title: Impaired performance in a test of decision-making by opiate-dependent tobacco smokers. Birthweight and cognitive development during childhood. Visual outcome in infants born to drug-misusing mothers prescribed methadone in pregnancy Survival and cessation in injecting drug users: prospective observational study of outcomes and effect of opiate substitution treatment Risk of death during and after opiate substitution treatment in primary care: prospective observational study in UK General Practice Research Database Maternal Smoking and Its Association With Birth Weight Foster-Placed and Adopted Children Exposed In Utero to Opiates and Other Substances: Prediction and Outcome at Four and a Half Years Profiles of Cognitive Dysfunction in Chronic Amphetamine and Heroin Abusers Methadone and perinatal outcomes: a prospective cohort study. Neonatal abstinence syndrome after methadone or buprenorphine exposure. The effects of prenatal exposure to buprenorphine or methadone on infant visual evoked potentials. Neurodevelopmental outcome after prenatal exposure to opiates The impact of postnatal and concurrent maternal depression on child behaviour during the early school years.
abstract: This study tested whether opiate dependence , tobacco smoking , or their combination accompanied impaired performance on the  gambling task ( GT )  , which tests decision-making .  GT previously detected impairments in patients with lesions of the ventromedial prefrontal cortex and in substance abusers . Four groups were matched on demographic characteristics and intelligence : methadone-maintained smokers ( n = 9 ) and nonsmokers ( n = 9 ) , and control ( i.e. , not opiate-dependent ) smokers ( n = 9 ) and nonsmokers ( n = 10 ) . The  Wisconsin Card Sorting Task ( WCST )  was administered to test whether differences in  GT performance reflected generalized deficits in prefrontal cortical function . While there were no significant group differences on the WCST , groups differed significantly on  GT performance ( F(3,31 ) = 2.95 , P = 0.048 ) , controlling for depressive symptom ratings and childhood attention deficit hyperactivity disorder .  Methadone-maintained smokers ( but not nonsmokers ) performed more poorly than either of the two control groups ( P = 0.007 versus smokers ; P = 0.024 versus nonsmokers ) . In a planned analysis of methadone-maintained subjects , smokers scored more poorly on  GT  than nonsmokers ( F(1,18 ) = 5.64 , P = 0.032 ) and had more treatment failures ( 67 % heroin use during the last 30 days versus 20 % ) . The findings suggest that among opiate-dependent individuals , tobacco smoking may be a marker for a more severe form of substance abuse disorder , reflecting impaired decision-making , as modeled by GT OBJECTIVES Low birthweight has been reported to be associated with lower IQ at school age . Further , some evidence suggests that the association extends across the range of normal birthweights . This study assessed the relationship of birthweight to cognitive development in the Port Pirie birth cohort . METHODS Of 723 singleton live births recruited into a prospect i ve birth cohort study , 601 , 548 , 494 and 375 children were followed at ages 2 , 4 , 7 and 11 - 13 years , respectively . The children 's developmental status was assessed using the Bayley Scales of Infant Development at age 2 years , the McCarthy Scales of Children 's Abilities at age 4 years , and the revised Wechsler Intelligence Scale for Children at ages 7 and 11 - 13 years . The association between birthweight and cognitive function was assessed with multiple linear regression , adjusting for a wide range of possible confounders . RESULTS The  mean birthweight was 3386 g ( SD : 517 ) . There was a statistically significant association between birthweight and cognitive performance at age 2 years ( adjusted deficit : 0.97 points per 100 g lighter ; 95 % CI : 0.4 - 1.5 ) , but the magnitude of this association gradually decreased and became statistically non-significant at later childhood . CONCLUSIONS The relationship between birthweight and cognitive development becomes progressively attenuated at increasing age . At older ages , socioenvironmental factors appear to play an increasingly important part in children 's cognitive development Background Flash visual evoked potentials ( VEPs ) were abnormal in a cohort of 100 neonates exposed to maintenance methadone in utero . This prospect i ve cohort study now describes clinical visual and electrophysiological outcomes at 6 months . Methods Visual assessment included modified Atkinson test battery ; strabismus , nystagmus , reduced visual acuity , delayed visual maturation or refractive error ( > 3 dioptres ) defined a fail . Pattern-onset VEPs were recorded to 120′ , 60′ and 15′ checks . Results 81 drug-exposed and 26 comparison infants ( 79 % and 52 % of the original cohorts ) were assessed at a median age of 27 weeks ( range 26–30 ) . 