Influence of inflammation as measured by alpha-1-acid glycoprotein on iron status indicators among HIV-positive postpartum Zimbabwean women.

OBJECTIVES: The acute phase response (APR) influences indicators of iron status. A recent WHO/CDC consultation recommended concurrent measurement of alpha-1-acid-glycoprotein (AGP) in surveys to control for the APR, and aid in interpreting iron status. They proposed further exploratory analyses using AGP. We examined whether the APR (measured by AGP) influences the expected relationships between iron status indicators in an HIV-infected population. SUBJECTS: We measured hemoglobin (Hb), serum ferritin (SF), transferrin receptor (TfR), erythropoietin (EPO) and AGP in a cross-sectional survey of 643 HIV-positive Zimbabwean women. RESULTS: SF was significantly higher in APR-positive (AGP>1 g/l) women (P<0.001), in whom there was no association between SF and Hb. TfR was inversely associated with Hb, in both APR-positive and APR-negative women (P<0.001). However, among anemic women (Hb<110 g/l), APR-positive women had marginally lower TfR concentrations (P=0.053). There was no difference in EPO response to decreasing Hb among APR-positive and APR-negative women. CONCLUSIONS: AGP captured the influence of the APR on iron indicators and their relationships with each other. The APR influenced SF and its relationship with Hb as expected. TfR behaved unexpectedly. Although TfR has been promoted as an iron indicator that is uninfluenced by the APR, TfR concentrations were depressed among anemic APR-positive women. Because TfR reflects iron deficiency and erythropoietic activity, pro-inflammatory cytokines associated with the APR may be inhibiting erythropoiesis, which is reflected by lower TfR concentrations. We support the WHO/CDC recommendation that AGP is a useful indicator to assess the influence of the APR on iron status indicators.

Elevated iron stores are associated with HIV disease severity and mortality among postpartum women in Zimbabwe.

OBJECTIVES: The relationship between Fe status and HIV infection is complex and poorly understood. While anaemia is a major complication of HIV infection, higher Fe stores may be associated with disease progression. There is limited and conflicting data available from Africa. DESIGN: Cross-sectional and prospective cohort study. SETTING, SUBJECTS AND METHODS: We examined the association between postpartum Fe status (Hb, serum ferritin (SF) and transferrin receptor (TfR)) and viral load (VL) and HIV-related mortality in 643 HIV-positive Zimbabwean women over a period of 12 months. RESULTS: In non-anaemic women a log10 increase in SF was associated with a 2.3-fold increase in VL (P = 0.019); this association was absent in anaemic women. In prospective analyses, a log10 increase in SF was associated with a 4-fold increase in mortality by 12 months (P = 0.002). Hb was negatively associated with VL (P = 0.001) and mortality (P = 0.047). The adverse associations between SF and both VL and mortality were found at SF concentrations > 45 microg/l (P < 0.05). Controlling for alpha1 acid glycoprotein, a marker of inflammation, attenuated the association between both SF and VL and mortality, but these remained significant. CONCLUSIONS: These results are consistent with the hypothesis that high Fe stores have adverse consequences in HIV infection. If adverse consequences are real, our data suggest that they occur at SF concentrations exceeding those consistent with adequate Fe nutriture.

Adoption of safer infant feeding and postpartum sexual practices and their relationship to maternal HIV status and risk of acquiring HIV in Zimbabwe.

OBJECTIVE: To examine the relationships between maternal knowledge and concern about HIV status, adoption of preventive practices and risk of acquiring HIV in Zimbabwe. METHODS: Knowledge and behavioural data were collected via interview from 2595 mothers enrolled in ZVITAMBO, a randomized trial of postpartum vitamin A supplementation that also offered education on safer infant feeding and sexual practices. Mothers were tested for HIV at delivery; those uninfected at baseline were retested during study follow-up. Logistic regression methods were used to identify variables associated with adoption of preventive behaviours and, for HIV-negative mothers, their relationship to risk of acquiring HIV post-delivery. RESULTS: A total of 518 mothers (20%) reported practicing safer sex and 289 mothers (11%) reported modifying their feeding behaviour because of HIV. Fear of transmitting HIV (50.4%) and protecting the baby's health (30.9%) were the most frequently cited reasons for behaviour change. Forty-nine HIV-negative mothers acquired HIV during the first postpartum year. After taking into account other significant covariates, mothers who were concerned about their own HIV status were 1.9 times more likely (95% CI: 1.05-3.52; P = 0.03), and those reporting safer sex practices were 58% less likely to become infected (adjusted odds ratio: 0.42; 95% CI: 0.17-1.04; P = 0.06). Married women who reported practicing abstinence to prevent HIV were 3.2 times more likely to become infected than non-abstaining mothers (P = 0.01), while there were no new HIV infections among abstaining single mothers. CONCLUSIONS: Greater emphasis should be given to safer sex practices among women who test negative in mother-to-child HIV prevention programmes.

