and other dis-
(J Med Screen 1998;5:20–21) orders were gathered on standard forms. The
infant was then referred to a paediatric
Keywords: neonatal screening; congenital hypothy- endocrinologist for further examination and
roidism; thyroid stimulating hormone; hyperthyrotropi- treatment. Follow up studies were carried out
naemia
both by the geneticist and the endocrinologist.
A statistical analysis of diVerences in frequen-
Neonatal screening for congenital hypothyr- cies of antenatal and perinatal abnormalities in
oidism, started in 1989, was the first genetic infants with transiently raised TSH levels and
screening programme in Estonia.1 those with normal levels was carried out using
Fisher’s test of exact probability. The data were
Department of Human
Biology and Genetics, coded and stored in a computerised database
Institute of General Methods at the institute laboratory.
and Molecular Blood samples were obtained from 99% of
Pathology, University newborns aged 3 to 5 days at three maternity Results and Discussion
of Tartu, Veski Street hospitals and transferred to filter paper cards A total of 20 021 infants (52.9% boys and
34, Tartu EE2400, (Schleicher and Schuell No 2992). These 47.1% girls) were screened. Of these, 86%
Estonia cards contained information about the sex, were Estonian subjects, 12% were Russian, and
R V Mikelsaar, associate
professor nationality, birth date, date on which the sam- 2% were of other nationalities. The recall rate
M Viikmaa, senior ple was taken, gestational age, birth weight, was 3.3% and the recall time was within three
scientific worker height, and abnormalities of the infants. The weeks for over 83% of infants. Of these, in
cards were stored in bags between 2°C and 8°C seven infants the TSH concentrations were
Women’s Hospital, for one to 14 days. high in the first sample (range 111.7–217.3
University of Tartu, Screening for congenital hypothyroidism µU/ml), and the diagnosis was confirmed by
Lossi Street 36, Tartu
EE2400, Estonia was carried out by measuring the concentra- measuring TSH, T4, and T3 in the serum. In
G Kudrjavtseva, tion of thyroid stimulating hormone (TSH) on four infants the thyroid scan showed thyroid
neonatologist a single dried blood spot specimen (punch size hypoplasia. A further three infants had left
3 mm with equivalent blood volume 4.8 µl by Estonia so a thyroid scan could not be carried
Children’s Outpatient packed cell volume 50%) using a solid phase out, but all had some clinical features of
Clinic, Tallinn EE0001, fluoroimmunoassay with the DELFIA neo- congenital hypothyroidism, such as a hoarse
Estonia
R Zordania, medical natal hTSH kits (Wallac Oy, Turku). The fluo- cry, prolonged icterus, a small umbilical hernia
geneticist rescence was read by the Arcus fluorometer etc. The median age of the infants at the start
1230 (LKB, Wallac). The intra-assay and inter- of treatment was 16 days (range 11–20).
Correspondence to: assay variations were 4.5–6.6% and 4.7–5.7% The estimated incidence of congenital hypo-
Dr Mikelsaar.
respectively. The results from 415 normal thyroidism was 1:2860, which is high but not
Accepted for publication newborns gave a cut oV value for TSH of 12 statistically diVerent from the incidences re-
13 November 1997 µU/ml (mean + 2SD). ported in the most countries in Europe
Neonatal screening for congenital hypothyroidism in Estonia 21
Table 1 Frequencies of antenatal and perinatal abnormalities in infants with a transiently cases transient neonatal hyperthyrotropinae-
raised thyroid stimulating hormone (TSH) level above the cut oV value (>12 µU/ml) and mia may be directly caused by a thyroid
with a normal TSH level (<12 µU/ml)
dysfunction that later appears as
Antenatal and perinatal Infants with raised TSH level Infants with normal TSH level hypothyroidism.9 A follow up study is needed
abnormalities (>12 µU/ml) (n=334) No (%) (<12 µU/ml) (n=8768) No (%) to answer this question.
