5 Systematic literature review and grading of evidence on the health effects of
5.4 Studies concerning mild to moderate iodine deficiency
5.4.3.1 Grading of fertility and birth outcomes
Six cohort studies on fertility and birth outcomes were identified in the literature review. In four of the five studies on birth outcomes, no association between iodine status and birth outcomes were found. In one of the studies on birth outcomes, a higher prevalence of preterm birth and low birth weight was found in mild to moderate iodine deficient women. In one of the studies, lower birth weight and higher risk of having a small for gestational age (SGA) newborn was found in severe iodine deficient women. It is therefore concluded that the evidence is limited (no conclusion) that mild to moderate iodine deficiency prior to conception or during pregnancy is associated with negative birth outcomes.
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5.5 Evidence table and grading of health effects related to mild to moderate iodine deficiency
The systematic literature searches for evidence on health effects associated with mild- and moderate iodine deficiency resulted in 131 studies.
As a result of quality assessment, one of these studies were categorised as an A-study, a total of 35 studies were categorised as B-studies, whereas a total of 95 studies were categorised as C-studies. The category C-studies (lowest quality score) were not considered further. The following sections are organised according to the health outcomes graded, starting with neurodevelopment, followed by thyroid function and finally birth outcomes. The grading of evidence for the outcomes neurodevelopment, thyroid function and birth outcomes is finally summarised in the evidence Tables in 5.5-1 and 5.5-2.
Table 5.5-1 Evidence based on the systematic literature review of mild to moderate iodine deficiency graded as limited – suggestive for neurodevelopmental outcomes. Positive association: Exposure and outcomes have the same direction. Negative association: Exposure and outcomes have the opposite direction.
Author,
Findings in bold Findings associated with
UIC Findings associated
with iodine intake Findings associated with iodine supplement use
performance IQ and global executive composite score.
Primary outcome - no
effect. Effect in favor of
placebo on expressive reading skills, writing skills, mapping test reading, mapping test mathematics and special education. school and spec. ed.
No association with supplement and neurodevelopment
Markhus, 2018 Cohort, n=851, 6, 12 and 18mo
78 µg/L 2 of 5 5 outcomes: Cognitive, receptive communication, expressive communication, gross motor and fine motor.
Pos. association between UIC <100 µg/L and language (expressive and receptive)
Neg. association with gross motor performance
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Findings in bold Findings associated with
UIC Findings associated
with iodine intake Findings associated with iodine supplement use
Murcia, 2018 Cohort, n=1803, 4-5y
123 µg/L 1 of 2 2 outcomes: Cognitive and motor
function. No associations for raw
UIC. After adj. for creatinine UIC < 150 µg/g Cr associated with reduced general cognitive score
Neg. association with scores on motor scale, no association with general cognitive score
No association with cognitive or motor scores
Robinson, 2018 Cohort,
n=654, 6-7y 108 µg/L 1 of 4 4 outcomes: Full scale IQ and executive function (CANTAB DMS, CANTAB IED and CANTAB SSP).
Pos. association between
and motor. No associations with
Bayley-III scores Pos. associations with maternal intake (<220
Abel, 2017a Cohort, n=33047, 3y
61 µg/L
122 µg/d 3 of 5 5 outcomes: Language delay, communication skills, motor milestone, fine motor skills and behavior problems.
Abel, 2017b Cohort, n=27945,
Neg. association with ADHD symptoms and diagnoses
Hynes, 2017 Cohort,
n=228, 15y 83 µg/L 1 of 4 4 outcomes: Reading, spelling,
grammar and writing. Pos. associations between UIC <150 µg/L and spelling Ghassabian,
2014 Cohort,
n=1525, 6 y 296.5 μg/g
creatinine 0 of 2 2 outcomes: Non-verbal IQ and
language comprehension. No associations Bath, 2013 Cohort,
n=958, 8-9y 91 µg/L 3 of 7 7 outcomes: Verbal and performance IQ, total IQ, words read per minute, reading accuracy, comprehension and reading scores.
