Prenatal exposure to opioids and neurodevelopment in infancy and childhood: A systematic review (original) (raw)
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Drug Safety, 2021
KEY POINTS Question. To evaluate the relationship between maternal prescription opioid use and incidence of neurodevelopmental disorders in children. Findings. In this retrospective cohort study, 7.6% of eligible children were exposed to prescription opioids during pregnancy. We observed no overall association between maternal prescription opioid use and the risk of neurodevelopmental disorders in children. However, significantly increased risks were observed in children with longer-term opioid exposure or high cumulative doses. Meaning. These findings suggest the need for a careful consideration of the benefits of opioid therapy during pregnancy versus potential risks of long-term neurodevelopmental disorders in children.
Prenatal Opioid Exposure: Neurodevelopmental Consequences and Future Research Priorities
Pediatrics
Neonatal opioid withdrawal syndrome (NOWS) has risen in prevalence from 1.2 per 1000 births in 2000 to 5.8 per 1000 births in 2012. Symptoms in neonates may include high-pitched cry, tremors, feeding difficulty, hypertonia, watery stools, and breathing problems. However, little is known about the neurodevelopmental consequences of prenatal opioid exposure in infancy, early childhood, and middle childhood. Even less is known about the cognitive, behavioral, and academic outcomes of children who develop NOWS. We review the state of the literature on the neurodevelopmental consequences of prenatal opioid exposure with a particular focus on studies in which NOWS outcomes were examined. Aiming to reduce the incidence of prenatal opioid exposure in the near future, we highlight the need for large studies with prospectively recruited participants and longitudinal designs, taking into account confounding factors such as socioeconomic status, institutional variations in care, and maternal us...
BMC Psychiatry, 2014
Background: It is assumed within the accumulated literature that children born of pregnant opioid dependent mothers have impaired neurobehavioral function as a consequence of chronic intrauterine opioid use. Methods: Quantitative and systematic review of the literature on the consequences of chronic maternal opioid use during pregnancy on neurobehavioral function of children was conducted using the Meta-analysis of Observational Studies in Epidemiology (MOOSE) and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. We searched Cinahl, EMBASE, PsychINFO and MEDLINE between the periods of January 1995 to January 2012. Results: There were only 5 studies out of the 200 identified that quantitatively reported on neurobehavioral function of children after maternal opioid use during pregnancy. All 5 were case control studies with the number of exposed subjects within the studies ranging from 33-143 and 45-85 for the controls. This meta-analysis showed no significant impairments, at a non-conservative significance level of p < 0.05, for cognitive, psychomotor or observed behavioural outcomes for chronic intra-uterine exposed infants and preschool children compared to non-exposed infants and children. However, all domains suggested a trend to poor outcomes in infants/children of opioid using mothers. The magnitude of all possible effects was small according to Cohen's benchmark criteria. Conclusions: Chronic intra-uterine opioid exposed infants and preschool children experienced no significant impairment in neurobehavioral outcomes when compared to non-exposed peers, although in all domains there was a trend to poorer outcomes. The findings of this review are limited by the small number of studies analysed, the heterogenous populations and small numbers within the individual studies. Longitudinal studies are needed to determine if any neuropsychological impairments appear after the age of 5 years and to help investigate further the role of environmental risk factors on the effect of 'core' phenotypes.
The immediate and long-term effects of prenatal opioid exposure
Frontiers in Pediatrics
The opioid epidemic has adversely affected neonates and children, yet the mechanisms by which it impacts this population are not well understood. Not only does prenatal opioid exposure result in short-term consequences shortly after birth, it also creates long-term sequelae that may predispose these children to physical, emotional, psychiatric, cognitive, and socioeconomic problems in the future. This article provides a scoping overview of the long-term effects of antenatal opioid exposure on neonates and children as well as quality improvement and research efforts to understand and mitigate this major public health concern.
Fifty Years of Research on Prenatal Substances: Lessons Learned for the Opioid Epidemic
Adversity and Resilience Science
Current efforts to design research on developmental effects of prenatal opioid exposure can benefit from knowledge gained from 50 years of studies of fetal alcohol and prenatal drug exposures such as cocaine. Scientific advances in neurobiology, developmental psychopathology, infant assessments, genetics, and imaging support the principles of developmental neurotoxicology that guide research in prenatal exposures. Important to research design is accurate assessment of amount, frequency, and timing of exposure which benefits from accurate self-report and biomarkers of exposure. Identifying and control of pre-and postnatal factors that impact development are difficult and dependent on appropriate research design and selection of comparison groups and measurement of confounding, mediating, and moderating variables. Polysubstance exposure has increased due to the number of prescribed and nonprescribed substances used by pregnant women and varying combinations of drugs may have differential effects on the outcome. Multiple experimental and clinical assessments of infant behavior have been developed but predicting outcome before 18-24 months of age remains difficult. With some exceptions, prenatal substance exposure effect sizes have been small, and cognitive and behavioral effects tend to be specific rather than global. Studies require large sample sizes, adequate retention, and support for social services in atrisk samples. The ethical and legal contexts and stigma associated with drug/alcohol use disorder should be considered in order to prevent harm to families in research programs. Recognition of the pervasive use of addictive substances in this nation should lead to broad scientific efforts to understand how substances affect child outcomes and to initiate prevention and intervention where needed.
