CE: ; MED/30507; Total nos of Pages: 8;

MED 30507

REVIEW

CURRENT
OPINION An update: maternal iodine supplementation,
thyroid function tests, and child
neurodevelopmental outcomes
Caroline T. Nguyen

Purpose of review
The impact of maternal iodine supplementation (MIS) during pregnancy on thyroid function and child
neurodevelopmental outcomes in areas of mild-to-moderate iodine deficiency (MMID) remains unclear.
Recent findings
Despite growing success of salt iodization programs, a 2022 meta-analysis found that 53% of pregnant
patients worldwide continue to have insufficient iodine intake during pregnancy. A 2021 randomized
controlled trial (RCT) found that MIS in women with mild iodine deficiency led to iodine sufficiency and
positive effects on maternal thyroglobulin. A 2021 cohort study of MIS initiated prior to pregnancy was
associated with lower thyroid-stimulating hormone (TSH), higher FT3, and FT4. Other cohort studies,
however, found that neither salt iodization nor MIS were adequate to meet pregnancy iodine needs. Data
have been mixed regarding maternal iodine status and pregnancy outcomes in patients of MMID. Meta-
analyses have not shown any clear benefit on infant neurocognitive outcomes with MIS of MMID patients.
A 2023 meta-analysis found that the prevalence of excess iodine intake in pregnancy was 52%.
Summary
MMID continues to exist during pregnancy. Salt iodization alone may be insufficient to ensure adequate
iodine status during pregnancy. There is an absence of high-quality data to support routine MIS in areas of
MMID. However, patients with specialized diets (vegan, nondairy, no seafood, noniodized salt, and so on)
may be at risk for inadequate iodine status in pregnancy. Excess iodine intake can be detrimental to the
fetus and should be avoided during pregnancy.
Keywords
iodine, neurodevelopmental, pregnancy, supplementation, thyroid

INTRODUCTION [2] as well as child neurodevelopmental outcomes

It is well accepted that severe iodine deficiency can
have detrimental effects on maternal and fetal
&
health [1 ,2]. Severe iodine deficiency during critical
phases of development leads to cretinism, charac-
terized by severe intellectual impairment and devel-
opmental delays [3–6]. Today, cretinism is rare
because of successful salt iodization programs
worldwide [7]. As of 2020, 118 countries had
adequate iodine intake as measured by urinary
iodine concentration (UIC) of school-aged children,
almost double the number from 2003 [8]. Never-
theless, mild-moderate iodine deficiency (MMID)
continues to exist in pregnancy throughout the
world, including in the USA, Australia, and two-
thirds of European countries that monitor iodine
in pregnancy [9–11].
MMID has been associated with an increased
risk for development of goiter and thyroid disorders
including executive function, intelligence quotient
(IQ), school performance, verbal and math skills,
and attention-deficit and hyperactive disorders [12–
18]. However, the data remain conflicting [19]. This
article aims to review the recent literature evaluating
maternal iodine supplementation (MIS) in areas of
MMID during pregnancy and its effect on thyroid
function and child neurodevelopment.
Departments of Clinical Medicine, Obstetrics, and Gynecology, Division
of Endocrinology, Metabolism, and Diabetes, Keck School of Medicine,
University of Southern California, Los Angeles, California, USA
Correspondence to Caroline T. Nguyen, MD, USC Keck School of
Medicine, University of Southern California, Keck School of Medicine,
Los Angeles, CA 90033, USA. Tel: +1 (323) 442-6179;
e-mail: caroline.nguyen@med.usc.edu
Curr Opin Endocrinol Diabetes Obes 2023, 30:000–000
DOI:10.1097/MED.0000000000000824

1752-296X Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved. www.co-endocrinology.com

Copyright © 2023 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
CE: ; MED/30507; Total nos of Pages: 8;
MED 30507

Thyroid

Table 1. Iodine intake based on urinary iodine

KEY POINTS
concentration [100]
 Iodized salt programs worldwide have had a Median urinary iodine concentration (mg/l) Iodine intake
significant impact in the reduction of severe iodine
deficiency (SID) in pregnancy. Pregnancy

 Pregnancy continues to be a time of mild-to-moderate <150 Insufficient

iodine deficiency (MMID) in countries with adequate 150--249 Adequate
iodine (I) status outside of pregnancy, including 250--499 Above requirements
the USA.
>500 Excessive
 The effect of MMID on thyroid function and perinatal Lactating patientsa
outcomes remain unclear, along with the efficacy of
maternal iodine supplementation (MIS) during <100 Insufficient
pregnancy in MMID areas. >100 Adequate

 The American Thyroid Association (ATA) and European a

Thyroid Association (ETA) recommend supplementing
with 150 mg I/day during pregnancy and in the
preconception period. However, there is no consensus
among professional organizations regarding routine
iodine supplementation in pregnancy in areas
of MMID.
 Those consuming plant-based, vegan, nondairy,
nonseafood, or noniodized salt diets may be especially
at risk for I deficiency in pregnancy.
 Excess I intake during pregnancy can be detrimental for
the fetus and should be avoided.
IODINE PHYSIOLOGY AND INTAKE
Iodine is essential in thyroid hormone production
and must come from our diet or supplementation.
Most individuals in the USA and Europe maintain
adequate iodine in their diet by use of iodized salt
and consuming foods high in iodine such as shell-
&
fish and dairy products [20 ]. Iodine requirements
increase during pregnancy because of increased glo-
merular filtration rate and urinary iodide loss [21],
increased thyroid hormone requirements of 30–50%
[22], and increased fetal iodine requirements [23].
Iodine sources for the fetus include food, maternal
endogenous thyroid hormone, or levothyroxine
tablets. Patients being treated for hyperthyroidism
or taking levothyroxine in preconception and preg-
nancy do not require iodine supplementation [2,24].
Mothers who are breastfeeding have increased daily
iodine requirements as iodine is secreted into breast
milk [25].
Measuring iodine status
Much of the iodine in the human body is within the
thyroid gland. However, 90% of iodine is excreted in
the urine. Therefore, iodine status is generally
assessed at the population level using spot UIC,
which has been demonstrated to approximate
Daily I requirements are increased in lactating mothers, but median UIC is
lower than during pregnancy because I excretion in the breastmilk.
24-h UIC [26]. Iodine to creatinine ratios (I:Cr) have
also been used in some studies. However, neither
spot or 24-h UIC is valid in individuals due to day-
to-day and diurnal variation in urinary iodine excre-
tion [27]. The WHO considers a median UIC of 150–
249 mg/l in a population reflective of adequate
iodine intake in pregnancy (Table 1) [100]. Severity
of iodine deficiency of a population is based
on median UIC of school-aged children, but these
criteria do not apply to pregnant and lactating
mothers (Table 2).
Is salt iodization sufficient?
Studies have shown salt iodization to be sufficient
[28–30] as well as insufficient [31–33] in achieving
adequate iodine status in pregnant patients. A 2022
systemic review and meta-analysis of 163 021 preg-
nant patients found overall prevalence of insuffi-
cient iodine intake of 53% [95% confidence interval
(95% CI): 47–60; I(2) ¼ 99.8%] despite progress in
Table 2. Iodine nutrition based on urinary iodine
concentration of school-aged children
Median urinary I (mg/l) Iodine status
<20 Severe iodine deficiency
20--49 Moderate iodine deficiency
50--99 Mild iodine deficiency
100--199 Adequate iodine nutrition
200--299 Likely adequate for pregnant and
lactating women, but may be more
than adequate for general
population
>300 Risk of adverse health consequences
In the absence of high-quality interventional data, there is no consensus
amongst professional organizations regarding routine iodine supplementation
in pregnancy.

