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R W Steketee

Publications and source records attributed to R W Steketee.

At least 37 records · Page 2Linked to original sources

Timing of maternal-infant HIV transmission: associations between intrapartum factors and early polymerase chain reaction results. New York City Perinatal HIV Transmission Collaborative Study Group.

OBJECTIVE: To investigate the hypothesis that labour and delivery events, perinatal characteristics, and maternal factors are only associated with intrapartum HIV transmission, and not with intrauterine HIV transmission. METHODS: In the New York City Perinatal HIV Transmission Collaborative Study 276 infants of HIV-infected women were followed prospectively and had results of early polymerase chain reaction (PCR) tests available. Among infected children, intrauterine infection was presumed if HIV DNA was detected by PCR in samples collected from children aged < or = 3 days, and intrapartum infection was presumed if HIV DNA was not detected in these early samples. The proportion of infants with presumed intrauterine and intrapartum infections were compared by selected intrapartum, perinatal and maternal characteristics. RESULTS: Presumed intrapartum infection was found in 7% of infants delivered by Cesarean section and, among infants delivered vaginally, those with longer duration of membrane rupture (> 4 h) were significantly more likely to have presumed intrapartum HIV infection (22%) than those with shorter duration (9%; P = 0.02). There were no differences in presumed intrauterine HIV infection by mode of delivery or longer duration of membrane rupture. Infants born preterm and small for gestational age had significantly higher risks of presumed intrapartum infection, but only those who were small for gestational age had higher risks of intrauterine infection. CONCLUSION: Our results support the notion that selected intrapartum conditions, long duration of membrane rupture prior to delivery in particular, are independent risk factors for maternal-infant transmission, and suggest that preterm infants may be especially vulnerable to intrapartum HIV exposure.

Birth Weight↗

The effect of maternal viral load on the risk of perinatal transmission of HIV-1. New York City Perinatal HIV Transmission Collaborative Study Group.

OBJECTIVE: To determine the effect of maternal viral load at delivery on the risk of perinatal transmission of HIV-1. DESIGN: A nested case-control study within a prospectively followed cohort of HIV-1-infected pregnant women and their infants. SETTING: The multicenter New York City Perinatal HIV Transmission Collaborative Study. PARTICIPANTS: Fifty-one women who gave birth to HIV-1 infected infants were frequency-matched within CD4+ cell count quintiles with 54 non-transmitting mothers. MAIN OUTCOME MEASURES: Maternal quantity of HIV-1 viral RNA was assayed in plasma obtained near delivery using the nucleic acid sequence-based amplification assay system. RESULTS: Viral RNA was detected in 73 (70%) out of 105 women and the median viral load was 16,000 RNA copies/ml in transmitters and 6,600 in non-transmitters (P < 0.01). When adjusted for maternal CD4+ count near delivery, women with measurable viral load were nearly sixfold more likely to transmit HIV-1 than women with viral load below detection [adjusted odds ratio (AOR), 5.8; 95% confidence interval (CI), 2.2 15.5]. The odds ratio for perinatal transmission of log10 viral load, adjusted for CD4 count was 2.7 (95% CI, 1.5-5.1). When stratified by the stage of HIV-1 disease, the only group with significant association between log10 viral load and transmission were AIDS-free women with CD4+ count > 500 x 10(6)/l (AOR, 9.1; 95% CI, 2.6-31.5). CONCLUSIONS: High maternal viral load increases the likelihood of perinatal transmission of HIV-1 in women without AIDS and advanced immunosuppression. HIV-1 infected pregnant women without advanced disease, shown by others to have the lowest risk of perinatal transmission, may benefit the most from efforts to identify and decrease viral load at delivery.

Adult↗

Effect of maternal CD4+ cell count, acquired immunodeficiency syndrome, and viral load on disease progression in infants with perinatally acquired human immunodeficiency virus type 1 infection. New York City Perinatal HIV Transmission Collaborative Study Group.

