Chloroquine as weekly chemoprophylaxis or intermittent treatment to prevent malaria in pregnancy in Malawi: a randomised controlled trial.

BACKGROUND: Sulfadoxine-pyrimethamine resistance threatens efficacy of intermittent preventive treatment of malaria during pregnancy, and alternative regimens need to be identified. With the return of chloroquine efficacy in southern Africa, we postulated that chloroquine either as an intermittent therapy or as weekly chemoprophylaxis would be more efficacious than intermittent sulfadoxine-pyrimethamine for prevention of malaria in pregnancy and associated maternal and newborn adverse outcomes. METHODS: We did an open-label, single-centre, randomised controlled trial at Ndirande Health Centre, Blantyre, in southern Malawi. We enrolled pregnant women (first or second pregnancy) at 20-28 weeks' gestation who were HIV negative. Participants were randomly assigned in a 1:1:1 ratio using a computer-generated list to either intermittent sulfadoxine-pyrimethamine (two doses of 1500 mg sulfadoxine and 75 mg pyrimethamine, 4 weeks apart), intermittent chloroquine (two doses of 600 mg on day 1, 600 mg on day 2, and 300 mg on day 3), or chloroquine prophylaxis (600 mg on day 1 then 300 mg every week). The primary endpoint was placental malaria in the modified intent-to-treat population, which consisted of participants who contributed placental histopathology data at birth. Secondary outcomes included clinical malaria, maternal anaemia, low birthweight, and safety. This trial is registered with ClinicalTrials.gov, number NCT01443130. FINDINGS: Between February, 2012, and May, 2014, we enrolled and randomly allocated 900 women, of whom 765 contributed histopathological data and were included in the primary analysis. 108 (14%) women had placental malaria, which was lower than the anticipated prevalence of placental malaria infection. Protection from placental malaria was not improved by chloroquine as either prophylaxis (30 [12%] of 259 had positive histopathology; relative risk [RR] 0·75, 95% CI 0·48-1·17) or intermittent therapy (39 [15%] of 253; RR 1·00, 0·67-1·50) compared with intermittent sulfadoxine-pyrimethamine (39 [15%] of 253). In protocol-specified analyses adjusted for maternal age, gestational age at enrolment, bednet use the night before enrolment, anaemia at enrolment, and malaria infection at enrolment, women taking chloroquine as prophylaxis had 34% lower placental infections than did those allocated intermittent sulfadoxine-pyrimethamine (RR 0·66, 95% CI 0·46-0·95). Clinical malaria was reported in nine women assigned intermittent sulfadoxine-pyrimethamine, four allocated intermittent chloroquine (p=0·26), and two allocated chloroquine prophylaxis (p=0·063). Maternal anaemia was noted in five women assigned intermittent sulfadoxine-pyrimethamine, 15 allocated intermittent chloroquine (p=0·038), and six assigned chloroquine prophylaxis (p>0·99). Low birthweight was recorded for 31 babies born to women allocated intermittent sulfadoxine-pyrimethamine, 29 assigned intermittent chloroquine (p=0·78), and 41 allocated chloroquine prophylaxis (p=0·28). Four women assigned intermittent sulfadoxine-pyrimethamine had adverse events possibly related to study product compared with 94 women allocated intermittent chloroquine (p<0·0001) and 26 allocated chloroquine prophylaxis (p<0·0001). Three women had severe or life-threatening adverse events related to study product, of whom all were assigned intermittent chloroquine (p=0·25). INTERPRETATION: Chloroquine administered as intermittent therapy did not provide better protection from malaria and related adverse effects compared with intermittent sulfadoxine-pyrimethamine in a setting of high resistance to sulfadoxine-pyrimethamine. Chloroquine chemoprophylaxis might provide benefit in protecting against malaria during pregnancy, but studies with larger sample sizes are needed to confirm these results. FUNDING: US National Institutes of Health

Maternal and fetal outcomes of induction of labour using oral misoprostol at New Somerset Hospital

Introduction: Induction of labour is commonly performed in clinical practice. Increasing rates of induction of labour worldwide has led to debate on whether elective induction improves the outcomes or simply leads to increased complications and healthcare costs. Maternal and neonatal complications and increased caesarean section (CS) rates associated with induction of labour are related to a variety of factors influencing the methods of induction. Misoprostol has been the drug of choice for induction of labour in developing countries for almost a decade. Different misoprostol regimens are used for induction of labour in different health facilities. New Somerset Hospital uses the standard protocol for induction of labour using misoprostol that the Western Cape Government adopted. This protocol has however not been audited. The main objective of the study was to determine the maternal and fetal outcomes of inductions of labour performed at New Somerset Hospital. Methods: This was a retrospective study conducted at New Somerset Hospital. We reviewed a random sample of medical records of patients who underwent induction of labour from 01 January 2014 to 31 December 2014. Ethics committee approval was granted by the Human Research Ethics Committee of the Faculty of Health Sciences of UCT. A total of 88 folders were sampled from 1029 women who had induction of labour. Results: There were a total of 6514 deliveries in 2014 of which 1029 had induction of labour, giving an induction rate of 15.8%. A total of 86 patients were included in the study. The mean age of the patients was 28.9 years (SD±6.586) with an age range of 16 to 44 years. The average gestational age at the time of induction of labour was 39.5 weeks with a range 35 to 42.6 weeks and 14.0% of the patients were HIV positive. The three main indications of induction of labour were hypertension in pregnancy (40.7%), prolonged pregnancy (27.9%) and pre-labour rupture of membranes (8.1%). Overall, 50 patients (58.1%) had vaginal delivery and 36 patients (41.9%) had caesarean delivery. There was a significant association between mode of delivery and time to delivery. Patients who delivered within 24 hours of commencement of induction of labour were more likely to have had a vaginal delivery (p = 0.005). The three main indications for caesarean delivery were fetal heart rate changes (n=30; 72.0%) followed by failed induction of labour (n=9; 21.0%) and cephalopelvic disproportion (n=3; 7.0 %). In terms of maternal outcomes, 2 patients (2.3%) had hyperstimulation of the uterus, 6 patients (7.0%) had postpartum hemorrhage, 8 patients (9.3%) had vaginal tears and 5 patients (5.9%) had an episiotomy performed during delivery. The mean birth weight was 3262.1g (SD±503.77) with a range of 1925 to 4515 grams. At five minutes the means Apgar score was 9.8(SD ± 0.62) with range of 6 to 10. A total of 38 babies (44.3%) had meconium stained liquor documented at delivery, three babies (3.4%) required neonatal resuscitation upon delivery. There were 10 (11.6%) babies that were admitted to NICU. Conclusion: In this study we found that the prevalence of induction of labour was 15.8%. Hypertension in pregnancy, prolonged pregnancy and pre-labour rupture of membranes are the three common indications for induction of labour. Successful vaginal delivery was achieved in 51.0% of the study population. The caesarean delivery rate was high, mostly due to CTG changes The current induction of labour protocol using oral misoprostol is associated with acceptable maternal and fetal outcomes