Interaction between isolated maternal hypothyroxinemia and pregnancy-related anxiety on preschooler’s internalizing and externalizing problems: A birth cohort study

Isolated maternal hypothyroxinemia (IMH) and pregnancy-related anxiety may increase the risk of offspring's emotional and behavioral problems, but little is known about their potential interactive effect on preschoolers' internalizing and externalizing problems.We conducted a large prospective cohort study in Ma'anshan Maternal and Child Health Hospital between May 2013 and September 2014. There were a total of 1372 mother-child pairs from the Ma'anshan birth cohort (MABC) included in this study. IMH was defined as the thyroid-stimulating hormone (TSH) level within the normal reference range (2.5-97.5th percentile) and the free thyroxine (FT4) level below the 2.5th percentile, and negative TPOAb. The pregnancy-related anxiety questionnaire (PRAQ) was used to assess women's pregnancy-related anxiety status in the first (1-13 weeks), second (14-27 weeks) and third (after 28 weeks) trimesters of pregnancy. The Achenbach Child Behavior Checklist (CBCL/1.5-5) was used to assess preschoolers' internalizing and externalizing problems.Preschoolers born of mothers with IMH and anxiety had an increased risk of anxious/depressed (OR = 6.40, 95% CI 1.89-21.68), somatic complaints (OR = 2.69, 95% CI 1.01-7.20), attention problems (OR = 2.95, 95% CI 1.00-8.69) and total problems (OR = 3.40, 95% CI 1.60-7.21). Particularly, mothers with IMH and anxiety was associated with an increased risk of preschool girls' anxious/depressed (OR = 8.14, 95% CI 1.74-38.08), withdrawn (OR = 7.03, 95% CI 2.25-21.92), internalizing problems (OR = 2.66, 95% CI 1.00-7.08), and total problems (OR = 5.50, 95% CI 2.00-15.10).IMH and pregnancy-related anxiety during pregnancy may synergistically increase the risk of internalizing and externalizing problems in preschooler children. This interaction is distinct in internalizing problems of preschool girls.