Anne Willoughby

MOTHER-TO-INFANT TRANSMISSION OF HUMAN IMMUNODEFICIENCY VIRUS TYPE 1: ASSOCIATION WITH PREMATURITY OR LOW ANTI-gp120

In a prospective study of pregnant women infected with human immunodeficiency virus type 1 (HIV-1) in Brooklyn, New York, USA, 16 (29%) of 55 evaluable infants were infected with HIV-1. 9 infants had paediatric acquired immunodeficiency syndrome, 6 had less severe clinical manifestations of HIV-1 infection, and 1 was symptom-free but was seropositive for HIV-1 beyond 15 months of age. The 10 infants born at 37 weeks of gestation or earlier were at higher risk of HIV-1 infection than infants born at 38 weeks of gestation or later (60% vs 22%) but the median age at appearance of disease was approximately 5 months in both groups. The HIV-1 transmission rate was not associated with predelivery levels of maternal T cells, anti-p24, or neutralising antibodies but it was higher, among full-term infants, for those with mothers in the lowest third of the distribution of anti-gp120 levels (53%). On immunoblot, transmitting mothers lacked a gp120 band but not other bands. Protection was not associated with antibody to recombinant peptides from the hypervariable region of the major neutralising gp120 epitope, and the anti-gp120 endpoint dilution titre was similar in transmitting and non-transmitting mothers. Mothers of uninfected full-term infants appear to confer immunological protection against HIV-1 infection of their offspring by way of a high-affinity antibody to a gp120 epitope, whose specificity has importance for vaccine development and possibly perinatal immunotherapy.

Prevalence of HIV infection in childbearing women in the United States

CD4 T-lymphocyte counts and Pneumocystis carinii pneumonia in pediatric HIV infection Kovacs A; Frederick T: Church J; Eller A; Oxtoby M; Mascola L University of Southern California Medical Cenier, 1129 N State St, Los Angeles. CA 90033, USA J AM MED ASSOC 1991 265113 (1698-1703) The relationship between CD4 T-lymphocyte counts and infection with the human immunodeficiency virus (HIV) is retrospectively investigated for 266 HIV-infected and uninfected children who were born to infected women, including 39 with Pneumocystis carinii pneumonia (PCP), in a population-based surveillance study. Of 21 perinatally HIVinfected children with PCP only 10 (48”/u) had CD4 Tlymphocyte counts that were less than 500 x IO6 cells/L (500 cells/mm3), compared with all 18 who were infected via blood transfusions or clotting factors. Among 88 children who were 1 year or younger, 18 (90%) of 20 PCP cases had CD4 Tlymphocyte counts that were less than 1500 x IO6 cells/L (1500 cells/mm3) compared with only five (IO%) of 48 children who did not have the acquired immunodeficiency syndrome (odds ratio, 77.4; 95% confidence interval, 19.7 to 313.4). The mean CD4 T-lymphocyte count was lower for the 39 PCP cases when compared with the 188 children who were at different stages of HIV infection and did not have the acquired immunodeficiency syndrome (AIDS) independent of age. The majority of perinatally HIV-infected children with PCP were 8 months or younger and 5O”/u were previously unknown to be infected. Thus, HIV-positive children should be identified early and followed closely. CD4 T-lymphocyte counts may be useful in monitoring HIV-positive children and determining when to begin PCP prophylaxis.

The influence of pregnancy on human immunodeficiency virus type 1 infection: Antepartum and postpartum changes in human immunodeficiency virus type 1 viral load

OBJECTIVE Our objective was to examine the influence of pregnancy on human immunodeficiency virus type 1 viral load by measuring human immunodeficiency virus type 1 ribonucleic acid levels during pregnancy and post partum. STUDY DESIGN One or more plasma or serum specimens obtained before and during the third trimester, and at 2, 12, and 24 months post partum were available for 160 human immunodeficiency virus type 1-seropositive women enrolled in the Mothers and Infants Cohort Study between January 1986 and January 1991. All specimens were frozen and stored at -70 degrees C until analyzed in batch for human immunodeficiency virus type 1 ribonucleic acid by polymerase chain reaction. A multivariate longitudinal random effects model was developed to examine changes in human immunodeficiency virus type 1 ribonucleic acid levels over time. RESULTS Overall, human immunodeficiency virus type 1 ribonucleic acid levels rose significantly during the study period, particularly during the second year post partum (mean, 0.09 log per year; 95% confidence interval, 0.03 to 0.15 logs per year; p = 0.005). However, the mean slope during pregnancy was not significantly different from zero (p = 0.65). CONCLUSION Pregnancy had little immediate effect on human immunodeficiency virus type 1 viral load in most human immunodeficiency virus type 1-seropositive women.

