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European Journal of Nutrition (2021) 60:4083–4091

https://doi.org/10.1007/s00394-021-02574-4

ORIGINAL CONTRIBUTION

Does maternal iodine supplementation during the lactation have


a positive impact on neurodevelopment of children? Three‑year follow
up of a randomized controlled trial
Pantea Nazeri1 · Zhale Tahmasebinejad2 · Elizabeth N. Pearce3 · Zinat Zarezadeh1 · Tahere Tajeddini1 ·
Parvin Mirmiran2,5 · Fereidoun Azizi4

Received: 15 October 2020 / Accepted: 27 April 2021 / Published online: 11 May 2021
© Springer-Verlag GmbH Germany, part of Springer Nature 2021

Abstract
Purpose The aim of this study was to examine, for the first time, the neurodevelopmental outcomes in children whose moth-
ers received different doses of iodine supplements during lactation.
Methods We conducted a follow-up study on children whose mothers participated in a randomized clinical trial to receive
placebo, 150 µg/day or 300 µg/day of iodine until 12 months postpartum. Child neurocognitive development was assessed
at 36 months of age using the Bayley Scales of Infant and Toddler Development Third Edition. Linear mixed-model analysis
was preformed to assess iodine supplement dose effects on child cognitive, language, and motor functions.
Results A total of 122 children provided neurodevelopmental data as follows: 300 µg/d iodine group: 45; 150 µg/d iodine
group: 35; and placebo group: 42. Cognitive scores were higher in children whose mothers received 150 µg iodine/d compared
to children whose mothers received placebo [102.8 (SD 13.2) vs. 99.2 (SD 10.5); β = 4.43, P = 0.032]. However, supplemen-
tation with 150 µg iodine/d had no effect on language or motor development. No significant differences were observed in
cognitive, language, or motor functions between children whose mothers received 300 µg iodine/d and those whose mothers
received 150 µg iodine/d or placebo.
Conclusion Maternal iodine supplementation with 150 µg/d during lactation may have a beneficial effect on child cognitive
development; however, we found no evidence of either improved or delayed neurodevelopmental outcomes in children whose
mothers received iodine supplements at doses higher than recommended. Further randomized controlled trials with larger
sample sizes are needed to confirm these results.
Clinical trial registry IRCT201303164794N8; registration date: 2013-05-20

Keywords Iodine · Supplementation · Lactation · Neurocognitive development · Early childhood

3
* Parvin Mirmiran Section of Endocrinology, Diabetes and Nutrition, Boston
mirmiran@endocrine.ac.ir University School of Medicine, Boston, USA
4
* Fereidoun Azizi Endocrine Research Center, Research Institute for Endocrine
azizi@endocrine.ac.ir Sciences, Shahid Beheshti University of Medical Sciences,
P.O. Box: 19395‑4763, Tehran, Iran
1
Family Health Institute, Breastfeeding Research Center, 5
Department of Clinical Nutrition and Dietetics, Faculty
Tehran University of Medical Sciences, Tehran, Iran
of Nutrition Sciences and Food Technology, National
2
Nutrition and Endocrine Research Center, Research Institute Nutrition and Food Technology Research Institute, Shahid
for Endocrine Sciences, Shahid Beheshti University Beheshti University of Medical Sciences, P.O. Box:
of Medical Sciences, P.O. Box: 19395‑4763, Tehran, Iran 19395‑4763, Tehran, Iran

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Vol.:(0123456789)
4084 European Journal of Nutrition (2021) 60:4083–4091

