Forced expiratory flow in uninfected infants and children born to HIV-infected mothers

The Pediatric Pulmonary and Cardiovascular Complications of Vertically Transmitted HIV (P(2)C(2) HIV) Study is a multicenter study examining pulmonary and cardiac outcomes in offspring of HIV-infected mothers. This portion of the P(2)C(2) study tests the hypothesis that infants exposed to, but uninfected by, maternal HIV have normal maximal expiratory flow at functional residual capacity (V'max,(FRC)). We obtained 500 measurements of V'max,(FRC) by rapid thoracic compression in 285 children ages 6-30 mo in five U.S. centers. The data were compared with those from a healthy cohort of children described elsewhere. V'max,(FRC) rose with height in a linear relationship. The slope of the regression line in the exposed infants did not differ statistically from the slope in the comparison group, but the intercept was about 20% lower (p < 0.001). Height and weight were comparable in the two cohorts, and the differences between intercepts persisted after adjusting for birth weight and gestational age. However, maternal HIV infection cannot be assumed to be the cause as the cohorts may have differed in other variables, such as socioeconomic status and frequency of maternal smoking and drug use. Also, measurements varied substantially within and between our five centers, probably in part because of different racial and ethnic distributions. In summary, maternal HIV infection probably has only a modest effect, if any, on maximal expiratory flow at functional residual capacity in uninfected infants.     

Disclosure of the diagnosis of HIV/AIDS to children born of HIV-infected mothers

HIV disease in perinatally infected patients is now treated as a chronic illness of childhood. The effective use of highly active anti-retroviral therapy has contributed to the improvements in the prognosis of this illness. As this population matures, the issue of disclosure of diagnosis becomes more significant and part of their comprehensive medical care. The importance of disclosure relates directly to medication adherence, treatment compliance, sexual exploration, fears associated with premature death, and the child's developing autonomy. disclosure of HIV disease to an infected child poses complex issues, such as transmissibility, maternal guilt, more than one family member with the virus, and the potential for social stigma and isolation, among others. A change in perspectives is currently taking place regarding the process of disclosure, whereby it may be approached as a gradual discussion process over the life of the child. A method of gradual and partial disclosure to the child with consistent support by a multi-disciplinary team of providers has been a successful strategy for many children cared for at the New York Hospital-Cornell University Medical Center. Of 73 perinatally HIV-infected children who are 6 years of age or older, 41% have had complete disclosure and another 19% are partially disclosed. Continuous communication and negotiation among the members of the team, which includes the parents and caregivers, are vital to the gradual process leading to complete disclosure.     

Diagnostic implication of specific immunoglobulin G patterns of children born to HIV-infected mothers

We analysed HIV-specific immunoglobulin G (IgG) responses to gag and env peptides in infants born to HIV-positive mothers. Questions of interest were whether there are early specific markers for prognosis, and whether any specific IgG is related to the prevention of vertical transmission of infection. Fifty-three children, 0-24 months old and born to HIV-1-infected mothers, were retrospectively divided into two groups based on HIV seroreactivity or non-reactivity at 15 months of age. Their sera were used to find reactivities important in diagnosis and/or prediction of the putative HIV disease. Three important findings emerged. First, a low IgG titer against the very immunodominant penv9 in newborns was found to be associated with rapid progression to AIDS. This difference was clearly reflected in the reactivity to a small peptide representing amino acid (aa) 598-606. The second interesting finding was the putative hypervariable loop on gp120 (especially aa 324-338), reactivity to which was found only in the uninfected group, and was seen in six out of 19 uninfected children under 6 months of age. This specific response was not caused by a generally high total anti-HIV reactivity, and may indicate a role of protective antibodies against vertical transmission. The response to this region in the infected group, on the other hand, was directed to the amino terminal half of the putative loop, in particular peptide 53, aa 304-318. Finally, response to a part of the amino terminal end of P17 was seen in seven out of eight infected children over 6 months of age.(ABSTRACT TRUNCATED AT 250 WORDS)     

Decline of maternal hepatitis a antibodies during the first 2 years of life in infants born in Turkey

