Alterations in immunoglobulin levels in uninfected children born to HIV infected women

Background Immunoglobulin levels are known to be elevated in HIV infected children. However, little is known about the effect of maternal HIV infection and the maternal altered immune system on immunoglobulin levels in uninfected children. As few data are available on immunoglobulins from young healthy children, we used data from uninfected children born to hepatitis C virus (HCV) infected women as a comparison. Methods Prospective data on immunoglobulin levels were available from birth to 5 years for children enrolled in the European Collaborative Study (ECS) of children born to HIV-1 infected women and from birth to 24 months for children enrolled in the European Paediatric HCV Network (EPHN). Children born to HIV/HCV co-infected women were excluded. Smoothers (running means) illustrated patterns of immunoglobulins over age by infection status. Associations between infant and maternal factors and child log10 total IgG, IgM and IgA levels were quantified in linear regression analyses allowing for repeated measures within child. Further analyses were performed using only data of HIV exposed uninfected children to investigate associations between child immunoglobulins and maternal immunological and virological factors and anti-retroviral therapy exposure. Results 1751 HIV uninfected, 190 HIV infected children (ECS), 173 HCV uninfected and 30 HCV infected children (EPHN) were included. HIV infected children had higher levels of all immunoglobulins compared to uninfected children over all ages. HIV uninfected children had significantly higher IgG, IgM and IgA levels than HCV uninfected children upto at least 24 months, adjusting for gender, prematurity and race. Prematurity was associated with significantly lower levels of immunoglobulins upto 24 months. Children born to African women had higher IgG and IgA levels upto 24 months than those born to white women but lower IgM in the first 6 months. Among HIV uninfected children higher IgG levels were associated with elevated maternal IgG levels, as well for measurements from 18 months to 5 years of age. No significant effect of maternal CD4 count was observed. ART exposure was associated with significantly lower IgG levels at 6-24 months. Race was not associated with immunoglobulin levels in multivariable analyses in this sub-group. Conclusions These findings indicate significant alterations in immunoglobulin levels in uninfected children born to HIV infected women. This suggests that exposure to an activated maternal immune system is associated with an altered humoral response in children without antigen stimulation, and warrants further research

The Functions of the Skin

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Routinely available cotrimoxazole prophylaxis and occurrence of respiratory and diarrhoeal morbidity in infants born to HIV-infected mothers in South Africa

Objectives. To examine the influence of cotrimoxazole (CTM) prophylaxis on incidence of lower  respiratory tract infections (LRTis) and diarrhoea.Design. A prospective observational cohort study. Morbidity and feeding data on infants born to HN-infected mothers were collected routinely at. clink visits at 1 week, 6 weeks and 3 months, and 3-monthly thereafter, with blood drawn for determining HIV status.Setting. Two hospitals in Durban, South Africa. In one hospital (King Edward VIII Hospital), infants born to HIVinfected mothers recieved CTM prophylaxis and in the other (McCord Hospital) infants did not  receive CTM prophylaxis,Subjects. Infants born to HIV-infected mothers.Outcome measures. Incidence of .LRTI and diarrhoea.Results, Ill. multivariate analysis controlling for breast-feeding status, number of clinic visits and HN infection status, HIVinfected infants with access to C1M prophylaxis had a significantly lower incidence of LRTI (82%) than those without access to prophylaxis. However in HIV-uninfected infants, this was not the case, CTM prophylaxis was associated with a non-significant increased risk for diarrhoea in both infected (odds ratio (OR) 1.58, p = 0.45) aud uninfected infants (OR 1.52, p = 0.10).Conclusions, This observational study .confirms current thinking that CTM prophylaxis is protective  against LRTis in HIV-infected children. However, because of a possible association between CTM prophylaxis and an increased risk of diarrhoea, HIV status of infants should be determined as early as possible in order to prevent tmnecessary exposure of uninfected infants to CTM prophylaxis, while further studies to quantify both beneficial and adverse effects. of CTM prophylaxis are undertaken

