Prenatal Exposure to Organohalogens, Including Brominated Flame Retardants, Influences Motor, Cognitive, and Behavioral Performance at School Age

BACKGROUND: Organohalogen compounds (OHCs) are known to have neurotoxic effects on the developing brain. OBJECTIVE: We investigated the influence of prenatal exposure to OHCs, including brominated flame retardants, on motor, cognitive, and behavioral outcome in healthy children of school age. METHODS: This study was part of the prospective Groningen infant COMPARE (Comparison of Exposure-Effect Pathways to Improve the Assessment of Human Health Risks of Complex Environmental Mixtures of Organohalogens) study. It included 62 children in whose mothers the following compounds had been determined in the 35th week of pregnancy: 2,2'-bis-(4 chlorophenyl)1,1'-dichloroethene, pentachlorophenol (PCP), polychlorinated biphenyl congener 153 (PCB-153), 4-hydroxy-2,3,3',4',5-pentachlorobiphenyl (4OH-CB-107),4OH-CB-146,4OH-CB-187,2,2',4,4'-tetrabromodipheryl ether (BDE-47), BDE-99, BDE-100, BDE-153, BDE-154, and hexabromocy-clododecane. Thyroid hormones were determined in umbilical cord blood. When the children were 5-6 years of age, we assessed their neuropsychological functioning: motor performance (coordination, fine motor skills), cognition (intelligence, visual perception, visuomotor integration, inhibitory control, verbal memory, and attention), and behavior. RESULTS: Brominated flame retardants correlated with worse fine manipulative abilities, worse attention, better coordination, better visual perception, and better behavior. Chlorinated OHCs correlated with less choreiform, dyskinesia. Hydroxylated polychlorinated biphenyls correlated with worse fine manipulative abilities, better attention, and better visual perception. The wood protective agent (PCP) correlated with worse coordination, less sensory integrity, worse attention, and worse visuomotor integration. CONCLUSIONS: Our results demonstrate for the first time that transplacental transfer of polybrominated flame retardants is associated with the development of children at school age. Because of the widespread use of these compounds, especially in the United States, where concentrations in the environment are four times higher than in Europe, these results cause serious concern

Artesunate-mefloquine combination therapy in acute Plasmodium falciparum malaria in young children: a field study regarding neurological and neuropsychiatric safety

BACKGROUND: Mefloquine-artesunate combination therapy for uncomplicated falciparum malaria is one of the treatments used in African children. Data concerning neurological safety in adults and children treated with mefloquine and artesunate combination therapy is well documented in Asia. Safety data for neurological and neuropsychiatric side effects of mefloquine and artesunate combination therapy in African children are scarce, although WHO recommends this therapy in Africa. METHODS: A phase IV, open label, single arm study was conducted among African children between 10 and 20 kg with acute uncomplicated falciparum malaria. They were treated over three consecutive days with a paediatric fixed-dose combination of artesunate (50 mg/d) and mefloquine (125 mg/d). Parasitological, clinical and neurological examinations and standardized questions about neuropsychiatric symptoms were carried out on days 0, 4, 7, 28 and 63. The primary objective was to assess the neurological and neuropsychiatric safety of artesunate-mefloquine combination therapy in young children. RESULTS: From December 2007 to March 2009, 220 children with uncomplicated Plasmodium falciparum malaria were treated with artesunate and mefloquine. 213 children were analysed according to study protocol. 50 neurological and neuropsychiatric adverse events occurred in 28 patients. Eleven drug-related neurological and neuropsychiatric adverse events occurred in eight patients. Sleeping disorders were present in 2.3%, neurological disorders in 1.4%, neuropsychiatric disorders in 1% and eating disorders in 0.5% of the patients. Adverse events were of mild to moderate intensity and resolved spontaneously. CONCLUSION: African children showed a low percentage of self-limited neurological and neuropsychiatric adverse events, confirming studies on neurological safety in Asian children treated with artesunate and mefloquine. Sleeping disorders were most frequently observed

Long-term outcome in relationship to neonatal transfusion volume in extremely premature infants: a comparative cohort study

<p>Abstract</p> <p>Background</p> <p>In premature born infants red blood cell (RBC) transfusions have been associated with both beneficial and detrimental sequels. Upon RBC transfusion, improvement in cerebral blood flow and oxygenation have been observed, while a more liberal transfusion policy may be associated with a better developmental outcome. The effect of the transfusion volume on long-term outcome is not known.</p> <p>Methods</p> <p>Observational follow-up study of a cohort of extremely premature born infants, treated in 2 neonatal intensive care units using a different transfusion volume (15 ml/kg in Unit A and 20 ml/kg in Unit B). The primary outcome was a composite of post discharge mortality, neuromotor developmental delay, blindness or deafness, evaluated at a mean corrected age (CA) of 24 months related to the transfusion volume/kg bodyweight administered during the postnatal hospital stay.</p> <p>Results</p> <p>Despite the difference in transfusion volume in clinically comparable groups of infants, they received a similar number of transfusions (5.5 ± 3.2 versus 5.5 ± 2.3 respectively in Unit A and B). The total transfused volume in unit A was 79 ± 47 ml/kg and 108 ± 47 ml/kg in unit B (p = 0.02). Total transfused RBC volume per kg bodyweight was not an independent predictor of the composite outcome (p = 0.96, OR 1.0 (CI 0.9-1.1).</p> <p>Conclusion</p> <p>There was no relationship between the composite outcome at 24 months CA and transfusion volume received during the post natal hospital stay. As there was no clinical advantage of the higher transfusion volume, a more restrictive volume will reduce total transfusion volume and donor exposure. Future research on the optimal transfusion volume per event to extreme preterm infants should include larger, prospective studies with a longer follow-up period through to childhood or even adolescence.</p

LEARN 2 MOVE 0-2 years:effects of a new intervention program in infants at very high risk for cerebral palsy; a randomized controlled trial

Background: It is widely accepted that infants at risk for cerebral palsy need paediatric physiotherapy. However, there is little evidence for the efficacy of physiotherapeutic intervention. Recently, a new intervention program, COPCA (Coping with and Caring for infants with special needs - a family centered program), was developed. COPCA has educational and motor goals. A previous study indicated that the COPCA-approach is associated with better developmental outcomes for infants at high risk for developmental disorders. LEARN 2 MOVE 0-2 years evaluates the efficacy and the working mechanisms of the COPCA program in infants at very high risk for cerebral palsy in comparison to the efficacy of traditional infant physiotherapy in a randomized controlled trial. The objective is to evaluate the effects of both intervention programs on motor, cognitive and daily functioning of the child and the family and to get insight in the working elements of early intervention methods.Methods/design: Infants are included at the corrected age of 1 to 9 months and randomized into a group receiving COPCA and a group receiving traditional infant physiotherapy. Both interventions are given once a week during one year. Measurements are performed at baseline, during and after the intervention period and at the corrected age of 21 months. Primary outcome of the study is the Infant Motor Profile, a qualitative evaluation instrument of motor behaviour in infancy. Secondary measurements focus on activities and participation, body functions and structures, family functioning, quality of life and working mechanisms. To cope with the heterogeneity in physiotherapy, physiotherapeutic sessions are video-recorded three times (baseline, after 6 months and at the end of the intervention period). Physiotherapeutic actions will be quantified and related to outcome.Discussion: LEARN 2 MOVE 0-2 years evaluates and explores the effects of COPCA and TIP. Whatever the outcome of the project, it will improve our understanding of early intervention in children with cerebral palsy. Such knowledge is a prerequisite for tailor-made guidance of children with CP and their families.Trial registration: The trial is registered under NTR1428.</p