Post-neonatal mortality, morbidity, and developmental outcome after ultrasound-dated preterm birth in rural Malawi: a community-based cohort study.

BACKGROUND: Preterm birth is considered to be associated with an estimated 27% of neonatal deaths, the majority in resource-poor countries where rates of prematurity are high. There is no information on medium term outcomes after accurately determined preterm birth in such settings. METHODS AND FINDINGS: This community-based stratified cohort study conducted between May-December 2006 in Southern Malawi followed up 840 post-neonatal infants born to mothers who had received antenatal antibiotic prophylaxis/placebo in an attempt to reduce rates of preterm birth (APPLe trial ISRCTN84023116). Gestational age at delivery was based on ultrasound measurement of fetal bi-parietal diameter in early-mid pregnancy. 247 infants born before 37 wk gestation and 593 term infants were assessed at 12, 18, or 24 months. We assessed survival (death), morbidity (reported by carer, admissions, out-patient attendance), growth (weight and height), and development (Ten Question Questionnaire [TQQ] and Malawi Developmental Assessment Tool [MDAT]). Preterm infants were at significantly greater risk of death (hazard ratio 1.79, 95% CI 1.09-2.95). Surviving preterm infants were more likely to be underweight (weight-for-age z score; p<0.001) or wasted (weight-for-length z score; p<0.01) with no effect of gestational age at delivery. Preterm infants more often screened positively for disability on the Ten Question Questionnaire (p = 0.002). They also had higher rates of developmental delay on the MDAT at 18 months (p = 0.009), with gestational age at delivery (p = 0.01) increasing this likelihood. Morbidity-visits to a health centre (93%) and admissions to hospital (22%)-was similar for both groups. CONCLUSIONS: During the first 2 years of life, infants who are born preterm in resource poor countries, continue to be at a disadvantage in terms of mortality, growth, and development. In addition to interventions in the immediate neonatal period, a refocus on early childhood is needed to improve outcomes for infants born preterm in low-income settings.

Group B Streptococcus and HIV infection in pregnant women, Malawi, 2008-2010.

To determine whether an association exists between group B streptococcus carriage and HIV infection, we recruited 1,857 pregnant women (21.7% HIV positive) from Queen Elizabeth Central Hospital, Blantyre, Malawi. Overall, group B streptococcus carriage was 21.2% and did not differ by HIV status. However, carriage was increased among HIV-positive women with higher CD4 counts.

Considerations in using US-based laboratory toxicity tables to evaluate laboratory toxicities among healthy malawian and Ugandan infants.

OBJECTIVES: To determine normal hematologic and selected blood chemistry values among healthy, full-term, non-HIV-exposed infants in Uganda and Malawi, and to determine the proportion of healthy babies with an apparent laboratory toxicity based on Division of AIDS toxicity tables. DESIGN: This was a cross-sectional laboratory study of infants from birth to 6 months of age. METHODS: Blood samples were collected from a total of 561 infants and analyzed according to age categories similar to those in the 2004 Division of AIDS toxicity tables. Select chemistry and hematology parameters were determined and values compared with those in the toxicity tables. RESULTS: In the first 56 days of life, there were few graded toxicities except for neutropenia in 2 of 10 (20%) Ugandan and 13 of 45 (29%) Malawian infants at birth. After 7 days, about 20% of the infants in Uganda and Malawi would have been classified as having a neutropenia whereas 47% and 53% of those more than 2 months of age in Uganda and Malawi respectively, would have been reported as having an abnormal hemoglobin. Chemistry findings were not different from US norms. CONCLUSIONS: These findings underscore the importance of establishing relevant local laboratory norms for infants.

The effect of human immunodeficiency virus and breastfeeding on the nutritional status of African children.