HIV-1 and HIV-2 prevalence and associated risk factors among postnatal women in Harare, Zimbabwe.

Studies of antenatal women form the predominant source of data on HIV-1 prevalence in Africa. Identifying factors associated with prevalent HIV is important in targeting diagnostic services and care. Between November 1997 and January 2000, 14,110 postnatal women from Harare, Zimbabwe were tested by ELISAs reactive to both HIV-1 and HIV-2; a subset of positive samples was confirmed with assays specific for HIV-1 and HIV-2. Baseline characteristics were elicited and modelled to identify risk factors for prevalent HIV infection. HIV-1 and HIV-2 prevalences were 32.0% (95% CI 31.2-32.8) and 1.3% (95% CI 1.1-1.5), respectively; 4% of HIV-1-positive and 99% of HIV-2-positive women were co-infected. HIV-1 prevalence increased from 0% among 14-year-olds to >45% among women aged 29-31 years, then fell to <20% among those aged>40 years. In multivariate analyses, prevalence increased with parity, was lower in married women than in single women, divorcees and widows, and higher in women with the lowest incomes and those professing no religion. Adjusted HIV-1 prevalence increased during 1998 and decreased during 1999. Age modified the effects of parity, home ownership and parental education. Among older women, prevalence was greater for women who were not homeowners. Among younger women, prevalence increased with parity and low parental education. None of these factors distinguished women co-infected with HIV-2 from those infected with HIV-1 alone. Prevalent HIV-1 infection is associated with financial insecurity and weak psychosocial support. The ZVITAMBO study apparently spanned the peak of the HIV-1 epidemic among reproductive women in Harare.

Changing stillbirth rates: quality of care or quality of patients?

OBJECTIVES: To explain the U-shaped curve of stillbirth rates (SBR) in Harare. DESIGN: A retrospective descriptive study. SETTING: Greater Harare Maternity Unit SUBJECTS: A 15pc (approx.) sample of deliveries recorded in Labour Ward registers in 1979, 1984 and 1989. MAIN OUTCOME MEASURE: Stillbirth or livebirth. RESULTS: Some changes over the three years (e.g. proportion of primipara) indicate that obstetric "riskiness" of the population changed in a way which could explain the changes in SBR. CONCLUSIONS: However SBR's of large babies (birth weight 2,500 g to 4,499 g) increased and decreased over the years implying that changes in quality of care may also have contributed to the changes in SBR.

PIP: The perinatal mortality rate at Zimbabwe's Greater Harare Maternity Unit has demonstrated a "U"-shaped curve since independence, from 40/1000 total births in 1980 to 35/1000 in 1984 and 50/1000 in 1991. To determine whether this trend reflects changes in the quality of perinatal care or changes in the obstetric risk level of the population, a retrospective review was conducted of a 15% sample of deliveries at the maternity unit and all 10 Harare City Maternity Clinics in 1979 (3431 cases), 1984 (4913 cases), and 1989 (4567 cases). The perinatal mortality rates for these years were 40, 34, and 47/1000 live births, respectively. The stillbirth rates were 32, 26, and 32/1000, respectively. For large babies (2500-4499 gm birth weight), these rates were 12.3, 9.2, and 13.4/1000, respectively. Maternal age remained unchanged in the 3 periods; however, there were significantly fewer primiparae and multiple births in 1984. The study was limited by a lack of data in the records on risk factors such as human immunodeficiency virus and social class. The changes in outcome for large babies implies that the quality of perinatal care improved until 1984, then declined.

Perinatal mortality statistics in Harare 1980-1989.

