1

Effect of Levothyroxine on Pregnant

Subclinical Hypothryoid Patients
and Rates of Pregnancy Loss
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Table of Contents

Abstract…………………………………………………………………………………….2

Introduction………………………………………………………………………………...3

Literature Review…………………………………………………………………………..4

Data Collection……………………………………………………………………………..7

Conclusion…………………………………………………………………………………12

References………………………………………………………………………………….12

Abstract

A common diagnosis during pregnancy is subclinical hypothyroidism (SCH) and is

defined as an elevated thyroid stimulating hormone (TSH) level of 4.01 to 9.99 mIU/L. The most

common symptoms of SCH are fatigue, weight gain, and hormonal changes, making it difficult

to diagnose since pregnancy and SCH have common symptoms. The common treatment for SCH

is levothyroxine (LT4), but many researchers say that stating LT4 earlier in pregnancy, before

pregnancy, and increasing the dosage should be added to the american thyroid association’s

guidelines. Iodine deficiency is another main cause of SCH and can be easily fixed by

supplements. An individual's lifestyle, lack of access or opportunities, or misinformation can

contribute to not getting tested for TSH. Many women who don't have access to TSH testing

areas or a practitioner's office usually come from low- income urban areas where resources are

not plentiful or adequate. The dosage for SCH is often too low, and should be increased during

pregnancy to maintain normal TSH levels and to keep up with differing hormone levels that are

already present during pregnancy. Miscarriage rates decline in a more promising manner when
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LT4 is prescribed in the first trimester as compared to the second or third. A new schedule should

be formed for TSH testing to ensure miscarriage rates continue to decline.

Hania Bajwa

Ms. Leila Chawkat

Independent Research GT Period 3

31 May 2022

“Effect of Levothyroxine on Pregnant Subclinical Hypothryoid Patients and Rates of

Pregnancy Loss”

Over twelve million Americans have been diagnosed with a thyroid disease. Thyroid

research is an ongoing and rapidly changing field for medical professionals. The thyroid gland is

responsible for creating and regulating the body’s hormonal functions, but certain factors such as

genetics, diet and especially pregnancy can cause it to become overworked, resulting in

subclinical hypothyroidism (SCH). It's one of the most common thyroid diseases among

pregnant women, and is popularly treated with levothyroxine (LT4). LT4 dosages must be

increased during pregnancy to account for changing hormone and thyroid stimulating hormone

(TSH) levels (American Thyroid Association, 2017). SCH often results in pregnancy loss and

adverse pregnancy outcomes if the correct dosage is not prescribed, given too late, or isn’t given

at all. Certain doctors and researchers have taken notice of this fact and worked to find a way to

combat this flaw in maternal and fetus care. They have explored different foods and medications

that might help the effects of SCH, like iodine consumption. Because it's harder to detect SCH

during pregnancy due to its mildness and similarity of symptoms to general pregnancy, many

researchers have increased the dosage of levothyroxine given. Since the women who are
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diagnosed with subclinical hypothyroidism (SCH) during pregnancy experience worse effects

than euthryoid women, like a higher rate of pregnancy loss, a new dosage of levothyroxine needs

to be clinically tried. This will help women recover faster from these abnormal thyroid functions.

Literature Review

Said to be one of the most varied diagnoses for pregnancy, subclinical hypothyroidism

(SCH) affects about 10% of adults, and is a “common diagnosis among women of reproductive

age (4% to 8%)” (Biondi 2019) (Maraka, 2018). It is usually defined as an elevated TSH level,

with a TSH range of 4.01 to 9.99 mIU/L (Yamamoto, 2020) (Han, 2021) (Javed, 2016). For

SCH, symptoms mainly include weight gain, fatigue, restlessness, diet changes, hormonal

changes, and mood swings. Since fatigue is one of the most common symptoms of SCH and

pregnancy, that makes it harder for doctors to determine whether or not to diagnose women for

SCH or another disease (Kiran, 2019) (Peeters, 2017). SCH is difficult to identify, and

“undiagnosed or subclinical hypothyroidism during pregnancy has been variably associated with

adverse maternal … outcomes in observational studies” (Yamamoto, 2020) (Zhu, 2021). Many of

the pregnant women included in these studies were observed to have extreme fatigue, a

detrimental symptom to have in todays’ society.

