Prevention of human immunodeficiency virus breastmilk transmission with copper oxide: proof-of-concept study.

BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) transmission through breastmilk is the chief modality through which HIV-1 is transmitted from HIV-1-infected mothers to their babies in developing countries, where alternative feeding options lack practical feasibility. The development of an approach to inactivate the HIV-1 virions ingested by an infant on a daily basis through breastmilk is thus of critical importance. METHODS: Copper has potent virucidal properties. Stoichiometric concentrations of copper ions inactivate the HIV-1 protease, which is essential for viral replication. Cell-free and cell-associated HIV-1 infectivity is inhibited when the virus is exposed to copper oxide in a dose-dependent manner. Passage of high titers of a wide range of HIV-1 isolates, spiked in culture medium, through filters containing copper oxide powder resulted in their deactivation. RESULTS: In the current study, we demonstrate that the infectivity of three different HIV-1 isolates, spiked in breastmilk obtained from HIV-1-seronegative donors, or of wild-type isolates found in breastmilk obtained from HIV-1-seropositive donors, is drastically reduced (>98%) when exposed to copper oxide. CONCLUSIONS: This study is proof of concept that copper oxide is efficacious against HIV-1 found in breastmilk and serves as the basis for further research aimed at determining the possible effects that copper may have on the nutritional and anti-infective properties of breastmilk. Furthermore, this supports the continuing study of the feasibility of developing a filtering device, such as an "at-the-breast" disposable shield that can be used discreetly and safely by HIV-1-infected mothers during breastfeeding.

The impact of maternal age on the effects of prenatal alcohol exposure on attention.

BACKGROUND: Prenatal exposure to alcohol has a variety of morphologic and neurobehavioral consequences, yet more than 10% of women continue to drink during pregnancy, placing their offspring at risk for fetal alcohol spectrum disorders (FASD). Identification of at-risk pregnancies has been difficult, in part, because the presence and severity of FASD are influenced by factors beyond the pattern of alcohol consumption. Establishing maternal characteristics, such as maternal age, that increase the risk of FASD is critical for targeted pregnancy intervention. METHODS: We examined the moderating effect of maternal age on measures of attention in 462 children from a longitudinal cohort born to women with known alcohol consumption levels (absolute ounces of alcohol per day at conception) who were recruited during pregnancy. Analyses examined the impact of binge drinking, as average ounces of absolute alcohol per drinking day. Smoking and use of cocaine, marijuana, and opiates were also assessed. At 7 years of age, the children completed the Continuous Performance Test, and their teachers completed the Achenbach Teacher Report Form. RESULTS: After controlling for covariates, stepwise multiple regression analyses revealed a negative relation between levels of prenatal binge drinking and several measures of attention. The interaction between alcohol consumption and maternal age was also significant, indicating that the impact of maternal binge drinking during pregnancy on attention was greater among children born to older drinking mothers. CONCLUSION: These findings are consistent with previous findings that children born to older alcohol-using women have more deleterious effects of prenatal alcohol exposure on other neurobehavioral outcomes.

Biobehavioral outcomes in adolescents and young adults prenatally exposed to cocaine: evidence from animal models.

Cocaine has been a popular illicit drug among drug-using pregnant women over the last three decades. Prenatal cocaine exposure (PCE) has significant effects on children's development throughout early childhood. Very few human studies, however, report the effects of PCE on adolescent or early-adult development. As knowledge about early childhood effects in human children was informed by animal studies, this review considers the effects of PCE on behavioral outcomes in adolescent and young adult animals and provides potential guidance for research in human children. Animal models prenatally exposed to cocaine manifest play deficits, decreased social interaction, and increased aggression during competition in adolescence and young adulthood. Altered behavioral adaptation after stress exposure, including hormonal response change, is also evident. Attention deficits are reported in adult offspring with PCE, not only in a novel environment, but also in a final task session, indicating effects of PCE on transition and maintenance of attention. Animal studies support that PCE effects may extend beyond early childhood and continue to adolescence and adulthood. Additionally, some studies highlight that behavioral changes in offspring with PCE born without teratogenesis remain latent and reveal themselves during adulthood when animals are under stress conditions. Based on the evidence from animal models, well-designed human studies are needed to elucidate the effects of PCE on older human children. Research models that combine behavioral measures with stressful challenges may hold potential in discerning a longer term influence of PCE.

Deactivation of human immunodeficiency virus type 1 in medium by copper oxide-containing filters.