Prematurity 14 (4.2) 379 (4.3) A family study was carried out in 71 infants
Asphyxia 11 (3.3) 253 (2.9) (34 boys, 37 girls) with transient neonatal
Hypotrophia 6 (1.8) 135 (1.5) hyperthyrotropinaemia and in 27 normal
Cardiac failure 4 (1.2)* 22 (0.2)*
Respiratory distress — 47 (0.5) infants (15 boys, 12 girls). Twenty families of
Congenital anomalies 3 (0.9) 55 (0.6) the 71 aVected infants (28%) had histories of
Diabetic fetopathia — 14 (0.2)
Cerebral dyscirculation — 15 (0.2)
thyroid diseases—17 families with goitre and
Caesarean section 8 (2.4)* 68 (0.8)* three with cancer of the thyroid gland. Eight
Down’s syndrome 1 (0.3) 7 (0.1) families of the 27 normal infants (30%) had a
*DiVerences were significant (p<0.01). history of goitre. Thus the data for normal and
aVected infants were not statistically diVerent.
(1:4000).2 3 The female:male ratio was 6:1 in We found no published reports of family stud-
agreement with previous findings that congeni- ies of infants with transient neonatal hyperthyro-
tal hypothyroidism is more common in girls tropinaemia, but our data showed no predispo-
than in boys.4 5 sition towards thyroid diseases in those with
In four of seven infants (57%)—three with transient neonatal hyperthyrotropinaemia.
congenital hypothyroidism and one with can-
cer of the thyroid gland—the mother also had We thank all the medical and nursing staV of the Women’s Hos-
thyroid disease. This indicates the possible ˜ ˜
pitals in Tartu, Polva, and Jogeva for collecting the dried blood
samples, and Dr B Adojaan, a paediatric endocrinologist for
importance of genetic factors as a cause of their kind cooperation.
congenital hypothyroidism and supports previ- This study was supported by grants from the Estonian
Science Foundation.
ous data indicating that congenital hypothyr-
oidism is inherited in more than 30% of cases.6
1 Mikelsaar RV-A, Mikelsaar A-V, Kudrjavtseva G. Newborn
Transient neonatal hyperthyrotropinaemia screening for congenital hypothyroidism in Estonia. Infant
occurred in 654 infants (3.3%) in whom the Screening 1992;15:17–18.
2 Delange F, Illig R, Rochiccioli P, et al. Progress report 1980
TSH concentration was initially slightly above on neonatal thyroid screening in Europe. Acta Paediatr
the cut oV value but normal on retesting. A Scand 1981;70:1–2.
3 Schoenberg D, Klett M. Screening for congenital hypothy-
comparison of the incidence of antenatal and roidism in the Federal Republic of Germany. Past, present
perinatal abnormalities in the infants with and future. In: Therrell BL, ed. Advances in neonatal screen-
ing. Amsterdam: Elsevier, 1987:25–30.
transient neonatal hyperthyrotropinaemia 4 Grant DB, Smith I. Survey of neonatal screening for
(n=334) and normal infants (n=8768) showed primary hypothyroidism in England, Wales and Northern
Ireland 1982–4. BMJ 1988;296:1355–8.
significant diVerences (p<0.01) only for car- 5 Beck-Peccoz P, Medri G. Congenital thyroid disease.
diac failure or caesarean section (table 1), Baillieres Clin Endocrinol Metab 1988;2:737–59.
6 Al-Jurayyan NAM, Al-Nuaim AA, El-Desouki MJ, et al.
which is in agreement with previous reports.7 Neonatal screening for congenital hypothyroidism in Saudi
According to a more detailed analysis it might Arabia: results of screening the first 1 million newborns.
Screening 1996;4:213–21.
be concluded that in our subjects the caesarean 7 Larsson A, Ljunggren J-G, Ekman K, et al. Screening for
section itself caused the transient neonatal congenital hypothyroidism. I. and II. Acta Paediatr Scand
1981;70:141–53.
hyperthyrotropinaemia, supporting the opin- 8 Harada S, Ichihara N, Arai J, et al. Influence of iodine excess
ion of Larsson et al,7 and was not caused by due to iodine-containing antiseptics on neonatal screening
for congenital hypothyroidism in Hokkaido prefecture,
intrauterine asphyxia or antiseptics containing Japan. Screening 1994;3:115–23.
iodine.8 The cause of the association of cardiac 9 Harada S, Ichihara N, Arai J, et al. Later manifestations of
congenital hypothyroidism predicted by slightly elevated
failure with transient neonatal hyperthyrotro- thyrotropin levels in neonatal screening. Screening 1995;3:
pinaemia remains unclear. Possibly, in some 181–92.
