As healthcare providers, we’ve long recognized the importance of maternal health in shaping pregnancy outcomes. What’s become clearer in recent years is the role of epigenetics, changes in gene expression that don’t alter DNA itself but influence how genes are turned on or off.

When we look at pregnancies complicated by obesity, DNA methylation patterns in the placenta are altered, with increased methylation suppressing genes that matter for nutrient transport and fetal growth. DNA hydroxymethylation, usually tied to active gene expression, tends to drop at the same time. One study found a 21 percent increase in methylated regions and a 31 percent decrease in hydroxymethylated regions in placentas from obese pregnancies compared with lean ones (Mitsuya K, Parker AN, Liu L, Ruan J, Vissers MCM, Myatt L. PLOS ONE. 2017, 12(10):e0186115).

These changes show up directly in the structure and function of the placenta. Inflammatory changes are common, disrupting hormonal signals and communication between maternal and fetal systems, while lipid buildup in placental cells interferes with normal function and impaired blood vessel development slows villous maturation, reducing the placenta’s ability to exchange oxygen and nutrients efficiently (Saben J, Lindsey F, Zhong Y, et al. Placenta. 2014, 35:171-177).

Mitochondrial function also suffers. Placental cells from obese pregnancies generate less ATP through oxidative phosphorylation. Less energy available means nutrient transport and other vital processes get compromised, which can directly affect fetal growth and development (Mele J, Muralimanoharan S, Maloyan A, Myatt L. Am J Physiol Endocrinol Metab. 2014, 307:E419-E425).

The clinical consequences are real. Growth restriction at one extreme, excessive growth at the other. Both ends of that spectrum carry a higher risk of metabolic problems later in life, including insulin resistance and obesity (Ornoy A. Reprod Toxicol. 2011, 32:205-212).

In practice, weight and metabolic health before and during pregnancy matter more than we once realized. Supporting women to reach a healthier weight before conception can reduce risks. During pregnancy, balanced diets built around whole foods, healthy fats, and complex carbohydrates can help improve metabolic stability. For women with metabolic dysfunction, medications such as metformin may play a role in improving insulin sensitivity.

Regular follow-up lets us track maternal health and fetal growth, and adjust care as needed. The goal reaches past the pregnancy itself. Reducing the child’s long-term risk of obesity and metabolic disease matters just as much.

Scott Rennie, D.O.
Board Certified in Obesity Medicine and Family Medicine

This blog is for educational purposes only and does not constitute individual medical advice. Always consult your own physician before making changes to your health, medications, or treatment plan.

Sources:

• 1. Mitsuya K, Parker AN, Liu L, Ruan J, Vissers MCM, Myatt L. Alterations in the placental methylome with maternal obesity and evidence for metabolic regulation. PLOS ONE. 2017;12(10):e0186115. https://pubmed.ncbi.nlm.nih.gov/29045485/
• 2. Saben J, Lindsey F, Zhong Y, et al. Maternal obesity is associated with a lipotoxic placental environment. Placenta. 2014;35(3):171-177. https://pubmed.ncbi.nlm.nih.gov/24484739/
• 3. Mele J, Muralimanoharan S, Maloyan A, Myatt L. Impaired mitochondrial function in human placenta with increased maternal adiposity. Am J Physiol Endocrinol Metab. 2014;307(5):E419-E425. https://pubmed.ncbi.nlm.nih.gov/25028397/
• 4. Ornoy A. Prenatal origin of obesity and their complications: gestational diabetes, maternal overweight and the paradoxical effects of fetal growth restriction and macrosomia. Reprod Toxicol. 2011;32(2):205-212. https://pubmed.ncbi.nlm.nih.gov/21620955/