BACKGROUND: The risk of HIV-1 infection is high among breast-fed children in sub-Saharan Africa. Monitoring the nutritional status can provide useful information to determine the effect of HIV infection and breast-feeding on child growth and development. We longitudinally assessed the nutritional status and determined its association with HIV infection and breast-feeding among Malawian children. METHODS: We analyzed data from 2 clinical trials to prevent mother-to-child transmission of HIV in Malawi. These trials were conducted during 2000-2003 before the current guidelines were implemented to breast-feed exclusively during the first 6 months and wean thereafter. The nutritional status of children was measured up to age 24 months, using z-scores. Age-specific differences in length-for-age (L/A), weight-for-age (W/A), and weight-for-length (W/L) were compared stratifying by gender and HIV infection status. Multivariable models examined the mean change in z-scores controlling for breast-feeding and other factors. RESULTS: In this analysis, 1589 children were included. Boys had significantly lower L/A scores and became stunted (z-score -<2 standard deviations) earlier than girls. HIV-infected children had significantly lower mean L/A and W/A z-scores than HIV-uninfected children and became stunted and underweight at an earlier age. In multivariable analysis not being breast-fed and being HIV infected were significantly (P < 0.001) associated with decreases in mean L/A, W/A, and W/L z-scores. CONCLUSIONS: This study shows the impact of infant HIV infection on growth and supports the critical importance of breast-feeding. Mother-to-child transmission of HIV programs should endeavor to preserve breast-feeding and find alternative measures to prevent postnatal HIV transmission.

Patients' satisfaction with reproductive health services at Gogo Chatinkha Maternity Unit, Queen Elizabeth Central Hospital, Blantyre, Malawi.

UNLABELLED: Patient satisfaction is an individual's state of being content with the care provided in the health system. It is important for reproductive health care providers to get feedback from women regarding satisfaction with reproductive health services. There is a dearth of knowledge about patient satisfaction in Malawi. AIM: The specific objective of the study was to determine the extent to which women are satisfied with the care they receive when they come to deliver at the Queen Elizabeth Central Hospital maternity unit. METHODS: A cross sectional study of postpartum women using interviewer administered semi-structured questionnaires was conducted between November 2008 and May 2009. The questionnaires captured mainly quantitative data. RESULTS: 1562 women were interviewed. Most women were housewives (79%) who were referred from Health Centres within the city. Ninety five percent delivered a live baby. The majority of women (97.3%) were satisfied with the care they received from admission through labour and delivery and the immediate postpartum period. Most women cited doctors' and nurses' reviews (65%) as what they liked most about the care they received during their stay in the unit. Most women expected to receive efficient and definitive care. The women's knowledge on patient's rights was extremely low (16%) and equally very few women were offered an opportunity to give an opinion regarding their care by the doctors and nurses in the maternity unit. CONCLUSION: Most women who deliver at the hospital are satisfied with the care offered. This satisfaction is mainly due to the frequent reviews of patients by nurses and doctors in the unit. There is a great need to educate both the population of women served and the health workers that serve them on patient's rights.

Frequency of gastroenteritis and gastroenteritis-associated mortality with early weaning in HIV-1-uninfected children born to HIV-infected women in Malawi.

BACKGROUND: We assessed gastroenteritis (GE) burden in 2 randomized trials conducted in Malawi to reduce postnatal HIV transmission before and after World Health Organization recommendations regarding exclusive breastfeeding for HIV-exposed infants were adopted. The 2 trials were the nevirapine/AZT (NVAZ, 2000-2003 with prolonged breastfeeding) and the Postexposure Prophylaxis to the Infant (PEPI, 2004-2007 with breastfeeding cessation by 6 months). METHODS: From NVAZ and PEPI trials data, GE frequency through age 12 months among HIV-negative exposed infants was evaluated. Overall and GE-related cumulative mortality rates were estimated using Kaplan-Meier curves. RESULTS: The frequency of at least one GE-related hospitalization was greater in PEPI vs. NVAZ after age 6 months (respectively, 2.9% vs. 0.1%, at 7-9 months and 1.6% vs. 0.2% at 10-12 months, P < 0.001). Cumulative GE-related mortality was significantly higher in PEPI than in NVAZ after age 6 months; at ages 9 and 12 months GE-related mortality was 19 and 24 per 1000 infants in PEPI vs. 7 and 12 per 1000 infants in NVAZ (P = 0.0002). CONCLUSIONS: Early weaning was associated with increased risk of severe GE and GE-related mortality among HIV-exposed infants. Strategies are urgently needed which allow longer breastfeeding while reducing the risk of HIV breast milk transmission in resource-limited settings.

