Maternal disease stage and child undernutrition in relation to mortality among children born to HIV-infected women in Tanzania

OBJECTIVE: To examine whether maternal HIV disease stage during pregnancy and child malnutrition are associated with child mortality. DESIGN: Prospective cohort study in Tanzania. METHODS: Indicators of disease stage were assessed for 939 HIV-infected women during pregnancy and at delivery, and children's anthropometric status was obtained at scheduled monthly clinic visits after delivery. Children were followed up for survival status until 24 months after birth. RESULTS: Advanced maternal HIV disease during pregnancy (CD4 count <350 vs. >or=350 cells/mm) was associated with increased risk of child mortality through 24 months of age (hazard ratio [HR] = 1.74, 95% confidence interval [CI]: 1.32 to 2.30). CD4 count <350 cells/mm was also associated with an increased risk of death among children who remained HIV-negative during follow-up (HR = 2.00, 95% CI: 1.36 to 2.94). Low maternal hemoglobin concentration and child undernutrition were related to an increased risk of mortality in this cohort of children. CONCLUSIONS: Low maternal CD4 cell count during pregnancy is related to increased risk of mortality in children born to HIV-infected women. Care and treatment for HIV disease, including highly active antiretroviral therapy to pregnant women, could improve child survival. Prevention and treatment of undernutrition in children remain critical interventions in settings with high HIV prevalence.     

Mortality in HIV-infected and uninfected children of HIV-infected and uninfected mothers in rural Uganda

OBJECTIVE: To estimate 2-year mortality rates in HIV-1-infected and uninfected infants born to HIV and HIV mothers. METHODS: Data are from a prospective study in rural Rakai District, Uganda. Infant HIV status (determined by polymerase chain reaction) was evaluated at 1 to 6 weeks postpartum and during breast-feeding, and maternal HIV viral load and CD4 levels were measured at the postpartum visit. Multivariate Cox proportional hazards models and Kaplan-Meier survival analysis were used to assess survival of infants by maternal and infant HIV status and by quartiles of viral load. Log-rank tests were used to test the equality of survival functions. RESULTS: Of the 4604 pregnant women, 16.9% were HIV, and the proportion of children infected was 20.9%. Median survival of HIV-infected infants was 23 months. Two-year child mortality rates were 128 of 1000 children born to HIV mothers, 165.5 of 1000 uninfected children born to HIV mothers, and 540.1 of 1000 HIV-infected children (P < 0.0001). Compared with children of HIV mothers, the hazard of child mortality was 2.04 (P < 0.001) if the mother was HIV and 3.78 (P < 0.001) if the infant was also infected. In the adjusted model, the highest quartiles of log10 HIV viral load in infants and mothers were associated with significantly increased hazard of child mortality (hazard ratio [HR] = 8.54 and HR = 2.50, respectively). Maternal CD4 counts <200 cells/mL were also significant predictors of child mortality (HR = 2.61). A total of 67.6% of HIV-infected children with viral loads above the median died by the age of 2 years and are in need of early antiretroviral therapy (ART). CONCLUSIONS: More than half of HIV-infected infants died at less than 2 years of age. Therefore, ART may need to be initiated earlier in HIV-infected African children.     

Effect of maternal HIV and malaria infection on pregnancy and perinatal outcome in Zimbabwe