Selective immunization of at-risk groups may reduce the incidence of hepatitis A infection, but only the inclusion of hepatitis A vaccine in a routine universal childhood immunization schedule would guarantee control of the infection. But the interference by maternally derived hepatitis A antibodies (anti-HAV) with the immunogenicity of inactivated hepatitis A vaccine is still important in the determination of the optimal age for hepatitis A vaccination. The hepatitis A vaccines have not been assessed widely in children under the age of 2 years and are not currently licensed for this age group in many countries. A prospective trial was performed to detect seroprevalence of maternal hepatitis A antibodies during the first 2 years of life among young infants born to hepatitis A antibody positive mothers in Turkey. We measured at-birth anti-HAV in 147 infants born in our hospital and in their mothers and then from the offspring at months 3, 6, 9, 12, 15, 18, 21, and 24. The prevalence of seropositivity among the mothers at birth were found similarly high (93.9%) to the studies previously done among the adults in our area. The prevalence of anti-HAV among children aged 0, 9, 12, 15, 18, and 21 months were 93.9%, 62.6%, 36.1%, 13.6%, 6.1%, and 0.7%, respectively. Although a proportion of infants still had measurable antibodies at 9 and 12 month of age, two thirds of the infants over the age of 12 months were at high risk of acquiring hepatitis A infection, as living in a endemic region.     

Interventions for developmental delays in children born to HIV-infected mothers: a systematic review

Children born to HIV-infected mothers have worse developmental outcomes compared to HIV-unexposed children. However, little is known about interventions to improve developmental outcomes in this population. This study systematically reviews the literature on interventions to improve development in children born to HIV-infected mothers. We systematically searched the following electronic bibliographic databases: Ovid MEDLINE, Embase, PsycINFO, Education Resources Information Center, and the Cochrane Database of Systematic Reviews. Studies were selected on the basis of defined inclusion criteria and excluded if antiretroviral medication was the only intervention. Titles, abstracts, and full texts were assessed by 2 independent reviewers. Data were collected on characteristics of the study design, intervention, and developmental outcomes measured. Risk of bias and strength of evidence were assessed on all included articles. Our search resulted in 11,218 records. After our initial review, 43 records were appraised in their entirety and 9 studies met all inclusion criteria. Six were performed in sub-Saharan Africa, while the remaining 3 were performed in the United States. Eight were randomized-controlled trials and one was a retrospective chart review. Four studies focused on caregiver-training, 2 studied massage therapy, and the remaining studies focused on maternal vitamin supplementation, video-based cognitive therapy, or center-based interventions. Massage therapy had the most consistent improvements in the domains measured, while caregiver training and cognitive therapy interventions had limited benefits. The center-based intervention showed no benefit. Only 3 studies had a low risk of bias, and 4 studies had good strength of evidence. Most studies found some benefit. However, these findings are limited by the quality of the study designs, small sample size, and heterogeneity of the interventions and assessments used to measure outcomes. There is a critical need for the creation of evidence-based interventions to promote development in this vulnerable population.     

HIV感染母亲分娩婴幼儿的体格生长发育状况研究

目的了解艾滋病病毒（HIV）感染母亲分娩的婴幼儿的体格生长发育状况。方法对我国4个艾滋病高发省的7个县／区,HIV感染母亲分娩的活产婴幼儿,分别在出生时、3、6、9、12、15、18月龄进行随访调查及生长发育监测,分析18月龄存活婴幼儿的体格生长发育指标。结果2005—2008年,共调查18月龄存活婴幼儿154名,其中HIV感染婴幼儿22名,非感染婴幼儿132名。结果：（1）HIV感染婴幼儿在6—18月龄的身长、体重明显低于非HIV感染婴幼儿（P〈O．05）,年龄别头围的差别无统计学意义。（2）与世界卫生组织（WHO）儿童生长标准比较,非HIV感染婴幼儿中,男、女童6月龄前的年龄别体重与该标准无差别,6月龄后的年龄别体重高于该标准（P〈O．05）;年龄别体重z值（wAz）和身长别体重z值（WHz）在-0．1～1之间;男、女童12月龄内的年龄别身长与该标准的差别无统计学意义,15—18月龄身长低于该标准（P〈0．05）,年龄别身长z值（HAz）和年龄别头围Z值在-0．1～-1之间。（3）HIV感染男、女童各月龄的体重、头围与WHO标准的差别无统计学意义,15—18月龄身长低于该标准;随访期间wAZ在O．2～-0．6之间,3月龄内wAZ下降较快,之后处于低水平状态;HAZ在0．1～-1．7之间,呈下降趋势,在6—12月龄接近-1,15—18月龄低于-1。结论HIV感染母亲分娩的非HIV感染婴幼儿的体格生长不足,身长、头围发育较差,而HIV感染婴幼儿更为严重。     

