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Biomedical subjects

M L Newell

Publications and source records attributed to M L Newell.

At least 55 records · Page 3Linked to original sources

Acceptability of voluntary HIV testing by pregnant women in developing countries: an international survey. Ghent International Working Group on Mother-to-Child Transmission of HIV.

OBJECTIVE: To evaluate acceptability of voluntary HIV counselling and testing (VCT) by pregnant women in the context of clinical trials assessing interventions to reduce mother-to-child transmission (MCT) of HIV in developing countries. METHODS: During September-October 1997, 13 studies located in West (Abidjan, Bobo Dioulasso), East (Nairobi, Mombasa, Dar Es Salaam, Blantyre, Lusaka, Harare) and South Africa (Soweto, Durban), and Thailand (Bangkok) were included in a cross-sectional mailing survey about the acceptability of VCT in antenatal clinics. Acceptance rate, return rate, overall acceptability of VCT (acceptance of both pre- and post-VCT sessions) were obtained using a standardized questionnaire. RESULTS: The median overall acceptability of VCT was 69% (range, 33-95%). Overall acceptability of VCT most frequently depended on return rates because acceptance rates were generally high. Where several studies were conducted in parallel in the same city or the same country, overall acceptability rates of HIV testing were generally comparable even if the intervention programmes differed. Overall acceptability rates of VCT were high in antenatal clinics where a particular effort in implementing VCT programmes had been made. CONCLUSIONS: This international survey shows that despite many obstacles, VCT is feasible and acceptable for pregnant women aiming to reduce their risk of transmitting HIV to their children.

AIDS Serodiagnosis↗

Infant feeding and risk of mother-to-child transmission of HIV-1 in São Paulo State, Brazil. São Paulo Collaborative Study for Vertical Transmission of HIV-1.

Although vertical transmission of HIV-1 can occur through breast-feeding, little is known about the effect of colostrum, duration of breast-feeding, mixing feeding, and nipple pathology. We used retrospective cohort data to examine the association between breast-feeding-related factors and transmission of HIV-1 from mother to child in São Paulo State, Brazil. Information on maternal and postnatal factors was collected by medical record review and interview. Infection status was determined for 434 children by anti-HIV-1 tests performed beyond 18 months of age or diagnosis of AIDS at any age. Among 168 breast-fed children, the risk of transmission of HIV-1 was 21%, compared with 13% (p = .01) among 264 children artificially fed. Breast-feeding was independently and significantly associated with mother-to-child transmission of HIV-1 after controlling for stage of maternal HIV-1 disease (odds ratio [OR] = 2.2; 95% confidence interval [CI], 1.3-3.8). A trend was shown toward an increased risk of transmission with longer duration of breast-feeding, a history of bleeding nipples, and introduction of other liquid food before weaning, but these associations were not statistically significant. History of colostrum intake or cracked nipples without bleeding were not associated with transmission. Most of the women who breast-fed were unaware of their HIV-1 infection status at the time of delivery. Avoidance of mixed feeding and withholding of breast-feeding in the presence of bleeding nipples should be considered in further research as strategies to reduce postnatal transmission of HIV-1 in settings in which safe and sustainable alternatives for breast-feeding are not yet available.

Bottle Feeding↗

International multicentre pooled analysis of late postnatal mother-to-child transmission of HIV-1 infection. Ghent International Working Group on Mother-to-Child Transmission of HIV.

BACKGROUND: An understanding of the risk and timing of mother-to-child transmission of HIV-1 in the postnatal period is important for the development of public-health strategies. We aimed to estimate the rate and timing of late postnatal transmission of HIV-1. METHODS: We did an international multicentre pooled analysis of individual data from prospective cohort studies of children followed-up from birth born to HIV-1-infected mothers. We enrolled all uninfected children confirmed by HIV-1-DNA PCR, HIV-1 serology, or both. Late postnatal transmission was taken to have occurred if a child later became infected. We calculated duration of follow-up for non-infected children from the time of negative diagnosis to the date of the last laboratory follow-up, or for infected children to the mid-point between the date of last negative and first positive results. We stratified the analysis for breastfeeding. FINDINGS: Less than 5% of the 2807 children in four studies from industrialised countries (USA, Switzerland, France, and Europe) were breastfed and no HIV-1 infection was diagnosed. By contrast, late postnatal transmission occurred in 49 (5%) of 902 children in four cohorts from developing countries, in which breastfeeding was the norm (Rwanda [Butare and Kigali], Ivory Coast, Kenya), with an overall estimated risk of 3.2 per 100 child-years of breastfeeding follow-up (95% CI 3.1-3.8), with similar estimates in individual studies (p=0.10). Exact information on timing of infection and duration of breastfeeding was available for 20 of the 49 children with late postnatal transmission. We took transmission to have occurred midway between last negative and first positive HIV-1 tests. If breastfeeding had stopped at age 4 months transmission would have occurred in no infants, and in three if it had stopped at 6 months. INTERPRETATION: Risk of late postnatal transmission is consistently shown to be substantial for breastfed children born to HIV-1-positive mothers. This risk should be balanced against the effect of early weaning on infant mortality and morbidity and maternal fertility.

