Associate Professor of Pediatrics Tufts University School of Medicine Boston, Massachusetts, United States
Background: Opioid-exposed neonates are born smaller but experience rapid catch-up growth in the first few months of life. Rapid growth trajectory in early life is associated with the risk of obesity in adulthood, although the molecular mechanisms and impact of this growth in opioid-exposed neonates are poorly understood. Adults with opioid use disorder have lower adiponectin levels (a fat-cell cytokine that sensitizes the body to insulin), predisposing them to cardiometabolic diseases. The effect of prenatal opioids on insulin sensitivity in opioid-exposed neonates has not been studied. Objective: To examine the impact of prenatal opioid exposure on adiponectin and body composition changes in the first 3 months of life. Design/Methods: Saliva samples of 20 opioid-exposed and 20 sex- and age-matched non-exposed neonates collected within 48 hours of birth underwent transcriptomic analysis of adiponectin and its receptor (ADIPOQ, ADIPOR1). Threshold cycle (Ct) values of these genes were normalized against GAPDH and YWHAZ. The expression of genes was stratified by exposure. Body composition was obtained using air displacement plethysmography and flank skinfold measurements in a separate subset of 15 opioid-exposed and 11 non-exposed neonates within the first 5 days of life and repeated in the first 3 months. Growth velocity was measured over time and compared between groups. Continuous data were analyzed using a student’s t-test and categorical data using a Chi-squared test. Results: Demographic data showed a higher incidence of maternal smoking and Hepatitis C infection status and smaller anthropometric (weight, length, head circumference) measurements in the opioid-exposed group (p < 0.05) (Table 1). The expression of ADIPOQ and ADIPOR1 was lower in the opioid-exposed group (p < 0.01 and 0.06, respectively), with both sexes affected equally (Figure). Opioid-exposed neonates had lower body mass, fat-free mass, skinfold, and length measurements at birth (p < 0.05). By 3 months of age, body composition measurements and growth velocity did not differ between the groups (Table 2). A trend towards faster skinfold changes was seen in opioid-exposed neonates compared to controls (1.95 ± 0.93% vs. 1.48 ± 0.86%).
Conclusion(s): Prenatal opioid exposure may impact developmental programming through a reduction in insulin sensitivity since birth and changes in body composition measurements over time that resemble rapid catch-up growth. Linking genomics with body composition and anthropometric measurements is critical in understanding the metabolic effects of prenatal opioid exposure.