BACKGROUND
Prenatal tobacco smoke exposure and preterm birth are associated with abnormal brain
and neurodevelopmental outcomes in infants. Studies that can disentangle indirect
mediating effects from direct effects of prenatal tobacco smoke exposure on sensitive
early brain magnetic resonance imaging biomarkers in very preterm infants are needed.
OBJECTIVE
This study aimed to determine whether prenatal tobacco smoke exposure in preterm infants
posed any direct effects on magnetic resonance imaging–determined global brain abnormality
score and secondary measures of brain abnormalities after removing any indirect mediating
effects of preterm birth on neurostructural outcomes.
STUDY DESIGN
We examined brain magnetic resonance imaging findings collected at 39 to 44 weeks
postmenstrual age from a prospective cohort of 395 infants born very preterm (gestational
age of ≤32 weeks). The primary outcome was global brain abnormality score, and the
secondary outcomes were global efficiency of structural connectome, diffuse white
matter abnormality volume, total brain tissue volume, total gray and white matter
volumes, and cerebellar volume. Maternal reports of smoking during pregnancy were
obtained. We performed multivariable linear regression analyses to examine the association
between prenatal tobacco smoke exposure and our magnetic resonance imaging outcomes,
controlling for prospectively collected confounders. Moreover, we performed a mediation
analysis to estimate the direct effects of prenatal tobacco smoke exposure on brain
abnormalities and any indirect effects through preterm birth.
RESULTS
Overall, 12.6% of infants had prenatal tobacco smoke exposure. Infants with prenatal tobacco smoke exposure had a higher median global brain abnormality
score than nonexposed infants (7 [interquartile range, 0–41] vs 5 [interquartile range,
0–34]; P≤.001); the findings remained significant (P<.001) after controlling for antenatal confounders. Global efficiency (P<.001), diffuse white matter volume (P=.037), and total brain tissue volume (P=.047) were significantly different between TSE groups in multivariable analyses.
On mediation analysis, preterm birth mediated between 0% and 29% of the indirect effect
of prenatal tobacco smoke exposure on several measures of brain abnormality outcomes.
Thus, prenatal tobacco smoke exposure had a direct adverse effect between 71% and
100% on brain injury or abnormal development.
CONCLUSION
Our study has identified multiple adverse effects of prenatal tobacco smoke exposure
on sensitive and objective measures of neonatal brain injury and abnormal development;
most cases seemed to be a direct effect of prenatal tobacco smoke exposure on fetal
brain development. The results underscored the significant adverse neurostructural
effects of prenatal tobacco smoke exposure to tobacco smoke pollutants.
Key words
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References
- Tobacco product use among adults - United States, 2020.MMWR Morb Mortal Wkly Rep. 2022; 71: 397-405
- Smoking during pregnancy.2022 (Available at) (Accessed May 23, 2022)
- Maternal smoking and preterm birth: an unresolved health challenge.PLoS Med. 2020; 17e1003386
- Association of maternal cigarette smoking and smoking cessation with preterm birth.JAMA Netw Open. 2019; 2e192514
- Births: final data for 2020.Natl Vital Stat Rep. 2021; 70: 1-50
- Understanding the placental biology of tobacco smoke, nicotine, and marijuana (THC) exposures during pregnancy.Clin Obstet Gynecol. 2022; 65: 347-359
- Early life exposure to nicotine: postnatal metabolic, neurobehavioral and respiratory outcomes and the development of childhood cancers.Toxicol Sci. 2020; 178: 3-15
- The effects of nicotine on development.Pediatrics. 2020; 145e20191346
- Smoking during pregnancy affects foetal brain development.Acta Paediatr. 2015; 104: 12-18
- Maternal smoking during pregnancy and fetal growth. Effects in preterm infants of gestational age less than 33 weeks.Swiss Med Wkly. 2010; 140: w13139
- The impact of intrauterine tobacco exposure on the cerebral mass of the neonate based on the measurement of head circumference.Brain Behav. 2012; 2: 243-248
