Safety of daily co-trimoxazole in pregnancy in an area of changing malaria epidemiology: a phase 3b randomized controlled clinical trial.
BACKGROUND
Antibiotic therapy during pregnancy may be beneficial and impacts positively on the reduction of adverse pregnancy outcomes. No studies have been done so far on the effects of daily Co-trimoxazole (CTX) prophylaxis on birth outcomes. A phase 3b randomized trial was conducted to establish that daily CTX in pregnancy is not inferior to SP intermittent preventive treatment (IPT) in reducing placental malaria; preventing peripheral parasitaemia; preventing perinatal mortality and also improving birth weight. To establish its safety on the offspring by measuring the gestational age and birth weight at delivery, and compare the safety and efficacy profile of CTX to that of SP.


METHODS
Pregnant women (HIV infected and uninfected) attending antenatal clinic were randomized to receive either daily CTX or sulfadoxine-pyrimethamine as per routine IPT. Safety was assessed using standard and pregnancy specific measurements. Women were followed up monthly until delivery and then with their offspring up to six weeks after delivery.


RESULTS
Data from 346 pregnant women (CTX = 190; SP = 156) and 311 newborns (CTX = 166 and SP = 145) showed that preterm deliveries (CTX 3.6%; SP 3.0%); still births (CTX 3.0%; SP 2.1%), neonatal deaths (CTX 0%; SP 1.4%), and spontaneous abortions (CTX 0.6%; SP 0%) were similar between study arms. The low birth weight rates were 9% for CTX and 13% for SP. There were no birth defects reported. Both drug exposure groups had full term deliveries with similar birth weights (mean of 3.1 Kg). The incidence and severity of AEs in the two groups were comparable.


CONCLUSIONS
Exposure to daily CTX in pregnancy may not be associated with particular safety risks in terms of birth outcomes such as preterm deliveries, still births, neonatal deaths and spontaneous abortions compared to SP. However, more data are required on CTX use in pregnant women both among HIV infected and un-infected individuals.


BACKGROUND
Clinicaltrials.gov NCT00711906.
Tropical Diseases Research Centre, Ndola, Zambia; International Health Unit, University of Antwerp, Antwerp, Belgium.
Christine
C
Manyando
Tropical Diseases Research Centre, Ndola, Zambia; International Health Unit, University of Antwerp, Antwerp, Belgium.
Eric M
EM
Njunju
Tropical Diseases Research Centre, Ndola, Zambia.
David
D
Mwakazanga
Tropical Diseases Research Centre, Ndola, Zambia.
Gershom
G
Chongwe
Choma District Health Management Team, Choma, Zambia.
Rhoda
R
Mkandawire
Tropical Diseases Research Centre, Ndola, Zambia.
Davies
D
Champo
Tropical Diseases Research Centre, Ndola, Zambia.
Modest
M
Mulenga
Institute of Tropical Medicine, Antwerp, Belgium.
Maaike
M
De Crop
Institute of Tropical Medicine, Antwerp, Belgium.
Yves
Y
Claeys
Institute of Tropical Medicine, Antwerp, Belgium; Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
Raffaella M
RM
Ravinetto
Institute of Tropical Medicine, Antwerp, Belgium.
Chantal
C
van Overmeir
Institute of Tropical Medicine, Antwerp, Belgium; Medical Research Council, Fajara, The Gambia.
Umberto D'
UD
Alessandro
International Health Unit, University of Antwerp, Antwerp, Belgium.
Jean-Pierre
JP
Van Geertruyden
D000328:Adult; D000962:Antimalarials / Q000008:administration & dosage* / Q000009:adverse effects; D001724:Birth Weight; D004334:Drug Administration Schedule; D005260:Female; D005865:Gestational Age; D015658:HIV Infections / Q000150:complications; D006801:Humans; D008288:Malaria / Q000150:complications* / Q000517:prevention & control*; D008297:Male; D018811:Maternal Exposure; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000517:prevention & control*; D015597:Pregnancy Complications, Parasitic / Q000517:prevention & control*; D011256:Pregnancy Outcome; D016896:Treatment Outcome; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000008:administration & dosage* / Q000009:adverse effects; D055815:Young Adult; D015024:Zambia
D000962:Antimalarials; D015662:Trimethoprim, Sulfamethoxazole Drug Combination