RESUMEN
Importance: Linking prenatal drug exposures to both infant behavior and adult cognitive outcomes may improve early interventions. Objective: To assess whether neonatal physical, neurobehavioral, and infant cognitive measures mediate the association between prenatal cocaine exposure (PCE) and adult perceptual reasoning IQ. Design, Setting, and Participants: This study used data from a longitudinal, prospective birth cohort study with follow-up from 1994 to 2018 until offspring were 21 years post partum. A total of 384 (196 PCE and 188 not exposed to cocaine [NCE]) infants and mothers were screened for cocaine or polydrug use. Structural equation modeling was performed from June to November 2023. Exposures: Prenatal exposures to cocaine, alcohol, marijuana, and tobacco assessed through urine and meconium analyses and maternal self-report. Main Outcomes and Measures: Head circumference, neurobehavioral assessment, Bayley Scales of Infant Development, Fagan Test of Infant Intelligence score, Wechsler Perceptual Reasoning IQ, Home Observation for Measurement of the Environment (HOME) score, and blood lead level. Results: Among the 384 mothers in the study, the mean (SD) age at delivery was 27.7 (5.3) years (range, 18-41 years), 375 of 383 received public assistance (97.9%) and 336 were unmarried (87.5%). Birth head circumference (standardized estimate for specific path association, -0.05, SE = 0.02; P = .02) and 1-year Bayley Mental Development Index (MDI) (standardized estimate for total of the specific path association, -0.05, SE = 0.02; P = .03) mediated the association of PCE with Wechsler Perceptual Reasoning IQ, controlling for HOME score and other substance exposures. Abnormal results on the neurobehavioral assessment were associated with birth head circumference (ß = -0.20, SE = 0.08; P = .01). Bayley Psychomotor Index (ß = 0.39, SE = 0.05; P < .001) and Fagan Test of Infant Intelligence score (ß = 0.16, SE = 0.06; P = .01) at 6.5 months correlated with MDI at 12 months. Conclusions and Relevance: In this cohort study, a negative association of PCE with adult perceptual reasoning IQ was mediated by early physical and behavioral differences, after controlling for other drug and environmental factors. Development of infant behavioral assessments to identify sequelae of prenatal teratogens early in life may improve long-term outcomes and public health awareness.
Asunto(s)
Cocaína , Inteligencia , Efectos Tardíos de la Exposición Prenatal , Humanos , Femenino , Embarazo , Adulto , Inteligencia/efectos de los fármacos , Lactante , Cocaína/efectos adversos , Estudios Prospectivos , Masculino , Adulto Joven , Adolescente , Conducta del Lactante/efectos de los fármacos , Estudios Longitudinales , Recién Nacido , Desarrollo Infantil/efectos de los fármacosRESUMEN
BACKGROUND: Naltrexone is a medication used to treat both opioid and alcohol use disorder with limited experience in pregnant individuals, particularly in comparison to more commonly utilized treatments such as buprenorphine-naloxone. The long-term outcomes of infants exposed to naltrexone has not been previously examined. AIMS: To compare the neurobehavioral outcomes of naltrexone versus buprenorphine-naloxone exposed infants. STUDY DESIGN: Multi-centered prospective cohort study. SUBJECTS: Pregnant people on prescribed buprenorphine-naloxone or naltrexone were enrolled during pregnancy and the dyad followed until 12 months after delivery. OUTCOME MEASURES: Infants were evaluated at 4-6 weeks corrected gestational age (CGA) using the NICU Neonatal Neurobehavioral Scale (NNNS) and at the 12-month CGA visit using the Ages and Stages Questionnaire, Third Edition (ASQ-3). RESULTS: There were 7 dyads in the naltrexone group and 34 in the buprenorphine-naloxone group. On the NNNS, infants exposed to naltrexone had higher median scores for arousal and excitability, and lower median scores for attention and regulation at 4-6 weeks CGA compared to the buprenorphine-naloxone group. None of the infants in the naltrexone group were monitored for NOWS and had shorter length of hospital stay compared with the buprenorphine-naloxone group. Although no statistically significant differences were observed, more infants in the buprenorphine-naloxone group were identified as at risk for development delays in the communication, problem solving, and personal social domains of the ASQ-3 at 12 months CGA. Results should be interpreted with caution given this study's small sample size and lack of a prospective comparison cohort. CONCLUSIONS: In this small cohort, there are differences noted in infant neurobehavior by NNNS at 4-6 weeks of age when comparing the buprenorphine-naloxone and naltrexone groups. At 12 months, ASQ-3 scores were similar but with percentage differences in potential development delay risk observed between the two groups. Larger cohort studies are needed to determine the long-term child outcomes after naltrexone exposure in pregnancy.