Human immunodeficiency virus infection in pregnant women under care at AIDS clinical trials centers in the United States.

: The federal government supports a nationwide network of medical centers to evaluate promising therapies against the human immunodeficiency virus (HIV) and the opportunistic infections and cancers that characterize AIDS. Forty-five obstetricians from the 49 medical centers receiving federal research support for the conduct of AIDS-related clinical trials, in preparation for a meeting, provided summary information about the number and clinical status of the known HIV-infected pregnant women under their care and the prenatal screening policies for HIV infection at their institutions. In the 12-month period before December 1989, an estimated 1000-1801 HIV-infected women delivered at these centers. The majority (82%) were asymptomatic, 12% were symptomatic, and 6% had AIDS. Routine T-cell testing of infected women was done as part of prenatal care in only 30 of 45 centers. Pneumocystis carinii pneumonia was reported in 35 women. Zidovudine was administered during pregnancy in 29 women. Formal prenatal screening policies have been implemented at the majority (43 of 45) of the medical centers. Most of the infected women identified at these centers chose to continue the pregnancy. With the increasing incidence of HIV infection in women, information concerning the clinical and immunologic state of pregnant infected women and the present use of antiretroviral and other related therapeutics during pregnancy can guide the approach to womens health care and is crucial to the design and implementation of AIDS clinical trials.

Maternal and pediatric AIDS in the United States: the current situation and future research directions

The epidemic of HIV infection and disease in women, adolescents and children represents a complexly intertwined biological and social challenge to health care workers and researchers alike. When considering various issues in confronting this epidemic, women must be viewed as individuals important in their own right, as the primary caretaker of their family members (both infected and uninfected), and as the sexual partners of men who may or may not be infected. Of the myriad of compelling biological questions facing AIDS researchers today, two of the most interesting involve the timing and determinants of vertical transmission and the natural history of HIV infection and disease in women. Scientifically, confronting this epidemic involves research into pathogenesis, epidemiology, natural history, treatment, and prevention of HIV infection. Primary emphasis in the research arena in HIV/AIDS in the United States is focused on therapeutic and prophylactic research. Other research issues are very important, including studies of early diagnostic techniques, behavioral research concerning reproductive choices, the role of breastfeeding in HIV transmission, HIV‐specific adolescent issues, and surrogate markers of disease progression.

Mother-to-Child Transmission of HIV

In December 2000, UNAIDS and the World Health Organization (WHO) shared their most recent grim statistics on HIV with the world health community. They estimated that there are 36.1 million adults and children living with HIV infection worldwide (1). Seventy percent of these infected individuals live in sub–Saharan Africa, where more than half of the HIV-infected adults are women. The percentages of female cases of HIV are estimated to range from 53% in Botswana and Nigeria to 58% in Rwanda and Niger (2). Furthermore, high HIV seroprevalence rates have been documented among African women of childbearing age (3). Some investigators have suggested and reported evidence that HIV-infected women have lower fertility rates than their uninfected counterparts (4). However, high rates of infection, especially among adolescent African women (5), assure the continuation of the pediatric HIV epidemic in Africa until Afro-centric strategies to prevent mother-to-child transmission (MTCT) of HIV are developed and effectively implemented. Of all HIV-infected children worldwide, 87% are estimated to live in Africa (1). A TIMING OF TRANSMISSION

796 DEVELOPMENTAL DELAY IN CHILDREN EXPOSED TO CHLORIDE DEFICIENT FORMULA

During 1978-1979, more than 20,000 infants may have been exposed to chloride-deficient formula (CDF). A number of these children were noted to suffer from severe metabolic alterations, principally hypochloremic metabolic alkalosis (HMA). The present study examined 21 children who were exposed to CDF and developed HMA. Pediatric records were reviewed, medical and feeding histories were obtained from the parents, and children were administered the Bayley Scales of Infant Development (BSID). The range of age at testing was 13 to 29 months (mean=23.2). The Bayley Mental Development Index (MDI) ranged from 67 to 127 (mean=98.5) Length of exclusive use of CDF without supplementation with solids or other milk/formula (LENEXC) had a significant negative correlation with MDI (r=-.55, p=.01). When length of exclusive use of CDF, age of onset of CDF use and age at testing were entered into a multiple regression analysis, LENEXC remained associated with MDI (R2=.39, p<.05). Sixteen of these children were re-examined at ages ranging from 40 to 51 months (mean=43.8) using the McCarthy Scales of Childrens Abilities. There was a significant negative correlation between LENEXC and the perceptual-performance scale (r=-.51, p<.05) and between LENEXC and the motor scale (r=-.52, p<.05). These data raise concern about the long-term outcome of these children.

