The effect of antenatal monthly sulphadoxine-pyrimethamine, alone or with azithromycin, on foetal and neonatal growth faltering in Malawi: a randomised controlled trial.

To examine the potential to reduce foetal and neonatal growth faltering through intermittent preventive treatment in pregnancy (IPTp) of malaria and reproductive tract infections with monthly sulphadoxine-pyrimethamine (SP), alone or with two doses of azithromycin. We enrolled 1320 women with uncomplicated second trimester pregnancies into a randomised, partially placebo controlled, outcome assessor-blinded clinical trial in Malawi. The participants received either two doses of SP (control), SP monthly (monthly SP) or SP monthly and azithromycin (1 g) twice (AZI-SP). Newborn size was measured within two days of birth and infant growth at four weeks of age. Babies in the AZI-SP group were on average (95% CI) 140 g (70-200) heavier at birth and 0.6 cm (0.2-0.9) longer at four weeks of age than control group babies. Corresponding differences between the monthly SP and control groups were 80 g (20-140) and 0.3 cm (-0.0 to 0.6). Compared with controls, babies in the AZI-SP group had a relative risk of 0.61 (0.40-0.93) for low birthweight, 0.60 (0.44-0.81) for stunting and 0.48 (0.29-0.79) for underweight at four weeks of age. Corresponding differences were similar but smaller between the monthly SP and control groups. An IPTp regimen with monthly SP given to all pregnant women is likely to increase mean birthweight and length at four weeks of age in malaria holoendemic areas. Adding azithromycin to the regimen appears to offer further benefits in reducing foetal and neonatal growth faltering.