Human immunodeficiency virus type 1 (HIV-1) can be transmitted through breast-feeding and through contaminated blood donations. Copper has potent biocidal properties and has been found to inactivate HIV-1 infectivity. The objective of this study was to determine the capacity of copper-based filters to inactivate HIV-1 in culture media. Medium spiked with high titers of HIV-1 was exposed to copper oxide powder or copper oxide-impregnated fibers or passed through copper-based filters, and the infectious viral titers before and after treatment were determined. Cell-free and cell-associated HIV-1 infectivity was inhibited when exposed to copper oxide in a dose-dependent manner, without cytotoxicity at the active antiviral copper concentrations. Similar dose-dependent inhibition occurred when HIV-1 was exposed to copper-impregnated fibers. Filtration of HIV-1 through filters containing the copper powder or copper-impregnated fibers resulted in viral deactivation of all 12 wild-type or drug-resistant laboratory or clinical, macrophage-tropic and T-cell-tropic, clade A, B, or C, HIV-1 isolates tested. Viral inactivation was not strain specific. Thus, a novel means to inactivate HIV-1 in medium has been developed. This inexpensive methodology may significantly reduce HIV-1 transmission from "mother to child" and/or through blood donations if proven to be effective in breast milk or plasma and safe for use. The successful application of this technology may impact HIV-1 transmission, especially in developing countries where HIV-1 is rampant.

Effects of high fruit-vegetable and/or low-fat intervention on breast nipple aspirate fluid micronutrient levels.

BACKGROUND: A change in diet is known to affect micronutrient levels in blood but to what extent diet can affect micronutrient levels in the breast is not yet well established. METHODS: Healthy, premenopausal women with a family history of breast cancer were randomized across four diet arms for 1 year in a 2 x 2 factorial design study: control, low-fat, high fruit-vegetable, and combination low-fat/high fruit-vegetable diets. Subjects were asked to collect breast nipple aspirate fluid (NAF) at 0, 6, and 12 months, and levels of micronutrients were measured in the fluid. RESULTS: A total of 122 women were enrolled, 97 were retained for 12 months, and sufficient NAF for analysis was available from 59 women at baseline, 49 at 6 months, and 50 at 12 months. Repeated measures mixed-model ANOVA was used to model the data using cholesterol levels and lactation duration as covariates, where appropriate. The high fruit-vegetable intervention, regardless of fat intake, significantly increased total carotenoid levels in NAF. In the low-fat arm, levels of total carotenoids decreased over time relative to control. Levels of total tocopherols and retinol did not change significantly. Levels of 15-F(2t)-isoprostane, a marker of lipid peroxidation, also did not change significantly over time, although there was a decrease observed in the combination arm. CONCLUSIONS: These results indicate that total carotenoid levels in NAF can be significantly increased in the breast NAF with a high fruit-vegetable diet. A low-fat diet that was achieved with little increase in fruit and vegetable intake, however, decreased NAF carotenoid levels.

The association between caregiver substance abuse and self-reported violence exposure among young urban children.

This study examined the relative importance of caregiver substance abuse as a correlate of child-reported exposure to violence. A total of 407 female African-American primary caregivers and their children age 6 to 7 were evaluated. The association between child report of violence and exposure to substance abuse by others (both within and outside the home) was considered after controlling for variance accounted for by child characteristics, caregiver characteristics, home environment, and neighborhood environment (including neighborhood crime). Caregiver alcohol abuse, children's witnessing of drug use in the home, and children's witnessing of drug deals all explained significant additional variance in violence exposure. These findings suggest that for early elementary-age children, meaningful prevention of violence exposure may be possible via addressing their exposure to substance abuse in their home and community.

Somatic complaints in children and community violence exposure.

Somatic complaints of children in primary care settings often go unexplained despite attempts to determine a cause. Recent research has linked violence exposure to stress symptomatology and associated somatic problems. Unknown, however, is whether specific physical symptom complaints can be attributed, at least in part, to violence exposure. Urban African-American 6- and 7-year-old children (N = 268), residing with their biological mothers, recruited before birth, and without prenatal exposure to hard illicit drugs participated. Children and mothers were evaluated in our hospital-based research laboratory, with teacher data collected by mail. Community violence exposure (Things I Have Seen and Heard), stress symptomatology (Levonn), and somatic complaints (teacher-and self-report items) were assessed. Additional data collected included prenatal alcohol exposure, socioeconomic status, domestic violence, maternal age, stress, somatic complaints and psychopathology, and child depression, abuse, and gender. Community violence witnessing and victimization were associated with stress symptoms (r = .26 and .25, respectively, p < .001); violence victimization was related to decreased appetite (r = .16, p < .01), difficulty sleeping (r = .21, p < .001), and stomachache complaints (r = .13, p < .05); witnessed violence was associated with difficulty sleeping (r = .13, p < .05) and headaches (r = .12, p < .05). All associations remained significant after control for confounding. Community violence exposure accounted for 10% of the variance in child stress symptoms, and children who had experienced community violence victimization had a 28% increased risk of appetite problems, a 94% increased risk of sleeping problems, a 57% increased risk of headaches, and a 174% increased risk of stomachaches. Results provide yet another possibility for clinicians to explore when treating these physical symptoms in children.