Asunto(s)
Naltrexona , Antagonistas de Narcóticos , Humanos , Femenino , Embarazo , Recién Nacido , Adulto , Naltrexona/efectos adversos , Naltrexona/administración & dosificación , Naltrexona/uso terapéutico , Antagonistas de Narcóticos/efectos adversos , Antagonistas de Narcóticos/administración & dosificación , Antagonistas de Narcóticos/uso terapéutico , Buprenorfina/efectos adversos , Buprenorfina/administración & dosificación , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Masculino , Combinación Buprenorfina y Naloxona/efectos adversos , Combinación Buprenorfina y Naloxona/uso terapéutico , Combinación Buprenorfina y Naloxona/administración & dosificación , Desarrollo Infantil/efectos de los fármacos , Lactante , Conducta del Lactante/efectos de los fármacos , Estudios Prospectivos , Trastornos Relacionados con Opioides/tratamiento farmacológico , Naloxona/administración & dosificación , Naloxona/efectos adversos , Naloxona/uso terapéutico , Complicaciones del Embarazo/tratamiento farmacológicoRESUMEN
Despite the high burden of pain experienced by hospitalised neonates, there are few analgesics with proven efficacy. Testing analgesics in neonates is experimentally and ethically challenging and minimising the number of neonates required to demonstrate efficacy is essential. EEG (electroencephalography)-derived measures of noxious-evoked brain activity can be used to assess analgesic efficacy; however, as variability exists in neonate's responses to painful procedures, large sample sizes are often required. Here, we present an experimental paradigm to account for individual differences in noxious-evoked baseline sensitivity which can be used to improve the design of analgesic trials in neonates. The paradigm is developed and tested across four observational studies using clinical, experimental, and simulated data (92 neonates). We provide evidence of the efficacy of gentle brushing and paracetamol, substantiating the need for randomised controlled trials of these interventions. This work provides an important step towards safe, cost-effective clinical trials of analgesics in neonates.
Hospitalized newborns often undergo medical procedures, like blood tests, without pain relief. This can cause the baby to experience short-term distress that may have negative consequences later in life. However, testing the effects of pain relief in newborns is challenging because, unlike adults, they cannot report how much pain they are experiencing. One way to overcome this is to record the brain activity of newborns during a painful procedure and to see how these signals are modified following pain relief. Randomized controlled trials are the gold standard for these kinds of medical assessments, but require a high number of participants to account for individual differences in how babies respond to pain. Finding ways to reduce the size of pain control studies could lead to faster development of pain relief methods. Here, Cobo, Hartley et al. demonstrate a way to reduce the number of newborns needed to test potential pain-relieving interventions. In the experiments, the brain activity of nine babies was measured after a gentle poke and after a painful clinically required procedure. Cobo, Hartley et al. found that the babies' response to the gentle poke correlated with their response to pain. Further data analysis revealed that this information can be used to predict the variability in pain experienced by different newborns, reducing the number of participants needed for pain relief trials. Next, Cobo, Hartley et al. used this new approach in two pilot tests. One showed that gently stroking an infant's leg before blood is drawn from their heel reduced their brains' response to pain. The second showed that giving a baby the painkiller paracetamol lessened the brain's response to immunisation. The new approach identified by Cobo, Hartley et al. may enable smaller studies that can more quickly identify ways to reduce pain in babies. Furthermore, this work suggests that gentle brushing and paracetamol could provide pain relief for newborns undergoing hospital acute procedures. However, more formal clinical trials are needed to test the effectiveness of these two strategies.
Asunto(s)
Encéfalo/efectos de los fármacos , Electroencefalografía , Conducta del Lactante/efectos de los fármacos , Manejo del Dolor , Dimensión del Dolor , Percepción del Dolor/efectos de los fármacos , Umbral del Dolor/efectos de los fármacos , Dolor/prevención & control , Acetaminofén/uso terapéutico , Factores de Edad , Analgésicos no Narcóticos/uso terapéutico , Recolección de Muestras de Sangre/efectos adversos , Encéfalo/fisiopatología , Ensayos Clínicos como Asunto , Simulación por Computador , Determinación de Punto Final , Femenino , Humanos , Recién Nacido , Masculino , Dolor/diagnóstico , Dolor/etiología , Dolor/fisiopatología , Manejo del Dolor/efectos adversos , Valor Predictivo de las Pruebas , Estudios Prospectivos , Proyectos de Investigación , Estudios Retrospectivos , Tacto Terapéutico , Resultado del Tratamiento , Vacunación/efectos adversosRESUMEN
BACKGROUND/AIM: Selenium (Se) levels in pregnancy have been linked to neurobehavioral development of the offspring. DNA methylation is a potential mechanism underlying the impacts of environmental exposures on fetal development; however, very few studies have been done elucidating the role of DNA methylation linking prenatal Se and child neurobehavior. We aimed to investigate the associations between placental Se concentration and epigenome-wide DNA methylation in two U.S. cohorts, and to assess the association between Se-related DNA methylation modifications and newborns' neurobehavior. METHODS: We measured placental Se concentrations in 343 newborns enrolled in the New Hampshire Birth Cohort Study and in 141 newborns in the Rhode Island Child Health Study. Genome-wide placental DNA methylation was measured by HumanMethylation450 BeadChip, and newborn neurobehavioral development was assessed by the NICU Network Neurobehavioral Scales (NNNS). We meta-analyzed the associations between placental Se concentration and DNA methylation in each cohort, adjusting for covariates. We also fit multiple linear regression and ordinal logistic regression for methylation and newborn NNNS summary scores. RESULTS: We identified five Se-related differentially methylated CpG sites. Among them was cg09674502 (GFI1), where selenium concentration was positively associated with methylation (ß-coefficient = 1.11, FDR-adjusted p-value = 0.045), and where we observed that a one percent methylation level increase was associated with a 15% reduced odds of higher muscle tone in the arms, legs and trunk of newborns, (OR [95% Confidence Interval, CI] = 0.85 [0.77, 0.95]). We also observed for each interquartile range (IQR) increase in selenium concentration in the placenta, there was 1.76 times greater odds of higher hypotonicity (OR [95% CI] = 1.76 [1.12, 2.82]). CONCLUSIONS: Placental selenium concentration was inversely associated with muscle tone of newborns, and hypermethylation of GFI1 could be a potential mechanism underlying this association.