2 www.co-endocrinology.com Volume 30  Number 00  Month 2023

Copyright © 2023 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
CE: ; MED/30507; Total nos of Pages: 8;
MED 30507
&
salt iodization policies [34 ]. An observational study
found that MIS along with salt iodization helped
improve UIC in pregnancy compared with salt iod-
ization alone or neither. However, patients
remained MMID with UIC 121.2, 76.3, and
52.2 mg/l, respectively [35]. A study of 2144 patients
in China reported that salt iodization, iodine-rich
food, and MIS were needed to meet iodine needs in
&
pregnancy [36 ]. Data regarding iodine intake in
& In the absence of high-quality interventional data, there is no consensus
pregnancy are lacking [20 ] and 40% of prenatal
vitamins do not contain any iodine [37].
Current recommendations
Currently, the WHO [25] and the National Academy
of Medicine [38] recommend 250 and 220 mg of
iodine daily during pregnancy, respectively
(Table 3). The American Thyroid Association
(ATA) [2] and European Thyroid Association (ETA)
[39] recommend supplementing with 150 mg
iodine/day during pregnancy and in the preconcep-
tion period. The American Congress of Obstetricians
and Gynecologists (ACOG) recommends 220 mg of
iodine daily, but notes that the role of routine MIS
in MMID is not clearly established [40,41] (Table 4).
IODINE AND THYROID FUNCTION
Studies evaluating the effect of iodine intake and
supplementation during pregnancy on maternal
and newborn thyroid function tests (TFTs) have
varying results. Several studies show beneficial effect
on one TFT, but not another [42–45] or on thyroid
volume but not on TFTs [46,47]. More recent studies
have added to the growing body of data but have not
brought clarity.
Iodine status, thyroid function tests, and
urinary iodine concentration
A 2022 observational study in China compared
pregnant patients in a MMID area to an iodine-
sufficient area and found that thyroid-stimulating
hormone (TSH) and FT3 were lower, but FT4 was
higher in the MMID area [48]. In a 2022 observa-
tional study in Turkey in a marginally iodine
Table 3. Daily iodine recommendations in pregnancy (mg)
WHO [25] National Academy of Medicine [38]
Pregnancy 250 220
Lactating 250 290
Iodine requirements increase in pregnancy due to increase urinary iodide loss
and increase iodine and thyroid hormone requirements by mother and fetus
and during lactation due to increased iodine loss in the breastmilk.
1752-296X Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2023 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
An update Nguyen
Table 4. Daily maternal iodine supplementation
recommendations in pregnancy (mg)
American Thyroid Association (ATA) [2] 150 mg
European Thyroid Association (ETA) [39] 150 mg
The American Congress of Obstetricians and No
Gynecologists (ACOG) [40]
recommendation
among professional organizations regarding routine iodine supplementation
in pregnancy.
sufficient population, UIC decreased throughout
pregnancy with a concomitant increase in TSH,
which remained within normal limits, but was
associated with a decrease in T3 and T4 [49]. A
2021 observational study in an iodine-sufficient
population in rural China found a similar decrease
in UIC and T3 throughout pregnancy, but a
U-shaped curve with TSH [50], while a 2020 obser-
vational study in South Africa with a salt iodization
program in place found an increase in UIC through-
out pregnancy [51].
Maternal iodine supplementation, iodine
intake, and thyroid function tests
A 2021 observational study in China comparing
women who took iodine supplements in preconcep-
tion and pregnancy to those who did not find a
&&
positive effect on maternal T4 [52 ]. An observatio-
nal study in Norway in a MMID area found MIS
started in the preconception period had a similar
beneficial effect with lower TSH and higher T3, T4
&
[53 ]. An RCT of 200 pregnant patients with MMID
in Sweden found MIS to have a positive effect on
maternal thyroglobulin and UIC, but not TSH or T4
&&
[54 ]. A 2021 observational study of 246 pregnant
patients who had MMID in the UK found that total
iodine intake was associated with lower thyroglo-
bulin and higher UIC [55]. However, a 2022 study of
4848 pregnant patients in China found that iodized
salt in cooking was not related to thyroid function
[33]. A 2020 systematic review and meta-analysis of
studies in MMID areas found MIS had no effect on
maternal and infant TFTs but did reduce maternal
thyroglobulin and thyroid volume in pregnancy
[56]. A 2021 systematic review and meta-analysis
on 14 trials over the last three decades showed
inconsistent results regarding maternal TSH and
thyroid volume with MIS. Most trials reported no
&&
effect on other maternal TFTs [57 ].
Timing of iodine supplementation may be of
importance [58]. An interventional study that eval-
uated MIS beginning 3 months preconception
www.co-endocrinology.com 3
CE: ; MED/30507; Total nos of Pages: 8;
MED 30507
Thyroid
compared with 12 weeks’ gestation found those
supplemented prior to pregnancy had higher UIC
[59]. A meta-analysis [56] of two RCTs [42,60] in
which 200–225 mg iodine per day administered
from the first trimester showed a significantly lower
median TSH in the iodine group compared with
placebo. Three prospective cohort studies in Italy
found lower TSH in those who started iodized salt
greater than 2 years preconception compared with
those who started in pregnancy, those who did not
use iodized salt in pregnancy, or those who took
daily 150 mg iodine supplement [35,61,62].
Maternal iodine supplementation and
newborn thyroid function
The limited studies evaluating newborn thyroid
function have also had conflicting results. Some
studies have reported positive effects of MIS with
newborn UIC, TFTs, and thyroid volume [43,45].