Addition of extended zidovudine to extended nevirapine prophylaxis reduces nevirapine resistance in infants who were HIV-infected in utero.

BACKGROUND: In the Post-Exposure Prophylaxis of Infants (PEPI)-Malawi trial, most women received single-dose nevirapine (NVP) at delivery, and infants in the extended study arms received single-dose NVP along with 1 week of daily zidovudine (ZDV), followed by either extended daily NVP or extended daily NVP and ZDV up to 14 weeks of age. Although extended NVP prophylaxis reduces the risk of postnatal HIV transmission, it may increase the risk of NVP resistance among infants who are HIV-infected despite prophylaxis. METHODS: We analyzed 88 infants in the PEPI-Malawi trial who were HIV-infected in utero and who received prophylaxis for a median of 6 weeks prior to HIV diagnosis. HIV genotyping was performed using the ViroSeq HIV Genotyping System. RESULTS: At 14 weeks of age, the proportion of infants with NVP resistance was lower in the extended NVP and ZDV arm than in the extended NVP arm (28/45, 62.2% vs. 37/43, 86.0%; P = 0.015). None of the infants had ZDV resistance. Addition of extended ZDV to extended NVP was associated with reduced risk of NVP resistance at 14 weeks if prophylaxis was stopped by 6 weeks (54.5 vs. 85.7%, P = 0.007) but not if prophylaxis was continued beyond 6 weeks (83.3 vs. 87.5%, P = 1.00). CONCLUSION: Addition of extended ZDV to extended NVP prophylaxis significantly reduced the risk of NVP resistance at 14 weeks in infants who were HIV-infected in utero, provided that HIV infection was diagnosed and the prophylaxis was stopped by 6 weeks of age.

The APPLe study: a randomized, community-based, placebo-controlled trial of azithromycin for the prevention of preterm birth, with meta-analysis.

BACKGROUND: Premature birth is the major cause of perinatal mortality and morbidity in both high- and low-income countries. The causes of preterm labour are multiple but infection is important. We have previously described an unusually high incidence of preterm birth (20%) in an ultrasound-dated, rural, pregnant population in Southern Malawi with high burdens of infective morbidity. We have now studied the impact of routine prophylaxis with azithromycin as directly observed, single-dose therapy at two gestational windows to try to decrease the incidence of preterm birth. METHODS AND FINDINGS: We randomized 2,297 pregnant women attending three rural and one peri-urban health centres in Southern Malawi to a placebo-controlled trial of oral azithromycin (1 g) given at 16-24 and 28-32 wk gestation. Gestational age was determined by ultrasound before 24 wk. Women and their infants were followed up until 6 wk post delivery. The primary outcome was incidence of preterm delivery, defined as <37 wk. Secondary outcomes were mean gestational age at delivery, perinatal mortality, birthweight, maternal malaria, and anaemia. Analysis was by intention to treat. There were no significant differences in outcome between the azithromycin group (n = 1,096) and the placebo group (n = 1,087) in respect of preterm birth (16.8% versus 17.4%), odds ratio (OR) 0.96, 95% confidence interval (0.76-1.21); mean gestational age at delivery (38.5 versus 38.4 weeks), mean difference 0.16 (-0.08 to 0.40); mean birthweight (3.03 versus 2.99 kg), mean difference 0.04 (-0.005 to 0.08); perinatal deaths (4.3% versus 5.0%), OR 0.85 (0.53-1.38); or maternal malarial parasitaemia (11.5% versus 10.1%), OR 1.11 (0.84-1.49) and anaemia (44.1% versus 41.3%) at 28-32 weeks, OR 1.07 (0.88-1.30). Meta-analysis of the primary outcome results with seven other studies of routine antibiotic prophylaxis in pregnancy (>6,200 pregnancies) shows no effect on preterm birth (relative risk 1.02, 95% confidence interval 0.86-1.22). CONCLUSIONS: This study provides no support for the use of antibiotics as routine prophylaxis to prevent preterm birth in high risk populations; prevention of preterm birth requires alternative strategies. TRIAL REGISTRATION: Current Controlled Trials ISRCTN84023116

