Related Experiment Video
Updated: May 23, 2025
Author Spotlight: Studying the Impact of Maternal Dietary Deficiencies on Long-Term Offspring Health Outcomes
Published on: June 28, 2024
Statistical analysis plan for the Prenatal Iodine Supplementation and Early Childhood Neurodevelopment (PoppiE)
Thomas R Sullivan1,2, Tim J Green3,4, Jacqueline F Gould3,5,6
1Women and Kids Theme, South Australian Health and Medical Research Institute, Level 7, Women's and Children's Hospital, 72 King William Road, North Adelaide, Adelaide, SA, 5006, Australia. thomas.sullivan@sahmri.com.
Insights
This study investigates prenatal iodine supplementation effects on child neurodevelopment. It aims to determine if higher iodine intake impacts development in women with sufficient dietary iodine.
Area of Science:
- Maternal and Child Health
- Nutritional Neuroscience
- Clinical Trials
Background:
- Observational studies link both low and high maternal iodine intake to adverse child neurodevelopment.
- Concerns exist that universal iodine supplementation may harm children whose mothers already consume adequate iodine.
Purpose of the Study:
- To evaluate the impact of prenatal iodine supplementation on early childhood neurodevelopment.
- To assess neurodevelopmental outcomes in infants born to mothers with sufficient dietary iodine intake.
Main Methods:
- The PoppiE trial is a multi-centre, blinded randomized controlled trial.
- Pregnant women with adequate dietary iodine intake were randomized to receive 20 µg/day (intervention) or 200 µg/day (control) of iodine.
- The primary outcome is infant developmental quotient at 24 months, assessed using the Bayley Scales of Infant Development, 4th Edition.
Main Results:
- Recruitment is complete, with data collection concluding in July 2026.
- The statistical analysis plan was finalized pre-database lock to prevent bias.
- This trial is the first to specifically investigate this population and intervention.
Conclusions:
- The PoppiE trial will provide crucial data on prenatal iodine supplementation in well-nourished populations.
- Findings will inform public health recommendations regarding iodine intake during pregnancy.
- Ensuring unbiased analysis through a pre-defined statistical plan is a key strength.
Background:
Observational evidence suggests both low and high iodine intakes in pregnancy are associated with poorer neurodevelopment in children. This raises concern that blanket recommendations for iodine supplementation in pregnancy may negatively impact child neurodevelopment in women with sufficient iodine intake from food alone.
Methods:
PoppiE (Prenatal Iodine Supplementation and Early Childhood Neurodevelopment) is a multi-centre, parallel, two-arm, clinician, researcher and participant blinded randomised controlled trial. Seven hundred fifty-four consenting pregnant women ≤ 13 weeks of gestation with an iodine intake of > 165 microg/day from food will be randomised to receive a multivitamin and mineral supplement containing 20 µg/day (intervention) or 200 µg/day (control) of iodine from enrolment until delivery. The primary outcome is the developmental quotient of infants at 24 months of age as assessed with the Cognitive Scale Score of the Bayley Scales of Infant Development, 4th Edition, to be analysed using linear regression with generalised estimating equations to account for multiple births. In this article, we comprehensively detail the planned statistical analyses of the PoppiE trial, including approaches to intercurrent events, methods for handling missing data and planned sensitivity analyses.
Conclusions:
PoppiE is the first trial to examine the effect of prenatal iodine supplementation on early childhood development in women with sufficient iodine intake from food. At the time of writing (February 2025), recruitment into the trial is complete and data collection is due to conclude in July 2026. The statistical analysis plan was finalised before the database lock, which will ensure study conclusions are not subject to bias due to data-driven analyses.
Trial Registration:
ClinicalTrials.gov NCT04586348. Registered on October 14, 2020.
