Fetal postprandial brain responses were slower in the offspring of women with GDM. This might indicate that gestational diabetes directly affects fetal brain development and may lead to central nervous insulin resistance in the fetus.

Habituation--the most basic form of learning--is used to evaluate central nervous system (CNS) maturation and to detect abnormalities in fetal brain development. In the current study, habituation, stimulus specificity and dishabituation of auditory evoked responses were measured in fetuses and newborns using fetal magnetoencephalography (fMEG). An auditory habituation paradigm consisting of 100 trains of five 500 Hz tones, one 750 Hz tone (dishabituator) and two more 500 Hz tones, respectively, were presented to 41 fetuses (gestational age 30-39 weeks) and 22 newborns or babies (age 6-89 days). A response decrement between the first and fifth tones (habituation), an increment between the fifth tone and the dishabituator (stimulus specificity) and an increment between the fifth (last tone before the dishabituator) and seventh tones (first tone after the dishabituator) (dishabituation) were expected. Fetuses showed weak responses to the first tone. However, a significant response decrement between the second and fifth tones (habituation) and a significant increment between the fifth tone and the dishabituator (stimulus specificity) were found. No significant difference was found for dishabituation nor was a developmental trend found at the group level. From the neonatal data, significant values for stimulus specificity were found. Sensory fatigue or adaptation was ruled out as a reason for the response decrement due to the strong reactions to the dishabituator. Taken together, the current study used fMEG to directly show fetal habituation and provides evidence of fetal learning in the last trimester of pregnancy.

Aims/hypothesis Fetal programming plays an important role in the pathogenesis of type 2 diabetes. The aim of the present study was to investigate whether maternal metabolic changes during OGTT influence fetal brain activity. Methods Thirteen healthy pregnant women underwent an OGTT (75 g). Insulin sensitivity was determined by glucose and insulin measurements at 0, 60 and 120 min. At each time point, fetal auditory evoked fields were recorded with a fetal magnetoencephalographic device and response latencies were determined. Results Maternal insulin increased from a fasting level of 67±25 pmol/l (mean ± SD) to 918±492 pmol/l 60 min after glucose ingestion and glucose levels increased from 4.4±0.3 to 7.4±1.1 mmol/l. Over the same time period, fetal response latencies decreased from 297±99 to 235±84 ms (p=0.01) and then remained stable until 120 min (235±84 vs 251±91 ms, p=0.39). There was a negative correlation between maternal insulin sensitivity and fetal response latencies 60 min after glucose ingestion (r=0.68, p=0.02). After a median split of the group based on maternal insulin sensitivity, fetuses of insulin-resistant mothers showed a slower response to auditory stimuli (283±79 ms) than those of insulin-sensitive mothers (178±46 ms, p=0.03). Conclusions/interpretation Lower maternal insulin sensitivity is associated with slower fetal brain responses. These findings provide the first evidence of a direct effect of maternal metabolism on fetal brain activity and suggest that central insulin resistance may be programmed during fetal development.