FACTORS INFLUENCING NEONATAL THYROID-STIMULATING HORMONE LEVEL
IN NAKHON PATHOM PROVINCE, THALAND
Samart Punpetch1,*, Kitipong Hancharean2,#
1
The degree of Master of Science (Public Health), Major in Infectious Diseases and
Epidemiology, Mahidol University, Thailand
2
Lecturer, Department of Epidemiology, Faculty of Public Health Mahidol University
*e-mail: samart4epmu@gmail.com, #e-mail: phkhc@mahidol.ac.th
Abstract
Background: Thyroid-stimulating hormone in circulation is particularly important for
pregnant women to have the correct amounts of thyroid stimulating hormone and neonatal
TSH levels must be regulated in order to ensure the healthy development of their babies,
especially the central nervous system and brain.(1,3), which hormone is one of the hormones
measured in newborns. The World Health Organization (WHO) has suggested that when a
sensitive assay is used on samples collected 3–4 days after birth, a <3% frequency of TSH
concentrations >5 mIU/L ( 11.2 mIU/L in serum) indicates iodine sufficiency in a
population.4-5 However, many studies have attempted to address influencing factors of
newborn TSH measurements in determining population iodine status and monitoring
intervention programs, and although some have proven to be successful but, most have
provided conflicting or uncertain data. This study was designed to investigate factors that
influencing neonatal TSH levels.
Methods: A case-controls study (1:4) was used to analyze data from questionnaires.
Results: Univariate analysis identified variables influencing the high neonatal TSH levels
(>11.2 µIU/L). Family income, gestational age at first visit of antenatal care, and iodine tablet
supplementation are association with the high neonatal TSH levels. Multivariate analysis
identified a number of variables that are independently associated with high neonatal TSH
levels (>11.2 µIU/L). Pregnant women who not receive a prenatal iodine tablets
supplementation was an increased risk of neonatal TSH levels above 11.2 µIU/L more than
who receive a prenatal iodine tablets supplementation (adjusted odds ratio = 7.41 (95%
confidence interval = 3.33 to 16.53).
Conclusions: In this study, neonate who has high TSH levels (>11.2 µIU/L) did not vary by
maternal education, history of abortion, alcohol drink during pregnancy, number of visit for
antenatal care, mode of delivery, preterm birth and birth weight of the neonate but was
associated with prenatal iodine tablets supplementation and other risk factors, including
family income, gestational age at the first antenatal care, and sex of the neonate
Keywords: thyroid-stimulating hormone, prenatal supplementation, iodine, neonatal
screening
Introduction
Thyroid stimulating hormone (TSH) is produced by the pituitary gland. Its role is
to regulate the production of hormones by the thyroid gland. Thyroid hormones such as
thyroxine (T4) and triiodothyronine (T3), are importance roles in the early normal growth and
development stages of most human organs, especially the central nervous system and brain. 1
Consequently, thyroid hormone is particularly important for pregnant women to have the
correct amounts of thyroid stimulating hormone and thyroid hormones to ensure the healthy
development of their babies.2
Thyroid stimulating hormone is one of the hormones measured in newborns. A
simple blood test can measure TSH in the circulation of the neonate, who has too much
concentration may indicate that their thyroid gland is not making enough thyroid hormone or
iodine deficiency. An adequate iodine intake in the mother is essential for the normal
synthesis of maternal and fetal thyroid hormones important for fetal brain development.
Insufficient iodine supply from the mother can result in a decreased synthesis of both T4 and
T3, with an increased concentration of TSH in the newborn.1,3 The World Health
Organization (WHO) has suggested that when a sensitive assay is used on Neonatal TSH
samples collected 3 – 4 days after birth, a <3% frequency of TSH concentrations >5 mIU/L
(dried cord blood spot sample collected at delivery)4-5 or 11.2 mU/l (Cord blood serum
collected at delivery) indicates iodine sufficiency in a population. A frequency of 3.0-19.9%
indicates mild iodine deficiency and frequencies of 20.0- 39.9% and above 40.0% indicate
moderate to severe iodine deficiency, respectively.6 However, many studies have attempted
to apply the frequency of neonatal TSH values >5 mIU/l in determining population iodine
status and monitoring intervention programs, and although some have proven to be successful
but, most have provided conflicting or uncertain data.
