Hannah Peavy

Incidence of premature birth and neonatal respiratory disease in infants of HIV-positive mothers

OBJECTIVE We sought to determine the prematurity rate in infants of HIV-positive mothers and to characterize the incidence and severity of neonatal respiratory disease in this population. STUDY DESIGN From 1990 to 1994, 600 live-born infants of HIV-infected mothers were enrolled prenatally (73%) or postnatally (27%) from five U.S. centers. Logistic regression was used to determine the association of HIV status in the infant with prematurity (< or = 37 weeks), low birth weight (< or = 2.5 kg), and very low birth weight (< or = 1.5 kg) rates. The incidence of respiratory distress syndrome (RDS), bronchopulmonary dysplasia, meconium aspiration syndrome, and neonatal pneumonia was compared with anticipated rates for gestational age and birth weight. RESULTS Very high rates of prematurity (19%), low birth weight (18.3%), and very low birth weight (3.3%) were found in the infants of HIV-positive mothers; and HIV infection in the infant was associated with younger gestational age. The overall incidence of RDS was 3% (17/600), which coincided with the anticipated rate, after adjusting for prematurity and birth weight. Only five infants (all < or = 1.5 kg) had bronchopulmonary dysplasia, and none required assisted ventilation beyond 14 days. Three term infants had mild meconium aspiration syndrome, and there were no cases of documented neonatal pneumonia. CONCLUSION Infants born to HIV-positive mothers exhibited high prematurity and low birth weight rates, and the odds of prematurity were higher in infants who were infected with HIV. Despite the high incidence of prematurity and perinatal risk of this population, incidence and severity of neonatal respiratory disease were not higher than would be expected from available neonatal data in populations not exposed to HIV.

Maternal and perinatal factors related to maternal-infant transmission of HIV-1 in the P2C2 HIV study : The role of EBV shedding

The association of maternal and perinatal factors with mother-infant transmission of HIV-1 was examined in a prospective multicenter cohort of singleton live births to 508 HIV-1-infected women with children of known HIV-1 infection status (91 [18%] HIV-1-infected, 417 [82%] uninfected). From multivariate logistic regression, independent predictors of HIV-1 transmission included maternal CD4 percentage (CD4%) (odds ratio [OR] per 10% increase in CD4% = 0.70; p = .003), ruptured membranes <24 hours (OR = 3.15; p = .02), and maternal bleeding (OR = 2.90; p = .03), whereas maternal zidovudine (ZDV) use was marginally associated (OR = 0.60; p = .08). The associations of maternal urinary cytomegalovirus (CMV) shedding, oropharyngeal Epstein-Barr virus (EBV) shedding, and serology profiles during pregnancy with HIV-1 transmission were examined in the subset of mothers in whom the CMV and EBV measurements were available. Maternal EBV seropositivity, CMV shedding, and CMV seropositivity were 100% (279 of 279), 7% (16 of 229), and 92% (270 of 274), respectively. These rates did not differ between transmitting and nontransmitting mothers. In univariate analyses, maternal EBV shedding was higher among transmitting than nontransmitting mothers (40 of 49 [82%] compared with 154 of 226 [68%]; p = .06) and was independently associated with transmission in multivariate logistic analyses adjusting for CD4%, ruptured membranes, and ZDV use, with an OR of 2.45 (95% confidence interval (CI), 1.03-5.84; p = .04). This permits the conclusion that EBV shedding is associated with maternal-infant HIV-1 transmission, independent of CD4%.

HIV Vertical Transmission Rate Determinations Are Subject to Differing Definitions and Therefore Different Rates

The HIV infection status of a cohort of 600 prospectively followed children born to HIV infected mothers was determined using HIV peripheral blood culture tests at 0, 3, and 6 months of age, HIV serology at > or = 15 months, and CDC AIDS criteria. We estimated transmission rates using five methods which differed in how HIV indeterminates are handled. These methods were applied at two points in time to illustrate effects of length of follow-up of the cohort on results. In January 1997, 30 months after the last birth, transmission rate estimates ranged from 15.5% (known positives/known positives x known negatives) to 18.1% (known positives x those with one positive culture x deaths/entire cohort minus those lacking negative cultures at age > or = 5 months). Estimates ranged from 14.8% to 20.7% using the subcohort of 284 children followed > or = 12 months as of May 1993. These results indicate that methods for assigning HIV infection status and for handling HIV indeterminates should be carefully defined when estimating transmission rates.

A National Heart, Lung, and Blood Institute History and Perspective on Lymphangioleiomyomatosis

The rapidly evolving progress in lymphangioleiomyomatosis (LAM) research is an ongoing story of exemplary patient advocacy, collaboration between private organizations and government, outstanding scientists, and good timing. LAM is a rare, slowly progressive disease characterized by the proliferation of smooth muscle-like cells and cystic lesions that gradually destroy the lungs. LAM also produces lesions in the lymphatic tissues and is often accompanied by renal angiomyolipomas. It may occur sporadically or it may be associated with tuberous sclerosis complex (TSC). LAM affects mostly young and middle-aged women and rarely affects men. In the mid 1990s, when the National Heart, Lung, and Blood Institute (NHLBI) first began supporting research on LAM, it was a disease of unknown origin with no effective treatment other than lung transplantation. Patients had no support network and were often being managed with high doses of progesterone or oophorectomy to abrogate the effect of estrogen. Since that time, establishment of LAM patient advocacy and support groups, increased support for research in LAM by the NHLBI, launching and completion of a LAM patient registry, and development of a LAM tissue bank have combined to result in substantial research accomplishments and progress in both basic and clinical LAM research. The role played by NHLBI in LAM research illustrates some of the unique features of the NIH in the American biomedical research enterprise. NHLBIs intramural program supported the first studies on this rare orphan disease, and established essential infrastructure to facilitate research. Patient registries and tissue repositories were created and made available to the scientific community. Patient advocates ensured that these resources were used and shared. Funding opportunities enabled investigators to link tissues and clinical data, rapidly advancing the cellular and molecular biologic understanding of the disease. Support of these activities is now more broadly supported, and the scientific opportunities explored by an increasing number of investigators. NHLBI looks forward to development of more effective therapies, bringing industry and other partners into this exciting field of science and medicine (Fig. 1). FIG. 1. Essential partners in biomedical research. Patient Advocacy LAM patients and patient interest groups have been and continue to be the vital core of the LAM research enterprise. They have participated directly in the research effort, giving, their time, blood, and tissues. LAM patients and advocates have also formed strong support networks, raised funds, organized patient and scientific meetings, lobbied, educated, served as advisors, and provided financial support for investigators, especially those at early stages of their careers. This effort was sparked by the parent of a LAM patient, and a tireless advocate who worked vigorously in the mid 1990s to garner support for developing a LAM patient registry and tissue bank. A “Labor of Love” campaign was launched that engaged patients, womens organizations, churches, schools, educators, and doctors in efforts to boost recognition and support for a registry. The timing was good for this type of patient involvement, as the scientific community was ripe for such a partnership following a decade of AIDS advocacy. The research establishment had come to appreciate patients working closely with investigators, having an active voice in the management of their disease, and lobbying vigorously for research and treatment. The LAM Treatment Alliance was created in 2005 and is accelerating LAM research by many means, including fund raising, creating a seminar series for investigators, sponsoring scientific meetings, awarding grants, and raising public awareness. (LAM Treatment Alliance website http://lamtreatmentalliance.org/index.html). The Alliance has been instrumental in aiding in the continued collection of tissue and distribution of materials.