Thyroid Peroxidase antibody
Positivity is Associated with
Depressive Symptoms during
pregnancy and the Postpartum
Maureen Groer, RN, Ph. D.
Jessica Heckel, DNP, PhD
candidate
TPO
• Thyroid peroxidase autoantibodies (TPO)
are present in 10% of pregnant women.
Their presence indicate an incipient
autoimmune process which increases
risks development of postpartum thyroiditis
(PPT).
TPO
• Microsomal enzyme catalyzing conversion of thyronine
to thyroxin
• If TPO positive in early pregnancy..chance if PPT is 50%
• TPO IgG1,2, 3 complement fixing
• TPO probably not causative…secondary aggravating
role in the disease
Postpartum thyroiditis
• Incidence…5-8%
• Risks :
–
–
–
–
preceding episode
FH of thyroid disease
Type 1 diabetes
Anti-TPO +
1. Lack of energy
2. Irritability
3. Nervousness
4. Weight loss
5.Weight gain
6. Sweating
7. Shaking hands
8. Palpitations
9. Heat Intolerance
10. Dry Hair
11.Puffy Face
12. Dry skin
13.Hair falling out
14. Constipation
15. Aches and pains
16.Tinglings or numbness
17. Cold intolerance
18. Poor Memory
19. Lack of concentration
20. Depression
Thyroid SCL
Literature review
• AID and depression
• TPO and depression in
pregnancy
• No studies following women
through the postpartum
Aims
• The goals of our research were to determine TPO status
at pregnancy and follow all TPO positive women through
the postpartum to analyze the relationships between
TPO status, development of PPT, and dysphoric moods
across time.
• A group of TPO negative women was included in order
to compare these relationships.
• The study was part of a larger parent study (R01NR05000) on trajectories of postpartum thyroiditis
Participants
• Pregnant women (n=631) were recruited at their prenatal
clinics at mid-pregnancy and identified as either TPO
positive or negative at that time.
• Exclusion criteria included : age <18 or >45 years;
known AID; previous thyroid disease; HIV +;
medications that affect immunity; chronic diseases;
serious mental illness; BMI <20; history of hyperemesis;
current multiple gestation; in vitro fertilization (IVF); fetal
abnormalities; unable to understand and speak the
recruiter’s (English and Spanish) language; and being
unable to participate in a six month postpartum follow up.
Participants
• All TPO positive (n=63) women were invited into the
postpartum phase of the study, while a convenience
sample of TPO negative women were selected by a
random number generator to participate in the
postpartum phase (n=72).
• All TPO positive women had TSH measured at time of
pregnancy testing, and at every later postpartum visit. A
subset of TPO negative women had TSH levels
measured during the postpartum. Women r received a
monthly home visit by a research nurse for 6 months. .
Instruments
• At the pregnancy visit, participants completed a
demographic questionnaire, the Profile of Mood States
(POMS), the Perceived Stress Scale (PSS).
• At the subsequent postpartum visits, these stress and
mood instruments were used, as well as the Thyroid
Symptom Checklist.
• Data on breastfeeding, medications, health behaviors
and health status were also collected by an investigator
developed instrument.
Thyroid status
• Targeted PE
• TSCL
• TSH levels (<.3, >3.0 mIU/L) measured by ELISA
(ALPCO)
• Prolactin levels measured 4 times in postpartum (week
one, months 1, 4,and 6)
TPO positives
• During pregnancy mean TPO IgG titer was 55.3, with a
range of 20 to 220 IU/ml
• TSH levels in all TPO positive women were in the
normal range at pregnancy testing.
• Of these 63 TPO positive women, 47 were enrolled in
the postpartum phase, with 16 being lost to follow up or
declining to enter into the postpartum phase.
Demographics:Ethnicity
TPO negative
Caucasian
African American
Asian/Pacific
Native American
Hispanic
Other
46.5%
12.9%
3.2%
1.6%
29%
6.5%
TPO positive
45.7%
14.3%
2.9%
0
28.6%
9.5%
Demographics:Income
TPO negative
$0-$14999
$15000-$24999
$25000-$39999
$40,000 +
16.5%
10.2%
8.7%
64.6%
TPO positive
18.2%
13.7%
12.9%
55.3%
Demographics:Education
Middle school
High school
College graduate
Post-graduate
TPO negative
7.8%
38.8
39.8%
13.6%
TPO positive
5.2%
42.2%
41.8%
10.8%
Demographics:Marital status
TPO negative
Divorced
Married
Single
23.2%
72.5%
4.4%
TPO positive
10%
63.15
26.9%
Statistical Analysis
• Data were examined for normality and log transformed if
necessary.
