In a study to be presented on February 15 between 8 a.m. and 10 a.m. PST, at the Society for Maternal-Fetal Medicine’s annual meeting, The Pregnancy Meeting ™, in San Francisco, California, researchers from Tufts Medical Center will present findings showing the effects of maternal obesity on a fetus, specifically in the development of the brain.

The study, conducted at the Mother Infant Research Institute (MIRI) at Tufts Medical Center in Boston, Mass., looked at the fetal development of 16 pregnant women, eight obese and eight lean, to see what effects maternal obesity had on fetal gene expression. Researchers have found that fetuses of obese women had differences in gene expression as early as the second trimester, compared to fetuses of women who were a healthy weight.. Of particular note were patterns of gene expression suggestive of abnormal brain development in fetuses of obese women.

During gestation, fetuses go through apoptosis, a developmental process of programmed cell death. However, fetuses of the obese women were observed to have decreased apoptosis, which is an important part of normal fetal neurodevelopment. Dr. Diana Bianchi, senior author of the study and executive director of MIRI, describes apoptosis as a pruning process, clearing out space for new growth.

“Women won’t be surprised to hear being obese while pregnant can lead to obesity in the child,” said Dr. Andrea Edlow, lead author of the study and fellow in Maternal-Fetal Medicine at Tufts Medical Center. “But what might surprise them is the potential effect it has on the brain development of their unborn child.”

It is too early to know the implications of their findings, but maternal obesity is a rapidly growing problem in the U.S., with one in three women being obese at conception. The conclusion of the study points to the role of gene expression studies such as this one in helping elucidate possible mechanisms for recently-described postnatal neurodevelopmental abnormalities in children of obese women, including increased rates of autism and altered hypothalamic appetite regulation.

The research team hopes their findings and any future data will push women looking to become pregnant to be healthier, minimizing risk to their child.

Drs. Bianchi and Edlow, say the next step in their research will be to use a mouse model to examine the genes that are differentially expressed in fetuses of obese women, genes that may be involved in abnormal fetal neurodevelopment.
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In addition to Edlow and Bianchi, research was conducted by Neeta Vora of Tufts Medical Center and University of North Carolina Division of Maternal-Fetal Medicine.; Lisa Hui, of Tufts Medical Center, Mother Infant Research Institute, Boston, Mass.; Heather Wick, of Tufts University Department of Computer Science, Medford, Mass.; and Janet Cowan, of Tufts Medical Center Department of Pathology, Boston, Mass.

The Society for Maternal-Fetal Medicine (est. 1977) is a non-profit membership group for obstetricians/gynecologists who have additional formal education and training in maternal-fetal medicine. The society is devoted to reducing high-risk pregnancy complications by providing continuing education to its 2,000 members on the latest pregnancy assessment and treatment methods. It also serves as an advocate for improving public policy, and expanding research funding and opportunities for maternal-fetal medicine. The group hosts an annual scientific meeting in which new ideas and research in the area of maternal-fetal medicine are unveiled and discussed.

Abstract 37: Decreased apoptosis in fetuses of obese women: implications for neurodevelopment

Andrea Edlow1, Neeta Vora1, Lisa Hui2, Heather Wick3, Janet Cowan4, Diana Bianchi2

1Tufts Medical Center, Mother Infant Research Institute, and Division of Maternal-Fetal Medicine, Boston, MA, 2Tufts Medical Center, Mother Infant Research Institute, Boston, MA, 3Tufts University, Department of Computer Science, Medford, MA, 4Tufts Medical Center, Department of Pathology, Boston, MA

OBJECTIVE: Maternal obesity affects the developing fetus. Second trimester amniotic fluid supernatant (AFS) contains cell-free fetal RNA (cffRNA) transcripts from multiple fetal organs, including the brain, thus providing real-time information about fetal development. We sought to understand the effects of maternal obesity on fetal gene expression by performing a functional genomic analysis of AFS.

STUDY DESIGN: We prospectively analyzed cffRNA in AFS of women with singleton fetuses undergoing clinically indicated 2nd trimester genetic amniocentesis. Eight obese gravidas (Ob, BMI ≥ 30) and 8 lean controls (L, BMI

< 25) were matched for gestational age and fetal sex. Exclusion criteria included abnormal karyotype and structural anomalies. CffRNA was extracted, amplified, and hybridized to whole genome expression arrays. Genes differentially regulated in 8/8 pairs were identified using paired t-test with the Benjamini-Hochberg correction. Functional analyses were performed using Ingenuity Pathways Analysis software.

RESULTS: Demographic characteristics are shown in Table 1. Paired analyses identified 205 differentially regulated genes. Apoptotic cell death was significantly down-regulated in fetuses of obese gravidas. This was most evident within nervous system pathways, specifically those involving cerebral cortex cells, hippocampal cells, and sympathetic neurons. Genes involved in resistance to apoptotic cell death (BCL2, BCL3) were among the most up-regulated in Ob, while the most down-regulated gene was the pro-apoptotic STK24. Docosahexaenoic acid signaling, which plays an important role in neuronal survival, was also identified as a key canonical pathway.

CONCLUSION: Decreased brain apoptosis is characteristic of fetuses of obese pregnant women. Because apoptosis is critical to normal neurodevelopment, these findings may have implications for postnatal neurodevelopmental abnormalities recently described in the offspring of obese women, including an increased incidence of autism and altered hypothalamic appetite regulation.

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Vicki Bendure
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202-374-9259
Society for Maternal-Fetal Medicine