Reduced Memory for Past Personal Events in Offspring of Hypothyroid Women May Reflect Smaller Hippocampi

Presentation Number: OR50-3
Date of Presentation: June 18th, 2013

Karen A Willoughby1, Mary Pat McAndrews2 and Joanne F Rovet*3
1McGill University, Montreal, QC, Canada, 2University of Toronto, Toronto, ON, Canada, 3University of Toronto, Toronto, Canada

Abstract

Introduction

The hippocampus is critically dependent on an adequate thyroid hormone (TH) supply throughout gestation. Offspring of women treated for hypothyroidism during pregnancy (HYPO) may be exposed to less TH, especially in early gestation when maternal TH is their sole source of hormone. We have previously described subtle memory deficits in HYPO that include poorer recall of past personal events or autobiographical memory (Willoughby et al, 2013), an ability that is critically dependent on an intact hippocampus. We do not know, however, if this deficiency reflects abnormal hippocampal development

Methods

Studied were 59 children aged 9-14 years, 27 HYPO and and 32 typically developing controls (CON) from a longitudinal cohort followed since birth. In HYPO, mothers had pre-existing or de novo hypothyroidism in pregnancy and elevated TSH in at least the first two trimesters (TRI).  Participants underwent two evaluations 4 months apart. Day 1 included a brief intelligence test, Children’s Autobiographical Interview (CAI), 1-hour structural MRI scan, and staged event (SE, tour of hospital). Day 2 included recall of staged event. Right and left hippocampi were manually traced and segmented into anterior and posterior subregions.

Results

HYPO scored moderately below CON in IQ and recalled fewer AM and staged event details, especially about events, time, and perceptual aspects (p<0.05). HYPO also had smaller right and left hippocampi (p<0.03), particularly right posterior and left anterior. In HYPO, second trimester maternal fT4 was associated with better semantic, emotional, and external detail recall (p<0.01), whereas third trimester fT4 was negatively associated with better event, place, internal detail recall (p<0.05). Third trimester TSH was negatively correlated with IQ and right posterior hippocampal size (p=0.003). Left anterior hippocampal volume was associated with better recall of select features in the AM interview and staged event.

Conclusion

Maternal hypothyroidism has longstanding effects on offspring IQ, AM, and hippocampal size linked to low TH levels in second half of pregnancy. Unexpected findings that higher maternal third trimester fT4 values were negatively correlated with some aspects of AM suggest need for tight control of maternal TH in late gestation.

 

Nothing to Disclose: KAW, MPM, JFR