Among a cohort of 152 infants perinatally infected with human immunodeficiency virus type 1, and their mothers, we correlated infant outcome with material CD4+ lymphocyte count and the presence of maternal acquired immunodeficiency syndrome near delivery. In a subset of 50 mother-infant pairs, we also correlated infant outcome with maternal quantitative viral burden as measured by the nucleic acid sequence based amplification system. We found that low maternal CD4+ cell count and high viral burden were associated with decreased time to category C disease or death in infants infected with human immunodeficiency virus type 1. In a multivariate analysis, high maternal viral load and maternal acquired immunodeficiency syndrome were independently associated with shorter time to category C disease or death in infants with human immunodeficiency virus type 1 infection. High viral load in pregnant women, independent of the presence of advanced maternal disease, appears to increase the risk of rapidly progressive disease in their infected offspring.

Acquired Immunodeficiency Syndrome↗

Early detection of perinatal human immunodeficiency virus (HIV) type 1 infection using HIV RNA amplification and detection. New York City Perinatal HIV Transmission Collaborative Study.

Early diagnosis of perinatally transmitted human immunodeficiency virus type 1 (HIV) infection can guide early interventions. HIV coculture and DNA polymerase chain reaction (DNA-PCR) detect few HIV-infected infants at birth and 90%-100% by age 3 months. Because extracellular HIV RNA may appear soon after infection, a plasma HIV RNA assay was compared with DNA-PCR for early detection of perinatally infected infants. Blood-draw specimens (108) obtained at the same time from 49 HIV-infected infants and 10 specimens from 8 uninfected infants were tested. HIV RNA and DNA-PCR positivity rates were 56% and 33%, respectively, in 36 specimens from 36 infants <28 days of age (binomial test, P = .001). Among 81 specimens obtained after age 14 days, 79 (98%) were positive by HIV RNA testing. No HIV-infected infant specimens were DNA-PCR-positive and HIV RNA-negative. All specimens from 8 uninfected infants were HIV RNA-negative. These results suggest that plasma HIV RNA was detectable earlier and more reliably than HIV DNA in perinatal infection.

Female↗

Vitamin A deficiency and maternal-infant transmissions of HIV in two metropolitan areas in the United States.

OBJECTIVE: To determine whether vitamin A deficiency is associated with maternal-infant HIV transmission among HIV-infected pregnant women in two United States cities. METHODS: Third trimester serum vitamin A levels were evaluated using high-performance liquid chromatography in 133 HIV-infected women who delivered livebirths during May 1986 to May 1994 and whose infants had known HIV infection status. RESULTS: Sixteen per cent (seven out of 44) of the transmitting mothers and 6% (five out of 89) of the non-transmitting mothers had severe vitamin A deficiency (< 0.70 mumol/l; P = 0.05). Maternal-infant transmission was also associated with prematurity < 37 weeks gestation (P = 0.02), and Cesarean section delivery (P = 0.04), CD4 percentage (P = 0.03) and marginally associated with duration of membrane rupture of > or = 4 h (P = 0.06) by univariate analysis. In a multivariate logistic regression model, severe vitamin A deficiency [adjusted odds ratio (AOR), 5.05; 95% confidence interval (CI), 1.20-21.24], Cesarean section delivery (AOR, 3.75; 95% CI, 1.10-12.87), and prematurity (AOR, 2.25; 95% CI, 1.22-4.13) were associated with transmission after adjusting for CD4+ percentage, and duration of membrane rupture. CONCLUSION: Increased risk of maternal-infant transmission was associated with severe vitamin A deficiency among non-breastfeeding women in these cohorts from the United States.

Adult↗

Longitudinal evaluation of severely anemic children in Kenya: the effect of transfusion on mortality and hematologic recovery.

OBJECTIVE: To determine the effect of transfusion on hematologic recovery and mortality among severely anemic children during and after hospitalization in rural Kenya. DESIGN: Prospective cohort. METHODS: We collected clinical and laboratory information on all severely anemic children (hemoglobin < 5.0 g/dl) and a 33% sample of children with hemoglobin < or = 5.0 g/dl who were admitted to the pediatric ward of a rural Kenyan hospital during a 6 month study period. Children were followed during hospitalization and at 4 and 8 weeks after admission. RESULTS: Overall, 303 (25%) of the 1223 hospitalized children had hemoglobin < 5.0 g/dl, 30% of whom died during the study period. Severely anemic children who were transfused had a higher mean hemoglobin level at discharge (9.0 g/dl) than non-transfused children (5.8 g/dl, P < 0.001) and maintained a higher mean hemoglobin during the 8-week follow-up period. However, the presence of malaria parasitemia on follow-up negated the benefit of transfusion on hematologic recovery at both 4- and 8-week visits (longitudinal linear model, least square means, P > 0.05). Transfusion was associated with improved survival among children with respiratory distress who received transfusions within the first 2 days of hospitalization. CONCLUSIONS: The use of transfusion can be improved by targeting use of blood to severely anemic children with cardiorespiratory compromise, improving immediate availability of blood, and treating severely anemic children with effective antimalarial therapy.

