Brain Development

We are conducting a double-blind, randomized, placebo-controlled trial (RCT; NCT04395196) of prenatal choline supplementation (1) to assess the effectiveness of maternal choline supplementation during pregnancy to mitigate effects of PAE on three primary outcomes: infant recognition memory and postnatal growth restriction (weight and head circumference); (2) to assess the efficacy of this supplementation for mitigating alcohol effects on the following secondary outcomes: infant eyeblink conditioning, postnatal length, and information processing speed. The study design was based on a pilot feasibility study in 70 heavy-drinking pregnant women. Infants in the choline-treated arm were more likely to meet criterion for eyeblink conditioning than those in the placebo arm. Infants born to both the choline- and placebo-treated mothers were small at birth, but those in the choline arm showed considerable catch-up growth in weight and head circumference by 6.5 months, which persisted through 12 months. At 12 months, infants in the choline arm showed markedly better recognition memory compared to placebo-treated on the Fagan Test of Infant Intelligence, which is known to have predictive validity for school-age IQ. Of note, infants with heavy prenatal alcohol exposure whose mothers were in the active choline treatment arm performed better on FTII novelty preference neurobehavioral testing than infants in an observational study that was running in parallel who had no prenatal alcohol exposure. These pilot findings indicate that any beneficial effects of prenatal choline supplementation seen may be due in part or entirely due to general beneficial effects on fetal brain development rather than mechanisms that are specific to the teratogenic effects of alcohol. Thus, we currently seek to enroll and randomize 50 alcohol-abstaining pregnant women to participate in an identical study protocol (same study procedures and primary and secondary outcomes) to NCT04395196, which includes only alcohol-consuming pregnant women. Effect sizes between this pilot, non-drinking group and the larger study of alcohol-consuming women will be compared to explore the degree to which prenatal choline supplementation benefits growth and neurobehavior in infants without prenatal alcohol exposure and to explore the degree to which beneficial treatment effects of choline are specific to prenatal alcohol exposure.

The MOBILE project is part of the dynamic European collaboration of the Human Brain Project (HBP). The overall aim of the project is to characterize brain structure and function in healthy subjects and patients with epilepsy, using a quantitative multimodal approach involving both neuroimaging (MRI, PET) and electrophysiology (EEG/MEG). The project is funded by the European HBP consortium, and the data acquired will ultimately be made available to the scientific community formed by this international collaboration. Several aspects of the project have already been initiated on the basis of extensions to previous authorizations, or as part of care activities. As part of this overall project, the present MOBILE-PET application concerns exclusively the performance of 18F-FDG PET (Positron Emission Tomography) imaging in the 30 healthy adult subjects in the protocol (aged 18 to 65, with inclusion parity for gender). This cerebral examination, performed at rest on a 45-minute 3D volume acquisition, enables quantitative measurement of the metabolic consumption of glucose underlying global synaptic activity, and to determine the associated connectivity. Around 1,500 examinations of this type are carried out each year in our department as part of care for patients with brain pathology, and over 10,000 for patients with cancer. This examination requires intravenous injection of a weakly radioactive tracer corresponding to a radiopharmaceutical which has been approved for marketing for over 20 years. We also carried out and finalized a similar project in 2007 on 60 healthy subjects, using a previous-generation PET camera (NCT00484523). The Nuclear Medicine Department holds clinical research authorizations for imaging in patients and healthy subjects (including early phase and first-in-man, although the present project does not fall into this research categarogy).

This study explores the relationship between brain development and infants' social emotion and communication ability, as well as the role of genetic factors and maternal exposure during pregnancy (e.g., environmental exposures and maternal inflammatory states). To provide a theoretical basis for precise intervention of infants' social emotion and communication problems and the overall improvement of brain development.