Long-term health outcomes in children born to mothers with diabetes: a population-based cohort study.
BACKGROUND
To examine whether prenatal exposure to parental type 1 diabetes, type 2 diabetes, or gestational diabetes is associated with an increased risk of malignant neoplasm or diseases of the circulatory system in the offspring.


RESULTS
We conducted a population-based cohort study of 1,781,576 singletons born in Denmark from 1977 to 2008. Children were followed for up to 30 years from the day of birth until the onset of the outcomes under study, death, emigration, or December 31, 2009, whichever came first. We used Cox proportional hazards model to estimate hazard ratios (HR) with 95% confidence intervals (95% CI) for the outcomes under study while adjusting for potential confounders. An increased risk of malignant neoplasm was found in children prenatally exposed to maternal type 2 diabetes (HR = 2.2, 95%CI: 1.5-3.2). An increased risk of diseases of the circulatory system was found in children exposed to maternal type 1 diabetes (HR = 2.2, 95%CI: 1.6-3.0), type 2 diabetes (HR = 1.4, 95%CI: 1.1-1.7), and gestational diabetes (HR = 1.3, 95%CI: 1.1-1.6), but results were attenuated after excluding children with congenital malformations. An increased risk of diseases of the circulatory system was also found in children exposed to paternal type 2 diabetes (HR = 1.5, 95%CI: 1.1-2.2) and the elevated risk remained after excluding children with congenital malformations.


CONCLUSIONS
This study suggests that susceptibility to malignant neoplasm is modified partly by fetal programming. Diseases of the circulatory system may be modified by genetic factors, other time-stable family factors, or fetal programming.
Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark. cw@soci.au.dk
Chun S
CS
Wu
Ellen A
EA
Nohr
Bodil H
BH
Bech
Mogens
M
Vestergaard
Jørn
J
Olsen
D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000209:etiology* / Q000235:genetics; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D048909:Diabetes Complications / Q000453:epidemiology*; D004198:Disease Susceptibility / Q000453:epidemiology*; D005260:Female; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000453:epidemiology* / Q000209:etiology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D016016:Proportional Hazards Models; D012737:Sex Factors