Asunto(s)
Metilación de ADN , Epigénesis Genética , Conducta del Lactante , Sistema Nervioso , Placenta , Selenio , Niño , Estudios de Cohortes , Epigenoma , Femenino , Humanos , Conducta del Lactante/efectos de los fármacos , Recién Nacido , Sistema Nervioso/efectos de los fármacos , New Hampshire , Embarazo , Selenio/toxicidadRESUMEN
OBJECTIVE: The consumption of illegal substances during pregnancy is an increasing social and medical issue. Main substances of prenatal drug exposure are beside tehtrahydrocannabinol (THC), opioids and methamphetamine. The effect of these substances on the long-term development of children remains uncertain. METHODS: Since 2012 newborn infants born at the university hospital of children at Leipzig which were prenatal exposed to drugs were followed long-term at the out-patient clinic for child protection. For 42 children with prenatal opioid or methamphetamine exposure the developmentent was analysed using the Bayley Scales (BSID III) at the age of 2-3 years. The children were compared with 84 unexposed control children. One case matched to 2 controls, adapted by age, gender, gestational age and birth weight. RESULTS: Motoric development between prenatal methylamphetamine, opioid exposed children and the control group showed no significant difference. Methylamphetamine exposed children (n=23) At 2 exposure show significantly lower scores in cognition and language (79,1 compared 95,9 of the control group), opioid exposed children have a slight cognitive deficits with a medium score of 91,7 (n=19). 56% of the methamphetamine group were developmentally retarded at the measurement date. Additionally, children had significant lower Bayley Scores which had single parent and/ or low educational and professional qualifications of their caregiver. Both substances increased the risk of postnatal complications to 46-53% despite of similar gestational ages in all groups. CONCLUSION: Children with prenatal methamphetamine or opioid exposure seem to have cognition and language deficits at 2 and 3 years of age. Methamphetamine might have a higher negative effect than opioids. The psychosocial risk factors associated with parental drug abuse are important for achieving age-appropriate development.
Asunto(s)
Analgésicos Opioides/toxicidad , Desarrollo Infantil/efectos de los fármacos , Cognición/efectos de los fármacos , Metanfetamina/toxicidad , Actividad Motora/efectos de los fármacos , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Niño , Preescolar , Femenino , Humanos , Lactante , Conducta del Lactante/efectos de los fármacos , Conducta del Lactante/psicología , Recién Nacido , Lenguaje , Embarazo , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Efectos Tardíos de la Exposición Prenatal/psicologíaRESUMEN
The use of psychotropic drugs during pregnancy and breastfeeding remains a controversial topic. There are several reasons for the controversy, ranging from the misperception that pregnancy is protective against mental illness, to the notion that women should be "pure" during pregnancy and avoid all extraneous substance use, and finally, to the stigma and misunderstanding of psychiatric illness and underestimation of how serious it can be. Fortunately, the currently available data are reassuring for most psychiatric medications-properly controlled studies indicate little to no risk for most (but not all) psychiatric medications.
Asunto(s)
Lactancia Materna , Trastornos Mentales/tratamiento farmacológico , Complicaciones del Embarazo/tratamiento farmacológico , Psicofarmacología/normas , Psicotrópicos/uso terapéutico , Femenino , Humanos , Conducta del Lactante/efectos de los fármacos , Recién Nacido , Embarazo , Psicotrópicos/efectos adversos , Trastornos Puerperales/tratamiento farmacológico , Estados UnidosRESUMEN
BACKGROUND: Phthalate have been detected widely in the environment; while several studies have indicated that prenatal phthalate exposure has adverse effects on neurodevelopment, the results were inconsistent. OBJECTIVE: We aimed to determine the current research status of the relationship between prenatal exposure to different types of phthalate and cognition and behavioral development in children. We conducted a systematic review to evaluate the current state of knowledge. METHODS: We systematically searched PubMed, Web of Science, and EMBASE electronic databases up to May 2018 with manual searches of the references of retrieved publications and relevant reviews. Only birth cohort studies that reported on the association between phthalate exposure and cognitive or behavioral development were included in this review. We evaluated the risk of bias for each of the included studies using a modified instrument based on the Cochrane Collaboration's "Risk of Bias" tool. RESULT: Twenty-six birth cohort studies met our inclusion criteria, nine of which investigated the impact of phthalate exposure during pregnancy on cognition, 13 on neurobehavior, and 4 on both cognition and neurobehavior. However, ten articles reported that the effect of prenatal exposure to phthalates on cognitive development was statistically significant, 15 articles reported that the effect of prenatal exposure to phthalates on neurobehavior was statistically significant. The effect of prenatal phthalate exposure on neurodevelopment differed according to sex, but the results are inconsistent, for instance, among the five studies investigating the association between mental development index (MDI) and Mono-n-butyl phthalate (MnBP), two of them showed a significantly decreasing MDI scores with increasing concentrations of MnBP among girls, but among boys one study showed the inverse association, another showed the positive association. CONCLUSION: Di(2-ethylhexyl) phthalate, dibutyl phthalate, butyl-benzyl phthalate and di-ethyl phthalate exposure during pregnancy was associated with lower cognitive scores and worse behavior in offspring, and sex-specific effects on cognitive, psychomotor, and behavioral development were identified, especially the impact of phthalate exposure on neurobehavior in boys.
