Maternal antioxidant treatment prevents the adverse effects of prenatal stress on the offspring's brain and behavior.

Maternal exposure to stress during pregnancy is associated with an increased risk of psychiatric disorders in the offspring in later life. The mechanisms through which the effects of maternal stress are transmitted to the fetus are unclear, however the placenta, as the interface between mother and fetus, is likely to play a key role. Using a rat model, we investigated a role for placental oxidative stress in conveying the effects of maternal social stress to the fetus and the potential for treatment using a nanoparticle-bound antioxidant to prevent adverse outcomes in the offspring. Maternal psychosocial stress increased circulating corticosterone in the mother, but not in the fetuses. Maternal stress also induced oxidative stress in the placenta, but not in the fetal brain. Blocking oxidative stress using an antioxidant prevented the prenatal stress-induced anxiety phenotype in the male offspring, and prevented sex-specific neurobiological changes, specifically a reduction in dendrite lengths in the hippocampus, as well as reductions in the number of parvalbumin-positive neurons and GABA receptor subunits in the hippocampus and basolateral amygdala of the male offspring. Importantly, many of these effects were mimicked in neuronal cultures by application of placental-conditioned medium or fetal plasma from stressed pregnancies, indicating molecules released from the placenta may mediate the effects of prenatal stress on the fetal brain. Indeed, both placenta-conditioned medium and fetal plasma contained differentially abundant microRNAs following maternal stress, and their predicted targets were enriched for genes relevant to nervous system development and psychiatric disorders. The results highlight placental oxidative stress as a key mediator in transmitting the maternal social stress effects on the offspring's brain and behavior, and offer a potential intervention to prevent stress-induced fetal programming of affective disorders.

The impact of an emergency hiring plan on the shortage and distribution of nurses in Kenya: the importance of information systems.

OBJECTIVE: To analyse the effect of Kenya's Emergency Hiring Plan for nurses on their inequitable distribution in rural and underserved areas. METHODS: We used data from the Kenya Health Workforce Informatics System on the nursing workforce to determine the effect of the Emergency Hiring Plan on nurse shortages and maldistribution. The total number of nurses, the number of nurses per 100,000 population and the opening of previously closed or new heath facilities were recorded. FINDINGS: Of the 18,181 nurses employed in Kenya's public sector in 2009, 1836 (10%) had been recruited since 2005 through the Emergency Hiring Plan. Nursing staff increased by 7% in hospitals, 13% in health centres and 15% in dispensaries. North Eastern province, which includes some of the most remote areas, benefited most: the number of nurses per 100,000 population increased by 37%. The next greatest increase was in Nyanza province, which has the highest prevalence of HIV infection in Kenya. Emergency Hiring Plan nurses enabled the number of functioning public health facilities to increase by 29%. By February 2010, 94% of the nurses hired under pre-recruitment absorption agreements had entered the civil service. CONCLUSION: The Emergency Hiring Plan for nurses significantly increased health services in Kenya's rural and underserved areas over the short term. Preliminary indicators of sustainability are promising, as most nurses hired are now civil servants. However, continued monitoring will be necessary over the long term to evaluate future nurse retention. The accurate workforce data provided by the Kenya Health Workforce Informatics System were essential for evaluating the effect of the Emergency Hiring Plan.

Organizational approaches to the HIV/AIDS crisis.

The Centers for Disease Control and Prevention (CDC) has played a major role in controlling the HIV/AIDS epidemic in the United States. After implementation of perinatal zidovudine therapy in 1994, the efforts of the CDC and others produced a dramatic decline in perinatal HIV transmission. However, in recent years, approximately 300 perinatally infected infants have been born annually in the United States. To further reduce this number, the CDC has identified four prevention goals: improve prenatal care, recommend HIV testing, ensure treatment for HIV-infected pregnant women, and ensure follow-up care. To address these goals, the CDC launched a prevention plan consisting of surveillance, research, outreach strategies, grant programs, evaluation efforts, and policy development. Globally, the CDC tailors this plan to meet the needs of developing countries. The CDC provides technical assistance to international organizations to help develop, implement, and evaluate global prevention programs. Specific international sites are targeted for new research and programs to reduce perinatal HIV transmission.

Epidemiology of HIV/AIDS in women and children in the USA.