Adverse neurodevelopmental outcome of infants exposed to opiate in-utero
Early Human Development, 2008
In-utero drug exposure is associated with increased risks of perinatal morbidity and mortality, however longer term neurodevelopmental outcome of survivors is poorly described. Aims: The aims of this paper are: (1) to review the published literature which examines neurodevelopmental outcome in infants with Neonatal Abstinence Syndrome (NAS) and (2) to report developmental follow-up data from a case-control study of babies exposed to opiate inutero. Methods: This study was conducted at Royal Prince Alfred Hospital in Sydney, NSW, through the multidisciplinary NAS service. Literature was reviewed after searching MEDLINE for relevant studies. Our own case-control study was conducted to examine neurodevelopmental outcome. A number of standardized neuropsychological tools were employed to assess these infants. Results: Results from previously published studies on outcome of infants with NAS were not reassuring as to reported 'normal development'. In our own case-control study, opiate-exposed infants were significantly more likely to have neurodevelopmental impairment compared to healthy control infants, when assessed at 18 months and 3 years of age. Conclusions: Infants exposed to opiates in-utero are at increased risk of neurodevelopmental problems throughout early childhood.
A Review of Neurobehavioral Challenges in Children Exposed Prenatally to Intrauterine Opioid
Journal of Pediatrics Review, 2017
Context: Substance abuse has remained a worldwide issue for many years and in recent decades there has been a major growth in the number of individuals consuming opioids. Several studies have discovered that young kids who have been exposed to opioids develop greater damages in overall intellectual capabilities and neurobehavioral functions than non-exposed children. Evidence Acquisition: The purpose of this study was to evaluate the surviving texts on the incidence of challenging behavior among kids due to prenatal medication contact. Overall, out of 84 identified manuscripts, 18 were established to consider intellectual, psychomotor, and behavior consequences in opioid-exposed infants, precollege and college children when matched with healthy no-opioid-exposed controls. Results: The results indicate that children exposed to opioid in utero may be cognitively affected over time, even once located in stable families on an actual early age. Somewhat, susceptibilities seem to rise by age for girls, and the unprotected boys persist behind non exposed boys entirely through infancy and into college age. Therefore, there looks to be a constant deleterious consequence of factors associated with prenatal medication contact over time. Conclusions: The results indicate children exposed to opioid in utero may be cognitively affected over time, even once located in stable families on an actual early age. The natural susceptibilities of prenatally drug-exposed children can affect initial intellectual skills which yet again are extremely associated with advanced mental capabilities. It is feasible that pre-and postnatal genetic susceptibilities and ecological issues cooperate in a transactional method through the child's lifespan.
Early Human Development, 2018
Background: International guidelines recommend the use of item based scales for the assessment of pain and sedation. In our previous study, the implementation of the Neonatal Pain Agitation and Sedation Scale (N-PASS), and the associated systematic assessment and treatment of pain and sedation reduced pain and over-sedation in our intervention group, but lead to a significant increase of individual opiate exposure. This increased opiate exposure was not associated with impaired motor and mental development at one year of age. As one-year follow-up is not necessarily representative for future outcomes, we retested our sample at three years of age. Methods: Fifty-three patients after (intervention group) and 61 before implementation (control group) of the N-PASS and the Vienna Protocol for the Management of Neonatal Pain and Sedation (VPNPS), were compared for motor, mental and behavioural development at three-years follow-up using the Bayley Scales of Infant Development. Results: Cumulative opiate exposure was not associated with mental (p = .31) and motor (p = .20) problems when controlling for other important medical conditions, but was associated to lower behavioural scores (p = .007). No statistically significant differences were found with regard to mental (p = .65), psychomotor (p = .12) and behavioural (p = .61) development before and after the implementation of the N-PASS and the VPNPS. Conclusion: Implementing a neonatal pain and sedation protocol increased opiate exposure without affecting neurodevelopmental outcome at three-years of age.
Effects of prenatal opiate exposure on brain development – a call for attention
Nature Reviews Neuroscience, 2009
The Perspective by Thompson, Levitt and Standwood (Prenatal exposure to drugs: effects on brain development and implications for policy and education 1 Nature Rev. Neurosci. 10, 303-312 (2009)) was very welcome. The authors' focus on the gap between scientific knowledge and societal policies is highly needed. In this regard, we find it timely to also point out the
Prematurity, Opioid Exposure and Neonatal Pain: Do They Affect the Developing Brain?
Neonatology, 2015
Traditionally, 10 years ago, children born preterm often routinely received morphine, especially during mechanical ventilation. Studies in neonatal rats, whose stage of brain development roughly corresponds to that of children born preterm, found negative long-term effects after pain and opioid exposure. We studied possible effects of prematurity, procedural pain and opioids in humans 10 years later. We hypothesized that these factors would negatively influence neurobiological, neuropsychological and sensory development later in life. We included 19 children born preterm who as neonates participated in an RCT on the short-term effects of morphine administration and who previously participated in our follow-up studies at ages 5 and 8/9 years. We assessed associations between brain morphology (n = 11), neuropsychological functioning (n = 19) and thermal sensitivity (n = 17) and prematurity, opioid exposure and neonatal pain. Significant correlations (coefficients 0.60-0.85) of gestati...