Pregnancy Complications and Deficits in Infant and Child
Intellectual Development Are Focus of New ATA Statement and Discussion
at Symposium on Thyroid Health in Pregnant Women
Experts in Women’s Health and Thyroid
Diseases Debate the Health Benefits and Costs of
Population-wide Screening of Women for Thyroid Problems
(FALLS CHURCH, VA)—Thyroid problems at any time during a
woman's pregnancy are associated with pregnancy-related complications
and may be detrimental to the infant’s neural development,
said the American Thyroid Association (ATA) in a statement released
today. This information was echoed by other experts in thyroid diseases
and fetal and women’s health at a recent symposium sponsored
by the the ATA and the American Association of Clinical Endocrinologists
(AACE).
In addition, the ATA statement calls for prospective studies looking
at population screening and treatment of asymptomatic – or
subclinical – hypothyroidism, also known as an underactive
thyroid. The organization of thyroid specialists also proposes public
education initiatives, including messages about maternal thyroid
health in over-the-counter pregnancy test kits.
The April 2 symposium in Alexandria, Va., titled The Impact
of Maternal Thyroid Status on Pregnancy and Fetal and Childhood
Development, brought together top researchers and clinicians
in obstetrics and gynecology, neonatology, and thyroid diseases
to explore important clinical and policy issues to educate caregivers
about the best diagnosis, treatment, and monitoring strategies as
well as public policy issues that influence how care is provided.
"Maternal hypothyroidism and autoimmune thyroid disease –
like Hashimoto's thyroiditis, a type of hypothyroidism, or underactive
thyroid – increase the risk of pregnancy complications, such
as miscarriage, prematurity, gestational hypertension, and pre-eclampsia,
as well as deficits of intellectual development in children,"
said Stephen H. LaFranchi, MD, of the Oregon Health & Science
University in Portland, Ore., and a co-chair of the symposium. "The
symposium tackled many unresolved issues, such as whether it is
time to consider pilot screening programs of women for maternal
hypothyroidism as a preventive measure, just as we screen newborns
for congenital hypothyroidism to prevent the condition’s harmful
effects."
The experts described why maternal thyroid hormone is so important
to the developing fetus. Gabriella Morreale de Escobar, MD, of the
Instituto de Investigaciones Biomedicas, "Alberto Sols,"
in Madrid, Spain, explained that the fetus depends solely on the
mother in the first half of gestation for thyroid hormone, especially
thyroxine, needed for the developing brain. She added that pregnant
women who are underproducing thyroxine are, therefore, at risk of
having children with lower IQs and learning problems, such as attention-deficit
hyperactivity disorder, whether or not their circulating thyroid-stimulating
hormone (TSH) concentrations are increased. The most frequent cause
of the inability of the maternal thyroid to produce enough thyroxine
for fetal brain development is an inadequate supply of iodine. Amounts
of this micronutrient, a necessary component of thyroid hormone,
are needed with the onset of pregnancy and are almost double those
needed by children and non-pregnant adults. "Intellectual impairments
of many children could be easily prevented by promoting the use
of iodine supplements taken before pregnancy throughout gestation
and lactation," Dr. Morreale said.
The ATA statement concurs, emphasizing that pregnant and nursing
women should take daily vitamin supplements that contain iodine,
at least 220 micrograms a day for pregnant women and 290 micrograms
daily for lactating women. Experts caution that only 35 percent
of prenatal vitamins contain iodine. Worldwide, iodine deficiency
remains the major factor responsible for intellectual impairment,
although, in the United States, says the ATA statement, iodine nutrition
is adequate. Even so, the statement goes further to say that new
data indicate that some U.S. women of reproductive age may be at
risk for slightly deficient intake. Furthermore, the ATA believes
there is a need for research to clarify the iodine nutrition status
of pregnant women in the United States, including measuring iodine
levels in breast milk and correlating with maternal iodine nutrition
and factors such as smoking.
The effect of environmental agents on thyroid function and iodine
nutrition was another important topic discussed at the symposium.
