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Iodine status in pregnancy and associations with infant neurodevelopmental outcomes
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Date
2025
Authors
Kelliher, Lisa
Journal Title
Journal ISSN
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Publisher
University College Cork
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Abstract
Adequate iodine intake in pregnancy is crucial for foetal brain development. Although the effects of severe iodine deficiency are well established, data on the effects of mild-to-moderate deficiency are mixed. Pregnant women are vulnerable to iodine deficiency due to higher requirements and lower dietary intakes of key dietary sources, particularly cows’ milk. The overall aim of this thesis was to assess the iodine status of Irish women and to evaluate the relationship between maternal iodine status in early gestation, and child neurodevelopmental outcomes through a series of original research studies.
Chapter 2 describes the development of an iodine food frequency questionnaire (I-FFQ), and its validation in a convenience sample of non-pregnant Irish women aged 18-50 years (n=100) using a 4-day Food Diary (FD) as the reference method. Due to the overlap in dietary sources of iodine and vitamin D, the I-FFQ was developed by refining an existing UCC Vitamin D questionnaire and validated using the method of triads, Bland-Altman analysis and classification of the tertiles of intake distribution. The I-FFQ demonstrated reasonable validity; coefficients for the I-FFQ and FD and UIC were 0.542, 0.800 and 0.228, respectively. Median (IQR) intakes were estimated at 161 (106, 217)µg/d and 133 (98, 182)µg/d for the I-FFQ and FD, respectively (P =0.001), and were moderately correlated (r=0.434). The I-FFQ classified 89% of participants into the same or adjacent tertile of intake as the FD. The median (IQR) UIC of Irish women of childbearing age was low [82 (49,139)]µg/d. The I-FFQ provides a reasonable estimate of habitual iodine intake in women and due to its simplicity and reproducibility may have applications in research for screening individuals at risk of iodine deficiency.
Chapter 3 provides an account of dietary iodine intakes in two human nutrition intervention studies: the Cork Vitamin D requirements in pregnant women (DMAT) and the Trial to Assess Vitamin D Requirements in Lactating Women (DMUMs) pregnancy and breastfeeding RCTs. Participants (n=156) provided vitamin D intake at baseline (≤18 week’ gestation) using a quantitative FFQ, which was validated for vitamin D and calcium intakes. Iodine intakes in the current study were calculated by applying food composition data from COFIDs (7th edition) and the Food Safety Authority of Ireland to the food intake data. Thyroid hormones (TSH, FT3, FT4) were assessed longitudinally and Tg in the first trimester using existing maternal sera from the DMAT and DMUMs RCTs. Analytes were measured in duplicate by chemiluminescence immunoassay via the Beckman Coulter DXI900 at the Clinical Biochemistry Laboratory, Cork University Hospital. Associations between diet and thyroid function were explored, through Spearman’s correlation and cross-classification of thyroid hormones across tertiles of intake. From our analysis, in euthyroid pregnant women (n=144) median (IQR) iodine intake was 293 (227, 371)μg/d and 13% had intakes below the IOM AR (200µg/d). There was a large differential in the prevalence below the IOM AR, between iodine containing supplement users and non-users (1.1% of and 34%, respectively). Milk made the largest contribution to iodine intake (42.7%). Nutritional supplements were the second highest contributor to iodine intake (30.1%). In breastfeeding mothers, (n=109) median (IQR) intakes were 197 (140, 280)µg/d and over half of women had intakes below the Institute of Medicine (IOM) Average Requirement (AR) (209µg/d). The prevalence of iodine containing supplement use was low (8% at first visit ). Cows’ milk made the largest contribution to iodine intake (62.6%), with fish coming second (8.0%). Associations between diet and thyroid hormones were assessed across the three trimesters and during breastfeeding. We did not observe any significant differences in thyroid function across thirds of the intake distribution, except for TSH in pregnant women at the midpoint visit. Isolated maternal hypothyroxinaemia was most prevalent in the third trimester (9.3%). Additionally, trimester specific normative reference ranges were determined for pregnant and breastfeeding women in the Irish population. Many women had low iodine intakes and although there were no associations between diet and thyroid function, the finding of 9% of women with isolated maternal hypothyroxinaemia in the third trimester is one with warrants further investigation of the long-term effects of inadequate iodine intake and thyroid function in this population.
In chapter 4 we conducted the first large scale assessment (n=1350) of maternal iodine status using existing biobanked data from the Cork arm of the European funded IMproved PRegnancy Outcomes by Early Detection (IMPROvED) study. Urinary iodine concentration (UIC) at 11 and 15-weeks’ gestation was quantified by the Sandell-Kolthoff (S-K) microplate colorimetric method and creatinine was measured on the Randox Monaco analyser. The non-dietary determinants of maternal UIC and I:Cr were explored in multivariate linear and logistic regression models. Low maternal iodine status was observed at both timepoints, 128µg/L and 125µg/L at 11 and 15 weeks, respectively. In fully adjusted models, iodine-containing nutritional supplement use and winter season of sampling were significant predictors of UIC (µg/L and UIC <150µg/L) at 15 weeks’ gestation. After correction for urine volume, supplement use, education, BMI, winter UIC sampling and age were significant predictors of I:Cr < 150µg/g. This study showed that most Irish women had insufficient iodine status during early pregnancy and there is a need to further evaluate the implications of low maternal intake on infant neurodevelopment.
The first assessment of maternal iodine status in pregnancy and its associations with child neurodevelopment was conducted in chapter 5. The Cork Nutrition and Development Maternal-Infant cohort (COMBINE), which was a follow up birth cohort to the IMPROvED study, assessed child neurodevelopment and behavioural outcomes up to 2 years, through psychologist led validated assessments: Bayley Scales of Infant and Toddler Development (3rd edition) (BSID-III) and the Child Behaviour Checklist (CBCL). Associations between maternal UIC/I:Cr and child neurodevelopment at 24 months was tested using multivariate linear and logistic regression. In fully adjusted multivariate linear regression models maternal UIC <100µg/L was negatively associated with child cognitive (β (95% CI): -3.97 (-7.70, -0.24), P = 0.037) and language (β (95% CI): -5.14 (-9.95, -0.34), P =0.036) composite scores, and with the combined cognitive and language scores (β (95% CI): -4.29 (-8.26, -0.32, P =0.034) (reflective of executive function). No significant observations were found between maternal urinary iodine status and child behaviour problem scores.
Conclusion
Overall, the results of this thesis indicate that iodine status is low among Irish pregnant and breastfeeding women, and in women of childbearing age. Low maternal iodine status in early pregnancy was associated with lower child language, cognition and executive functioning at 2 years, which is concerning as there are currently no policies for mandatory fortification or supplementation and awareness of the importance of the role of iodine in health is low.
Description
Keywords
Iodine intake , Iodine status , Child neurodevelopment , Pregnancy
Citation
Kelliher, L. 2025. Iodine status in pregnancy and associations with infant neurodevelopmental outcomes. PhD Thesis, University College Cork.