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Updated: Apr 5, 2026

Author Spotlight: Studying the Impact of Maternal Dietary Deficiencies on Long-Term Offspring Health Outcomes
Published on: June 28, 2024
Maternal hypothyroxinaemia in early pregnancy and school performance in 5-year-old offspring
Anna M E Noten1, Eva M Loomans2, Tanja G M Vrijkotte1
1Department of PediatricsVU University Medical Center, PO Box 7057, 1007 MB Amsterdam, The NetherlandsDepartment of EpidemiologyDocumentation and Health Promotion, Public Health Service Amsterdam, Amsterdam, The NetherlandsDepartment of Developmental PsychologyTilburg University, Tilburg, The NetherlandsDepartment of Public HealthAcademic Medical Center, University of Amsterdam, Amsterdam, The NetherlandsDepartment of Epidemiology and BiostatisticsVU University Medical Center, Amsterdam, The NetherlandsDepartment of Pediatric EndocrinologyAcademic Medical Center, Emma Children's Hospital, University of Amsterdam, Amsterdam, The NetherlandsDepartment of Health SciencesVU University, Amsterdam, The Netherlands.
Insights
Maternal hypothyroxinaemia during early pregnancy may affect children's arithmetic skills. Low maternal free thyroxine (T4) levels were linked to poorer school performance in 5-year-olds, but not language skills.
Area of Science:
- Endocrinology
- Neurodevelopment
- Pediatric Health
Background:
- Overt hypothyroidism in pregnancy is linked to lower child IQ.
- Subtle maternal thyroid dysfunction may impair offspring neurodevelopment.
- The impact of first-trimester hypothyroxinaemia on school performance requires investigation.
Purpose of the Study:
- To assess the effect of maternal hypothyroxinaemia in early pregnancy on school performance at age 5.
- To determine if low maternal free thyroxine (T4) levels impact arithmetic and language test scores.
Main Methods:
- Longitudinal study of 1196 mother-child pairs.
- Maternal serum free T4 and TSH measured at median 12.9 weeks gestation.
- School performance assessed at age 5 using national arithmetic and language tests.
Main Results:
- Maternal hypothyroxinaemia (lowest 10% free T4) associated with increased odds of subnormal arithmetic performance (OR 1.61, P=0.03).
- Association weakened after inverse-probability weighting (OR 1.48, P=0.09).
- No significant association found between maternal hypothyroxinaemia and language performance or TSH levels.
Conclusions:
- Maternal hypothyroxinaemia in early pregnancy may be associated with reduced arithmetic performance in 5-year-old children.
- No association observed with language test performance.
- Results warrant cautious interpretation due to potential non-response bias.
Objective:
Overt hypothyroidism in pregnant women is associated with a lower intelligence quotient in their children. More recently, subtle decreases in maternal thyroid function have also been associated with neurodevelopmental impairment in offspring. We tested the effect of hypothyroxinaemia during early pregnancy on school performance.
Design:
This was a longitudinal study that included the data of 1196 mother-child pairs from the Amsterdam Born Children and Their Development study.
Methods:
Maternal serum free thyroxine (T4) and TSH were obtained at a median gestational age of 12.9 (interquartile range: 11.9-14.3) weeks. School performance was assessed at age 5 years and based on scores obtained in arithmetic and language tests from the national monitoring and evaluation system. Poor school performance was defined as a test result <25th percentile and subnormal school performance as a result <50th percentile of the norm population. To estimate the impact of possible non-response bias, we conducted inverse-probability weighted analyses.
Results:
Maternal hypothyroxinaemia (i.e., a maternal free T4 in the lowest 10% of distribution) was associated with a 1.61 (95% CI: 1.05-2.47) -fold increased odds of subnormal arithmetic performance after adjustment for confounders (P=0.03). However, the odds ratio dropped to 1.48 (95% CI: 0.94-2.32) after inverse-probability weighting (P=0.09). No such relations were found with TSH.
Conclusions:
Maternal hypothyroxinaemia at the end of the first trimester was associated with reduced performance in an arithmetic test, but not in a language test, in 5-year-old offspring. However, our results should be interpreted carefully because of possible non-response bias.
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