90 % of drug-exposed infants had been additionally exposed to illicit drugs and 41 % to excess alcohol in utero . 40 % of the drug-exposed cohort failed clinical visual assessment : the relative risk of abnormal assessment was 5.1 ( 95 % CI 1.3 to 20 ; p=0.02 ) . Nystagmus was particularly common . VEP peak times were slower and amplitudes smaller in drug-exposed infants , of whom 70 % had one or more abnormal VEP parameter . Abnormal visual outcome at 6 months was not associated with the pattern of additional drug exposure or a history of neonatal abstinence . Conclusions Abnormal visual electrophysiology in infants born to drug-misusing mothers prescribed maintenance methadone  persists to 6 months of age , and is associated with abnormal clinical visual assessment Objectives To examine survival and long term cessation of injecting in a cohort of drug users and to assess the influence of opiate substitution treatment on these outcomes . Design Prospect i ve open cohort study . Setting A single primary care facility in Edinburgh . Participants 794 patients with a history of injecting drug use presenting between 1980 and 2007 ; 655 ( 82 % ) were followed up by interview or linkage to primary care records and mortality register  , or both , and contributed 10 390 person years at risk ; 557 ( 85 % ) had received opiate substitution treatment .  Main outcome measures Duration of injecting : years from first injection to long term cessation , defined as last injection before period of five years of non-injecting ; mortality before cessation ; overall survival . Results In the entire cohort 277 participants achieved long term cessation of injecting , and 228 died . Half of the survivors had poor health related quality of life . Median duration from first injection to death was 24 years for participants with HIV and 41 years for those without HIV . For each additional year of opiate substitution treatment the hazard of death before long term cessation fell 13 % ( 95 % confidence interval 17 % to 9 % ) after adjustment for HIV , sex , calendar period , age at first injection , and history of prison and overdose . Conversely exposure to opiate substitution treatment was inversely related to the chances of achieving long term cessation . Conclusions Opiate substitution treatment in injecting drug users in primary care reduces this risk of mortality , with survival benefits increasing with cumulative exposure to treatment . Treatment does not reduce the overall duration of injecting Objective To investigate the effect of opiate substitution treatment at the beginning and end of treatment and according to duration of treatment . Design Prospect i ve cohort study . Setting UK General Practice Research Data base Participants Primary care patients with a diagnosis of substance misuse prescribed methadone or buprenorphine during 1990 - 2005 . 5577 patients with 267 003 prescriptions for opiate substitution treatment followed-up ( 17 732 years ) until one year after the expiry of their last prescription , the date of death before this time had elapsed , or the date of transfer away from the practice . Main outcome measures Mortality rates and rate ratios comparing periods in and out of treatment adjusted for sex , age , calendar year , and comorbidity ; st and ardised mortality ratios comparing opiate users ’ mortality with general population mortality rates . Results Crude mortality rates were 0.7 per 100 person years on opiate substitution treatment and 1.3 per 100 person years off treatment ; st and ardised mortality ratios were 5.3 ( 95 % confidence interval 4.0 to 6.8 ) on treatment and 10.9 ( 9.0 to 13.1 ) off treatment . Men using opiates had approximately twice the risk of death of women ( morality rate ratio 2.0 , 1.4 to 2.9 ) . In the first two weeks of opiate substitution treatment the crude mortality rate was 1.7 per 100 person years : 3.1 ( 1.5 to 6.6 ) times higher ( after adjustment for sex , age group , calendar period , and comorbidity ) than the rate during the rest of time on treatment . The crude mortality rate was 4.8 per 100 person years in weeks 1 - 2 after treatment stopped , 4.3 in weeks 3 - 4 , and 0.95 during the rest of time off treatment : 9 ( 5.4 to 14.9 ) , 8 ( 4.7 to 13.7 ) , and 1.9 ( 1.3 to 2.8 ) times higher than the baseline risk of mortality during treatment . Opiate substitution treatment has a greater than 85 % chance of reducing overall mortality among opiate users if the average duration approaches or exceeds 12 months . Conclusions Clinicians and patients should be aware of the increased mortality risk at the start of opiate substitution treatment and immediately after stopping treatment . Further research is needed to investigate the effect of average duration of opiate substitution treatment on drug related mortality OBJECTIVE : Maternal smoking has been associated with a reduction in  newborn birth weight .  