LSTM Home > LSTM Research > LSTM Online Archive

The APPLe Study: A Randomized, Community-Based, Placebo-Controlled Trial of Azithromycin for the Prevention of Preterm Birth, with Meta-Analysis

Van Den Broek, Nynke, White, Sarah, Goodall, Mark, Ntonya, Chikondi, Kayira, Edith, Kafulafula, George and Neilson, James P (2009) 'The APPLe Study: A Randomized, Community-Based, Placebo-Controlled Trial of Azithromycin for the Prevention of Preterm Birth, with Meta-Analysis'. PLoS Medicine, Vol 6, Issue 12, e1000191.

[img]
Preview
Text
Plos_Medicine_6_12_e1000191.pdf - Published Version
Available under License Creative Commons Attribution.

Download (530kB) | Preview

Abstract

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.

Item Type: Article
Subjects: QV Pharmacology > Anti-Bacterial Agents. Tissue Extracts > QV 350 Anti-bacterial agents (General or not elsewhere classified)
WA Public Health > Health Problems of Special Population Groups > WA 310 Maternal welfare
WA Public Health > Health Problems of Special Population Groups > WA 395 Health in developing countries
WA Public Health > Statistics. Surveys > WA 900 Public health statistics
WQ Obstetrics > Pregnancy Complications > WQ 225 Spontaneous abortion. Fetal death
Faculty: Department: Groups (2002 - 2012) > Child & Reproductive Health Group
Digital Object Identifer (DOI): https://doi.org/10.1371/journal.pmed.1000191
Depositing User: Users 19 not found.
Date Deposited: 12 Nov 2010 09:32
Last Modified: 06 Feb 2018 13:02
URI: http://archive.lstmed.ac.uk/id/eprint/1684

Actions (login required)

Edit Item Edit Item
Downloads per month over past year