Asunto(s)
Conducta Infantil/efectos de los fármacos , Desarrollo Infantil/efectos de los fármacos , Cognición/efectos de los fármacos , Disruptores Endocrinos/efectos adversos , Sistema Nervioso/efectos de los fármacos , Síndromes de Neurotoxicidad/etiología , Ácidos Ftálicos/efectos adversos , Efectos Tardíos de la Exposición Prenatal , Factores de Edad , Niño , Preescolar , Femenino , Edad Gestacional , Humanos , Lactante , Conducta del Lactante/efectos de los fármacos , Recién Nacido , Masculino , Sistema Nervioso/crecimiento & desarrollo , Síndromes de Neurotoxicidad/fisiopatología , Síndromes de Neurotoxicidad/psicología , Embarazo , Desempeño Psicomotor , Medición de Riesgo , Factores de Riesgo , Factores SexualesRESUMEN
BACKGROUND: Skin-to-skin contact after birth between mother and baby has immediate and long-term advantages. Widström's 9 Stages of Newborn Behavior offer an opportunity to evaluate a baby in the natural, expected and optimal habitat. Intrapartum drugs, including fentanyl administered via epidural and synthetic oxytocin (synOT), have been studied in relation to neonatal outcomes with conflicting results. AIMS: Determine the effects of common intrapartum medications on the instinctive behavior of healthy newborns during the first hour after birth through a prospective cohort study. STUDY DESIGN: Video record newly-born term infants during the first hour after birth while in skin-to-skin contact with mother. Code and analyze videos using Widström's 9 Stages; compare with the labor medications mothers received. SUBJECTS: Convenience sample of sixty-three low-income mothers self-selected to labor with or without intrapartum analgesia. OUTCOME MEASURES: Duration of time infants spend in each of Widström's 9 Stages for four cohorts: 1) exposed to no synOT or epidural fentanyl during labor, 2) exposed to fentanyl (but not synOT), 3) exposed synOT (but not fentanyl), 4) exposed to both fentanyl and synOT. RESULTS: A strong inverse correlation was found between intrapartum exposure to fentanyl and synOT and the normal behavior of an infant, as measured by time in each Stage. CONCLUSIONS: Intrapartum exposure to the drugs fentanyl and synOT is associated with altered newborn infant behavior, including suckling, while in skin-to-skin contact with mother during the first hour after birth. Widström's 9 Stages offer an opportunity to analyze newborn behavior whilst in the optimal habitat of the infant.
Asunto(s)
Anestesia Obstétrica/efectos adversos , Conducta del Lactante/efectos de los fármacos , Adulto , Anestesia Obstétrica/métodos , Anestésicos Intravenosos/administración & dosificación , Anestésicos Intravenosos/efectos adversos , Llanto , Femenino , Fentanilo/administración & dosificación , Fentanilo/efectos adversos , Humanos , Recién Nacido , Masculino , Movimiento , Oxitocina/administración & dosificación , Oxitocina/efectos adversos , Sueño , Conducta en la LactanciaRESUMEN
BACKGROUND: People in war zones are exposed to heavy metal contamination deriving from new-generation weapons, in addition to exposure to psychologically traumatizing war events. Pregnant women and their children-to-be are particularly vulnerable to both biological and psychological war effects. OBJECTIVE: The aim of the current study was to analyse the impact of maternal prenatal heavy metal contamination on infant emotional development and to examine the potential moderating role of maternal symptoms of post-traumatic stress disorder (PTSD) in the association between heavy metal load and infant emotional development. METHODS: The participants were 502 Palestinian mothers, pregnant in their first trimester during the 2014 War on Gaza. The mothers were recruited at their delivery (T1) and followed at the infants' age of 6-7 months (T2; N = 392). The load of five weapon-related heavy metals (chromium, mercury, vanadium, strontium, and uranium) was analysed by Inductively Coupled Plasma Mass Spectrometry (ICP/MS) from mothers' hair samples at childbirth (T1). Assessment of maternal PTSD symptoms was based on the Harvard Trauma Questionnaire (HTQ) and infant emotional development on the Infant Behavior Questionnaire (IBQ), both reported by mothers (T2). RESULTS: Two of the analysed metals, chromium and uranium, adversely predicted children's early emotional development, indicated by decreased positive affectivity, increased negative emotionality, and problems in early orientation and regulation. Mother's PTSD did not moderate the impact of heavy metal contamination on children's emotional development. CONCLUSIONS: Adverse impact of war is not limited to those who experience it directly, but is passed on to future generations through multiple mechanisms. International organizations are obliged to protect parents and infants from the modern weaponry in wars.
