What is the effect of maternal obesity on the brain development of offspring?

By Dr. Priyom Bose, Ph.D.Mar 22 2023Reviewed by Aimee Molineux

During the perinatal period, the maternal diet and behavior affect the developmental trajectory of the offspring. Several studies have indicated maternal depression and obesity enhance the risk of neuropsychiatric disease in offspring.

Recently, scientists reviewed the mechanisms associated with the maternal microbiome, breast milk composition, maternal and placental metabolites, altered maternal care, and inflammation, which influences the brain development of the offspring. This review has been published in Metabolites.

Obesity during pregnancy 

Obesity is a metabolic disorder that is prevalent globally. Nevertheless, this disorder can be prevented with lifestyle modification. In 2017, the Royal College of Obstetricians and Gynaecologists discovered that around a quarter of pregnant women in the UK were obese. A similar obesity rate has been reported across continental Europe.

Excessive gestational weight gain (GWG) is another common occurrence during pregnancy among women residing in Western countries, such as the USA and Australia, and the UK. Women with high BMI values before becoming pregnant are at an elevated risk of excessive GWG and retaining weight postpartum. Many pregnant women gain excessive weight because of the high fat intake in their diet during pregnancy.

Recently, researchers have investigated how maternal diet and obesity influence maternal and offspring behavior. These studies have shown that psychiatric diseases can be transmitted to offspring through poor maternal health during gestation and in the early phase of the newborn’s life.

Maternal obesity was directly associated with attention deficit hyperactivity disorder (ADHD), irrespective of birth weight. Pre-pregnancy obesity was linked with difficulties with emotional intensity in children. In addition, many of these children experience several behavioral issues, such as dissociative disorders, obsessive-compulsive disorder, and eating disorders.

Underlying factors 

Scientists have identified some of the factors that influence the neurodevelopment and emotional behavior of children. Animal studies using rodents and nonhuman primate (NHP) offsprings indicated how maternal peripartum high-fat diet affects the offspring's brain and behavior. An in vivo rat model study revealed that expression of TLR4 and CD11b, which are markers for the central nervous system (CNS)-resident microglia, were considerably upregulated in the juvenile offspring of obese rats fed with a highly saturated fat diet.

Under normal circumstances, TLR4 is activated for strong pro-inflammatory responses to bacterial endotoxin. TLR4 activation mediates central inflammatory signaling and modifies brain metabolism. Compared to the healthy control group, the basal level of IL-1β protein was found to be significantly increased in the hippocampus and periphery (liver) of the juvenile and adult offspring of high-fat diet (HFD)-fed dams. These alterations in the HFD-exposed offspring were linked to enhanced anxiety. In addition, maternal HFD (mHFD) consumption during gestation was found to increase anxiety-like behavior in juvenile female NHP offspring. Furthermore, disturbances in the serotonergic system were observed along with a decrease in the cerebrospinal fluid levels of serotonin.

Ethological studies have indicated that Infant primates raised in absence of maternal care develop severe social deficits and get attached to inanimate objects that provide a sense of comfort. During the early postnatal period, maternal care or neglect plays a crucial role in the child’s neurodevelopment. Clinical studies have also shown the relationship between child maltreatment and their altered neurobiology and behavior.

Preclinical studies have indicated some of the mechanisms that mediate the effect of maternal neglect. The theory of fetal programming entails exposure to considerable neglect or other stressors during the early postnatal phase influences the child’s brain development. Not much evidence has been documented regarding the effect of maternal-diet-induced obesity on the offspring’s behaviors.

Maternal obesity might affect an offspring's brain and behavior due to changes in the maternal and offspring gut microbiome. Maternal gut dysbiosis induced by diet or antimicrobial treatment affects the offspring’s microbiome, which in turn influences offspring brain development and behavior. Microbial metabolites contribute to fetal nourishment, which is important for the origins of immunity and neurodevelopment.

More research is required to fully understand how obesity-induced changes in the maternal microbiome influence offspring neurodevelopment and behavior. In most obese mothers there is a deficiency of Bifidobacteria spp. or Lactobacillus spp, which reduce beneficial metabolites. 

Obesity is an inflammatory condition, which is associated with a persistent increase in circulating pro-inflammatory cytokines (e.g., IL-6). Several studies have indicated that obesity during gestation aggravates inflammation, which affects fetal development.

Human milk is highly dynamic in composition. Human milk becomes fully mature after four to six weeks postpartum. It contains essential nutrients and growth factors for infant health and development. Maternal BMI impacts the overall breast milk composition, which is associated with the offspring’s psychopathology. Animal studies using mice have shown that maternal obesity during lactation can influence metabolic inflammation and precocious pubertal development in the offspring.

Conclusions

Appropriate dietary changes to improve metabolic health could be beneficial for women prior to, during, and after pregnancy. In addition, modification of maternal microbiota could be beneficial in mitigating the risk of metabolic and/or mood disorders in the newborn. In the future, personalized probiotic treatment could be designed, which would be beneficial for both the mother and child.