Pregnancy RelatedPhase 4PoppiENCT04586348
Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
A Phase 4 study testing Low Iodine Supplement and Standard Iodine Supplement in people with Pregnancy Related and Neurodevelopmental Disorders, run by South Australian Health and Medical Research Institute at 1 site in Australia.
Trial summary
A randomized controlled trial to determine the effect of reducing iodine from vitamin and mineral supplements for pregnant women who have adequate iodine intakes (>165 μg/d from food alone) on cognitive development of children at 24 months of age. Read more about this study
- Who is it for?
- Ages 16 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- Pregnancy Related, Neurodevelopmental Disorders, Nutrition Disorder, Fetal
- What is being tested?
- Low Iodine Supplement and Standard Iodine Supplement
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 794 participants
- Where
- 1 siteAustralia
- Study dates
- 18 Jan 2021to Dec 2025
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- Women only
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- Pregnant women ≤13 weeks of gestation.
- Consume greater than 165 µg/d of iodine from food alone based on our validated Iodine Specific Food Frequency Questionnaire (I-FFQ).
- English is main language spoken at home as child will need to understand and take instruction in English to participate in the neurodevelopmental assessment.
- Able to give informed consent.
Who cannot join
- Known history of thyroid disease.
- Previous child diagnosed with thyroid dysfunction.
- Carrying a fetus with a known or suspected congenital abnormality.
Trial locations and contacts
1 site in 1 country.
Australia1 site
South Australian Health and Medical Research Institute
North Adelaide, South Australia, 5081
About this study
A randomized controlled trial to determine the effect of reducing iodine from vitamin and mineral supplements for pregnant women who have adequate iodine intakes (>165 μg/d from food alone) on cognitive development of children at 24 months of age.
Read the detailed description
It is known that severe iodine deficiency during pregnancy leads to profound intellectual disabilities in the child. Following results of a 2004 national survey of school-aged children showing that mild iodine deficiency had re-emerged in the south-eastern parts of Australia, the Australian government mandated the addition of iodine to salt used in bread making to increase population iodine intake. It is also recommended that all pregnant and lactating women take an additional iodine supplement containing 150 µg/d of iodine.
Since this time, further evidence has emerged from cohort studies that children born to women with high iodine intake (as well as low iodine intake) have poorer neurodevelopmental scores, suggesting that more tailored supplementation may be a better strategy. Our PoppiE trial will determine if limiting iodine supplementation in women who already consume adequate iodine from food, improves cognitive scores in early childhood.
A total of 754 pregnant women from around Australia who are ≤13 weeks of gestation will be enrolled and randomised to receive a standard prenatal vitamin and mineral supplement with a reduced amount of iodine (20 μg - intervention) or a standard prenatal vitamin and mineral supplement with 200 μg of iodine (control). The control supplement contains a level of iodine to match the amount in most commonly used vitamin and mineral supplements sold in Australia. Infant neurodevelopment at 24 months of age will be assessed using the Bayley-IV and conducted at participating centres or a location convenient to the family.
- Being tested
- Low Iodine Supplement, Standard Iodine Supplement
- Keywords
- Iodine, Supplementation
- Medical subject headings
- Neurodevelopmental Disorders, Fetal Nutrition Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low Iodine SupplementCombination product
Multivitamin and mineral supplement with reduced iodine
Standard Iodine SupplementCombination product
Multivitamin and mineral supplement with standard amount of iodine to match current leading brands of prenatal supplements
| Study group | Role | What they receive |
|---|---|---|
| Low Iodine Supplement | Experimental | Iodine (potassium iodide) 20 μg Beta carotene (All trans-beta- carotene) 1500 μg; Vitamin E (dl-alphatocopheryl acetate) 13.5 mg AT; Vitamin D3 (cholecalciferol) 10 μg; Vitamin C (ascorbic acid granular) 60 mg; Niacinamide 18 mg; Pantothenic acid (calcium d- pantothenate) 6 mg; Vitamin B6 (DC pyridoxine hydrochloride) 1.9 mg; Vitamin B1 (thiamine mononitrate) 1.4 mg; Vitamin B2 (riboflavin) 1.4 mg; Biotin 30 μg; Vitamin B12 (methyl-cobalamin) 2.6 μg; Folic Acid 0.4 mg; Levomefolic acid 0.1 mg; Calcium (carbonate DC) 250 mg; Magnesium (oxide granular) 50 mg; Iron (ferrous fumarate) 20 mg; Zinc (oxide) 10 mg; Manganese (sulphate) 2 mg; Copper (sulphate) 1 mg; Selenium (rice chelate) 30 μg Receives: Combination Product: Low Iodine Supplement |
| Standard Iodine Supplement | Active comparator | Iodine (potassium iodide) 200 μg Beta carotene (All trans-beta- carotene) 1500 μg; Vitamin E (dl-alphatocopheryl acetate) 13.5 mg AT; Vitamin D3 (cholecalciferol) 10 μg; Vitamin C (ascorbic acid granular) 60 mg; Niacinamide 18 mg; Pantothenic acid (calcium d- pantothenate) 6 mg; Vitamin B6 (DC pyridoxine hydrochloride) 1.9 mg; Vitamin B1 (thiamine mononitrate) 1.4 mg; Vitamin B2 (riboflavin) 1.4 mg; Biotin 30 μg; Vitamin B12 (methyl-cobalamin) 2.6 μg; Folic Acid 0.4 mg; Levomefolic acid 0.1 mg; Calcium (carbonate DC) 250 mg; Magnesium (oxide granular) 50 mg; Iron (ferrous fumarate) 20 mg; Zinc (oxide) 10 mg; Manganese (sulphate) 2 mg; Copper (sulphate) 1 mg; Selenium (rice chelate) 30 μg Receives: Combination Product: Standard Iodine Supplement |
What is being measured
The primary outcome is the main question the study is designed to answer.
