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Published on: April 14, 2010
Sex-Dependent Gene Expression in Infants with Neonatal Opioid Withdrawal Syndrome
Elizabeth Yen1, Tomoko Kaneko-Tarui2, Robin Ruthazer3
1Department of Pediatrics, Floating Hospital for Children/Tufts University School of Medicine, Boston, MA.
Insights
Prenatal opioid exposure impacts infant feeding behaviors through sex-specific gene expression changes. Salivary biomarkers may predict withdrawal severity and hospital stay duration in Neonatal Opioid Withdrawal Syndrome (NOWS) infants.
Area of Science:
- Neuroscience
- Genetics
- Pediatrics
Background:
- Neonatal Opioid Withdrawal Syndrome (NOWS) is a growing concern in newborns exposed to opioids in utero.
- Hyperphagia is a common symptom in NOWS infants, but its underlying molecular mechanisms, particularly sex-specific effects, are not fully understood.
- Understanding these mechanisms is crucial for developing targeted interventions.
Purpose of the Study:
- To investigate the sex-specific molecular mechanisms of in utero opioid exposure on hypothalamic and reward genes.
- To identify salivary biomarkers associated with hyperphagia and withdrawal severity in NOWS.
- To explore correlations between gene expression, feeding behavior, and length of hospital stay.
Main Methods:
- Prospective saliva collection from 50 newborns with prenatal opioid exposure and 50 controls matched for sex and gestational age.
- Transcriptomic analysis of 4 key feeding regulatory genes (NPY2R, POMC, LEPR, DRD2) in saliva.
- Correlation of normalized gene expression with feeding volume and length of stay in infants with NOWS requiring pharmacotherapy.
Main Results:
- Dopamine type 2 receptor (DRD2) expression was significantly higher in males than females with NOWS.
- Leptin receptor (LEPR) expression was higher in males than females with NOWS requiring pharmacotherapy.
- DRD2 expression correlated with feeding intake, and NPY2R expression correlated with length of stay.
Conclusions:
- Prenatal opioid exposure induces sex-dependent alterations in hypothalamic feeding regulatory gene expression.
- Salivary gene expression analysis holds potential for predicting hyperphagia, withdrawal severity, and length of stay in NOWS infants.
- These findings highlight the importance of considering sex in NOWS research and clinical management.
Objectives:
To evaluate salivary biomarkers that elucidate the molecular mechanisms by which in utero opioid exposure exerts sex-specific effects on select hypothalamic and reward genes driving hyperphagia, a hallmark symptom of infants suffering from neonatal opioid withdrawal syndrome (NOWS).
Study Design:
We prospectively collected saliva from 50 newborns born at ≥34 weeks of gestational age with prenatal opioid exposure and 50 sex- and gestational age-matched infants without exposure. Saliva underwent transcriptomic analysis for 4 select genes involved in homeostatic and hedonic feeding regulation (neuropeptide Y2 receptor [NPY2R], proopiomelanocortin [POMC], leptin receptor [LEPR], dopamine type 2 receptor [DRD2]). Normalized gene expression data were stratified based on sex and correlated with feeding volume on day of life 7 and length of stay in infants with NOWS requiring pharmacotherapy.
Results:
Expression of DRD2, a hedonistic/reward regulator, was significantly higher in male newborns compared with female newborns with NOWS (Δ threshold cycle 10.8 ± 3.8 vs 13.9 ± 3.7, P = .01). In NOWS requiring pharmacotherapy expression of leptin receptor, an appetite suppressor, was higher in male subjects than female subjects (Δ threshold cycle 8.4 ± 2.5 vs 12.4 ± 5.1, P = .05), DRD2 expression significantly correlated with intake volume on day of life 7 (r = 0.58, P = .02), and expression of NPY2R, an appetite regulator, negatively correlated with length of stay (r = -0.24, P = .05).
Conclusions:
Prenatal opioid exposure exerts sex-dependent effects on hypothalamic feeding regulatory genes with clinical correlations. Neonatal salivary gene expression analyses may predict hyperphagia, severity of withdrawal state, and length of stay in infants with NOWS.
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