Fetal and Infancy Growth Pattern, Cord and Early Childhood Plasma Leptin, and Development of Autism Spectrum Disorder in the Boston Birth Cohort

Abstract

Leptin is a pro-inflammatory cytokine that plays an important role in energy homeostasis. Emerging evidence suggests that leptin levels are altered in children with autism spectrum disorder (ASD); however this has not been studied prospectively. Rapid growth during infancy and early childhood has been implicated in ASD, but the evidence is inconsistent. Since leptin is involved in growth and is a potential risk factor for ASD, we explored the associations between 1) cord, early childhood leptin and ASD; and 2) birth weight for gestational age, early childhood weight gain and ASD. We also assessed the mediating role of leptin in the relationship between weight gain during infancy and ASD. This study was conducted in a sample of 822 subjects from the Boston Birth Cohort. ASD was defined from diagnostic codes in electronic medical records. Extremely rapid weight gain during infancy was associated with a greater ASD risk and this persisted after adjusting for potential confounders (aOR: 3.11; 95% CI: 1.37, 7.07). Similarly, children that had higher plasma leptin levels, prior to ASD diagnosis, had an increased ASD risk in both unadjusted and adjusted models (aOR: 7.87; 95% CI: 2.06, 30.04). Further, early childhood leptin indirectly mediated the relationship between rapid weight gain and ASD. No associations were found between birth weight for gestational age, cord leptin and risk of ASD. Our findings provide a basis to further explore whether the combination of early life growth pattern and a biomarker such as leptin can predict ASD earlier.

Maternal excessive gestational weight gain as a risk factor for autism spectrum disorder in offspring: a systematic review

“…Any dysregulation in fetal leptin levels leads to mental health impairments and neurodevelopmental disorders, including ASD [ 44 ]. High plasma leptin in early childhood has been proposed as a potential biomarker for ASD [ 45 ] and increased circulating leptin is consistently observed in individuals with ASD [ 44 , 46 , 47 ]. According to previous investigations, fetal leptin levels are affected by maternal leptin levels [ 48 , 49 ].…”

Relationship of prenatal maternal obesity and diabetes to offspring neurodevelopmental and psychiatric disorders: a narrative review

“…Altered leptin levels have been implicated in depression [ 94 ]. Elevated early childhood leptin levels in plasma, but not in cord blood, have been associated with an increased risk for autism [ 95 ], and associations between leptin levels and other behaviors have been reported from rodent models [ 93 ].…”

The zebrafish subcortical social brain as a model for studying social behavior disorders

“…The authors argue that a dysregulated HPI/HPA axis may be responsible for the social deficit phenotype. In humans, an elevated leptin level has been associated with autism (Ashwood et al, 2008; Blardi et al, 2010; Raghavan et al, 2018) and Rett syndrome (Blardi et al, 2007, 2009), whereas a decrease in leptin is linked to schizophrenia and depression (Kraus et al, 2001; Atmaca et al, 2003).…”