Infant Developmental quotient (DQ)
The Bayley Scales of Infant and Toddler Development, 4th Edition Cognitive Scale score has a mean of 100 and standard deviation of 15, where higher scores indicate a better outcome. As the Bayley scales are age-standardized scales the exact minimum and maximum score depends on the exact age of the child at the time of the assessment, hence we have instead provided the mean and standard deviation (as is the norm when reporting standardized psychometric assessments).
Measured: 24 months of age
Secondary outcomes (9)
Language development of infants using Bayley-IV
The Bayley Scales of Infant and Toddler Development, 4th Edition Language Scale score has a mean of 100 and standard deviation of 15, where higher scores indicate a better outcome.
Measured: 24 months of age
Motor development of infants
The Bayley Scales of Infant and Toddler Development, 4th Edition Motor Scale score has a mean of 100 and standard deviation of 15, where higher scores indicate a better outcome.
Measured: 24 months of age
Behavioral and emotional development
Behavioral and emotional development of infants using the Infant Toddler Social Emotional Assessment (ITSEA). The Infant-Toddler Social \& Emotional Assessment scale has range of 0-100 where higher T scores indicate a worse outcome.
Measured: 24 months of age
Health service utilization
Health service utilisation of children assessed through data linkage of the Medicare Benefits Schedule, Pharmaceutical Benefits Scheme to evaluate the cost effectiveness of the intervention.
Measured: 24 months of age
Length of gestation
The gestational age in days at birth (or other event of interest) will be determined from the estimated date of delivery using the equation [280 - (estimated date of delivery - date of birth)].
Measured: Birth
Infant Birth Anthropometrics
Infant weight, length and head circumference will be analysed, using both the raw measurements and Z-scores for corresponding gestational age and sex, using means and standard deviations.
Measured: Birth
Admission to special care baby unit (level 2 nursery).
Any admission to a special care baby unit or level 2 nursery up to 28 days post birth.
Measured: The neonatal period including birth to 28 days of age
Thyroid stimulating hormone (TSH) level
Ascertained from Neonatal Screening Test
Measured: Within 5 days of birth
Infant Anthropometrics
Average weight, height and head circumference measurements at 24 months of age will be converted to z-scores using WHO growth standards. For preterm infants, corrected age at the time of the measurement rather than chronological age will be used in deriving the z-scores.
Measured: 24 months of age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Oct 2020
- Study start18 Jan 2021
- Primary completionMay 2025 (estimated)
- Study completionDec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Pregnancy RelatedStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- A multi-centre, randomised, controlled, clinician, researcher and participant blinded trial with two parallel groups. An independent statistician not otherwise involved in the study or data analysis will generate and keep the randomisation schedule. The computer-generated schedule will allocate women to intervention or control groups in the ratio of 1:1 using randomly permuted blocks of size 6 and 8, with stratification for state of enrolment. Randomisations will be performed by approved study staff via a secure web-based randomisation service.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 794 participants (actual)
Sponsor and investigators
- Lead sponsor
- South Australian Health and Medical Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Women's and Children's Hospital, Australia, Flinders Medical Centre, Mater Mothers' Hospital, The Royal Women's Hospital, Royal North Shore Hospital
- Responsible party
- Principal investigator, Karen Best, South Australian Health and Medical Research Institute
- Investigators
- Karen P Best, PhD, Principal investigator, South Australian Health and Medical Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04586348
- Sponsor's protocol ID
- PoppiE
- Acronym
- PoppiE
- Status last verified
- Apr 2024
- First submitted
- 30 Sep 2020
- Last updated
- 3 Apr 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Access to study data may be granted, upon review and approval of the HREC, trial steering committee and in accordance with SAHMRI W\&K 'Guidelines and Agreement for the use of materials in an ancillary study associated with original clinical trials or cohort studies.
