buprenorphine and Neurodevelopmental-Disorders

To combine meta-analyses of multiple long-term outcomes in children prenatally exposed to methadone or buprenorphine through their mothers' Opioid maintenance therapy (OMT) with a systematic review of similar outcomes in experimental animals.. The Medline, Embase, Web of Science, CINAHL, Cochrane and Epistemonikos databases were searched through August 30, 2018. Clinical studies measuring effects on cognitive, behavioral or visual outcomes in 3 months or older children prenatally exposed to OMT and control group(s) were included for meta-analyses. Experimental animal studies with similar exposures and outcomes were included in a systematic review. The three authors independently performed abstract screenings and full-text reviews, and extracted the data. One author performed the meta-analyses.. The pooled results of the meta-analyses showed worse cognitive, psychomotor, behavioral, attentional and executive functioning, and affected vision in children born to mothers who were in OMT during pregnancy compared to children without prenatal drug exposure (overall effect size = 0.49, 95% confidence interval = 0.38, 0.59, p < 0.00001). Many of the experimental animal studies showed impaired outcomes after prenatal exposure to methadone or buprenorphine. The clinical results may be biased, e.g., with the OMT group having more concurrent risk factors than the unexposed comparison group. There are few studies of older children.. Children born to mothers in OMT show worse outcomes for a number of different behaviors and impaired vision compared to children born to nonusers. Experimental animal studies indicate that there might be a causal relationship between prenatal methadone or buprenorphine exposure and subsequent negative outcomes.

Topics: Analgesics, Opioid; Animals; Buprenorphine; Child; Female; Humans; Infant, Newborn; Male; Methadone; Neurodevelopmental Disorders; Opiate Substitution Treatment; Pregnancy; Prenatal Exposure Delayed Effects; Vision Disorders

Substance use among pregnant women is a major public health issue. Both prescription opioid use and illicit opioid abuse have increased dramatically in recent years. Prolonged in utero drug exposure may result in neonatal abstinence syndrome (NAS), an acute multisystemic clinical entity that occurs in the first days of life. This syndrome is caused by abrupt discontinuation of fetal exposure to licit or illicit drugs chronically consumed by the mother during pregnancy and transmitted to the fetus through the placenta. It usually requires prolonged hospitalization and may have long-term effects. The interplay of many factors contributes to its clinical heterogeneity, and its pathophysiology has not been fully unveiled. The first step in NAS management consists of nonpharmacologic interventions and includes promoting breastfeeding when not contraindicated. If withdrawal signs become severe, pharmacotherapy is needed. The Finnegan scoring system supports care providers across the pharmacotherapy process from initiation through the monitoring phase, until weaning and discontinuation. However, a standardized approach to pharmacotherapy is still lacking. Morphine is usually the first-line agent to treat NAS. Methadone is a valid option, but its safety profile is not completely known. Phenobarbital, despite its lack of effect on gastrointestinal symptoms and unfavorable pharmacologic features, has been identified as a second-line agent to be used in infants unresponsive to opiates. Although buprenorphine and clonidine seem promising, their use requires further validation. Long-term developmental effects of NAS therapy call for more-comprehensive, longitudinal assessments. In this article, key points for use of recommended therapies are outlined, and directions for future research are suggested.

Topics: Analgesics, Opioid; Antidepressive Agents; Buprenorphine; Female; Humans; Infant, Newborn; Methadone; Neonatal Abstinence Syndrome; Neurodevelopmental Disorders; Opiate Substitution Treatment; Pregnancy