We sought to estimate how the pattern of maternal smoking throughout pregnancy influences newborn size . METHODS : One hundred sixty pregnant smoking women were enrolled in a prospect i ve study . We collected data on maternal age , education , prepregnancy body mass index , and parity , as well as alcohol and illicit drug use . Cigarette use was defined as self-reported consumption before pregnancy , at the time of study enrollment , and in the third trimester . Statistical analyses were performed based on bivariate correlations and multiple linear regression . RESULTS : Of the smoking parameters examined , maternal third-trimester cigarette consumption was the strongest predictor of birth weight percentile ( partial r = –0.23 , P < .001 ) . For each additional cigarette per day that a participant smoked in the third trimester , there was an estimated 27 g reduction in birth weight . Prepregnancy smoking volume was not significantly associated with birth weight percentile in bivariate ( r = –0.06 , P = .47 ) or multivariable analyses . Additional factors contributing to birth weight include gestational age ( partial r = 0.69 , P < .001 ) , maternal body mass index ( partial r = 0.23 , P < .001 ) , and parity ( partial r = 0.16 , P < .004 ) . In total , these 4 variables explain 61 % of the variance in newborn birth weight . CONCLUSION : Maternal third-trimester cigarette consumption is a strong and independent predictor of birth weight percentile . This supports the hypothesis that reductions in maternal cigarette consumption during pregnancy will result in improved birth weight , regardless of the prepregnancy consumption levels . LEVEL OF EVIDENCE : ABSTRACT . This article presents a Norwegian prospect i ve , longitudinal study of children prenatally exposed to opiates and other substances under conditions of minimal postnatal social risk . Outcome at 4½ years of age is presented . The study reports on the prediction of later intellectual performance , on the basis of the children ’s prenatal , perinatal , and early developmental status , as well as the foster or adoptive parents ’ socioeconomic level . Significant differences were found between the substance-exposed group and the comparison group on the Bayley Scales at age 1 year and on the McCarthy Scales at age 4½ years . The findings showed that although the mean cognitive scores were within normal limits at age 4½ years , a special weakness in the area of visual-motor and perceptual abilities was detected among the substance-exposed children . It is indicated that these areas of performance are especially sensitive to the effect of prenatal adversity . A special vulnerability among the substance-exposed boys , detected at an earlier age , persisted at 4½ years . The study indicates that even if children experience adequate caregiving , the accumulation of biomedical risk factors associated with prenatal substance exposure is still a potential determinant of developmental problems , especially in the area of perceptual-performance functions . The study also hints at differential influences of biomedical and environmental variables on outcome at age 4½ years Groups of subjects whose primary drug of abuse was amphetamine or heroin were compared , together with age- and IQ-matched control subjects . The study consisted of a neuropsychological test battery which included both conventional tests and also computerised tests of recognition memory , spatial working memory , planning , sequence generation , visual discrimination learning , and attentional set-shifting . Many of these tests have previously been shown to be sensitive to cortical damage ( including selective lesions of the temporal or frontal lobes ) and to cognitive deficits in dementia , basal ganglia disease , and neuropsychiatric disorder . Qualitative differences , as well as some commonalities , were found in the profile of cognitive impairment between the two groups . The chronic amphetamine abusers were significantly impaired in performance on the extra-dimensional shift task ( a core component of the Wisconsin Card Sort Test ) whereas in contrast , the heroin abusers were impaired in learning the normally easier intra-dimensional shift component . Both groups were impaired in some of tests of spatial working memory . However , the amphetamine group , unlike the heroin group , were not deficient in an index of strategic performance on this test . The heroin group failed to show significant improvement between two blocks of a sequence generation task after training and additionally exhibited more perseverative behavior on this task . The two groups were profoundly , but equivalently impaired on a test of pattern recognition memory sensitive to temporal lobe dysfunction . These results indicate that chronic drug use may lead to distinct patterns of cognitive impairment that may be associated with dysfunction of different components of cortico-striatal circuitry AIMS Methadone use in pregnancy has been associated with adverse perinatal outcomes and neonatal abstinence syndrome ( NAS ) . This study aim ed to examine perinatal outcomes and NAS in relation to ( i ) concomitant drug use and ( ii ) methadone dose . DESIGN Prospect i ve cohort study . SETTING Two tertiary care maternity hospitals . PARTICIPANTS A total of 117 pregnant women on methadone maintenance treatment recruited between July 2009 and July 2010 . MEASUREMENTS Information on concomitant drug use was recorded with the Addiction Severity Index . Perinatal outcomes included pre-term birth ( < 37 weeks ' gestation ) , small-for-gestational-age ( < 10th centile ) and neonatal unit admission . NAS outcomes included : incidence of medically treated NAS , peak Finnegan score , cumulative dose of NAS treatment and duration of hospitalization . FINDINGS Of the 114 liveborn infants 11 ( 9.6 % ) were born pre-term , 49 ( 42.9 % ) were small-for-gestational-age , 56 ( 49.1 % ) had a neonatal unit admission and 29 ( 25.4 % ) were treated medically for NAS . Neonates exposed to methadone-only had a shorter hospitalization than those exposed to methadone and concomitant drugs ( median 5.0 days versus 6.0 days , P = 0.03 ) . Neonates exposed to methadone doses ≥80 mg required higher cumulative doses of morphine  treatment for NAS ( median 13.2 mg versus 19.3 mg , P = 0.03 ) . The incidence and duration of NAS did not differ between the two dosage groups . CONCLUSIONS The incidence and duration of the neonatal abstinence syndrome is not associated with maternal methadone dose , but maternal opiate , benzodiazepine or cocaine use is associated with longer neonatal hospitalization BACKGROUND Methadone , a full mu-opioid agonist , is the recommended treatment for opioid dependence during pregnancy . However , prenatal exposure to methadone is associated with a neonatal abstinence syndrome ( NAS ) characterized by central nervous system hyperirritability and autonomic nervous system dysfunction , which often requires medication and extended hospitalization . Buprenorphine , a partial mu-opioid agonist , is an alternative treatment for opioid dependence but has not been extensively studied in pregnancy . METHODS We conducted a double-blind , double-dummy , flexible-dosing , r and omized , controlled study in which buprenorphine and methadone were compared for use in the comprehensive care of 175 pregnant women with opioid dependency at eight international sites . Primary outcomes were the number of neonates requiring treatment for NAS , the peak NAS score , the total amount of morphine needed to treat NAS , the length of the hospital stay for neonates , and neonatal head circumference . RESULTS Treatment was discontinued by 16 of the 89 women in the methadone group ( 18 % ) and 28 of the 86 women in the buprenorphine group ( 33 % ) . A comparison of the 131 neonates whose mothers were followed to the end of pregnancy according to treatment group ( with 58 exposed to buprenorphine and 73 exposed to methadone ) showed that the former group required significantly less morphine ( mean dose , 1.1 mg vs. 10.4 mg ; P<0.0091 ) , had a significantly shorter hospital stay ( 10.0 days vs. 17.5 days , P<0.0091 ) , and had a significantly shorter duration of treatment for the neonatal abstinence syndrome ( 4.1 days vs. 9.9 days , P<0.003125 ) ( P values calculated in accordance with prespecified thresholds for significance ) . There were no significant differences between groups in other primary or secondary outcomes or in the rates of maternal or neonatal adverse events . CONCLUSIONS These results are consistent with the use of buprenorphine as an acceptable treatment for opioid dependence in pregnant women . ( Funded by the National Institute on Drug Abuse ; Clinical Trials.gov number , NCT00271219 . ) This study compared the neurological development of 4 month old infants exposed to buprenorphine or methadone during pregnancy to that of a control group of non-exposed infants . Participants were 30 buprenorphine-maintained women , 22 methadone-maintained women and 33 non opioid-dependent controls , and their infants . Women were enrolled during pregnancy as part of an open-label non-r and omised flexible-dosing longitudinal study . Groups were matched for maternal age , parity , gravida , and tobacco and alcohol use . Infant neurological development was assessed by measuring latency of pattern reversal visual evoked potentials ( VEP ) . One-way between groups analyses of variance ( ANOVA ) were