Other studies have not found a relationship between
iodine and newborn TSH [63,64]. Interestingly, an
observational study in China found an association
between maternal TSH and neonatal TSH, with
declining neonatal TSH with MIS, but only in
patients with thyroid-peroxidase antibody (TPOAb)
negativity. This finding was not seen in those who
were TPOAb positive, suggesting that TPOAb status
may have impaired iodine transport in the thyroid
&&
and placenta [52 ]. An RCT evaluating MIS found
no effect on offspring thyroid volume or cord blood
TSH [28]. A 2017 Cochrane Review including 14
studies with 11 trials involving over 2700 patients
evaluating MIS in areas of MMID found that MIS
decreased the likelihood of maternal postpartum
hyperthyroidism by 68%, but there was no differ-
ence in maternal or neonatal hypothyroidism [65].
A 2021 systematic review and meta-analysis found
five of six trials showed improvement in UIC of
infants associated with MIS. However, seven of eight
trials did not find any significant difference in neo-
natal TSH between the intervention and control
groups. No trials reported an effect of MIS on other
neonatal TFTs. Two of four trials found significant
increase in thyroglobulin concentration in cord
blood of neonates born to mothers not taking
MIS. Two of three studies found smaller thyroid
gland size in infants of mothers with MIS compared
&&
to those of nonsupplemented [57 ].
IODINE AND PREGNANCY OUTCOMES
Data regarding MMID and pregnancy outcomes
have also been conflicting. A large 2020 observatio-
nal study from Norway found that those with MIS
had reduced risk of preeclampsia and increased fetal
4 www.co-endocrinology.com
Copyright © 2023 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
growth [66]. Findings from another 2020 observatio-
nal study from Tehran showed higher risk of preterm
birth in those with deficient UIC and TSH at least
4 mIU/ml [67]. However, two other large observatio-
nal studies did not find worse pregnancy outcomes
associated with MMID [68,69]. A 2023 review of four
meta-analysis (MAs) [17,70–72] evaluating the rela-
tionship between iodine status and pregnancy and
neonatal outcomes suggests a U-shaped correlation
between iodine status and maternal and neonatal
&&
consequences [73 ]. The same review of three MAs
&&
[56,57 ,65] evaluating intervention trials did not
provide a clear conclusion on the benefit of MIS in
pregnant women in areas with MMID in regards to
maternal and neonatal outcomes [73 ].
&&
IODINE AND CHILD
NEURODEVELOPMENTAL OUTCOMES
Iodine deficiency during pregnancy affects offspring
cognition via thyroid hormone production. Both
severe iodine deficiency and MMID have been asso-
ciated with adverse neurodevelopmental outcomes.
However, the effect of MIS on neurodevelopmental
outcomes in areas of MMID remains unclear.
Iodine intake and child neurodevelopmental
outcomes
A 2017 Norwegian observational study in a MMID
population found that low iodine intake from diet
was associated with offspring language delay, behav-
ioral problems, and fine motor skills at age three, but
MIS did not affect outcomes [12]. A 2022 observa-
tional study in Japan evaluated iodine intake
through diet along with kelp and seaweed in a
marginally iodine-sufficient population and found
an increased risk for delay in communication, fine
motor, and problem solving at 1 and 3 years of age in
those with the lower quintile for intake compared
with those with the highest [74]. However, an obser-
vational study in India did not find an association
between maternal UIC and mental and motor devel-
opment, although in an iodine-sufficient popula-
tion [75]. Nevertheless, a 2021 study in the UK in a
MMID population also did not find an association
with adverse neurodevelopmental outcomes of off-
spring [55].
Maternal iodine supplementation and child
neurodevelopmental outcomes
Two older RCTs evaluating MIS in Spain reported
some benefit to cognition. In the first, neurodevel-
opment was assessed at 18 months of age in 440
pregnant patients supplemented with 200 mg iodine
Volume 30  Number 00  Month 2023
CE: ; MED/30507; Total nos of Pages: 8;
MED 30507
daily, begun at gestational week 4–6, 12–14, or at
term with the earliest supplementation resulting in
higher offspring neurodevelopmental scores [15]. In
the second study, children of pregnant patients
supplemented with 300 mg iodine daily had behav-
ior assessments in better agreement with their age.
However, those who were supplemented were
assessed at age 5.5 months, while those who were
not supplemented were assessed at 12.4 months of
age [76].
An RCT in Spain evaluating cognition at
12.8 months found a significant benefit with MIS.
However, significance disappeared when adjusted
for gestational age at birth [28]. An RCT in India
and Thailand with 200 mg iodine daily in a popula-
tion considered MMID (UIC 131 mg/l) found no
difference in cognition when assessed at 6 weeks
and at 5.4 years of age [60]. A meta-analysis of this
study along with a second RCT [77] that had similar
design with 150–200 mg potassium iodide tablets
daily administered from early pregnancy compared
with placebo using the same cognitive assessment
tool to assess children at a similar age of 1.5–2 years
showed no effect of MIS compared with placebo on
child cognitive, language, or motor scores [56].
A 2021 systematic review evaluating three RCTs
[60,77,78] and one nonrandomized trial [76] and
four observational cohorts [77–80] found no signifi-
cant improvement in children’s mental develop-
ment index and behavioral development index in
the supplemented group [81]. Psychomotor devel-
opment index showed improvement in the poorer
gross motor skills and differences in response time
to sound in the supplemented group [81]. A 2021
