Smoking and pregnancy: Epigenetics and developmental origins of the metabolic syndrome

Abstract

Maternal smoking causes lower birth weight, birth defects, and other adverse pregnancy outcomes. Epidemiological evidence over the past four decades has grown stronger and the adverse outcomes attributed to maternal smoking and secondhand smoke exposure have expanded. This review presents findings of latent and persistent metabolic effects in offspring of smoking mothers like those observed in studies of maternal undernutrition during pregnancy. The phenotype of offspring of smoking mothers is like that associated with maternal undernutrition. Born smaller than offspring of nonsmokers, these children have increased risk of being overweight or obese later. Plausible mechanisms include in utero hypoxia, nicotine‐induced reductions in uteroplacental blood flow, placental toxicity, or toxic growth restriction from the many toxicants in tobacco smoke. Studies have reported increased risk of insulin resistance, type 2 diabetes and hypertension although the evidence here is weaker than for overweight/obesity. Altered DNA methylation has been consistently documented in smoking mothers' offspring, and these epigenetic alterations are extensive and postnatally durable. A causal link between altered DNA methylation and the phenotypic changes observed in offspring remains to be firmly established, yet the association is strong, and mediation analyses suggest a causal link. Studies examining expression patterns of affected genes during childhood development and associated health outcomes should be instructive in this regard. The adverse effects of exposure to tobacco smoke during pregnancy now clearly include permanent metabolic derangements in offspring that can adversely affect life‐long health.

Smoking and Smoking Cessation in the Risk for Fetal Growth Restriction and Low Birth Weight and Additive Effect of Maternal Obesity

“…The main factors affecting fetal growth include the placenta, which guarantees the flow of nutrients to the fetus [14][15][16]. Factors causing hypoxia and reductions of blood flow in the placenta may increase the risk of FGR, SGA, and LBW [2,7]. Mechanisms of an increase or decrease in studied risk have not been univocally explained, like the processes of risk intensification in women who give up smoking in the second/third trimester.…”

“…In recent decades, attention has been paid to factors impacting the fetal environment as important elements of the concept of the development of health and disease (DOHaD) [1,2]. Adverse birth outcomes have been associated not only with increased perinatal mortality and offspring neurodevelopmental disorders but also with long-term adverse health effects [1,3].…”

“…Adverse birth outcomes have been associated not only with increased perinatal mortality and offspring neurodevelopmental disorders but also with long-term adverse health effects [1,3]. In particular, abnormal (low and high) birth weight has been associated with a higher risk of "non-communicable diseases" such as obesity/overweight or diabetes mellitus and cardiovascular diseases [1][2][3][4][5].…”

“…Cigarette smoking is a modifiable environmental factor associated with many adverse pregnancy results, such as low birth weight, preterm birth, and higher newborn mortality [2,4,[6][7][8]. Tobacco smoke contains several thousand chemicals that can be harmful to the placenta and pass through the placenta to the fetus [2,3]. An important component of tobacco smoke, nicotine can interfere with the physiological transformation of spiral arteries and increase the risk of pregnancy complications [4,9].…”

Thyroid redox imbalance in adult Wistar rats that were exposed to nicotine during breastfeeding

“…In contrast, female NIC offspring displayed higher T 3 and T 4 plasma levels; thyroids had higher TSHr and TPO protein expression, higher CAT and lower GPx activities, accompanied by higher 4-HNE, AR and ERα protein expressions. Epidemiological and experimental studies have shown that prenatal nicotine exposure induces obesity and increases the risk of diseases later in life 18 . Nicotine exposure, specifically during lactation, compromises milk yield 19 and induces adaptive changes in the offspring that lead to metabolic disorders, which include: overweight, insulin and leptin resistance and thyroid dysfunction 9,10,20 .…”