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Biomedical subjects

M L Newell

Publications and source records attributed to M L Newell.

At least 73 records · Page 4Linked to original sources
PubMed1997

Human immunodeficiency virus infection and mode of delivery.

Most children acquire human immunodeficiency virus (HIV) infection vertically from an infected mother. Indirect evidence suggests that a substantial proportion of infection is acquired around the time of delivery, which suggests that this would be an appropriate time to intervene. If intrapartum transmission of HIV occurs primarily through direct exposure of the infant to cell-associated or free HIV in genital secretions or blood during passage through the birth canal, or by ascending infection, caesarean section performed prior to labour might reduce the risk of transmission. There is insufficient evidence to justify routine caesarean section deliveries for HIV-infected women, and a randomized clinical trial of mode of delivery has started in Europe.

Cesarean Section↗
PubMed1996

Detection of virus in vertically exposed HIV-antibody-negative children.

BACKGROUND: HIV-infected mothers can transmit their infection to their children in utero or at delivery (vertical transmission). There have been cases of children who were reported as acquiring infection vertically and later clearing the infection. We report the frequency of this phenomenon in a European cohort study. METHODS: In four centres of the European Collaborative Study of children born to HIV-infected mothers, 299 children became HIV-antibody-negative and 264 of these had been followed up with virus culture and PCR for viral DNA at least once. FINDINGS: Nine of the 264 children were positive by virus culture or PCR, and subsequently seroreverted. Two of the nine tested virus-positive after they became antibody-negative. Six cases were virus-positive early in life and became negative thereafter, which is consistent with clearance of infection. The pattern was less clear in the other three. The nine cases had had their last virus test at age 16-101 months. All nine children had been bottlefed only. Eight had been delivered vaginally. The children had no HIV-related symptoms and received no anti-HIV treatments. Based on only those children who had two or more positive virological tests, we estimate that 2.7% (6/219) cleared or "tolerated" the virus. INTERPRETATION: The detection of virus or viral DNA in "uninfected" children born to HIV-infected mothers was rare and was not associated with clinical disease or immunological abnormalities. The timing of samples will affect the documentation of clearance since, in uninfected children of HIV-positive mothers who cleared the virus, viraemia was intermittent. Current paediatric opinion is to inform parents of children who serorevert that the child is not HIV-infected.

Child, Preschool↗
PubMed1996

Characteristics of pregnant HIV-1 infected women in Europe. European Collaborative Study.

There is a growing number of infected women in Europe and an increasing proportion of these have acquired their infection through heterosexual contact. Most infected women are of childbearing age and thus increasing numbers of children are at risk of acquiring infection. In this paper we examine the socio-demographic characteristics and trends in mode of acquisition of infection of 1690 infected women from 7 countries enrolled in the European Collaborative Study, a prospective multi-centre study of children born to women known to be HIV infected at or before the time of delivery. The majority of women were white, primiparae, married or cohabiting and born in Europe. Two-thirds had a history of injecting drug use (IDU), most commonly involving heroin. Although patterns of transmission varied by centre, there was a relative increase in heterosexual transmission over the study period. A history of needle-sharing among IDUs was common, but needle-sharing during pregnancy significantly declined between 1987 and 1994.

Adult↗
PubMed1996

Salivary testing for human immunodeficiency virus type 1 infection in children born to infected mothers in Sao Paulo, Brazil. The Sao Paulo Collaborative Study for Vertical Transmission of HIV-1.

OBJECTIVE: To validate a method for salivary testing for HIV infection in children older than 12 months. METHODS: Oral fluid samples were collected via sponge foam swabs from children born to HIV-positive mothers and were tested for antibodies to HIV-1 and HIV-2 with an IgG antibody capture enzyme-linked immunosorbent assay and a modified Western blot for confirmation. In each child serum antibody status was the standard used to validate the salivary antibody test. RESULTS: We obtained 331 oral fluid samples from children born to HIV-positive mothers. The specificity and sensitivity of salivary testing compared with results on sera were both 100% (297 of 297 (95% confidence interval 98.8 to 100%) and 34 of 34 (95% confidence interval 89.7 to 100%), respectively). Compliance in the study population increased from 91% to 97% when mothers were offered the opportunity to provide oral fluid from their children instead of blood specimens. CONCLUSION: Salivary testing provides an accurate and acceptable noninvasive method for assessing the HIV infection status of children born to infected mothers by using IgG antibody capture enzyme-linked immunosorbent assay alone with a strategy of duplicate retesting of reactive specimens.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Vertical transmission of HIV-1: maternal immune status and obstetric factors. The European Collaborative Study.

