open access: Nature Reviews: Key Advances in Medicine

ENDOCRINOLOGY
THYROID DISEASE IN PREGNANCY IN 2011
Thyroid function—effects on mother
and baby unraveled
Anthony P. Weetman
The complex relationship between pregnancy and thyroid function, and its clinical effect on mother and baby,
continued to stimulate research in 2011. Key advances were made on three important issues: how long
maternal thyroid function affects fetal thyroid hormone levels; whether thyroid autoimmunity affects pregnancy
outcome; and the prevalence of permanent hypothyroidism after postpartum thyroiditis.
Weetman, A. P. Nat. Rev. Endocrinol. 8, 69–70 (2012); published online 6 December 2011; doi:10.1038/nrendo.2011.217
The fetal thyroid gland starts to develop at
12 weeks of gestation, and for the first half of
pregnancy, transplacental passage of maternal
thyroid hormone is essential for normal
fetal development. Failure to deliver sufficient
thyroid hormone to the fetus causes impaired
neurological development, although whether
other elements of fetal development are also
affected remains unclear. The essentially
normal outcome in neonates with congenital
hypothyroidism promptly treated with levothyroxine
after birth suggests that maternal
thyroid hormones also have a fetal role in the
second half of pregnancy.
In a prospective survey of 886 pregnant
Dutch women published in 2011, neonates
born to mothers who had high-normal TSH
levels (above the 97.5 th percentile) one or
more times during pregnancy had lower
total T 4 levels when routine screening was
performed for congenital hypothyroidism
than neonates born to mothers whose TSH
levels had remained below the 97.5 th percentile.
1 This result contrasts with that of a
previous study that showed no relationship
between maternal and neonatal thyroid function,
2 a difference possibly related to the use
of pregnancy-specific refer ence ranges for
TSH measurement in the 2011 study.
Although the women with high-normal
TSH levels had normal free T 4 levels, the TSH
levels might reflect a resetting of the
pituitary–thyroid axis, which resulted in
less T 4 being available to cross the placenta.
Alternatively, an unsuspected increase in
placental deiodinase activity might have
been responsible for low T 4 availability to
the fetus. Low gestational age was associated
with low neonatal thyroxine levels in
this and previous studies, which raises the
possibility that maternal thyroid function
throughout pregnancy, rather than just the
first trimester, is an important determinant
of gestational outcome. Detailed sampling of
maternal thyroid function is required to
investigate this hypo thesis further.
In a related study from 2011, maternal thyroid
function variables measured at 28 weeks
gestation were compared with those measured
in the umbilical cord at birth in 616
preg nancies in the UK. 3 Maternal free T 4 and
cord free T 4 values showed a positive correlation,
and maternal TSH levels were inversely
corre lated with cord free T 4 levels. This evidence
by Shields and co-investigators is consistent
with that of the Dutch study 1 and
sug gests that maternal thyroid function has
a measurable effect on fetal thyroid hormone
levels throughout pregnancy.
Shields et al. also examined the effect of
thyroid hormone levels on various parameters
of fetal growth. Cord free T 4 levels
were associated with birth weight, length and
skin-fold thickness. These results imply that
fetal thyroid hormone levels have an important
role in regulating fetal growth, especially
when taken in conjunction with the results
of animal experiments. 4 An unexplained
finding was that birth weight was negatively
associated with maternal free T 4 levels, given
that maternal and cord free T 4 levels were
positively associated.
Together, these two studies highlight the
intricacy of the maternal–fetal relationship
with regard to thyroid function and its clinically
important effects on fetal growth and
ges tational age. Studies with detailed assessment
of maternal thyroid function throughout
the third trimester that incorpo rate
assess ment of placental deiodinase activity
are needed. Variable iodine intake is also a
con founding factor that needs addressing,
given the surprising discovery in 2011 of
inade quate dietary supplies in the UK and
in other countries. 5
Multiple studies have shown that euthyroid
pregnant woman with positive thyroid peroxidase
(TPO) antibodies have an increased
risk of spontaneous mis carriage and possibly
preterm delivery. Two mechanisms might be
responsible. Firstly, even though ‘euthyroid’,
these women may have subtle impairment
of thyroid function, and the effects of maternal
thyroid function on the fetus, as discussed
above, are responsible. Secondly, thyroid
auto immunity dis torts the immunological
balance required to maintain tolerance to
the fetal semi-allograft. 6
In 2011, a study of 245 TPO-antibodypositive
women with TSH levels