Introduction for iodine sufficiency during the first year of life). Supple-
mentation of lactating mothers with either 300 or 150 µg
Infancy and early childhood are critical periods for brain iodine/d had no effect on infant growth parameters. These
development due to rapid growth of brain structure and observations raised the following questions: (1) whether
function that occurs in the earliest years of life [1]. It has iodine supplementation during lactation is beneficial in
been estimated that nearly 19 million babies born globally improving neurocognitive development in children, despite
every year are at risk of brain damage and reduced cog- baseline adequacy of iodine status, (2) if so, whether the
nitive function due to iodine deficiency [2]. Iodine is an recommended dose of 150 µg iodine/d is optimal for this
essential component of thyroid hormones which support purpose, and (3) whether there is a dose–response effect
neurodevelopmental processes through neurogenesis, neu- for neurodevelopmental outcomes in infants whose moth-
ronal migration, axon and dendrite growth, synaptogen- ers received higher-dose iodine supplementation. There-
esis, and myelination [3]; therefore, adequate iodine intake fore, in this follow-up study, for the first time, we assessed
is necessary for normal brain growth and cognitive devel- cognitive, language, and motor development in children
opment [4, 5]. It is well-documented that severe iodine whose mothers received different doses of iodine supple-
deficiency in utero and in early life can result in impaired ments during lactation.
mental function, poor school performance, and reduced
intellectual ability [6].
Although the World Health Organization does not rec-
ommend iodine supplementation for pregnant women, Methods
lactating mothers, or infants in countries with effective
iodized salt programs [7], major medical societies such Study design and participants
as the American Thyroid Association [8], the Endocrine
Society [9], and the American Academy of Pediatrics [10] This was a three-year follow-up study of infants and mothers
recommend that pregnant women and lactating moth- who participated in the randomized clinical trial of iodine
ers should take daily supplements containing 150 µg of supplementation in Tehran, Iran [16].
iodine. There is currently no definitive evidence regarding
the benefits of iodine supplementation during pregnancy
on infant/child neurocognitive development in regions Design of the original trial
of mild-moderate iodine deficiency [11]. Some studies
not only did not report any beneficial effects but actually The original trial was conducted between October 2014 and
reported potential negative effects on neurodevelopment of January 2016 to investigate the effects of maternal iodine
children following maternal iodine supplementation [12, supplementation during lactation on iodine status and
13]. To date, few studies have investigated the potential growth parameters of breastfed infants during the first year
effects of iodine supplementation during lactation, and of life. A detailed description of the design and methods of
existing studies have mainly focused on the iodine sta- the original trial (www.​irct.​ir; IRCT201303164794N8) has
tus and thyroid function of lactating mothers and infants been published elsewhere [16]. In brief, 180 lactating moth-
[14–16]. No study thus far has examined the effects of ers and their newborns who were referred to four health-
iodine supplementation on child neurocognitive develop- care centers in Tehran were randomly assigned to treatment
ment. In addition, there is limited data available on associ- groups: placebo, 150 µg/d iodine, or 300 µg/d iodine, and
ations between urinary or breast milk iodine concentration, followed-up for 12 months. Inclusion criteria were as fol-
indicators of iodine status in infants, and neurodevelop- lows: healthy mothers with no history of thyroid disorders,
mental outcomes [17]. not currently using iodine-containing supplements and dis-
We recently reported the results of a multi-center ran- infectants, had a singleton birth, and intended to breastfeed
domized, double-blind, placebo-controlled trial regard- exclusively; healthy infants aged 3–5 days, born full-term
ing the effects of different doses of iodine supplements (gestational age 37–42 weeks) and at a normal birth weight
(i.e. placebo vs. 150 µg/d and 300 µg/d of iodine) on the (2500–4200 g). Newborns with thyroid stimulating hormone
iodine status of lactating mothers and infants residing in concentration outside of the reference range (> 5 mIU/l in
an area of overall iodine sufficiency [16]. The findings heel-prick blood samples) were excluded and referred for
indicated that although the urinary iodine concentrations treatment. In lactating mothers and infants, urinary and
in infants of the 300 µg iodine/d group increased signifi- breast milk iodine concentrations and anthropometric meas-
cantly, the iodine status of infants in all groups studied urements were assessed as the primary outcomes at 1, 2,
were ≥ 100 µg/l (a recommended population cut-off point 4, 6, 9, and 12 months during routine health visits. Mean
compliance with supplementation was 85% (SD 12).

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European Journal of Nutrition (2021) 60:4083–4091 4085

Follow‑up study the original trial to the current follow-up study. Reasons
for excluding children in the follow-up study were unwill-
Between December 2017 and June 2018, mothers in the ingness to participate, change of city, loss of contact, and
original trial were contacted and invited to enroll in the history of seizure. We re-enrolled 128 children whose
neurodevelopmental study when their child was 36 months mothers provided informed consent to participate in this
of age. Figure 1 shows the flow chart of participation from follow-up assessment and a total of 122 children provided