Adolescent↗

Cost-effectiveness of short-course zidovudine to prevent perinatal HIV type 1 infection in a sub-Saharan African Developing country setting.

OBJECTIVE: To evaluate the cost-effectiveness of a short-course zidovudine program to prevent perinatal transmission of human immunodeficiency virus (HIV) type 1 in sub-Saharan African country settings. DESIGN AND SETTING: Several clinical trials of short-course zidovudine during pregnancy for prevention of perinatal transmission of HIV are under way in developing countries in sub-Saharan Africa. A decision model was used to examine the cost-effectiveness of zidovudine programs in a hypothetical 1-year birth cohort in a sub-Saharan African setting from the perspective of the health care system and of society. A completed short course of zidovudine was assumed to reduce perinatal HIV transmission from 25% to 16.5%, approximately one half of the effect of the longer-course zidovudine. Estimates of program costs, lifetime HIV-related health care costs, and lost productivity costs were derived from the published literature and from preliminary data available from sites of planned clinical trials. Sensitivity analyses were conducted on all relevant parameters. MAIN OUTCOME MEASURES: Medical costs, lost productivity costs, program costs, cost savings, and incremental cost-effectiveness, expressed as cost per infant HIV infection prevented. RESULTS: The model estimated that a national zidovudine program in a setting with 12.5% HIV seroprevalence would reduce perinatal HIV incidence by 12% (4.9 infections per 1000 births). The costs to the health care system would be $3748 per infant HIV infection prevented. When productivity losses were included in the model, the cost decreases to $1115 per infant HIV infection prevented. The cost to implement a national zidovudine program including the cost of counseling, testing, and drugs, would be $2 million per 100,000 births or $20 per pregnant woman. In the base case, decreases in the cost of counseling and testing and increases in maternal HIV prevalence, zidovudine efficacy, and medical and lost productivity costs improved cost-effectiveness of the zidovudine program. CONCLUSIONS: Assuming demonstrable efficacy of short-course zidovudine prevention of perinatal HIV, a national perinatal HIV prevention program with zidovudine in most sub-Saharan African country settings would reduce the incidence of infant HIV infection and, in some settings, provide societal savings; however, substantial initial investment in such programs will be required. Where health care resources are limited, as in these regions, allocation of resources to a perinatal zidovudine program will need to be considered in the context of resources required for other pressing medical care needs.

Africa South of the Sahara↗

Comparability of treatment groups and risk factors for parasitemia at the first antenatal clinic visit in a study of malaria treatment and prevention in pregnancy in rural Malawi.

The problems of Plasmodium falciparum infection in pregnant women have been described in numerous sub-Saharan African countries, but the frequency of parasitemia at the first antenatal visit and risk factors for infection have not been fully investigated. During a prospective antimalarial treatment and prophylaxis trial in pregnant women in Malawi (three groups receiving a chloroquine regimen and one group receiving a mefloquine regimen), we examined women at their first antenatal clinic visit to evaluate these issues and to verify that subjects in the study treatment/prevention arms were similar. Among 4,127 women with enrollment blood smear results, 1,836 (44.5%) were parasitemic. The highest infection rates and densities were observed in primigravidas (66% infected, geometric mean parasite density [GMPD] = 1,588 parasites/mm3 of whole blood), followed by second pregnancies (46% infected, GMPD = 615 parasites/mm3) and subsequent pregnancies (29% infected, GMPD = 238 parasites/mm3), (P < 10(-6) for both infection prevalence and density, by chi-square test for trend). Significant risk factors for parasitemia at first antenatal clinic visit in a multivariate model included low gravidity, high transmission season, no use of prophylaxis before first antenatal clinic visit, young age (< 20 years), human immunodeficiency virus (HIV) infection, low hematocrit, short stature, and second trimester (compared with third trimester). Women in the different treatment arms of the study were generally similar in many characteristics; statistically significant differences, where present, were small. Targeting malaria control efforts to women in their first or second pregnancy and during the high transmission season will be an important strategy to reach most parasitemic women and minimize resource expenditure. Women infected with HIV had a 55% increased risk of parasitemia at their first antenatal clinic visit and may represent an additional important risk group whose numbers may be increasing and who may benefit from identification and management for malaria.

