Socio-demographic and obstetric characteristics of study participants
The total of 1,161 pregnant women participated in the study with median (IQR) age of 25 (18-44) years old. Most of them were married (73.7%) with primary education level (60.9%) and attended ANC visits at least 4 times (66.9%) during their recent pregnancies. They reported to have used various malaria preventive measures such as IRS (57.9%) and ITN (98.1%), and anaemia preventive strategies including mebendazole (96.6%) and FEFO (97.9%) (Table 1). Twenty-eight (2.4%) women reported to have contracted malaria at least once during their recent pregnancies; 19 used artemether-lumefantrine, 3 artesunate injection, 1 quinine tablets, 1 dihydroartemisinin-piperaquine (DP) and 4 could not recall the names of the antimalarial drugs they used. Fifteen (1.3%) pregnant women had fever with no confirmed no malaria.
At delivery, half of the women gave birth to male or female babies at mean (±SD) gestation age of 38.8(±1.6) weeks with birth weight of 3.1 (±0.46) Kg. The proportions of primigravida, secundigravida and multigravida among the study participants were 38.4%, 28.3% and 33.3%, respectively (Table 1).
The uptake of optimal IPTp-SP doses
The total of 397 (34.2%) women used ≤2 doses while 764 (65.8%) used ≥3 doses of IPTp-SP. Most of the participants’ characteristics such as participants age, gravidity and education level were not associated with the uptake of IPTp-SP (p>0.05). On univariate analysis the uptake of IPTp-SP was associated with marital status (p=0.02) and ANC attendance (p<0.01). After adjusting for covariates, the use of ≥3 doses of IPTp-SP was significantly associated with increased attendance to ANCs (p = <0.01). Those who attended ≥4 ANC visits had six times higher odds of taking ≥3 doses of IPTp-SP than those who attended ≤3 ANC visits (aOR, 5.91; 95% CI, 4.49-7.76; p = <0.01) (Table 2).
Effect of IPTp-SP doses on placental malaria
Placental malaria by histology was detected in 42 (3.62%) out of the 1,161 study participants. Three (7.1%) out of the 42 pregnant women with peripheral malaria had placental malaria (p=0.002), accounting for 21-fold risk of placental malaria than those without peripheral parasitaemia (aOR, 21.37; 95% CI, 4.47-102.08; p<0.001). Of all participants with placental malaria, 2.5% (n=42) had active infection, whereas 0.40% had active-chronic infection and 0.50% had past infection. Out of 397 pregnant women who used ≤2 doses of IPTp-SP, 16 (4.0%) of them had placental malaria. For 764 pregnant women who used ≥3 doses of IPTp-SP, 26 (3.4%) of them had placental malaria. Sub-optimal doses (≤2 doses) of IPTp-SP did not increase the risk of placental malaria among pregnant women (p=0.97) (Table 3).
Out of 1,119 placental blood samples that were microscopically confirmed to be negative for malaria parasites, 4/286(1.4%) had submicroscopic placental malaria. Of these participants with submicroscopic placental malaria, 3 (1.58%) of them used ≥3 IPTp-SP doses while 1 (1.04%) used ≤2 IPTp-SP doses. PCR positive samples revealed that, all the submicroscopic infections were due to P. falciparum species (Table 2).
Effect of sub-optimal IPTp-SP doses on adverse birth outcomes
Out of 1,161 pregnant women, the prevalence of maternal anaemia and foetal anaemia was 43.8% and 10.1%, respectively. Peripheral malaria was significantly associated with maternal anaemia and not foetal anemia. Women with peripheral malaria had six times risk of maternal anaemia than those who had no malaria infection (aOR, 5.83; 95%CI, 1.10-30.92; p = 0.04). In multivariable analysis, the use of ≤2 IPTp-SP doses increased the risk of maternal anaemia by 1.36 times higher compared to the use of ≥3doses (aOR, 1.36; 95%CI, 1.04-1.79; p = 0.02), Table 4.
The use of sub-optimal IPTp-SP doses did not increase the risk of foetal anaemia (cOR, 0.84; 95%CI, 0.56-1.27; p=0.41). Further analysis revealed that, pregnant women who had anaemia were 2 times at increased risk of delivering anemic babies (aOR, 1.9; 95% CI, 1.31-2.87; p = <0.01). Other characteristics of pregnant women such as age, marital status, education level, number of ANC visits, use of FEFO, mebendazole, ITN, IRS, gestation age, gravidity and placental malaria were not associated with maternal and foetal anemia.
Also, the risk of preterm delivery was not increased by the use of sub-optimal IPTp-SP doses, however, factors such as primigravidity and IRS were associated with preterm delivery as we reported previously (37). Women who did not use ITN had increased risk of preterm delivery three-times higher than those who used ITN (aOR,3.39; 95%CI, 1.078-10.67; p=0.04). In addition, women who had <4 ANC visits had two-fold risk of preterm delivery compared to those who attended ≥4 ANC visits (aOR, 2.05; 95%CI, 1.26-3.33; p=0.004).
Effect of Sulfadoxine plasma concentration at birth on peripheral and placental malaria and adverse birth outcomes
SDX was detected in 218 (92.0%) out of 237 participants. Majority (60.1%) of those who had detectable SDX used ≥3 doses of IPTp-SP. In the analyzed samples (n=237), 79 (33.3%) samples had detectable SDX levels but could not be quantified (plasma concentration was <3μg/ml). Three (1.3%) participants had detectable and quantified SDX concentration despite of reporting to have not taken any dose of IPTp-SP throughout their recent pregnancies. Out of 19 (8.0%) women who had undetectable SDX in plasma, 13 (68.4%) used ≤2doses of IPTp-SP. Six (2.5%) participants who reported to have used ≥3doses of IPTp-SP had no detectable SDX in plasma.
The overall geometric mean plasma SDX concentration was 10.76± 2.51μg/mL. The geometric mean concentration for women who used ≥3 IPTp-SP doses was 10.46±2.50μg/mL, while those who used ≤2 doses was 11.24±2.54μg/mL. There was no difference in the geometric mean of plasma concentration between women who used sub-optimal versus optimal IPTp-SP doses (p=0.65) (Figure 1A).
There was no statistical association between prevalence of peripheral malaria and low SDX concentration (p=0.37). In addition, the differences in SDX plasma concentration at birth had no effect on placental malaria among the study participants (p=0.24), Table 5.
There was a slight increase in maternal Hb concentration with plasma concentration of SDX at delivery, but this relationship was weak (spearman’s correlation=0.02) (Figure 1B). The geometric mean of plasma SDX between anemic and non-anemic women was not statistically different (p=0.49). Similarly, the differences of geometric SDX concentration at birth was not associated with low birth weight, foetal anaemia and preterm delivery (p>0.05), Table 5.