220 mother-infant pairs enrolled during 3-5 days postpartum


At 3-5 days postpartum

40 mother-infant pairs
declined to participate

180 mother-infant pairs randomly assigned

60 pairs allocated to 300 60 pairs allocated to 150 60 pairs allocated to


µg I /d group µg I /d group placebo group
Followed until 1 year

At age 12 months

50 pairs completed follow up 43 pairs completed follow up 51 pairs completed follow up


Followed until 3 years

At age 36 months

4 ineligible for follow-up 7 ineligible for follow-up 5 ineligible for follow-up

46 included in 36 included in 46 included in


neurodevelopmental study neurodevelopmental study neurodevelopmental study

4 excluded due to
1 excluded due to lack of 1 excluded due to child
unwillingness to continue
child cooperation illness
collaboration

45 completed the study 35 completed the study 42 completed the study

Fig. 1  Flow chart of participation from the original trial to the current follow-up study

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4086 European Journal of Nutrition (2021) 60:4083–4091

neurodevelopmental data as follows: 300 µg/d iodine group: were expressed as categorical and continuous variables,
45; 150 µg/d iodine group: 35; and placebo group: 42. With- and normality was assessed by the Kolmogorov-Smirnove
drawal from participation was mostly attributed to unwilling- test and a histogram chart. Non- and normally distributed
ness to continue collaboration (n = 1), child illness (n = 1), variables within groups (i.e., placebo, 150 µg/d iodine, or
or lack of child cooperation (n = 6). Structured interviews 300 µg/d iodine) were compared using Kruskal–Wallis and
were conducted to collect information on household demo- ANOVA, respectively. Significant differences in categori-
graphic and socioeconomic data (including parents’ age, cal variables were determined using chi-square analysis, Phi
education, and occupation and child kindergarten attend- coefficient and Cramer’s V measures. Linear mixed-model
ance) and detailed medical history (including that of severe analysis was used to assess iodine supplement dose effects
illness and hospitalization). Ethical approval for the follow- on child cognitive, language, and motor development. For
up study was obtained from the ethics committee of Tehran each continuous outcome variable, a separate mixed model
University of Medical Sciences. was derived with the fixed effect for treatment group and
For neurodevelopment assessment, the children, accom- participants as the random effect. Covariates included in the
panied by their mothers, were provided free transportation neurodevelopmental analyses were: maternal age, education,
to a central health care center and were assessed privately occupation, gestational age, child’s birth weight, sex, age,
in a test room to reduce distractions. The Bayley Scales and kindergarten attendance. All statistical analyses were
of Infant and Toddler Development, third edition (also performed using Stata software version 12.0 (StataCorp,
known as Bayley-III) was administrated by two trained and College Station, TX, USA). A two-tailed P value < 0.05 was
experienced staff members who were blinded to the treat- considered statistically significant.
ment group assignment. Neurocognitive development was
assessed on three key scales: (1) cognitive, (2) language
(including the receptive communication and expressive Results
communication subsets), and (3) motor (including the fine
motor and gross motor subsets) using items administered to Baseline characteristics of children and their mothers
the child. The social-emotional and adaptive behavior scales included in the neurodevelopmental assessment are pre-
of Bayley-III were not administered, as these items have not sented in Table 1. Characteristics of both children and
been standardized for Iranian culture. Validity and reliability mothers at the enrollment did not differ among treatment
of the Iranian version of the Bayley-III had been previously groups, except for date of last pregnancy. Mothers in the
determined and this test is confirmed to be appropriate for 300 µg/d iodine group had shorter interpregnancy interval,
Persian-speaking children aged 1–42 months [18]. Briefly, compared to those in the 150 µg/d iodine or placebo groups
the cognition scale of the Bayley-III assessed the child’s (P = 0.028). Medical history and kindergarten attendance
performance in several cognitive areas, such as exploration during the follow-up period did not vary by study group.
and manipulation, object relatedness, concept formation, No significant differences were found in demographic or
and memory. The receptive communication subset included baseline biochemical characteristics between children who
items that assessed child’s vocabulary development related were followed-up and those who were not followed-up (data
to objects and pictures, social referencing, and verbal com- not shown).
prehension. The expressive communication subset included Figure 2 shows the mean Bayley-III subscales (cogni-
items that assess child’s preverbal communications and tion, expressive communication, receptive communica-
vocabulary development. The fine and gross motor subsets tion, fine motor and gross motor) and composite scores
were associated with child’s quality of movement, axial (cognitive, language, and motor) of children at 36 months
motor abilities, and coordination. The original test scores in the three intervention groups. The mean (SD) cogni-
were converted to composite scores that are age-standard- tive, language, and motor development in different groups
ized with a normative mean of 100 and standard deviation were: 300 µg iodine/d group: 101.2 (8.8), 101.1 (12.6),
of 15. Bayley-III composite scores of < 85 were classified as and 93.2 (12.8); 150 µg iodine/d group: 102.8 (13.2), 99.8
neurodevelopmental delay. We planned to assess childhood (14.5), and 96.3 (14.5); and placebo group: 99.2 (10.5),
neurodevelopment at 36 months of age, but the children were 99.2 (13.9), and 91.0 (16.4), respectively. There were no
assessed at a mean age of 39.7 months due to logistical study significant differences in any of the subscales or composite
delays. scores of Bayley-III between the children of mothers who
received different doses of iodine supplements and those
Statistical analysis who received placebo during lactation. Frequency of neu-
rodevelopmental delays in cognitive, language, and motor
The frequency distribution (percentage), mean [standard domains in the treatment groups were: 300 µg iodine/d
deviation (SD)], and median [interquartile range (IQR)] group: 2.2, 8.9, and 22.2%; 150 µg iodine/d group: 8.6,

