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Developmental Biology - Brain Development

Fetal Alcohol Syndrome Detected in Womb

Magnetic resonance imaging in rhesus macaques detects effects of binge drinking early in pregnancy...


New images reveal the earliest impairments to nonhuman primate fetal brain development due to alcohol ingested by the mother, in a study led by scientists at Oregon Health & Science University involving rhesus macaques.
Magnetic resonance imaging showed impairments to brain growth during the third trimester of pregnancy, even though the fetus was exposed to alcohol only during the first trimester.

The research, published in the Proceedings of the National Academy of Sciences, highlights the danger of binge drinking early in a pregnancy, even before a woman realizes she's pregnant. It also suggests the potential benefit of using in-utero imaging to detect signs of fetal-alcohol syndrome before birth.
"The earlier the detection, the better. Predicting risks for specific impairments means that therapy can start soon after the baby is born, when the brain has the greatest plasticity."

Chris Kroenke PhD, Associate Professor, Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton; Advanced Imaging Research Center, Oregon Health & Science University, Portland; Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon, USA.

The study builds upon recent advancements in the quality and resolution of magnetic resonance imaging methods used to examine the fetal brain in utero.
"The goal of this study was to assess the sensitivity of this common clinical diagnostic to detect the impact of drinking binge level intakes of alcohol [4-6 drinks] early in pregnancy to model patterns of drinking in women before they know they are pregnant."

Kathleen Grant PhD, Professor and Chief, Division of Neuroscience, Oregon National Primate Research Center at OHSU.

Researchers at the primate center monitored a total of 28 pregnant macaques, measuring brain development through MRIs at three stages of pregnancy. In an experiment that would not be possible to conduct in people, half of the macaques consumed the daily human equivalent of six alcoholic drinks per day while the rest consumed no alcohol.
Imaging during the course of the pregnancy revealed a difference in fetal brain development by the 135th day of a 168-day gestational term, at the beginning of the third trimester. Imaging revealed no difference with the control group measured during the second trimester.

Electrophysiological recordings of the brains following MRI suggest the differences are functionally significant.

Aside from validating the potential usefulness of MRI as an early diagnostic tool for fetal alcohol syndrome, researchers believe the images are of high quality and useful for comparison by other scientists in the field.

Significance
Early diagnosis of fetal alcohol spectrum disorder (FASD) is necessary for initiating early therapy, and is the most effective way to reduce risk of long-term adverse outcomes. This study utilized a nonhuman primate model of FASD, and is the first to exploit in utero MRI to detect the effects of early-pregnancy drinking on the fetal brain. Alterations in motor-related brain regions become detectable with in utero MRI at the beginning of the third-trimester equivalent in human pregnancy. Follow-up electrophysiological measurements demonstrated that the MRI-identified brain abnormalities are associated with aberrant brain function. These findings demonstrate the sensitivity of in utero MRI, and inform future clinical studies on the timing and brain region of greatest sensitivity to early ethanol exposure.

Abstract
One factor that contributes to the high prevalence of fetal alcohol spectrum disorder (FASD) is binge-like consumption of alcohol before pregnancy awareness. It is known that treatments are more effective with early recognition of FASD. Recent advances in retrospective motion correction for the reconstruction of three-dimensional (3D) fetal brain MRI have led to significant improvements in the quality and resolution of anatomical and diffusion MRI of the fetal brain. Here, a rhesus macaque model of FASD, involving oral self-administration of 1.5 g/kg ethanol per day beginning prior to pregnancy and extending through the first 60 d of a 168-d gestational term, was utilized to determine whether fetal MRI could detect alcohol-induced abnormalities in brain development. This approach revealed differences between ethanol-exposed and control fetuses at gestation day 135 (G135), but not G110 or G85. At G135, ethanol-exposed fetuses had reduced brainstem and cerebellum volume and water diffusion anisotropy in several white matter tracts, compared to controls. Ex vivo electrophysiological recordings performed on fetal brain tissue obtained immediately following MRI demonstrated that the structural abnormalities observed at G135 are of functional significance. Specifically, spontaneous excitatory postsynaptic current amplitudes measured from individual neurons in the primary somatosensory cortex and putamen strongly correlated with diffusion anisotropy in the white matter tracts that connect these structures. These findings demonstrate that exposure to ethanol early in gestation perturbs development of brain regions associated with motor control in a manner that is detectable with fetal MRI.

Authors
Xiaojie Wang, Verginia C. Cuzon Carlson, Colin Studholme, Natali Newman, Matthew M. Ford, Kathleen A. Grant and Christopher D. Kroenke.


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May 22 2020   Fetal Timeline   Maternal Timeline   News



New MRI imaging techniques reveal damage to primate fetal brains at the beginning of the third trimester resulting from drinking alcohol. Image public domain.


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