In the USA, the AIDS epidemic has shown dramatic increases among women and children in the past decade with more than 70,000 cases in women and 7000 cases in children reported. Acquired immunodeficiency syndrome is the seventh leading cause of death in children aged 1-4 years and the fourth leading cause of death among women aged 25-44 years. Data from the National Survey of Childbearing Women, a blinded serosurvey of blood specimens left over from routine metabolic screening of most infants born in the USA, indicate that approximately 7000 HIV-infected women have given birth each year for the past several years. Human immunodeficiency virus infection disproportionately affects African-Americans and women of Hispanic ethnicity. Most cases in women and children have come from states along the east coast and large urban areas. Pneumocystis carinii pneumonia (PCP) continues to be the most commonly reported opportunistic infection in children with AIDS. As of 31 December, 1995, 2383 cases of PCP had been reported to the Centers for Disease Control and Prevention. Revised guidelines for PCP prophylaxis published in 1995 will hopefully provide a better means for preventing this deadly infection in children with AIDS. In 1994, a clinical trial (ACTG 076) found that the risk of perinatal transmission could be reduced by two-thirds with the use of a zidovudine regimen given antenatally, during labor and delivery, and postnatally to the infant. The US Public Health Service published guidelines based on these results, recommending voluntary HIV counseling and testing for all pregnant women in the USA and zidovudine therapy for those women found to be HIV-infected. Since implementation of these guidelines, cases of perinatally acquired AIDS in children have begun to decrease. Adequate resources for provision of care, outreach to women who do not receive prenatal care, training of healthcare personnel and attention to the many social and psychological needs of HIV-infected women and their children are key factors for further reduction of HIV infection in children.

Overview of perinatal HIV infection.

The global HIV epidemic is having a profound impact on the health and survival of children. As of 1994, it is estimated that about 2 million children worldwide (WHO, 1994) and 12 thousand children in the United States are HIV infected (Davis et al. 1995). Almost all HIV infection among infants and young children are from mother-to-infant transmission. By the year 2000, HIV is projected to infect 40 million men, women, and children unless effective prevention strategies are developed. Perinatal HIV transmission rates currently vary from 14-40% with the lowest rates being seen in Europe and highest rates in Africa. Known risk factors for perinatal transmission include advanced maternal HIV disease, lower CD4+ counts, and increased viral burden during pregnancy. Observational cohort data suggest that prenatal vitamin A levels, maternal drug use, and duration of membrane rupture during labor also are related to risk of transmission. The United States clinical trial utilizing an antiretroviral (zidovudine [AZT]) prenatally, intrapartum, and for 6 weeks to the infant demonstrated that perinatal HIV transmission was reduced by two-thirds. This dramatic result gives strong encouragement that simpler perinatal prevention strategies applicable to developing countries may also be successful. A number of international studies are underway or planned including perinatal vitamin A and micronutrient trials in Africa.

Preventing perinatal transmission of HIV--costs and effectiveness of a recommended intervention.

OBJECTIVE: To calculate the national costs of reducing perinatal transmission of human immunodeficiency virus through counseling and voluntary testing of pregnant women and zidovudine treatment of infected women and their infants, as recommended by the Public Health Service, and to compare these costs with the savings from reducing the number of pediatric infections. METHOD: The authors analyzed the estimated costs of the intervention and the estimated cost savings from reducing the number of pediatric infections. The outcome measures are the number of infections prevented by the intervention and the net cost (cost of intervention minus the savings from a reduced number of pediatric HIV infections). The base model assumed that intervention participation and outcomes would resemble those found in the AIDS Clinical Trials Group Protocol 076. Assumptions were varied regarding maternal seroprevalence, participation by HIV-infected women, the proportion of infected women who accepted and completed the treatment, and the efficacy of zidovudine to illustrate the effect of these assumptions on infections prevented and net cost. RESULTS: Without the intervention, a perinatal HIV transmission rate of 25% would result in 1750 HIV-infected infants born annually in the United States, with lifetime medical-care costs estimated at $282 million. The cost of the intervention (counseling, testing, and zidovudine treatment) was estimated to be $ 67.6 million. In the base model, the intervention would prevent 656 pediatric HIV infections with a medical care cost saving of $105.6 million. The net cost saving of the intervention was $38.1 million. CONCLUSION: Voluntary HIV screening of pregnant women and ziovudine treatment for infected women and their infants resulted in cost savings under most of the assumptions used in this analysis. These results strongly support implementation of the Public Health Service recommendations for this intervention.

Efficacy of antenatal zidovudine in reducing perinatal transmission of human immunodeficiency virus type 1. The New York City Perinatal HIV Transmission Collaborative Study Group.

