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The negative effects of pregestational diabetes are due to high blood sugar and insulin levels primarily during the first trimester of pregnancy (in contrast to gestational diabetes, which can lead to fetal complications during the second and third trimester). Since this period is when many of the major internal structures and organs of the fetus is decided, pre-existing diabetes can lead to congenital abnormalities. These include abnormal development of the heart and the central nervous system (brain and spinal cord). Strong correlations have been reported between diabetes and sacral agenesis, holoprosencephaly, and longitudinal limb deficiency. With regards to the heart, increased likelihood of truncus arteriosus, atrioventricular septal defect, and single ventricle complex has been found.

Pre-existing diabetes can also lead to complications in the neonate after birth, including neonatal jaundice, hypoglycemia, and macrosomia. Pregestational diabetes does not, however, increase the likelihood of diseases due to chromosomal alterations (eg: Down Syndrome).