R. Thomas Zoeller, PhD, Professor of Biology at the University of
Massachusetts in Amherst, said that ammonium perchlorate, a contaminant
in some water supplies, is known to reduce the ability of the body
to use existing iodine. Moreover, PCBs (polychlorinated biphenyls)
are known to influence thyroid function and thyroid hormone action,
which can alter iodine uptake during pregnancy and lactation. PCBs
also appear to influence thyroid hormone action in tissues, including
the developing brain. Thiocyanates in cigarette smoke are as a negative
factor as well. "Chemicals in the environment can affect thyroid
function in the mother and fetus and thyroid hormone ‘signaling
action’ in the developing brain," concluded Dr. Zoeller.
Another potential problem related to hypothyroidism was described
at the symposium by Daniel Glinoer, MD, PhD, who heads the Thyroid
Investigation Clinic & Endocrine Section at the University Hospital
Saint Pierre in Brussels, Belgium. "Five percent to 8 percent
of women carry thyroid autoantibodies," he stated. These autoantibodies
are strongly linked to the occurrence of miscarriage as well as
a condition that occurs after delivery, called post-partum thyroiditis.
Symptoms include depression, fatigue, and difficulty nursing. "Subclinical
hypothyroidism – when the person has no visible symptoms and
the condition is only detectable through labortary tests –
is often undiagnosed, and the severity of hypothyroidism increases
with gestational time." He estimated, "Five percent to
10 percent of the young female population could be affected, which
has negative public health consequences.” Dr. Glinoer also
discussed hyperthyroidism – an overactive thyroid –
explaining that it is “relatively uncommon in pregnancy but
can be severe if untreated."
Kenneth J. Leveno, MD, Gillette Professor of Obstetrics and Gynecology
at the University of Texas Southwestern Medical Center at Dallas
and Chief of Obstetrics at Parkland Health and Hospital System,
brought in the view of the obstetrician-gynecologist in stating
that he does not believe that all women should be screened for thyroid
dysfunction at this time because the current evidence is insufficient
to warrant such universal screening. He added, "Given that
the prevalence of subclinical hypothyroidism is about 2.5 percent
in the United States and there are about 4 million births each year,
appoximately 100,000 pregnant women would have to be treated. To
do this is unjustified at this time."
The Medical Director of the March of Dimes, Nancy Green, MD, discussed
the guidelines issued by the American College of Obstetricians and
Gynecologists (ACOG) in 2002, which she noted were based primarily
on consensus and expert opinion. ACOG stated at that time that there
were insufficient data to warrant routine screening of asymptomatic
pregnant women for hypothyroidism. ACOG recommended that testing
of thyroid function may be performed in women with a personal history
of thyroid disease or symptoms of thyroid disease.
The March of Dimes, said Dr. Green, appreciates the ATA's current
review of the issue, which is in consideration of whether routine
maternal thyroid screening and treatment – before conception
and/or in early pregnancy – improves child cognitive development.
The March of Dimes is focused on this issue primarily if it helps
prevent pediatric harm. In addition, the March of Dimes is currently
conducting a national campaign to prevent preterm birth, a side
effect of maternal hypothyroidism.
Preterm birth, as Brian M. Casey, MD, Associate Professor of Obstetrics
and Gynecology at the University of Texas Southwestern Medical Center
at Dallas, pointed out, is the most common recognized cause of neuropsychological
dysfunction in children. After reviewing the association of subclinical
hypothyroidism with preterm birth, he concluded that "Prematurity
may explain some of the neurodevelopmental abnormalities associated
with maternal thyroid insufficiency."
The ATA statement emphasizes this research finding, stating that
"pregnant mothers with overt or subclinical hypothyroidism
are at an increased risk for premature delivery." Other important
research findings highlighted by the ATA statement include –
- Pregnant mothers with detectable thyroid autoantibodies and
normal thyroid function are at an increased risk for miscarriage
and for postpartum thyroid disease,
- Pregnant mothers with thyroid hormone deficiency or TSH elevation
during pregnancy may have children at risk of mild impairment
in their intellectual function and motor skills, and
- Pregnant women being treated with thyroid hormone replacement
often require a 30-percent to 50-percent increase in their thyroid
hormone dose.
The ATA believes that the magnitude of these problems should be
clarified, and programs should be developed to manage these health
issues.