Pregnancy outcomes among mothers infected with human immunodeficiency virus and uninfected control subjects

Pregnancy outcomes among mothers infected with human immunodellciency virus and uninfected control subjects Minkoff HL: Henderson C; Mendez H: Gail MH; Holman S; Willoughby A: Goedett JJ; Rubinstein A; Stratton P; Walsh JH; Landesman SH Department of Obstetrics and Gynecology, State University qj’ New York Health Science Center, Bos 24, 450 Clarkson Ave. Brooklyn. NY 11203-2098. USA AM J OBSTET GYNECOL 1990, l63/5 l(l598-1604) Between June 26, 1985. and Feb. 24, 1989, IO1 seropositive pregnant women and 129 seronegative pregnant women from the same prenatal clinics in Brooklyn and the Bronx were recruited into a prospective study of human immunodeficiency virus infection in pregnant women and their offspring. This report details the course of pregnancy and short-term neonatal outcomes of 91 seropositive women and 126 seronegative women who gave birth during the study period. Seropositive mothers were significantly more likely to have sexually transmitted diseases (17.6% vs 7.1%. p = 0.017) and medical complications (43.0% vs 25’%, p = 0.006) during pregnancy. No other obstetric complications (e.g. , chorioamnionitis, endometritis, toxemia, or placental problems) were associated with serologic status. After controlling for confounding variables (drug use, tobacco use, age of mother, and clinic), we found that the mother’s serologic status was not significantly associated with birth weight, gestational age, head circumference, or Apgar scores among live infants. For example, after adjustment on confounders we found that children born to seropositive mothers weighed about 7 gm more than children of seronegative mothers (95% confidence interval, ! 80 to 194 gm). We conclude that in this population human immunodeficiency virus infection has little demonstrable impact on the status at birth of live neonates.

Immunosuppression in pregnant women infected with human immunodeficiency virus

One hundred two pregnant women at high risk of infection with the human immunodeficiency virus (62 who were drug abusers and 40 of Haitian origin) were prospectively examined for immunologic changes during and after pregnancy. Among the 63 human immunodeficiency virus-negative women, levels of CD4+ (helper) cells fell to a nadir at 8 weeks before delivery and rose rapidly just before delivery. The level of CD8+ (cytotoxic/suppressor) cells rose slowly from midpregnancy to delivery. Among the 37 human immunodeficiency virus-positive pregnant women, levels of CD4+ cells fell during pregnancy (except for a transient weak increase just before delivery) and did not recover in the postpartum period. Levels of CD8+ cells were consistently higher in human immunodeficiency virus-positive than human immunodeficiency virus-negative women. Post partum the CD8+ cells in human immunodeficiency virus-negative women stabilized at delivery levels, whereas they increased greatly in human immunodeficiency virus-positive women. The loss of CD4+ cells in human immunodeficiency virus-positive women appeared to be faster during pregnancy than in the postpartum period. These data support the hypothesis that pregnancy may accelerate human immunodeficiency virus-induced depletion of CD4+ cells and increase the risk of acquired immunodeficiency syndrome.

Serious infections during pregnancy among women with advanced human immunodeficiency virus infection

Obstetrics and gynecology in the USSR Petrikovsky BM; Hoegsberg B Department of Obstetrics and Gynecology, State University of New York at Stony Brook, Stony Broke, NY II 794-8091. USA OBSTET. GYNECOL. 1990,75/l (128-130) Knowledge of Soviet obstetrics and gynecology has been mostly inaccessible to Western physicians. We share our experience regarding medical education and practice in the USSR. Medical education lasts 6 years and is followed by 2 years of postdoctorate training. Residency is limited to clinical obstetrics and gynecology. No formal subspecialty training exists. Research projects are funded and guided by the Health Ministry and Academy of Medical Science. Most articles are published in Russian and are therefore unknown to physicians in the West. Modern medical technology is not available in the practice of obstetrics and gynecology. Abortion remains the leading method of contraception. Perinatal and infant mortality in the USSR is higher than that in comparable Western countries.