Long-term Cognitive Implications of Intrauterine Hyperglycemia in Adolescent Offspring of Women With Type 1 Diabetes (the EPICOM Study).
Exposure to maternal diabetes in utero may have a negative impact on the developing brain. The objective was to examine long-term cognitive consequences of intrauterine hyperglycemia in adolescent offspring of women with type 1 diabetes and to ascertain a possible association with maternal HbA1c.



Offspring of a prospectively followed cohort of women with type 1 diabetes (n = 277) participated in a follow-up examination at the age of 13-19 years. A control group from the background population was identified (n = 301). Cognitive function was evaluated using Reynolds Intellectual Assessment Scales and classified into indices of composite intelligence, verbal and nonverbal intelligence, and composite memory. Frequencies of reading and writing problems and attendance to classes for children with learning difficulties were assessed.



Offspring of women with type 1 diabetes scored lower in all normalized and standardized intelligence indices compared with controls: composite intelligence (95.7 vs. 100, P = 0.001), verbal intelligence (96.2 vs. 100, P = 0.004), nonverbal intelligence (96.4 vs. 100, P = 0.008), and composite memory (95.7 vs. 100, P = 0.001). A higher frequency of diabetes-exposed offspring had parent-reported learning difficulties in primary school. Differences between groups remained after adjustment for confounders and potential mediators. We found no direct association between maternal HbA1c and offspring cognitive function in the exposed group.



Adolescent offspring of women with type 1 diabetes had lower cognitive function compared with a control group, also after adjustment for confounders and potential mediators. These differences may reflect direct harmful effects of maternal diabetes on neurodevelopment in the offspring.
Center for Pregnant Women with Diabetes, Rigshospitalet, Copenhagen, Denmark Department of Obstetrics, Rigshospitalet, Copenhagen, Denmark Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark birgitte.bytoft@regionh.dk.
Birgitte
0000-0002-5615-4354
B
Bytoft
Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.
Sine
S
Knorr
Department of Endocrinology, Odense University Hospital, Odense, Denmark Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.
Zuzana
Z
Vlachova
Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark Department of Growth and Reproduction, Rigshospitalet, Copenhagen, Denmark.
Rikke B
RB
Jensen
Center for Pregnant Women with Diabetes, Rigshospitalet, Copenhagen, Denmark Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark Department of Endocrinology, Rigshospitalet, Copenhagen, Denmark.
Elisabeth R
ER
Mathiesen
Department of Endocrinology, Odense University Hospital, Odense, Denmark.
Henning
H
Beck-Nielsen
Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.
Claus H
CH
Gravholt
Department of Endocrinology, Odense University Hospital, Odense, Denmark Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark Department of Gynecology and Obstetrics, Odense University Hospital, Odense, Denmark.
Dorte M
DM
Jensen
Department of Gynecology and Obstetrics, Nordsjaellands Hospital, Hilleroed, Denmark.
Tine D
TD
Clausen
Section of Environmental Health, Department of Public Health and Center for Healthy Aging, University of Copenhagen, Copenhagen, Denmark.
Erik L
EL
Mortensen
Center for Pregnant Women with Diabetes, Rigshospitalet, Copenhagen, Denmark Department of Obstetrics, Rigshospitalet, Copenhagen, Denmark Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Peter
P
Damm
D000293:Adolescent; D001786:Blood Glucose / Q000378:metabolism; D003071:Cognition; D060825:Cognitive Dysfunction / Q000097:blood / Q000175:diagnosis*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000097:blood* / Q000175:diagnosis; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D015999:Multivariate Analysis; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000097:blood*; D011297:Prenatal Exposure Delayed Effects / Q000097:blood / Q000175:diagnosis*; D011446:Prospective Studies; D012574:Schools; D055815:Young Adult
D001786:Blood Glucose; D006442:Glycated Hemoglobin