OBJECTIVE: To investigate the effect of isolated or concomitant infection with malaria and HIV on pregnancy and neonatal outcome. METHODS: Data were collected on pregnant women admitted during the rainy seasons in the obstetric division of a district referral hospital in northern Zimbabwe in 2000 and 2001. The effects of malaria and HIV infection were determined by multivariate analysis. RESULTS: The prevalence of HIV seropositivity and symptomatic malaria in 986 pregnant women was 8.3% and 14.7%, respectively. HIV-infected women were more likely to develop malaria attacks during pregnancy than seronegative women (odds ratio [OR] = 3.96, 95% confidence interval (CI): 2.42-6.46). Malaria and HIV infections were associated with increased risk of stillbirth (OR = 4.74, 95% CI: 1.34-16.78) and preterm delivery (OR = 4.10, 95% CI: 2.17-7.75), respectively. They were independently associated with increased risk of low birth weight (malaria: OR = 10.09, 95% CI: 6.50-15.65; HIV: OR = 3.16, 95% CI: 1.80-5.54) and very low birth weight (malaria: OR = 5.04, 95% CI: 1.00-25.43; HIV: OR = 10.74, 95% CI: 2.12-54.41), low Apgar score (malaria: OR = 4.45, 95% CI: 1.42-13.94; HIV: OR = 5.94, 95% CI: 1.66-21.30), and fetal growth restriction (malaria: OR = 3.98, 95% CI: 2.51-6.30; HIV: OR = 4.07, 95% CI: 2.40-6.92). Dual infection with malaria and HIV was associated with increased risk of maternal, perinatal, and early infant death. CONCLUSIONS: Women with single HIV or malaria infection have a significantly increased risk of adverse outcomes of pregnancy and childbirth. Dual infection has additional detrimental effects on maternal and infant survival in an area where HIV and malaria coexist.     

Selenium status, pregnancy outcomes, and mother-to-child transmission of HIV-1

BACKGROUND: Among HIV-infected pregnant women, low selenium status may increase risk of mother-to-child transmission (MTCT) of HIV and poor pregnancy outcomes (low birthweight, small for gestational age, preterm birth, and fetal death) through several mechanisms, such as by promoting maternal HIV disease progression, viral shedding in the genital tract, and development of mastitis. However, there is no direct epidemiologic evidence on these relations among HIV-infected pregnant women. OBJECTIVE: To investigate the association between selenium status during pregnancy and pregnancy outcomes, MTCT of HIV, and child mortality. DESIGN: Baseline plasma selenium measurements from HIV-positive pregnant women (n = 670) were obtained between 12-27 weeks of gestation and mother-child pairs were followed prospectively until 24 months after delivery. RESULTS: Low plasma selenium levels were associated with increased risks of fetal death, child death, and HIV transmission through the intrapartum route. Low selenium status was not associated with risks of low birthweight or preterm birth but was associated with an apparently lower risk of small for gestational age. CONCLUSION: Adequate selenium status may be beneficial for some but not all pregnancy outcomes. Further studies are needed to better understand the role of selenium status in pregnancy outcomes, HIV transmission, and child health.     

Maternal viral load,CD4 cell count and vertical transmission of HIV-1

HIV load and CD4 cell numbers were measured among 95 HIV infected women during pregnancy in order to determine their value as prognostic markers for transmission of virus from mother to infant. Among the 94 live births, 13 children were infected with HIV, 69 were uninfected and 12 were of unknown infection status. HIV RNA levels, as measured by nucleic acid sequence based amplification, were significantly higher (P < 0.001) in women who transmitted virus than among those who did not transmit and maternal viral load was a stronger predictor of transmission than CD4 cell number. The predicted rate of transmission relative to maternal HIV RNA was 2% at 1,000 copies, 11% at 10,000 copies and 40% at 100,000 copies/ml. Little variation in viral load occurred during pregnancy and there was an association between viral load and prematurity, the mean gestation at delivery decreasing by 1.3 weeks for every 10-fold increase in maternal HIV RNA (P = 0.007). This study demonstrates that a high level of maternal HIV RNA is a risk factor for transmission of virus to the infant and maternal viral load is of more value as a prognostic marker for transmission risk than CD4 cell number. High viral load is also associated with premature delivery. Maternal viral load is therefore a useful marker on which to base management decisions during pregnancy. J. Med. Virol. 54:113–117, 1998. © 1998 Wiley-Liss,Inc.     

