Prenatal exposure to cigarette smoking is associated with a decrease in arousal in infants

doi:10.1016/S0022-3476(99)70324-0

The Journal of Pediatrics

Volume 135, Issue 1, July 1999, Pages 34-38

https://doi.org/10.1016/S0022-3476(99)70324-0 Get rights and content

Abstract

Objective: Sudden infant death syndrome has been related to both exposure to prenatal cigarette smoke and impaired arousability from sleep. We evaluated whether healthy infants born to mothers who smoked during pregnancy had higher auditory arousal thresholds than those born to mothers who did not smoke and whether the effects of smoking occurred before birth. Study design: Twenty-six newborns were studied with polygraphic recordings for 1 night: 13 were born to mothers who did not smoke, and 13 were born to mothers who smoked (>9 cigarettes per day). Other infants with a median postnatal age of 12 weeks were also studied, 21 born to nonsmoking mothers and 21 born to smoking mothers. White noise of increasing intensity was administered during rapid eye movement sleep to evaluate arousal and awakening thresholds. Results: More intense auditory stimuli were needed to induce arousals in newborns (P = .002) and infants (P = .044) of smokers than in infants of nonsmokers. Behavioral awakening occurred significantly less frequently in the newborns of smokers (P = .002) than of nonsmokers. Conclusions: Newborns and infants born to smoking mothers had higher arousal thresholds to auditory challenges than those born to nonsmoking mothers. The impact of exposure to cigarette smoke occurred before birth. (J Pediatr 1999;135:34-8)

Section snippets

Patients

Sixty-eight infants were studied. They were selected at random from a larger group of infants recruited for a research program on sleep-related behavior. The infants were eligible for this study if during gestation their mothers either did not smoke (defined as nonsmokers) or smoked >9 cigarettes per day (defined as smokers). There were 26 newborns studied while still in the nursery, where smoking was prohibited; 13 were born to nonsmokers and 13 to smokers.

At the time of testing, all newborns

RESULTS

Of the 34 smoking mothers, 25 smoked 10 to 20 cigarettes per day, and 9 smoked more than 20 cigarettes per day. No difference was found between trimesters with regard to smoking frequency. No smoking mother reported cessation of smoking during pregnancy. Regular smoking of 10 to 50 cigarettes per day was reported by 21 of 34 husbands of mothers who smoked and by 3 of 31 husbands of mothers who did not smoke (P < .001). No difference was seen between mothers who smoked and those who did not for

DISCUSSION

Significantly greater auditory stimuli were needed to induce polygraphic arousals in infants of mothers who smoked than in infants of mothers who did not smoke. Behavioral awakenings also occurred less frequently in infants of smokers than in infants of nonsmokers. Previous studies had shown that infants born to smoking mothers had decreased reactions and orientation to auditory stimuli during the first 2 weeks of life.⁷ At 2 to 3 months of age, infants of smokers challenged during a daytime

Acknowledgements

We thank Dr R. Harper and Dr C. Marcus for their critical review of the manuscript.

References (22)

HJ Hoffman et al.
Epidemiology of the sudden infant death syndrome: maternal, neonatal, postneonatal risk factors
Clin Perinatol
(1992)
TA Slotkin et al.
Loss of neonatal hypoxia tolerance after prenatal nicotine exposure: implications for sudden infant death syndrome
Brain Res
(1995)
DW. Saxton
The behaviour of infants whose mothers smoke in pregnancy
Early Hum Dev
(1978)
RA Greenberg et al.
Ecology of passive smoking by young infants
J Pediatr
(1989)
EA Mitchell et al.
Smoking and the sudden infant death syndrome
Pediatrics
(1993)
KW Lewis et al.
Deficient hypoxia awakening response in infants of smoking mothers: possible relationship to sudden infant death syndrome
J Pediatr
(1995)
NM Newman et al.
Arousal deficit: Mechanisms of the sudden infant death syndrome?
Aust Paediatr J
(1989)
HC Kinney et al.
Early developmental changes in (₃ H) nicotine binding in human brainstem
Neuroscience
(1993)
J Milerad et al.
Nicotine attenuates the ventilatory response to hypoxia in the developing lamb
Pediatr Res
(1995)
P Franco et al.
Decreased cardiac responses to auditory stimulation during prone sleep
Pediatrics
(1996)

T Anders et al.