meta-analysis of three trials [60,77,82] found no
differences observed in cognitive, language, or
motor development and did not demonstrate any
clear benefit on infant neurocognitive outcomes
&&
with MIS of MMID patients [57 ].
Complications associated with excessive
iodine consumption
Both hypo-and hyperthyroidism can occur in preg-
nancy due to excess iodine [83]. The sodium-iodide
symporter (NIS) transports excess iodine into the
thyroid, resulting in transient inhibition of TPO and
a decrease in thyroid hormone synthesis, known as
the Wolff-Chaikoff effect (WCE) [84]. With contin-
ued exposure, there is a decrease in NIS expression
resulting in decreased iodine transport and resump-
tion of thyroid hormone synthesis, referred to as
escape from the WCE. Failure of the WCE leads to
iodine-induced hyperthyroidism, typically seen in
patients with nodular goiter. Patients with thyroid
autoimmunity may not escape from the WCE
1752-296X Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2023 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
An update Nguyen
leading to iodine-induced hypothyroidism. Fetuses
do not develop the ability to escape from the WCE
until around 36 weeks’ gestation and are at an
increased risk for development of fetal hypothyroid-
ism and goiter [85,86].
UIC more than 250 mg/l has been associated
with an increased risk of hypothyroxinemia and
subclinical hypothyroidism [87,88]. Maternal hypo-
thyroxinemia in pregnancy has been associated
with decreased psychomotor and language delay,
lower IQ, increased risk of autism in offspring
[89,90]. Subclinical hypothyroidism is associated
with miscarriage, gestational hypertension, prema-
ture delivery, and neuropsychological development
[91–94]. A 2023 systematic review and meta-analy-
sis reported a prevalence of excessive iodine intake
in pregnancy of 52% with associated maternal thy-
roid dysfunction noted, including subclinical hypo-
thyroidism, subclinical and overt hyperthyroidism,
and hypothyroxinemia as well as newborn macro-
&&
somia and thyroid dysfunction [95 ].
Excess iodine has also been associated with
adverse fetal neurodevelopment. UIC below and
above 150 mg/l has been associated with an increased
risk for language delay [12]. Children of mothers with
lowest and highest quartile iodine intake had lower
cognitive, language, and motor scores at 18 months,
greater odds of developmental delay, and smaller
&&
total gray matter [13,96 ]. A recent large study of
1530 children found a trend toward low verbal IQ in
offspring whose mothers had UIC at least 500 mg/l
[97 ]. MIS at least 150 mg/day compared with less
&
than 100 mg/day was associated with reduced psycho-
motor scores [80]. However, a recent study in Korea
of 349 pregnant patients with median dietary iodine
intake of 459 mg/day found no relationship to mater-
nal thyroid function or neonatal outcomes [98].
Populations that have historically and consistently
consumed high daily iodine intake may be excep-
tions [99]. The ATA recommends against exceeding
500 mg iodine per day from diet and supplements
during pregnancy [2].
CONCLUSION
Iodine deficiency is the leading cause of preventable
intellectual deficits worldwide. With global health
initiatives and universal salt iodization programs,
iodine deficiency disorders such as cretinism are
now rare. However, the efficacy of MIS in areas of
MMID remains unclear in the absence of high-qual-
ity evidence. Inconsistences in study results may be
secondary to variation in maternal prepregnancy
and baseline iodine status, dose and form of iodine
supplementation, timing of supplementation, tim-
ing of laboratory testing, differences in cognitive
www.co-endocrinology.com 5
CE: ; MED/30507; Total nos of Pages: 8;
MED 30507
Thyroid
tests used to assess child neurodevelopment, and
age of assessment. Well designed RCTs are needed
but may not be feasible in areas wherein iodine
supplementation is already common.
With persistent MMID in pregnancy, the ATA
and ETA recommends MIS with 150 mg iodine daily.
However, no consensus between professional organ-
izations regarding routine MIS in MMID areas exists
due to the lack of high-quality data. Although
assessing iodine levels in individuals is not reliable
or recommended, physicians should assess patients
for risk of iodine deficiency during preconception
counseling, pregnancy, and lactation. In addition to
patients from areas of iodine deficiency, patients
who have restricted diets (i.e., vegan, nondairy, or
solely noniodized salt) may also be at an increased
risk for iodine deficiency. Timing of iodine supple-
mentation or iodized salt may be important with
earlier initiation associated with greater benefit. The
ATA recommends beginning MIS 3 months prior to
conception. Excess iodine supplementation can be
detrimental for the fetus and offspring and should
be avoided.
Acknowledgements
None.
Financial support and sponsorship
None.
Conflicts of interest
There are no conflicts of interest.
REFERENCES AND RECOMMENDED
READING
Papers of particular interest, published within the annual period of review, have
been highlighted as:
& of special interest
&& of outstanding interest
1. Pearce EN, Zimmermann MB. The prevention of iodine deficiency: a history.
& Thyroid 2023; 33:143–149.
An overview of critical scientifc discoveries and advances in public health nutrition
related to the prevention of iodine deficiency disorders in the United States and
worldwide.
2. Alexander EK, Pearce EN, Brent GA, et al. 2017 Guidelines of the American
Thyroid Association for the Diagnosis and Management of Thyroid Disease
During Pregnancy and the Postpartum. Thyroid 2017; 27:315–389.
3. Cao XY, Jiang XM, Dou ZH, et al. Timing of vulnerability of the brain to iodine
deficiency in endemic cretinism. N Engl J Med 1994; 331:1739–1744.