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European Journal of Nutrition (2021) 60:4083–4091 4087

Table 1  Baseline characteristics Characteristics Treatment groups


of children and their mothers
included in neurodevelopmental 300 µg I/d 150 µg I/d Placebo
study by treatment groups (n = 45) (n = 35) (n = 42)

Childrena
Sex
Boy 29 (64.4) 20 (57.1) 21 (50.0)
Girl 16 (35.6) 15 (42.9) 21 (50.0)
Birth weight (g) 3310 ± 446 3375 ± 381 3391 ± 395
Birth length (cm) 50.3 ± 2.0 50.1 ± 1.9 50.1 ± 2.5
Birth head circumference (cm) 34.8 ± 1.4 35.4 ± 1.3 35.2 ± 1.2
Weight-for- age Z score − 0.02 ± 0.92 0.15 ± 0.85 0.18 ± 0.82
Weight-for- length Z score − 0.43 ± 1.41 − 0.07 ± 1.23 − 0.16 ± 1.37
Length-for- age Z score 0.36 ± 1.06 0.31 ± 1.08 0.33 ± 1.33
Head circumference-for- age Z score 0.51 ± 1.17 0.96 ± 1.02 0.84 ± 1.04
Thyrotropin (mIU/l) 1.00 (0.40–1.80) 1.40 (0.80–2.30) 0.90 (0.47–1.32)
Urinary iodine concentration (µg/l) 228.5 (72.5–283.2) 121.5 (45.8–281.0) 174.6 (85.6–395.3)
Mothersa
Age (yr) 27.5 ± 4.5 28.6 ± 5.0 29.2 ± 4.7
Education degree
Primary 11 (24.4) 11 (31.4) 19 (46.3)
Secondary 26 (57.8) 17 (48.6) 14 (31.4)
Higher 8 (17.8) 7 (20.0) 8 (19.5)
Occupation
Employee 3 (6.7) 3 (8.6) 1 (2.4)
Housewives 42 (93.3) 32 (91.4) 41 (97.6)
Parity
Primiparity 24 (53.3) 12 (34.3) 14 (33.3)
Multiparity 21 (46.7) 23 (65.7) 28 (66.7)
Date of last pregnancy (yr) 2.2 ± 2.9 4.3 ± 4.0 4.6 ± 5.0
Gestational age (wk) 37.9 ± 2.0 38.1 ± 1.6 38.3 ± 1.9

Values are median [interquartile range (IQR)], mean ± SD, or n (%), unless otherwise stated
a
No significant differences were found in baseline characteristics among the treatment groups, except for
date of last pregnancy

