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

'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).