conducted to test the statistical significance of differences between the mean latencies of the peak response to two different sized checkerboard patterns ( 48 ' and 69 ' of retinal arc ) . Infants prenatally exposed to methadone had significantly prolonged latencies , compared with infants in the control group and infants prenatally exposed to buprenorphine , in response to checks of 48 ' and 69 ' . VEP latencies of infants prenatally exposed to buprenorphine did not differ significantly from controls for either check size . After adjustment for covariates , prenatal exposure to methadone remained a significant predictor of VEP response to checks of 48 ' , but not 69 ' . Maternal self-reported used of marijuana during pregnancy made a significant unique contribution to the variance in P1 latencies for both check sizes . Data from this controlled , non-r and omised study suggest that buprenorphine may confer an advantage over methadone as a maintenance drug during pregnancy in terms of infant neural development at 4 months of age Abstract To study the developmental effects of prenatal exposure to opiates , a prospect i ve follow up study of 34 drug-exposed ( opiates and nicotine ) and 42 reference infants ( nicotine exposure only ) was conducted from January 1992 to September 1995 . At the time of delivery , 12 of 34 mothers used opiates without medical control . Twenty-two mothers participated in a methadone maintenance programme .  At 1 year , the average Griffiths Developmental Quotient ( DQ ) was lower in the drug-exposed group ( mean : 100.5 vs. references 107.9 ; P < 0.001 ) . This difference was mainly due to lower subscales “ locomotor ” ( mean 100.8 vs. 111.4 ; P < 0.05 ) and “ intellectual performance ” ( mean 100.8 vs. 108.5 ; P < 0.05 ) in the drug-exposed group . Severe developmental retardation mean DQ ( −2 SD ) was diagnosed in 2 drug-exposed infants . Mild developmental retardation ( mean DQ : 1 SD– > 2 SD ) was found in 7 drug-exposed and in 3 reference infants ( P < 0.05 ) . Neurological abnormalities were found more frequently in the drug-exposed group ( 11 vs. 3 infants ; P < 0.01 ) . Among the opiate-exposed infants , the subscales “ hearing and speech ” and “ intellectual performance ” were lower in the uncontrolled drug-using than in the methadone group . The 17 fostered infants showed no difference in developmental outcome compared with the 10 infants living with their biological parents ( mean DQ : 100.0 versus 101.3 ) . Conclusions At 1 year infants prenatally exposed to opiates are at risk for mild psychomotor developmental impairment BACKGROUND This prospect i ve study explores the ongoing impact of early and subsequent maternal depression on offspring behaviour in the early school years . METHODS Seventy five mothers recruited into a longitudinal study were assessed for symptoms of depression when their children were 4 , 12 and 15 months , 4 years and later when the children were 6 - 8 years of age . Mothers , fathers , and school teachers were asked to report on children 's internalising and externalising behaviour problems . RESULTS Exposure to maternal depression during the first postpartum year was related to mother reports of child internalising and externalising problems in the early school years . Although depression in the first year predicted later internalising problems , effects for externalising behaviour problems were mediated by concurrent depression . Relations between concurrent maternal depression and externalising problems were confirmed by teacher ratings . Interestingly , the severity of symptoms at four months was significantly correlated with behaviour problems seven years later . LIMITATIONS Attrition over successive study contacts and therefore limited statistical power is acknowledged . Findings may be a conservative estimate of associations between maternal depression and later child behaviour problems . Also , the high prevalence of depressive symptomatology in the population from which the sample was drawn may limit the generalisability of results . CONCLUSIONS Findings confirm the importance of early identification and treatment for mothers with postnatal depression , given the likelihood of ongoing depression and relations with later child behaviour problems . From a practical point , severity of early symptoms may be a reliable index of those mothers and children at greatest risk
target: 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 pre-school children compared to non-exposed infants and children .
  However , all domains suggested a trend to poor outcomes in infants/children of opioid using mothers .
  Conclusions Chronic intra-uterine opioid exposed infants and pre-school 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 .
background: 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 .