P. Reed Larsen, MD, a Professor of Medicine at Harvard Medical
School and Chief of the Endocrinology Division at Brigham &
Women’s Hospital in Boston, asserted that there is not yet
data that backs up the need for population-wide screening; however,
he emphasized that the "threshold should be low for identifying
at-risk women for screening. These factors include women who have
a family or personal history of thyroid disease, goiter, diabetes,
history of miscarriage, or symptoms suggesting hypothyroidism."
The ATA also makes this assertion.
As for women who have known hypothyroidism before conception, Dr.
Larsen strongly advised that physicians should provide pre-pregnancy
counseling about the risks and changes in therapy that are needed.
It is also important that these women have their thyroid hormone
levels – TSH, in particular – checked as soon as pregnancy
is confirmed. He and his colleagues have shown that many of these
women will need to increase their thyroxine replacement as much
as 50 percent in the first trimester.
"With these steps, as well as careful monitoring of TSH, we
should be able to maintain normal thyroid hormone availability to
the fetus during this critical period of development before fetal
thyroid maturation occurs," added Dr. Larsen.
John H. Lazarus, MA, MD, Professor of Clinical Endocrinology at
the University of Wales College of Medicine, Llandough Hospital
in Cardiff, Wales, United Kingdom, added that there is substantial
evidence from both retrospective and prospective studies suggesting
that early gestational low maternal circulating thyroxine –
a thyroid hormone, also known as T4 – concentrations adversely
affect neonatal and child development at least to age 7.
Acknowledging the current lack of clinical trial data, he presented
preliminary information about a current randomized, prospective
study called CATS (Controlled Antenatal Thyroid Screening), which
aims to ascertain if screening for thyroid function in early pregnancy
is justified. The study plans to enroll 22,000 women when they are
less than 16 weeks gestation and will look at whether treating thyroid
disorders with thyroxine therapy during pregnancy can prevent adverse
outcomes. Following delivery, the children will be tested with appropriate
psychological evaluation at ages 2 and 5.
Paul Ladenson, MD, Director of the Division of Endocrinology and
Metabolism at Johns Hopkins Medical School in Baltimore reviewed
the benefits and costs of identifying pregnant women at risk of
hypothyroidism. He concluded that "gestational hypothyroidism
probably occurs with a significant incidence; TSH testing can diagnose
the condition and thyroxine can treat it; and maternal and fetal
consequences appear to be clinically significant based on anecdote
and small clinical trials, and reversibility could be predicted."
However, he added, "Evidence from definitive prospective, randomized
clinical trials is lacking, and the cost of this new preventive
medical intervention would be substantial."
" While most of the experts agreed that current scientific
data falls short of supporting immediate widespread population screening
for thyroid disease and thyroid autoimmunity," said Gregory
Brent, MD, of the UCLA School of Medicine and the ATA Secretary,
"there is sufficient information to recommend some interim
measures and guidance for additional data that is required to design
an effective screening program."
The ATA statement includes a "plan for action" that calls
on governmental institutions, such as the Centers for Disease Control
and Prevention; professionals organizations, such as the ATA and
AACE; and nongovernmental groups, such as the March of Dimes, to
implement a coordinated program of patient education, practice review,
and research on the impact of maternal thyroid status on pregnancy
and fetal and childhood development.
The ATA
statement is available at www.thyroid.org.
Founded in 1923, the ATA is a professional society of 900 U.S.
and international physicians and scientists who specialize in the
research and treatment of thyroid diseases. The Association is dedicated
to promoting scientific and public understanding of the biology
of the thyroid gland and its disorders, so as to improve methods
for their prevention, diagnosis, and management. The ATA fosters
excellence in research, patient care, and education of patients,
the public, and the medical and scientific communities while guiding
public policy about the prevention and management of thyroid diseases.
AACE was established in 1991 and is the country's largest professional
organization of clinical endocrinologists. Its membership consists
of more than 4,600 clinical endocrinologists devoted to providing
care for patients with endocrine disorders. Endocrinologists are
physicians whose advanced, specialized training enables them to
be experts in the care of endocrine diseases, such as obesity, diabetes,
thyroid disorders, growth hormone deficiency, osteoporosis, cholesterol
disorders and hypertension.
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