Neonatal TSH is a sensitive indicator of an inadequate supply of thyroid hormone
to the developing brain. This principle underpins the application of newborn TSH screening
as an indicator of maternal and hence population iodine nutrition. Thus, neonatal TSH
screening may be a powerful and underused tool in monitoring iodine nutrition in mothers
and babies.4-5 However, multiple factors other than maternal iodine status can an influence
measurement of newborn TSH, including the timing of the heel-prick collection, maternal or
newborn exposure to iodine-containing antiseptics, the collection paper employed for the
bloodspot and the TSH assay methodology.2 Furthermore, many studies have explored the
impact of maternal, fetal, and delivery characteristics on neonatal thyroid hormones status
include mode of delivery, birth order, maternal age, gestational diabetes, alcohol use during
pregnancy and the sex of the neonate are independently associated with thyroid hormone
levels.7
To improve understanding derived from past studies, we conducted multivariate
analyses to simultaneously examine the association between neonatal TSH level measures
and many factors such as maternal factors, delivery factors, and infant factors that affects the
high neonatal TSH level (>11.2 mU/l). The result of this study will be useful for improving
in the context of the maternal and child health care and in the context of neonatal TSH
screening for monitoring iodine status in Thailand.
The Neonatal Screening Program as nationwide screening due to the high
incidence of congenital hypothyroidism, especially in iodine deficient areas of the country.
In 2005, this program became mandatory and the screening service was provided to all
newborns in all hospitals in Thailand. This screening result during 2007-2011 showed all
provinces of Thailand had sufferred with iodine deficiency and the severity levels of iodine
deficiency disorders (IDD) in area were mild IDD (% IDD 3.0 - 9.9) to low IDD (% IDD
10.0 - 19.9).8
The surveillance and evaluation system of the prevention and control of IDD in
Region 4 found that the degree of severity was mild IDD to low IDD in area; there are the
percentages of IDD as 16.00, 18.48, 16.23, 13.47, and 9.80, respectively.9 Nakhon Pathom
province was the mild IDD to low IDD area during 2007-2011, which is not the highest
problem of a country, but when compared prevalence of iodine deficiency of a country found
that is more prevalence than the country annually. Consequently, this study investigated the
factors such as maternal factors, delivery factors, and infant factors influencing neonatal TSH
in Nakhon Pathom province, Thailand
Methodology
This study is a case-controls study, matched case and control 1:4. We study in
Nakhon Pathom province of Thailand; the study sites include Sampran district,
Nakhonchaisri district and Banglen district were selected by purposive sampling. The Study
populations were Thai pregnant women with deliver at Sampran hospital, Nakhonchaisri
hospital and Banglen hospital since 2011 to 2012, and who live in three districts of Nakhon
Pathom province less than a year. The study population had neonatal TSH screening report
and linkage name and address of pregnant women by medical record, and met the following
criteria.
Inclusion criteria
1. Pregnant women who lives in Sampran district, Nakhon Pathom province
during pregnancy, and early pregnancy for at least one year.
2. Neonates of Pregnant women who will have report of neonatal TSH levels
under the national neonatal screening program during in 2012 from Sampran hospital.
3. Pregnant women who will consent to participate in the interview by using
questionnaires.
Exclusion criteria
1. Participants will have loss of data include the maternal iodine intake from
iodine tablets use, dietary of seafood and iodized seasoning during pregnancy.
The study populations were divided into two groups by the criteria of cases and
controls group, which have the following definition;
Case was pregnant women who have neonates with neonatal TSH levels in the
serum at 48 hours of life are greater than 11.2 mU / l.
Control was pregnant women who have neonates with neonatal TSH levels in the
serum at 48 hours of life are less than or equal to 11.22 mU / l.
The estimate of sample size of study is 350 which divide into 70 cases and 110
controls; this paper presented only 60% (51cases and 198 controls) of sample of study.
The study population was confirmed the cases and controls by neonatal TSH
level. The sampling frame was listed of the name of participants, 220 samples will be drawn
by random from all pregnant women.
We were collected data by questionnaire, which include characteristics of mother,
iodine tablets use during pregnancy, consumption of seafood and others food that containing
iodine consumption of iodized salt and others iodized seasoning product, and characteristics
of the neonate.
All data from questionnaires was checked for accuracy and entered into the
computer file for the analysis. After the completeness of data will find the accuracy and the
researchers develop the coding for recording data. The data analysis using SPSS software, the
statistical analysis as carried out as follows;
1. Descriptive statistics: frequency, percentage, means and standard deviation. It
can be used to describe the samples.
2. The analytic statistic: The following statistic was used;
2.1 Univariate analysis will carry out to study the association with the
single exposure variable and neonatal iodine deficiency using chi-square test and logistic
regression technique.
2.2 Multivariate analysis will carry out to study the association with many
exposure variables and neonatal iodine deficiency, controlling the confounding effect of each
variable using multiple logistic regression technique.