- Prenatal tobacco smoke exposure and neurological impairment at 10 years of age among children born extremely preterm: a prospective cohort.BJOG. 2021; 128: 1586-1597
- Maternal smoking during pregnancy and regional brain volumes in preterm infants.J Pediatr. 2010; 156 (185–90.e1)
- Born too soon: the global epidemiology of 15 million preterm births.Reprod Health. 2013; 10: S2
- Risk of preterm and early term birth by maternal drug use.J Perinatol. 2019; 39: 286-294
- Rates of substance and polysubstance use through universal maternal testing at the time of delivery.J Perinatol. 2022; 42: 1026-1031
- Evaluation of long-term outcomes associated with preterm exposure to antenatal corticosteroids: a systematic review and meta-analysis.JAMA Pediatr. 2022; 176e220483
- Cognitive function of youths born to mothers with opioid and poly-substance abuse problems during pregnancy.Child Neuropsychol. 2017; 23: 159-187
- Exposure to prenatal secondhand smoke and early neurodevelopment: Mothers and Children's Environmental Health (MOCEH) study.Environ Health. 2019; 18: 22
- Advanced neuroimaging and its role in predicting neurodevelopmental outcomes in very preterm infants.Semin Perinatol. 2016; 40: 530-541
- Early cortical maturation predicts neurodevelopment in very preterm infants.Arch Dis Child Fetal Neonatal Ed. 2020; 105: 460-465
- New MR imaging assessment tool to define brain abnormalities in very preterm infants at term.AJNR Am J Neuroradiol. 2013; 34: 2208-2214
- Associations of newborn brain magnetic resonance imaging with long-term neurodevelopmental impairments in very preterm children.J Pediatr. 2017; 187 (58–65.e1)
- Novel diffuse white matter abnormality biomarker at term-equivalent age enhances prediction of long-term motor development in very preterm children.Sci Rep. 2020; 10: 15920
- Objectively diagnosed diffuse white matter abnormality at term is an independent predictor of cognitive and language outcomes in infants born very preterm.J Pediatr. 2020; 220: 56-63
- Automatically quantified diffuse excessive high signal intensity on MRI predicts cognitive development in preterm infants.Pediatr Neurol. 2013; 49: 424-430
- Structural connectivity relates to perinatal factors and functional impairment at 7years in children born very preterm.Neuroimage. 2016; 134: 328-337
- Diffuse white matter abnormality in very preterm infants at term reflects reduced brain network efficiency.NeuroImage Clin. 2021; 31102739
- Perinatal risk and protective factors in the development of diffuse white matter abnormality on term-equivalent age magnetic resonance imaging in infants born very preterm.J Pediatr. 2021; 233 (58–65.e3)
- The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies.Epidemiol. 2007; 18: 800-804
- Associations between early structural magnetic resonance imaging, Hammersmith infant neurological examination, and general movements assessment in infants born very preterm.J Pediatr. 2021; 232 (80–6.e2)
- Association between brain structural network efficiency at term-equivalent age and early development of cerebral palsy in very preterm infants.Neuroimage. 2021; 245118688
- Automated processing pipeline for neonatal diffusion MRI in the developing Human Connectome Project.Neuroimage. 2019; 185: 750-763
- Multi-contrast human neonatal brain atlas: application to normal neonate development analysis.Neuroimage. 2011; 56: 8-20
- Efficiency and cost of economical brain functional networks.PLoS Comput Biol. 2007; 3: e17
- The developing human connectome project: a minimal processing pipeline for neonatal cortical surface reconstruction.Neuroimage. 2018; 173: 88-112
- Atlas-guided quantification of white matter signal abnormalities on term-equivalent age MRI in very preterm infants: findings predict language and cognitive development at two years of age.PLoS One. 2013; 8: e85475
- Rates of early intervention services in very preterm children with developmental disabilities at age 2 years.J Paediatr Child Health. 2008; 44: 276-280
- Mediation analysis: a practitioner's guide.Annu Rev Public Health. 2016; 37: 17-32
- Acute histologic chorioamnionitis independently and directly increases the risk for brain abnormalities seen on magnetic resonance imaging in very preterm infants.Am J Obstet Gynecol. 2022; 227 (623.e1–13)