OBJECTIVE: To estimate the effect of maternal factors and events around the time of delivery on HIV-1 vertical transmission risk. DESIGN: Prospective study. SETTING: Twenty-two obstetric and paediatric clinics in seven European countries. PATIENTS OR OTHER PARTICIPANTS: Mothers identified as HIV-infected before or at delivery and their children. MAIN OUTCOME MEASURE: Paediatric HIV infection. RESULTS: By November 1995, 1846 mothers with 1945 children had been enrolled. The vertical transmission rate was 16.4% (95% confidence interval, 14.5-18.3). Parity, maternal age, race, mode of HIV acquisition, injecting drug use and sex of infant were not statistically significantly associated with risk of transmission. Children delivered vaginally were more likely to be infected than those delivered by Caesarean section. However, in vaginal deliveries the procedures used, duration of ruptured membranes or length of second-stage labour were not related to transmission. Transmission increased almost linearly with decreasing CD4 cell count, but there was no such trend for CD8 cell count. Women with CD4 cell counts below 200 x 10(6)/l were significantly more likely to deliver early (chi 2 for trend, 14.02; P < 0.001). Very premature infants were at increased risk of infection, but after about 35 weeks gestation the transmission rate remained stable, with no increase in late pregnancy. This trend was confirmed after allowing for maternal CD4 cell count. CONCLUSIONS: The rate of vertical transmission increases linearly with decreasing maternal CD4 cell count. Women with fewer than 200 x 10(6) CD4 cells/l have an increased risk of premature delivery, which would affect timing of interventions. The stable transmission rate after 35 weeks gestation suggests little acquisition of infection during late pregnancy.

Europe↗
PubMed1995

Use of polymerase chain reaction and quantitative antibody tests in children born to human immunodeficiency virus-1-infected mothers.

The diagnosis of human immunodeficiency virus (HIV) infection in children born to HIV-infected mothers is complicated by the presence of passively acquired maternal antibodies, and exclusion of infection in these infants remains problematic. The use of genome detection by polymerase chain reaction (PCR) amplification and the quantification of anti-HIV-1 antibodies were examined as methods for early diagnosis. Blood samples were taken from 84 non-breast-fed infants of HIV-infected mothers in five Italian and Spanish centres, a subgroup of children enrolled in the European Collaborative Study (ECS) for whom clinical and immunological information has been documented from birth. Whole blood was added to glycigel cryopreservative, stored, and tested in the United Kingdom by a nested PCR method. Antibody to HIV-1 was detected and quantified by titration using a gelatin particle agglutination test. PCR sensitivity and specificity were assessed. Twenty-one of the 84 children tested were infected. The estimated PCR sensitivity ranged from 0% (95% CI 0-26%) on day 1, 57% (19-85) on day 7, to 63% (33-92) on day 30. The negative predictive value of PCR ranged from 85% (83-88) on day 0 to 98% (94-100) at 3 months of age. On average, the level of maternal antibody halved every 33 days (31-36.5) in uninfected children. Between 6 and 9 months of age, increases in antibody titres in infected children were not more informative than absolute levels. These findings suggest that antibody measurement may supplement genomic diagnosis and that this collection method provides an alternative to the use of dried blood spots.

Age Factors↗
PubMed1995

Vertical transmission of HIV-1: risks and prevention.

HIV can be transmitted from mother to child before, during, or after birth, but the relative contribution of each route remains unclear. Indirect evidence suggests that a substantial proportion of transmission occurs late in pregnancy or around the time of delivery. In Europe, the rate of vertical transmission is around 15-20% and is associated with maternal HIV status, mode of delivery and length of time from rupture of membranes, and breastfeeding. A number of interventions to reduce vertical transmission have been suggested including avoidance of breastfeeding, caesarean section delivery, disinfection of the birth canal, passive and active immunization, and anti-retroviral therapy. Several clinical trials to evaluate such approaches are ongoing or being planned. The costs of the various options are likely to limit implementation.