A manual of standardized terminology, technique and criteria for scoring of states of sleep and wakefulness in newborn infants

(1971)

Cited by (141)

Decreasing smoking during pregnancy: Potential economic benefit of reducing sudden unexpected infant death
2020, Preventive Medicine
Sudden Unexpected Infant Death (SUID) remains the leading cause of death among U.S. infants age 1–12 months. Extensive epidemiological evidence documents maternal prenatal cigarette smoking as a major risk factor for SUID, but leaves unclear whether quitting reduces risk. This Commentary draws attention to a report by Anderson et al. (Pediatrics. 2019, 143[4]) that represents a breakthrough on this question and uses their data on SUID risk reduction to delineate potential economic benefits. Using a five-year (2007–11) U.S. CDC Birth Cohort Linked Birth/Infant Death dataset, Anderson et al. demonstrated that compared to those who continued smoking, women who quit or reduced smoking by third trimester decreased the adjusted odds of SUID risk by 23% (95% CI, 13%–33%) and 12% (95% CI, 2%–21%), respectively. We applied these reductions to the U.S. Department of Health and Human Services' recommended value of a statistical life in 2020 ($10.1 million). Compared to continued smoking during pregnancy, the economic benefits per woman of quitting or reducing smoking are $4700 (95% CI $2700–$6800) and $2500 (95% CI, $400–$4300), respectively. While the U.S. obtained aggregate annual economic benefits of $0.58 (95% CI, 0.35–0.82) billion from pregnant women who quit or reduced smoking, it missed an additional $1.16 (95%CI 0.71–1.60) billion from the women who continued smoking. Delineating the health and economic impacts of decreasing smoking during pregnancy using large epidemiological studies like Anderson et al. is critically important for conducting meaningful economic analyses of the benefits-costs of developing more effective interventions for decreasing smoking during pregnancy.
Cigarette smoke exposure effects on the brainstem expression of nicotinic acetylcholine receptors (nAChRs), and on cardiac, respiratory and sleep physiologies
2019, Respiratory Physiology and Neurobiology
Cigarette smoking during pregnancy is the largest modifiable risk factor for adverse outcomes in the infant. Investigations have focused on the psychoactive component of cigarettes, nicotine. One proposed mechanism leading to adverse effects is the interaction between nicotine and its nicotinic acetylcholine receptors (nAChRs). Much data has been generated over the past three decades on the effects of cigarette smoke exposure (CSE) on the expression of the nAChRs in the brainstem and physiological parameters related to cardiac, respiration and sleep, in the offspring of smoking mothers and animal models of nicotine exposure. This review summarises this data and discusses the main findings, highlighting that findings in animal models closely correlate with those from human studies, and that the major brainstem sites where the expression level for the nAChRs are consistently affected include those that play vital roles in cardiorespiration (hypoglossal nucleus, dorsal motor nucleus of the vagus, nucleus of the solitary tract), chemosensation (nucleus of the solitary tract, arcuate nucleus) and arousal (rostral mesopontine sites such as the locus coeruleus and nucleus pontis oralis). These findings provide evidence for the adverse effects of CSE during and after pregnancy to the infant and the need to continue with the health campaign advising against CSE.
Low cerebrospinal fluid hypocretin levels during sudden infant death syndrome (SIDS) risk period
2017, Sleep Medicine
Citation Excerpt :
During the first 6 months of life, the frequency of spontaneous movement changes with age [18–20]. As normal infants mature, their ability to arouse in response to hypoxia in NREM sleep [21], to auditory stimulation [22] or vibrotactile stimuli in REM sleep [23] diminishes by 2–3 months of age. This data could be related to the decrease in hypocretin levels during this risk period for SIDS.
The temporal association between sudden infant death syndrome (SIDS) and sleep suggests that the arousability from sleep provides a protective mechanism for survival. Recently, the hypocretin system, which promotes wakefulness, has been implicated in SIDS, since it has been reported that SIDS victims have fewer hypocretin neurons than infants who have died from other causes. To understand the role of hypocretin in SIDS, it is essential to better understand how this system matures. The present study compared cerebrospinal fluid (CSF) hypocretin in children aged 2–6 months, which is the age of peak incidence for SIDS, to both younger and older children.
Hypocretin levels were measured in CSF samples from 101 children who underwent a clinically relevant lumbar puncture. Children were separated into five age groups: 0–2 months, 2–6 months, 1–5 years, 5–10 years, and 10–18 years.
Hypocretin levels were not significantly different between 1–5 years, 5–10 years, and 10–18 years. Therefore, these three groups were pooled into a single one (1–18 years) for further analysis. Between the 0–2 month, 2–6 month, and 1–18 year groups, a significant difference in CSF hypocretin levels existed (p = 0.001). Simple comparisons showed that CSF hypocretin levels in the 2–6 month age group were significantly lower than hypocretin levels in both the 0–2 month and 1–18 year group (p < 0.001 and p = 0.008, respectively), but not significantly between 0–2 month and 1–18 year children.
The CSF hypocretin levels were lower at the age of peak incidence for SIDS. This could underlie an increased vulnerability to SIDS at this specific age.
Developmental toxicity of nicotine: A transdisciplinary synthesis and implications for emerging tobacco products
2017, Neuroscience and Biobehavioral Reviews
Citation Excerpt :
Failure of this response mechanism could contribute to SIDS risk (Richardson et al., 2009; McNamara and Sullivan, 2000; Schneider et al., 2008). Maternal smoking and smokeless tobacco use during pregnancy are associated with increased risk of neonatal apnea, while maternal smoking is also associated with a decreased arousal response (Richardson et al., 2009; Kahn et al., 1994; Franco et al., 1999; Horne et al., 2004; Sawnani et al., 2004; Stephan-Blanchard et al., 2010; Gunnerbeck et al., 2011; Chang et al., 2003). The administration of nicotine to pregnant ewes can evoke the same deficit in newborn lambs (Hafstrom et al., 2002).
While the health risks associated with adult cigarette smoking have been well described, effects of nicotine exposure during periods of developmental vulnerability are often overlooked. Using MEDLINE and PubMed literature searches, books, reports and expert opinion, a transdisciplinary group of scientists reviewed human and animal research on the health effects of exposure to nicotine during pregnancy and adolescence. A synthesis of this research supports that nicotine contributes critically to adverse effects of gestational tobacco exposure, including reduced pulmonary function, auditory processing defects, impaired infant cardiorespiratory function, and may contribute to cognitive and behavioral deficits in later life. Nicotine exposure during adolescence is associated with deficits in working memory, attention, and auditory processing, as well as increased impulsivity and anxiety. Finally, recent animal studies suggest that nicotine has a priming effect that increases addiction liability for other drugs. The evidence that nicotine adversely affects fetal and adolescent development is sufficient to warrant public health measures to protect pregnant women, children, and adolescents from nicotine exposure.
Brain Orexin Receptors and Nicotine
2016, Neuropathology of Drug Addictions and Substance Misuse
Nicotine has been shown to affect appetite, sleep and arousal, and addiction and reward, all functions known to be regulated by the brain region known as the hypothalamus. The orexins (hypocretins) are synthesized in the hypothalamus and data have shown their direct role in regulating the same functions as nicotine. This chapter summarizes data regarding the brain expression of the orexinergic system, including prepro-orexin, orexin A, orexin B, and the two orexin receptors, 1 and 2, after nicotine exposure and discusses the implications of these considering their physiological roles.
Brain Orexin Receptors and Nicotine
2016, Neuropathology of Drug Addictions and Substance Misuse Volume 1: Foundations of Understanding, Tobacco, Alcohol, Cannabinoids and Opioids
Nicotine has been shown to affect appetite, sleep and arousal, and addiction and reward, all functions known to be regulated by the brain region known as the hypothalamus. The orexins (hypocretins) are synthesized in the hypothalamus and data have shown their direct role in regulating the same functions as nicotine. This chapter summarizes data regarding the brain expression of the orexinergic system, including prepro-orexin, orexin A, orexin B, and the two orexin receptors, 1 and 2, after nicotine exposure and discusses the implications of these considering their physiological roles.

