The impact of maternal diabetes on the future health and neurodevelopment of the offspring: a review of the evidence

Abstract

Maternal health during gestational period is undoubtedly critical in shaping optimal fetal development and future health of the offspring. Gestational diabetes mellitus is a metabolic disorder occurring in pregnancy with an alarming increasing incidence worldwide during recent years. Over the years, there is a growing body of evidence that uncontrolled maternal hyperglycaemia during pregnancy can potentially have detrimental effect on the neurodevelopment of the offspring. Both human and animal data have linked maternal diabetes with motor and cognitive impairment, as well as autism spectrum disorders, attention deficit hyperactivity disorder, learning abilities and psychiatric disorders. This review presents the available data from current literature investigating the relationship between maternal diabetes and offspring neurodevelopmental impairment. Moreover, possible mechanisms accounting for the detrimental effects of maternal diabetes on fetal brain like fetal neuroinflammation, iron deficiency, epigenetic alterations, disordered lipid metabolism and structural brain abnormalities are also highlighted. On the basis of the evidence demonstrated in the literature, it is mandatory that hyperglycaemia during pregnancy will be optimally controlled and the impact of maternal diabetes on offspring neurodevelopment will be more thoroughly investigated.

Effects of a Diabetic Microenvironment on Neurodegeneration: Special Focus on Neurological Cells

“…In recent years, numerous findings on maternal diabetes based on the studies in both humans and animals [ 149 , 150 , 151 , 152 , 153 ], indicates that maternal diabetes may be linked to the development of neurological diseases or disorders in offspring due to the activation of chronic inflammatory responses in the brain [ 154 ]. Perea et al reported in a prospective study that prenatal exposure to gestational diabetes mellitus elevates the risk of attention deficit/hyperactivity disorder (ADHD) in offspring, while postnatal exposure was not identified as a risk factor for developing ADHD [ 155 ].…”

Insulitis in human type 1 diabetes: lessons from an enigmatic lesion

“…Other diabetes variants have also been defined which include familial conditions associated with specific genetic mutations, 3 , 4 as well as forms of gestational diabetes arising during pregnancy. 5 …”

Preventing Childhood Neurodisability

“…There is also an increase in erythropoiesis creating a relative iron deficiency in the foetus. The net result is an increase in motor impairment, cognitive disability, autism spectrum disorders (ASD) and language disability, attention deficit hyperactive disorder (ADHD) and psychiatric disorders as depicted in Figure 1 ( 4 ). This is in addition to previously well documented maldevelopment of the cardiovascular and skeletal systems as a consequence of gestational diabetes.…”

“…The latter is an umbrella term that includes cognitive disability, ASD, ADHD and specific learning disorders like dyslexia. Our current understanding suggests that many of these cases could be prevented by addressing diabetes in pregnancy and nutritional deficiencies in iron and other trace elements ( 4 , 5 ).…”