Dietary docosahexaenoic acid supplementation in children with autism.

OBJECTIVE: The aim of the study was to determine whether docosahexaenoic acid (DHA) supplementation improves the behavior of children with autism. METHODS: A group of 3- to 10-year-old children with autism were randomized in a double-blind fashion to receive a supplement containing 200 mg of DHA or a placebo for 6 months. The parents and the investigator completed the Clinical Global Impressions-Improvement scale to rate changes in core symptoms of autism after 3 and 6 months. The parents completed the Child Development Inventory and the Aberrant Behavior Checklist, and both parents and teachers completed the Behavior Assessment Scale for Children (BASC) at enrollment and after 6 months. RESULTS: A total of 48 children (40 [83%] boys, mean age [standard deviation] 6.1 [2.0] years) were enrolled; 24 received DHA and 24 placebo. Despite a median 431% increase in total plasma DHA levels after 6 months, the DHA group was not rated as improved in core symptoms of autism compared to the placebo group on the CGI-I. Based on the analysis of covariance models adjusted for the baseline rating scores, parents (but not teachers) provided a higher average rating of social skills on the BASC for the children in the placebo group compared to the DHA group (P = 0.04), and teachers (but not parents) provided a higher average rating of functional communication on the BASC for the children in the DHA group compared to the placebo group (P = 0.02). CONCLUSIONS: Dietary DHA supplementation of 200 mg/day for 6 months does not improve the core symptoms of autism. Our results may have been limited by inadequate sample size.

Effects of early maternal docosahexaenoic acid intake on neuropsychological status and visual acuity at five years of age of breast-fed term infants.

OBJECTIVE: We previously reported better psychomotor development at 30 months of age in infants whose mothers received a docosahexaenoic acid (DHA) (22:6n-3) supplement for the first 4 months of lactation. We now assess neuropsychological and visual function of the same children at 5 years of age. STUDY DESIGN: Breastfeeding women were assigned to receive identical capsules containing either a high-DHA algal oil (∼200 mg/d of DHA) or a vegetable oil (containing no DHA) from delivery until 4 months postpartum. Primary outcome variables at 5 years of age were measures of gross and fine motor function, perceptual/visual-motor function, attention, executive function, verbal skills, and visual function of the recipient children at 5 years of age. RESULTS: There were no differences in visual function as assessed by the Bailey-Lovie acuity chart, transient visual evoked potential or sweep visual evoked potential testing between children whose mothers received DHA versus placebo. Children whose mothers received DHA versus placebo performed significantly better on the Sustained Attention Subscale of the Leiter International Performance Scale (46.5 ± 8.9 vs 41.9 ± 9.3, P < .008) but there were no statistically significant differences between groups on other neuropsychological domains. CONCLUSIONS: Five-year-old children whose mothers received modest DHA supplementation versus placebo for the first 4 months of breastfeeding performed better on a test of sustained attention. This, along with the previously reported better performance of the children of DHA-supplemented mothers on a test of psychomotor development at 30 months of age, suggests that DHA intake during early infancy confers long-term benefits on specific aspects of neurodevelopment.

Pulmonary vein stenosis with collateralization via esophageal varices: Long-term follow-up after successful treatment with drug-eluting stent.

OBJECTIVE: We describe the long-term follow-up of a child with recurrent hemoptysis due to severe pulmonary vein stenosis decompressing via collaterals to esophageal varices. DESIGN: Case report SETTING: Tertiary children's hospital PATIENT: Single child through ages 2- to 11-year old INTERVENTIONS: The child underwent cutting balloon angioplasty, bare metal stenting, and implantation of a PTFE-covered stent, all of which failed rapidly. Only after placement of a paclitaxel drug eluting stent did he have prolonged relief from hemoptysis and long-term patency of the treated vein. The stents were serially dilated to keep up with somatic growth of the child, eventually culminating in the need to induce intentional stent fracture. CONCLUSIONS: We highlight novel transcatheter techniques to treat this vexing condition, discuss mechanisms of disease treatment and progression, and present the only patient with this rare combination of lesions to have achieved both longstanding pulmonary vein patency and resolution of esophageal varices.

Comparison of the validity of direct pediatric developmental evaluation versus developmental screening by parent report.

To compare the validity of direct pediatric developmental evaluation with developmental screening by parent report, parents completed a developmental screen (the Child Development Review), a pediatrician performed a direct developmental evaluation (Capute Scales), and a psychologist administered the Bayley Scales of Infant Development to a group of 30-month-old children. The agreement between these instruments was tested. All developmental quotient scores derived from the Capute Scales were more highly correlated with concurrent Bayley Mental Development Index scores than developmental quotient scores derived from the Child Development Review. Differences between developmental quotient scores derived from the Capute Scales and corresponding Bayley Mental Development Index scores were significantly smaller than those derived from the Child Development Review. Thus, direct pediatric developmental evaluation more reliably predicted concurrent Mental Development Index scores at 30 months of age than developmental screening by parent report. Increased emphasis on training of pediatric health care providers in direct developmental evaluation should be considered.

Effects of n-3 fatty acids during pregnancy and lactation.

n-3 Fatty acids exert important effects on eicosanoid metabolism, membrane properties, and gene expression and therefore are biologically important nutrients. One n-3 fatty acid, docosahexaenoic acid, is an important component of neural and retinal membranes and accumulates rapidly in the brain and retina during the later part of gestation and early postnatal life. It is reasonable to hypothesize that maternal n-3 fatty acid intakes might have significant effects on several pregnancy outcomes as well as on subsequent infant visual function and neurodevelopmental status. Studies, both observational and interventional, assessing the influence of n-3 fatty acids during pregnancy or the early postpartum period on duration of gestation and infant size at birth, preeclampsia, depression, and infant visual function and neurodevelopment have been reported. n-3 Fatty acid intakes (both in terms of absolute amounts of docosahexaenoic acid and eicosapentaenoic acid and the ratio of these 2 fatty acids) varied widely in these studies, however, and no clear consensus exists regarding the effects of n-3 fatty acids on any of these outcomes. The available data suggest a modest effect of these fatty acids on increasing gestational duration and possibly enhancing infant neurodevelopment. Although data from earlier observational studies suggested a potential role of these fatty acids in decreasing the incidence of preeclampsia, this has not been confirmed in randomized, prospective trials. Because of the paucity of data from randomized, prospective, double-blind trials, the effect of n-3 fatty acids on depression during pregnancy or the early postpartum period remains unresolved.

Effects of maternal docosahexaenoic acid intake on visual function and neurodevelopment in breastfed term infants.

BACKGROUND: Normal brain and visual development is thought to require exogenous docosahexaenoic acid (DHA; 22:6n-3) intake, but the amount needed is debatable. Because the supplementation of breastfeeding mothers with DHA increases the DHA content of their infants' plasma lipids, we hypothesized that it might also improve brain or visual function in the infants. OBJECTIVE: The objective was to determine the effect of DHA supplementation of breastfeeding mothers on neurodevelopmental status and visual function in the recipient infant. DESIGN: Breastfeeding women received capsules containing either a high-DHA algal oil ( approximately 200 mg DHA/d) or a vegetable oil (no DHA) for 4 mo after delivery. Outcome variables included the fatty acid pattern of maternal plasma phospholipid and milk lipids 4 mo postpartum, the fatty acid pattern of plasma phospholipids and visual function in infants at 4 and 8 mo of age, and neurodevelopmental indexes of the infants at 12 and 30 mo of age. RESULTS: Milk lipid and infant plasma phospholipid DHA contents of the supplemented and control groups were approximately 75% and approximately 35% higher, respectively, at 4 mo postpartum. However, neither the neurodevelopmental indexes of the infants at 12 mo of age nor the visual function at 4 or 8 mo of age differed significantly between groups. In contrast, the Bayley Psychomotor Development Index, but not the Mental Development Index, of the supplemented group was higher (P < 0.01) at 30 mo of age. CONCLUSION: DHA supplementation of breastfeeding mothers results in higher infant plasma phospholipid DHA contents during supplementation and a higher Bayley Psychomotor Development Index at 30 mo of age but results in no other advantages either at or before this age.

Lipids with an emphasis on long-chain polyunsaturated fatty acids.

In addition to their role as a source of energy, several fatty acids are important components of cell membranes and/or precursors of biologically important eicosanoids. The long-chain polyunsaturated fatty acids, docosahexaenoic acid (DHA) and arachidonic acid (AA), are important for optimal visual function and neurodevelopment. These fatty acids are present in human milk but, until recently, have not been included in formulas marketed in the United States. Although the results of clinical trials assessing the effect of DHA and AA intakes on visual and cognitive development have been inconsistent, some studies suggest benefits. Adequate intake of these fatty acids may be especially important for the preterm infant.

Concurrent and predictive validity of the cognitive adaptive test/clinical linguistic and auditory milestone scale (CAT/CLAMS) and the Mental Developmental Index of the Bayley Scales of Infant Development.

The Cognitive Adaptive Test/Clinical Linguistic and Auditory Milestone Scale (CAT/CLAMS) was designed for use by primary pediatric health care providers to identify children with developmental delays. This study assesses the concurrent and predictive validity of CAT/CLAMS developmental quotient (DQ) scores and the Mental Developmental Index (MDI) of the Bayley Scales of Infant Development in healthy children without risk factors for developmental delay. Overall CAT/CLAMS DQ scores correlated significantly with Bayley MDI scores at both 12 (r = 0.393; p = 0.008) and 30 months (r = 0.742; p = 0.0001) of age. Overall CAT/CLAMS DQ scores at 12 months of age also correlated modestly with Bayley MDI scores at 30 months of age (r = 0.181; p = 0.036). Despite its modest predictive validity at 12 months, its satisfactory concurrent validity plus its ease and speed of administration make the CAT/CLAMS a reasonable choice for assessment of early development by primary pediatric health care providers.

Docosahexaenoic acid and lactation.

Docosahexaenoic acid (DHA) is an important component of membrane phospholipids in the retina and brain and accumulates rapidly in these tissues during early infancy. DHA is present in human milk, but the amount varies considerably and is largely dependent on maternal diet. This article reviews data addressing the impact of different DHA intakes by lactating women on infant and maternal outcomes to determine if available data are sufficient to estimate optimal breast milk DHA content and estimate dietary reference intakes (DRIs) for DHA by breast-feeding mothers. Results of published observational studies and interventional trials assessing the impact of maternal DHA intake (or breast milk DHA content) on infant visual function, neurodevelopment, and immunologic status were reviewed. Studies related to the potential impact of DHA intake on depression or cognitive function of lactating women also were reviewed. Although only a limited number of studies are available in the current medical literature, and study results have not been consistent, better infant neurodevelopment and/or visual function have been reported with higher vs. lower levels of breast milk DHA. The effect of DHA intake on the incidence or severity of depression in lactating women is not clear. Increasing breast milk DHA content above that typically found in the US, by increasing maternal DHA intake, may confer neurodevelopmental benefits to the recipient breast-fed infant. However, current data are insufficient to permit determination of specific DRIs during this period.

Reevaluation of the DHA requirement for the premature infant.

The long-chain polyunsaturated fatty acid (LC-PUFA) intake in preterm infants is crucial for normal central nervous system development and has the potential for long-lasting effects that extend beyond the period of dietary insufficiency. While much attention has focused on improving their nutritional intake, many premature infants do not receive an adequate DHA supply. We demonstrate that enterally fed premature infants exhibit daily DHA deficit of 20mg/kg.d, representing 44% of the DHA that should have been accumulated. Furthermore, the DHA content of human milk and current preterm formulas cannot compensate for an early DHA deficit which may occur during the first month of life. We recommend breast-feeding, which supplies preformed LC-PUFA, as the preferred method of feeding for preterm infants. However, to fulfill the specific DHA requirement of these infants, we recommend increasing the DHA content of human milk either by providing the mothers with a DHA supplement or by adding DHA directly to the milk. Increasing the DHA content above 1% total fatty acids appears to be safe and may enhance neurological development particularly that of infants with a birth weight below 1250 g. We estimate that human milk and preterm formula should contain approximately 1.5% of fatty acid as DHA to prevent the appearance of a DHA deficit and to compensate for the early DHA deficit.

The Test of Variables of Attention (TOVA): internal consistency (Q1 vs. Q2 and Q3 vs. Q4) in children with attention deficit/hyperactivity disorder (ADHD).

The internal consistency of the Test of Variables of Attention (TOVA) was examined in a cohort of 6- to 12-year-old children (N = 63) strictly diagnosed with ADHD. The internal consistency of errors of omission (OMM), errors of commission (COM), response time (RT), and response time variability (RTV) of different test conditions (stimulus infrequent condition [Q1 vs. Q2] and stimulus frequent condition [Q3 vs. Q4]) was assessed via correlation analyses. All TOVA index scores under investigation assessing its internal consistency exhibited statistically significant correlations. All correlations fell in the moderate-high range.

Roles of long-chain polyunsaturated fatty acids in the term infant: developmental benefits.

Docosahexaenoic acid (DHA) and arachidonic acid (ARA) are two long-chain polyunsaturated fatty acids (LCPUFAs) found naturally in human milk. DHA and ARA have been receiving increased attention from health care professionals and the public. Research suggests that DHA intake and status have a significant impact on visual and cognitive development in breastfed infants. For formula-fed infants, studies have shown mixed results from DHA or DHA plus ARA supplementation. There are several important differences among LCPUFA studies with term infants that may contribute to the differing results, including levels of LCPUFA added to the formula, variations in test methods, ages of infants evaluated, and sources of LCPUFA. Nevertheless, several expert groups recommend that infant formulas be supplemented with DHA and ARA. Recommendations for term infants for DHA and ARA range from 0.2 percent to 0.4 percent and from 0.35 percent to 0.7 percent of the fatty acids, respectively.

Performance on a visual sustained attention and discrimination task is associated with urinary excretion of norepineprhine metabolite in children with attention-deficit/hyperactivity disorder (AD/HD).

The degree of association between performance on a sustained attention task requiring visual discrimination and urinary excretion of catecholamine metabolites was examined in a cohort of 6- to 12-year-old children (n = 31) strictly selected and diagnosed with attention-deficit/hyperactivity disorder (AD/HD) according to DSM-IV and other strict criteria. Sustained visual attention and discrimination were measured using the Test of Variables of Attention (T.O.V.A.). Urinary excretion of dopamine (DA) and norepinephrine (NE) metabolites was measured by reversed high-pressure liquid chromatography (HPLC). Pearson product-moment correlations were used to investigate the relationship between T.O.V.A. errors of omission (OMM), errors of commission (COM), response time (RT), and response time variability (RTV) and catecholamine metabolites of DA and NE. All T.O.V.A. indexes under investigation were significantly correlated with urinary excretion of NE metabolites, but correlations were low-to-moderate in magnitude (.37-.50). In contrast, there were no statistically significant correlations between T.O.V.A. indices and DA metabolites. These findings and their concordance with past research in human adults and animals, as well as theoretical issues associated with the present results, are discussed.

Effect of maternal docosahexaenoic acid supplementation on postpartum depression and information processing.

OBJECTIVE: The purpose of this study was to determine the effect of docosahexaenoic acid supplementation on plasma phospholipid docosahexaenoic acid content and indices of depression and information processing for women who breast-feed. STUDY DESIGN: Mothers who planned to breast-feed their infants were assigned randomly in a double-masked fashion to receive either docosahexaenoic acid (approximately 200 mg/d) or placebo for the first 4 months after the delivery. Major outcome variables included plasma phospholipid fatty acid patterns and scores on a self-rating questionnaire of current depression symptoms. A structured clinical interview of depression, scores on another self-rating questionnaire of depression symptoms, and a laboratory measure of information processing were obtained in subgroups of the total population. RESULTS: Plasma phospholipid contents of docosahexaenoic acid at baseline were 3.15 +/- 0.78 and 3.31 +/- 0.70 (mg/dL of total fatty acids) in the docosahexaenoic acid and placebo groups, respectively. After 4 months, the plasma phospholipid docosahexaenoic acid content of the docosahexaenoic acid group was 8% higher (3.40 +/- 0.97 mg/dL), whereas that of the placebo group was 31% lower (2.27 +/- 0.87 mg/dL). Despite the higher plasma phospholipid docosahexaenoic acid content of the supplemented group after 4 months, there was no difference between groups in either self-rating or diagnostic measures of depression; information processing scores of the two groups also did not differ. CONCLUSION: Docosahexaenoic acid supplementation ( approximately 200 mg/d) for 4 months after the delivery prevented the usual decline in plasma phospholipid docosahexaenoic acid content of women who breastfeed but did not influence self-ratings of depression, diagnostic measures of depression, or information processing.