View all citing articles on Scopus

^☆: Supported by the Fondation Erasme.

^☆☆: Reprint requests: André Kahn, MD, Pediatric Sleep Unit, University Children’s Hospital Reine Fabiola, av. J. J. Crocq 15, B-1020 Brussels, Belgium.

^★: 0022-3476/99/$8.00 + 0 9/21/98374

View full text

Prenatal exposure to cigarette smoking is associated with a decrease in arousal in infants☆,☆☆,★

Abstract

Section snippets

Patients

RESULTS

DISCUSSION

Acknowledgements

Clin Perinatol

Brain Res

Early Hum Dev

J Pediatr

Smoking and the sudden infant death syndrome

Pediatrics

Deficient hypoxia awakening response in infants of smoking mothers: possible relationship to sudden infant death syndrome

J Pediatr

Arousal deficit: Mechanisms of the sudden infant death syndrome?

Aust Paediatr J

Early developmental changes in (3 H) nicotine binding in human brainstem

Neuroscience

Nicotine attenuates the ventilatory response to hypoxia in the developing lamb

Pediatr Res

Decreased cardiac responses to auditory stimulation during prone sleep

Pediatrics

A manual of standardized terminology, technique and criteria for scoring of states of sleep and wakefulness in newborn infants

Early developmental changes in (₃ H) nicotine binding in human brainstem