Exposure to substance abuse in the womb: Is it linked to adverse health effects during adult life?

In an earlier post we commented briefly on how early-life exposure to substances such as alcohol, tobacco, cocaine, and heroin can increase the chances of birth defects. The question we intend to answer now is whether this kind of exposure has long-term health effects. A review published in 2013 by A.M. Vaiserman summarizes the research on this subject. The author concluded that substance abuse by a mother not only affects her child's health around the time of birth, but also causes adverse effects that are long-term and are established by epigenetic mechanisms.

Epigenetic regulation, which includes the mechanisms discussed in the linked post, has been shown to have an important role in the programming of late-onset pathologies, including type-2 diabetes, neurodegenerative diseases, and cancer. Substance abuse during pregnancy can affect the programming occurring in the developing embryo or fetus, and consequently increase the chance of pathology. There are currently more findings about the effects of prenatal substance abuse on the health outcome of the infant than on the adult. However, research on this area is increasing and yielding interesting results that link prenatal substance abuse with more long-term health consequences than what was known before.

Developmental impairments induced by prenatal exposure to substance abuse

Imagine a world where each living individual upholds the secrets of past generations. This world is not a pop up from a fiction novel, but rather the reality of many organisms whose genetic expression is orchestrated and fine tuned by an epigenetic machinery. Recent scientific breakthroughs have discouraged the traditional belief that the epigenome is of a stagnant nature, and have thus progressed the idea that the machinery’s multiple modifications are dynamic as well as susceptible to environmental outcomes. 

The human epigenome is particularly sensitive to secondary, nonnormative environmental factors such as early exposure to psychoactive substances (alcohol, smoke, tobacco, cocaine, etc.)  that can drive epigenetic changes in gametes, consequently prolonging the effects of the exposure beyond the current generation and into future, unexposed generations. The most profound influence on epigenetic states occurs during prenatal life, more specifically during gametogenesis and embryogenesis, where progressive waves of genome-wide demethylation and re-methylation increase genetic/environmental stimuli vulnerability and result in the potential acquirement or deletion of epigenetic markings that can stimulate both short or long term effects on fetal programming via mechanisms of epigenetic memory. Substance abuse during pregnancy interferes with the normal epigenetic machinery, triggering a series of impairments in crucial environmental inputs of fetal programming such as the placenta, uterine tissue, offspring-mother hormonal balance, and proper maternal blood supply. 

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Alcohol exposure can severely impair human physical and neurobehavioral development with the obstruction of epigenetic markings potentially directing organ development, hormonal balance, and normal metabolic development. Prenatal exposure to alcohol has also been linked to aberrant genetic expression induced by alterations in genes controlling methylation, chromatin remodeling and protein synthesis, including histone hyperacetylation, hypermethylation in genes controlling metabolic pathways, and hypomethylation in genes associated with development, genomic imprinting and chromatin remodeling. Nicotine intake has been associated with pulmonary malformation and metabolic syndromes such as obesity, high blood pressure, and altered glucose homeostasis including a resistance to insulin both in the first and second generation offspring. Prenatal tobacco exposure can potentially influence global and gene-specific DNA methylation by targeting imprints in males. Smoking is also believed to alter brain plasticity and proper neurological development through promoter methylation in genes crucial for brain development such as BDNF, and has further been linked to neurotransmitter impairment in the fetal heart. Cannabis is also believed to cause neurotransmitter impairment, specifically by decreasing the expression of DRD2 (dopamine receptor D2) mRNA in the brain, increasing addiction vulnerability in the growing fetus. On the other hand, exposure to illicit drugs such as cocaine, heroin and amphetamine has of late been associated with the development of malignant neoplasms and heart dysfunction leading to shorter lifespans. 

Although DNA methylation remains the most studied epigenetic mechanism underlying substance-exposure diseases, it is by no means the sole contributor. Substance abuse has shown to trigger multiple epigenetic pathways, with most inducing an overall gene downregulation. Therefore, determining which epigenetic regulators are vital participants and stressors in prenatal development would help improve pregnancy outcomes via the potential control of diseases and undesirable complications.

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Bibliography 

Vaiserman, A. M. (2013). Long-term health consequences of early-life exposure to substance abuse: an epigenetic perspective. Journal of Developmental Origins of Health and Disease, 4(4), 269–279. doi:10.1017/S2040174413000123

Pregnancy and Substance Abuse

Substance abuse is a worldwide problem that affects many people, regardless of societal level, gender and age. As defined by the World Health Organization it's the use of harmful psychoactive substances - be it drugs or alcohol - that can lead to a dependency or strong desire to take the drug without concern of consequences. Some of the most commonly abused substances include alcohol, cocaine, heroin and tabacco. One major problem is the use of these controlled substances during pregnancy. It's been shown that using certain drugs in this time period significantly increases the chances for birth defects, premature babies, underweight babies and still born births. This outcome lies on the fact that almost all drugs are known to cross the placenta and have some degree of effect upon the fetus. The effects of an array of drugs on the development of babies have been studied since the 1960's with the cigarette. Prenatal smoke exposure has been linked to increased risk for diseases, poor psychological and developmental outcomes, reduced birth weight and behavioral disorders later in life. A difficulty in predicting and establishing potential side effects of drugs on the fetus is due to the fact that the effect will depend on the time of pregnancy, dosage, and route of the drug.

 

In the following blog posts it will be reviewed and informed some of the ways it's been shown that substance abuse during pregnancy affects the epigenetics of fetal development that leads to some of the outcomes mentioned above.