TABLE 13.

Antenatal Malaria Chemoprophylaxis or IPT

SourceLocation and Type of TrialInterventionMaternal OutcomePerinatal/Neonatal Outcome
Wolfe et al283Kenya; periurban setting; cost-effectiveness evaluation of treatment regimenUsing existing data from western Kenya (not an intervention study, no women enrolled), article compared 4 strategies of malaria prophylaxis using SP for effectiveness and cost-effectiveness, including 2-dose SP (1500 mg sulfadoxine, 75 mg pyrimethamine), monthly SP, HIV testing and an SP regimen, and a case management approach including SP.The monthly SP regimen was the most effective strategy for reducing LBW associated with malaria. The 2-dose SP and monthly SP regimens would prevent 172 and 229 more LBW births out of a cohort of 10 000 pregnant women, respectively, compared with the case management approach. At HIV seroprevalence rates >10%, the monthly SP regimen is the most cost-effective strategy. At HIV seroprevalence rates < 10%, the 2-dose SP regimen would be the most cost-effective option.
Ndyomugyenyi et al279Uganda; rural setting; DBRCTPrimigravidae in their first and second trimester (n = 860) were randomized to: group A (n = 284), oral 300 mg CQ base, placebo iron and placebo folate; group B (n = 282), placebo of all 3 interventions; group C (n = 294), weekly oral elemental iron 120 mg/d and folic acid 5 mg, placebo CQ.The risk of being anemic at delivery was lower in group A (25.6%) and group C (24.7%) compared to group B (38.1%) (P = .01).Women in group A had a significantly lower frequency of LBW (2%) than women in group B (9%) (P = .009). There was no significant difference in the frequency of LBW between groups B and C, or groups A and C.
Shulman et al274Kenya; rural setting; DBRCTWomen presenting between 16–30 wk of gestation (n = 1264) were given 1, 2, or 3 doses of SP, depending on stage of pregnancy (n = 640). Another group (n = 624) was given placebo.Lower rates of severe anemia (<8 g/dL) were seen in the intervention group, with an overall protective efficacy of 39% (P = .0001). A protective effect of intervention was also seen for malarial parasitemia (85%, P = .0001) and placental parasite infection (17%, P = .027).Although the intervention decreased the stillbirth rate (22%), the results did not reach significance. There was no effect on premature birth rates. The intervention decreased NMR by 38%, but this result was not significant; similarly, the PMR decreased 32%, but this result was not significant.
Parise et al280Kenya; periurban setting; RCT2077 pregnant women were enrolled in the study. The Case Management (CM) group (n = 736) received medication only upon presentation with fever and parasitemia. The 2-dose group (n = 680) received SP at enrollment and again in the third trimester. The third group (n = 661) received SP monthly.Compared to the CM group (27%), the 2-dose (12%) and monthly treatment groups (9%) had lower rates of placental malaria infection (P < .001). The monthly regimen was more effective in decreasing third trimester anemia rates and also in decreasing placental infection among HIV-positive women (P = .002).No differences between groups were seen in rates of stillbirths, premature births, spontaneous abortions, or neonatal mortality. The stillbirth rate was 2.1% in the CM group, 2.6% in the 2-dose group, and 37% in the monthly group. The NMR was 1.2% in the CM group, 1.3% in the 2-dose group, and 0.3% in the monthly group. Birth weight was significantly increased in the 2-dose SP and the monthly SP groups (mean birth weight 3079 ± 585 g and 3198 ± 528 g, respectively) compared to the CM group (3183 ± 534 g).
Verhoeff et al282Malawi; rural setting; QTAll pregnant women (n = 525) received SP (1500 mg sulfadoxine, 75 mg pyrimethamine) at the time of pregnancy registration and between weeks 28–34 of gestation; some received an additional dose if they developed malaria.Those who received 2 or 3 doses delivered significantly heavier babies (mean difference 257 g, P < .01) than those who received only 1 dose. The incidence of LBW in primigravidae and multigravidae who had been given 2 doses was half that seen in subjects who had been given 1 dose (33.9% vs 13.5%, P = .009, and 13.9% vs 6.5%, P = .02, respectively).