4. Pharoah P, Buttfield IH, Hetzel BS. Neurological damage to the fetus
resulting from severe iodine deficiency during pregnancy. Int J Epidemiol
2012; 41:589–592.
5. Thilly CH, Delange F, Lagasse R, et al. Fetal hypothyroidism and maternal
thyroid status in severe endemic goiter. J Clin Endocrinol Metab 1978;
47:354–360.
6. Toloza FJK, Motahari H, Maraka S. Consequences of severe iodine deficiency in
pregnancy: evidence in humans. Front Endocrinol (Lausanne) 2020; 11:409.
7. Chen ZP, Hetzel BS. Cretinism revisited. Best Pract Res Clin Endocrinol
Metab 2010; 24:39–50.
8. Zimmermann MB, Andersson M. Global endocrinology: Global perspectives
in endocrinology: coverage of iodized salt programs and iodine status in
2020. Eur J Endocrinol 2021; 185:R13–R21.
9. Zimmermann MB, Gizak M, Abbott K, et al. Iodine deficiency in pregnant
women in Europe. Lancet Diabetes Endocrinol 2015; 3:672–674.
6 www.co-endocrinology.com
Copyright © 2023 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
10. Gizak M. Moving toward optimal iodine status. Iodine Global Network 2016;
http://www.ign.org/newsletter/idd_nov16_global_scorecard_2016.pdf.
11. Caldwell KL, Pan Y, Mortensen ME, et al. Iodine status in pregnant women in the
National Children’s Study and in U.S. women (15-44 years), National Health
and Nutrition Examination Survey 2005–2010. Thyroid 2013; 23:927–937.
12. Abel MH, Caspersen IH, Meltzer HM, et al. Suboptimal maternal iodine
intake is associated with impaired child neurodevelopment at 3 years of age
in the Norwegian Mother and Child Cohort Study. J Nutr 2017;
147:1314–1324.
13. Zhou SJ, Condo D, Ryan P, et al. Association between maternal iodine intake
in pregnancy and childhood neurodevelopment at age 18 months. Am J
Epidemiol 2019; 188:332–338.
14. Hynes KL, Otahal P, Hay I, Burgess JR. Mild iodine deficiency during
pregnancy is associated with reduced educational outcomes in the offspring:
9-year follow-up of the gestational iodine cohort. J Clin Endocrinol Metab
2013; 98:1954–1962.
15. Berbel P, Mestre JL, Santamaria A, et al. Delayed neurobehavioral develop-
ment in children born to pregnant women with mild hypothyroxinemia during
the first month of gestation: the importance of early iodine supplementation.
Thyroid 2009; 19:511–519.
16. Bath SC, Steer CD, Golding J, et al. Effect of inadequate iodine status in UK
pregnant women on cognitive outcomes in their children: results from the
Avon Longitudinal Study of Parents and Children (ALSPAC). Lancet 2013;
382:331–337.
17. Levie D, Korevaar TIM, Bath SC, et al. Association of maternal iodine status
with child IQ: a meta-analysis of individual participant data. J Clin Endocrinol
Metab 2019; 104:5957–5967.
18. Abel MH, Ystrom E, Caspersen IH, et al. Maternal iodine intake and offspring
attention-deficit/hyperactivity disorder: results from a large prospective co-
hort study. Nutrients 2017; 9:1239.
19. Monaghan AM, Mulhern MS, McSorley EM, et al. Associations between
maternal urinary iodine assessment, dietary iodine intakes and neurodeve-
lopmental outcomes in the child: a systematic review. Thyroid Res 2021;
14:14.
20. Bath SC, Verkaik-Kloosterman J, Sabatier M, et al. A systematic review of
& iodine intake in children, adults, and pregnant women in Europe-comparison
against dietary recommendations and evaluation of dietary iodine sources.
Nutr Rev 2022; 80:2154–2177.
A systematic review of 57 studies comprising 22 national surveys and 35 sub-
national studies evaluating iodine intake data in Europe. Just 32% of national
surveys included iodized salt when estimating iodine intake. Milk, dairy products,
fish, and eggs were important contributors to intake in many countries, suggesting
limited sources in plant-based diets.
21. Okosieme OE, Khan I, Taylor PN. Preconception management of thyroid
dysfunction. Clin Endocrinol (Oxf) 2018; 89:269–279.
22. Alexander EK, Marqusee E, Lawrence J, et al. Timing and magnitude of
increases in levothyroxine requirements during pregnancy in women with
hypothyroidism. N Engl J Med 2004; 351:241–249.
23. Glinoer D. The importance of iodine nutrition during pregnancy. Public Health
Nutr 2007; 10:1542–1546.
24. Jastrzebska H, Kochman M, Bartoszewicz Z, et al. Iodine supplementation
during pregnancy of hypothyroid women treated with L-thyroxine neither
influences neonatal TSH nor prevents decrease in maternal free thyroid
hormone concentrations in second and third trimesters. Endokrynol Pol
2016; 67:367–374.
25. Secretariat WHO, Andersson M, de Benoist B, et al. Prevention and control
of iodine deficiency in pregnant and lactating women and in children less than
2-years-old: conclusions and recommendations of the Technical Consulta-
tion. Public Health Nutr 2007; 10:1606–1611.
26. Perrine CG, Cogswell ME, Swanson CA, et al. Comparison of population
iodine estimates from 24-h urine and timed-spot urine samples. Thyroid
2014; 24:748–757.
27. Konig F, Andersson M, Hotz K, et al. Ten repeat collections for urinary iodine
from spot samples or 24-h samples are needed to reliably estimate individual
iodine status in women. J Nutr 2011; 141:2049–2054.
28. Santiago P, Velasco I, Muela JA, et al. Infant neurocognitive development is
independent of the use of iodised salt or iodine supplements given during
pregnancy. Br J Nutr 2013; 110:831–839.
29. Gonzalez-Martinez S, Riestra-Fernandez M, Martinez-Morillo E, et al. Nutri-
tional iodine status in pregnant women from Health Area IV in Asturias
(Spain): iodised salt is enough. Nutrients 2021; 13:.
30. Jaiswal N, Melse-Boonstra A, Sharma SK, et al. The iodized salt programme
in Bangalore, India provides adequate iodine intakes in pregnant women and
more-than-adequate iodine intakes in their children. Public Health Nutr 2015;
18:403–413.