Postnatal HIV-1 transmission after cessation of infant extended antiretroviral prophylaxis and effect of maternal highly active antiretroviral therapy.

BACKGROUND: The association between postnatal human immunodeficiency virus type 1 (HIV-1) transmission and maternal highly active antiretroviral therapy (HAART) after infant extended antiretroviral prophylaxis was assessed. METHODS: A follow-up study was conducted for the Post-Exposure Prophylaxis of Infants trial in Blantyre, Malawi (PEPI-Malawi). In PEPI-Malawi, breast-feeding infants of HIV-infected women were randomized at birth to receive a either control regimen (single-dose nevirapine plus 1 week of zidovudine); the control regimen plus nevirapine to age 14 weeks; or the control regimen plus nevirapine and zidovudine to age 14 weeks. Infant HIV infection, maternal CD4 cell count, and HAART use were determined. Maternal HAART use was categorized as HAART eligible but untreated (CD4 cell count of <250 cells/microL, no HAART received), HAART eligible and treated (CD4 cell count of <250 cells/microL, HAART received), and HAART ineligible (CD4 cell count of 250 cells/microL). The incidence of HIV infection and the association between postnatal HIV transmission and maternal HAART were calculated among infants who were HIV negative at 14 weeks. RESULTS: Of 2318 infants, 130 (5.6%) acquired HIV infection, and 310 mothers (13.4%) received HAART. The rates of HIV transmission (in cases per 100 person-years) were as follows: for the HAART-eligible/untreated category, 10.56 (95% confidence interval [CI], 7.91-13.82); for the HAART-eligible/treated category, 1.79 (95% CI, 0.58-4.18); and for the HAART-ineligible category, 3.66 (95% CI, 2.86-4.61). The HIV transmission rate ratio for the HAART-eligible/treated category versus the HAART-eligible/untreated category, adjusted for infant prophylaxis, was 0.18 (95% CI, 0.07-0.44). CONCLUSIONS: Postnatal HIV transmission continues after cessation of infant prophylaxis. HAART-eligible women should start treatment early for their own health and to reduce postnatal HIV transmission to their infants.

Intrapartum antibiotic exposure and early neonatal, morbidity, and mortality in Africa.

BACKGROUND: Infants born to women who receive intrapartum antibiotics may have higher rates of infectious morbidity and mortality than unexposed infants. OBJECTIVE: Our goal was to determine the association of maternal intrapartum antibiotics and early neonatal morbidity and mortality. METHODS: We performed secondary analysis of data from a multisite randomized, placebo-controlled clinical trial of antibiotics to prevent chorioamnionitis-associated mother-to-child transmission of HIV-1 and preterm birth in sub-Saharan Africa. Early neonatal morbidity and mortality were analyzed. In an intention-to-treat (ITT) analysis, infants born to women randomly assigned to antibiotics or placebo were compared. In addition, non-ITT analysis was performed because some women received nonstudy antibiotics for various clinical indications. RESULTS: Overall, 2659 pregnant women were randomly assigned. Of these, 2466 HIV-1-infected and HIV-1-uninfected women delivered 2413 live born and 84 stillborn infants. In the ITT analysis, there were no significant associations between exposure to antibiotics and early neonatal outcomes. Non-ITT analyses showed more illness at birth (11.2% vs 8.6%, P = .03) and more admissions to the special care infant unit (12.6% vs 9.8%, P = .04) among infants exposed to maternal intrapartum antibiotics than among unexposed infants. Additional analyses revealed greater early neonatal morbidity and mortality among infants of mothers who received nonstudy antibiotics than of mothers who received study antibiotics. CONCLUSIONS: There is no association between intrapartum exposure to antibiotics and early neonatal morbidity or mortality. The associations observed in non-ITT analyses are most likely the result of women with peripartum illnesses being more likely to receive nonstudy antibiotics.

