Association of HIV-1 Envelope-Specific Breast Milk IgA Responses with Reduced Risk of Postnatal Mother-to-Child Transmission of HIV-1.

UNLABELLED: Infants born to HIV-1-infected mothers in resource-limited areas where replacement feeding is unsafe and impractical are repeatedly exposed to HIV-1 throughout breastfeeding. Despite this, the majority of infants do not contract HIV-1 postnatally, even in the absence of maternal antiretroviral therapy. This suggests that immune factors in breast milk of HIV-1-infected mothers help to limit vertical transmission. We compared the HIV-1 envelope-specific breast milk and plasma antibody responses of clade C HIV-1-infected postnatally transmitting and nontransmitting mothers in the control arm of the Malawi-based Breastfeeding Antiretrovirals and Nutrition Study using multivariable logistic regression modeling. We found no association between milk or plasma neutralization activity, antibody-dependent cell-mediated cytotoxicity, or HIV-1 envelope-specific IgG responses and postnatal transmission risk. While the envelope-specific breast milk and plasma IgA responses also did not reach significance in predicting postnatal transmission risk in the primary model after correction for multiple comparisons, subsequent exploratory analysis using two distinct assay methodologies demonstrated that the magnitudes of breast milk total and secretory IgA responses against a consensus HIV-1 envelope gp140 (B.con env03) were associated with reduced postnatal transmission risk. These results suggest a protective role for mucosal HIV-1 envelope-specific IgA responses in the context of postnatal virus transmission. This finding supports further investigations into the mechanisms by which mucosal IgA reduces risk of HIV-1 transmission via breast milk and into immune interventions aimed at enhancing this response. IMPORTANCE: Infants born to HIV-1-infected mothers are repeatedly exposed to the virus in breast milk. Remarkably, the transmission rate is low, suggesting that immune factors in the breast milk of HIV-1-infected mothers help to limit transmission. We compared the antibody responses in plasma and breast milk of HIV-1-transmitting and -nontransmitting mothers to identify responses that correlated with reduced risk of postnatal HIV-1 transmission. We found that neither plasma nor breast milk IgG antibody responses were associated with risk of HIV-1 transmission. In contrast, the magnitudes of the breast milk IgA and secretory IgA responses against HIV-1 envelope proteins were associated with reduced risk of postnatal HIV-1 transmission. The results of this study support further investigations of the mechanisms by which mucosal IgA may reduce the risk of HIV-1 transmission via breastfeeding and the development of strategies to enhance milk envelope-specific IgA responses to reduce mother-to-child HIV transmission and promote an HIV-free generation.

Hostile attributional bias and aggressive behavior in global context.

We tested a model that children's tendency to attribute hostile intent to others in response to provocation is a key psychological process that statistically accounts for individual differences in reactive aggressive behavior and that this mechanism contributes to global group differences in children's chronic aggressive behavior problems. Participants were 1,299 children (mean age at year 1 = 8.3 y; 51% girls) from 12 diverse ecological-context groups in nine countries worldwide, followed across 4 y. In year 3, each child was presented with each of 10 hypothetical vignettes depicting an ambiguous provocation toward the child and was asked to attribute the likely intent of the provocateur (coded as benign or hostile) and to predict his or her own behavioral response (coded as nonaggression or reactive aggression). Mothers and children independently rated the child's chronic aggressive behavior problems in years 2, 3, and 4. In every ecological group, in those situations in which a child attributed hostile intent to a peer, that child was more likely to report that he or she would respond with reactive aggression than in situations when that same child attributed benign intent. Across children, hostile attributional bias scores predicted higher mother- and child-rated chronic aggressive behavior problems, even controlling for prior aggression. Ecological group differences in the tendency for children to attribute hostile intent statistically accounted for a significant portion of group differences in chronic aggressive behavior problems. The findings suggest a psychological mechanism for group differences in aggressive behavior and point to potential interventions to reduce aggressive behavior.

The ecocultural context and child behavior problems: A qualitative analysis in rural Nepal.