11.4, and 25.7%; and placebo group: 2.4, 11.9, and 23.8%, Discussion
respectively; the differences among the three groups were
not statistically significant (Table 2). To the best of our knowledge, this study is the first to exam-
The effects of different doses of iodine supplementation ine the effects of maternal iodine supplementation during
during lactation on child cognitive, language, and motor lactation on neurocognitive development in children at
development at 36 months, using the linear mixed-model 36 months of age. In this randomized placebo-controlled
analysis, are shown in Table 3. Cognitive scores were trial, we found that children whose mothers received 150 µg
significantly higher in children whose mothers received iodine/d had significantly better scores in cognitive, but not
150 µg iodine/d compared to children whose mothers in motor or language, development than control children
received placebo (β = 4.43; 95% CI 0.38, 8.47; P = 0.032). whose mothers received placebo. However, supplementation
However, supplementation of 150 µg iodine/d in mothers of lactating mothers with 300 µg iodine/d had no effect in
was not associated with beneficial effects on language or any of the neurodevelopmental outcomes in children, com-
motor development in children. No significant differences pared to the 150 µg iodine/d and placebo groups.
in cognitive, language, and motor scores were observed It is well known that brain and central nervous system
between children whose mothers received 300 µg iodine/d develops rapidly in utero and up to age 3 years. The majority
and those whose mothers received 150 µg iodine/d or of prior studies have focused on the adverse effects of iodine
placebo. deficiency during pregnancy on child neurodevelopment

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4088 European Journal of Nutrition (2021) 60:4083–4091

a 20 for optimal brain growth and cognitive development. In a


300 µg I/d study by Wu et al., the only prior study available, higher
150 µg I/d
breast milk iodine concentrations at few days postpartum
BSITD III scores

15 Placebo
were associated with better infant motor development, spe-
10 cifically gross motor function [17]. It has been shown that
lactating mothers with higher iodine intakes had a greater
5 fractional iodine excretion in their breast milk, however,
with inadequate iodine intake, a relatively constant pro-
0 portion (approximately 33%) of total iodine was excreted
in breast milk [22]. We previously observed significantly
ve

or
om

or
m

ot
ot
iti

co

sc

m
m
gn

re
p

increased breast milk iodine concentration in mothers who


ss
ne
Co

ce

ro
Fi
Ex
Re

G
received 300 or 150 µg iodine/d compared to placebo; how-
b ever, neurocognitive development of children showed incon-
150
300 µg I/d sistent results between the two supplemented groups. This
150 µg I/d interesting observation indicates that child neurodevelop-
BSITD III scores

100
Placebo mental outcomes may vary across different levels of breast
milk iodine concentration.
Studies in iodine-deficient school-aged children have
clearly shown that iodine supplementation was associated
50

with improvement in cognitive function [23]; however, data


0 regarding the effect of iodine supplementation for mildly-
Cognitive Language Motor
moderately iodine deficient pregnant women for child neu-
Fig. 2  Comparison of neurodevelopmental scores in children at age rocognitive development are still inconclusive. In a recent
36 months by treatment groups. a BSITD-III scaled scores; b BSITD- meta-analysis of randomized clinical trials by Dineva et al.
III composite scores. The box represents the 25th to the 75th percen-
tile of the data. The solid line inside the box indicates the median no differences were found in cognitive, language, or motor
value and the dot beside the line indicates the mean value. BSITD scores between children born to women who received iodine
Bayley Scales of Infant and Toddler Development supplementation during pregnancy and those born to non-
supplemented women [11]. Some studies demonstrated
that the effect of iodine on the neurocognitive develop-
Table 2  Frequency of neurodevelopmental delay (< 85) in children at ment of children varies at different stages of pregnancy and
age 36 months by treatment groups emphasized the necessity of initiating iodine supplementa-
Outcome Treatment groups tion before or as early as possible during the pregnancy to
ensure the adequacy of fetal neurodevelopment [24]. Sev-
300 µg I/d 150 µg I/d Placebo
(n = 45) (n = 35) (n = 42) eral medical and public health advisory groups have rec-
ommended continuation of iodine supplementation during
BSITD-III, cognitive score lactation, however, its necessity for optimizing child neu-
Normal 44 (97.8)ab 32 (91.4) 41 (97.6) rodevelopmental outcomes is yet to be investigated. In our
Cognitive delay 1 (2.2) 3 (8.6) 1 (2.4) previous study, the baseline median UIC in lactating moth-
BSITD-III, language score ers was < 100 µg/l in all treatment groups [300 µg iodine/d
Normal 41 (91.1)ab 31 (88.6) 37 (88.1) group: 70 (40–116) µg/l; 150 µg iodine/d group: 71 (38–111)
Language delay 4 (8.9) 4 (11.4) 5 (11.9) µg/l; and placebo group: 97 (45–154) µg/l]. However, on
BSITD-III, motor score the basis of urinary iodine levels in their infants indicating
Normal 35 (77.8)ab 26 (74.3) 32 (76.2) iodine sufficiency, we declared that lactating mothers resid-
Motor delay 10 (22.2) 9 (25.7) 10 (23.8) ing in an iodine sufficient area with effective salt iodization
BSITD-III Bayley Scales of infant and Toddler Development-III program have no need for iodine supplementation [16]. The
a
Values are number and percentage in parenthesis present follow-up study showed that supplementation of lac-
b
No significant differences were found among the treatment groups tating mothers with 150 µg iodine/d had a beneficial effect
on cognitive function in children at age 36 months.
Few studies to date have explored the effect of iodine
[19–21]. However, the effect of iodine status during lac- excess on child neurocognitive development. For instance,
tation on infant/child neurocognitive outcomes remains Aakre et al. investigated early childhood neurodevelopmental
poorly understood. Exclusively breastfed infants are entirely status in association with iodine excess in a cross-sectional
dependent on adequate iodine concentration in breast milk study. The authors concluded that high iodine intakes can be