Influence of lactation history on breast nipple aspirate fluid yields and fluid composition.

Analysis of nipple aspirate fluid (NAF) can be useful for understanding the impact that various lifestyle factors have on the biology of the breast. In this study, breast NAF was obtained at baseline from premenopausal women who volunteered for a dietary intervention trial. The influence of lactation history on both fluid yields and fluid composition was explored. We examined the levels of fat-soluble micronutrients (tocopherols, carotenoids, retinol), one lipid oxidation product (8-isoprostane), cholesterol, and protein in NAF. Roughly half of the women in the trial had never lactated, but this did not affect fluid yields appreciably. Carotenoid and tocopherol levels were significantly higher in NAF from women who lactated 6 months or more versus women who had lactated for shorter periods of time or never, but 8-isoprostane, protein, and cholesterol levels were not affected appreciably by lifetime lactation history. Longer times after weaning were associated with higher cholesterol levels, and there also was a suggestion the fat-soluble micronutrients declined with time after weaning. This is of interest since high cholesterol levels in breast fluid have been associated with an increased breast cancer risk, while carotenoids and tocopherols are thought to be protective. The results of this study provide further evidence of the potential benefits of prolonged lactation via its influence on NAF composition.

A rational approach for discovering and validating cancer markers in very small samples using mass spectrometry and ELISA microarrays.

Identifying useful markers of cancer can be problematic due to limited amounts of sample. Some samples such as nipple aspirate fluid (NAF) or early-stage tumors are inherently small. Other samples such as serum are collected in larger volumes but archives of these samples are very valuable and only small amounts of each sample may be available for a single study. Also, given the diverse nature of cancer and the inherent variability in individual protein levels, it seems likely that the best approach to screen for cancer will be to determine the profile of a battery of proteins. As a result, a major challenge in identifying protein markers of disease is the ability to screen many proteins using very small amounts of sample. In this review, we outline some technological advances in proteomics that greatly advance this capability. Specifically, we propose a strategy for identifying markers of breast cancer in NAF that utilizes mass spectrometry (MS) to simultaneously screen hundreds or thousands of proteins in each sample. The best potential markers identified by the MS analysis can then be extensively characterized using an ELISA microarray assay. Because the microarray analysis is quantitative and large numbers of samples can be efficiently analyzed, this approach offers the ability to rapidly assess a battery of selected proteins in a manner that is directly relevant to traditional clinical assays.

Prenatal exposure to binge drinking and cognitive and behavioral outcomes at age 7 years.

OBJECTIVE: The goal of this study was to examine differential effects of amount and pattern of prenatal alcohol exposure on child outcome. STUDY DESIGN: Alcohol use was assessed at each prenatal visit, and IQ and behavior were measured at age 7 years. RESULTS: After control for confounders, the amount of exposure was unrelated to IQ score and behavior for >500 black 7-year-old children. However, children who were exposed to binge drinking were 1.7 times more likely to have IQ scores in the mentally retarded range and 2.5 times more likely to have clinically significant levels of delinquent behavior. CONCLUSION: During prenatal care, clinicians should attend not only to amount but also to the pattern of alcohol intake, because of the elevated risk for cognitive deficits and long-term behavioral abnormality.

Birth to age 7 growth of children prenatally exposed to drugs: a prospective cohort study.

Prenatal exposure to cocaine, alcohol, and cigarettes has been linked to decreased birth weight and length. Unclear, however, is whether growth deficits persist into childhood. Women who were pregnant, African-American, not HIV-positive, and who delivered singleton infants were extensively screened throughout pregnancy for cocaine, alcohol, cigarette, and other illicit drug use. Of the approximately 1100 eligible subjects, 665 families were located at a 7-year postbirth follow-up and 540 participated. After appropriate control for potential confounders and prenatal exposures, prenatal exposure to cocaine, alcohol, and cigarettes each independently predicted birth weight and length. At age 7, prenatal cocaine exposure was significantly related to height deficits after accounting for other prenatal exposures and significant confounders. Children at age 7 exposed to cocaine in utero were up to 1 in. shorter and twice as likely to fall below the 10th percentile in height as the control children after accounting for other significant confounders including other prenatal exposures. Maternal age moderated the relation between prenatal exposures and child growth. Children born to women over 30 and exposed to cocaine were up to 2 in. shorter and four times more likely to have clinically significant height deficits at age 7. Children of older women and exposed to moderate-to-high levels of alcohol prenatally were up to 14 lb lighter and five times more likely to fall below the 10th percentile in weight. Similar growth restriction was not associated with prenatal exposures for children born to younger mothers. These outcomes add to the growing body of literature detailing long-term effects of prenatal drug exposure, suggesting differential effects for cocaine and alcohol, and indicating that maternal age may moderate these effects. Mechanisms for growth restriction and failure of catch-up under conditions of prenatal exposures are presented, suggesting further study of these developmental outcomes.