TUESDAY, Feb. 19, 2013 (MedPage Today) — Having an obese mother may alter early fetal brain development, a gene expression analysis suggested.

Second trimester amniotic fluid showed significantly lower expression of genes involved in the normal process of central nervous system (CNS) apoptosis that makes room for neurons, Andrea Edlow, MD, of Tufts Medical Center in Boston, and colleagues found.

Fetuses of obese women also had a nine-fold increased expression of the apolipoprotein D gene (APOD), which normally is neuroprotective but may be harmful when overexpressed, they reported here at the Society for Maternal-Fetal Medicine meeting.

However, that doesn't necessarily mean that these children will have structurally abnormal brains or functional impacts, warned Mary D'Alton, MD, of New York Presbyterian/Columbia University Medical Center in New York City, who co-chaired the session where the results were presented.

She called the study results "interesting but I would be extremely cautious" when interpreting them, she said in an interview. "This is a very preliminary investigation, and the last thing we would want to do is scare people without any kind of detailed information."

Regardless, obese women should be getting preconception counseling, she pointed out. "We don't need to wait on that," she told MedPage Today. "There are many other reasons women should reduce their weight."

Obesity in women has been linked to poorer cognitive performance, higher incidence of autism spectrum disorders, and more attention deficit-hyperactivity disorder (ADHD) in their children in prior observational studies, Edlow noted.

Rat studies have shown structural brain changes and differences in apoptosis gene expression and neuronal migration of progenitor cells in the fetal brain associated with maternal obesity. Knocking out a gene for CNS apoptosis in rodents led to a severe brain anomaly.

"While we commonly perceive apoptosis to be a response to harmful stimuli, apoptosis actually plays a critical role in normal neurodevelopment," she explained.

Her group examined discarded supernatant from clinically-indicated second trimester amniocentesis from eight obese women (body mass index of 30 kg/m2) and eight controls (BMI <25 kg/m2), all with singleton pregnancies free from anomalies and matched for gestational age and sex.

Cell-free fetal RNA extracted from the amniotic fluid showed consistent differences in expression for 205 genes, with roughly half upregulated and the rest downregulated.

The most downregulated gene for the obese versus lean women's offspring was the pro-apoptotic gene STK24, with 2.5-fold down regulation of the similarly pro-apoptosis CASP9.

Genes that resist apoptotic cell death were upregulated in the obesity-exposed fetuses, with 7.6-fold higher BCL2 expression and twofold higher BCL2L1 expression.

Using a functional analysis, significant upregulation was seen in five genes involved in apoptosis of cerebral cortex cells, four involved in cell death of hippocampal cells, and four of sympathetic neuron apoptosis.

Four genes involved in viability of dendritic cells were downregulated significantly among the obese women's offspring.

Edlow acknowledged the lack of data on preexisting diabetes or other conditions in the mothers.

"Given the epidemic of maternal obesity in this country, we hope that these preliminary findings in a small group of women will form the foundation for future research and, hopefully, intervention," she concluded.

It may be possible to mitigate the harmful downstream effects of genes that are dysregulated with medication, she told MedPage Today.

This study provides the scientific underpinnings to help explain epidemiologic links, commented Donna Johnson, MD, of the Medical University of South Carolina in Charleston, who served as the meeting program chair.

"This study shows that there's an alteration of the fetal gene environment," she told MedPage Today. "This is just more scientific evidence this is the way this occurs."

Source: Maternal Obesity May Alter Fetal Brain