Maternal Thyroid Hormone Replacement Therapy Exposure and Language and Communication Skills of Offspring at 8 Years of Age

Abstract

Importance: Hypothyroidism during pregnancy is associated with neurodevelopmental delays in the offspring. However, it remains unknown whether prenatal thyroid hormone replacement therapy (THRT) has benefits regarding children's language and communication skills.

Objective: To quantify associations between prenatal THRT exposure and risk of language impairment diagnosis and parent-reported symptoms of language and communication skill deficits in offspring at 8 years of age.

Design, setting, and participants: The Norwegian Mother, Father and Child Cohort Study (MoBa), a nationwide population-based cohort study, recruited pregnant women from throughout Norway between June 1999 and December 2008. MoBa was linked to several nationwide registries: the Norwegian Medical Birth Registry, Norwegian Prescription Database, and Norwegian Patient Registry. For this study, the analyzed cohort was restricted to singleton pregnancies resulting in a live-born infant, enrolled in the MoBa between 2005 and 2008. Statistical analysis was performed from January 2 to May 7, 2019.

Exposures: In both study samples, mother-child pairs were categorized into 3 mutually exclusive groups: THRT exposure during pregnancy, based on dispensed prescription records; unexposed to THRT during pregnancy (population comparison); and mothers initiating THRT after delivery (THRT after delivery), comprising incident postpartum THRT users.

Main outcomes and measures: Two defined study samples were analyzed with different outcome measures. In the Norwegian Patient Registry sample, outcome was defined by a diagnosis of language and speech impairment. In the MoBa sample, children were followed up until age 8 years via parental self-completed questionnaires. Hazard ratios were calculated for language impairment diagnosis, estimated by Cox proportional hazards regression. Standardized mean score (β) was calculated for parent-reported symptoms of language and communication deficits, estimated using generalized linear models.

Results: The Norwegian Patient Registry sample included 53 862 mother-child pairs (mean [SD] age, 30.4 [4.6] years; offspring, 26 145 girls and 27 717 boys; 1204 pairs exposed to THRT [2.2%]) and the MoBa sample included 23 686 mother-child pairs (mean [SD] age, 30.8 [4.4] years; offspring, 11 536 girls and 12 150 boys; 532 pairs exposed to THRT [2.2%]). Language and speech impairment diagnosis was not significantly associated with prenatal THRT exposure compared with the unexposed group (adjusted hazard ratio, 0.75; 95% CI, 0.38-1.43) or the THRT after delivery group (adjusted hazard ratio, 0.63; 95% CI, 0.26-1.53). Language outcomes also did not significantly differ between these groups.

Conclusions and relevance: There was no significant difference in child outcomes between children exposed to THRT in the prenatal period compared with children in the population comparison group. These results support current guidelines recommending hypothyroidism treatment during pregnancy. Future research should further examine the use of THRT after delivery or a proper disease comparison group.

Figure 1.. Flowchart of Study Samples

ATC indicates Anatomical Therapeutic Chemical Classification System code; MBRN, Medical Birth Registry of Norway; MoBa, Norwegian Mother, Father and Child Cohort Study; MoBa Q1, MoBa questionnaire 1; MoBa Q3, MoBa questionnaire 3; MoBa Q8-y, MoBa questionnaire at child age 8 years; NorPD, Norwegian Prescription Database; NPR, Norwegian Patient Registry; and THRT, thyroid hormone replacement therapy. ^aThe NorPD was established in 2004, thus required restriction of the MoBa population to pregnancies recruited from 2005. ^bChildren who were born alive but died between birth and 2 years of age, emigrated, or had unknown follow-up status. ^cHyperthyroid diagnosis (International Classification of Diseases and Related Health Problems, 10th Revision [ICD-10] code e05), and other thyroid diagnosis (ICD-10 code e0-other) from the MBRN.

Figure 2.. Main and Sensitivity Analyses in the Norwegian Patient Registry Study Sample

HR indicates hazard ratio; THRT, thyroid hormone replacement therapy. ^aCrude effect estimates HR, 0.95; 95% CI, 0.55-1.62. ^bCrude effect estimates HR, 0.93; 95% CI, 0.51-1.69. ^cCrude effect estimates HR, 1.14; 95% CI, 0.49-1.56. ^dCrude effect estimates HR, 1.05; 95% CI, 0.64-1.71. ^eCrude effect estimates HR, 0.52; 95% CI, 0.22-1.23. ^fCrude effect estimates HR, 0.56; 95% CI, 0.22-1.42. ^gCrude effect estimates HR, 0.42; 95% CI, 0.15-1.14. ^hCrude effect estimates HR, 0.45; 95% CI, 0.16-1.28.