Antenatal Thyroid

Screening and
Childhood Cognitive
Function
Doni Saputra

Introduction

Active secretion of thyroid hormone in the fetus

does not start until about 18 to 20 weeks
gestation

High levels of thyrotropin in women during

pregnancy have been associated with impaired
cognitive development in their offspring.

Methods
Study
Participan
ts

From 10 centers in the United Kingdom and 1

center in Italy

Exclusion criteria were an age of less than 18 years,

a gestational age of more than 15 weeks 6 days,
twin pregnancies, and known thyroid disease

Study
Procedure
s

Blood samples were sent to the laboratory at the

University Hospital of Wales, Cardiff, or to Ospedale
SantAnna, Turin, Italy, for measurement of
thyrotropin and free T4 levels
Patients in the screening group who had posi- tive
results were treated with levothyroxine (recommended starting dose, 150 g per day).

Methods

Outcomes and Assesments

The primary outcome was the IQ.

IQ was assessed with the use of the Wechsler Preschool and Primary Scale of Intelligence, third edition
(2003)

IQ assessments were performed by two psychologists

in the United Kingdom and one in Turin.

Methods

Statistical Analysis

Compared with the use of t-tests for continuous variables

with a Gaussian distribution and the Wilcoxon rank-sum
test for those with a non- Gaussian distribution.

The chi-square test was used for categorical variables.

The primary analysis was performed according to the

intention-to-treat principle

A t-test was used to compare standardized IQ test results

of the children between the screening and control groups,
and the chi-square test was used to compare the
proportion of children with an IQ of less than 85

Results
Characteristic
Gestational age at screening (Weeks,
Days)
Median
Interquartile range
Thyrotroponin (mIU/liter)
UK
Median
Interquartile range
Turin
Median
Interquartile range
Free T4
UK (pmol/liter)
Median
Interquartile range
Turin (pg/ml)
Median
Interquartile range

Screening
Group

Control
Group

12.3
11.6 13.6

12.3
11.6 13.5

3.8
1.5 4.7

3.2
1.2 4.2

3.1
1.3 4.0

2.4
1.3 3.9

11.1
10.5 13.3

11.2
10.5 13.2

7.4
7.1 8.6

7.4
7.2 8.3

Results
Characteristic

Screening
Group

Control
Group

68
59 - 78

67
59 80

Age when mother left full-time education

(%)
16yr
17 18
19yr

34
27
39

33
26
41

Age when father left full-time education

(%)
16yr
17 18
19yr

51
18
31

42
23
35

Maternal age at delivery (yr)

305.4

315.3

Paternal age at delivery (yr)

325.9

336.3

55

51

Maternal Weight (kg)

Median
Interquartile range

Male children (%)

Age at psychological testing (yr)

Results
Test

IQ
Mean
<85 (% of
Children)
CBCL T score
Mean
Brief-P T score
Median
Interquartile
range

Screening
Group (N =
390)

Control
Group
(N = 404)

Diff (95% CI)

P
valu
e

99.213.3
12.1

100.013.3
14.1

0.8 (1.1 to
2.6)
2.1 (2.6 to
6.7)

0.40
0.39

44.412.4

45.113.6

0.7 (1.2 to
2.5)

0.49

40
47 55

40
47 55

0.59

Discussion

This study found no significant difference in IQ

scores between 3-year-old children born to
women who were randomly assigned to the
screening group at about 12 weeks gestation
and treated for reduced thyroid function before
20 weeks gestation (median, 13 weeks 3 days)
and children born to women with reduced
thyroid function who were randomly assigned
to the control group.

Discussion

A study in 1971 described impaired intellectual

development in children born to women with
noniodine-deficient hypothyroidism during
pregnancy

A subsequent study showed an IQ level of less

than 85 in 19% of the children of women with a
high thyrotropin level, as compared with 5% of
the children of euthyroid women in the control
group

Discussion
There may
be more
specific
cognitive
impairments
associated
with
maternal
hypothyroidi
sm

Associated with psychomotor deficit in

infancy and at the age of 2 to 3 years, as
well as with delays in the development of
expressive language.
decrement of orientation the ability to
attend to visual and auditory stimuli and
overall alertness)
Visual abnormalities

Behavioral changes

A possible explanation for the negative results

of this study is that screening was performed
and levothyroxine therapy initiated too late in
gestation to have a major influence on brain
development

However, in post hoc analyses, we like- wise

did not find a benefit of screening and treatment in the subgroup of women who started
treat- ment earlier, although it should be
acknowledged that our trial was not powered
for this assessment.

Discussion

A limitation of this study is that about 24% of

the women were lost to follow-up.

Most of these women could not be contacted,

with similar pro- portions in the screening and
control groups, but 19 women from the
screening group and 41 from the control group
declined to have their child assessed.

Current guidelines do not recommend routine

antenatal screening for hypothyroidism in
pregnancy.

This study provides support for these

guidelines, since we found no benefit of routine
screening for maternal hypothyroidism at about
12 to 13 weeks gestation in the prevention of
im- paired childhood cognitive function.