Wasting during pregnancy increases the risk of mother-to-child HIV-1 transmission

OBJECTIVES: To examine whether wasting during pregnancy, as measured by weight loss and low weight gain, is associated with increased mother-to-child transmission (MTCT) of HIV-1. METHODS: This was a cohort study in Dar es Salaam, Tanzania, among 957 HIV-1-infected pregnant women. Weight was measured at the first prenatal visit and every month thereafter until delivery. Weight loss was defined as a weekly rate of weight gain 0 and /=167 g/wk, weight loss during pregnancy was related to higher risk of intrauterine MTCT (adjusted relative risk [RR] = 2.32, 95% CI = 1.23-4.36, P = 0.009), HIV positive at birth or fetal death (RR = 2.13, 95% CI = 1.40-3.24, P = 0.0004), and HIV positive at birth or early neonatal death (RR = 1.96, 95% CI = 1.26-3.07, P = 0.003). The rate of weight gain during the 3rd trimester was inversely related to the risk of intrapartum/early breast-feeding transmission (adjusted P value, test for trend = 0.05). CONCLUSIONS: Weight loss during pregnancy increases the risk of early MTCT. Identifying causes of wasting during pregnancy may provide clues for new strategies to prevent MTCT.     

Rate,Predictors, and Consequences of Late Antenatal Booking in a National Cohort Study of Pregnant Women With HIV in Italy

Objective: To evaluate the prevalence and consequences of late antenatal booking (13 or more weeks gestation) in a national observational study of pregnant women with HIV. Methods: The clinical and demographic characteristics associated with late booking were evaluated in univariate analyses using the Mann-Whitney U test for quantitative data and the chi-square test for categorical data. The associations that were found were re-evaluated in multivariable logistic regression models. Main outcomes were preterm delivery, low birthweight, nonelective cesarean section, birth defects, undetectable (<50 copies/mL) HIV plasma viral load at third trimester, delivery complications, and gender-adjusted and gestational age-adjusted Z scores for birthweight. Results: Rate of late booking among 1,643 pregnancies was 32.9%. This condition was associated with younger age, African provenance, diagnosis of HIV during pregnancy, and less antiretroviral exposure. Undetectable HIV RNA at third trimester and preterm delivery were significantly more prevalent with earlier booking (67.1% vs 46.3%, P < .001, and 23.2% vs 17.6, P = .010, respectively), whereas complications of delivery were more common with late booking (8.2% vs 5.0%, P = .013). Multivariable analyses confirmed an independent role of late booking in predicting detectable HIV RNA at third trimester (adjusted odds ratio [AOR], 1.7; 95% CI, 1.3-2.3; P < .001) and delivery complications (AOR, 1.8; 95% CI, 1.2-2.8; P = .005). Conclusions: Late antenatal booking was associated with detectable HIV RNA in late pregnancy and with complications of delivery. Measures should be taken to ensure an earlier entry into antenatal care, particularly for African women, and to facilitate access to counselling and antenatal services. These measures can significantly improve pregnancy management and reduce morbidity and complications in pregnant women with HIV.     

Relationship between maternal serum vascular endothelial growth factor concentration in early pregnancy and fetal and placental growth.

Vascular endothelial growth factor (VEGF) has important effects on endothelial cells increasing cell proliferation, permeability and nitric oxide production; concentrations of VEGF in the maternal serum increase during the first 10 weeks of pregnancy. In this study, the relationship of maternal serum VEGF with maternal health during pregnancy and with fetal and placental size at mid-pregnancy and at term was investigated. Serum was obtained from 539 Caucasian women with singleton pregnancies between 8 and 20 weeks of pregnancy (mean 14 weeks). Total serum VEGF concentrations were measured by direct competitive radioimmunoassay. Fetal size and placental volume were measured by ultrasound between 16 and 20 weeks gestation. Birthweight, placental weight and anthropometric measurements of the baby were obtained after delivery. Serum VEGF concentrations were found to be higher in women with a lower weight before pregnancy (P = 0.01) and in those carrying a female fetus (P = 0.002). VEGF concentrations were positively correlated with placental volume (r = 0.17, P = 0.0001) but not with fetal size between 16 and 20 weeks gestation. Serum VEGF concentrations were positively correlated with both birthweight (r = 0.10, P = 0.02) and placental weight at delivery (r = 0.13, P = 0.003). The data presented support the view that VEGF may be one of the factors involved in mediating the maternal cardiovascular adaptation to pregnancy.     

