596 - Umbilical cord miRNA to understand accelerated growth in opioid-exposed neonates: A pilot study

Publication Number: 4584.596

Marissa Chow, Floating Hospital for Children at Tufts Medical Center, Boston, MA, United States; Francesca Carasi-Schwartz, Floating Hospital for Children at Tufts Medical Center, Boston, MA, United States; Tomoko Kaneko-Tarui, Tufts University School of Medicine, Boston, MA, United States; Nicholas Heger, Tufts University School of Medicine, Boston, MA, United States; Mario Cordova, Director of Neonatology at Lowell General Hospital, Boston, MA, United States; Ronnelle King, Floating Hospital for Children at Tufts Medical Center, Greenland, NH, United States; Elizabeth Yen, Tufts Medicine Pediatrics-Boston Children's, Boston, MA, United States

Background: Opioid-exposed neonates are often born small and grow with an unclear trajectory. Our laboratory has previously demonstrated lower expression of salivary adiponectin receptor 1 (ADIPOR1) at birth in opioid-exposed than non-exposed neonates. The opioid-related dysregulation of adiponectin signaling may affect insulin sensitivity and metabolic outcomes. Adult data indicate that microRNAs (e.g., miR-221-3p, miR-222-3p, miR-149-3p, and miR-9-3p) regulate ADIPOR1 and body mass index (BMI), however, this has not been studied in opioid-exposed neonates.

Objective: Examine the effect of maternal opioid use on the regulation of adiponectin signaling at birth and infant growth trajectory in the first year of life.

Design/Methods: In this IRB approved prospective observational study, umbilical cord serum collected at birth from 10 opioid-exposed and 5 non-exposed neonates underwent RT-qPCR analysis for miR-221-3p, miR-222-3p, miR-149-3p, miR-9-3p, normalized against miR-191-5p and miR-16-5p. Saliva samples collected within 24 hours of birth underwent transcriptomic analysis to quantify expression of ADIPOR1, normalized against GAPDH and YWHAZ. Maternal and demographic data included race/ethnicity, delivery method, Apgar scores, GA, sex, anthropometric measurements (birth weight/BW, head circumference/HC, length/L, and percentiles), BMI, and percent change in BMI (% ΔBMI (Yr 1-Birth)). Continuous data were analyzed using a Student's t-test, and categorical data using a Fisher's exact test. Significance was set at p< 0.05.

Results: Demographic and anthropometric measurements were similar across cohorts (Table). As shown in Fig. A, umbilical cord miR-221-3p was significantly higher in opioid-exposed than non-exposed neonates (ΔCt -2.87±0.47 vs -3.94±1.18, respectively, p=0.02). Salivary expression of ADIPOR1 was comparable between groups (ΔCt -1.85±1.16 vs -1.40±1.29, p=0.53). Despite the lower BMI at birth, opioid-exposed neonates had an accelerated growth (Fig. B) and a greater % ΔBMI at one year of age (39.5% vs. 27.1%, p=0.25) (Fig. A).

Conclusion(s): Greater expression of umbilical cord serum miR-221-3p suggests its potential as an early biomarker for accelerated growth in opioid-exposed neonates. The small sample size may limit the ability to detect a significant difference in ADIPOR1 expression across cohorts. Alternatively, miR-221-3p may modulate other genes in addition to ADIPOR1. Future studies will include a larger sample size and additional genes in the adiponectin pathway.

Table. Demographic and Clinical Data
CS: cesarean section, GBS: group B streptococcus, Hep: hepatitis, BMI: body mass index, Yr: year. Data are presented as mean ± standard deviation or median (interquartile range) for continuous measures, and N(%) for categorical measures. Bolded p values indicate significance.

Figure. Accelerated growth in opioid-exposed neonates may be mediated by miR-221-3p.
The level of miR-221-3p (regulator of adiposity through its action on adiponectin signaling) was significantly higher in the opioid-exposed group (panel A, left). Higher miR-221-3p was accompanied by a lower (albeit comparable) expression of ADIPOR1 (panel A, middle) and a greater percentage of BMI change at one year in opioid-exposed neonates (panel A, right). Although starting with a lower BMI at birth, opioid-exposed neonates had a higher BMI by one year of age (panel B). *p < 0.05, Δ=delta, Ct=threshold cycle, ADIPOR1=adiponectin receptor 1, BMI=body mass index, Yr=year.