Maternal opioids downregulate adiponectin receptor signaling and alter growth in offspring: pilot study

Opioid use disorder (OUD) has been linked to cardiometabolic diseases in adults through reductions in adiponectin-an adipocytokine with insulin-sensitizing effects. Opioid use during pregnancy dysregulates neonatal growth and may predispose to adult-onset diseases, but the impact of maternal OUD on neonatal adiponectin signaling has not been studied. As receptor activation is important for physiological effects, we made a priori decision to measure adiponectin receptor expression. We hypothesize that maternal OUD also reduces adiponectin receptor level in offspring (primary outcome) and alters growth (secondary outcome). To test our hypothesis, we conducted a prospective, observational pilot study and compared the expression of salivary adiponectin receptor 1/ADIPOR1 and anthropometric and body composition (fat and fat-free mass) measurements between opioid-exposed and age-matched non-exposed neonates born at ≥34 weeks' gestation. Data were stratified by exposure and sex using a Student's t-test. Significance was set at p < 0.05. A total of 67 neonates (35 opioid-exposed, 32 non-exposed neonates) were enrolled. Compared to healthy, non-exposed neonates, the expression of ADIPOR1 was reduced in opioid-exposed neonates (0.27-fold, p < 0.01), with the lowest expression in those requiring pharmacotherapy (0.048-fold, p < 0.001). Despite the smaller anthropometric measurements in the exposed than non-exposed neonates (2,915 ± 625 grams vs. 3,209 ± 345 grams, p = 0.02), opioid-exposed neonates had comparable adiposity to non-exposed neonates (fat mass percentage 8.60 ± 4.52% vs. 8.53 ± 4.00%, p = 0.95). Less breast milk was used in the exposed than non-exposed group (25.7% vs. 71.9%, p < 0.01). Maternal OUD may be associated with aberrant growth and excess adiposity in offspring through its effect on adiponectin signaling, predisposing these neonates to cardiometabolic risks.