Infant feeding practices of women in a perinatal HIV-1 prevention study in Nairobi, Kenya

OBJECTIVE: To determine feeding practices and nutritional status of infants born to HIV-1-infected women. METHODS: Feeding plans and practices were evaluated by questionnaires and focus group discussions. Infants were weighed at 1 and 6 weeks and tested for HIV-1 at 6 weeks. RESULTS: Of 128 women seen after delivery, 111 completed the study. Mothers who planned to breast feed were more likely to feed their infants as planned (86% vs. 55%; P < 0.001). Women opted to breast feed due to financial constraints, partner influence, and fear of losing confidentiality. Women who reported that their partners were willing to have HIV-1 testing were less likely to be breast feeding at 6 weeks (odds ratio [OR] = 0.3, 95% confidence interval [CI]: 0.1-0.8; P = 0.01). At 6 weeks, more infants were mixed fed (31% vs. 21%; P = 0.05) than at 1 week. Lower infant weight at 6 weeks was associated with not breast feeding (P = 0.001), HIV-1 infection (P = 0.05), birth weight <3000 g (P = 0.01), maternal employment (P = 0.02), and paying <$12.5 per month in house rent (among infants not breast fed; P = 0.05). CONCLUSIONS: Replacement feeding was difficult, particularly without partner support in HIV-1 testing. Mixed feeding was common and increased by 6 weeks. Mothers of low socioeconomic status who opt not to breast feed require support to avoid nutritional compromise of infants.     

The occurrence of vaginal infections among HIV-infected and high-risk HIV-uninfected women: longitudinal findings of the women's interagency HIV study

OBJECTIVES: To evaluate changes over time in rates of bacterial vaginosis (BV), trichomoniasis (TV), and yeast vaginitis (YV) among HIV-infected and similar HIV-uninfected women. METHODS: Two thousand fifty-six HIV-infected women and 554 HIV-uninfected women were evaluated semiannually from 1994 until March 2003 in a prospective cohort study. BV was diagnosed by Gram stain, TV by wet mount, and YV by symptoms with microscopically visible hyphae or positive culture. Trends were assessed using Poisson models. RESULTS: At baseline, BV was present in 42.8% and 47.0% of HIV-infected and uninfected women (P = 0.21), TV in 6.1% and 7.8% (P = 0.17), and YV in 10.0% and 3.8% (P < 0.001). Over time, rates of BV and TV decreased significantly in both groups, whereas rates of YV declined only among HIV-infected women. Risk of BV was not associated with HIV status, whereas HIV-infected women had a lower risk of TV. Highly active antiretroviral therapy (HAART) use was associated with decreased risk of all 3 infections. CONCLUSIONS:: Declines in BV, TV, and YV represent decreased morbidity for HIV-infected women and, potentially, decreased risk of transmission of HIV, because each has been associated with increased genital detection of HIV.     

Does exposure to antiretroviral therapy affect growth in the first 18 months of life in uninfected children born to HIV-infected women?

Uninfected children born to HIV-infected women are exposed antenatally to antiretroviral therapy, but it is uncertain whether this affects growth in early life. We analyzed weight, height, and occipitofrontal circumference (OFC) in 1912 children from a cohort study: 1304 had no or monotherapy exposure and 608 had combination therapy exposure. The mean z-score for birth weight or OFC did not differ by exposure category in 1513 term children or in 78 born at <34 weeks; the 266 born from 34 to 36 weeks were heavier if exposed to combination therapy. Children with combination therapy exposure born at 34 to 36 weeks reached the 25th centile for weight and OFC earlier than those not exposed born at 34 to 36 weeks (median: birth vs. 3 months; P = 0.003 [weight], P = 0.004 [OFC]), whereas children exposed to combination therapy born at <34 weeks reached the 25th centile for OFC later than those born at <34 weeks not exposed (median: 15 vs. 7 months; P = 0.004). Gestational age and maternal illicit drug use were strongly associated with growth, but the effect of combination therapy exposure was marginal (adjusted coefficients: weight, -0.10 [P = 0.019]; height, -0.12 [P = 0.008]; and OFC, -0.14 [P = 0.001]). Although the effect of combination therapy exposure is minimal, long-term monitoring of these children is important.     

