The effect of maternal smoking and drinking during pregnancy upon (3)H-nicotine receptor brainstem binding in infants dying of the sudden infant death syndrome: initial observations in a high risk population

Abstract

The high rate of the sudden infant death syndrome (SIDS) in American Indians in the Northern Plains (3.5/1000) may reflect the high incidence of cigarette smoking and alcohol consumption during pregnancy. Nicotine, a neurotoxic component of cigarettes, and alcohol adversely affect nicotinic receptor binding and subsequent cholinergic development in animals. We measured (3)H-nicotine receptor binding in 16 brainstem nuclei in American Indian SIDS (n = 27) and controls (n = 6). In five nuclei related to cardiorespiratory control, (3)H-nicotinic binding decreased with increasing number of drinks (P < 0.03). There were no differences in binding in SIDS compared with controls, except upon stratification of prenatal exposures. In three mesopontine nuclei critical for arousal there were reductions (P < 0.04) in binding in controls exposed to cigarette smoke compared with controls without exposure; there was no difference between SIDS cases with or without exposure. This study suggests that maternal smoking and alcohol affects (3)H-nicotinic binding in the infant brainstem irrespective of the cause of death. It also suggests that SIDS cases are unable to respond to maternal smoking with the "normal" reduction seen in controls. Future studies are needed to establish the role of adverse prenatal exposures in altered brainstem neurochemistry in SIDS.

Figure 1

Computer‐generated specific activity mosaics of ³H‐nicotinic binding in the brainstem at the levels of (A) caudal midbrain; (B) mid pons; (C) mid medulla. Tritiated nicotine binding is highest in the principle inferior olive (PO), nucleus pontis oralis (PoO), locus coeruleus (LC), interpeduncular nucleus (IPN) and raphé dorsalis (RD). High binding was also observed in the substantia nigria (SN) though measurements were not made in this region. Brainstem levels standardized to the same scale. Scale bar: 0.4 cm.

Figure 2

Developmental profiles of ³H‐nicointe binding in the sudden infant death syndrome (SIDS, closed circles) and control infants (open circle). When SIDS and control data are combined, there is a significant decrease in ³H‐binding with increasing postconceptional age in all nuclei sampled. Illustrated are (A) the raphé dorsalis (P = 0.003) and (B) the locus coeruleus (P = 0.002).

Figure 3

Tritiated‐nicotinic receptor binding in the brainstem nuclei in the sudden infant death syndrome (SIDS) and control groups stratified by history of maternal smoking status and controlling for postconceptional age (mean ± SEM). In the (A) locus coeruleus (P = 0.039), (B) periaqueductal gray (P = 0.005) and (C) raphé dorsalis (P = 0.011), there is a significant reduction in ³H‐nicotinic binding in control infants whose mothers smoked during pregnancy (n = 4) compared with control infants not exposed to maternal smoke (n = 2). Significant differences in binding are not found between SIDS infants exposed to cigarette smoke and SIDS infants not exposed.

Figure 4

Regression analysis of ³H‐nicotine binding by the average number of alcoholic beverages during pregnancy, illustrated in two of five nuclei with significant changes. (A) Nucleus of the solitary tract (P = 0.021), (B) Hypoglossal nucleus (P = 0.023). sudden infant death syndrome (SIDS, closed circles) and controls (open circles).