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Thyroid Disease in Pregnancy
closure of the fontanelles, and congestive heart failure starting in the first few
Table 2: Guidelines for Daily Dietary Iodine Intake in Pregnancy
days after birth and lasting for three to six months,
41
when the infant’s blood
TSI titer from the mother has dissipated. Severe neonatal or infantile Institute of Medicine
62
220µg
hyperthyroidism may require treatment with antithyroid drugs, beta blockers,
World Health Organization
63
200–300µg
and, rarely, drugs that decrease the conversion of T4 to T3, such as
Endocrine Society
59
250µg
dexamethasone. Finally, transient neonatal pituitary hypothyroidism following
In comparison, an iodine intake of 150µg/day is recommended for non-pregnant adults
and adolescents.
62
a hyperthyroid phase from uncontrolled maternal Graves’ disease has been
described in Japan.
48
Autoimmunity in Pregnancy and the Post-partum Period
Thyroid autoimmunity is common, with TPO Ab detectable in 13% of the US
Surgery population,
65
although the prevalence varies according to sex, age, and
Thyroidectomy is only rarely required for the treatment of refractory racial/ethnic group.
66
The TPO antibody positivity is less frequent in
hyperthyroidism, medication non-compliance, or when severe side effects of African-American women than white women.
67
Most TPO Ab-positive
antithyroid drugs are present. When necessary, thyroidectomy is best women do not have clinical hypothyroidism, although, as demonstrated by
performed in the second trimester.
49
our recent data
3
and others,
2,68
they do tend to have higher serum TSH and
lower free T4 values in the first trimester of pregnancy than women without
Hypothyroidism in Pregnancy detectable thyroid antibodies.
Maternal hypothyroidism, as characterized by an elevated TSH value,
occurs in an estimated 2.5% of all US pregnancies.
50
The fetal thyroid does Relationship Between Thyroid Peroxidase Antibody
not begin to concentrate iodine until weeks 10–12 of gestation and is not Positivity and Obstetric Risks
controlled by fetal pituitary TSH until approximately 20 weeks of The first report of increased miscarriage risk in association with
gestation.
51
Prior to this, the fetus is reliant on maternal T4, which crosses antithyroid antibodies was published in 1990.
69
Since then, multiple
the placenta in very small quantities.
52
Since thyroid hormone is required observational studies have demonstrated a two- to three-fold risk for
for normal neurodevelopment,
53
even mildly low maternal T4 in pregnancy miscarriage among TPO Ab-positive women compared with TPO Ab-
may result in cognitive delays in offspring,
54,55
as may elevated maternal negative women, even in those with normal thyroid function.
70–72
serum TSH values.
5,56
However, one recent study found no relationship Some,
73–75
but not all,
76,77
studies have found associations between thyroid
between isolated maternal hypothyroxinemia in early pregnancy and autoimmunity and increased rates of recurrent miscarriage. A two- to
adverse perinatal events, such as low birthweight, low Apgar scores, three-fold increase in the rate of miscarriage in women with TPO Ab
requirement for intensive care unit monitoring, respiratory distress undergoing assisted reproductive technology has been seen in four out
syndrome, major malformations, and neonatal death.
57
of six studies performed to date.
78–83
The presence of antithyroid
antibodies has also been associated with a three-fold risk for premature
Women with pre-existing hypothyroidism require larger amounts of delivery before 37 weeks of gestation.
84
Another prospective study found
L-thyroxine starting in the first trimester of pregnancy due to increased a two-fold risk for very pre-term delivery (<32 weeks of gestation) in
TBG levels and increased deiodination of T4 by the placenta. It has been women with positive TPO Ab, but no increased risk for moderately
recommended that L-thyroxine doses be increased by 30% as soon as pre-term delivery (32–37 weeks of gestation).
85
Finally, the presence of
pregnancy is confirmed, with close monitoring and dose adjustments TPO Ab in early pregnancy has also been associated with increased risk
thereafter as necessary.
58
Ideally, a serum TSH level should be obtained as for post-partum thyroiditis.
86
soon as pregnancy occurs. A conservative upper limit for TSH in the first
trimester of pregnancy is 2.5mU/l, rising to 3.0mU/l for the second and The reasons for the associations between antithyroid antibodies and risks
third trimesters.
8,59
Following delivery, L-thyroxine requirements typically for miscarriage and premature delivery remain unclear. They may be due
decrease to pre-pregnancy levels and serum TSH levels should be to a direct effect of the antithyroid antibodies, or the antithyroid
monitored closely.
60
antibodies may serve as a marker for other, causative, autoimmune
syndromes. Alternatively, antithyroid antibodies may simply indicate
Iodine Requirements in Pregnancy limited thyroid functional reserve.
87
If TPO Ab-positive women are more
Thyroid hormone synthesis is dependent on adequate iodine intake, and an likely to develop hypothyroidism during pregnancy, this hypothyroidism
assurance of iodine sufficiency is especially important in pregnancy, when may be the cause of their obstetric complications.
maternal thyroid hormone production normally increases by about 50%. The
glomerular filtration rate of iodide also increases early in pregnancy, increasing Treatment of Pregnant Women with Thyroid Peroxidase
renal iodide clearance and decreasing the circulating pool of plasma iodine.
61
Antibody Positivity
Due to the increased thyroid hormone production, increased renal iodine There has been one randomized clinical trial demonstrating that the treatment
losses, and fetal iodine requirements in pregnancy, dietary iodine requirements of euthyroid TPO Ab-positive women without a prior history of miscarriage
are higher in pregnancy than they are for non-pregnant adults. Guidelines for could prevent adverse obstetric outcomes.
84
The observations are most likely
daily dietary iodine intake during pregnancy are presented in Table 2.
62,63,59
Due related to correction of mild thyroid hypofunction in the treated women, since
to concern about possible mild iodine deficiency among some US women of L-thyroxine therapy would not be expected to eliminate underlying
childbearing age, the American Thyroid Association (ATA) has recommended autoimmunity. This study was performed in Italy, an area of mild to moderate
that all US and Canadian women receive dietary supplements containing dietary iodine deficiency, so the generalizability to women in the US is limited
150µg iodine each day during pregnancy and lactation.
64
and the study has not yet been replicated.
US OBSTETRICS & GYNECOLOGY 53
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