Maternal early second trimester pregnancy weight in relation to birth outcome among Bengalee Hindus of Kolkata, India

OBJECTIVE: The study examined to what degree maternal early second trimester pregnancy weight is useful and efficient in predicting birth outcome of Bengalee women. SUBJECTS AND METHODS: The cross-sectional retrospective study was conducted in a government general hospital in South Kolkata, India. This hospital serves the needs of people belonging to lower and lower middle class socio-economic groups. Data were collected by one-to-one interview for confirmation of age, history of last menstrual period (LMP) including medical disorders. Mother's weight was recorded at 14-18 weeks of pregnancy from the history of LMP. Birth weight was measured within 24h of delivery and gestational age was assessed by Ballard's method using newborn physical and neurological maturity scoring. Of the 331 Bengalees, 295 mother-baby pairs met the recruitment criteria and were included in this study. RESULT: Mean +/- SD maternal early second trimester pregnancy weight and birth weight were 45.9+/-7.0kg and 2612+/-371g, respectively. The difference in mean weight (3.74kg) between mothers who delivered low birth weight (LBW) and normal birth weight (NBW) babies was statistically significant (t = 4.497, p < 0.001). Overall, the prevalence of LBW was nearly 34%. A higher incidence of LBW and lower mean birth weight was observed in first quartile or low weight (< or =40 kg) mothers. The rate of LBW decreased (chi2 =14.47, p<0.01) and mean birth weight increased significantly with increasing maternal weight (F=9.218, p<0.001). Risk ratio (RR) for LBW, intrauterine growth retardation (IUGR) and preterm birth in low weight (first quartile or <40.0 kg) mothers were 2.72 (95% confidence interval (CI): 1.45-5.10), 3.54 (95% CI: 1.17-10.74) and 1.97 (95% CI: 0.56-6.90), respectively, compared with heavier (>50.0kg) mothers. Finally, the present data showed that the maternal weight of <46.0 kg is the best cut-off for detecting LBW with 66% sensitivity and 75% negative predictive power. CONCLUSION: The findings suggest a positive association between maternal early second trimester pregnancy weight and birth outcome. The present study provided an efficient cut-off point for detecting LBW. Antenatal caregivers in health institutions and community health workers in the field can use this cut-off value for screening pregnant women at early second trimester.     

The use of viral culture and p24 antigen testing to diagnose human immunodeficiency virus infection in neonates. The HIV Infection in Newborns French Collaborative Study Group.

BACKGROUND. Early diagnosis of human immunodeficiency virus (HIV) infection in infants born to infected mothers is important for the infants' medical care, but the presence of maternal antibodies makes serologic tests uninformative. METHODS. In a cohort study of 181 infants born to HIV-infected mothers, we assessed the diagnostic value of HIV viral culture and testing for the presence of p24 antigen. The infants were tested at birth, again during the first 3 months, then followed and tested at the age of at least 18 months. RESULTS. Of the 181 infants, 3 died of HIV infection and 37 were seropositive after the age of 18 months. Viral cultures at birth were positive in 19 of the 40 infected infants and in none of the uninfected infants, yielding a sensitivity of 48 percent (95 percent confidence interval, 32 to 63 percent) and a specificity of 100 percent (95 percent confidence interval, 97 to 100 percent). By the age of three months, 30 of the 40 infants (75 percent) had positive cultures; again, there were no false positive results among the infants who were tested a second time, of the 141 who remained uninfected. The sensitivity of testing for p24 antigen at birth was only 18 percent, with a specificity of 100 percent. The presence of p24 antigen at birth was associated with the development of early and severe HIV-related disease (P less than 0.04). CONCLUSIONS. Viral culture at birth can correctly identify about half of newborns with HIV infection. The fact that this usually sensitive technique fails to identify about half the ultimately infected neonates suggests that vertical transmission of HIV may occur late in pregnancy or during delivery.     