Bouvier et al281Malawi; rural setting; RCTIn the observational phase, women (n = 126) were given malaria chemoprophylaxis as CQ 300 mg/wk in a single dose along with iron. In the intervention phase the drug regimen was combined PROG 200 mg/d and CQ 300 mg/wk.In the observational phase, hematocrit decreased during the rainy season, whereas in the intervention phase, hematocrit increased regardless of season.An annual cycle of birth weight was observed in the observation phase, whereas no seasonal variation in birth weight was observed in the intervention phase.
Steketee et al258Malawi; rural setting; RCT1766 pregnant women were enrolled: group A received CQ 25 mg/kg divided over 2 d, followed by 300 mg weekly; group B received CQ 25 mg/kg divided over 2 d and repeated every 4 wk; group C received CQ 300 mg of base weekly; and group D received a single mefloquine (MQ) dose of 750 mg followed by 250 mg weekly.The multivariance model suggested that improvement of birth weight among offspring of women using MQ was directly related to the drug's effect on clearance of placental infection.MQ use was a significant protective factor for LBW (OR: 1.4; CI: 1.03–1.9; P = .03). In contrast, poorly effective malaria prevention (ie, CQ use) was significantly associated with IUGR-LBW (OR: 1.63; CI: 1.16–2.29). Proportion of LBW in MQ treated mothers was 12.5% vs 15.5% in those treated with CQ (P = .05).
Cot et al284Cameroon; rural and periurban setting; RCT266 pregnant women were enrolled. The CQ group (n = 136) received a 300 mg oral dose weekly until delivery. The controls (n = 135) were untreated.CQ prophylaxis provided a 32% protective effect against malarial placental infection (OR: 0.68; CI: 0.46–0.99, P = .043).Infants born to mothers who received CQ prophylaxis were significantly heavier (mean difference: 207.5 g; P = .02) than the infants born to untreated mothers. There was a 62% decrease in the LBW rate due to the intervention (OR: 0.38; CI: 0.16–0.89; P = .017).
Greenwood et al276The Gambia; rural setting; RPCTData were collected from pregnant women (n = 406) during the course of 2 controlled trials of chemoprophylaxis with Maloprim (pyrimethamine 25 mg and dapsone 100 mg) administered every 2 wk after registration with a TBA (n = 200). The control group (n = 206) was untreated.No difference was observed in maternal mortality (5/206 in the Maloprim group vs 4/200 among those receiving placebo).Stillbirth rates among offspring of women who received chemoprophylaxis were about one-half that of offspring of women who received placebo (62/1000 vs 116/1000), although the difference was not statistically significant. PMR and NMR decreased by 33% and 14%, respectively, in the intervention group.
Menendez et al155The Gambia; rural setting; DBRCTPrimigravid women (n = 230, enrolled over 3 y) were randomized to receive weekly either 1 tablet of Maloprim (pyrimethamine12.5 mg and dapsone 100 mg) or placebo.Women in the intervention group had 86% less parasitemia compared to the placebo group (P < .01).Women taking Maloprim gave birth to heavier babies (mean difference: 153 g; P = .02; χ21 df = 1.2) than the placebo. There was no effect on the stillbirth rate.
Schultz et al287Malawi; rural setting; RCT357 pregnant women were recruited for the trial. The CQ/CQ group (n = 104) received an initial treatment dose of CQ (25 mg base/kg) followed by CQ (300 mg base) weekly. The SP/CQ group (n = 117) received an initial treatment dose of SP (1500 mg sulfadoxine, 75 mg pyrimethamine) followed by CQ (300 mg base) weekly until delivery. The SP/SP group (n = 136) received an initial treatment dose of SP with a second dose at the beginning of the third trimester.The SP/SP regimen was the most effective and consistent in decreasing parasitemia in pregnant women by 83%. The SP/SP regimen was also the most effective in decreasing placental infection (32%, 26% and 9% in the CQ/CQ, SP/CQ SP/SP groups, respectively, P = .006).There were no significant differences in birth weight, LBW or prematurity rates among the 3 regimens.