Right now, in the field of thyroid physiology medicine, the most common treatment for

SCH is “levothyroxine, [which] has been recognized as the most effective and convenient

drug…reducing the risk of adverse pregnancy outcomes'' (Han, 2021). As women start to

develop the symptoms mentioned earlier, their practitioner might increase the dosage of LT4

treatment. Currently, “about 1.20-1.75 mcg/kg/day of LT4 is commonly prescribed,” with

specific foods to avoid while on medication (Casey, 2017). These foods include soy products,

processed foods, espresso, and antacids that contain aluminum, magnesium or calcium, to avoid
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altering the chemical composition and consumption of LT4 (Interview with Dr. Maraka, 2022). It

is extremely important to get tested for one’s TSH levels annually, before one wishes to become

pregnant, and during every trimester of pregnancy. The women included in their study “who

were 35 years of age or older, who were nulliparous, who were from an urban area, who had

gestational hypertension or who had other medical disorders were more likely to have TSH

measured during pregnancy, whereas those who smoked were less likely to have TSH measured

during pregnancy” (Yamamoto, 2020) (Khasawneh, 2020). An individual's lifestyle, lack of

access or opportunities, or misinformation can contribute to not getting tested. Many women

who don't have access to TSH testing areas or a practitioner's office usually come from low-

income urban areas where resources are not plentiful or adequate (Interview with Dr. Maraka,

2022).

The dosage for LT4 depends on the individual since everyone’s needs vary especially

during pregnancy. However, doctors have expressed that “current practice patterns may

contribute to overdiagnosis of hypothyroidism and overtreatment during pregnancy and

postpartum” (Yamamoto, 2020) (Nazarpour, 2018) (Taylor, 2019). This is due to the

recommendation that a TSH upper limit of “2.5 mIU/L in the first trimester and 3.0 mIU/L in the

second and third trimesters'' are administered, but that may also depend on the individual’s

thyroid physiology and chemical composition (Yamamoto, 2020). To avoid being given the

wrong dosage of LT4, one should be tested often for TSH levels, and being tested before

pregnancy is extremely crucial to the mother’s health as well as the fetus’s (Maraka, 2018)

(Duntas, 2019). Ensuring that the mother’s TSH levels are adequate to sustain her and the baby,

doctors can then increase the dosage for subclinical hypothyroidism, which almost always needs

the dosage to be increased. Because after all, “even a mild maternal thyroid hormone deficiency
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has a negative impact on pregnancy outcome and offspring mental development” (Han, 2021).

The physiology of the thyroid gland requires constant medication and treatment if functions are

imapred, proving the need for increasing the dosage for the patient's safety (Ząbczyńska, 2018).

Iodine, the chemical responsible for making sure that LT4 is absorbed by the thyroid gland, is

essential to ensure full benefits of the medication. The patients that don’t take iodine through

their diet or through supplements will not have any improvements by starting their thyroid

medication earlier (Chung, 2014) (Leung, 2012).

The data collection consists of four studies, all of which are meta analyses, to ensure that

the most accurate and extensive data is utilized in this recommendation. It includes information

gathered that contribute to the final conclusion, a higher dosage of LT4 administered to begin

with and extra testing for TSH levels. The author of this paper conducted an interview with Dr.

Sypridoula Maraka of the University of Arkansas for Medical Sciences (UAMS), and learned

that based on the information gained and looking at more peer reviewed sources, a higher

dosage will decrease pregnancy loss rates in SCH women (Interview with Dr. Maraka, 2022).

