Clinical trial NCT00791466: Maternal Iodine Supplementation and Effects on Thyroid Function and Child Development
Official title: Iodine Supplementation in Pregnant Women Living in Mild-to-moderately Iodine Deficient Areas in India and Thailand: Effects on Pregnancy Outcome and Infant Development
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Iodine Deficiency
Infant Development
Keywords: Iodine deficiency
Pregnancy
Thyroid function
Infant development
Growth
Lead sponsor: Wageningen University
Sponsor class: OTHER
Collaborators: name: St. John's Research Institute
name: Mahidol University
name: Unilever R&D
name: Swiss National Science Foundation
name: Nestlé Foundation
First posted: 2008-11-14
Enrollment: 829
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Rationale: In regions of severe endemic goiter, the adverse effects of in utero iodine deficiency on neuromotor development are well established: randomized controlled trials of iodine supplements given to iodine deficient mothers before pregnancy or during early pregnancy improve motor and cognitive performance of their offspring. However, the potential adverse effects of mild-to-moderate iodine deficiency during pregnancy are unclear. Inadequate thyroid function in the fetus and newborn are the likely cause of brain damage in iodine deficiency.

Objective: To determine whether the daily oral administration of 200 µg iodine to pregnant women in areas of mild-to-moderate iodine deficiency improves maternal and newborn thyroid function, pregnancy outcome, birth weight, infant growth and cognitive performance.

Study design: Double-blind randomized controlled multicentre trial. Study population: Pregnant women (18-40 years) presenting at the clinic for their first prenatal visit will be recruited at two research sites, namely St. Martha's hospital in Bangalore, India and Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. At each site, 400 women will be recruited.

Intervention: Half of the women will be randomized to iodine treatment (200 µg per day) and the other half to placebo throughout pregnancy.

Main study parameters/endpoints: Differences between group means in indicators of thyroid function, birth outcome, urinary iodine, breast milk iodine, infant growth, and psychomotor development.


Eligibility criteria: Inclusion Criteria:

* Age 18-40 years;
* Gestational age: ≤ 14 weeks (as judged by the date of the last menstrual period);
* Single pregnancy;
* Non-lactating;
* Planned residence in the area for the duration of the study (3 years).

Exclusion Criteria:

* TSH levels outside the normal range
* History of serious medical conditions such as HIV, hypertension, diabetes, renal, hepatic or cardiovascular disease, thyroid disorders, mental disorders;
* Use of iodine supplement.

Primary outcomes:
measure: Current primary outcome: Infant cognitive and motor development
timeFrame: Regular intervals up till 6 years of age
measure: Original primary outcome: Maternal thyroid function
timeFrame: 3-month intervals during pregnancy, at delivery
Secondary outcomes:
measure: Birth outcome
timeFrame: At delivery
measure: Maternal and infant urinary iodine
timeFrame: Regular intervals during pregnancy up till 2 years after delivery
measure: Breast milk iodine
timeFrame: 3 and 6 months after delivery
measure: Long-term follow up
timeFrame: Child age 2-6 years
Other outcomes:
Locations:
city: Bangalore
country: India
facility: St. Johns Medical College and Research Institute
city: Bangkok
country: Thailand
facility: Insitute of Nutrition, Mahidol University (INMU)
Study officials:
affiliation: Wageningen University
name: Michael Zimmermann, Prof. dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Wageningen University
name: Alida Melse-Boonstra, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Melse-Boonstra A, Gowachirapant S, Jaiswal N, Winichagoon P, Srinivasan K, Zimmermann MB. Iodine supplementation in pregnancy and its effect on child cognition. J Trace Elem Med Biol. 2012 Jun;26(2-3):134-6. doi: 10.1016/j.jtemb.2012.03.005. Epub 2012 May 8.
citation: Gowachirapant S, Melse-Boonstra A, Winichagoon P, Zimmermann MB. Overweight increases risk of first trimester hypothyroxinaemia in iodine-deficient pregnant women. Matern Child Nutr. 2014 Jan;10(1):61-71. doi: 10.1111/mcn.12040. Epub 2013 Aug 13.
citation: Jaiswal N, Melse-Boonstra A, Thomas T, Basavaraj C, Sharma SK, Srinivasan K, Zimmermann MB. High prevalence of maternal hypothyroidism despite adequate iodine status in Indian pregnant women in the first trimester. Thyroid. 2014 Sep;24(9):1419-29. doi: 10.1089/thy.2014.0071. Epub 2014 Jul 21.
citation: Gowachirapant S, Jaiswal N, Melse-Boonstra A, Galetti V, Stinca S, Mackenzie I, Thomas S, Thomas T, Winichagoon P, Srinivasan K, Zimmermann MB. Effect of iodine supplementation in pregnant women on child neurodevelopment: a randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol. 2017 Nov;5(11):853-863. doi: 10.1016/S2213-8587(17)30332-7. Epub 2017 Oct 10.
citation: Verhagen NJE, Gowachirapant S, Winichagoon P, Andersson M, Melse-Boonstra A, Zimmermann MB. Iodine Supplementation in Mildly Iodine-Deficient Pregnant Women Does Not Improve Maternal Thyroid Function or Child Development: A Secondary Analysis of a Randomized Controlled Trial. Front Endocrinol (Lausanne). 2020 Oct 6;11:572984. doi: 10.3389/fendo.2020.572984. eCollection 2020.