• T-tests were performed for analyzing group differences.
• Repeated measures mixed model ANOVAs were
performed to analyze differences over time. ANCOVA
was done to covary age and marital status for effects on
the depression symptoms/ TPO relationship.
• The effect of PPT development on the relationships was
analyzed.
• Cronbach alphas were computed for the PSS and the
POMS subscales
Statistical Analysis
• The Cronbach alpha reliabilities were 0.839 for the PSS,
0.91 for the POMS-depression , 0.89 for the POMSanger scale, and .85 for the POMS Total Mood
Disturbance.
Pregnancy Mood
• The 63 TPO positive pregnant women had statistically
significantly higher scores on the POMS depressiondejection subscale (8.5) compared to TPO negative
women (5.9) at the time of pregnancy measurement
(t=2.2 (df=590), p=.028).
• There were 48 cases of women in the total pregnancy
sample (6.8%) with scores of 20 or greater on the
POMS-depression-subscale, indicating possible clinical
depression. Twice as many TPO positive women had
scores of 20 or greater compared to TPO negative
women. The difference was significant (t (df=590 )= 2.2,
p=.03).
Postpartum Mood
• At the initial postpartum testing, there were no
differences in BMI, and reproductive history (number of
pregnancies, preterm births, miscarriages, ectopic
pregnancies) between the TPO positive and negative
women. There were no differences in socioeconomic
status, exercise, breastfeeding, smoking, or family
histories of thyroid disease between TPO positive and
negative. The only difference between the 2 groups at
time one was age (TPO + slightly older and marital
status (TPO+ more divorced, less single).
Postpartum Mood
• Of the 47 TPO positive women, 64% developed PPT at
some point during the first six postpartum months.
• These women with PPT had higher scores on
hypothyroid symptoms (F (df=1,739)=6.7, p=.013) but
not on hyperthyroid symptoms on the Thyroid Symptom
Checklist compared to TPO negative women.
• Three TPO positive women developed visible goiters,
while 9 had palpable thyroid glands.
• TPO positive women without PPT did not score
differently on the thyroid symptom checklist compared to
TPO negative women.
• .
Postpartum Mood
•
there were differences by TPO status on the POMS.
Depression symptom reports were higher across the
postpartum for TPO positive mothers. Anger subscale
scores (F (1.131)=6.4, p=.013) and total mood
disturbance scores (F(1,130)=5.3, p=.023) were also
higher in the TPO positive group than in the TPO
negative group
Depression
(F (1,129)=9.1, p=.009)
Anger
F (1,131)=6.4, p=.013)
Total Mood Disturbance
(F(1,130)=5.3, p=.023)
Perceived Stress
Breastfeeding
• More TPO positive (74.3%) then TPO negative women
(49.3%) were breastfeeding in this study (calculated as
mean frequencies over the first three postpartum
months).
• However, prolactin was not significantly different in TPO
positive compared to negative women or in women who
developed postpartum thyroiditis.
Discussion
• The findings support a relationship between dysphoric
moods and TPO antibody status across the perinatal
period.
• The relationship between TPO positivity (and
autoimmune disease, in general) and depression may be
bidirectional. Individuals with autoimmune disease are
more likely to become depressed, and depressed
individuals are more likely to have altered immune status
• Inflammatory cytokines can alter brain neurochemistry
systemic and trigger depression. It has even been
hypothesized that depression may have an autoimmune
origin
Discussion
• Both depression and autoimmune disease are far more
common in females than males, and reproductive
hormones have been thought to play some role. Further
research into pathophysiological mechanisms, whereby
anti-thyroid antibodies, in particular, can lead to
dysphoria, and even clinical depression, is needed.
• . Currently, TPO antibody status is not routinely
measured during pregnancy, but this study suggests that
the risk for perinatal depressive symptoms is increased
by TPO positivity. Postpartum dysphoria and depression
might be not only predicted but actually prevented
through routine TPO antibody status determination
Limitations
This study has limitations related to the instrument used
for screening dysphoria symptoms vs. clinical
depression, and the relatively small number of TPO
positive women.