Kaposi sarcoma-associated herpesvirus serum DNA and antibodies not associated with subsequent non-Hodgkin lymphoma risk

Our objective was to analyze, in formula-fed infants, correlates of HIV mother-to-child transmission, including cytomegalovirus (CMV) infection. HIV-infected infants were matched with HIV uninfected by maternal HIV RNA in a case-control design. Infant CMV infection was determined by CMV IgG at 18 months and timed by earlier CMV IgM or CMV DNA. Correlations were assessed using logistic regression. In utero HIV infection was independently associated with congenital CMV infection (P = 0.01), intrapartum HIV infection with congenital-plus-intrapartum/neonatal CMV infection (P = 0.01), and overall HIV with overall CMV infection (P = 0.001), and prematurity (P = 0.004). Congenital and acquired CMV infections are strong independent correlates of mother-to-child HIV transmission.     

Maternal Schistosomiasis japonica is associated with maternal, placental, and fetal inflammation

Schistosomes infect ～40 million women of childbearing age and result in the elaboration of proinflammatory cytokines that have been implicated in fetal growth restriction. In murine models and two observational studies in humans, schistosome infection during pregnancy was associated with reduced birth weight, although a recent treatment trial in Schistosoma mansoni did not detect this association. We conducted an observational study among 99 pregnant women living in an area of Schistosoma japonicum endemicity in the Philippines. We enrolled women at 32 weeks gestation and measured S. japonicum and geohelminth infection intensity. We collected maternal peripheral blood at 32 weeks gestation and placental and cord blood at delivery to assess inflammatory status. At delivery, we collected a placental-tissue sample and measured birth weight. In multivariate models adjusted for geohelminths, maternal schistosomiasis was associated with increased levels of inflammatory cytokines in maternal peripheral (tumor necrosis factor alpha [TNF-α] and interleukin 10 [IL-10]), placental (TNF-α, IL-6, TNF-α receptor II [RII], and IL-1β), and cord (IL-1β and TNF-α RII) blood, as well as acute subchorionitis and increased TNF-α production by syncytiotrophoblasts assessed by immunohistochemistry (all P < 0.05). After adjusting for confounders, placental IL-1β, and TNF-α production by syncytiotrophoblasts was independently associated with decreased birth weight (both P < 0.05). Our data indicate that maternal schistosomiasis results in a proinflammatory signature that is detectable in maternal, placental, and fetal compartments, and a subset of these responses are associated with decreased birth weight. This potential mechanistic link between maternal schistosomiasis and poor birth outcomes will contribute to the debate regarding treatment of maternal schistosome infections.     

Serum ovalbumin-specific immunoglobulin G responses during pregnancy reflect maternal intake of dietary egg and relate to the development of allergy in early infancy

BACKGROUND: The value of allergen elimination diets during pregnancy for primary prevention of infant allergy has been questioned. However, dietary compliance may influence effectiveness. OBJECTIVES: To monitor egg intake during a randomized controlled trial of egg avoidance throughout pregnancy and lactation by serial measurements of serum ovalbumin (OVA) IgG concentration in conjunction with dietary diary record and also, to analyse specific IgG concentrations at birth in relation to infant allergic outcome. METHODS: Pregnant women, with personal or partner atopy, were randomized to complete dietary egg exclusion or an unmodified healthy diet before 20 weeks gestation. The infants were evaluated for atopy at 6 months of age. Serum food-specific IgG concentrations were determined by ELISA in maternal samples collected at study recruitment and during labour, and in infant samples at birth (umbilical cord). RESULTS: Serum-specific IgG to OVA, but not the unrelated allergen, cow's milk beta-lactoglobulin, decreased over pregnancy in egg-avoiding women only (P<0.001). Cord OVA IgG concentration correlated with maternal IgG at delivery (r=0.944; P<0.001), and for infants born to atopic women, cord concentration was higher than that of their mother's (P<0.001). Infants with the lowest and highest cord IgG concentrations were the least likely, and those with mid-range concentrations were the most likely, to be atopic by 6 months of age (P=0.008). CONCLUSION: Serum OVA IgG concentration reflects egg consumption, thereby indicating dietary allergen doses to which the developing immune system might be exposed. Trans-placental maternal IgG must be considered among early life factors that regulate infant atopic programming.     

