Perinatal snus exposure and cardiovascular function in the child

Sammanfattning: Maternal use of smoking tobacco during pregnancy is one of the most important preventable risk factors during pregnancy. Maternal smoking is associated with alterations in autonomic cardiac control and long-term cardiovascular effects on blood pressure and arterial wall properties. Earlier studies have had difficulties in determining the specific contributions of prenatal and postnatal exposures, respectively, as well as distinguishing acute from chronic effects, as these children are frequently exposed to smoking both before birth and during childhood. The specific role of nicotine is also unclear as smoking contains many toxic combustion agents in addition to nicotine. While cigarette smoking is decreasing globally, other forms of tobacco- and nicotine-containing products are gaining in popularity and in Sweden and Norway, use of smokeless tobacco (Swedish Snus) is increasing among women. Snus delivers high doses of nicotine to the fetus so we hypothesized that prenatal snus exposure had long term cardiovascular associations with increased blood pressure, arterial wall stiffness, intima media thickness and altered autonomic cardiac control in the offspring. We also aimed to investigate the levels of nicotine and metabolites in the breastmilk of snus- using mothers. We included women from a larger national cohort with women recruited during early pregnancy during 2006‒2011, residing in Stockholm, Östersund and Umeå. The pregnant women were grouped, based on their tobacco use at inclusion, into snus users, smokers or tobacco-free controls. Dual users were excluded. At infant age one to two months, we tested the infant’s heart rate variability and also the infant’s urine and mother’s breastmilk for nicotine and metabolites. At child age 5-6 years, we tested heart rate variability, blood pressure, carotid intima media thickness and calculated arterial stiffness based on pulsatile changes in pressure and diameters. Heart rate variability showed a higher low frequency/high frequency (LF/HF) ratio, indicating a lower vagal activity, in infants with snus exposure in utero compared with tobacco-free controls and the ratio was similar to that seen in smoke-exposed children. Breastmilk from snus users showed high levels of nicotine and cotinine. In addition, nicotine was still detected in breastmilk after more than 12 hours of abstention. The snus-exposed 5‒6- year-old children showed higher systolic blood pressure, higher LF/HF ratio and stiffer arterial walls than tobacco-free controls. There was no significant difference in carotid intima media thickness between snus-exposed children and controls. In conclusion, several long-lasting associations with prenatal snus exposure were discovered, indicating a prenatal programming of the cardiovascular function. Pregnant women should be recommended to abstain from all tobacco- and nicotine-containing products during the entire pregnancy.