Perinatal and neonatal mortality rates, in the Greater Harare Maternity Unit, which showed a modest decline from 1980 to 1985, have rise dramatically since then. Half of the rise in neonatal mortality rate is due to increased numbers and an increased mortality rate in babies of birth weight less than 1001g. There is also an increase in the numbers of deaths of large babies. There is a strong case for a broad-based on-going enquiry into the reasons for such changes.

PIP: Physicians used birth data on all neonatal and fetal deaths between 1980-89 submitted by the City Health Department, Harare Maternity Hospital, and 10 Harare City Clinics to determine various perinatal mortality rates. all the rates fell in the beginning of the 1980s: neonatal mortality rate (NNMR) 17-15 (1980-85), perinatal mortality rate (PMR) 40-35 (1980-85), fetal death rate (FDR) 21-20 (1983-85), and PMR for booked patients (bPMR) 26-24 (1981-85). Between 1986-89, however, all the rates increased; NNMR 19-23, PMR 41-47, FDR 24-26, and bPMR 25-38. There was a 53% rise in the NNMR and a 30% rise in the PMR. Deaths among neonates 1000gm accounted for 50% of the increase in NNMR. Prematurity was responsible for these deaths. They constituted the birth category with the most considerable increase in the proportion of deaths among all births after 1985 (3.5-8/1000 live births). In 1985, out of about 130 total births of neonates weighing 1000gm 45 infants survived compared with 20 out of about 235 such births in 1987. Deaths among neonates 2500gm increased steadily after 1985 (4-6) and were responsible for 25% of the increase in the NNMR. The major cause of death among the large neonates was birth asphyxia. The physicians proposed 2 testable hypotheses for the increases: demographic changes in mothers and rising prevalence of HIV infection. Other possible reasons included inadequate number of midwives and anesthetists, lack of electronic fetal heart rate monitors, and poor morale among nurses and junior medical staff. The physicians recommended that a broad-base investigation or a series of investigations into the reasons for these increases begin soon, e.g., the creation of a National Perinatal Epidemiology Unit and community-base studies. Data should include births at private maternity clinics, births assisted by traditional birth attendants, and home births.

Neonatal surgery in Harare Hospital.

The records of newborn babies with surgical conditions seen at Harare Hospital in 1988 were reviewed. Survival rates for the commonest major conditions, oesophageal atresia with tracheo-oesophageal fistula, small bowel atresia and gastroschisis, were respectively 20 percent, 50 percent and 0 percent. Avoidable or unsatisfactory factors were encountered during the hospital course of 54 percent of all babies and 76 percent of those who died. Suggestions are made for improving the outcome for babies with neonatal surgical conditions.

The obstetric management of non-immunological hydrops.

During the past 8 years, non-Rhesus hydrops has been observed in 31 pregnancies extending beyond 28 weeks gestation. Only three of the babies survived. Antenatal diagnosis is possible by ultrasound examination and although 27 of our patients had at least one indication for this procedure, only 22 were so investigated and in 13, fetal hydrops was demonstrated. Twenty-three were delivered before 36 weeks gestation, 10 by caesarean section of whom none survived; 16 babies were stillborn. Fourteen infants had major cardiovascular anomalies and six had other major malformations. In five infants, infection was thought to be causally related to fetal hydrops and in only four could no cause for the hydrops be found. In five pregnancies the cause of hydrops was discovered antenatally; this influenced subsequent management and two of the five survived. The unexpected appearance of a very abnormal fetal heart rate pattern requires the exclusion of fetal anomaly and non-immunological hydrops. When a diagnosis of non-immune hydrops is made its underlying cause should be sought without delay so that specific treatment may be instituted in the few cases where this is appropriate. A high incidence of complications of the third stage of labour should be anticipated. Subsequent pregnancies are likely to be normal.

Non-immunologic hydrops fetalis: a review of 27 cases.

Twenty seven babies with severe non-haemolytic hydrops fetalis were born during a 7 1/4 year period (1/1400 total births). Thirteen were live born and admitted to the intensive care nursery, but only three survived. The survivors differed from those live born infants who died in the neonatal period in that the cause of the hydrops was discovered antenatally, their serum concentrations of total protein and albumin were normal, and they had no structural anomaly. A scheme of investigation of the severely hydropic fetus in the antenatal period is outlined and the role of active obstetric management is evaluated.