Chewing Tobacco During Pregnancy: Nicotine Concentration and Outcomes

A research report has found that chewing tobacco by pregnant women can lead to an increase in nicotine levels in the biological samples of both the mother and newborn. Smoking may also be associated with adverse outcomes for both the mother and the newborn.

In central Australia, indigenous women use a wild tobacco plant called Nicotiana spp. (locally known as pituri) as a chewable form of smokeless tobacco, consistently throughout pregnancy and breastfeeding. The objective is to describe the biological concentrations of nicotine and metabolites in maternal and newborn samples, and examine the relationship between self-reported tobacco use by mothers and outcomes for both mother and newborn.

Method

A Central Australian indigenous mother, who planned to give birth at Alice Springs Hospital in the Northern Territory of Australia, has provided biological samples of herself and her newborn. These samples include maternal blood, arterial and venous umbilical cord blood, amniotic fluid, maternal and neonatal urine, and breast milk. The nicotine concentration and five metabolites of these samples were analyzed.

Result

A total of 73 female participants were included in the study, who self-reported as non-tobacco users (n=31), tobacco chewers (n=19), or smokers (n=23).

Not all biological samples come from all mothers and newborns. In those areas where samples were taken, the total concentration of nicotine and metabolites in the plasma, urine, breast milk, umbilical cord blood, and newborn urine on the first day was higher for chewers compared to smokers and non-smokers. Blood glucose levels were higher for tobacco-exposed mothers (chewers and smokers) with elevated blood glucose compared to tobacco-exposed mothers with normal blood glucose, and this was related to increased birth weight in newborns. Newborns exposed to higher maternal nicotine levels were more likely to be admitted to neonatal intensive care units. By the third day, the urine concentration of tobacco-exposed newborns had decreased compared to the first day, although these concentrations remained higher than those of newborns in the non-tobacco group.

Conclusion

This study provides the first evidence that maternal tobacco chewing is associated with increased levels of nicotine in both mothers and newborns, and that smoking may be linked to adverse outcomes for both. Screening for all tobacco and nicotine product use during pregnancy, rather than simply focusing on smoking, will provide a more comprehensive assessment and help determine exposure to tobacco and nicotine more accurately. This knowledge will better inform care for pregnant women and fetuses, shift focus to targeted smoking cessation strategies, and ultimately improve long-term clinical outcomes, not only for this vulnerable population but for a wider population as well.

Reader Information

In this study, Aboriginal women from central Australia chose to use the term "Indigenous" to refer to themselves, while "Aboriginal" was used to refer to a wider group of Indigenous Australians. This choice was preserved in the report of the study results.

In non-Westernized populations, using smokeless tobacco (SLT) instead of smoking is a common form of tobacco use [1]. Data from 140 countries/regions indicate that an estimated 90 million women aged 15 or older use SLT products [1, 2]. SLT refers to a type of tobacco product that is not smoked but rather used as a solid, paste, or powder for the nasal, oral, or skin route of administration [1]. Commonly used products include snuff, nasal snuff, toombak, paan, mishri, soluble tobacco lozenges, and sticks.

Nicotine is the main pharmacologically active and addictive compound found in tobacco. SLT, or smokeless tobacco, allows for the extraction and absorption of nicotine and other compounds from the tobacco plant without the need for contact with tobacco smoke. Indigenous Australians in the central region of the country use a wild tobacco plant called pituri, which they also refer to as SLT. They dry the plants and mix them with wood ash from specific trees, chew them into balls (called quids) and keep them in their cheek pouches for extended periods. The pituri plant is preferred for use because it has been found to have nicotine content as high as 11mg/g. Adding high alkaline wood ash to the liquid will raise its pH, thereby increasing the proportion of non-protonated (free base) nicotine, which in turn increases the absorption of nicotine through the oral mucosa. Wet liquid extracted from the cheek pouch is often saved for later use behind the ear, creating a potential transdermal nicotine delivery route. Habitual use of pituri is established in early life and continues throughout pregnancy and breastfeeding.

Nicotine is a stimulant of the nicotinic acetylcholine receptor (nAChR) but acts as an antagonist on two nAChR subunits. It produces a wide range of general, reproductive, and pregnancy-specific biphasic reactions, transitioning from initial stimulation to depression in a dose-dependent and cumulative manner, influenced by various individual factors including genetics, age, gender, and pregnancy. Nicotine crosses the placenta and accumulates in the fetus and placenta, with higher ratios in umbilical cord blood than in maternal serum, and binds to nAChR during fetal development and immaturity.

Nicotine has a half-life of approximately two hours and is primarily metabolized in the liver through the CYP2A6 pathway, with secondary sites being the brain, kidney, and lungs. This short half-life results in significant fluctuations in serum plasma nicotine levels. Cotinine, a major metabolite of nicotine, has a half-life of approximately 17 hours and has serum concentrations ten times higher than nicotine, providing a more stable biomarker of nicotine exposure. Other major metabolites include 3’-hydroxycotinine, nornicotine, nicotine glucuronide, and nicotine-N-oxide. Nicotine and its metabolites are excreted by the kidneys, with excretion rates depending on urine pH. During pregnancy, CYP2A6 activity is significantly induced, increasing the plasma clearance rate of nicotine by 60% and cotinine by 140%, resulting in a nearly 50% reduction in cotinine's half-life from 17 hours to 9 hours. These changes are clinically significant because, compared to before or early pregnancy, the decrease in nicotine and cotinine concentrations in late pregnancy may not necessarily reflect reduced nicotine exposure but rather a faster metabolism. The immature CYP2A6 activity in fetuses and newborns reduces their ability to metabolize nicotine, resulting in a longer plasma half-life for nicotine (11.2 hours versus 2 hours in adults) and comparable elimination of cotinine (16.3 hours compared to adults’ 17 hours).

Extensive research over the past 60 years has shown that smoking, using smokeless tobacco, and/or exposure to secondhand smoke can have negative consequences for both mothers and newborns [19,20,21,22,23]. For mothers, these consequences may include delayed conception, increased risk of miscarriage, ectopic pregnancy, and elevated blood sugar levels [24,25,26,27,28]. At the macroscopic level of the fetus, nicotine exposure is associated with shortened gestational age (premature birth before 37 weeks), low birth weight (LBW), and malformations [29]. Gestational length and birth weight are critical indicators of fetal health and are significantly influenced by maternal glucose levels. Additionally, for newborns exposed to elevated maternal glucose levels, transitioning from a high blood sugar intrauterine environment to independent blood sugar control after birth may be challenging [30,31,32] and increases the likelihood of neonatal admission to a special care nursery (SCN) [33,34]. At the microscopic level of the fetus, nicotine has teratogenic effects on nAChRs and neurophysiology, increasing the risk that adverse effects will persist.

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