Risks to the children born to mothers with autoimmune diseases

This article reviews current information regarding the development and long-term effects on children born to women with connective tissue diseases. There are few data on specific effects attributed to the underlying maternal disease, but fetal growth restriction and preterm birth are relatively common. Antenatal use of prednisone as treatment for these disorders appears to be safe, and most children have developed normally. However, there is growing concern that prolonged fetal exposure to other glucocorticoids such as dexamethasone or betamethasone may lead to decreased growth and abnormal neuronal development. Low birth weight is reportedly associated with long-term medical complications such as adult-onset hypertension. Evidence also suggests that immunosuppressive agents taken during pregnancy might predispose the progeny to autoimmune disorders, malignancies and reproductive problems. Further research is warranted to determine that there are no unrecognized long-term risks to the offspring of these women.     

Enterovirus antibody levels during the first two years of life in prediabetic autoantibody-positive children

AIMS/HYPOTHESIS: We evaluated the role of enterovirus infections in the pathogenesis of Type I (insulin-dependent) diabetes mellitus by monitoring enterovirus antibody levels in prediabetic children who turned positive for diabetes-associated autoantibodies in a prospective birth cohort study. METHODS: Serial serum samples taken during prospective observation starting at birth were analysed for IgG and IgA class antibodies against enterovirus antigens including purified coxsackievirus B4, echovirus 11, poliovirus 1 and a synthetic enterovirus peptide antigen using enzyme immunoassay. Maternal samples taken at the end of the third month of pregnancy were also studied. Analyses were done from 21 childen who developed autoantibodies and from 104 autoantibody-negative control children who were matched for the time of birth, gender and HLA susceptibility alleles. For comparison, adenovirus antibodies were also analysed from all samples collected. RESULTS: IgG class enterovirus antibody levels were high in maternal samples and in cord blood in both case and control children. After birth the IgG levels decreased reaching a nadir at the age of 6 months. No IgA class antibodies were detected at birth but started to emerge postnatally. Antibody levels did not differ between the autoantibody positive and the control children during the first 6 months of life. From 6 months to 24 months of age, the autoantibody positive children had higher IgG and IgA levels against coxsackievirus B4, echovirus 11 and the synthetic enterovirus peptide antigens than control children but poliovirus 1 and adenovirus antibodies were closely similar in the two groups. The difference between children with autoantibodies and control children was predominantly seen among boys and among those with the HLA-DQB1*0302/x genotype. CONCLUSIONS/INTERPRETATION: Our data show that children who seroconverted for diabetes-associated auto-antibodies develop stronger humoral immune responses to coxsackievirus B4, echovirus 11 and a synthetic enterovirus peptide antigen than children who remained negative for autoantibodies. Poliovirus antibodies induced by uniform vaccinations did not differ between the prediabetic and control children suggesting that the regulation of antibody responses to enteroviruses is not disturbed. Accordingly, the results imply a stronger enterovirus exposure in prediabetic children supporting the role of enteroviruses in the pathogenesis of Type I diabetes.     

Failure to test children of HIV-infected mothers in South Africa: implications for HIV testing strategies for preschool children

Objectives To assess the uptake of HIV testing among preschool children with HIV‐positive mothers in a peri‐urban population‐based study in KwaZulu‐Natal, South Africa, an area of high HIV prevalence. Methods All children 4–6 years old and their primary caregivers from the area were invited to participate. All participants were asked about prior HIV testing and were offered counselling and voluntary HIV testing irrespective of previous testing. Twenty‐seven HIV‐infected mothers were interviewed to identify barriers to testing their children. Results One thousand five hundred and eighty‐three children (88% of eligible children) and their caregivers participated. Of the biological mothers, 86% were previously tested for HIV (27% tested positive). Among the surviving 244 children born to an infected mother, only 41% had been tested for HIV (23% tested positive). Subsequently, 90% of previously untested children of infected mothers underwent HIV testing (9.3% were positive). Overall seroprevalence among study children was 4.9%. All infected mothers interviewed endorsed the belief that children of HIV‐infected women should be tested for HIV. Women who missed opportunities for antenatal HIV testing reported no systematic testing of their children at later ages. Conclusions In this community with high HIV prevalence, HIV testing of children is infrequent despite high testing coverage among caregivers. The low proportion of children tested for HIV, particularly those of infected mothers, is of great concern as they are at high risk for morbidity and mortality associated with untreated childhood HIV infection. HIV testing programs should strengthen protocols to include children, especially for those who missed PMTCT opportunities in infancy.     