Publications
Sullivan TR, Green TJ, Gould JF, Makrides MM, Best KP. Statistical analysis plan for the Prenatal Iodine Supplementation and Early Childhood Neurodevelopment (PoppiE) randomised controlled trial. Trials. 2025 May 19;26(1):162. doi: 10.1186/s13063-025-08863-1.
PubMed 40390018Best KP, Gould JF, Makrides M, Sullivan T, Cheong J, Zhou SJ, Kane S, Safa H, Sparks A, Doyle LW, McPhee AJ, Nippita TAC, Afzali HHA, Grivell R, Mackerras D, Knight E, Wood S, Green T. Prenatal iodine supplementation and early childhood neurodevelopment: the PoppiE trial - study protocol for a multicentre randomised controlled trial. BMJ Open. 2023 May 10;13(5):e071359. doi: 10.1136/bmjopen-2022-071359.
PubMed 37164467
Study at a glance
From the registry record, last updated by the sponsor on 3 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
- ClinicalTrials.gov ID
- NCT04586348
- Acronym / sponsor ID
- PoppiE / PoppiE
- Keywords
- Iodine, Supplementation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 794 participants (actual)
- Lead sponsor
- South Australian Health and Medical Research InstituteUniversity, hospital or other
- Collaborators
- Women's and Children's Hospital, Australia, Flinders Medical Centre, Mater Mothers' Hospital, The Royal Women's Hospital, Royal North Shore Hospital
- Study start
- 18 Jan 2021 (actual)
- Primary completion
- May 2025 (estimated)
- Study completion
- Dec 2025 (estimated)
- First posted
- 14 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A randomized controlled trial to determine the effect of reducing iodine from vitamin and mineral supplements for pregnant women who have adequate iodine intakes (>165 μg/d from food alone) on cognitive development of children at 24 months of age.
Detailed description
It is known that severe iodine deficiency during pregnancy leads to profound intellectual disabilities in the child. Following results of a 2004 national survey of school-aged children showing that mild iodine deficiency had re-emerged in the south-eastern parts of Australia, the Australian government mandated the addition of iodine to salt used in bread making to increase population iodine intake. It is also recommended that all pregnant and lactating women take an additional iodine supplement containing 150 µg/d of iodine.
Since this time, further evidence has emerged from cohort studies that children born to women with high iodine intake (as well as low iodine intake) have poorer neurodevelopmental scores, suggesting that more tailored supplementation may be a better strategy. Our PoppiE trial will determine if limiting iodine supplementation in women who already consume adequate iodine from food, improves cognitive scores in early childhood.
A total of 754 pregnant women from around Australia who are ≤13 weeks of gestation will be enrolled and randomised to receive a standard prenatal vitamin and mineral supplement with a reduced amount of iodine (20 μg - intervention) or a standard prenatal vitamin and mineral supplement with 200 μg of iodine (control). The control supplement contains a level of iodine to match the amount in most commonly used vitamin and mineral supplements sold in Australia. Infant neurodevelopment at 24 months of age will be assessed using the Bayley-IV and conducted at participating centres or a location convenient to the family.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- A multi-centre, randomised, controlled, clinician, researcher and participant blinded trial with two parallel groups. An independent statistician not otherwise involved in the study or data analysis will generate and keep the randomisation schedule. The computer-generated schedule will allocate women to intervention or control groups in the ratio of 1:1 using randomly permuted blocks of size 6 and 8, with stratification for state of enrolment. Randomisations will be performed by approved study staff via a secure web-based randomisation service.