Fertility intentions of HIV-1 infected and uninfected women in Malawi: a longitudinal study.

This study aimed to determine changes in fertility intentions of HIV-1 infected and uninfected reproductive age women in Blantyre, Malawi. Participants were asked about their fertility intentions at baseline and at 3-month visits for 1 year. Time-to-event statistical models were used to determine factors associated with changes in fertility intentions. Overall, 842 HIV uninfected and 844 HIV infected women were enrolled. The hazard of changing from wanting no more children at baseline to wanting more children at follow-up was 61% lower among HIV infected women compared to HIV uninfected women (P < 0.01) after adjusting for other factors, while HIV infected women were approximately 3 times more likely to change to wanting no more children. The overall pregnancy rate after 12 months was 14.9 per 100 person-years and did not differ among 102 HIV uninfected and 100 infected women who became pregnant. HIV infection is a significant predictor of fertility intentions over time.

Morbidity and mortality among a cohort of human immunodeficiency virus type 1-infected and uninfected pregnant women and their infants from Malawi, Zambia, and Tanzania.

BACKGROUND: Morbidity and mortality patterns among pregnant women and their infants (before antiretroviral therapy was widely available) determines HIV-1 diagnostic, monitoring, and care interventions. METHODS: Data from mothers and their infants enrolled in a trial of antibiotics to reduce mother-to-child-transmission of HIV-1 at 4 sub-Saharan African sites were analyzed. Women were enrolled during pregnancy and follow-up continued until the infants reached 12 months of age. We describe maternal and infant morbidity and mortality in a cohort of HIV-1-infected and HIV-1-uninfected mothers. Maternal and infant factors associated with mortality risk in the infants were assessed using Cox proportional hazard modeling. RESULTS: Among 2292 HIV-1-infected mothers, 166 (7.2%) had a serious adverse event (SAE) and 42 (1.8%) died, whereas no deaths occurred among the 331 HIV-1 uninfected mothers. Four hundred twenty-four (17.8%) of 2383 infants had an SAE and 349 (16.4%) died before the end of follow-up. Infants with early HIV-1 infection (birth to 4-6 weeks) had the highest mortality. Among infants born to HIV-1-infected women, maternal morbidity and mortality (P = 0.0001), baseline CD4 count (P = 0.0002), and baseline plasma HIV-1 RNA concentration (P < 0.0001) were significant predictors of infant mortality in multivariate analyses. CONCLUSIONS: The high mortality among infants with early HIV-1 infection supports access to HIV-1 diagnostics and appropriate early treatment for all infants of HIV-1-infected mothers. The significant association between stage of maternal HIV-1 infection and infant mortality supports routine CD4 counts at the time of prenatal HIV-1 testing.

Extended antiretroviral prophylaxis to reduce breast-milk HIV-1 transmission.