Child survival in children born to HIV-2 infected women in Guinea-Bissau, West Africa

We have retrospectively studied the effect of maternal HIV-2 infection and other risk factors on child survival at a family planning centre in Bissau, Guinea-Bissau. A total of 2109 women were included, and the seroprevalence of HIV-2 was 5.7%. Overall child mortality of all live births (n=5912) reported by the women (standardized for age of the mother) was slightly higher among children of HIV-2 seropositive mothers (16.3%) compared with children of HIV seronegative women (14.6%) (not significant). There was a significant association between low level of maternal education and increased child mortality, but no difference in the level of education was found between HIV-2 seropositive and seronegative women.     

Pulmonary mechanics in normal infants and young children during first 5 years of life

To characterize lung function in young children we measured lung compliance and pulmonary conductance in 40 normal infants and children ranging in age from the newborn period to 5 years. Inspiratory and expiratory flow was measured by a pneumotachograph, esophageal pressure through a water-filled feeding tube, and functional residual capacity (FRC) by a N2 washout technique. The esophageal pressure change per breath [(mean +/- SD) 7.3 +/- 1.4 cm H2O] and specific compliance (75 +/- 13 ml/cm H2O/L-FRC) did not change with growth. Specific conductance was high (0.60 L/s/cm H2O/L-FRC) in preterm infants, decreasing rapidly with initial growth but minimally beyond 10 kg of body weight, and stabilizing at 0.10 L/s/cm H2O/L-FRC. During the age period studied, compliance increased approximately x 25 whereas conductance only rose five-fold. The changes in compliance and conductance were well correlated to FRC, body weight, and length. These findings suggest that in the last trimester of pregnancy the airways are already well developed and postnatal lung growth occurs mainly by formation of new alveoli, leading to a proportional increase in FRC and lung compliance. Postnatally, conductance increases much more slowly than FRC, resulting in a rapid drop in specific conductance.     

Evaluation of diagnostic tests for HIV infection in infants born to HIV-infected mothers in Switzerland

Children born to HIV-infected women in Switzerland were tested every 3 months for HIV-reactive serum immunoglobulin (Ig) G, IgM and IgA antibodies by Western blot, viral antigen, virus replicating in T-lymphocyte cultures, and immunologic and clinical parameters. At birth, 27% were isolation-positive, 68% had IgM, 48% IgA and 10% circulating antigen. The proportion of IgM and IgA declined to about 18 and 27%, respectively, during the first 2 years. Detection of circulating antigen was less frequently positive than virus isolation in all age and disease groups. Clinical symptoms were only seen in infants or children who were or had been positive for IgM and/or IgA, but only 39% of children positive for these markers have developed disease so far. Clinical symptoms combined with signs of immunodeficiency were seen only in children who were isolation-positive or had evidence of HIV-reactive IgA or child-produced IgG. Absorption studies showed that Western blot-detected IgM and IgA antibodies were of two types: 42% were directed against various HIV proteins, while the rest represented rheumatoid-factor-like IgM or IgA binding to HIV-specific IgG. HIV-specific IgG antibodies were detected in all samples up to the age of 12 months and were still found in 83% of infants 13-18 months old. We observed weak HIV-specific IgG above the age of 15 months with no other signs of HIV infection, suggesting that the demonstration of antibodies in children beyond this age does not necessarily indicate HIV infection.     

Health-related quality of life and patient-provider relationships in HIV-infected patients during the first three years after starting PI-containing antiretroviral treatment

The aim of this study was to investigate factors associated with better health-related quality of life (HRQL) during the first three years after starting PI-containing antiretroviral treatment. Clinical, social and behavioural data from the APROCO cohort enabled us to analyze simultaneously the association between HRQL and patients' relationships with their health care providers. A self-administered questionnaire collected information about HRQL (MOS-SF36) and relationships with medical staff (trust and satisfaction with information). Two aggregate scores, the physical (PCS) and mental (MCS) component summaries (adjusted for baseline HRQL), were used as dependent variables in the linear regressions to identify factors associated with HRQL. We had complete longitudinal data for 360 of the 611 patients followed through M36. Factors independently associated with a high MCS were (male) gender, no more than one change in treatment, (few) self-reported symptoms and trust in the physician. Factors independently associated with high PCS levels were employment, no children, (few) self-reported symptoms and satisfaction with the information and explanations provided by the medical staff. These results underline the need to improve patient-provider relationships to optimize long-term HRQL. Socio-behavioural interventions should focus on this goal.