Childhood abuse is associated with methylation of multiple loci in adult DNA

Childhood abuse is associated with increased adult disease risk, suggesting that processes acting over the long-term, such as epigenetic regulation of gene activity, may be involved. DNA methylation is a critical mechanism in epigenetic regulation. We aimed to establish whether childhood abuse was associated with adult DNA methylation profiles

Paternal obesity is associated with IGF2 hypomethylation in newborns: results from a Newborn Epigenetics Study (NEST) cohort

Data from epidemiological and animal model studies suggest that nutrition during pregnancy may affect the health status of subsequent generations. These transgenerational effects are now being explained by disruptions at the level of the epigenetic machinery. Besides in vitro environmental exposures, the possible impact on the reprogramming of methylation profiles at imprinted genes at a much earlier time point, such as during spermatogenesis or oogenesis, has not previously been considered. In this study, our aim was to determine associations between preconceptional obesity and DNA methylation profiles in the offspring, particularly at the differentially methylated regions (DMRs) of the imprinted Insulin-like Growth Factor 2 (IGF2) gene

Spontaneous Clearance Of Vertically Acquired Hepatitis C Infection: Implications For Testing And Treatment

BACKGROUND: Current guidelines recommend that infants born to women with hepatitis C (HCV) viremia are screened for HCV antibody at age 18 months, and if positive, referred for RNA testing at 3 years to confirm chronic infection. This policy is based in part on analyses suggesting 25%-40% of vertically acquired HCV infections clear spontaneously within 4-5 years. METHODS: Data on 179 infants with HCV RNA and/or anti-HCV evidence of vertically acquired infection in three prospective European cohorts were investigated. Ages at clearance of infection were estimated taking account of interval censoring and delayed entry. We also investigated clearance in initially HCV RNA negative infants in whom RNA was not detectable until after 6 weeks. RESULTS: Clearance rates are initially high then decline slowly. Apparently, many infections clear before they can be confirmed. An estimated 65.9% (50.1-81.6) of confirmed infections cleared by 5 years, at a median 12.4 (7.1-18.9) months. If treatment began at age 6 months, 18 months or 3 years, at least 59.0% (42.0-76.9), 39.7% (17.9-65.9), and 20.9% (4.6-44.8) of those treated would clear without treatment. In seven (6.6%) confirmed infections, RNA was not detectable until after 6 weeks, and in 2 (1.9%) not until after 6 months. However, all such cases subsequently cleared. CONCLUSIONS: Most confirmed infection clears by age 3 years. Treatment before age 3, if it was available, would avoid loss to follow-up, but would result in substantial over-treatment

Overall vertical transmission of HCV, transmission net of clearance, and timing of transmission

Background: It is widely accepted that the risk of HCV vertical transmission (VT) is 5-6% in mono-infected women, and that 25-40% of HCV infection clears spontaneously within 5 years. However, there is no consensus on how VT rates should be estimated, and there is a lack of information on VT rates “net” of clearance. // Methods: We re-analysed data on 1749 children in 3 prospective cohorts to obtain coherent estimates of overall VT rate and VT rates “net” of clearance at different ages. Clearance rates were used to impute the proportion of uninfected children who had been infected and then cleared before testing negative. The proportion of transmission early in utero, late in utero and at delivery was estimated from data on the proportion of HCV RNA positive within three days of birth, and differences between elective caesarean and non-elective caesarean deliveries. // Findings: Overall VT rates were 7.2% (95% credible interval 5.6-8.9) in mothers who were HIV negative and 12.1% (8.6-16.8) in HIV-co-infected women. The corresponding rates net of clearance at 5 years were 2.4% (1.1-4.1) and 4.1% (1.7-7.3). We estimated that 24.8% (12.1-40.8) of infections occur early in utero, 66.0% (42.5-83.3) later in utero, and 9.3% (0.5-30.6) during delivery. // Conclusion: Overall VT rates are about 24% higher than previously assumed, but the risk of infection persisting beyond age 5 years is about 38% lower. The results can inform design of trials of to prevent or treat pediatric HCV infection, and strategies to manage children exposed in utero