Seeing that it is certain that the dosage for SCH is often too low, it should be increased during

pregnancy to maintain normal TSH levels and to keep up with differing hormone levels that are

already present during pregnancy (Rao, 2019). Furthermore, rates of pregnancy loss decline

rapidly when the mother is given LT4 if she has SCH (Maraka 2017). Miscarriage rates decline

in a more promising manner when LT4 is prescribed in the first trimester as compared to the

second or third. The most miscarriage rates occured in the second trimester, during gestational

weeks 13 to 28.
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Data Collection

Source (with Study design: definition of dosage of pregnancy Ultimate

author, methods, SCH–not Levothyroxine loss Assessment
participants, applicable for (LT4) (miscarriage
publication
timeframe, most studies from
date, etc.
results GW13-28)

Effect of - systematic “Subclinical different for all found that

levothyroxine review and hypothyroidis 13 studies 31% relative supplementatio
supplementatio meta analysis m (SCH) is included risk reduction n of LT4
of 13 studies defined as an in pregnancy treatment
n on
elevated serum loss by LT4 decreased the
pregnancy loss -8 were thyrotropin supplementatio risk of
and preterm randomized (TSH) level n among pregnancy loss
birth in women controlled with normal pregnant rate, but not
with trials and 5 serum women with for preterm
subclinical were thyroxine (T4) SCH birth delivery.
hypothyroidis retrospective level and “As these
studies affects 3–8% 14 % decrease subgroup
m and thyroid
of women of in pregnancies analyses were
autoimmunity: -7970 patients childbearing with assisted based on a
a systematic all over the age” reproduction limited number
review and globe “recommended but not for of studies,
meta-analysis upper naturally further
-Meng Rao, reference limit conceived research is
Zhengyan for TSH is 2.5 pregnancies needed to draw
mIU/L during firm
Zeng, etc
the first “Five studies conclusions.”
-may 2019 trimester and reported the
3.0 mIU/L effects of LT4 thyroid
during the supplementatio function
second and n on PLR in screening prior
third women with to ART cycles
trimesters” SCH. The for infertile
meta-analysis women
revealed a appears
significant necessary
decrease in the because timely
risk of LT4
pregnancy loss supplementatio
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(RR = 0.43, n after SCH

95% CI: diagnosis
0.26–0.72) could decrease
with LT4 the risk of
supplementatio pregnancy
n” loss”

systematic NA “Miscarriage “fail to

review and was reported demonstrate
Impact of meta analysis in all six trials evidence of
levothyroxine of randomized (n=1427) and benefit from
in women with controlled was defined as levothyroxine
positive trials pregnancy loss treatment for
at less than 20 pregnancy
thyroid
(total of 2263 weeks” outcomes in
antibodies on women thyroid
pregnancy autoimmune
outcomes: a women with
systematic normal thyroid
review and function and
meta-analysis subclinical
hypothyroidis
of randomized
m.”
controlled
trials
-Lorraine Lau,
Jamie L.
Benham
-feb 2021

Thyroid Retrospective defined as of the 843, 832 Pregnancy loss “Thyroid

hormone cohort study untreated (98.7%) among treated hormone
treatment 5405 pregnant thyroid prescribed women: 10.6% treatment was
among women with stimulating levothyroxine associated with
pregnant subclinical hormone at a median among decreased risk
women with hypothyroidis (TSH) dose of 50 µg untreated of pregnancy
subclinical m concentration women: 13.5% loss among
hypothyroidis 2.5-10 mIU/L. significantly women with
m: US national -843 treated more women “odds of subclinical
assessment with LT4 “estimated to receiving pregnancy loss hypothyroidis
-spyridoula (15.6%) affect up to treatment in were lower in m, especially
maraka, 15% of the Northeast treated women those with
raphael -4562 not pregnancies in and West than than in pre-treatment
mwangi treated the US” in the Midwest untreated TSH
- jan 2017 (84.4%) and South women if their concentrations
regions of the pre-treatment of 4.1-10
US TSH mIU/L”
concentration
was 4.1-10 “, in theory,
mIU/L” full
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implementatio
n of these
guidelines
would lead to
levothyroxine
treatment
being started
in up to 600
000 pregnant
women in the
US each year”

“We found that

use of thyroid
hormone was
associated with
decreased risk
of pregnancy
loss, but it was
also associated
with increased
risk of preterm
delivery,
gestational
diabetes, and
pre-eclampsia.
”
“clinicians are
encouraged to
use a shared
decision
making
approach.”