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European Journal of Nutrition (2021) 60:4083–4091 4089

Table 3  Effects of different doses of iodine supplementation during lactation on neurodevelopmental outcomes in children at age 36 months

a key contributor to thyroid dysfunction and poorer devel- status [31, 32]; however, no consensus has been reached
opmental status in young children (aged 18–48 months), as regarding the optimal cutoff value for thyroglobulin concen-
assessed using the Ages and Stages Questionnaires, third tration to indicate iodine status during pregnancy or lacta-
edition [25]. However, in this present study, excessive iodine tion. Additionally, its association with neurodevelopmental
intakes in infants whose mothers received 300 µg iodine/d outcomes remains unclear.
during lactation had no observed effect on neurocognitive The main strength of the current study is the randomized
development at 36 months of age. Available studies have controlled trial design with 3 year follow-up that enabled
shown inconsistent results regarding the effect of excessive us to demonstrate a causative link between maternal iodine
iodine intake on thyroid function during infancy. In some, supplementation during lactation and subsequent neurocog-
excess iodine intakes were associated with a high prevalence nitive development in children. However, there are some
of subclinical hypothyroidism [26, 27], while others reported limitations that need to be acknowledged. Because the final
no thyroid dysfunction in infants exposed to high doses of sample size in each treatment group was relatively small,
iodine [28]. However, the long-term consequences are still caution should be taken in interpretation of these results.
unknown and need further investigations. Although randomization should have minimized the effect
It is noteworthy that although median UIC is a well- of known and unknown confounders, we did not measure
accepted, cost-efficient, and easily measured indicator for intelligence of mothers and household income, which are
determining iodine status at the population level, it reflects known to influence child neurodevelopmental outcomes.
iodine intakes over a short time period and the intra-individ- Child neurocognitive development was evaluated using
ual variation is huge [29]. Other recommended markers for an internationally recognized tool; measuring the specific
iodine status include thyroid volume—a sensitive marker for domains of cognitive and psychomotor development using
severe iodine deficiency over a period of months or years, more precise methods may provide more accurate data in
and thyroid hormones, such as thyroid stimulating hormone, this regard.
thyroxine, and tri-iodothyronine, which are weak markers In conclusion, the present study demonstrated that mater-
of iodine status because the levels typically remain within nal iodine supplementation with 150 µg/d during lactation
the normal reference range during mild-to-moderate iodine may have a beneficial effect on child cognitive develop-
deficiency [30]. Recent studies suggest that thyroglobulin, a ment. There was no evidence of either improved or delayed
thyroid-specific protein, may be a better indicator of iodine neurodevelopmental outcomes in children whose mothers