Blotting, Western↗

Breastfeeding, genetic, obstetric and other risk factors associated with mother-to-child transmission of HIV-1 in Sao Paulo State, Brazil. Sao Paulo Collaborative Study for Vertical Transmission of HIV-1.

OBJECTIVES: To evaluate the effect of maternal, obstetric, neonatal and post-natal factors on the risk of vertical transmission of HIV-1. DESIGN: Multicentre retrospective cohort study. SETTING: Obstetric and paediatric clinics in four cities in Sao Paulo State, Brazil. MAIN OUTCOME: Child's HIV-1 infection status. METHODS: Data were collected by standardized record abstraction and interview on 553 children born to women identified as HIV-1-infected before or at delivery. Paediatric infection was determined by immunoglobulin G anti-HIV-1 tests at age 18 months or by AIDS diagnosis at any age. Multivariate logistic regression was used to assess the effect of potential risk factors on vertical transmission of HIV-1. RESULTS: HIV-1 infection status was determined for 434 children (follow-up rate of 78%); 69 were classified as HIV-1-infected [transmission risk, 16%; 95% confidence interval (CI), 13-20%]. In multivariate analysis, advanced maternal HIV-1 disease [odds ratio (OR), 4.5; 95% CI, 2.1-9.5], ever breastfed (OR, 2.2; 95% CI, 1.2-4.2), child's negative Rhesus blood group (OR, 2.5; 95% CI, 1.2-5.5), third trimester amniocentesis (OR, 4.1; 95% CI, 1.2-13.5) and black racial group (OR, 0.3; 95% CI, 0.1-0.9) were independently and significantly associated with mother-to-child transmission of HIV-1. Transmission was increased marginally with prematurity, more than 10 lifetime sexual partners and prolonged duration of membrane rupture. No association was found between child's HIV-1 infection and mode of delivery or serological evidence of syphilis during pregnancy. CONCLUSION: These findings support the importance of severity of maternal HIV-1 disease in the risk of vertical transmission of HIV-1, indicate measures to reduce transmission by avoiding amniocentesis and breastfeeding and suggest that race and Rhesus blood type may be markers for genetic susceptibility to infection.

Alcohol Drinking↗

Maternal viral load, CD4 cell count and vertical transmission of HIV-1.

HIV load and CD4 cell numbers were measured among 95 HIV infected women during pregnancy in order to determine their value as prognostic markers for transmission of virus from mother to infant. Among the 94 live births, 13 children were infected with HIV, 69 were uninfected and 12 were of unknown infection status. HIV RNA levels, as measured by nucleic acid sequence based amplification, were significantly higher (P < 0.001) in women who transmitted virus than among those who did not transmit and maternal viral load was a stronger predictor of transmission than CD4 cell number. The predicted rate of transmission relative to maternal HIV RNA was 2% at 1,000 copies, 11% at 10,000 copies and 40% at 100,000 copies/ml. Little variation in viral load occurred during pregnancy and there was an association between viral load and prematurity, the mean gestation at delivery decreasing by 1.3 weeks for every 10-fold increase in maternal HIV RNA (P = 0.007). This study demonstrates that a high level of maternal HIV RNA is a risk factor for transmission of virus to the infant and maternal viral load is of more value as a prognostic marker for transmission risk than CD4 cell number. High viral load is also associated with premature delivery. Maternal viral load is therefore a useful marker on which to base management decisions during pregnancy.

CD4 Lymphocyte Count↗

Routine vaccination and vaccine-preventable infections in children born to human immunodeficiency virus-infected mothers. European Collaborative Study.