Levothyroxine Systematic NA different for all “ “Treatment of

and the risk of Review and studies in the levothyroxine SCH with
adverse Meta-Analysis meta analysis treatment levothyroxine
pregnancy among women during
outcomes in 7342 women “initiated with SCH was pregnancy is
women with included levothyroxine associated with associated with
subclinical during the first a decreased decreased risks
hypothyroidis trimester with risk of of pregnancy
m: a only two pregnancy loss loss and
systematic studies (RR: 0.79; neonatal
review and addressing the 95% CI: death.”
meta-analysis effects of 0.67–0.95)”
-magnus bein initiating “untreated
and oriana yu levothyroxine hypothyroidis
-dec 2021 at other times m during
during pregnancy may
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pregnancy” lead to
deficiencies in
fetal
neurocognitive
development
and lower
intelligence
quotient (IQ)
in the
offspring”

“meta-analysis
by Rao et al.
[17] showed
that
levothyroxine
treatment
among women
with SCH and
women with
thyroid
autoimmune
disease was
associated with
a decreased
risk of
pregnancy loss
and preterm
birth compared
to women who
received no
treatment”

This is an ethnographic meta analysis of four systematic reviews. These four systematic

reviews attempted to discern that SCH is often given as low doses necessary for pregnant women

and were appropriate for an analysis of SCH patients. They analyze many professionally peer

reviewed studies that have already positively impacted and contributed to the field of obstetrics

and endocrine medicine. This is also quantitative since it analyzes numbers. One can decide on

these methods by considering the fact that meta analyses take into account many more sources
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and subjects than a single study would, and then based on those studies, develops a medically

sound thesis.

Many endocrinologists use levothyroxine as the prime medication for treating subclinical

hypothyroidism (SCH), but it is often underestimated how much of it should be prescribed

(Maraka, 2017). For the studies that administered levothyroxine in subclinical hypothyroid

patients as opposed to not administering it at all, they found that the rate of pregnancy loss was

significantly decreased. This is a crucial breakthrough for further research and sets a precedent

for doctors now. Because SCH is often missed during a routine checkup by a physician while

pregnant, it is harder to estimate how many people are suffering from the effects of SCH.

However, it is certain that the dosage is often too low and should be increased during pregnancy

to maintain normal TSH levels, as well as keep up with differing hormone levels that are already

present during pregnancy (Rao, 2019). The limitations that these studies have is that some of the

studies included in one meta analysis exhibit high levels of publication bias, which may affect

the data. It can skew the results, altering the reading reached by the researchers. If this was to be

done again, new sources without any implications of minimal bias would be selected, to further

aid the medical field with this paper.

From this research and data collection results, the world is closer to finding a more

permanent schedule for thyroid patients. This data will aid professionals of the medical field,

specifically gynecologists, endocrinologists, and obstetricians. They will learn how to better

administer dosages of levothyroxine and what it does to a subclinical hypothyroid pregnant

patient. Since all of the sources that are analyzed above are meta analyses, it's a larger

collection of studies and patients opposed to four single studies. The researchers have taken

extra care and have already analyzed professional peer-reviewed sources. The new knowledge
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that can be extrapolated from these results is a new schedule of administering levothyroxine

doses, since it's proven that the earlier it is administered, the faster TSH levels become normal.

Therefore, this is beneficial to both the mother and the fetus.

Conclusion

A meta analysis of these four meta analyses proved to be an effective method of

explaining that healthcare providers need to start administering higher doses of levothyroxine to

the subclinical hypothyroid patients in order to prevent the risk of misacarriage. From reviewing

the sources used in the literature review, a new schedule should be formed to and added to the

ATA’s recommendations for thyroid care.

From this meta analysis, one can conclude that this will benefit the world of thyroid

physiology research and how it relates to pregnant subclinical hypothyroid patients. A new

schedule for administering levothyroxine may be created, which is proven by this research. Also,

it's proven that doses of levothyroxine must be increased during pregnancy, which benefits

maternal TSH levels, therefore positively affecting the fetus.

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