31. Wang Z, Zhu W, Mo Z, et al. An increase in consuming adequately iodized
salt may not be enough to rectify iodine deficiency in pregnancy in an iodine-
sufficient area of China. Int J Environ Res Public Health 2017; 14:.
32. Apaydin M, Demirci T, Ozdemir Baser O, et al. The effects of salt consump-
tion habits on iodine status and thyroid functions during pregnancy. Turk J
Med Sci 2021; 51:766–771.
33. Cui Y, Wang Y, Hou C, et al. Iodine in household cooking salt no longer plays
a crucial role in iodine status of residents in Tianjin, China. Eur J Nutr 2022;
61:2435–2449.
Volume 30  Number 00  Month 2023
CE: ; MED/30507; Total nos of Pages: 8;
MED 30507
34. Patriota ESO, Lima ICC, Nilson EAF, et al. Prevalence of insufficient iodine
& intake in pregnancy worldwide: a systematic review and meta-analysis. Eur J
Clin Nutr 2022; 76:703–715.
An extensive evaluation of 61 studies and 163 021 pregnant women reports a
prevalence of insufficient iodine intake was 53% [95% CI: 47–60; I(2) ¼ 99.8%]
with higher prevalence in areas of inadequate iodine status.
35. Moleti M, Di Bella B, Giorgianni G, et al. Maternal thyroid function in different
conditions of iodine nutrition in pregnant women exposed to mild-moderate
iodine deficiency: an observational study. Clin Endocrinol (Oxf) 2011;
74:762–768.
36. Sun R, Fan L, Du Y, et al. The relationship between different iodine sources
& and nutrition in pregnant women and adults. Front Endocrinol (Lausanne)
2022; 13:924990.
A study of 2145 pregnant women found that iodized salt, iodine-rich food, and
iodine supplements were needed to meet the I needs of pregnancy.
37. Patel A, Lee SY, Stagnaro-Green A, et al. Iodine content of the best-selling
United States Adult and Prenatal Multivitamin Preparations. Thyroid 2019;
29:124–127.
38. Institute of Medicine FaNB. Dietary reference intakes for Vitamin A, Vitamin K,
Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum,
Nickel, Silicon, Vanadium, and Zinc. Washington, DC: National Academy
Press. 2001.
39. Lazarus J, Brown RS, Daumerie C, et al. 2014 European thyroid association
guidelines for the management of subclinical hypothyroidism in pregnancy
and in children. Eur Thyroid J 2014; 3:76–94.
40. Thyroid Disease in Pregnancy: ACOG Practice Bulletin, Number 223.
Obstet Gynecol 2020; 135:e261–e274.
41. Taylor PN, Okosieme OE, Dayan CM, Lazarus JH. Therapy of endocrine disease:
impact of iodine supplementation in mild-to-moderate iodine deficiency: sys-
tematic review and meta-analysis. Eur J Endocrinol 2014; 170:R1–R15.
42. Censi S, Watutantrige-Fernando S, Groccia G, et al. The effects of iodine
supplementation in pregnancy on iodine status, thyroglobulin levels and
thyroid function parameters: results from a randomized controlled clinical
trial in a mild-to-moderate iodine deficiency area. Nutrients 2019; 11:.
43. Nohr SB, Jorgensen A, Pedersen KM, Laurberg P. Postpartum thyroid
dysfunction in pregnant thyroid peroxidase antibody-positive women living
in an area with mild to moderate iodine deficiency: is iodine supplementation
safe? J Clin Endocrinol Metab 2000; 85:3191–3198.
44. Nohr SB, Laurberg P. Opposite variations in maternal and neonatal thyroid
function induced by iodine supplementation during pregnancy. J Clin En-
docrinol Metab 2000; 85:623–627.
45. Glinoer D, De Nayer P, Delange F, et al. A randomized trial for the treatment of
mild iodine deficiency during pregnancy: maternal and neonatal effects. J Clin
Endocrinol Metab 1995; 80:258–269.
46. Antonangeli L, Maccherini D, Cavaliere R, et al. Comparison of two different
doses of iodide in the prevention of gestational goiter in marginal iodine
deficiency: a longitudinal study. Eur J Endocrinol 2002; 147:29–34.
47. Romano R, Jannini EA, Pepe M, et al. The effects of iodoprophylaxis on
thyroid size during pregnancy. Am J Obstet Gynecol 1991; 164:482–485.
48. Chen Y, Guo W, Pan Z, et al. Exploration of the optimal range of urinary iodine
concentration in Chinese pregnant women in mildly iodine-deficient and
-sufficient areas. Eur J Nutr 2022; 61:1221–1230.
49. Kose Aktas A, Gokcay Canpolat A, Aydin U, et al. Intensifying iodine deficiency
throughout trimesters of pregnancy in a borderline iodine-sufficient urban area,
Ankara, Turkey. Biol Trace Elem Res 2022; 200:2667–2672.
50. Wang Y, Zhang Z, Chen F, et al. Iodine nutrition status and thyroid function of
women at different phases of gestation in an iodine sufficient rural area. Asia
Pac J Clin Nutr 2021; 30:99–103.
51. Siro SS, Zandberg L, Ngounda J, et al. Iodine status of pregnant women living
in urban Johannesburg, South Africa. Matern Child Nutr 2022; 18:e13236.
52. Guo F, Liu Y, Ding Z, et al. Supplemental iodine-containing prenatal multi-
&& vitamins use and the potential effects on pregnancy outcomes in a mildly
iodine-deficient region. J Endocrinol Invest 2021; 44:443–452.
First study to investigate the efficiency of iodine-containing supplements in mildly
iodine-deficient pregnant women based on different TPOAb status. Association of
maternal TSH with neonatal TSH only in TPO Ab negative women with reduction in
neonatal TSH with I supplementation.
53. Naess S, Markhus MW, Strand TA, et al. Iodine nutrition and iodine supplement
& initiation in Association with thyroid function in mildly-to-moderately iodine-
deficient pregnant and postpartum women. J Nutr 2021; 151:3187–3196.
A cohort study of 137 pregnant women that found that iodine-containing supple-
ment initiated prepregnancy and continuing through pregnancy was associated
with lower TSH, and higher fT3 and fT4 concentrations, which may suggest
improved thyroid function. These findings support the notion that optimization of
iodine intake should start before pregnancy.
54. Manousou S, Eggertsen R, Hulthen L, Filipsson Nystrom H. A randomized,