| Arm | Type | Receives |
|---|---|---|
| Low Iodine Supplement | Experimental | Combination Product: Low Iodine SupplementIodine (potassium iodide) 20 μg Beta carotene (All trans-beta- carotene) 1500 μg; Vitamin E (dl-alphatocopheryl acetate) 13.5 mg AT; Vitamin D3 (cholecalciferol) 10 μg; Vitamin C (ascorbic acid granular) 60 mg; Niacinamide 18 mg; Pantothenic acid (calcium d- pantothenate) 6 mg; Vitamin B6 (DC pyridoxine hydrochloride) 1.9 mg; Vitamin B1 (thiamine mononitrate) 1.4 mg; Vitamin B2 (riboflavin) 1.4 mg; Biotin 30 μg; Vitamin B12 (methyl-cobalamin) 2.6 μg; Folic Acid 0.4 mg; Levomefolic acid 0.1 mg; Calcium (carbonate DC) 250 mg; Magnesium (oxide granular) 50 mg; Iron (ferrous fumarate) 20 mg; Zinc (oxide) 10 mg; Manganese (sulphate) 2 mg; Copper (sulphate) 1 mg; Selenium (rice chelate) 30 μg |
| Standard Iodine Supplement | Active comparator | Combination Product: Standard Iodine SupplementIodine (potassium iodide) 200 μg Beta carotene (All trans-beta- carotene) 1500 μg; Vitamin E (dl-alphatocopheryl acetate) 13.5 mg AT; Vitamin D3 (cholecalciferol) 10 μg; Vitamin C (ascorbic acid granular) 60 mg; Niacinamide 18 mg; Pantothenic acid (calcium d- pantothenate) 6 mg; Vitamin B6 (DC pyridoxine hydrochloride) 1.9 mg; Vitamin B1 (thiamine mononitrate) 1.4 mg; Vitamin B2 (riboflavin) 1.4 mg; Biotin 30 μg; Vitamin B12 (methyl-cobalamin) 2.6 μg; Folic Acid 0.4 mg; Levomefolic acid 0.1 mg; Calcium (carbonate DC) 250 mg; Magnesium (oxide granular) 50 mg; Iron (ferrous fumarate) 20 mg; Zinc (oxide) 10 mg; Manganese (sulphate) 2 mg; Copper (sulphate) 1 mg; Selenium (rice chelate) 30 μg |
Who may qualify
- Ages
- 16 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- Pregnant women ≤13 weeks of gestation.
- Consume greater than 165 µg/d of iodine from food alone based on our validated Iodine Specific Food Frequency Questionnaire (I-FFQ).
- English is main language spoken at home as child will need to understand and take instruction in English to participate in the neurodevelopmental assessment.
- Able to give informed consent.
Key exclusion criteria (3 listed)
- Known history of thyroid disease.
- Previous child diagnosed with thyroid dysfunction.
- Carrying a fetus with a known or suspected congenital abnormality.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Low Iodine SupplementMultivitamin and mineral supplement with reduced iodine | Combination product | Low Iodine Supplement |
| Standard Iodine SupplementMultivitamin and mineral supplement with standard amount of iodine to match current leading brands of prenatal supplements | Combination product | Standard Iodine Supplement |
Primary outcome
Infant Developmental quotient (DQ)
Time frame: 24 months of age
The Bayley Scales of Infant and Toddler Development, 4th Edition Cognitive Scale score has a mean of 100 and standard deviation of 15, where higher scores indicate a better outcome. As the Bayley scales are age-standardized scales the exact minimum and maximum score depends on the exact age of the child at the time of the assessment, hence we have instead provided the mean and standard deviation (as is the norm when reporting standardized psychometric assessments).
9 secondary outcomes
Language development of infants using Bayley-IV
Time frame: 24 months of age
Motor development of infants
Time frame: 24 months of age
Behavioral and emotional development
Time frame: 24 months of age
Health service utilization
Time frame: 24 months of age
Length of gestation
Time frame: Birth
Infant Birth Anthropometrics
Time frame: Birth
Admission to special care baby unit (level 2 nursery).
Time frame: The neonatal period including birth to 28 days of age
Thyroid stimulating hormone (TSH) level
Time frame: Within 5 days of birth
Infant Anthropometrics
Time frame: 24 months of age
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Apr 2024.
- Derived from this study: PubMed 40390018Sullivan TR, Green TJ, Gould JF, Makrides MM, Best KP. Statistical analysis plan for the Prenatal Iodine Supplementation and Early Childhood Neurodevelopment (PoppiE) randomised controlled trial. Trials. 2025 May 19;26(1):162. doi: 10.1186/s13063-025-08863-1.
- Derived from this study: PubMed 37164467Best KP, Gould JF, Makrides M, Sullivan T, Cheong J, Zhou SJ, Kane S, Safa H, Sparks A, Doyle LW, McPhee AJ, Nippita TAC, Afzali HHA, Grivell R, Mackerras D, Knight E, Wood S, Green T. Prenatal iodine supplementation and early childhood neurodevelopment: the PoppiE trial - study protocol for a multicentre randomised controlled trial. BMJ Open. 2023 May 10;13(5):e071359. doi: 10.1136/bmjopen-2022-071359.
- Individual participant dataSharing planned: Yes. Access to study data may be granted, upon review and approval of the HREC, trial steering committee and in accordance with SAHMRI W\&K 'Guidelines and Agreement for the use of materials in an ancillary study associated with original clinical trials or cohort studies.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Karen P Best, PhD principal investigator
South Australian Health and Medical Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Low Iodine Supplement and Standard Iodine Supplement in people with Pregnancy Related and Neurodevelopmental Disorders, run by South Australian Health and Medical Research Institute at 1 site in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 3 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Infant Developmental quotient (DQ) (time frame: 24 months of age). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04586348, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Apr 2024.