Neurobehavioral consequences of chronic intrauterine opioid exposure in infants and preschool children: a systematic review and meta-analysis

<b>Background</b><p></p> 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.<p></p> <b>Methods</b><p></p> 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.<p></p> <b>Results</b><p></p> 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 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. The magnitude of all possible effects was small according to Cohen’s benchmark criteria.<p></p> <b>Conclusions</b><p></p> 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. 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

Relationship Between Anti-DFS70 Autoantibodies and Oxidative Stress

Background: The anti-DFS70 autoantibodies are one of the most commonly and widely described agent of unknown clinical significance, frequently detected in healthy individuals. It is not known whether the DFS70 autoantibodies are protective or pathogenic. One of the factors suspected of inducing the formation of anti-DFS70 antibodies is increased oxidative stress. We evaluated the coexistence of anti-DFS70 antibodies with selected markers of oxidative stress and investigated whether these antibodies could be considered as indirect markers of oxidative stress. Methods: The intensity of oxidative stress was measured in all samples via indices of free-radical damage to lipids and proteins such as total oxidant status (TOS), concentrations of lipid hydroperoxides (LPH), lipofuscin (LPS), and malondialdehyde (MDA). The parameters of the non-enzymatic antioxidant system, such as total antioxidant status (TAS) and uric acid concentration (UA), were also measured, as well as the activity of superoxide dismutase (SOD). Based on TOS and TAS values, the oxidative stress index (OSI) was calculated. All samples were also tested with indirect immunofluorescence assay (IFA) and 357 samples were selected for direct monospecific anti DFS70 enzyme-linked immunosorbent assay (ELISA) testing. Results: The anti-DFS70 antibodies were confirmed by ELISA test in 21.29% of samples. Compared with anti-DFS70 negative samples we observed 23% lower concentration of LPH (P =.038) and 11% lower concentration of UA (P =.005). TOS was 20% lower (P =.014). The activity of SOD was up to 5% higher (P =.037). The Pearson correlation showed weak negative correlation for LPH, UA, and TOS and a weak positive correlation for SOD activity. Conclusion: In samples positive for the anti-DFS70 antibody a decreased level of oxidative stress was observed, especially in the case of samples with a high antibody titer. Anti-DFS70 antibodies can be considered as an indirect marker of reduced oxidative stress or a marker indicating the recent intensification of antioxidant processes

Perturbations of peripheral B lymphocyte homoeostasis in children with systemic lupus erythematosus

Objective: To investigate the distribution of peripheral B cell subpopulations of children with active and inactive systemic lupus erythematosus (SLE) compared with healthy controls. Methods: Peripheral B cell subpopulations of 11 children with SLE (6 with active and 5 with inactive disease) and 14 age matched normal healthy children were analysed. Active disease was diagnosed in children with a flare of SLE, who received treatment by IV cyclophosphamide or IV methylprednisolone pulse to control the disease. Additionally, the peripheral B cells of the children with SLE were compared with those of 13 consecutive patients with adult onset SLE. Results: No major difference was found in the frequency and total number of CD27(-)/CD19(+) naïve B cells and CD27(+)/CD19(+) memory B cells between patients with active and inactive lupus and healthy controls, but there was a significant increase in CD27(high) expressing plasma blasts in patients with active SLE. These cells coexpress CD38(+), HLA-DR(dim), surface Ig(low) and lack the expression of CD20 but are clearly positive for intracellular Ig, indicative of early plasma cells. Most CD138(+) cells coexpress CD27(high)/CD19(+). The enhanced frequency of peripheral plasma blasts in children with active SLE is consistent with previous findings in adult patients with SLE, whereas a relative predominance of CD27(+) memory B cells was only identified in the adult patients. Conclusions: Profound abnormalities in the distribution of B cell compartments are more pronounced in older patients with SLE, but an enhanced frequency and cell number of peripheral plasma blasts is characteristic of both diseases during active stages. Thus detection of CD27(high) plasma blasts significantly correlates with active lupus in both children and adults

Developmental outcome in children with intrauterine exposure to substances

The developmental outcome of children born to Swiss substance-dependent mothers in a residential treatment program was studied in a sample of 61 children ranging from infancy to preadolescence (mean age = 5.10, SD = 3.10 years) by use of age-appropriate tests of intelligence. A large list of biological and psychosocial risk factors was tested for associations with outcome in the children. The mean profile of test findings across all age ranges was significantly lower than population norms and there was an excess of children with subnormal intellectual functioning. Performance IQ was associated negatively only with intrauterine substance exposure, but with none of the other risk factors. Among the various substances, predominantly heroin or methadone were responsible for this association when controls for nicotine or cannabis consumption were made. The study provides further evidence that intrauterine exposure to heroin and methadone negatively affects the developmental outcome in the offspring of substance-dependent mothers

Oral application of bacterial lysate in infancy decreases the risk of atopic dermatitis in children with 1 atopic parent in a randomized, placebo-controlled trial

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