&& double-blind study of iodine supplementation during pregnancy in Sweden:
pilot evaluation of maternal iodine status and thyroid function. Eur J Nutr
2021; 60:3411–3422.
An RCT evaluating intervention of daily supplement containing 150 mug of iodine
to a group of pregnant women with mild iodine deficiency found improved iodine
status from mild ID to iodine sufficiency and a positive impact on maternal
thyroglobulin.
1752-296X Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2023 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
An update Nguyen
55. Threapleton DE, Waiblinger D, Snart CJP, et al. Prenatal and postpartum
maternal iodide intake from diet and supplements, urinary iodine and thyroid
hormone concentrations in a region of the United Kingdom with mild-to-
moderate iodine deficiency. Nutrients 2021; 13:230.
56. Dineva M, Fishpool H, Rayman MP, et al. Systematic review and meta-
analysis of the effects of iodine supplementation on thyroid function and child
neurodevelopment in mildly-to-moderately iodine-deficient pregnant women.
Am J Clin Nutr 2020; 112:389–412.
57. Nazeri P, Shariat M, Azizi F. Effects of iodine supplementation during
&& pregnancy on pregnant women and their offspring: a systematic review
and meta-analysis of trials over the past 3 decades. Eur J Endocrinol 2021;
184:91–106.
A systematic review of studies over the past three decades found iodine
supplementation during pregnancy can improve iodine status in pregnant
women and their offspring but meta-analysis did not show evidence of improved
growth or neurodevelopmental outcomes in infants of iodine-supplemented
mothers.
58. Liberman CS, Pino SC, Fang SL, et al. Circulating iodide concentrations
during and after pregnancy. J Clin Endocrinol Metab 1998; 83:3545–3549.
59. Young AE, Kemp JF, Uhlson C, et al. Improved first trimester maternal iodine
status with preconception supplementation: the Women First Trial. Matern
Child Nutr 2021; 17:e13204.
60. Gowachirapant S, Jaiswal N, Melse-Boonstra A, et al. Effect of iodine
supplementation in pregnant women on child neurodevelopment: a rando-
mised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol
2017; 5:853–863.
61. Moleti M, Lo Presti VP, Campolo MC, et al. Iodine prophylaxis using iodized
salt and risk of maternal thyroid failure in conditions of mild iodine deficiency.
J Clin Endocrinol Metab 2008; 93:2616–2621.
62. Moleti M, Trimarchi F, Tortorella G, et al. Effects of maternal iodine nutrition
and thyroid status on cognitive development in offspring: a pilot study.
Thyroid 2016; 26:296–305.
63. Fuse Y, Ohashi T, Yamaguchi S, et al. Iodine status of pregnant and
postpartum Japanese women: effect of iodine intake on maternal and
neonatal thyroid function in an iodine-sufficient area. J Clin Endocrinol Metab
2011; 96:3846–3854.
64. Schulze KJ, Gernand AD, Khan AZ, et al. Newborn micronutrient status
biomarkers in a cluster-randomized trial of antenatal multiple micronutrient
compared with iron folic acid supplementation in rural Bangladesh. Am J Clin
Nutr 2020; 112:1328–1337.
65. Harding KB, Pena-Rosas JP, Webster AC, et al. Iodine supplementation for
women during the preconception, pregnancy and postpartum period. Co-
chrane Database Syst Rev 2017; 3:CD011761.
66. Abel MH, Caspersen IH, Sengpiel V, et al. Insufficient maternal iodine intake
is associated with subfecundity, reduced foetal growth, and adverse preg-
nancy outcomes in the Norwegian Mother, Father and Child Cohort Study.
BMC Med 2020; 18:211.
67. Nazarpour S, Ramezani Tehrani F, Amiri M, et al. Maternal urinary iodine
concentration and pregnancy outcomes: Tehran Thyroid and Pregnancy
Study. Biol Trace Elem Res 2020; 194:348–359.
68. Cui X, Yu H, Wang Z, et al. No association was found between mild iodine
deficiency during pregnancy and pregnancy outcomes: a follow-up study
based on a birth registry. Biol Trace Elem Res 2022; 200:4267–4277.
69. Torlinska B, Bath SC, Janjua A, et al. Iodine status during pregnancy in a
region of mild-to-moderate iodine deficiency is not associated with adverse
obstetric outcomes; results from the Avon Longitudinal Study of Parents and
Children (ALSPAC). Nutrients 2018; 10:.
70. Nazeri P, Mirmiran P, Kabir A, Azizi F. Neonatal thyrotropin concentration and
iodine nutrition status of mothers: a systematic review and meta-analysis. Am
J Clin Nutr 2016; 104:1628–1638.
71. Nazeri P, Shab-Bidar S, Pearce EN, Shariat M. Do maternal urinary iodine
concentration or thyroid hormones within the normal range during pregnancy
affect growth parameters at birth? A systematic review and meta-analysis.
Nutr Rev 2020; 78:747–763.
72. Wan S, Jin B, Ren B, et al. The relationship between high iodine consumption
and levels of autoimmune thyroiditis-related biomarkers in a Chinese popula-
tion: a meta-analysis. Biol Trace Elem Res 2020; 196:410–418.
73. Croce L, Chiovato L, Tonacchera M, et al. Iodine status and supplementation
&& in pregnancy: an overview of the evidence provided by meta-analyses. Rev
Endocr Metab Disord 2023; 24:241–250.
A review of meta-analyses suggests a role of iodine status during pregnancy in
determining maternal and child outcomes, but three meta-analyses evaluating the
results of intervention trials failed to show benefit of iodine supplementation in
pregnant women in areas with MMID.
74. Hisada A, Takatani R, Yamamoto M, et al. Maternal iodine intake and
neurodevelopment of offspring: the Japan Environment and Children’s Study.
Nutrients 2022; 14:1826.
75. Lean MI, Lean ME, Yajnik CS, et al. Iodine status during pregnancy in India
and related neonatal and infant outcomes. Public Health Nutr 2014;
17:1353–1362.
76. Velasco I, Carreira M, Santiago P, et al. Effect of iodine prophylaxis during
pregnancy on neurocognitive development of children during the first two