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4090 European Journal of Nutrition (2021) 60:4083–4091

received iodine supplement at doses higher than recom- 4. Delange F (2000) The role of iodine in brain development. Proc
mended. To the best of our knowledge, no prior study has Nutr Soc 59:75–79. https://​doi.​org/​10.​1017/​s0029​66510​00000​
94
been conducted to assess the neurodevelopmental effects of 5. Delange F (2001) Iodine deficiency as a cause of brain damage.
iodine supplementation during lactation; therefore, it is dif- Postgrad Med J 77:217–220
ficult to draw definitive conclusions at present. Further ran- 6. Zimmermann MB (2009) Iodine deficiency. Endocr Rev 30:376–
domized controlled trials involving larger sample sizes and 408. https://​doi.​org/​10.​1210/​er.​2009-​0011
7. Andersson M, de Benoist B, Delange F, Zupan J (2007) Preven-
longer follow-up periods are needed to confirm our findings tion and control of iodine deficiency in pregnant and lactating
and examine whether the benefits of iodine supplementation women and in children less than 2-years-old: conclusions and
persist into the school years and beyond. recommendations of the Technical Consultation Iodine require-
ments during pregnancy, lactation and the neonatal period and
Acknowledgements This study was supported by financial grant from indicators of optimal iodine nutrition Iodine deficiency as a cause
Tehran University of Medical Sciences (grant number 97-02-91-37843) of brain damage The role of iodine in brain development. Public
and Research Institute for Endocrine Sciences, Shahid Beheshti Univer- Health Nutr 10:1606–1611. https://​doi.​org/​10.​1017/​S1368​98000​
sity of Medical Sciences (grant number 480), Tehran, Iran. 73610​04
8. Stagnaro-Green A, Abalovich M, Alexander E, Azizi F, Mestman
J, Negro R, Nixon A, Pearce EN, Soldin OP, Sullivan S, Wiersinga
Authors contribution PN contributed to design the study concept, data W (2011) Guidelines of the American Thyroid Association for the
collection and interpretation, and writing, reading, and final approval diagnosis and management of thyroid disease during pregnancy
of the manuscript; JT contributed to the data analysis and interpreta- and postpartum. Thyroid 21:1081–1125. https://​doi.​org/​10.​1089/​
tion, and writing, reading and final approval of the manuscript; ENP thy.​2011.​0087
contributed to design the study concept, and writing, reading, and final 9. De Groot L, Abalovich M, Alexander EK, Amino N, Barbour L,
approval of the manuscript; ZZ and TT contributed to data collection Cobin RH, Eastman CJ, Lazarus JH, Luton D, Mandel SJ, Mest-
and interpretation, and writing, reading and final approval of the manu- man J, Rovet J, Sullivan S (2012) Management of thyroid dysfunc-
script; PM and FA supervised the study procedure and contributed to tion during pregnancy and postpartum: an Endocrine Society clin-
writing, reading and final approval of the manuscript. ical practice guideline. J Clin Endocrinol Metab 97:2543–2565.
https://​doi.​org/​10.​1210/​jc.​2011-​2803
Funding This study was supported by financial grant from Tehran 10. Leung AM, Pearce EN, Braverman LE, Stagnaro-Green A (2014)
University of Medical Sciences (grant number 97–02-91–37843) and AAP recommendations on iodine nutrition during pregnancy and
Research Institute for Endocrine Sciences, Shahid Beheshti University lactation. Pediatrics 134:e1282. https://​doi.​org/​10.​1542/​peds.​
of Medical Sciences (grant number 480), Tehran, Iran. 2014-​2111A
11. Dineva M, Fishpool H, Rayman MP, Mendis J, Bath SC (2020)
Availability of data and material The data that support the findings Systematic review and meta-analysis of the effects of iodine sup-
of this study are available on request from the corresponding authors. plementation on thyroid function and child neurodevelopment in
mildly-to-moderately iodine-deficient pregnant women. Am J Clin
Nutr. https://​doi.​org/​10.​1093/​ajcn/​nqaa0​71
Declarations 12. Abel MH, Caspersen IH, Meltzer HM, Haugen M, Brandlistuen
RE, Aase H, Alexander J, Torheim LE, Brantsaeter AL (2017)
Conflict of interest None of the authors has any personal or financial Suboptimal maternal iodine intake is associated with impaired
conflicts of interest. child neurodevelopment at 3 years of age in the Norwegian mother
and child cohort study. J Nutr 147:1314–1324. https://​doi.​org/​10.​
Ethics approval Ethical approval for the follow-up study was obtained 3945/​jn.​117.​250456
from the ethics committee of Tehran University of Medical Sciences. 13. Gowachirapant S, Jaiswal N, Melse-Boonstra A, Galetti V, Stinca
S, Mackenzie I, Thomas S, Thomas T, Winichagoon P, Srinivasan
Consent to participate Written informed consent was obtained after the K, Zimmermann MB (2017) Effect of iodine supplementation in
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