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). 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. 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. 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. 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.

Background: Maternal smoking during pregnancy has been associated with higher blood pressure and autonomic imbalance in the offspring. However, it has been difficult to determine the selective prenatal and postnatal contributions as children frequently have been exposed to smoking both before and after birth. The specific role of nicotine is also unclear. We aimed to determine whether exclusive prenatal exposure to nicotine from maternal use of smokeless tobacco (Swedish snus) in pregnancy was associated with blood pressure and autonomic heart rate control in their children. Methods and Results: We measured oscillometric blood pressures in forty 5‐ to 6‐year‐old children with snus exposure in fetal life (n=21) and in tobacco‐free controls (n=19). Taking the child′s age and height into account, snus‐exposed children had 4.2 (95% CI , 0.2–8.1) mm Hg higher systolic blood pressure than controls ( P =0.038). The corresponding sex‐, age‐, and height‐standardized systolic blood pressure centiles were 61 and 46 (95% CI of the difference, 2–28) ( P =0.029). Heart rate variability was tested in 30 of the children. The spectral heart rate variability variable low‐frequency/high‐frequency ratio was higher (median, 0.69; interquartile range, 0.45–1.21) in snus‐exposed children than in controls (median, 0.21; interquartile range, 0.32–0.57; P =0.034). Conclusions: Prenatal snus exposure was associated with higher systolic blood pressure and altered heart rate variability at 6 years of age. These findings may indicate adverse prenatal programming of nicotine, but implications for cardiovascular health in later life remain to be studied. Meanwhile, women should be recommended to abstain from all types of tobacco and nicotine products during pregnancy.

Aim: The aim of this structured review was to discuss knowledge of nicotine use during pregnancy and long‐term effects on children's cardiovascular function.Methods: PubMed and MEDLINE were searched for original papers that covered various forms of nicotine exposure during pregnancy and this identified 314 papers published in English from inception of the databases to 1 March 2021. The research focus was prenatal exposure that had long‐term effects on the cardiovascular system. The search was expanded from the reference list of the selected papers, which identified another 17 papers.Results: The 34 original papers that were included covered 172,696 subjects from foetuses to 19 years of age. Cardiovascular autonomic dysfunction was discussed in 12 of the papers and 16 studies reported on blood pressure. The remaining studies covered structural or functional changes in arterial wall or heart. There were convincing data on autonomic dysfunction and increased blood pressure. Some data were conflicting and problems with misclassification of exposure were evident.Conclusion: Prenatal nicotine exposure was associated with long‐term developmental changes in the cardiovascular system and regulation. There were no safe periods, doses or nicotine products during pregnancy and women should abstain when planning a pregnancy.

Aim: Using snus, an oral moist tobacco, has increased among pregnant women in Sweden, the only European Union country where sales are legal. This study evaluated whether snus generated similar concentrations of nicotine and its metabolites in breastmilk to cigarette smoking.Methods: We analysed 49 breastmilk samples from 33 nursing mother – 13 snus users, six cigarette smokers and 14 controls – for concentrations of nicotine, cotinine and 3‐hydroxycotinine. The mothers were recruited at antenatal clinics in Sweden from 2007 to 2012.Results: The median nicotine concentration in breastmilk of the snus users was 38.7 ng/mL (0–137) versus 24.0 ng/mL (0–56) in smokers, with median cotinine levels of 327.6 ng/mL (37–958) versus 164.4 ng/mL and median 3‐hydroxycotinine levels of 202.7 ng/mL (28–452) versus 112.4 (0–231), respectively. Nicotine was still detected in the breastmilk of eight of the 13 snus users after abstaining from tobacco for a median duration of 11 hours (0.6–12.5), while the breastmilk of the smokers was nicotine‐free after four hours’ abstinence.Conclusion: Snus users had high levels of nicotine and metabolites in their breastmilk and nicotine was found even after 12.5 hours of abstinence.

Background: Arterial stiffening and increased intima‐media thickness can be seen as early as childhood and are associated with increased risk of cardiovascular events in adult life. The authors hypothesized that exposure to prenatal smokeless tobacco (Swedish snus) without additional nicotine exposure after the breastfeeding period would be associated with increased arterial stiffness and intima‐media thickening in preschool children. Methods and Results: This was a longitudinal follow‐up cohort study of children aged 5 to 6 years exposed to high doses of nicotine in utero. Women exclusively using snus and unexposed controls were enrolled in early pregnancy (gestational age range, 6–12 weeks). Exposure data were collected during and after pregnancy with questionnaires from both groups. For this study, only children of women using >48 mg nicotine per day during their entire pregnancy were included in the exposure group. Outcomes were determined in 40 healthy children (21 exposed to snus in utero). Ultrasonography of the common carotid artery was used to determine carotid intima‐media thickness and calculate arterial stiffness index from the relationship between pulsatile changes in arterial diameter and arterial pressure. Children exposed to snus in fetal life had higher carotid stiffness (median 4.1 [interquartile range (IQR), 2.4–5] versus 2.9 [IQR, 2.1–3.5]; P =0.014) than tobacco‐free controls. Carotid strain (relative diameter change) was lower in children exposed to snus (mean 16% [SD, 5.7%] versus 21% [SD, 6.6%]) than in controls ( P =0.015). Carotid intima‐media thickness did not differ significantly between children exposed to snus and controls. Conclusions: Exposure to snus during fetal life was associated with a stiffer carotid artery in preschool children.

Objectives: To investigate the relationship between maternal disease, anti-rheumatic treatment, autoantibody levels and foetal atrioventricular (AV) conduction. Methods: A total of 324 pregnancies from two groups of anti-Ro/La autoantibody-positive women were included. The Surveillance group consisted of pregnancies with known anti-Ro positivity followed from early pregnancy; n = 302, including nine with AV block (AVB), and the Bradycardia group with no prior knowledge of anti-Ro/La autoantibodies and referred upon detection of foetal bradycardia, with a subsequent AVB II-III diagnosis (n = 22). Foetal AV conduction and routine anti-Ro52, anti-Ro60 and anti-La autoantibody levels were analysed. Results: Women with primary Sjögren disease (SjD) had longer foetal AV time intervals (130.5 ± 11.9 vs 125.8 ± 8.7 ms, P = 0.002) compared with autoantibody-positive women with neither SjD nor SLE. Notably, AZA, mostly used in women with SLE, was associated with shorter foetal AV time intervals compared with autoantibody-positive pregnancies without AZA treatment (122.5 ± 8.9 vs 128.7 ± 11.0 ms, P = 0.038). For antibody-based prediction, anti-Ro52, anti-Ro60 and anti-La antibody levels obtained from routine assays could identify nearly 20% of pregnancies as low risk, and high levels (≥8 U/ml) of anti-La antibodies were associated with an increased risk of AVB I–III (OR = 6.0, 1.26–28.5). However, the positive predictive value for AVB II–III of the three autoantibodies did not reach 5% for a sensitivity of 100%. Conclusion: This report, based on over 20 years of surveillance of anti-Ro positive pregnancies, identifies associations between maternal disease, their treatments and foetal AV conduction. Routine detection assays for anti-Ro/La antibodies had low performance in predicting AVB among an anti-Ro/La positive population.