Researchers discovered that when pregnant animals received prednisone (a common steroid medication), their offspring developed more liver problems later in life, especially when eating a high-fat diet. The study found that prednisone changes how a protective protein called Serpina3c works in the liver, making it harder for the body to process fats and sugar. The good news? When scientists boosted levels of this protective protein after birth, they could reverse the damage and prevent liver disease from developing. This research suggests that doctors may need to carefully weigh the benefits and risks of using steroids during pregnancy, and it opens doors to new treatments for liver disease.

The Quick Take

  • What they studied: Whether taking prednisone (a steroid medicine) during pregnancy increases the risk of fatty liver disease in children, and whether a specific protective protein could prevent this problem.
  • Who participated: Pregnant rats and mice were given prednisone during pregnancy. Their babies were then fed high-fat diets after birth to see if they developed liver disease. Male and female offspring were studied separately.
  • Key finding: Babies exposed to prednisone before birth developed significantly more fatty liver disease when eating high-fat food compared to unexposed babies. Male offspring were affected more severely than females. Importantly, increasing a protective protein called Serpina3c after birth prevented the disease from developing.
  • What it means for you: If you took prednisone during pregnancy, this doesn’t mean your child will definitely develop liver disease, but it suggests monitoring liver health and promoting healthy eating habits may be especially important. This research may eventually lead to new preventive treatments, though more human studies are needed before any changes to medical practice.

The Research Details

Scientists conducted experiments using pregnant rodents (rats and mice) to mimic what happens in humans. Pregnant animals received prednisone doses equivalent to what doctors prescribe to people during pregnancy. After birth, the offspring were fed high-fat diets to stress their livers and see if disease developed. Researchers then examined liver tissue and measured various markers of liver function and disease.

The scientists used advanced genetic testing (RNA-seq) to identify which genes and proteins changed in the livers of exposed offspring. They discovered that a protective protein called Serpina3c was significantly reduced. They then tested whether artificially increasing this protein after birth could reverse the damage and prevent disease.

The study included both male and female animals to see if sex differences existed in how prenatal prednisone exposure affected liver disease risk. This is important because men and women sometimes respond differently to health threats.

Using animal models allows researchers to carefully control all variables and study long-term effects that would be impossible to study directly in humans. This approach helps identify the specific biological mechanisms (the ‘why’ and ‘how’) behind disease development. The finding that increasing a single protein could reverse damage is particularly valuable because it suggests a specific target for future treatments.

This study was published in a peer-reviewed scientific journal, meaning other experts reviewed the work before publication. The research used multiple animal models (both rats and mice) and both laboratory and living animal experiments, which strengthens confidence in the findings. However, because this is animal research, results may not perfectly translate to humans. The study was well-designed with clear controls, but human studies would be needed to confirm these findings apply to people.

What the Results Show

Offspring exposed to prednisone before birth showed reduced ability to take up glucose (blood sugar) and burn fatty acids in their livers, both before and after birth. When these offspring ate high-fat diets, they developed significantly more severe fatty liver disease compared to unexposed offspring. Male offspring showed greater disease severity than females, suggesting sex plays a role in how prenatal steroid exposure affects liver health.

The key discovery was that prednisone exposure reduced levels of a protective protein called Serpina3c in the liver. This reduction allowed harmful molecules (chymase and Ang II) to accumulate, which activated a receptor called AT1R. This activation triggered a cascade of problems: the liver couldn’t process glucose properly, couldn’t burn fats efficiently, and fatty deposits accumulated.

At the molecular level, prednisone (converted to prednisolone in the body) activated a pathway that reduced chemical tags (H3K27ac) on the DNA that normally keeps the Serpina3c gene active. This explains why the protective protein was reduced—the gene was essentially ’turned down’ by the steroid exposure.