Adolescent↗

The problem of malaria and malaria control in pregnancy in sub-Saharan Africa.

Plasmodium falciparum infection in pregnant women frequently leads to placental infection and low birth weight (< 2,500 grams) of the infant, particularly in the areas of high malaria transmission found in sub-Saharan Africa. Low birth weight is widely known to be an important risk factor for early infant mortality. To reduce the risk that maternal infection poses to child survival, many antenatal clinic programs recommend and provide antimalarial chemoprophylaxis, often with chloroquine (CQ) as a recommended element for antenatal care. Prior to the 1980s, despite widespread advocacy for this intervention, little was known about the effect of this intervention strategy. As an introduction to the Mangochi Malaria Research Project, which examined the efficacy of several antimalarial regimens using CQ or mefloquine in pregnant women in Malawi, we describe the background of knowledge regarding malaria infection in pregnant African women and the important elements of an intervention and prevention strategy.

Africa South of the Sahara↗

Malaria parasite infection during pregnancy and at delivery in mother, placenta, and newborn: efficacy of chloroquine and mefloquine in rural Malawi.

Despite international recommendations to use malaria treatment and prevention in pregnant women in malaria-endemic areas, few studies have evaluated the efficacy of available antimalarial regimens. This issue is of particular concern in the face of spreading chloroquine (CQ)-resistance of Plasmodium falciparum in malarious areas of sub-Saharan Africa. In a prospective trial in rural Malawian pregnant women, we examined three regimens using CQ (including the existing national policy regimen) and one regimen using mefloquine (MQ). The efficacy of the regimens was determined by comparing rates of clearance of initial parasitemia; prevention of breakthrough infection; and parasitemia at delivery in maternal peripheral blood, placental blood, and in infant umbilical cord blood. Among 1,528 parasitemic women at enrollment, 281 (18.4%) had persistent infections; and among 1,852 initially aparasitemic women, 320 (17.3%) had breakthrough parasitemia on one or more follow-up visits. Compared with women on MQ, women on a CQ regimen were at significantly greater risk of persistent and breakthrough infection (odds ratios [OR] = 30.9 and 11.1, respectively, P < 10(-6)). Other significant risk factors for persistent and breakthrough infections in a multivariate model included first pregnancy; enrollment in the rainy or postrainy season; maternal age < or = 25 years; seropositivity to the human immunodeficiency virus (HIV) (persistent infections only); and no use of antimalarial prophylaxis before enrollment (breakthrough infections only). At delivery, compared with women on MQ, women on a CQ regimen were at significantly greater risk of peripheral, placental, or umbilical cord blood parasitemia (OR = 8.7, 7.4, and 4.1, respectively, P < 10(-6)). Additional risk factors for parasitemia at delivery in multivariate models included first pregnancy; delivery in the rainy or postrainy season; HIV-seropositivity; and maternal age < or = 25 years (risk for peripheral and placental blood parasitemia only). Maternal anemia (hematocrit < 30%) at enrollment or at delivery was not associated with persistent or breakthrough parasitemia or parasitemia at deliver in these multivariate models. While factors leading to increased malaria parasite exposure (high transmission seasons) and lowered or altered host immune response (low pregnancy number, young age, and HIV infection) are important risk factors for malaria in pregnant women, the use of an ineffective intervention (CQ in a setting with CQ-resistant parasites) was the most important determinant of P. falciparum parasitemia in these pregnant women. Strategies to reduce the impact of malaria in pregnant women must use efficacious interventions and may need to consider targeting the intervention to the most susceptible women during the seasons of high malaria exposure.