Information on vaccinations and vaccine-preventable infections collected in a prospective study of children born to human immunodeficiency virus (HIV)-infected mothers was analysed for reports of adverse reactions and to estimate the clinical efficacy of vaccines. No vaccinated, HIV-infected child developed measles (56 child-years' follow-up), mumps (33), rubella (33) or pertussis (239), and only one adverse reaction - to Bacillus Calmette-Guerin (BCG) - was reported. These findings provide limited evidence of the safety and efficacy of routine vaccination of HIV-infected children.

Chickenpox↗

Social care of children born to HIV-infected mothers in Europe. European Collaborative Study.

Children of HIV-infected women are likely to be profoundly affected by their mothers' infection, regardless of their own infection status and their number will increase with the spread of infection among women in Europe. This article describes the family circumstances and social care of 1,123 children born to HIV-infected women enrolled in the European Collaborative Study and followed prospectively from birth. Most mothers were white, married or cohabiting, asymptomatic and had a history of drug use, with 45% currently using injecting drugs at the time of enrollment. Seventy percent of children were cared for by their mothers and/or fathers consistently in their first four years of life, but by age eight an estimated 60% will have lived away from their parents (i.e. with foster or adoptive parents, other relatives or in an institution). Whether or not a child was infected did not influence the likelihood of living in alternative care. Maternal injecting drug use, single parenthood and health status were the major reasons necessitating alternative care. The type of alternative care varied according to maternal characteristics, child's age and geographic location. The mothers of 98 children had died and average age at maternal death was four years.

Adoption↗

A review of hepatitis C virus (HCV) vertical transmission: risks of transmission to infants born to mothers with and without HCV viraemia or human immunodeficiency virus infection.

BACKGROUND: Hepatitis C virus (HCV) vertical transmission studies have reported conflicting findings, possibly due to differences in HCV transmission risk factors among maternal populations, or to methodological differences. METHODS: Systematic review of worldwide published and unpublished HCV vertical transmission studies. Standardized diagnostic criteria were applied to minimize methodological differences, and transmission rates recalculated according to maternal HCV viraemic and human immunodeficiency virus (HIV) infection status. RESULTS: In all, 976 eligible infants from 28 studies were followed up sufficiently for recalculation of transmission rates. Overall transmission rates were less than 10% in 8/12 studies of HIV negative mothers, compared with 2/7 studies comprising at least 50% HIV-coinfected mothers. Rates from 409 viraemic mothers in 15 studies ranged from 0% to 41%, being less than 10% from HIV negative mothers in 6/13 studies and from HIV positive mothers in 1/6 studies. Nine studies measured maternal viraemia levels, with only 2/30 transmitting mothers having < 10(6) copies/ml of HCV RNA. Eight transmissions were identified overall from non-viraemic mothers. Significant transmission rate variation remained after accounting for maternal viraemia and HIV coinfection, possibly due to differences in other vertical transmission risk factors, in frequencies of postnatal transmission, or residual differences in study methodologies. CONCLUSIONS: Overall, HCV transmission is largely restricted to infants born to HCV viraemic mothers, and low risks among most HIV negative mothers may be due to lower HCV viraemia levels. International agreement on standardized diagnostic criteria for HCV vertical transmission would facilitate pooling of individual findings, to allow more precise transmission estimates and further investigation of risk factors.

Adult↗

A randomised trial of mode of delivery in women infected with the human immunodeficiency virus.

OBJECTIVE: During the pilot phase of a trial to evaluate the effectiveness of caesarean section delivery compared with vaginal delivery in reducing mother-to-child transmission of human immunodeficiency virus (HIV) infection, the feasibility of randomisation to mode of delivery was assessed. DESIGN: At 36 weeks of pregnancy, women infected with HIV were randomly allocated to either caesarean section delivery at 38 weeks or vaginal delivery. Information was also collected on the reasons why women were not enrolled, either because they refused or had a contraindication. SETTING: Fifty-one centres in six European countries. POPULATION: Pregnant women with confirmed HIV-1 infection. MAIN OUTCOME MEASURES: Randomisation. RESULTS: Three-hundred and thirty-nine women had been randomised by the end of 1996, the large majority from Italy (n = 250) and France (n = 54), with 22 from South Africa, three from Sweden, nine from Barcelona and one from London. A further 150 women were eligible but had not been randomised. Forty-eight women (14%) were not delivered according to the arm to which they were randomised; the majority (n = 44) were changed from vaginal to caesarean section delivery. There is wide variation between European countries in the acceptability and adherence to the mode of delivery trial. CONCLUSION: The pilot phase of this trial has shown that in some settings randomisation to mode of delivery is feasible and acceptable, but that in other settings clinicians and pregnant women are more reluctant to be randomised. Pending further information on transmission rates and accrual, enrollment into the trial continues.