Asunto(s)
Desarrollo Infantil/efectos de los fármacos , Emociones/efectos de los fármacos , Metales Pesados/toxicidad , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Efectos Tardíos de la Exposición Prenatal/psicología , Exposición a la Guerra/efectos adversos , Adulto , Niño , Desarrollo Infantil/fisiología , Emociones/fisiología , Femenino , Cabello/química , Cabello/efectos de los fármacos , Humanos , Lactante , Conducta del Lactante/efectos de los fármacos , Conducta del Lactante/fisiología , Conducta del Lactante/psicología , Masculino , Medio Oriente/epidemiología , Embarazo , Efectos Tardíos de la Exposición Prenatal/epidemiología , Encuestas y CuestionariosRESUMEN
The aim of this study was to analyse the published literature on the potential effects of manganese exposure from drinking water on school-age children, with emphasis on cognitive, and neurodevelopment and behavioural effects. A systematic review of up-to-date scientific evidence published from 2006 to 2017 was conducted using Science Direct. A further search was carried out using PubMed and Web of Science. A total of 21 studies were reviewed and categorised into 12 cognitive and 9 neurodevelopment and behavioural effects. The most utilised cognitive test was the Wechsler Intelligence Scale for Children (WISC) or some subtests from it. 10 of the 12 studies on cognitive effects reported an adverse effect of manganese exposure from drinking water on children. 3 out of the 9 studies on neurodevelopment and behavioural effects reported that manganese exposure from drinking water was associated with poorer neurobehavioural performances in school children. 4 others implied the presence of some sex-specific associations with manganese exposure. 1 study suggested that children suffering from attention deficit hyperactivity disorder (ADHD) may be more susceptible to manganese exposure. Another study suggested that manganese was a beneficial nutrient as well as a neurotoxicant. Regardless of the limitations of the studies analysed, the adverse effects of manganese exposure from drinking water on school-aged children is sufficiently demonstrated. Further investigation into the subject to address inconsistencies in existing studies is recommended.
Asunto(s)
Conducta del Adolescente/efectos de los fármacos , Desarrollo del Adolescente/efectos de los fármacos , Encéfalo/efectos de los fármacos , Conducta Infantil/efectos de los fármacos , Desarrollo Infantil/efectos de los fármacos , Agua Potable/análisis , Intoxicación por Manganeso/etiología , Manganeso/efectos adversos , Contaminantes Químicos del Agua/efectos adversos , Adolescente , Factores de Edad , Encéfalo/crecimiento & desarrollo , Niño , Preescolar , Cognición/efectos de los fármacos , Femenino , Humanos , Lactante , Conducta del Lactante/efectos de los fármacos , Inteligencia/efectos de los fármacos , Masculino , Intoxicación por Manganeso/diagnóstico , Intoxicación por Manganeso/fisiopatología , Intoxicación por Manganeso/psicología , Medición de Riesgo , Factores de RiesgoRESUMEN
AIM: We examined associations between neurological alterations in infants born to smoking mothers and breastfeeding success at discharge and three months of age. METHODS: This 2016 study compared 35 normal weight infants born to smoking mothers at 37-41 weeks and 35 matched controls born to non-smoking mothers at the Maternity Hospital of Careggi University, Florence, Italy. Neonatal behaviour was evaluated using the neurological soft signs (NSS) component of the Graham-Rosenblith Scale. Breastfeeding variables were measured using the LATCH score that covers: breast latching, audible swallowing, type of nipple, mother's comfort and help they needed to hold their baby to their breast. A questionnaire on excessive crying and feeding was distributed at discharge, and further data were collected during a three-month telephone interview. RESULTS: At discharge, the infants born to smoking mothers had a significantly lower LATCH score and significantly poorer performance on several items of the NSS component than the controls. The LATCH score and number of NSS were inversely proportional. At the three-month follow-up only 57.1% of the smoking group infants were breastfeeding compared with 87.5% of the control infants (p < 0.01). CONCLUSION: Infants with smoking mothers displayed altered neurobehavioural profiles and had a difficult start to breastfeeding.
Asunto(s)
Lactancia Materna/estadística & datos numéricos , Conducta del Lactante/efectos de los fármacos , Efectos Tardíos de la Exposición Prenatal , Fumar/efectos adversos , Estudios de Casos y Controles , Femenino , Humanos , Recién Nacido , Masculino , EmbarazoRESUMEN
BACKGROUND: Few studies have systematically described relationships between clinical-behavioural signs, electroencephalographic (EEG) patterns and age during emergence from anaesthesia in young children. OBJECTIVE: To identify the relationships between end-tidal sevoflurane (ETsevoflurane) concentration, age and frontal EEG spectral properties in predicting recovery of clinical-behavioural signs during emergence from sevoflurane in children 0 to 3 years of age, with and without exposure to nitrous oxide. The hypothesis was that clinical signs occur sequentially during emergence, and that for infants aged more than 3 months, changes in alpha EEG power are correlated with clinical-behavioural signs. DESIGN: An observational study. SETTING: A tertiary paediatric teaching hospital from December 2012 to August 2016. PATIENTS: Ninety-five children aged 0 to 3 years who required surgery below the neck. OUTCOME MEASURES: Time-course of, and ETsevoflurane concentrations at first gross body movement, first cough, first grimace, dysconjugate eye gaze, frontal (F7/F8) alpha EEG power (8 to 12âHz), frontal beta EEG power (13 to 30âHz), surgery-end. RESULTS: Clinical signs of emergence followed an orderly sequence of events across all ages. Clinical signs occurred over a narrow ETsevoflurane, independent of age [movement: 0.4% (95% confidence interval (CI), 0.3 to 0.4), cough 0.3% (95% CI, 0.3 to 0.4), grimace 0.2% (95% CI, 0 to 0.3); Pâ>â0.5 for age vs. ETsevoflurane]. Dysconjugate eye gaze was observed between ETsevoflurane 1 to 0%. In children more than 3 months old, frontal alpha EEG oscillations were present at ETsevoflurane 2.0% and disappeared at 0.5%. Movement occurred within 5âmin of alpha oscillation disappearance in 99% of patients. Nitrous oxide had no effect on the time course or ETsevoflurane at which children showed body movement, grimace or cough. CONCLUSION: Several clinical signs occur sequentially during emergence, and are independent of exposure to nitrous oxide. Eye position is poorly correlated with other clinical signs or ETsevoflurane. EEG spectral characteristics may aid prediction of clinical-behavioural signs in children more than 3 months.