Adolescent↗

The effect of malaria and malaria prevention in pregnancy on offspring birthweight, prematurity, and intrauterine growth retardation in rural Malawi.

While there is broad evidence for the adverse effects of Plasmodium falciparum infection in pregnancy, and the World Health Organization recommends preventive strategies, there is markedly reduced efficacy in sub-Saharan Africa of the most widely available, affordable and used antimalarial drug for chemoprophylaxis-chloroquine (CQ). During 1987-1990, we studied pregnant women in an area of high malaria endemicity in rural Malawi to compare the efficacy of CQ (the drug recommended by national policy) with mefloquine (MQ, a relatively new and highly effective antimalarial) in preventing low birth weight (LBW) due to prematurity and intrauterine growth retardation (IUGR). Among 1,766 women monitored during at least their last six weeks of pregnancy with observed ingestion of their regimen and facility delivery of a live born singleton, their babies had a mean +/- SD birth weight of 2,905 +/- 461 gm and 16.8% had LBW. In a multivariate analysis, factors significantly associated with LBW included: first birth (odds ratio [OR] = 4.27), female infant (OR = 2.92), maternal human immunodeficiency virus infection (OR = 2.66), low maternal weight (OR = 1.95), and placental blood P. falciparum infection (OR = 1.71). Factors significantly associated with IUGR-LBW included first birth, female infant, low maternal weight, and placental malaria. Factors significantly associated with preterm-LBW included maternal syphilis infection, umbilical cord blood malaria, first birth, low maternal weight, and female infant. Use of an effective antimalarial (MQ) was protective against LBW through its effect on reducing placental and umbilical cord blood malaria infection. The proportion of LBW babies born to women on MQ (12.5% [parity-adjusted for the population of delivering women]) was significantly lower than the proportion born to women on CQ (15.5%; P = 0.05). Effective prevention of malaria in pregnant women in malaria-endemic settings may reduce the likelihood of LBW by 5-14%, and may reduce the amount of preventable LBW by more than 30%. When evaluating antenatal care programs, health policy makers must consider providing an effective preventive drug (either MQ or other drugs identified in additional studies, e.g., sulfa-pyrimethamine compounds) as a means to prevent low birth weight and its consequences.

Adolescent↗

Impairment of a pregnant woman's acquired ability to limit Plasmodium falciparum by infection with human immunodeficiency virus type-1.

In Africa, the human immunodeficiency virus (HIV) is the most serious emerging infection and Plasmodium falciparum malaria is one of the most prevalent infectious diseases. Both infections have serious consequences in pregnant women, their fetuses, and infants. We examined the association between HIV and P. falciparum in pregnant women enrolled in a malaria chemoprophylaxis study in rural Malawi. Pregnant women (n = 2,946) were enrolled at their first antenatal clinic visit (mean 5.6 months of pregnancy), placed on one of three chloroquine regimens, and followed through delivery. Plasmodium falciparum parasitemia was measured at enrollment, monthly thereafter, at delivery, and 2-6 months postpartum; placental and newborn (umbilical cord blood) infection was measured for hospital-delivered infants. Serum collected during pregnancy was tested for antibodies to HIV by enzyme-linked immunoassay with Western blot confirmation. Parasitemia was detected in 46% of 2,946 women at enrollment and 19.1% at delivery; HIV seroprevalence was 5.5%. The prevalence and geometric mean density (GMPD) of parasitemia at enrollment and at delivery were higher in HIV-seropositive(+) than in HIV-seronegative(-) women (at enrollment: 57% prevalence and a GMPD of 1,558 parasites/mm3 versus 44% and 670/mm3, respectively; P < 0.0001; and at delivery: 35% and 1,589/mm3 versus 18% and 373/mm3; P < 0.0005). Placental infection rates were higher in HIV(+) compared with HIV(-) women, (38% versus 23%; P < 0.0005). This association was strongest in multigravidas. Compared with infants born to HIV(-) women, newborns born to HIV(+) women had higher rates of umbilical cord blood parasitemia. Both HIV(+) and HIV(-) women had similar rates of parasitemia 2-6 months postpartum. The HIV infection diminishes a pregnant woman's capacity to control P. falciparum parasitemia and placental and newborn infection, the major determinants of the impact of P. falciparum on fetal growth and infant survival.