BACKGROUND: Effective strategies are urgently needed to reduce mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) through breast-feeding in resource-limited settings. METHODS: Women with HIV-1 infection who were breast-feeding infants were enrolled in a randomized, phase 3 trial in Blantyre, Malawi. At birth, the infants were randomly assigned to one of three regimens: single-dose nevirapine plus 1 week of zidovudine (control regimen) or the control regimen plus daily extended prophylaxis either with nevirapine (extended nevirapine) or with nevirapine plus zidovudine (extended dual prophylaxis) until the age of 14 weeks. Using Kaplan-Meier analyses, we assessed the risk of HIV-1 infection among infants who were HIV-1-negative on DNA polymerase-chain-reaction assay at birth. RESULTS: Among 3016 infants in the study, the control group had consistently higher rates of HIV-1 infection from the age of 6 weeks through 18 months. At 9 months, the estimated rate of HIV-1 infection (the primary end point) was 10.6% in the control group, as compared with 5.2% in the extended-nevirapine group (P<0.001) and 6.4% in the extended-dual-prophylaxis group (P=0.002). There were no significant differences between the two extended-prophylaxis groups. The frequency of breast-feeding did not differ significantly among the study groups. Infants receiving extended dual prophylaxis had a significant increase in the number of adverse events (primarily neutropenia) that were deemed to be possibly related to a study drug. CONCLUSIONS: Extended prophylaxis with nevirapine or with nevirapine and zidovudine for the first 14 weeks of life significantly reduced postnatal HIV-1 infection in 9-month-old infants. (ClinicalTrials.gov number, NCT00115648.)

Natural history and risk factors associated with early and established HIV type 1 infection among reproductive-age women in Malawi.

BACKGROUND: Data evaluating the biological events and determinants of early human immunodeficiency virus type 1 (HIV-1) infection are limited in sub-Saharan Africa. We examined plasma viral levels and trends during early and established HIV-1 infection among reproductive-age women who participated in a randomized trial to treat genital tract infection in Malawi. We also assessed the association of injectable hormonal contraceptive use with HIV-1 infection. METHODS: We studied 3 groups of women who were infected or uninfected with HIV-1: seroconverters, seroprevalent women, and seronegative women. Questionnaires and blood samples were collected at baseline and every 3 months for 1 year. The virus set point in seroconverters and levels and trends of viral load over time were determined. The associations of injectable hormonal contraceptive use with HIV-1 infection and viral load were assessed using conditional logistic regression and mixed-effect models, respectively. RESULTS: In the original clinical trial, 844 women infected with HIV-1 and 842 women not infected with HIV-1 were enrolled. Of 31 women who experienced seroconversion during 12 months, 27 were matched with 54 seroprevalent and 54 seronegative women. The estimated median plasma virus set point was 4.45 log(10) copies/mL (interquartile range, 4.32-5.14 log(10) copies/mL). Injectable hormonal contraceptive use was significantly associated with HIV-1 seroconversion (adjusted odds ratio, 10.42; P = .03) but not with established HIV-1 infection. Among the seroconverters, a statistically significant interaction was found between the linear association of viral load and time of injectable hormonal contraceptive use (regression coefficient, -0.14; P = .02). CONCLUSION: Knowledge of virus set point and trends of viral load in HIV-1 seroincident and seroprevalent asymptomatic women could assist in antiretroviral treatment management.

'I don't want all my babies to go to the grave': perceptions of preterm birth in Southern Malawi.

OBJECTIVE: to investigate perceptions of preterm birth, infections in pregnancy and perinatal mortality among women, men and health-care providers in Namitambo, Southern Malawi. DESIGN: a qualitative study using focus-group discussions, critical incidence narrative and key informant interviews. The framework approach to qualitative analysis was used. SETTING: Namitambo, a rural area in southern Malawi. PARTICIPANTS: women who have experienced preterm delivery, groups of mothers, fathers and grandmothers, health-care providers, traditional birth attendants and healers. FINDINGS: four key inter-related themes grounded in community interpretative frameworks emerged: (1) community conceptualisations of preterm birth (the different terminologies used); (2) perceived causes of preterm birth (i.e. both 'modern' and 'traditional; illnesses, violence, witchcraft, ideas relating to impurity, heavy work, inadequate food and inappropriate use of medicine); (3) perceived strategies to prevent preterm birth (i.e. using formal health services, treatment for sexually transmitted infections, using condoms and stopping violence); and (4) barriers to realising these strategies, such as lack of food, money and women's autonomy in health seeking. KEY CONCLUSIONS: similarities and differences exist in understanding between healthcare providers and the community. Additional dialogue and action is needed within the health sector and community to address the problem of preterm births. This includes strategies to enable health-care providers and community members to reflect on their perceptions and practices (e.g. through action research and interactive drama); identify and build on areas of common concern (i.e. poor pregnancy outcome) and enter into partnerships with non-formal providers. Action is also needed beyond the health sector (e.g. in campaigns to reduce gender-based violence).

