Prenatal Iodine Supplementation and Early Childhood Neurodevelopment

Pregnancy Related Clinical Trial

— PoppiE  

Official title:

Prenatal Iodine Supplementation and Early Childhood Neurodevelopment

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04586348
• Other study ID #: PoppiE
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: January 18, 2021
• Est. completion date: December 2025

Study information

• Verified date: April 2024
• Source: South Australian Health and Medical Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 794
• Est. completion date: December 2025
• Est. primary completion date: May 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 16 Years and older

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• Known history of thyroid disease.
• Previous child diagnosed with thyroid dysfunction.
• Carrying a fetus with a known or suspected congenital abnormality.

Related Conditions & MeSH terms

• Neurodevelopmental Disorders
• Nutrition Disorder, Fetal
• Nutrition Disorders
• Pregnancy Related

Intervention

Combination Product:
• Low Iodine Supplement
Multivitamin and mineral supplement with reduced iodine
• Standard Iodine Supplement
Multivitamin and mineral supplement with standard amount of iodine to match current leading brands of prenatal supplements

Locations

Country	Name	City	State
Australia	South Australian Health and Medical Research Institute	North Adelaide	South Australia

Sponsors (6)

Lead Sponsor	Collaborator
South Australian Health and Medical Research Institute	Flinders Medical Centre, Mater Mothers' Hospital, Royal North Shore Hospital, The Royal Women's Hospital, Women's and Children's Hospital, Australia

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Proportion of participants with pre-eclampsia	Clinical diagnosis of pre-eclampsia as recorded in the participants handheld record.	At any time throughout current pregnancy
Other	Proportion of participants with induction of labour and reason for induction.	As recorded in the participants handheld record.	Delivery
Other	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
Other	Proportion of participants with gestational diabetes	Clinical diagnosis of gestational diabetes as recorded in the participants handheld record.	At any time throughout current pregnancy
Other	Proportion of participants with induced labour	As recorded in the participants handheld record.	Delivery
Other	Proportion of participants with vaginal delivery	Vaginal or caesarean delivery	Delivery
Other	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)
Other	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)
Other	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)
Other	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)
Other	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)
Primary	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
Secondary	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
Secondary	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.	24 months of age
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Thyroid stimulating hormone (TSH) level	Ascertained from Neonatal Screening Test	Within 5 days of birth
Secondary	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