Most importantly, when researchers artificially increased Serpina3c levels after birth in exposed offspring, it reversed all these problems. The harmful cascade was blocked, liver glucose and fat metabolism improved, and fatty liver disease was prevented.

The study demonstrated that the harmful effects of prenatal prednisone exposure were not limited to one species or sex, as similar patterns appeared in both rats and mice, and in both males and females (though males were more severely affected). The research also showed that the damage occurred through a specific, identifiable biological pathway, which is important for developing targeted treatments. The fact that increasing one protein could reverse multiple downstream problems suggests this protein is a critical control point in the disease process.

Previous research has shown that various environmental exposures during pregnancy (including stress and certain medications) can increase disease risk in offspring—a concept called ‘fetal programming.’ This study adds to that knowledge by identifying a specific mechanism linking prenatal steroid exposure to liver disease. While steroids are sometimes necessary during pregnancy to treat serious maternal conditions, this research suggests the long-term consequences for offspring deserve more attention. The identification of Serpina3c as a protective factor is novel and opens new research directions.

This research was conducted in animals, not humans, so results may not directly apply to people. The study used high-fat diets to trigger disease in offspring, which is an artificial stress that may not perfectly represent real-world conditions. The sample sizes and specific numbers of animals used were not detailed in the abstract. The study doesn’t tell us how common prenatal prednisone exposure is or how many exposed children actually develop liver disease. Additionally, the research doesn’t address whether lower doses of prednisone or shorter exposure periods have similar effects, which is clinically important since doctors sometimes use prednisone briefly during pregnancy.

The Bottom Line

Based on this research (moderate confidence, as it’s animal-based): If you took prednisone during pregnancy, discuss your child’s liver health with their pediatrician. Promote healthy eating habits and regular physical activity for your child, as these reduce fatty liver disease risk regardless of prenatal exposures. This research should not discourage necessary prednisone use during pregnancy when medically indicated—the benefits of treating serious maternal conditions often outweigh risks. Future human studies may lead to screening or preventive treatments for exposed children.

This research is most relevant to: pregnant women considering or taking prednisone, parents who took prednisone during pregnancy, pediatricians caring for children with prenatal steroid exposure, and researchers developing new liver disease treatments. People without prenatal steroid exposure can still benefit from the general message that healthy eating and exercise protect liver health. This is NOT a reason to avoid necessary steroid treatment during pregnancy.

In the animal studies, liver disease developed over weeks to months after birth when offspring ate high-fat diets. In humans, fatty liver disease typically develops over years. If preventive treatments based on this research are developed, benefits would likely take months to years to become apparent. Lifestyle changes (diet and exercise) can show benefits within weeks to months.

Want to Apply This Research?

  • If you have a history of prenatal prednisone exposure, track weekly servings of high-fat foods and daily physical activity minutes. Aim for fewer than 3 servings of fried or high-fat foods weekly and at least 150 minutes of moderate activity weekly. This creates a simple, measurable baseline for liver-protective behaviors.
  • Set a specific goal: ‘Replace one high-fat snack daily with a fruit or vegetable snack’ and ‘Add 15 minutes of walking on 3 days this week.’ These small changes are easier to maintain than dramatic overhauls and directly address the high-fat diet risk factor identified in this research.
  • Use the app to log dietary fat intake and exercise weekly. Set a monthly reminder to discuss liver health with your doctor (including any family history of liver disease). If available, track any liver function test results from annual check-ups. This creates a long-term picture of whether lifestyle changes are supporting liver health.

This research is based on animal studies and has not been tested in humans. Prednisone is sometimes medically necessary during pregnancy to treat serious maternal conditions—this research should not discourage its use when medically indicated. The benefits of treating maternal illness often outweigh potential risks to the fetus. If you took prednisone during pregnancy or are considering it, discuss the specific risks and benefits with your obstetrician. This article is for educational purposes only and should not replace professional medical advice. Consult your healthcare provider before making any changes to your health regimen or your child’s diet based on this research.