Late postnatal transmission of HIV-1 and associated factors.

BACKGROUND: The present study was undertaken to determine the risk and timing of late postnatal transmission (LPT) of human immunodeficiency virus type 1 (HIV-1). METHODS: Breast-fed infants previously enrolled in 2 trials of antiretroviral prophylaxis were monitored in Malawi. Kaplan-Meier and proportional hazard models assessed cumulative incidence and association of factors with LPT. RESULTS: Overall, 98 infants were HIV infected, and 1158 were uninfected. The cumulative risk of LPT at age 24 months was 9.68% (95% confidence interval, 7.80%-11.56%). The interval hazards at 1.5-6, 6-12, 12-18, and 18-24 months were 1.22%, 4.05%, 3.48%, and 1.27%, respectively. CONCLUSIONS: The risk of LPT beyond 6 months is substantial. Weaning at 6 months could prevent >85% of LPT.

Fetal fibronectin and adverse infant outcomes in a predominantly human immunodeficiency virus-infected African population: a randomized controlled trial.

OBJECTIVE: To evaluate the relationship between fetal fibronectin and preterm birth and maternal-to-child transmission of human immunodeficiency virus (HIV) in an African population of predominantly HIV-infected women. METHODS: During a trial of second trimester and intrapartum antibiotics compared with placebo to prevent chorioamnionitis and reduce preterm birth and mother-to-child transmission of HIV, vaginal fluid was collected before antibiotics (20-24 weeks) and after treatment at 28 weeks and assayed for fetal fibronectin. Pregnancy outcomes of 2,353 women delivering liveborn singleton infants are presented. RESULTS: Positive fetal fibronectin assays (50 ng/mL or more) were detected in 4.2% and 4.9% of samples at 20-24 weeks and 28 weeks. Positive fetal fibronectin assays at 28 weeks but not at 20-24 weeks were associated with lower mean birthweight (199 g, P<.001); lower mean gestational age (2 weeks, P<.001); six-fold higher rate of preterm birth less than 32 weeks (10.8% compared with 1.9%, odds ratio 6.3, 95% confidence interval 3.2-12.3) and a two-fold higher rate of preterm birth less than 37 weeks (38.7 compared with 22.0%, odds ratio 2.3, 95% confidence interval 1.5-3.3). Also, at 28 weeks, as the fetal fibronectin values increased, each of the outcomes worsened, and every test of trend was significant. An association between elevated fetal fibronectin levels and mother-to-child transmission of HIV was present at 20 to 24 weeks but not at 28 weeks. Antibiotic treatment at 20 to 24 weeks was not associated with fetal fibronectin levels at 28 weeks. CONCLUSION: In a population of predominantly HIV- infected African women, fetal fibronectin concentrations at 28 but not at 20-24 weeks were associated with increased risk of preterm birth. The associations were stronger for early preterm birth and when fetal fibronectin levels were higher. High levels of fetal fibronectin were positively associated with mother-to-child transmission of HIV at 20 -24 but not at 28 weeks. Antibiotic treatment did not influence fetal fibronectin levels. CLINICAL TRIAL REGISTRATION: www.clinicalTrials.gov, NCT00021671 LEVEL OF EVIDENCE: I.

Intermittent intravaginal antibiotic treatment of bacterial vaginosis in HIV-uninfected and -infected women: a randomized clinical trial.

