Maternal Iodine Status, Thyroid Function during Pregnancy, and Child Neurodevelopment

Thyroid hormone regulates the brain development of the fetus. The fetus does not have a mature thyroid gland until mid-pregnancy and is dependent on the transfer of thyroid hormone via the placenta. Adequate maternal thyroid hormone concentrations are therefore essential for an optimal development of the fetal brain. Sufficient iodine intake is also important because iodine is a component of thyroid hormone. This dissertation investigated which factors determine the iodine status (i.e., urinary iodine concentration) of pregnant women, how iodine status is associated with thyroid function during pregnancy, and how maternal iodine status and thyroid function during pregnancy are related to the IQ score, the risk of ADHD, and autistic traits of the child. This was investigated by means of prospective cohort research. Besides that we identified country specific dietary determinants, younger (pregnant) women, with a higher BMI and a low intake of dairy products had a greater risk of a lower iodine status. Lower iodine status was associated with only small differences in thyroid function (i.e., higher total thyroxine and a lower thyroid stimulating hormone concentration). Women with an adequate iodine intake had the lowest risk of thyroid autoantibody positivity. A lower iodine status in the first 14 weeks of pregnancy and a low concentration of free thyroxine were associated with a lower IQ score. Maternal iodine status was not associated with ADHD or autistic traits. A low and a high free thyroxine concentration were associated with a higher risk of autistic traits, but firm conclusions could not be drawn. There was no consistent evidence for an association between maternal thyroid function during pregnancy and child ADHD

Maternal Iodine Status During Pregnancy Is Not Consistently Associated with Attention-Deficit Hyperactivity Disorder or Autistic Traits in Children

BACKGROUND: Severe iodine deficiency during pregnancy can cause intellectual disability, presumably through inadequate placental transfer of maternal thyroid hormone to the fetus. The association between mild-to-moderate iodine deficiency and child neurodevelopmental problems is not well understood. OBJECTIVES: We investigated the association of maternal iodine status during pregnancy with child attention-deficit hyperactivity disorder (ADHD) and autistic traits. METHODS: This was a collaborative study of 3 population-based birth cohorts: Generation R (n = 1634), INfancia y Medio Ambiente (n = 1293), and the Avon Longitudinal Study of Parents and Children (n = 2619). Exclusion criteria were multiple fetuses, fertility treatment, thyroid-interfering medication use, and pre-existing thyroid disease. The mean age of assessment in the cohorts was between 4.4 and 7.7 y for ADHD symptoms and 4.5 and 7.6 y for autistic traits. We studied the association of the urinary iodine-to-creatinine ratio (UI/Creat) <150 μg/g-in all mother-child pairs, and in those with a urinary-iodine measurement at ≤18 weeks and ≤14 weeks of gestation-with the risk of ADHD or a high autistic-trait score (≥93rd percentile cutoff), using logistic regression. The cohort-specific effect estimates were combined by random-effects meta-analyses. We also investigated whether UI/Creat modified the associations of maternal free thyroxine (FT4) or thyroid-stimulating hormone concentrations with ADHD or autistic traits. RESULTS: UI/Creat <150 μg/g was not associated with ADHD (OR: 1.2; 95% CI: 0.7, 2.2; P = 0.56) or with a high autistic-trait score (OR: 0.8; 95% CI: 0.6, 1.1; P = 0.22). UI/Creat <150 μg/g in early pregnancy (i.e., ≤18 weeks or ≤14 weeks of gestation) was not associated with a higher risk of behavioral problems. The association between a higher FT4 and a greater risk of ADHD (OR: 1.3; 95% CI: 1.0, 1.6; P = 0.017) was not modified by iodine status. CONCLUSIONS: There is no consistent evidence to support an association of mild-to-moderate iodine deficiency during pregnancy with child ADHD or autistic traits

The association of maternal thyroid autoimmunity during pregnancy with child IQ

Context Thyroperoxidase antibody (TPOAb) positivity is a major risk factor for gestational thyroid dysfunction. During the first 18 to 20 weeks of pregnancy, high concentrations of human chorionic gonadotropin (hCG) stimulate the thyroid to ensure adequate thyroid hormone availability for the developing fetus. However, TPOAb-positive women have an impaired thyroidal response to hCG stimulation. Objective To study the association of maternal TPOAb positivity during pregnancy with child IQ. Design, Setting, and Participants This study was embedded in two prospective birth cohorts: Generation R (Rotterdam, the Netherlands) and Avon Longitudinal Study of Parents and Children (ALSPAC; United Kingdom). Mother-child pairs with available data on early pregnancy TPOAb (≤18 weeks of gestation) and offspring IQ were included (n = 3637 for Generation R and n = 2396 for ALSPAC). Main Outcome Measures Child IQ at 5 to 10 years of age. Results In Generation R, TPOAb positivity was associated with a 2.0 ± 0.9-point lower mean child IQ (P = 0.03). Sensitivity analyses showed negative effect estimates already from TPOAb concentrations considerably lower than currently used manufacturer cutoffs. In ALSPAC, neither TPOAb positivity nor TPOAb concentrations below manufacturer cutoffs were associated with child IQ (TPOAb positivity: 0.7 ± 1.0; P = 0.45). Adjustment for maternal TSH or free T4 concentrations or urinary iodine/creatinine ratio did not change the results. Conclusion TPOAb positivity during pregnancy was associated with lower child IQ in Generation R but not in ALSPAC. Further studies are needed to elucidate whether differences between the study populations, such as maternal iodine status, could be the underlying cause for these differences

Association of maternal iodine status with child IQ: a meta-analysis of individual-participant data

Dataset, supplement to the article (to be added later