Mutabingwa et al278Tanzania; rural setting; RCT312 women were enrolled in the study and randomly assigned to 1 of 3 prophylaxis regimens were employed. The CQ group (n = 107) received CQ 300 mg once weekly, and the PROG group (n = 116) received PROG 200 mg daily. The CQ + PROG group (n = 89) received a combination of CQ and PROG in the above dosages.The mean Hb of primigravidae was highest in the PROG group (10 ± 1.6 g/dL after 2 mo of beginning prophylaxis) and lowest in the CQ group (9.4 ± 1.6 g/dL).Primigravidae in the CQ + PROG group delivered heavier infants (mean weight: 2.89 ± 0.52 kg) than primigravidae in the PROG group (2.79 ± 0.42 kg) or CQ group (2.71 ± 0.34), respectively. The CQ group had the highest frequency of LBW (21%) compared to 12% for the PROG group and 15% for the CQ + PROG group.
Nyirjesy et al277Zaire; rural setting; PCSStudy compared pregnant females presenting for intrapartum management (n = 302) who took CQ prenatally versus those who did not take CQ.CQ prophylaxis prevented maternal malaria (RR: 0.4; CI: 0.16–1.0).CQ prophylaxis prevented fetal malaria (RR: 0.2; CI: 0.09–0.44), significantly decreased the risk of perinatal mortality by 62% (OR: 0.38; CI: 0.16–0.80) and reduced LBW by 61%.
Cot et al720West Africa; urban setting; RCTWomen in the treatment group (n = 745) were given CQ 300 mg once weekly; controls (n = 719) were given no malarial prophylaxis.The RR of placental infection in the treated group decreased with increasing duration of prophylaxis; women treated >12 wk had an RR of 0.14 (CI: 0.06–0.3; P = .00004).There was no effect of treatment on birth weight and LBW rates.
Greenwood et al275The Gambia; rural setting; RPCTOnce a woman reported to the TBA that she was pregnant, she was allocated to receive 1 tablet of Maloprim (pyrimethamine 25 mg and dapsone 100 mg) every 2 wk or placebo. 1208 pregnant women participated in the study, and 1049 received Maloprim from a TBA.Level of parasitemia was lower, 19% vs 38%, in primigravidae and 8% vs 20% among multigravidae receiving chemoprophylaxis with Maloprim compared to placebo. The medication also was effective in increasing the mean hematocrit, from 26.6 to 30.1 g/dL (P < .05) in primigravid women.Compared to women who did not report to the TBA and were not given medication or placebo, the women who received Maloprim had a 69% lower stillbirth rate. The reduction was less marked when the Maloprim group was compared to placebo (11% lower stillbirth rate). Early NMR was 25% and 32% for the Maloprim and placebo groups, respectively. Late NMR was 10% and 13% for the Maloprim and placebo groups, respectively. Women using Maloprim delivered heavier babies (mean difference in birth weight among treated primigravidae 159 g; CI: 8–310 g). There was a 72% reduction in the LBW rate among the offspring of Maloprim-treated women (P < .05).
van Eijk et al286Kenya; rural hospital setting; PCSData on frequency of IPT using SP and birth outcomes (vital status, birth weight, gender, and presence of congenital abnormalities) were collected over a 12-mo period for 2302 consecutive deliveries in a provincial hospital in western Kenya.IPT (>1 dose of SP) was associated with a reduction in placental malaria (OR: 0.56; CI: 0.39–0.95). There was a substantial reduction in parasitemia among most women who had received IPT; however, women who had received IPT but remained parasitemic had similar parasite density to women who had never received IPT.IPT (>1 dose of SP) was associated with a reduction in LBW (OR: 0.65; CI: 0.45–0.95). 1 dose of IPT was associated with a mean increase in birth weight of 54 g (CI: 12–120 g; P = .11). ≥2 doses of IPT were associated with a mean increase in birth weight of 128 g (CI: 42–213 g; P = .004).