Commonly used paradigms for studying child psychopathology emphasize individual-level factors and often neglect the role of context in shaping risk and protective factors among children, families, and communities. To address this gap, we evaluated influences of ecocultural contextual factors on definitions, development of, and responses to child behavior problems and examined how contextual knowledge can inform culturally responsive interventions. We drew on Super and Harkness' "developmental niche" framework to evaluate the influences of physical and social settings, childcare customs and practices, and parental ethnotheories on the definitions, development of, and responses to child behavior problems in a community in rural Nepal. Data were collected between February and October 2014 through in-depth interviews with a purposive sampling strategy targeting parents (N = 10), teachers (N = 6), and community leaders (N = 8) familiar with child-rearing. Results were supplemented by focus group discussions with children (N = 9) and teachers (N = 8), pile-sort interviews with mothers (N = 8) of school-aged children, and direct observations in homes, schools, and community spaces. Behavior problems were largely defined in light of parents' socialization goals and role expectations for children. Certain physical settings and times were seen to carry greater risk for problematic behavior when children were unsupervised. Parents and other adults attempted to mitigate behavior problems by supervising them and their social interactions, providing for their physical needs, educating them, and through a shared verbal reminding strategy (samjhaune). The findings of our study illustrate the transactional nature of behavior problem development that involves context-specific goals, roles, and concerns that are likely to affect adults' interpretations and responses to children's behavior. Ultimately, employing a developmental niche framework will elucidate setting-specific risk and protective factors for culturally compelling intervention strategies.

Child work and labour among orphaned and abandoned children in five low and middle income countries.

BACKGROUND: The care and protection of the estimated 143,000,000 orphaned and abandoned children (OAC) worldwide is of great importance to global policy makers and child service providers in low and middle income countries (LMICs), yet little is known about rates of child labour among OAC, what child and caregiver characteristics predict child engagement in work and labour, or when such work infers with schooling. This study examines rates and correlates of child labour among OAC and associations of child labour with schooling in a cohort of OAC in 5 LMICs. METHODS: The Positive Outcomes for Orphans (POFO) study employed a two-stage random sampling survey methodology to identify 1480 single and double orphans and children abandoned by both parents ages 6-12 living in family settings in five LMICs: Cambodia, Ethiopia, India, Kenya, and Tanzania. Regression models examined child and caregiver associations with: any work versus no work; and with working <21, 21-27, and 28+ hours during the past week, and child labour (UNICEF definition). RESULTS: The majority of OAC (60.7%) engaged in work during the past week, and of those who worked, 17.8% (10.5% of the total sample) worked 28 or more hours. More than one-fifth (21.9%; 13% of the total sample) met UNICEF's child labour definition. Female OAC and those in good health had increased odds of working. OAC living in rural areas, lower household wealth and caregivers not earning an income were associated with increased child labour. Child labour, but not working fewer than 28 hours per week, was associated with decreased school attendance. CONCLUSIONS: One in seven OAC in this study were reported to be engaged in child labour. Policy makers and social service providers need to pay close attention to the demands being placed on female OAC, particularly in rural areas and poor households with limited income sources. Programs to promote OAC school attendance may need to focus on the needs of families as well as the OAC.

Maternal HIV-1 envelope-specific antibody responses and reduced risk of perinatal transmission.

Despite the wide availability of antiretroviral drugs, more than 250,000 infants are vertically infected with HIV-1 annually, emphasizing the need for additional interventions to eliminate pediatric HIV-1 infections. Here, we aimed to define humoral immune correlates of risk of mother-to-child transmission (MTCT) of HIV-1, including responses associated with protection in the RV144 vaccine trial. Eighty-three untreated, HIV-1-transmitting mothers and 165 propensity score-matched nontransmitting mothers were selected from the Women and Infants Transmission Study (WITS) of US nonbreastfeeding, HIV-1-infected mothers. In a multivariable logistic regression model, the magnitude of the maternal IgG responses specific for the third variable loop (V3) of the HIV-1 envelope was predictive of a reduced risk of MTCT. Neutralizing Ab responses against easy-to-neutralize (tier 1) HIV-1 strains also predicted a reduced risk of peripartum transmission in secondary analyses. Moreover, recombinant maternal V3-specific IgG mAbs mediated neutralization of autologous HIV-1 isolates. Thus, common V3-specific Ab responses in maternal plasma predicted a reduced risk of MTCT and mediated autologous virus neutralization, suggesting that boosting these maternal Ab responses may further reduce HIV-1 MTCT.

A Longitudinal Investigation of Infant Gesture Use and Parent Speech: Unique and Dynamic Influences on Infant Vocabulary Acquisition

How do infants learn word meanings? Research has established the impact of both parent and child behaviors on vocabulary development, however the processes and mechanisms underlying these relationships are still not fully understood. Much existing literature focuses on direct paths to word learning, demonstrating that parent speech and child gesture use are powerful predictors of later vocabulary. However, an additional body of research indicates that these relationships don’t always replicate, particularly when assessed in different populations, contexts, or developmental periods.

