ABSTRACT
OBJECTIVE: To systematically review and meta-analyze the association between neonatal abstinence syndrome (NAS) and adverse health or educational childhood outcomes. STUDY DESIGN: An all-language search was conducted across 11 databases between January 1, 1975, and September 3, 2019; 5865 titles were identified. Observational studies of children between 28 days and 16 years of age, in whom a diagnosis of NAS was documented, were included. Outcomes included reasons for hospital admissions, childhood diagnoses, developmental outcomes, and academic attainment scores. All studies underwent independent review by 2 trained reviewers, who extracted study data and assessed risk of bias using the Newcastle Ottawa Tool. RESULTS: Fifteen studies were identified that included 10 907 children with previous NAS and 1 730 213 children without previous NAS, aged 0-16 years. There was a strong association between NAS and subsequent child maltreatment (aOR, 6.49; 95% CI, 4.46-9.45; I2 = 52%), injuries and poisoning (aOR, 1.34; 95% CI, 1.21-1.49; I2 = 0%), and a variety of mental health conditions. Studies consistently demonstrated an increased incidence of strabismus and nystagmus among those with previous NAS. Children with NAS also had lower mean academic scores than the control group in every domain of testing across age groups. CONCLUSIONS: NAS is significantly associated with future child maltreatment, mental health diagnoses, visual problems, and poor school performance. Owing to the necessary inclusion of nonrandomized studies, incomplete reporting among studies, and likely unadjusted confounding, this review does not suggest causation. However, we highlight associations requiring further investigation and targeted intervention, to positively impact the life course trajectories of this growing population of children.
Subject(s)
Neonatal Abstinence Syndrome/complications , Neonatal Abstinence Syndrome/psychology , Adolescent , Child , Child Development , Child, Preschool , Humans , Infant , Infant, NewbornABSTRACT
This population-based study showed that maternal opioid plus marijuana use during pregnancy was associated with increased odds of prematurity and low birth weight but lower odds of neonatal abstinence syndrome and prolonged hospitalization compared with opioid exposure without marijuana use. Further research should evaluate the biologic mechanisms responsible for these outcomes.
Subject(s)
Marijuana Abuse/epidemiology , Marijuana Use/adverse effects , Neonatal Abstinence Syndrome/epidemiology , Opioid-Related Disorders/epidemiology , Adolescent , Adult , Analgesics, Opioid/adverse effects , Cannabis/adverse effects , Child , Data Collection , Databases, Factual , Female , Hospitalization , Humans , Infant, Low Birth Weight , Infant, Newborn , Infant, Newborn, Diseases/epidemiology , Infant, Newborn, Diseases/prevention & control , Male , Marijuana Abuse/complications , Marijuana Abuse/prevention & control , Marijuana Smoking/adverse effects , Massachusetts/epidemiology , Neonatal Abstinence Syndrome/complications , Neonatal Abstinence Syndrome/prevention & control , Opioid-Related Disorders/complications , Opioid-Related Disorders/prevention & control , Outcome Assessment, Health Care , Pregnancy , Pregnancy Complications , Young AdultABSTRACT
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.
Subject(s)
Analgesics, Opioid/adverse effects , Gene Expression , Hyperphagia/etiology , Neonatal Abstinence Syndrome/genetics , Saliva/chemistry , Case-Control Studies , Female , Gene Expression Profiling , Genetic Markers , Humans , Infant, Newborn , Male , Neonatal Abstinence Syndrome/complications , Pilot Projects , Pro-Opiomelanocortin/genetics , Prospective Studies , Receptors, Dopamine D2/genetics , Receptors, Leptin/genetics , Receptors, Neuropeptide Y/genetics , Severity of Illness Index , Sex FactorsABSTRACT
In this retrospective cohort study, we assessed the incidence of torticollis in infants with a history of neonatal abstinence syndrome. Understanding the elevated risk of torticollis in this population is important for early identification and treatment.