Prenatal nicotine exposure (PNE) caused by maternal cigarette-smoking is linked to defects in auditory and visual sensory processing, behavior, memory, language, and generalized intelligence. Exposure to environmental tobacco smoke (ETS), in utero and early life is also related to neurocognitive deficits, behavioral disorders, and lower IQ measured in childhood and adolescence. The human brain undergoes massive growth, differentiation and maturation in utero and the first year of life, making it especially vulnerable to neurotoxic insult. Nicotine, a well-documented neural teratogen, crosses the placental and blood brain barriers to bind to nicotinic acetylcholine receptors, which are extensively involved in growth, connectivity and function of developing fetal and infant neural circuits. Thus PNE or ETS may have long term impact on neurochemical, neural circuitry, and behavioral development. Nicotine exposure from breast milk of smoking mothers or from breast milk of non-smoking mothers living with a smoker, may also contribute added nicotine exposure during early brain development. Quantification of infant nicotine levels from these multiple sources has been done in few studies, and fewer still have studied nicotine in association with very early brain and neurocognitive function. Methods: We propose to use auditory event-related potentials (ERP) in young infants with and without perinatal nicotine exposure, to study biological markers of neural aberration that may herald future neurocognitive deficits. We will examine sensory and higher order auditory cognitive processing in 3 groups of infants: 50 infants of mothers who smoke (PNE), 50 infants of non-smoking mothers living with a smoker (ETS), and 50 infants from smoke-free homes (CTL). We will measure biomarkers of nicotine exposure in maternal hair, urine and expired air, and in infant urine. We will use well- validated tools to estimate age-appropriate development focusing on items dependent upon auditory processing. A long term goal is to identify and refine a neurophenotype of nicotine's detrimental effects on the developing brain, in order to inform early interventions in this important at-risk population. We plan to use acquired findings to support an application for more detailed, longitudinal study.

Public Health Relevance

Cigarette-smoke in the home during pregnancy and early life are risk factors for poor performance on memory, language, attention and IQ tests later in childhood. In addition to all the other well known health risks of smoking, the hidden costs of nicotine-induced damage to early brain development may be particularly burdensome, starting before birth and lasting a lifetime. We propose to study brain activity in sleeping 4-month old infants, using state-of-the-art electrophysiological (EEG) techniques to compare the effects of maternal cigarette-smoking and second-hand smoke to smoke-free environments. We will measure nicotine exposure during pregnancy using a small sample of mothers'hair, and nicotine exposure during early postpartum with by-products of nicotine in urine from infants and mothers. We will relate both to levels of brain activity and markers of neurocognitive development at measured at 4 and 12 months of age. To the extent that nicotine imposes damage to developing neural circuits, the effects on productivity, achievement and quality of life will be borne by the most vulnerable 'involuntary smokers.'Greater understanding of the early effects of nicotine on neural substrates of cognitive development will, therefore, provide public health benefit.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21DA031316-02
Application #
8437138
Study Section
Child Psychopathology and Developmental Disabilities Study Section (CPDD)
Program Officer
Sirocco, Karen
Project Start
2012-03-15
Project End
2014-02-28
Budget Start
2013-03-01
Budget End
2014-02-28
Support Year
2
Fiscal Year
2013
Total Cost
$177,600
Indirect Cost
$57,600
Name
University of North Carolina Chapel Hill
Department
Psychiatry
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
King, Erin; Campbell, Alana; Belger, Aysenil et al. (2018) Prenatal Nicotine Exposure Disrupts Infant Neural Markers of Orienting. Nicotine Tob Res 20:897-902