The current study examines the relationships between infant gesture, parent speech, and infant vocabulary over the course of the second year (10-22 months of age). Through the use of detailed coding of dyadic mother-child play interactions and a combination of quantitative and qualitative data analytic methods, the process of communicative development was explored. Findings reveal non-linear patterns of growth in both parent speech content and child gesture use. Analyses of contingency in dyadic interactions reveal that children are active contributors to communicative engagement through their use of gestures, shaping the type of input they receive from parents, which in turn influences child vocabulary acquisition. Recommendations for future studies and the use of nuanced methodologies to assess changes in the dynamic system of dyadic communication are discussed.

Correlates of poor health among orphans and abandoned children in less wealthy countries: the importance of caregiver health.

BACKGROUND: More than 153 million children worldwide have been orphaned by the loss of one or both parents, and millions more have been abandoned. We investigated relationships between the health of orphaned and abandoned children (OAC) and child, caregiver, and household characteristics among randomly selected OAC in five countries. METHODOLOGY: Using a two-stage random sampling strategy in 6 study areas in Cambodia, Ethiopia, India, Kenya, and Tanzania, the Positive Outcomes for Orphans (POFO) study identified 1,480 community-living OAC ages 6 to 12. Detailed interviews were conducted with 1,305 primary caregivers at baseline and after 6 and 12 months. Multivariable logistic regression models describe associations between the characteristics of children, caregivers, and households and child health outcomes: fair or poor child health; fever, cough, or diarrhea within the past two weeks; illness in the past 6 months; and fair or poor health on at least two assessments. PRINCIPAL FINDINGS: Across the six study areas, 23% of OAC were reported to be in fair or poor health; 19%, 18%, and 2% had fever, cough, or diarrhea, respectively, within the past two weeks; 55% had illnesses within the past 6 months; and 23% were in fair or poor health on at least two assessments. Female gender, suspected HIV infection, experiences of potentially traumatic events, including the loss of both parents, urban residence, eating fewer than 3 meals per day, and low caregiver involvement were associated with poorer child health outcomes. Particularly strong associations were observed between child health measures and the health of their primary caregivers. CONCLUSIONS: Poor caregiver health is a strong signal for poor health of OAC. Strategies to support OAC should target the caregiver-child dyad. Steps to ensure food security, foster gender equality, and prevent and treat traumatic events are needed.

Due to her tender age: Black girls and childhood on trial in South Carolina, 1885-1920

Drawing on local criminal court records in western and central South Carolina, this dissertation follows the legal experiences of black girls in South Carolina courts between 1885 and 1920, a time span that includes the aftermath of Reconstruction and the foundational years of Jim Crow. While scholars continue to debate the degree to which black children were included in evolving conversations about childhood and child protection, this dissertation argues that black girls were critical to turn-of-the century debates about all children's roles in society. Far from invisible in the courts and jails of their time, black girls found themselves in the crosshairs of varying forms of power --including intraracial community surveillance, burgeoning local government, Progressive reform initiatives and military policy -- particularly when it came to matters of sexuality and reproduction. Their presence in South Carolina courts established boundaries between early childhood, adolescence and womanhood and pushed legal stakeholders to consider the legal implication of age, race, and gender in criminal proceedings. Age had a complicated effect on black girls' legal encounters; very young black girls were often able to claim youth and escape harsher punishments, while courts often used judicial discretion to levy heavier sentences to adolescents and violent girl offenders. While courts helped to separate early childhood from the middle years, they also provided a space for African-American children and family to engage a legal system that was moving rapidly toward disenfranchising blacks.

Monitoring maternal Beta carotene and retinol consumption may decrease the incidence of neurodevelopmental disorders in offspring.

