The association of prenatal alcohol exposure with brain development during the first 1000 days of life: a systematic review

Background: The first 1000 days of life form a critical period for lifelong health, growth and neurodevelopment. Prenatal exposure to toxic substances, such as alcohol (PAE), can impact both short- and long-term offspring health. However, knowledge on PAE and brain development in early life is limited. Objectives: This systematic review investigated associations between PAE and brain development during the first 1000 days of life. Search strategy This systematic review was registered in PROSPERO at CRD42022355144. The literature search was performed from inception until February 2024, in EMBASE, MEDLINE, Web of Science, PsycINFO, and the Cochrane Library. Selection criteria Studies investigating PAE and brain development during the first 1000 days, using ultrasound, magnetic resonance imaging (MRI) or diffusion tensor imaging (DTI) were included. Data collection and analysis Our search initially identified 3618 articles, of which 16 were included. Collected information extracted from the articles included: study period, study population, design, methodology, exposure information, imaging type (ultrasound, MRI or DTI), brain measurements and study results. Main results The findings suggest inconsistent associations between PAE and early brain development. Ultrasound studies on PAE and brain size report no clear relations. Some postnatal MRI studies reported smaller thalami, amygdalae and hippocampi in alcohol exposed neonates. Postnatal DTI studies ( n =5) examining network integrity and connectivity reported bidirectional results in multiple brain networks. Conclusions: This systematic review highlights the need for further research on first trimester brain development, timing and quantity of alcohol exposure. Longitudinal assessments and standardized procedures for neuroimaging are crucial to understand the impact of PAE on early brain development.