The Metabolic Consequences of Intrauterine Growth Restriction

 Intrauterine growth restriction (IUGR) is when a fetus does not reach its expected size during pregnancy and is assigned a birth weight or length below the 10th percentile for its age. IUGR can bring significant risks to neonatal health and has long-term consequences on metabolic functions. The understanding of metabolic changes due to IUGR is crucial for developing effective treatments for these health risks. This review will examine the current knowledge on the metabolic changes in IUGR individuals as well as the effects of IUGR on metabolism. 

Animals have played a crucial role in studying IUGR metabolism showing that IUGR leads to long-lasting harmful impacts on growth, development, and metabolic functions. Research using rat models shows that IUGR can lead to alterations in glucose metabolism. Studies where rats were subjected to low-protein diets in utero showed an increased risk of developing insulin resistance and glucose intolerance later in life. The result of these studies are the outcome of a change in gene expression leading to insulin signaling and glucose transport. 

IUGR mice also showed increased body fat in their fat tissue leading to changes in their metabolism. Mice born IUGR most of the time have a higher number of fat cells that are inflamed. Inflammation can mess with metabolic processes, making the mice insulin resistant and cause a change in fat handling as they are less likely to burn fat. These studies have provided valuable insights to help understand the metabolism of people with IUGR. 

The leading cause of IUGR in humans is preeclampsia. Preeclampsia affects 2-8 percent of all pregnancies and is characterized by high blood pressure and damage to organs. Since preeclampsia reduces blood flow to the placenta, it results in reduced oxygen and nutrient supply to the fetus. This condition can lead to chronic hypoxia and nutrient deficiency, which affects fetal growth and development. 

Another major cause of IUGR is poor nutrition during pregnancy, which leads to insufficient nutrients for the fetus. Another cause is multiple pregnancies because it places increased stress on the mother’s body. Additionally, maternal infections, smoking, and alcohol consumption is linked to an increased risk of IUGR. Type 2 diabetes is more likely to arise in people born with IUGR because of insulin resistance. Due to metabolic differences, insulin resistance, and changes in hormones IUGR is more likely to lead to higher levels of body fats. Having higher levels of body fat can lead to many health problems. More body fat promotes insulin resistance making it hard for the body to control its sugar levels. People with IUGR who are already at risk for insulin resistance, by having more body fat it can make this problem worse and increase the risk for type 2 diabetes. 

In people with IUGR, their fat tissue often gets inflamed. This disturbs how insulin works, causing problems with their metabolism. This inflammation happens because there are high levels of substances like TNF-α and IL-6. These substances interfere with insulins ability to regulate blood sugar leading to insulin resistance. Also, these individuals usually have a lack of adiponectin which is a hormone that helps insulin work better. The combination of inflammation and reduced adiponectin makes it harder for insulin to function properly, increasing the risk of metabolic problems. Also, due to IUGR individuals storing more fat in the liver and producing more glucose than it regularly would, it leads to insulin resistance as the fat tissue sends more fatty acids to the liver than it is able to handle. The liver accumulates fat because of an overflow of fatty acids which leads to liver damage and metabolic issues. 

Muscle metabolism is also impaired in IUGR individuals. IUGR individuals experience a reduction in the ability to absorb glucose as well as burn energy efficiently. This reduces the overall energy for essential bodily functions and increases the risk of metabolic diseases. Since muscles are key to managing glucose, a dysfunction can lead to an imbalance in the metabolism system. They also oftentimes have less muscle mass which in turn affects their metabolic efficiency contributing to insulin resistance. 

Epigenetic changes have been seen in IUGR individuals which are linked to metabolic issues. This can alter gene expression, increasing the risk of metabolic diseases. For example, there are differences in methylation in IUGR individuals due to insulin signaling which adds to their metabolic problems. Understanding these epigenetic mechanisms would be the first step into finding a cure for the metabolic issues in IUGR individuals

In summary, being IUGR significantly affects one’s metabolic system. Understanding these effects, through animal and human models, is key to improving the outcomes for those affected by IUGR. Future research should focus on finding specific molecular pathways to see the metabolic risks associated with IUGR. 

Written by: Sofia Bonomi

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