OBJECTIVE: Assess efficacy of intermittent intravaginal metronidazole gel treatment in reducing frequency of bacterial vaginosis (BV). DESIGN: Randomized, double-masked, placebo-controlled phase 3 trial. SETTING: Postnatal and family planning clinics of the Queen Elizabeth Central Hospital and two health centers in Blantyre, Malawi. PARTICIPANTS: Nonpregnant HIV-uninfected and -infected women. INTERVENTION: Intravaginal metronidazole treatment and placebo gels provided at baseline and every 3 mo for 1 y. OUTCOME MEASURES: PRIMARY: Cross-sectional and longitudinal comparisons of BV frequency at baseline, 1 mo after product dispensation (post-treatment evaluation [PTE]), and every quarterly visit. Secondary: Effect of treatment on BV clearance and recurrence. RESULTS: BASELINE: 842 HIV-uninfected and 844 HIV-infected women were enrolled. The frequency of BV at baseline in treatment and placebo arms, respectively, was 45.9% and 46.8% among HIV-uninfected women, and 60.5% and 56.9% among HIV-infected women. PRIMARY OUTCOMES: At the PTEs the prevalence of BV was consistently lower in treatment than placebo arms irrespective of HIV status. The differences were statistically significant mainly in HIV-uninfected women. Prevalence of BV was also reduced over time in both treatment and placebo arms. In a multivariable analysis that controlled for other covariates, the effect of intravaginal metronidazole treatment gel compared with placebo was not substantial: adjusted relative risk (RR) 0.90, 95% confidence interval (CI) 0.83-0.97 in HIV-uninfected women and adjusted RR 0.95, 95% CI 0.89-1.01 in HIV-infected women. SECONDARY OUTCOMES: Intravaginal metronidazole treatment gel significantly increased BV clearance (adjusted hazard ratio [HR] 1.34, 95% CI 1.07-1.67 among HIV-uninfected women and adjusted HR 1.29, 95% CI 1.06-1.58 among HIV-infected women) but was not associated with decreased BV recurrence. SAFETY: No serious adverse events were related to use of intravaginal gels. CONCLUSION: Intermittent microbicide treatment with intravaginal gels is an innovative approach that can reduce the frequency of vaginal infections such as BV.

The impact of breastfeeding on the health of HIV-positive mothers and their children in sub-Saharan Africa.

OBJECTIVE: We assessed the impact of breastfeeding by women infected with human immunodeficiency virus (HIV)-1 on their morbidity and risk of mortality and on the mortality of their children. METHODS: We analysed longitudinal data from two previous randomized clinical trials of mother-to-child transmission of HIV conducted between April 2000 and March 2003 in the Republic of Malawi, Africa. Mothers infected with HIV, and their newborns, were enrolled at the time of their child's birth; they then returned for follow-up visits when the child was aged 1 week, 6-8 weeks and then 3, 6, 9, 15, 18, 21 and 24 months. Patterns of breastfeeding (classified as exclusive, mixed or no breastfeeding), maternal morbidity and mortality, and mortality among their children were assessed at each visit. Descriptive and multivariate analyses were performed to determine the association between breastfeeding and maternal and infant outcomes. FINDINGS: A total of 2000 women infected with HIV were enrolled in the original studies. During the 2 years after birth, 44 (2.2%) mothers and 310 (15.5%) children died. (Multiple births were excluded.) The median duration of breastfeeding was 18 months (interquartile range (IQR)=9.0-22.5), exclusive breastfeeding 2 months (IQR=2-3) and mixed feeding 12 months (IQR=6-18). Breastfeeding patterns were not significantly associated with maternal mortality or morbidity after adjusting for maternal viral load and other covariates. Breastfeeding was associated with reduced mortality among infants and children: the adjusted hazard ratio for overall breastfeeding was 0.44 (95% confidence interval (CI)=0.28-0.70), for mixed feeding 0.45 (95% CI=0.28-0.71) and for exclusive breastfeeding 0.40 (95% CI=0.22-0.72). These protective effects were seen both in infants who were infected with HIV and those who were not. CONCLUSION: Breastfeeding by women infected with HIV was not associated with mortality or morbidity; it was associated with highly significant reductions in mortality among their children.