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| Name | Class |
|---|---|
| Women's and Children's Hospital, Australia | OTHER_GOV |
| Flinders Medical Centre | OTHER_GOV |
| Mater Mothers' Hospital | OTHER |
| The Royal Women's Hospital |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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 |
|
| 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Low Iodine Supplement | Combination Product | Multivitamin and mineral supplement with reduced iodine |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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). | 24 months of age |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 24 months of age |
| Motor development of infants |
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of participants with pre-eclampsia | Clinical diagnosis of pre-eclampsia as recorded in the participants handheld record. | At any time throughout current pregnancy |
| Proportion of participants with induction of labour and reason for induction. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Karen P Best, PhD | South Australian Health and Medical Research Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| South Australian Health and Medical Research Institute | North Adelaide | South Australia | 5081 | Australia |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40390018 | Derived | 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. | |
| 37164467 | Derived | Best 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. |
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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.
Following final data analysis and primary publication
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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| ID | Term |
|---|---|
| D065886 | Neurodevelopmental Disorders |
| D048070 | Fetal Nutrition Disorders |
| ID | Term |
|---|---|
| D001523 | Mental Disorders |
| D005315 | Fetal Diseases |
| D011248 | Pregnancy Complications |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
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| UNKNOWN |
| Royal North Shore Hospital | OTHER |
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.
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Intervention and Control supplements will be packaged by Factors Group of Companies and labelled by contracted pharmaceutical personnel who are not involved in the trial. Study supplement bottles will be identified only by the blinded Product ID to match the randomisation schedule prepared by an independent statistician.
Research Personnel will access the Randomisation Module in REDCap and women will be allocated a random, unique, re-identifiable randomisation ID. Women will be issued with supplements labelled to match their unique assigned code.
| Standard Iodine Supplement | Combination Product | Multivitamin and mineral supplement with standard amount of iodine to match current leading brands of prenatal supplements |
|
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. |
| 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. | 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. | 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)]. | 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. | 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. | The neonatal period including birth to 28 days of age |
| Thyroid stimulating hormone (TSH) level | Ascertained from Neonatal Screening Test | 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. | 24 months of age |
As recorded in the participants handheld record.
| Delivery |
| Proportion of participants with postpartum hemorrhage | Clinical diagnosis of postpartum hemorrhage as recorded in the participants handheld record. | Within 24 hours of delivery of the infant |
| Proportion of participants with gestational diabetes | Clinical diagnosis of gestational diabetes as recorded in the participants handheld record. | At any time throughout current pregnancy |
| Proportion of participants with induced labour | As recorded in the participants handheld record. | Delivery |
| Proportion of participants with vaginal delivery | Vaginal or caesarean delivery | Delivery |
| Proportion of Maternal Adverse Events per group | Side effects and tolerability of supplements will be assessed through routine data collection. | From the date of randomization until delivery of the infant (up to 40 weeks) |
| Proportion of Maternal Serious Adverse Events per group | Maternal admissions to intensive care during the intervention period. Maternal death in the intervention period. | From the date of randomization until the date of delivery (up to 40 weeks) |
| Proportion of Fetal/Infant Serious Adverse Events | Fetal Mortality (after randomisation and prior to birth) including; miscarriage/terminations (pregnancy loss <20 weeks of gestation); stillbirth (intrauterine fetal death ≥20 weeks of gestation). Infant Mortality including; neonatal death (death of a live born infant in the first 28 days of life); infant death (death of an infant after the first 28 days of life). Major congenital anomalies. | From the date of randomization until the infant is 24 months of age (up to 144 weeks) |
| Economic Evaluation | A within-trial cost-effectiveness analysis will be conducted comparing costs and outcomes of the trial arms. The analysis will take into account a range of cost items including cost of interventions (i.e., dietary supplements) and cost of eligibility screening. Medicare data and data held by the State departments of health will be used to estimate direct health care costs associated with the management of poor developmental health outcomes over the study period including pharmaceuticals, out of hospital services (e.g., doctor visits), and hospital services (including emergency department presentations). | From the date of randomization until the infant is 24 months of age (up to 144 weeks) |
| Urinary Iodine Concentration | At baseline, median iodine concentration by state will be determined to confirm state differences in iodine status that have been previously identified and to determine balance between the two treatment groups. At 28 weeks we will examine median UIC by treatment group to assess group compliance and the success of the intervention. | At baseline (enrolment <13 weeks of gestation) and mid-pregnancy (28 weeks of gestation) |
| D000091642 | Urogenital Diseases |
| D044342 | Malnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |