Martha Neuringer

Visual acuity, erythrocyte fatty acid composition, and growth in term infants fed formulas with long chain polyunsaturated fatty acids for one year

The CNS and the retina are enriched in long chain polyunsaturated (LCP) fatty acids, specifically docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (AA, 20:4n-6), which are present in human milk but not in most infant formulas. In the present study of 134 formula-fed and 63 breast-fed infants, we prospectively evaluated whether providing a source of DHA and AA or DHA alone in formula would increase red blood cell (RBC) phospholipid levels of these fatty acids, enhance visual function, or affect growth during the first year. Healthy term infants <7 d old were randomized to be fed formulas containing linoleic acid (≈10% kcal) andα-linolenic acid (≈1% kcal) plus (1) no added LCP fatty acids (control formula), (2) DHA (0.12 wt% fatty acids) and AA (0.43 wt%) from egg yolk phospholipid (AA + DHA formula), or (3) DHA (0.2 wt%) from fish oil (DHA formula). A breast-fed group was studied concurrently and permitted formula supplementation after 3 mo. Visual acuity was measured using both the acuity card procedure and a visual evoked potential method at 2, 4, 6, 9, and 12 mo. Infants fed the control formula had 10-40% lower RBC levels of DHA and AA than infants in the breast-fed group. Infants fed the AA+ DHA formula had levels of both LCP within ≈10% of the values for infants in the breast-fed group, and infants fed the DHA formula had 25-55% higher DHA levels and 15-40% lower AA levels. There were no differences in growth or in visual function during this 12-mo feeding study.

Unique checkpoints during the first cell cycle of fertilization after intracytoplasmic sperm injection in rhesus monkeys.

Intracytoplasmic sperm injection has begun an era of considerable improvements in treating male infertility. Despite its success, questions remain about the dangers of transmitting traits responsible for male infertility, sex and autosomal chromosome aberrations and possible mental, physical and reproductive abnormalities. We report here the first births of rhesus monkeys produced by intracytoplasmic sperm injection at rates greater or equal to those reported by clinics. Essential assumptions about this process are flawed, as shown by results with the preclinical, nonhuman primate model and with clinically discarded specimens. Dynamic imaging demonstrated the variable position of the second meiotic spindle in relation to the first polar body; consequently, microinjection targeting is imprecise and potentially lethal. Intracytoplasmic sperm injection resulted in abnormal sperm decondensation, with the unusual retention of vesicle-associated membrane protein and the perinuclear theca, and the exclusion of the nuclear mitotic apparatus from the decondensing sperm nuclear apex. Male pronuclear remodeling in the injected oocytes was required before replication of either parental genome, indicating a unique G1-to-S transition checkpoint during zygotic interphase (the first cell cycle). These irregularities indicate that the intracytoplasmic sperm injection itself might lead to the observed increased chromosome anomalies.

Polyunsaturated fatty acid status and neurodevelopment: A summary and critical analysis of the literature

The rationale for randomized trials designed to measure the effects of variable docosahexaenoic acid (DHA) status on neurodevelopment in human infants came from earlier studies of neurodevelopment in animals that were deficient in DHA owing to diets low in α-linolenic acid. The session on neurodevelopment looked at the results of these animal studies and discussed outcomes that appear to be analogous in human infants with variable DHA status. Presentations focused mainly on measures of development that may be attributed to more specific developmental domains (e.g., visual attention, recognition memory, problem-solving), some of which have been shown to be affected by long-chain polyunsaturated fatty acid (LCPUFA) status. This paper derives from discussions that took place during the session and reviews subsequent developments in this area. Although more difficult to interpret, global measures of infant development (e.g., the Bayley Scales of Infant Development, and Brunet-Lezine) can only suggest a relationship to specific developmental domains, but they have been applied in some randomized trials of LCPUFA and infant development. Those results are also summarized here.

Growth and Development of Premature Infants Fed Predominantly Human Milk, Predominantly Premature Infant Formula, or a Combination of Human Milk and Premature Formula

Background In a recent meta-analysis, human milk feeding of low birth-weight (LBW) infants was associated with a 5.2 point improvement in IQ tests. However, in the studies in this meta-analysis, feeding regimens were used (unfortified human milk, term formula) that no longer represent recommended practice. Objective To compare the growth, in-hospital feeding tolerance, morbidity, and development (cognitive, motor, visual, and language) of LBW infants fed different amounts of human milk until term chronologic age (CA) with those of LBW infants fed nutrient-enriched formulas from first enteral feeding. Methods The data in this study were collected in a previous randomized controlled trial assessing the benefit of supplementing nutrient-enriched formulas for LBW infants with arachidonic acid and docosahexaenoic acid. Infants (n = 463, birth weight, 750–1,800 g) were enrolled from nurseries located in Chile, the United Kingdom, and the United States. If human milk was fed before hospital discharge, it was fortified (3,050–3,300 kJ/L, 22–24 kcal/oz). As infants were weaned from human milk, they were fed nutrient-enriched formula with or without arachidonic and docosahexaenoic acids (3,300 kJ/L before term, 3,050 kJ/L thereafter) until 12 months CA. Formula fed infants were given nutrient-enriched formula with or without added arachidonic and docosahexaenoic acids (3,300 kJ/L to term, 3,050 kJ/L thereafter) until 12 months CA. For the purposes of this evaluation, infants were categorized into four mutually exclusive feeding groups: 1) predominantly human milk fed until term CA (PHM-T, n = 43); 2) ≥ 50% energy from human milk before hospital discharge (≥ 50% HM, n = 98); 3) < 50% of energy from human milk before hospital discharge (< 50% HM, n = 203); or 4) predominantly formula fed until term CA (PFF-T, n = 119). Results PFF-T infants weighed approximately 500 g more at term CA than did PHM-T infants. This absolute difference persisted until 6 months CA. PFF-T infants were also longer (1.0–1.5 cm) and had larger head circumferences (0.3–1.1 cm) than both PHM-T and ≥ 50% HM infants at term CA. There was a positive association between duration of human milk feeding and the Bayley Mental Index at 12 months CA (P = 0.032 full and P = 0.073 reduced, statistical models) after controlling for the confounding variables of home environment and maternal intelligence. Infants with chronic lung disease fed ≥ 50% HM until term CA (n = 22) had a mean Bayley Motor Index about 11 points higher at 12 months CA compared with infants PFF-T (n = 24, P = 0.033 full model). Conclusion Our data suggest that, despite a slower early growth rate, human milk fed LBW infants have development at least comparable to that of infants fed nutrient-enriched formula. Exploratory analysis suggests that some subgroups of human milk fed LBW infants may have enhanced development, although this needs to be confirmed in future studies.

Animal models of age related macular degeneration

Age related macular degeneration (AMD) is the leading cause of vision loss of those over the age of 65 in the industrialized world. The prevalence and need to develop effective treatments for AMD has lead to the development of multiple animal models. AMD is a complex and heterogeneous disease that involves the interaction of both genetic and environmental factors with the unique anatomy of the human macula. Models in mice, rats, rabbits, pigs and non-human primates have recreated many of the histological features of AMD and provided much insight into the underlying pathological mechanisms of this disease. In spite of the large number of models developed, no one model yet recapitulates all of the features of human AMD. However, these models have helped reveal the roles of chronic oxidative damage, inflammation and immune dysregulation, and lipid metabolism in the development of AMD. Models for induced choroidal neovascularization have served as the backbone for testing new therapies. This article will review the diversity of animal models that exist for AMD as well as their strengths and limitations.

The role of docosahexaenoic acid in retinal function

An important role for docosahexaenoic acid (DHA) within the retina is suggested by its high levels and active conservation in this tissue. Animals raised on n-3-deficient diets have large reductions in retinal DHA levels that are associated with altered retinal function as assessed by the electroretinogram (ERG). Despite two decades of research in this field, little is known about the mechanisms underlying altered retinal function in n-3-deficient animals. The focus of this review is on recent research that has sought to elucidate the role of DHA in retinal function, particularly within the rod photoreceptor outer segments where DHA is found at its highest concentration. An overview is also given of human infant studies that have examined whether a neonatal dietary supply of DHA is required for the normal development of retinal function.

Home cage behavior of rhesus monkeys with long-term deficiency of omega-3 fatty acids

In an observational study with a blind observer, rhesus monkeys deficient in omega-3 (omega-3 or n-3) fatty acids initiated more bouts of stereotyped behavior in their home cages than monkeys fed a matched control diet abundant in omega-3 fatty acids. Locomotion bouts were also more frequent in deficient monkeys, but nonstereotyped locomotion did not differ. Both stereotyped behavior and the sum of all behavioral bouts were more frequent in 4-5-year-old than in 2-3-year-old monkeys, and stereotype decreased after meals in males but not females. The stereotyped behaviors associated with a deficit in omega-3 fatty acids were those typical of rhesus monkeys raised as partial social isolates or those whose surroundings have been disrupted.

The role of n-3 fatty acids in visual and cognitive development; Current evidence and methods of assessment

Low levels of dietary n-3 fatty acids during development lead to changes in the electroretinogram and visual acuity in rats, monkeys, and human infants. Additional aspects of vision can be measured in infants and may provide further useful information about the nature of the changes induced by n-3 fatty acid deficiency and their potential long-term relevance for formula-fed human infants. Several tests are available to assess the development of specific cognitive functions such as visual recognition and short-term memory. These measures can provide information that is not now available to test the hypothesis that n-3 fatty acids are important for other aspects of neural function, including intellectual or cognitive development.

Infant vision and retinal function in studies of dietary long-chain polyunsaturated fatty acids: methods, results, and implications

Animal and human studies have documented several effects of different dietary and tissue concentrations of long-chain polyunsaturated fatty acids (LCPUFAs) on retinal function and vision. The enhanced visual development associated with increased intakes of LCPUFAs, particularly docosahexaenoic acid (DHA), provides the strongest evidence for the importance of these fatty acids in infant nutrition. The 2 primary visual measures used to assess the efficacy of infant formula LCPUFA supplementation are the electroretinogram and visual acuity. This review briefly describes the methodology, neural basis, and interpretation of these measures, as well as other measures of visual development that may be used to extend the functional evaluation of infants fed formulas with different fatty acid compositions.

Visual attention in infant monkeys: effects of dietary fatty acids and age.

Effects of dietary essential fatty acids on visual attention were explored longitudinally in infant rhesus monkeys with a visual paired-comparison paradigm. Sets of primate faces and of patterns were presented at Weeks 2, 5, 9, and 13 to 9 infants deficient in omega-3 fatty acids and 8 fed a standard nursery diet. Familiarization to 1 member of each pair preceded simultaneous presentation of both stimuli. Infants fed the deficient diet showed longer individual looks in both immediate and 24-hr tests. Duration of looks decreased with age to familiar but not to novel stimuli. The proportion of time looking at the novel stimulus (% novel) increased with age but was not affected by diet. Look duration and % novel were differentially affected and may reflect different underlying processes.