In a randomized trial in Malawi of azithromycin versus placebo in over 2,000 pregnant women, Jim Neilson and colleagues show no benefit of azithromycin for a number of outcomes including preterm birth and prenatal death

A Sen

A Shennan

AH Shennan

C Giorlandino

C Young

Chikondi Ntonya

DL Hoyert

EC Eichenwald

Edith Kayira

George Kafulafula

GM Vermeulen

Gordon C. Smith

GRW Jones

H Honest

HN Simhan

J Langhoff-Roos

J Martines

J Thinkhamrop

JA McGregor

James P. Neilson

JC Hauth

JE Lawn

JE Overall

JM Bland

JP Neilson

K Challis

L Kalilani

LS Chitty

M Clarke

M Sarkar

Mark Goodall

NR van den Broek

Nynke R. van den Broek

P Steer

R Romero

R Smith

RL Goldenberg

RM Chico

S Kenyon

S Saigal

Sarah A. White

TE Taha

VK Paul

W Pitiphat

English

PubMed

BackgroundPremature 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 FindingsWe 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 &lt;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 (&gt;6,200 pregnancies) shows no effect on preterm birth (relative risk 1.02, 95% confidence interval 0.86–1.22).ConclusionsThis 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.</p

Van Den Broek, Nynke R.

White, Sarah

Goodall, Mark

Ntonya, Chikondi

Kayira, Edith

Kafulafula, George

Neilson, James P.

LSTM Research Portal

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

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. = 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).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.Please see later in the article for the Editors' Summar

van den Broek Nynke R.

White Sarah A.

Goodall Mark

Ntonya Chikondi

Kayira Edith

Kafulafula George

Neilson James P.

Public Library of Science (PLOS)

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 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

Van Den Broek, Nynke

Neilson, James P

LSTM Online Archive

Crossref

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.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 6,200 pregnancies) shows no effect on preterm birth (relative risk 1.02, 95% confidence interval 0.86-1.22).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.Current Controlled Trials ISRCTN8402311

Nynke R van den Broek

Sarah A White

James P Neilson

Directory of Open Access Journals

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

Abstract

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Public Library of Science (PLOS)

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