Maternal smoking during pregnancy, and the lasting effects on both developing foetuses and adults, remain a major concern for global health. Research into the genetics and epidemiology of maternal smoking effects is uncovering just how deep these impacts go. This article brings together insights from human foetal studies and large-scale analyses of ageing adults, focusing on how exposure in utero shapes childhood and lifelong health.

Understanding Maternal Smoking During Pregnancy

Despite prevention campaigns, maternal smoking during pregnancy is still a pressing issue. Around 2% of women globally smoke during pregnancy, with much higher rates in some regions such as Europe (8%) and the Americas (6%). Children exposed in utero face not just immediate risks, but also far-reaching health consequences that continue into adulthood. These include increased chances of preterm birth, miscarriage, and even heightened risks of diseases and mental health challenges later in life.

Maternal Smoking Effects in the Population

The adverse effects of maternal smoking during pregnancy span a variety of outcomes:

• Immediate pregnancy and neonatal risks
  • Increased preterm birth
  • Stillbirth and neonatal mortality
  • Miscarriage and restricted foetal growth
• Lifelong health concerns
  • Elevated risk of neurological disorders
  • Higher rates of type II diabetes, obesity, and cardiovascular illnesses
  • Pulmonary dysfunction and persistent health issues
  • Greater likelihood of the child becoming a smoker

By understanding the full scope of maternal smoking effects, prevention strategies can become more targeted and effective.

The Science: Genetics and Biology of Maternal Smoking Effects

How Maternal Smoking During Pregnancy Affects the Foetus

Recent studies have used genetic and RNA sequencing techniques to provide a clearer picture of what happens inside developing babies. Analysing foetal liver tissues, researchers have found that maternal smoking impacts genetic expression at a fundamental level—influencing the activity of thousands of genes. Male foetuses appear especially vulnerable, showing more significant gene disturbance in pathways relating to inflammation, brain function, addiction, and even cancer risk.

Key Biological Pathways Impacted

• Inflammation and Immunity:

Male foetuses exposed to smoke in utero had more pronounced changes in inflammatory and immune signalling, which may make them more vulnerable to disease.

• Metabolism:

Both sexes showed shifts in metabolism pathways, but these were especially strong in females, affecting how their bodies process essential nutrients.

• Synaptic and Nervous System Development:

Nicotine and chemicals from tobacco disrupted genes connected with neurodevelopment and addiction, suggesting why children of maternal smokers may face mental health or addiction challenges later.

Tobacco-Specific Compounds

Elements like polycyclic aromatic hydrocarbons (PAHs) in tobacco smoke were identified as significant regulators, altering how genes work and possibly increasing cancer risks later in life.

Long-Term Effects of Maternal Smoking During Pregnancy

Evidence from the UK Biobank

The UK Biobank, a study of over half a million adults, offered vital data to trace the impact of maternal smoking into middle age and later. Participants provided information on their lifestyle, genetics, and their mothers’ habits during pregnancy. Researchers found clear links between in utero exposure and adult health. These included:

• Higher risk of chronic illnesses:

Men exposed in utero were more likely to develop gout, type II diabetes, and cancer.

Women faced increased risk of heart and digestive diseases, mental health struggles, and musculoskeletal conditions.

• Lifestyle links:

Children of maternal smokers more often had higher BMI and risky drinking habits. Socioeconomic deprivation was also more common, suggesting complex, layered impacts.

Sex-Specific Differences

Not all effects were equal between the sexes. The research highlighted that male offspring, in particular, carried a greater mortality risk from maternal smoking during pregnancy. For men who smoked as adults and were exposed in utero, five-year mortality risk increased by 16%. For women, the risks were present but less sharp and less connected to later smoking habits.

Genetic and Epigenetic Insights Into Maternal Smoking Effects

Genetic Signals and Epigenetic Changes

Studies identified disruptions in genes related to addiction (such as CHRNA3, CHRNA4, CHRNA5), neurodegeneration (IREB2), fatty acid metabolism (FADS2), and brain health (ST3GAL3) in those exposed to maternal smoking. These changes were mostly epigenetic, meaning the harmful effects resulted from environmental changes to gene expression, rather than being passed down directly in the DNA.

What is Epigenetics?

Epigenetics involves chemical modifications to DNA that do not change the genetic code itself, but affect how genes are switched on or off. Maternal smoking can leave lasting epigenetic marks, predisposing offspring to health problems throughout life.

Preventing Maternal Smoking Effects Across Generations

Despite growing knowledge, maternal smoking during pregnancy persists globally, especially among women with lower socioeconomic status. Public health advice, support systems, and educational outreach are crucial to reduce these numbers.

Why Prevention Matters

• The effects are lifelong and span physical, mental, and social wellness.
• Risks can be reduced:

Adult male offspring of maternal smokers who never took up smoking themselves saw their heightened mortality risk practically disappear.

• Intergenerational consequences:

Smoking in one generation has consequences that echo in the next.

The Importance of Ongoing Research

This study stands out for its integration of data from both developing foetuses and adults in a large population cohort. The use of genetic, transcriptomic, and epidemiological analysis offers valuable insights, but also comes with limitations. Relying on self-reported data, differences in tissue samples, and confidence intervals in mortality analysis mean that even more extensive studies are needed. Additionally, data on paternal smoking was lacking, limiting the full understanding of parental influence.

Source: Science Direct