New York City women (321) enrolled during 1986-1993 in an observational cohort study were analyzed retrospectively to determine the effectiveness of antenatal zidovudine in reducing perinatal transmission of human immunodeficiency virus type 1 (HIV-1) in women with various CD4+ lymphocyte counts (< 200, 200-499, > 499/microL). When CD4+ lymphocyte level was controlled for, women prescribed zidovudine during pregnancy were less likely to transmit HIV-1 to their infants (adjusted odds ratio, 0.36; 95% confidence interval, 0.14-0.92). There was no conclusive evidence that efficacy of zidovudine depended on CD4+ lymphocyte level, suggesting that women with severe CD4+ cell depression, who are at highest risk of transmitting HIV-1, may also benefit from zidovudine. Antenatal zidovudine treatment alone may substantially lower the risk of perinatal HIV-1 transmission. These data are consistent with the results of AIDS Clinical Trial Group protocol 076 and suggest that a substantial portion of zidovudine's protective effect may occur when used during the antenatal period.

CD4+ T lymphocytopenia in children: lack of evidence for a new acquired immunodeficiency syndrome agent.

We investigated children with CD4+ T lymphocytopenia to determine the magnitude and public health impact of this condition and to investigate possible causes. Children < 13 years old with CD4+ T lymphocyte counts below age-adjusted cutoffs (age < 24 months, 1000 cells/microliters; age > or = 24 months, 300 cells/microliters) or < 20% on 2 separate measurements were considered to have CD4+ T lymphocytopenia. We solicited information from clinicians and public health departments on these children and their families and collected blood for immunologic and retroviral testing. We identified 18 children (10 boys; 14 African-Americans) with a median age of 10 months at their first low CD4+ T lymphocyte measurement. Three children had had opportunistic infections and two still had low CD4+ T lymphocyte counts 5 and 7 years later. Of the 11 children born to human immunodeficiency virus (HIV)-infected mothers 7 were asymptomatic. Specimens from all children were negative for HIV and human T lymphotropic virus antibodies and negative for HIV by culture or polymerase chain reaction. Among 12 families interviewed no other HIV-seronegative family or household member had illnesses suggestive of immunosuppression. We conclude that negative retroviral tests and lack of illness among their family members do not support the hypothesis that a retrovirus causes CD4+ T lymphocytopenia among these children.(ABSTRACT TRUNCATED AT 250 WORDS)

Reducing the risk of perinatal HIV transmission through zidovudine therapy: treatment recommendations and implications.

In recent years, human immunodeficiency virus (HIV) infection has emerged as a leading cause of death among young children, most of whom acquired their infection perinatally. Without effective prevention efforts, transmission of HIV through heterosexual sex will continue to increase among women, and the number of perinatally infected children will mirror this increase. In 1994, researchers at the National Institutes of Health and its collaborators announced results from a randomized clinical trial indicating that zidovudine therapy administered to a select group of HIV-infected pregnant women and their newborns reduced the risk of perinatal transmission by two-thirds. This article reviews this clinical trial and its significant findings, discusses the ensuing recommendations from the US Public Health Service, discusses their implications for prenatal counseling and testing, and describes future research needs.

Epidemiology of pediatric human immunodeficiency virus infection in the United States.

Human Immunodeficiency Virus (HIV) infection is a growing problem for children worldwide. As of 31 December 1992, 4249 children with Acquired Immunodeficiency Syndrome (AIDS) under 13 years of age had been reported to the US Centers for Disease Control and Prevention (CDC). HIV is transmitted to children predominantly from their mothers. Nearly all cases of HIV infection acquired from blood transfusions in the United States occurred before donor-screening practices were implemented in March 1985. In 1991, approximately 7000 HIV-infected women gave birth to a liveborn infant in the United States, for a prevalence of 1.7 per 1000 women. Despite recent advances in prophylactic therapy for opportunistic infections, Pneumocystis carinii pneumonia remains the most common AIDS-defining illness in children in the United States. If these cases are to be prevented, children born to HIV-infected mothers will need to be identified early and monitored appropriately for CD4+ cell counts to determine the need for prophylaxis.

Epidemiology of pediatric human immunodeficiency virus infection in the United States.

HIV infection is an important cause of morbidity and mortality in the pediatric population. Providers of health care to children need to be aware of the problem and the characteristics of the most affected populations. Early diagnosis of HIV infection is critical for initiating appropriate antiviral therapy and prophylactic treatment for opportunistic infections. Attending to the myriad of social problems these families face is equally important for providing an optimal chance for prolonged survival and a reasonably high quality of life.