Asunto(s)
Periodo de Recuperación de la Anestesia , Anestesia por Inhalación/métodos , Anestésicos por Inhalación/administración & dosificación , Ondas Encefálicas/efectos de los fármacos , Encéfalo/efectos de los fármacos , Electroencefalografía , Sevoflurano/administración & dosificación , Factores de Edad , Anestesia por Inhalación/efectos adversos , Anestésicos por Inhalación/efectos adversos , Encéfalo/fisiopatología , Preescolar , Femenino , Fijación Ocular/efectos de los fármacos , Humanos , Lactante , Conducta del Lactante/efectos de los fármacos , Masculino , Actividad Motora/efectos de los fármacos , Óxido Nitroso/administración & dosificación , Valor Predictivo de las Pruebas , Estudios Prospectivos , Recuperación de la Función , Sevoflurano/efectos adversos , Factores de TiempoRESUMEN
The potential for commonly used anesthetics and sedatives to cause neuroapoptosis and other neurodegenerative changes in the developing mammalian brain has become evident in animal studies over the past 15 years. This concern has led to a number of retrospective studies in human infants and young children, and some of these studies observed an association between exposure to general anesthesia as an infant, and later neurobehavioral problems in childhood. This association is particularly evident for prolonged or repeated exposures. Because of the significant growth of fetal interventions requiring sedation and analgesia for the fetus, or because of maternal anesthetic effects, this concern about anesthetic neurotoxicity is relevant for the fetus. The potential for anesthetic neurotoxicity is the most important clinical and research problem in the field of pediatric anesthesiology. This review will first briefly summarize the rapid brain growth and development in the fetus and neonate. Next, animal model data of anesthetic neurotoxicity in the fetus and neonate will be presented, followed by a review of recent human clinical anesthetic neurotoxicity trials. Finally, the rationale for studying dexmedetomidine as a potential neuroprotectant agent in anesthetic neurotoxicity will be reviewed along with study design for two human clinical trials involving dexmedetomidine.
Asunto(s)
Anestesia/efectos adversos , Anestésicos/efectos adversos , Encéfalo/efectos de los fármacos , Desarrollo Infantil/efectos de los fármacos , Neurogénesis/efectos de los fármacos , Neuronas/efectos de los fármacos , Síndromes de Neurotoxicidad/etiología , Factores de Edad , Animales , Apoptosis/efectos de los fármacos , Conducta Animal/efectos de los fármacos , Encéfalo/crecimiento & desarrollo , Encéfalo/patología , Niño , Conducta Infantil/efectos de los fármacos , Preescolar , Dexmedetomidina/uso terapéutico , Modelos Animales de Enfermedad , Edad Gestacional , Humanos , Lactante , Conducta del Lactante/efectos de los fármacos , Neuronas/patología , Fármacos Neuroprotectores/uso terapéutico , Síndromes de Neurotoxicidad/fisiopatología , Síndromes de Neurotoxicidad/prevención & control , Síndromes de Neurotoxicidad/psicologíaRESUMEN
Use and abuse of prescription opioids and concomitant increase in Neonatal Abstinence Syndrome (NAS), a condition that may lead to protracted pharmacological treatment in more than 60% of infants, has tripled since 2000. This study assessed neurobehavioral development using the NICU Network Neurobehavioral Scale in 6-week old infants with prenatal methadone exposure who did (NAS+; n = 23) or did not (NAS-; n = 16) require pharmacological treatment for NAS severity determined by Finnegan Scale. An unexposed, demographically similar group of infants matched for age served as comparison (COMP; n = 21). NAS+, but not NAS- group, had significantly lower scores on the regulation (p < .01) and quality of movement (p < .01) summary scales than the COMP group. The NAS+ and NAS- groups had higher scores on the stress-abstinence scale than the COMP group (p < .05). NAS diagnosis (NAS +) was associated with poorer regulation and quality of movement at 6 weeks of age compared to infants without prenatal methadone exposure from the same demographic.
