Postnatal nutritional treatment of neurocognitive deficits in fetal alcohol spectrum disorder.

Ethanol is the most important teratogen agent in humans. Prenatal alcohol exposure can lead to a wide range of adverse effects, which are broadly termed as fetal alcohol spectrum disorder (FASD). The most severe consequence of maternal alcohol abuse is the development of fetal alcohol syndrome, defined by growth retardation, facial malformations, and central nervous system impairment expressed as microcephaly and neurodevelopment abnormalities. These alterations generate a broad range of cognitive abnormalities such as learning disabilities and hyperactivity and behavioural problems. Socioeconomic status, ethnicity, differences in genetic susceptibility related to ethanol metabolism, alcohol consumption patterns, obstetric problems, and environmental influences like maternal nutrition, stress, and other co-administered drugs are all factors that may influence FASD manifestations. Recently, much attention has been paid to the role of nutrition as a protective factor against alcohol teratogenicity. There are a great number of papers related to nutritional treatment of nutritional deficits due to several factors associated with maternal consumption of alcohol and with eating and social disorders in FASD children. Although research showed the clinical benefits of nutritional interventions, most of work was in animal models, in a preclinical phase, or in the prenatal period. However, a minimum number of studies refer to postnatal nutrition treatment of neurodevelopmental deficits. Nutritional supplementation in children with FASD has a dual objective: to overcome nutritional deficiencies and to reverse or improve the cognitive deleterious effects of prenatal alcohol exposure. Further research is necessary to confirm positive results, to determine optimal amounts of nutrients needed in supplementation, and to investigate the collective effects of simultaneous multiple-nutrient supplementation.

Choline supplementation in children with fetal alcohol spectrum disorders: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Fetal alcohol spectrum disorders (FASDs) are conditions characterized by physical anomalies, neurodevelopmental abnormalities, and neurocognitive deficits, including intellectual, executive, and memory deficits. There are no specific biological treatments for FASDs, but rodent models have shown that prenatal or postnatal choline supplementation reduces cognitive and behavioral deficits. Potential mechanisms include phospholipid production for axonal growth and myelination, acetylcholine enhancement, and epigenetic effects. OBJECTIVE: Our primary goal was to determine whether postnatal choline supplementation has the potential to improve neurocognitive functioning, particularly hippocampal-dependent memory, in children with FASDs. DESIGN: The study was a double-blind, randomized, placebo-controlled pilot trial in children (aged 2.5-5 y at enrollment) with FASDs (n = 60) who received 500 mg choline or a placebo daily for 9 mo. Outcome measures were Mullen Scales of Early Learning (primary) and the elicited imitation (EI) memory paradigm (secondary). RESULTS: The administration proved feasible, and choline was well tolerated. Participants received a dose on 88% of enrolled days. The only adverse event linked to choline was a fishy body odor. Choline supplementation improved the secondary outcome (EI) only after immediate recall performance was controlled for, and the outcome was moderated by age. The treatment effect on EI items recalled was significant in the younger participants (2.5- to ≤4.0-y-olds); the young choline group showed an increase of 12-14 percentage points greater than that of the young placebo group on delayed recall measures during treatment. However, there was a marginal baseline difference in delayed item recall between the young choline and placebo groups as well as a potential ceiling effect for item recall, both of which likely contributed to the observed treatment effect. We also observed a trend toward a negative effect of choline supplementation on the immediate EI recall of ordered pairs; the young placebo group showed an increase of 8-17 percentage points greater than that of the choline group during treatment. There was an inverse relation between choline dose (in mg/kg) and memory improvement (P = 0.041); the data suggest that weight-adjusted doses may be a better alternative to a fixed dose in future studies. Limitations included trend-level baseline differences in performance, the post-hoc determination of age moderation, and potential ceiling effects for the memory measure. CONCLUSIONS: This pilot study suggests that an additional evaluation of choline supplementation as an intervention for memory functioning in children with FASDs is warranted. The observed interaction between age and choline's effect on EI suggests that potential sensitive periods should be considered in future work. This trial was registered at clinicaltrials.gov as NCT01149538.

[Fetal alcohol syndrome and fetal alcohol effects: importance of early diagnosis and nutritional treatment]. / Sindrome de alcoholismo fetal y efectos del alcohol sobre el feto: importancia del diagnóstico precoz y del manejo nutricional.

BACKGROUND: Fetal alcohol syndrome (FAS) and fetal alcohol effects (FAE) encompass a pattern of birth defects in persons whose mothers ingested alcohol during pregnancy. People with FAE display fewer of the FAS traits. AIM: To assess the prevalence and features of these affections in a secondary nutritional recovery centre. PATIENTS AND METHODS: All charts of children admitted between 1985 and 1995 were reviewed, and those children diagnosed as having a FAS or FAE by a geneticist were considered for this study. Birth, maternal, social and economic characteristics, psychomotor abilities (using Denver test) and response to nutritional treatment were assessed. RESULTS: During the study period, 1572 infants were admitted to the centre, and 1.97% (70% female) were diagnosed as having a FAS or FAE. These infants were admitted at 11.1 +/- 4.5 months of age and discharged after 96.7 +/- 58.1 months of hospitalisation. Mean mother's age was 33 +/- 7 years, and all belonged to low socioeconomic levels. Mean birth weight was 2048 +/- 431 g and 2469 +/- 619 g in children with FAS and FAE respectively (p < 0.03). Children with FAE performed better for gross and fine motor abilities than those with FAS. No differences were observed for language performance. Sixty five percent of children with FAS and 71% of children with FAE had an adequate weight and height increment during nutritional therapy. A multiple regression analysis showed that age at admission and gestational age were significant predictors of weight gain during therapy. CONCLUSIONS: Alcohol has teratogenic effects on the foetus that affect craneal size and psychomotor development. Alcohol also affects pre and post natal growth.

Sindrome de alcoholismo fetal y efectos del alcohol sobre el feto: importancia del diagnóstico precoz y del manejo nutricional / Fetal alcohol syndrome and fetal alcohol effects among children in a secondary nutritional recovery centre

Background: Fetal alcohol syndrome (FAS) and fetal alcohol effects (FAE) encompass a pattern of birth defects in persons whose mothers ingested alcohol during pregnancy. People with FAE display fewer of the FAS traits. Aim: To assess the prevalence and features of these affections in a secondary nutritional recovery centre. Patients and methods: All charts of children admitted between 1985 and 1995 were reviewed, and those children diagnosed as having a FAS or FAE by a geneticist were considered for this study. Birth, maternal, social and economic characteristics, psychomotor abilities (using Denver test) and response to nutritional treatment were assessed. Results: During the study period, 1572 infants were admitted to the centre, and 1.97 percent (70 percent female) were diagnosed as having a FAS or FAE. These infants were admitted at 11.1 ñ 4.5 months of age and discharged after 96.7 ñ 58.1 months of hospitalisation. Mean mother's age was 33 ñ 7 years, and all belonged to low socioeconomic levels. Mean birth weight was 2048 ñ 431 g and 2469 ñ 619 g in children with FAS and FAE respectively (p< 0.03). Children with FAE performed better for gross and fine motor abilities than those with FAS. No differences were observed for language performance. Sixty five percent of children with FAS and 71 percent of children with FAE had an adequate weight and height increment during nutritional therapy. A multiple regression analysis showed that age at admission and gestational age were significant predictors of weight gain during therapy. Conclusions: Alcohol has teratogenic effects on the foetus that affect craneal size and psychomotor development. Alcohol also affects pre and post natal growth