Female↗
PubMed1995

The management of pregnancy and delivery in HIV-infected women in Europe.

In view of the increasing heterosexual spread of HIV and reports of interventions which reduce the rate of mother to child transmission, a postal questionnaire survey was performed to determine the strategies for the management of pregnancy and delivery in HIV-infected women in 56 obstetric centres in 21 European countries. A response rate of 96% was achieved. Antenatal testing for HIV infection was routinely offered in 96% of centres. Pre- and post-test counselling was available in most centres and was mainly provided by the obstetrician; only 12 centres had trained counsellors. Compared to uninfected women, infected women made more antenatal visits in 36% of centres and had more screening tests in 30% of centres. Some delivery procedures (e.g. use of scalp electrodes) were less common in infected than in uninfected women. Nearly half the centres prescribe Zidovudine to infected women; most prescribed it specifically to reduce HIV vertical transmission. Disinfection of the birth canal and elective caesarean sections for infected women were routinely performed in 22% and 18% of centres, respectively. The survey revealed different approaches to the management of infected pregnant women both between and within countries, which may partly be due to limited knowledge of what constitutes optimal management, especially in relation to interventions to reduce vertical transmission. Randomised control trials are required to establish the most effective intervention.

Blood Transfusion↗
PubMed1995

The European Collaborative Study: clinical and immunological characteristics of HIV 1-infected pregnant women.

OBJECTIVE: To describe the changing clinical and immunological characteristics and timing of diagnosis of HIV-infected pregnant women enrolled in the European Collaborative Study. DESIGN: A prospective study of the mothers of children enrolled in the European Collaborative Study on children born to HIV-infected women. SETTING: Twenty-one European centres in seven countries. SUBJECTS: One thousand six hundred and ninety HIV-infected women and their 1754 deliveries. RESULTS: The proportion of women in whom HIV infection had been diagnosed before pregnancy increased significantly over time, from 7% in 1984-1985 to 65% in 1994 (P < 0.001). The prevalence of breastfeeding, which was related to the timing of diagnosis, significantly declined over the study period. The mean CD4 count was 510 cells/mm3, and there was a significant decline in average CD4 count over the study period. Black women had a significantly lower CD4 count than white women. From survival analysis it is estimated that five years after delivery 14% of women will have died and 24% will have developed CDC stage IV disease. CONCLUSIONS: Timing of diagnosis is of critical importance if mother-to-child transmission is to be reduced through avoidance of breastfeeding and zidovudine therapy and effective antenatal screening policies have become increasingly important. The rate of progression of maternal disease highlights the implications of HIV infection for their children, both infected and uninfected.

Antiviral Agents↗
PubMed1995

A risk-benefit assessment of zidovudine in the prevention of perinatal HIV transmission.

Mother-to-child transmission is the main mode of acquisition of HIV infection for children, and the estimated rate of vertical transmission ranges from 15 to 20% in Europe, 15 to 25% in the US and 25 to 35% in Africa. Vertical transmission is associated with clinical and immunological progression of disease in the mother, breastfeeding and possibly with vaginal delivery. Recently, the findings of the American/French AIDS Clinical Trial Group (ACTG) trial 076 showed that in women with mildly symptomatic HIV disease and no prior treatment with antiretroviral drugs during the pregnancy, zidovudine (ZDV, 3'-azido-3'-deoxythymidine, AZT) reduced the risk of vertical transmission when administered during pregnancy and delivery and to the infant in the first 6 weeks of life. No significant adverse effects were observed in either the mothers or neonates. Although the results of the American/French trial on the use of zidovudine to prevent vertical transmission are encouraging, many questions remain unanswered. The optimal timing of administration of zidovudine is unknown, as is its effectiveness in women with clinical characteristics that differ from those of the women in the trial. Concern has been expressed about the possibility of long term effects of exposure of zidovudine during pregnancy, both for the mother and the infant (of whom 4 out of 5 are uninfected anyway) and the implications for antenatal screening. Further trials with different zidovudine regimens and other strategies to prevent vertical transmission are being planned in several countries.

Acquired Immunodeficiency Syndrome↗