Cesarean Section↗

Morbidity and mortality in European children vertically infected by HIV-1. The French Pediatric HIV Infection Study Group and European Collaborative Study.

Based on 392 infected children enrolled in two European prospective studies of infants born to HIV-infected women, with similar standard protocols, HIV disease progression in the first 6 years of life is described, using the 1994 CDC paediatric HIV classification. Most children had developed minor (A) or moderately severe (B) illness in the first 4 years of life, although usually it was transient in nature. Progression to U.S. Centers for Disease Control and Prevention (CDC) group C disease or HIV-related death is an estimated 20% (95% confidence interval 16-24%) during the first year of life, and 4.7% (3.3-6.5%) per year thereafter, giving a cumulative incidence of 36% (30-43%) by 6 years. The mortality rate at 6 years is 26% (20-32%). Two thirds of the children alive at 6 years had only minor symptoms, and one third had a CD4+ cell distribution of > 25% despite previous clinical manifestations and a transient period of moderate immune deficiency. Differences in zidovudine monotherapy between the two cohorts were not associated with the mortality rate. However, the risk of severe bacterial infections was lower in the French cohort, in which the use of antibacterial prophylaxis was more common. The early, severe form of HIV disease affects approximately 20% of infants, and after 6 years 75% of infected children are still alive. This has important implications for health-care planning.

Adult↗

Use of polymerase chain reaction and antibody tests in the diagnosis of vertically transmitted hepatitis C virus infection.

Data on patterns of polymerase chain reaction (PCR) and antibody test results in infants born to hepatitis C virus (HCV)-infected mothers were systematically reviewed to aid development of optimum testing schedules and diagnostic criteria for vertically exposed infants and to facilitate early identification of infected infants. Survival and cross-sectional analyses were used to estimate the timing of initial PCR positivity and subsequent PCR negativity in infected infants, and maternal antibody loss in uninfected infants was estimated as a weighted average of individual study findings. Of 74 eligible infants with strong evidence of HCV infection, an estimated 89% (90% confidence interval, 80-95%) were first PCR positive by 3 months of age, and less than 10% had subsequent PCR negativity attributable to intermittent viraemia or resolved infection in the first 18 months of life. The negative predictive value of PCR at 3 months of age was greater than 98% at an assumed rate of 5% vertical transmission, but as low as 88% at 25% transmission. The inclusion of 22 infants, each with a single PCR-positive result, increased the estimated frequency of resolved infections but made little difference to other estimates. A minority of PCR-positive infants had periods of antibody negativity by second- or third-generation assays, and among 297 uninfected infants, maternal antibody was not detected beyond 18 months. Thus, the majority of infected infants may be persistently PCR positive from 3 months of age, and the negative predictive value of PCR at 3 months is generally high. However, poor repeatability of PCR, inadequate infant follow-up, and inclusion of postnatally infected infants limits interpretation of the pooled data. Further studies using standardised PCR methodologies are needed.

Cross-Sectional Studies↗

European contribution to the science, prevention and management of HIV infection.

The objectives of the European Commission Biomed AIDS Programme are to enable Europe to pool its intellectual and financial resources in the control, treatment and prevention of HIV infection and AIDS. In order to facilitate this aim the Commission has allocated 40 to 50 million ECU over the past 6 years for concerted action of the Biomed projects on AIDS by the countries of the European Union. This is only a small proportion of the real cost spent by the member countries on this epidemic.

AIDS Vaccines↗

Pregnancy and HIV infection in Europe.

Human immunodeficiency virus (HIV) seroprevalence among pregnant women varies between and within countries and is generally higher in urban than in rural areas. In the European Collaborative Study, heterosexual transmission is increasing and most women are asymptomatic, although the overall mean CD4 count is declining over time. There seems to be little evidence of an increased risk of pregnancy or delivery complications in HIV-infected pregnancies. Most studies have found no increase in adverse pregnancy outcomes, although further research is needed. Prospective studies suggest that pregnancy does not promote accelerated disease progression in asymptomatic women. Despite earlier concerns, three recent studies suggest that pregnancy is not associated with deterioration of immunocompetence. The increasing number of infected pregnant women requires adequate planning for the future care of their children.

Disease Progression↗