Retinoic acids (13-cis and 13-trans) are known teratogens, and their precursor is retinol, a form of vitamin A. In 1995, Rothman et al demonstrated an association between excessive vitamin A, >10,000 IU/day, during the first trimester of pregnancy and teratogenic effects, particularly in the central nervous system. However, vitamin A deficiency has long been known to be deleterious to the mother and fetus. Therefore, there may be a narrow therapeutic ratio for vitamin A during pregnancy that has not previously been fully appreciated. Neurodevelopmental disorders may not be apparent by macroscopic brain examination or imaging, and proving the existence of a behavioral teratogen is not straightforward. However, an excess of retinoic acid and some neurodevelopmental disorders are both associated with abnormalities in cerebellar morphology. Physical and chemical evidence strongly supports the notion that beta carotene crosses the placenta and is metabolized to retinol. Only very limited amounts of beta carotene are stored in fetal fat cells as evidenced by the fact that maternal fat is yellow from beta carotene, whereas non-brown neonatal fat is white. Furthermore, newborns of carotenemic mothers do not share the yellow complexion of their mothers. The excess 13-trans retinoic acid derived from metabolized beta carotene in the fetus increases the concentration of the more teratogenic 13-cis retinoic acid since the isomerization equilibrium is shifted to the left. Therefore, this paper proposes that consideration be given to monitoring all potential sources of fetal 13-cis and 13-trans retinoic acid, including nutritional supplements, dietary retinol, and beta carotene, particularly in the first trimester of pregnancy.

Dispersal and Integration in Female Chimpanzees

In chimpanzees, most females disperse from the community in which they were born to reproduce in a new community, thereby eliminating the risk of inbreeding with close kin. However, across sites, some females breed in their natal community, raising questions about the flexibility of dispersal, the costs and benefits of different strategies and the mitigation of costs associated with dispersal and integration. In this dissertation I address these questions by combining long-term behavioral data and recent field observations on maturing and young adult females in Gombe National Park with an experimental manipulation of relationship formation in captive apes in the Congo.

To assess the risk of inbreeding for females who do and do not disperse, 129 chimpanzees were genotyped and relatedness between each dyad was calculated. Natal females were more closely related to adult community males than were immigrant females. By examining the parentage of 58 surviving offspring, I found that natal females were not more related to the sires of their offspring than were immigrant females, despite three instances of close inbreeding. The sires of all offspring were less related to the mothers than non-sires regardless of the mother’s residence status. These results suggest that chimpanzees are capable of detecting relatedness and that, even when remaining natal, females can largely avoid, though not eliminate, inbreeding.

Next, I examined whether dispersal was associated with energetic, social, physiological and/or reproductive costs by comparing immigrant (n=10) and natal (n=9) females of similar age using 2358 hours of observational data. Natal and immigrant females did not differ in any energetic metric. Immigrant females received aggression from resident females more frequently than natal females. Immigrants spent less time in social grooming and more time self-grooming than natal females. Immigrant females primarily associated with resident males, had more social partners and lacked close social allies. There was no difference in levels of fecal glucocorticoid metabolites in immigrant and natal females. Immigrant females gave birth 2.5 years later than natal females, though the survival of their first offspring did not differ. These results indicate that immigrant females in Gombe National Park do not face energetic deficits upon transfer, but they do enter a hostile social environment and have a delayed first birth.

Next, I examined whether chimpanzees use condition- and phenotype-dependent cues in making dispersal decisions. I examined the effect of social and environmental conditions present at the time females of known age matured (n=25) on the females’ dispersal decisions. Females were more likely to disperse if they had more male maternal relatives and thus, a high risk of inbreeding. Females with a high ranking mother and multiple maternal female kin tended to disperse less frequently, suggesting that a strong female kin network provides benefits to the maturing daughter. Females were also somewhat less likely to disperse when fewer unrelated males were present in the group. Habitat quality and intrasexual competition did not affect dispersal decisions. Using a larger sample of 62 females observed as adults in Gombe, I also detected an effect of phenotypic differences in personality on the female’s dispersal decisions; extraverted, agreeable and open females were less likely to disperse.

Natural observations show that apes use grooming and play as social currency, but no experimental manipulations have been carried out to measure the effects of these behaviors on relationship formation, an essential component of integration. Thirty chimpanzees and 25 bonobos were given a choice between an unfamiliar human who had recently groomed or played with them over one who did not. Both species showed a preference for the human that had interacted with them, though the effect was driven by males. These results support the idea that grooming and play act as social currency in great apes that can rapidly shape social relationships between unfamiliar individuals. Further investigation is needed to elucidate the use of social currency in female apes.

I conclude that dispersal in female chimpanzees is flexible and the balance of costs and benefits varies for each individual. Females likely take into account social cues present at maturity and their own phenotype in choosing a settlement path and are especially sensitive to the presence of maternal male kin. The primary cost associated with philopatry is inbreeding risk and the primary cost associated with dispersal is delay in the age at first birth, presumably resulting from intense social competition. Finally, apes may strategically make use of affiliative behavior in pursuing particular relationships, something that should be useful in the integration process.