title: Prenatal Exposure to Snus Alters Heart Rate Variability in the Infant.
abstract: BACKGROUND
  Maternal use of smoked tobacco during pregnancy causes significant morbidity and mortality in the human infant including alterations in autonomic control with increased risk of sudden infant death syndrome. We hypothesized that maternal snus (smokeless tobacco) use during pregnancy affects autonomic cardiac regulation in the infant, as measured by heart rate variability (HRV) and the low frequency and high frequency ratio (LF/HF ratio).
  
  
  METHODS
  A prospective observational study of 56 infants of women who used snus (n = 23) or cigarettes (n = 13) during pregnancy versus tobacco- and nicotine-free controls (n = 19). The nicotine dose was estimated by questionnaires at 4 timepoints pre- and post-natally. The infants' urine cotinine concentration and HRV during 2 hours of sleep were studied 1-2 months after birth.
  
  
  RESULTS
  LF/HF ratio was higher in snus (mean 3.31; 95% CI 2.78-3.83) and smoke (3.51;2.54-4.47) compared to controls (2.15; 1.76-2.54, p = .002). Early prenatal nicotine exposure "without" any further exposure increased the LF/HF ratio (3.19; 2.55-3.84, p = .02). Continuous prenatal nicotine exposure "without" postnatal exposure was also associated with a residual increase in LF/HF ratio (4.40; 3.38-5.42, p < .001). There was no difference between infants exposed to smokeless versus smoked tobacco, suggesting a common constituent (nicotine) altering autonomic cardiac regulation.
  
  
  CONCLUSIONS
  Infants to mothers who used snus during pregnancy showed lower vagal activity with an increased LF/HF ratio compared to controls, and similar to infants of smokers. Even early prenatal exposure to snus has a lasting impact on autonomic cardiac regulation suggesting a fetal "re-programing" of the developing autonomic nervous system.
  
  
  CONCLUSIONS
  The results indicate that smokeless tobacco (Swedish snus) affects the developing autonomic nervous system during gestation. Even if exposure is interrupted during the first or second trimester, effects in autonomic cardiac regulation are seen in the 1-2 month-old infant. This underlines the importance of abstaining from all types of tobacco use during the whole pregnancy. Our findings may also have more general relevance to other routes by which nicotine can be delivered to a fetus and newborn.
authors.affiliation: Department of Women's and Children's Health, Pediatric Cardiology Unit, Karolinska Institute, Stockholm,Sweden.
authors.forename: Felicia
authors.initials: F
authors.lastname: Nordenstam
authors.affiliation: Department of Women's and Children's Health, Pediatric Cardiology Unit, Karolinska Institute, Stockholm,Sweden.
authors.forename: Bo
authors.initials: B
authors.lastname: Lundell
authors.affiliation: Department of Women's and Children's Health, Neonatal Unit, Karolinska Institute, Stockholm,Sweden.
authors.forename: Gary
authors.initials: G
authors.lastname: Cohen
authors.affiliation: Department of Learning, Information, Management, Ethics, Karolinska Institute, Stockholm,Sweden.
authors.forename: Mesfin K
authors.initials: MK
authors.lastname: Tessma
authors.affiliation: Department of Medicine, Clinical Epidemiology Unit, Karolinska Institute, Stockholm,Sweden.
authors.forename: Pauline
authors.initials: P
authors.lastname: Raaschou
authors.affiliation: Department of Women's and Children's Health, Neuropediatric Unit, Karolinska Institute, Stockholm, Sweden.
authors.forename: Ronny
authors.initials: R
authors.lastname: Wickström
mesh_terms: D000328:Adult; D001145:Arrhythmias, Cardiac / Q000209:etiology* / Q000503:physiopathology; D001341:Autonomic Nervous System / Q000187:drug effects; D004562:Electrocardiography; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000209:etiology* / Q000503:physiopathology; D011446:Prospective Studies; D013548:Sweden / Q000453:epidemiology; D014030:Tobacco, Smokeless / Q000009:adverse effects*