Adolescent↗

Malaria treatment and prevention in pregnancy: indications for use and adverse events associated with use of chloroquine or mefloquine.

In sub-Saharan Africa, women frequently report a variety of symptoms during pregnancy, some of which indicate possible illness. Given the adverse impact of malaria in pregnancy, these events may be important for at least two reasons: it may be possible to use reported fever illness as a determinant of which women need an antimalarial intervention, and, it is possible that adverse symptoms following the antimalarial intervention may be important determinants of continued adherence to the prevention regimen. In a cohort of pregnant women enrolled at first antenatal clinic visit in rural Malawi, we evaluated reported fever, determined parasitemia, and placed the women on antimalarial regimens containing chloroquine (CQ) or mefloquine (MQ). We then systematically evaluated reported symptoms following antimalarial drug use after initial therapeutic doses and subsequent prophylactic doses, and monitored women throughout their pregnancy and at delivery. Among 4,187 enrolled women, 1,048 (25%) reported at least one febrile episode during pregnancy before their first antenatal clinic visit. Factors associated with this reported fever included low parity, enrollment in the rainy season, human immunodeficiency virus seropositivity, use of antimalarial prophylaxis before enrollment, high socioeconomic status, normal (compared to low) maternal height and weight, and literacy. Fever before the first antenatal clinic visit was reported by 24.4% of parasitemic women and 25.4% of aparasitemic women; the sensitivity and specificity of fever to identify parasitemic women was 24% and 71%, respectively. In contrast, the sensitivity and specificity of first or second pregnancy to identify parasitemic women was 71% and 57%, respectively. Among women on a CQ or MQ regimen, approximately 60% reported side effects (e.g., itching, dizziness, and gastrointestinal disturbances) after a treatment dose and approximately 25% reported side effects after a prophylactic dose; rates and types of symptoms reported were similar in the CQ and MQ groups. Few serious side effects were observed and rates of fetal loss were low and similar in the groups. Reliance on fever illness will be wholly inadequate to identify parasitemic women; therefore, our findings support existing World Health Organization recommendations that presumptive treatment and prevention regimens should be offered to all pregnant women. When resources are inadequate to offer antimalarial prophylaxis to all pregnant women, women in their first or second pregnancy may be a more appropriate target group than pregnant women with reported fever. Education regarding expected minor side effects may reduce rates of poor compliance and improve the effectiveness of the prevention effort.

Adolescent↗

Transplacental transmission of Plasmodium falciparum in rural Malawi.

Malaria during pregnancy may result in fetal exposure to malaria when parasites are transmitted across the placenta. To document the rate of transplacental passage of Plasmodium falciparum and to identify the risk factors for congenitally acquired malaria infection, we examined umbilical cord blood for malaria parasites from 2,080 newborn infants born to mothers enrolled in a study of malaria prophylaxis during pregnancy. Cord blood parasitemia was detected in 140 (6.7%) newborn infants with a geometric mean density of 187 parasites/microliter (range 12-99, 752 parasites/microliter). The likelihood of umbilical cord blood parasitemia was closely linked to the parasite density of placental malaria infection and the density of maternal peripheral blood parasitemia at the time of delivery; all babies born to women with both placental and peripheral blood parasitemia densities > or = 10,000/microliter had cord blood parasitemia. In a multivariate logistic regression model, male sex, premature delivery, and placental and maternal peripheral blood malaria parasitemia were independently associated with a baby being born with umbilical cord blood parasitemia. In this setting, highly endemic for malaria, transplacental transmission of malaria from infected placentae occurs frequently and is directly related to the density of maternal malaria infection.

Adolescent↗

The effect of placental malaria infection on perinatal mortality in rural Malawi.