- Magnesium sulphate for fetal neuroprotection at imminent risk for preterm delivery: a systematic review with meta-analysis and trial sequential analysis.BJOG. 2020; 127: 1180-1188
- Outcome at 4.5 years of children born after expectant management of early-onset hypertensive disorders of pregnancy.Am J Obstet Gynecol. 2011; 204 (510.e1–9)
- Influence of second-hand smoke and prenatal tobacco smoke exposure on biomarkers, genetics and physiological processes in children-an overview in research insights of the last few years.Int J Environ Res Public Health. 2020; 17: 3212
- Prenatal tobacco exposure and brain morphology: a prospective study in young children.Neuropsychopharmacology. 2014; 39: 792-800
- Volumetric MRI study of brain in children with intrauterine exposure to cocaine, alcohol, tobacco, and marijuana.Pediatrics. 2008; 121: 741-750
- Developmental toxicity of nicotine: a transdisciplinary synthesis and implications for emerging tobacco products.Neurosci Biobehav Rev. 2017; 72: 176-189
- Cigarettes and the developing brain: picturing nicotine as a neuroteratogen using clinical and preclinical studies.Tzu Chi Med J. 2012; 24: 157-161
- Effect of prenatal smoking cessation interventions on birth weight: meta-analysis.J Matern Fetal Neonatal Med. 2019; 32: 332-338
- Vitamin C supplementation for pregnant smoking women and pulmonary function in their newborn infants: a randomized clinical trial.JAMA. 2014; 311: 2074-2082
- Cost effectiveness of vitamin C supplementation for pregnant smokers to improve offspring lung function at birth and reduce childhood wheeze/asthma.J Perinatol. 2018; 38: 820-827
- Association between maternal smoking during pregnancy and low birthweight: effects by maternal age.PLoS One. 2016; 11e0146241
- Maternal cigarette smoking before and during pregnancy and the risk of preterm birth: a dose-response analysis of 25 million mother-infant pairs.PLoS Med. 2020; 17e1003158
- Extent of nicotine and cotinine transfer to the human fetus, placenta and amniotic fluid of smoking mothers.Dev Pharmacol Ther. 1985; 8: 384-395
- Maternal tobacco exposure and cotinine levels in fetal fluids in the first half of pregnancy.Obstet Gynecol. 1999; 93: 25-29
- Nicotinic acetylcholine receptors and nicotinic cholinergic mechanisms of the central nervous system.Annu Rev Pharmacol Toxicol. 2007; 47: 699-729
- Early exposure to nicotine during critical periods of brain development: mechanisms and consequences.J Pediatr Biochem. 2010; 1: 125-141
- The long-term effects of prenatal nicotine exposure on neurologic development.J Midwifery Womens Health. 2010; 55: 143-152
- Developmental regulation of nicotinic acetylcholine receptors within midbrain dopamine neurons.Neuroscience. 2007; 144: 1347-1360
- Fetal and adolescent nicotine administration: effects on CNS serotonergic systems.Brain Res. 2001; 914: 166-178
- Effect of maternal smoking on fetal catecholamine concentrations at birth.Pediatr Res. 2003; 53: 119-124
- Prenatal exposure of rats to nicotine causes persistent alterations of nicotinic cholinergic receptors.Brain Res. 2009; 1250: 88-100
- Neurological repercussions of neonatal nicotine exposure: a review.Int J Dev Neurosci. 2022; 82: 3-18
- Cincinnati Infant Neurodevelopment Early Prediction Study (CINEPS) Group. Early brain abnormalities in infants born very preterm predict under-reactive temperament.Early Hum Dev. 2020; 144104985
Article info
Publication history
Published online: December 30, 2022
Accepted:
December 26,
2022
Received:
December 9,
2022
Footnotes
The authors report no conflict of interest.
This research was supported, in part, by the National Institute of Environmental Health Sciences (grant numbers R01 ES03743 and R01 ES027815) and the National Institute of Neurological Disorders and Stroke (grant number R01 NS094200 and R01 NS096037).
Cite this article as: Mahabee-Gittens EM, Kline-Fath BM, Harun N, et al. Prenatal tobacco smoke exposure and risk for brain abnormalities on magnetic resonance imaging at term in infants born very preterm. Am J Obstet Gynecol MFM 2023;XX:x.ex–x.ex.
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