Journal Article

Statistical analysis plan for the Prenatal Iodine Supplementation and Early Childhood Neurodevelopment (PoppiE) randomised controlled trial

Gould, Jacqueline F., Best, Karen P., Green, Tim J., Sullivan, Thomas R., Makrides, Maria M.

2025

Overview

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 μg/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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Age / Babies / Biomedicine / Care and treatment / Child development / Child Development - drug effects / Child development deviations / Child, Preschool / Cognition - drug effects / Cognitive development / Cohort analysis / Data Interpretation, Statistical / Developmental disabilities / Dietary supplements / Dietary Supplements - adverse effects / Female / Food / Food and nutrition / Health aspects / Health Sciences / Humans / Hypotheses / Hypothesis testing / Infant / Infant, Newborn / Iodine / Iodine - administration & dosage / Iodine - adverse effects / Iodine in the body / Medical statistics / Medicine / Medicine & Public Health / Methods / Miscarriage / Multicenter Studies as Topic / Multiple births / Nervous system diseases / Pregnancy / Pregnant women / Prenatal care / Prenatal Care - methods / Prevention / Randomised controlled trial / Randomized Controlled Trials as Topic / Risk factors / Statistical analysis / Statistical analysis plan / Statistics for Life Sciences / Stillbirth / Supplementation / Testing / Time Factors / Update