years of life. J Clin Endocrinol Metab 2009; 94:3234–3241.
www.co-endocrinology.com 7
CE: ; MED/30507; Total nos of Pages: 8;
MED 30507
Thyroid
77. Zhou SJ, Skeaff SA, Ryan P, et al. The effect of iodine supplementation in
pregnancy on early childhood neurodevelopment and clinical outcomes:
results of an aborted randomised placebo-controlled trial. Trials 2015;
16:563.
78. Abel MH, Brandlistuen RE, Caspersen IH, et al. Language delay and poorer
school performance in children of mothers with inadequate iodine intake in
pregnancy: results from follow-up at 8 years in the Norwegian Mother and
Child Cohort Study. Eur J Nutr 2019; 58:3047–3058.
79. Markhus MW, Dahl L, Moe V, et al. Maternal iodine status is associated with
offspring language skills in infancy and toddlerhood. Nutrients 2018;
10:1270.
80. Murcia M, Rebagliato M, Iniguez C, et al. Effect of iodine supplementation
during pregnancy on infant neurodevelopment at 1 year of age. Am J
Epidemiol 2011; 173:804–812.
81. Machamba AAL, Azevedo FM, Fracalossi KO, do CCFS. Effect of iodine
supplementation in pregnancy on neurocognitive development on offspring
in iodine deficiency areas: a systematic review. Arch Endocrinol Metab 2021;
65:352–367.
82. Brucker-Davis F, Ganier-Chauliac F, Gal J, et al. Neurotoxicant exposure
during pregnancy is a confounder for assessment of iodine supplementation
on neurodevelopment outcome. Neurotoxicol Teratol 2015; 51:45–51.
83. Liu L, Liu J, Wang D, et al. Effect of urinary iodine concentration in pregnant
and lactating women, and in their infants residing in areas with excessive
iodine in drinking water in Shanxi Province, China. Biol Trace Elem Res 2020;
193:326–333.
84. Leung AM, Braverman LE. Consequences of excess iodine. Nat Rev En-
docrinol 2014; 10:136–142.
85. Theodoropoulos T, Braverman LE, Vagenakis AG. Iodide-induced hypothyr-
oidism: a potential hazard during perinatal life. Science 1979;
205:502–503.
86. Hardley MT, Chon AH, Mestman J, et al. Iodine-induced fetal hypothyroidism:
diagnosis and treatment with intra-amniotic levothyroxine. Horm Res Paediatr
2018; 90:419–423.
87. Shi X, Han C, Li C, et al. Optimal and safe upper limits of iodine intake for early
pregnancy in iodine-sufficient regions: a cross-sectional study of 7190
pregnant women in China. J Clin Endocrinol Metab 2015; 100:1630–1638.
88. Corcino CM, Berbara T, Saraiva DA, et al. Variation of iodine status during
pregnancy and its associations with thyroid function in women from Rio de
Janeiro, Brazil. Public Health Nutr 2019; 22:1232–1240.
89. Pop VJ, Brouwers EP, Vader HL, et al. Maternal hypothyroxinaemia during
early pregnancy and subsequent child development: a 3-year follow-up
study. Clin Endocrinol (Oxf) 2003; 59:282–288.
8 www.co-endocrinology.com
Copyright © 2023 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
90. Li Y, Shan Z, Teng W, et al. Abnormalities of maternal thyroid function during
pregnancy affect neuropsychological development of their children at 25-
30 months. Clin Endocrinol (Oxf) 2010; 72:825–829.
91. Maraka S, Ospina NM, O’Keeffe DT, et al. Subclinical hypothyroidism in
pregnancy: a systematic review and meta-analysis. Thyroid 2016; 26:580–590.
92. Consortium on T, Pregnancy-Study Group on Preterm B, Korevaar TIM,
Derakhshan A, Taylor PN, et al. Association of thyroid function test abnorm-
alities and thyroid autoimmunity with preterm birth: a systematic review and
meta-analysis. JAMA 2019; 322:632–641.
93. Thompson W, Russell G, Baragwanath G, et al. Maternal thyroid hormone
insufficiency during pregnancy and risk of neurodevelopmental disorders in
offspring: a systematic review and meta-analysis. Clin Endocrinol (Oxf) 2018;
88:575–584.
94. Chen J, Zhu J, Huang X, et al. Subclinical hypothyroidism with negative for
thyroid peroxidase antibodies in pregnancy: intellectual development of
offspring. Thyroid 2022; 32:449–458.
95. Candido AC, Vieira AA, de Souza Ferreira E, et al. Prevalence of excessive
&& iodine intake in pregnancy and its health consequences: systematic review
and meta-analysis. Biol Trace Elem Res 2023; 201:2784–2794.
The first systematic review and meta-analysis of studies evaluating excess iodine
intake in pregnancy found that the prevalence of excessive iodine intake in 10 736
pregnant women in different regions of the world was 52%.
96. Mulder TA, Korevaar TIM, Peeters RP, et al. Urinary iodine concentrations in
&& pregnant women and offspring brain morphology. Thyroid 2021; 31:964–972.
The first study investigating the association of mild-to-moderate maternal iodine
deficiency during pregnancy with offspring brain MRI outcomes found a low UI/
Creat (<150 mug/g) during pregnancy was nominally associated with smaller total
gray matter volume, but this did not survive correction for multiple testing.
97. Kampouri M, Tofail F, Rahman SM, et al. Gestational and childhood urinary
& iodine concentrations and children’s cognitive function in a longitudinal
mother-child cohort in rural Bangladesh. Int J Epidemiol 2023; 52:144–155.
First study to evaluate child cognitive abilities in relation to iodine intake in
Bangladesh. Both low UIC less than 150 mug/l and high UIC at least
500 mug/l was associated with decreased verbal scores.
98. Ju DL, Cho SW, Chung CW, et al. High intakes of iodine among women
during pregnancy and the postpartum period has no adverse effect on thyroid
function. Eur J Nutr 2023; 62:239–249.
99. Orito Y, Oku H, Kubota S, et al. Thyroid function in early pregnancy in
Japanese healthy women: relation to urinary iodine excretion, emesis, and
fetal and child development. J Clin Endocrinol Metab 2009; 94:1683–1688.
100. WHO. Assessment of iodine deficiency disorders and monitoring their
elimination: a guide for programme managers. Geneva: WHO; 2007.
Volume 30  Number 00  Month 2023