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Toddlers’ neurodevelopmental deficits linked with maternal diabetes


– Children born to obese women with insulin resistance during pregnancy showed significantly impaired neurodevelopment at 2 years of age, compared with children born to obese mothers without insulin resistance in a prospective observational study with 75 pregnant women.

The neurodevelopmental deficits were specific for the domains of motor function and attention, and the deficits correlated with several markers of abnormal glucose and fat metabolism in the insulin-resistant women, Alison G. Cahill, MD, said at the annual Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine.

“The differences in neurodevelopment appear to not be global but instead specifically affect domains of motor development and attention,” said Dr. Cahill, chief of maternal fetal medicine at Washington University in St. Louis. “These findings are consistent with results from animal studies that suggest certain brain regions are more sensitive than others to metabolic abnormalities” while in utero.

“These are among the first data in humans to characterize the impact of metabolic abnormalities on brain development,” she added.

Dr. Alison G. Cahill Mitchel L. Zoler/Frontline Medical News

Dr. Alison G. Cahill

Dr. Cahill’s study enrolled 75 women with singleton pregnancies at 33-35 weeks gestation: 25 women selected as obese and with type 2 diabetes requiring insulin treatment, 25 obese women without insulin resistance, and 25 lean women without insulin resistance. The women gave birth to 65 children who were followed out to 2 years old: 23 born to the obese women with insulin resistance, and 21 in each of the two control groups. The women in the three groups had similar demographic profiles.

Dr. Cahill said that results from the lean mothers uniformly matched those from the obese mothers without insulin resistance, and so for brevity she only reported results from the obese control group.

Average gestational age at birth was 37 weeks in the insulin-resistant mothers and 38.7 weeks among the obese mothers without insulin resistance, a significant difference. Birth weight averaged 3,617 g in the mothers with insulin resistance and 3,373 g in the mothers without insulin resistance, a difference that was not statistically significant.

Dr. Cahill and her associates assessed the 2-year-olds with a battery of behavioral and functional assessments. They measured motor function, cognition, and language with the Bayley Scales of Infant and Toddler Development, prespecified as the study’s primary endpoint. They also applied the Modified Checklist for Autism in Toddlers (M-CHAT), as well as the Infant-Toddler Social and Emotional Assessment (ITSEA) to assess competence, externalizing, internalizing, and dysregulation.

The results of these analyses showed statistically significant deficits for the motor composite score on the Bayley assessment and for the competence component of the ITSEA assessment, Dr. Cahill reported. The average composite Bayley motor score was 88 in children from mothers with insulin resistance and 98 in the control children, a statistically significant difference.

Further analyses showed that the motor deficit was primarily in fine motor function, and that motor scores were depressed throughout the entire cohort of children born to mothers with insulin resistance.

Depressed competence scores on the ITSEA assessment reflect attention abnormalities, she explained.

A final analysis examined the correlation between the motor deficits identified and various metabolic tests of fat, glucose, and protein metabolism run on the enrolled mothers during the last weeks of gestation. This showed significant links between depressed motor development and maternal lipolytic rate, plasma free fatty acids, and hepatic glucose output.

This finding “suggests an association between abnormal lipid and glucose metabolism in mothers and aspects of neurodevelopment” in their children, Dr. Cahill said.

Dr. Cahill had no disclosures.

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