Results
Table 1 presents the distribution (numbers and column percentage) of cases and
controls groups by maternal factor, neonate factor and delivery factors.
Maternal factors
Maternal age at pregnancy, most of participants of cases and controls were 25-34
years 49 % and 31.1%, respectively. (P-value = 0.006)
Education, most of participant of cases and controls had the education at high
school 56.8% and 66.7%, respectively.
Family income, most of cases had the family income > 15,000 bath 41% and
controls had the family income < 10,000 bath. (p value =0.006)
History of abortion, most cases and controls did not have the history of abortion
88.2% and 92.9%, respectively.
Alcohol drink during pregnancy, most of cases and controls did not drink alcohol
(90.2%, 96%)
Gestational age at the first visit for antenatal care, most of case and control had
>12 weeks of gestational age at the first visit for antenatal care 58.8% and 73.7%,
respectively. (P-value =0.037)
Number of visit for antenatal care, most of cases and controls had number of visit
for ANC <5 times 76.5%, 73.7%, respectively.
Iodine tablet supplementation, most of cases did not took the iodine tablet
supplement 56.9% and controls group had took the iodine table supplement 84.8 (p
value<0.001)
Neonate factor
Birth Order of the neonate, most of cases had the 1st of birth order 70.6% and
controls had the other or more than 164.1%, respectively. (P-value <0.001)
Sex of neonate, most of case was male 62.7% and control was female 56.1 %.
( p value=0.017)
Preterm birth, most of cases and controls did not Preterm birth 86.3% and 89.9%,
respectively.
Birth weight, most of cases and controls had birth weight of baby between 2,5002,999 gram 47.1% and 51.5%, respectively.
Delivery Factor
Mode of delivery, most of cases and controls had vaginal delivery 88.4% and
85.4%, respectively.
Table 2 presents the distribution Odds ratio with 95% confidence intervals by
using univariate analyses. High levels of neonatal TSH at delivery (>11.2 mIU/L) were not
associated with maternal age (modeled both continuously and categorically) and birth order
of the neonate. Family income, the pregnancy who had the family income <10,000, 10,00015,499 bath had the risk to high levels of neonatal TSH two-tree times of pregnancy who had
family income > 15,000 bath (OR=2.721, CI=1.32-5.61), (OR=3.084, CI= 1.34-7.08),
respectively. Gestational age at the first visit for antenatal care, The pregnancy who had the
Gestational age at the first visit for antenatal care<12 weeks had the risk to high levels of
neonatal TSH two times of the pregnancy who had Gestational age at the first visit for
antenatal care > 12 weeks. (OR=1.97, CI= 1.04-3.73). Iodine tablet supplementation, the
pregnancy who had did not took the iodine tablet supplement had the risk to high levels of
neonatal TSH seven times of the pregnancy who had took the iodine tablet.(OR= 7.382, CI=
3.75-14.52). In addition, Sex of neonate, the pregnancy who had female neonate had the risk
to high levels of neonatal TSH two times of pregnancy who had male neonate. (OR= 2.149,
CI = 1.14-4.05).
Table 1. Number and percentage of cases and control by variable
Characteristics
Age at pregnancy
Education
Family income
Birth order of the neonate
History of abortion
Alcohol drink
Gestational age at the first
visit for antenatal care
Number of visit
for ANC
Iodine tablet
supplementation
Sex of neonate
Mode of delivery
Premature
Birth weight
case
controls
n
%
n
%
≤ 20
9
17.6
62
31.3
20-24
11
21.6
66
33.3
25-34
25
49.0
62
31.3
≥ 35
6
11.8
8
4.0
< high school
6
11.8
26
13.1
high school
29
56.8
132
66.7
>high school
16
31.4
40
20.2
<10,000฿
19
37.20
96
48.5
10,000-15,499 ฿
11
21.6
63
31.8
≥15,000฿
21
41.2
39
19.7
1 th
36
70.6
71
35.9
other
15
29.4
127
64.1
yes
6
11.8
14
7.1
no
45
88.2
184
92.9
yes
5
9.8
7
3.5
no
46
90.2
190
96.0
≥12 weeks
30
58.8
146
73.7
<12 weeks
21
41.2
52
26.3
<5 times
39
76.5
146
73.7
≥5 times
12
23.5
52
26.3
no
29
56.9
30
15.2
yes
22
43.1
168
84.8
female
19
37.3
111
56.1
male
32
62.7
87
43.9
vaginal delivery
43
84.3
169
85.4
caesarean section
8
15.7
29
14.6
yes
7
13.7
20
10.1
no
44
86.3
178
89.9
<2,500 g
5
9.8
13
6.6
2,500 - 2,999 g
24
47.1
102
51.5
3,000 - 3,499 g
14
27.4
69
34.8
≥ 3,500 g
8
15.7
14
7.1
P-value