Asunto(s)
Conducta del Lactante/efectos de los fármacos , Metadona/uso terapéutico , Antagonistas de Narcóticos/uso terapéutico , Síndrome de Abstinencia Neonatal/tratamiento farmacológico , Adulto , Femenino , Humanos , Lactante , Conducta del Lactante/fisiología , Recién Nacido , Masculino , Metadona/farmacología , Antagonistas de Narcóticos/farmacología , Síndrome de Abstinencia Neonatal/psicología , Tratamiento de Sustitución de Opiáceos , Adulto JovenRESUMEN
CONTEXT: Multiple studies have concluded that urine drug screens rarely change clinical management. The rapid comprehensive urine drug screen (RCUDS) at our institution detects over 300 substances using a combination of EIA and GC/MS and typically takes 2-5 h for completion. OBJECTIVE: We sought to determine whether this RCUDS altered management in the pediatric population. METHODS: All patients >1 month and <18 years of age in which a RCUDS was completed from 1 January 2012 to 31 December 2012 were eligible for the study. Assuming that clinical management would not be altered in at least 90% of cases with a confidence interval of 95%, an alpha error of 5%, we calculated a sample size of 122 cases to ensure adequate study power. Four board-certified medical toxicologists reviewed 160 cases. Cases were assigned to the toxicologists based on a random-number generator. In addition, each toxicologist reviewed 12 random cases from the other three toxicologist's cases to determine inter-rater reliability. All four toxicologists reviewed any case in which a RCUDS was believed to have changed management. RESULTS: A total of 908 RCUDS were performed during the study period, and 160 were selected for study. Mean age was 10.5 years; male = 83, female = 77. Most were ordered from the ED (101/160 = 63%), followed by the inpatient unit (36/160 = 23%), outpatient (14/160 = 9%), and ICU (9/160 = 6%). 111/160 (69%) had a history of ingestion. Of the 160 randomly chosen cases, only three cases were found in which overall clinical management was altered based on the results of the RCUDS. All three cases were children <3 years old with a RCUDS positive for amfetamines. In all the three cases, police, Division of Family Services (DFS), and social work were involved. In no case did the acute clinical management change occurred due to the results of the RCUDS. CONCLUSIONS: The RCUDS rarely changed management in patients at our institution. Further study is warranted.
Asunto(s)
Maltrato a los Niños/diagnóstico , Psicotrópicos/efectos adversos , Psicotrópicos/orina , Detección de Abuso de Sustancias/métodos , Urinálisis , Adolescente , Conducta del Adolescente/efectos de los fármacos , Factores de Edad , Biomarcadores/orina , Niño , Preescolar , Femenino , Cromatografía de Gases y Espectrometría de Masas , Humanos , Técnicas para Inmunoenzimas , Lactante , Conducta del Lactante/efectos de los fármacos , Masculino , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Estudios RetrospectivosRESUMEN
BACKGROUND: Vitamin B12 deficiency is one of the most common micronutrient deficiencies and is associated with poor cognitive development and growth. Vitamin B12 is crucial for normal cell division and differentiation, and it is necessary for the development and myelination of the central nervous system. The aim of the present study is to measure the effect of daily supplementation of vitamin B12 on the neurodevelopment and growth of young children in Nepal. METHODS/DESIGN: We are conducting an individually randomized, double-blind, placebo-controlled trial with 600 marginally stunted children 6-11 months old (length for age less than -1 z-score). Children are randomized to receive a lipid-based paste containing vitamin B12 or placebo daily for 12 months. The main outcomes are changes in growth (z-scores) and in neurodevelopment measured by the Bayley Scales of Infant and Toddler Development, Third Edition, from baseline until the end of the study. DISCUSSION: If vitamin B12 supplementation benefits early child development and growth, this will have consequences for dietary recommendations for malnourished children worldwide. TRIAL REGISTRATIONS: ClinicalTrials.gov Identifier: NCT02272842 . Registered on 21 October 2014. Universal Trial Number: U1111-1161-5187. Registered on 8 September 2014.
Asunto(s)
Desarrollo Infantil , Suplementos Dietéticos , Vitamina B 12/administración & dosificación , Complejo Vitamínico B/administración & dosificación , Factores de Edad , Biomarcadores/sangre , Estatura/efectos de los fármacos , Lista de Verificación , Protocolos Clínicos , Suplementos Dietéticos/efectos adversos , Método Doble Ciego , Femenino , Humanos , Lactante , Conducta del Lactante/efectos de los fármacos , Masculino , Nepal , Sistema Nervioso/efectos de los fármacos , Sistema Nervioso/crecimiento & desarrollo , Pruebas Neuropsicológicas , Proyectos de Investigación , Factores de Tiempo , Resultado del Tratamiento , Vitamina B 12/efectos adversos , Complejo Vitamínico B/efectos adversos , Aumento de Peso/efectos de los fármacosRESUMEN
AIM: The consequences that intrapartum administration of hormones can have on breastfeeding are unclear. The aim of the study is to determine if synthetic intrapartum oxytocin, used routinely for induction/stimulation, has a relationship to initiation/duration of breastfeeding. PATIENTS AND METHODS: We conducted a cohort study that was carried out in a tertiary university hospital distinguished by WHO-UNICEF as a BFHI (Baby-Friendly Hospital Initiative). A group of 53 mother and newborn dyads who had been exposed to intrapartum synthetic oxytocin were compared with 45 nonexposed dyads. A breastfeeding questionnaire was administered by a midwife blind to patient group through phone calls 3 and 6 months after delivery. RESULTS: No statistically significant differences were observed between the two groups in the rates of mothers exclusively breastfeeding (EBF) or nonexclusively breastfeeding. The percentage of those who were EBF when discharged was 97.3% in the oxytocin-nonexposed group and 87.1% in the oxytocin-exposed group (p = 0.14). At 3 months, the group rates of exclusive breastfeeding were 72.5% in the nonoxytocin-exposed group versus 65.9% in the oxytocin-exposed group (p = 0.71). At 6 months, rates of breastfeeding were 31.4% versus 27.9% (p = 0.53) in the oxytocin-nonexposed and oxytocin-exposed groups, respectively. CONCLUSIONS: In this study, no statistically significant effect of intrapartum synthetic oxytocin administration was observed pertaining to the initiation or duration of breastfeeding.