Perinatal deaths (fetal or infant deaths from the 28th week of pregnancy up to the seventh day after birth) occur as a result of adverse conditions during pregnancy, labor, and delivery, or in the first few days of life. Placental malaria infection is known to increase the risk of delivery of a low birth weight infant, thus, potentially increasing the risk of perinatal and infant mortality. To better understand the relationship among the adverse events in pregnancy, including placental malaria infection, adverse conditions in labor, and birth weight to perinatal mortality, we investigated the perinatal mortality among a cohort of infants born to rural Malawian women for whom placental malaria infection status and birth weight were documented. Among the 2,063 mother-singleton infant pairs, there were 111 perinatal deaths (53.8 perinatal deaths per 1,000 births). The risk of perinatal death increased as birth weight decreased. Risk factors identified for perinatal mortality among all infants excluding birth weight included abnormal delivery (cesarean section, breech, or vacuum extraction), a history of a late fetal or neonatal death in the most recent previous birth among multiparous women, reactive maternal syphilis serology, nulliparity, and low socioeconomic status. Placental malaria infection was not associated with increased perinatal mortality, but was associated with lower perinatal mortality among normal birth weight (> or = 2,500 g) infants (odds ratio = 0.35, 95% confidence interval = 0.14, 0.92). Interventions to address these risk factors could have a substantial impact on reducing perinatal mortality in this population.

Adolescent↗

Prospective assessment of mortality among a cohort of pregnant women in rural Malawi.

Maternal mortality has recently received attention as a neglected public health problem in many developing countries where mortality rates are estimated to be 8-200 times those in developed countries. Most maternal mortality estimates in sub-Saharan Africa have used retrospective methods because of the lack of large population-based studies. The Mangochi Malaria Research Project, a trial of antimalarial chemoprophylaxis in pregnant women, provided an opportunity to examine prospectively mortality among the study women. Among 4,053 monitored pregnant women, 27 women were known to have died during pregnancy, labor, delivery and the one-year follow-up period. Three women died during the antenatal period and 12 died within six weeks of delivery for an estimated maternal mortality rate of 370 per 100,000 pregnant women; this rate was consistent with rates reported from retrospective surveys in Malawi. Twelve women died between three and 10 months after delivery, and the mortality rate in this nonmaternal period was estimated to be 341 per 100,000. Mortality rates in the maternal and nonmaternal periods were surprisingly similar. Human immunodeficiency virus type-1 (HIV-1) infection and anemia were strongly associated with death in the nonmaternal period. Mortality among infants of mothers who died was 3.7 times higher than the rate of death among infants born to mothers who survived. This study highlights that for rural Malawian women, pregnancy and delivery are risky periods, that the death of the mother adversely affects the survival of her children, and that HIV and anemia are important contributors to nonmaternal mortality in reproductive-age women. Strategies to reduce mortality among women of child-bearing age in sub-Saharan Africa must focus on decreasing the complications of pregnancy and delivery, and address important preventable causes of death, such as anemia and HIV infection.

Cause of Death↗

Malaria infection in infancy in rural Malawi.

Malaria infection is thought to be relatively infrequent in infants less than 90 days of age in sub-Saharan Africa. In a rural area of Malawi with intense malaria transmission, we examined the occurrence of malaria infection during infancy and risk factors for parasitemia in the first three months of life in the cohort of infants delivered to women in the Mangochi Malaria Research Project. Among 3,915 liveborn singleton infants, 3,432 (87.7%) were seen at least once during infancy (first 12 months of life); of these, malaria blood smear results were available on 2,649 (77.2%). Overall, in a cross-sectional analysis, 23.3% of infants at three months of age were infected with Plasmodium falciparum; this proportion increased to more than 30% during the high transmission season. By the age of 10 months, 60-80% of the infants were infected, depending on the season. Geometric mean parasite density increased each month after two months of age and plateaued at seven months of age. In a life-table analysis, the median time to acquisition of a positive smear was 199 days. Factors independently associated with smear positivity at < 4 months of age included visit during high transmission season (adjusted odds ratio [AOR] = 4.1), maternal smear positivity at the same visit (AOR = 3.5), history of infant fever in the previous two weeks (AOR = 2.8), birth during the rainy season (AOR = 1.7), low socioeconomic status (AOR = 1.6), and low maternal education (AOR = 1.5). The specificity of a recent fever history for malaria infection in early infancy was high (> 70%). Intervention strategies to reduce the risk of early infant infection need to be targeted toward mothers of infants at high risk.

Age Factors↗