0.006
0.233
0.006
<0.001
0.276
0.064
0.037
0.690
<0.001
0.017
0.852
0.458
0.185
Table 2. Odds ratio with 95% confidence intervals
variable
Age at pregnancy
Family income
Birth order of neonatepregnancy
Gestational age at the first visit for
antenatal care
Iodine tablet supplementation
Sex of neonate
≤ 20
20-24
25-34
≥ 35
<10,000฿
10,000-15,499 ฿
≥15,000฿
1th
Other
≥12 Weeks
<12 Weeks
No
Yes
Female
Male
Odds ratio
1.15
1.00
0.41
0.22
2.721
3.084
1.00
1.68
1.00
1.97
1.00
95%CI
0.45 - 2.96
0.19 - 0.91
0.07 - 0.77
1.32 - 5.61
1.34 - 7.08
0.90 - 3.15
1.04 - 3.73
-
7.382
1.00
2.149
1.00
3.75 - 14.52
1.14 - 4.05
-
The results of the multivariate models are shown in Table 3, presents the
distribution Odds ratio adj. with 95% confidence intervals by using multivariate analyses to
simultaneously examine the association between high levels of neonatal TSH measures and
many factors such as maternal factors, delivery factors, and infant factors. When adjust age at
pregnancy, family income, birth order of neonate, gestational age at the first visit for
antenatal care, and sex of neonate found that the pregnancy who did not take iodine tablet
supplementation had the risk to high levels of neonatal TSH seven times of pregnancy who
take the iodine tablet supplementation (adjust OR= 7.41, 95% CI: 3.33-16.53).
Table 2. Odds ratio (adj.) with 95% confidence intervals
Odds ratio (adj.)
0.38
1.00
0.39
0.21
1.60
2.61
1.00
1.60
1.00
1.49
95%CI
0.12 - 1.24
0.16 - 0.98
0.47 - 0.98
0.65 - 3.90
0.99 - 6.85
0.67 - 3.81
0.69 - 3.21
<12 Weeks
1.00
-
No
Yes
Female
Male
7.41
1.00
1.35
1.00
3.33 - 16.53
0.62 - 2.95
-
variable
Age at pregnancy
Family income
Birth order of neonate
Gestational age at the first visit
for antenatal care
Iodine tablet supplementation
Sex of neonate
≤ 20
20-24
25-34
≥ 35
<10,000฿
10,000-15,499 ฿
≥15,000฿
1th
Other
≥12 Weeks
Discussion and Conclusion
In Thailand, Iodine Deficiency Disorders (IDD) have been recognized as a
serious public health problem for over 50 years.10 Until recently, immediate measures on
prevention of iodine deficiency during pregnancy by iodine tablets supplementation; all
pregnant women must obtained iodine tablets at the time of their first visit to antenatal clinics
of the government and private health facilities since 1st October 2010 onwards, which
received during pregnancy and continuing while breastfeeding.
Maternal behavioral factors including nutrition may also impact thyroid function.
Iodine intake is among the most important nutritional factors influencing thyroid hormone
level, as it is required for thyroid hormone synthesis,11 when dietary iodine is insufficient,
compensatory mechanisms enable the thyroid gland to hoard more of the available iodine and
more efficiently reuse iodide that is released when T4 is converted to T3.12 During
pregnancy, iodine availability is especially important due to the increased demand placed on
the maternal thyroid system. It has been shown that maternal iodine deficiency is related to
higher TSH concentrations in the newborn, such that, at a population level, the cumulative
TSH shifts to the right as the severity of iodine deficiency increases.
Many studies have explored the impact of maternal iodine supplementation on
thyroid hormones and TSH at birth, mostly in the context of public health programs to
provide iodine supplementation. The result of this study was The use of iodine tablet during
pregnancy in the prevention of iodine deficiency is the solution adopted by normal TSH
concentrations level, which concordantly the Rebagliato M. study13 found that there was an
increased risk of TSH above 3 µU/l in women who consumed 200 µg or more of iodine
supplements daily compared with those who consumed less than 100 µg/day (adjusted odds
ratio = 2.5 (95% confidence interval = 1.2 to 5.4)) and Rajatanavin R. study14 found that a
low concentration of iodine in the urine of a rural mother was associated with a five-fold
greater chance of her neonate having a serum TSH concentration higher than neonates born in
Bangkok, concordantly
this studyThe use of iodine tablet during pregnancy in the
prevention of iodine deficiency is the solution adopted by normal TSH concentrations level.
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