Asunto(s)
Lactancia Materna , Conducta del Lactante/efectos de los fármacos , Oxitócicos/farmacología , Oxitocina/farmacología , Conducta en la Lactancia/efectos de los fármacos , Lactancia Materna/estadística & datos numéricos , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Madres , Oxitócicos/efectos adversos , Oxitócicos/farmacocinética , Oxitocina/efectos adversos , Oxitocina/farmacocinética , Embarazo , Atención Prenatal , Estudios Prospectivos , España , Conducta en la Lactancia/fisiología , Factores de TiempoRESUMEN
Sleep problems are frequently seen during the postpartum period. Some mothers need to use sedative agents for insomnia. Amitriptyline is a tricyclic antidepressant that has sedative effects. Despite no adverse reports, data on safety for the maternal use of this medication on breastfed infants are limited. This case report presents severe sedation and poor feeding in the breastfed baby of a woman using amitriptyline at 10 mg/day.
Asunto(s)
Amitriptilina/administración & dosificación , Amitriptilina/farmacocinética , Antidepresivos/farmacocinética , Lactancia Materna/efectos adversos , Depresión Posparto/tratamiento farmacológico , Conducta del Lactante/efectos de los fármacos , Leche Humana/química , Periodo Posparto/psicología , Adulto , Amitriptilina/efectos adversos , Antidepresivos/administración & dosificación , Antidepresivos/efectos adversos , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Hipnóticos y Sedantes/uso terapéutico , Recién Nacido , Trastornos del Inicio y del Mantenimiento del Sueño/tratamiento farmacológico , Resultado del Tratamiento , TurquíaRESUMEN
AIM: It is unclear whether low-to-moderate alcohol consumption during pregnancy affects child development. This study examined the effects that a mother's self-reported alcohol consumption had on her pregnancy and her child's birth, behaviour and development. METHODS: We asked 291 Swedish women to report their alcohol consumption before and during pregnancy using the Alcohol Use Disorders Identification Test (AUDIT); provide data on their pregnancy, labour and neonatal period; and complete a child behaviour and development questionnaire when their child was one year and six months of age. The mothers were separated into four subgroups based on their AUDIT scores. RESULTS: There were no group differences in gestational length, but children were shorter at birth if their mother drank during pregnancy. Mothers with the highest alcohol consumption before pregnancy were generally younger and more likely to smoke, have unplanned pregnancies and have children who displayed behavioural problems than controls who reported abstinence before and during pregnancy. Mothers who drank more during pregnancy than before were more likely to have had abortions and unplanned pregnancies and less likely to breastfeed for more than six months. CONCLUSION: Our results suggested that low-to-moderate alcohol consumption during pregnancy may negatively influence a child's development and behaviour in several ways.
Asunto(s)
Depresores del Sistema Nervioso Central/efectos adversos , Desarrollo Infantil/efectos de los fármacos , Etanol/efectos adversos , Conducta del Lactante/efectos de los fármacos , Efectos Tardíos de la Exposición Prenatal , Adulto , Consumo de Bebidas Alcohólicas/efectos adversos , Estudios de Casos y Controles , Femenino , Trastornos del Espectro Alcohólico Fetal/fisiopatología , Trastornos del Espectro Alcohólico Fetal/psicología , Humanos , Lactante , Persona de Mediana Edad , Embarazo , Adulto JovenRESUMEN
The role of prenatal Selective Serotonin Reuptake Inhibitor (SSRI) exposure and SLC6A4 promoter methylation status in shaping soothability at 3 and 6 months of age, for infants exposed to antidepressant medication prenatally (n = 46) and those not exposed (n = 69) was investigated. SSRI exposure status and duration of exposure (number of days) were examined along with neonatal methylation status at mean CpG 9,10 and via factor analysis across 10 CpG sites yielding PC1 (CpGs sites: 3,4,5,7) and PC2 (CpG 1,8). Analyses revealed interactions for methylation markers and SSRI exposure variables. A significant interaction between SSRI exposure and mean SLC6A4 methylation at CpG 9,10 and separately for PC1 emerged, controlling for multiple birth/medical and background covariates (e.g., Apgar scores, maternal education). Increased neonatal methylation status was associated with increased soothability changes from 3 to 6 months among infants prenatally exposed to SSRIs.