Pos. association between UIC<150 µg/L and verbal IQ, reading accuracy and comprehension
Hynes, 2013 Cohort,
n=228, 9y 81 µg/L 3 of 7 7 outcomes: Literacy (reading,
spelling, grammar, writing, Pos. association between UIC <150 µg/L and
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Findings in bold Findings associated with
UIC Findings associated
with iodine intake Findings associated with iodine supplement use
numeracy, English-literacy score
and mathematics-numeracy score. spelling, grammar and English grammer
psychomotor development. Neg. association with
Bayley-II PDI in 1 of 3 regions, and overall when including data from Murcia 2011.
Murcia, 2011 Cohort,
n=691, 1y 134 μg/L 0 of 2 2 outcomes: Mental and
psychomotor scales. No associations No associations Neg. association with Bayley-II PDI matrix reasoning, symbol search, letter-number sequencing and marking, symbol search, rapid object naming, Raven’s Coloured Progressive Matrices, Bead threading, Digit span and Coding.
Pos. associations with rapid target marking, symbol search, rapid object naming, Raven’s Coloured
Progressive Matrices
Table 5.5-2 Evidence based on the literature review of mild to moderate iodine deficiency graded as limited – no conclusion for thyroid function and birth outcomes and fertility.
Chen, 2019 Cross-sectional, n=14230 1 of 5 205 µg/L 5 outcomes: TgAbs, serum TSH, TPOAbs, fT4 and fT3.
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Wang, 2019 Cross-sectional, n=2808 1 of 3 165 µg/L 3 outcomes: TPOAb positivity, TgAb positivity, Thyroid autoimmunity (TAI) defined as a combination of positivity for one or both of TPOAb or TgAb.
Fan, 2018 Cross-sectional, n=2647 1 of 5 134 µg/L 5 outcomes: Thyroid nodules, Tvol, TSH, TPOAb and TGAb.
Krejbjerg,
trimester) TSH, fT4, TT4, fT3, TT3, TPOAb positivity, TgAb positivity, borderline significant for the rest (0.05>p<0.1).
Sun, 2019 Cross-sectional, n=7073 2 of 2 154 µg/L (1st
trimester) TPOAb positivity, TgAb positivity.
Abel, 2018 Cross-sectional, n=2910 2 of 5 59 µg/L
121 µg/d 5 outcomes: TSH, fT4, fT3, TPOAb and TgAb.
Moreno-Reyes,
2013 Cross-sectional, n=1311 1 of 6 117 µg/L (1st
trimester) 6 outcomes: Tg, TSH, TPOAb, TgAb, fT3 and fT4.
Rebagliato,
2010 Cross-sectional, n=1844 0 of 2 137 µg/L (1st
trimester) 2 outcomes: fT4 and TSH.
School
children Skeaff, 2012 Cross-sectional, n=1153,
5-14y 2 of 4 68 µg/L 4 outcomes: Serum Tg, serum TSH, plasma fT4 and fT3.
Mills, 2019 Cohort, n=329 0 of 1 Not available 1 outcome: Pregnancy loss.
Snart, 2019 Cohort, n=541 0 of 4 134 µg/L 4 outcomes: Birth weight, birth weight centile (primary outcome), small for gestational age (SGA) and spontaneous preterm birth.
Torlinska,
2018 Cohort, n=3140 0 of 2 95 µg/L 2 outcomes: Pregnancy/infant loss, or with other adverse pregnancy outcomes.
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Population group exposed
Author,
year Study design, N,
age Finding of total
main outcomes measured
Median UIC Median iodine intake
Outcomes measured.
Findings in bold Charoenratana
2016 Cohort, n=410 3 of 12 151 µg/L 12 outcomes: Gestational week at birth, birthweight, stillbirth, Intrauterine growth restriction, preterm birth, LBW, Low Apgar score 1 min, Low Apgar score 5 min, antepartum haemorrhage, PIH, GDM and Caesarean delivery.
Alvarez-Pederol 2009 Cohort, n=657 2 of 2 95 µg/L (1st
trimester) 2 outcomes: Birth weight and SGA.
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