Cord blood and pre-school biomarkers mediating the relationship between maternal obesity and offspring behavioural development

The relationship between maternal obesity and its negative effects on offspring behaviour has been relatively well evoked (Jenabi et al., 2019). In three French cohorts (EDEN, ELFE and EPIPAGE 2), we have recently observed a detrimental association between maternal obesity and child behavioural outcomes such as hyperactivity and peer-relationship problems during childhood (article under review). However, the potential biological mechanisms behind this association are still unknown. Inflammation has been postulated as one potential mechanism, as maternal obesity is associated with immune system activation that is believed to have adverse consequences on the developing fetal brain, with long-term consequences (Boulanger-Bertolus et al., 2018). A second potential mechanism is alterations in the fetal steroid or hormonal environment. Obese women have increased levels of leptin which have been correlated to higher placental, umbilical cord and fetal leptin levels (Edlow, 2017). Leptin is believed to have a role in fetal brain development, specifically behavioural regulation (Valleau & Sullivan, 2014).

To our knowledge, only one study has considered inflammatory markers or hormones as part of this relationship (Minatoya et al., 2017). In a Japanese cohort, maternal obesity was associated with increased total behavioural problems in offspring, and in subsequent analyses, increased cord blood leptin levels were inversely associated with behavioural problems, the opposite relationship to what was hypothesized (Minatoya et al., 2018). Nevertheless, the mediating role of inflammatory cytokines has not been studied, though increased cytokines levels in cord blood have been associated with behavioural problems in children at 5 years (Barbosa et al., 2020).

References
Jenabi E, Bashirian S, Khazaei S, Basiri Z. The maternal prepregnancy body mass index and the risk of attention deficit hyperactivity disorder among children and adolescents: A systematic review and meta-analysis. Korean Journal of Pediatrics. 2019;62(10):374-379.doi:10.3345/kjp.2019.00185

Boulanger-Bertolus J, Pancaro C, Mashour GA. Increasing Role of Maternal Immune Activation in Neurodevelopmental Disorders. Frontiers in Behavioral Neuroscience. 2018;12(October):1-6. doi:10.3389/fnbeh.2018.00230

Edlow AG. Maternal obesity and neurodevelopmental and psychiatric disorders in offspring. Prenatal Diagnosis. 2017;37(1):95-110. doi:10.1002/pd.4932

Valleau JC, Sullivan EL. The impact of leptin on perinatal development and psychopathology. Journal of Chemical Neuroanatomy. 2014;61-62:221-232. doi:10.1016/j.jchemneu.2014.05.001

Minatoya M, Itoh S, Araki A, et al. Associated factors of behavioural problems in children at preschool age: the Hokkaido study on environment and children’s health. Child: Care, Health and Development. 2017;43(3):385-392. doi:10.1111/cch.12424

Minatoya M, Itoh S, Araki A, et al. Association between fetal adipokines and child behavioral problems at preschool age: The hokkaido study on environment and children’s health. International Journal of Environmental Research and Public Health. 2018;15(1). doi:10.3390/ijerph15010120

Barbosa S, Khalfallah O, Forhan A, et al. Immune activity at birth and later psychopathology in childhood. Brain, Behavior, & Immunity – Health. 2020;8(July):100141. doi:10.1016/j.bbih.2020.100141