Elevated Amniotic Fluid Interleukin-6 Levels During the Early Second Trimester Are Associated With Greater Risk of Subsequent Preterm Delivery

PROBLEM: Subclinical intra-amniotic infection is often associated with preterm delivery and may precede it by several weeks. We tested the hypothesis that Interleukin-6 (IL-6) may be elevated in the midtrimester amniotic fluid of pregnancies destined to deliver preterm. METHODS: A historical cohort study was designed to compare the amniotic fluid (AF) concentrations of IL-6 at 14–20 weeks in a group of women subsequently delivering at ≤ 34 weeks (n = 13) with those of women delivering at term (n = 166). Included were singleton gestations with no evidence of fetal structural or chromosomal abnormalities, or maternal conditions known to be associated with preterm delivery (n = 179). Levels of IL-6 were measured by immunoassay and correlated with demographic and pregnancy outcome information. Statistical analysis included correlation, one-way ANOVA after log-transformation, contingency tables, logistic regression, and receiver operator characteristic (ROC) curve analysis. RESULTS: There was an inverse correlation between AF IL-6 levels at 15–20 weeks and gestational age at delivery (r = ?0.16, P = 0.03). Women delivering at ≤ 34 weeks had significantly higher median AF IL-6 levels (570 pg/ml versus 330 pg/ml, P < 0.0001), rate of African American race (50% versus 12%, P = 0.004), and of infants with birth weights < 10th centile (31% versus 7%, P = 0.02) than women delivering at ≥ 37 weeks. Logistic regression analysis showed that IL-6 was independently associated with PTD at ≤ 34 weeks after controlling for race and birth weight centiles (P = 0.039). CONCLUSIONS: AF IL-6 at 15–20 weeks can identify patients at risk for PTD at ≤ 34 weeks, suggesting that a portion of PTD cases have inciting events that take place during the early second trimester. CAPSULE: Midtrimester amniotic fluid IL-6 concentrations are significantly higher in women subsequently delivering preterm at ≤34 weeks compared with those delivering at term.     

Mortality during the first 24 months after delivery in relation to CD4 T-lymphocyte levels and viral load in a cohort of breast-feeding HIV-1-infected women in Dar es Salaam, Tanzania

The objective of this study was to analyze the mortality during the first 24 months after delivery in relation to CD4 T-lymphocyte levels and viral load at enrollment (36 weeks of gestation) in a cohort of HIV-1-seropositive breast-feeding women at the Dar es Salaam site of the multicenter Petra trial (a mother-to-child HIV-1 transmission intervention trial using antiretroviral therapy). Antiretroviral treatment was not available in this setting apart from the short treatment given within the trial around delivery to prevent mother-to-child transmission of HIV. T-lymphocyte subsets were determined by flow cytometry. Plasma HIV-1 RNA was quantified by the Amplicor HIV-1 RNA Monitor v 1.5 assay. Mortality after delivery was analyzed using the life-table technique and Cox regression. The analysis included 266 mothers. The CD4 cell counts at enrollment were <200 cells/mm in 14.5% of the mothers. The viral load at enrollment was >100,000 RNA copies/mL in 33.6% of the mothers. The mortality 24 months after delivery was 6.7% (95% CI = 3.1-10.1%). The mortality 24 months after delivery was 29.9% (95% CI = 13.1-46.9%) for mothers with <200 CD4 cells/mm at enrollment, 3.3% (95% CI = 0-6.6%) for mothers with 200-499 CD4 cells/mm, 2.9% (95% CI = 0-7.1%) for mothers with >500 CD4 cells/mm (P = 0.0000), 15.0% (95% CI = 6.6-23.4%) for mothers with viral load >100,000 copies/mL at enrollment, and 2.8% (95% CI = 0-5.6%) for mothers with viral load <100,000 copies/mL (P = 0.0000). In the multivariate analysis CD4 cell counts and viral load were both independent risk factors for mortality (P < 0.001 and P = 0.004, respectively). In conclusion, the mortality was high among women with severe immunosuppression or high viral load at enrollment, but not in the rest of the women. CD4 lymphocyte count in late pregnancy was a better predictor of death within 2 years than was viral load. The results support the World Health Organization recommendation to initiate antiretroviral treatment in resource-limited settings in HIV-1-infected adults with CD4 cell counts <200/mm and show that this is appropriate also among perinatal women.