Dataset Information

Overall, anti-malarial, and non-malarial effect of intermittent preventive treatment during pregnancy with sulfadoxine-pyrimethamine on birthweight: a mediation analysis.

ABSTRACT:

Background

Trials of intermittent preventive treatment (IPTp) of malaria in pregnant women that compared dihydroartemisinin-piperaquine with the standard of care, sulfadoxine-pyrimethamine, showed dihydroartemisinin-piperaquine was superior at preventing malaria infection, but not at improving birthweight. We aimed to assess whether sulfadoxine-pyrimethamine shows greater non-malarial benefits for birth outcomes than does dihydroartemisinin-piperaquine, and whether dihydroartemisinin-piperaquine shows greater antimalarial benefits for birth outcomes than does sulfadoxine-pyrimethamine.

Methods

We defined treatment as random assignment to sulfadoxine-pyrimethamine or dihydroartemisinin-piperaquine before pooling individual participant-level data from 1617 HIV-uninfected pregnant women in Kenya (one trial; n=806) and Uganda (two trials; n=811). We quantified the relative effect of treatment on birthweight (primary outcome) attributed to preventing placental malaria infection (mediator). We estimated antimalarial (indirect) and non-malarial (direct) effects of IPTp on birth outcomes using causal mediation analyses, accounting for confounders. We used two-stage individual participant data meta-analyses to calculate pooled-effect sizes.

Findings

Overall, birthweight was higher among neonates of women randomly assigned to sulfadoxine-pyrimethamine compared with women assigned to dihydroartemisinin-piperaquine (mean difference 69 g, 95% CI 26 to 112), despite placental malaria infection being lower in the dihydroartemisinin-piperaquine group (relative risk [RR] 0·64, 95% CI 0·39 to 1·04). Mediation analyses showed sulfadoxine-pyrimethamine conferred a greater non-malarial effect than did dihydroartemisinin-piperaquine (mean difference 87 g, 95% CI 43 to 131), whereas dihydroartemisinin-piperaquine conferred a slightly larger antimalarial effect than did sulfadoxine-pyrimethamine (8 g, -9 to 26), although more frequent dosing increased the antimalarial effect (31 g, 3 to 60).

Interpretation

IPTp with sulfadoxine-pyrimethamine appears to have potent non-malarial effects on birthweight. Further research is needed to evaluate monthly dihydroartemisinin-piperaquine with sulfadoxine-pyrimethamine (or another compound with non-malarial effects) to achieve greater protection against malarial and non-malarial causes of low birthweight.

Funding

Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bill & Melinda Gates Foundation, and Worldwide Antimalarial Resistance Network.

SUBMITTER: Roh ME

PROVIDER: S-EPMC7303957 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundIntermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended in HIV-negative women to avert malaria, while this relies on cotrimoxazole prophylaxis (CTXp) in HIV-positive women. Alternative antimalarials are required in areas where parasite resistance to antifolate drugs is high. The cost-effectiveness of IPTp with alternative drugs is needed to inform policy.MethodsThe cost-effectiveness of 2-dose IPTp-mefloquine (MQ) was compared with IPTp-SP in HIV-negative women (Benin, Gabon, Mozambique and Tanzania). In HIV-positive women the cost-effectiveness of 3-dose IPTp-MQ added to CTXp was compared with CTXp alone (Kenya, Mozambique and Tanzania). The outcomes used were maternal clinical malaria, anaemia at delivery and non-obstetric hospital admissions. The poor tolerability to MQ was included as the value of women's loss of working days. Incremental cost-effectiveness ratios (ICERs) were calculated and threshold analysis undertaken.ResultsFor HIV-negative women, the ICER for IPTp-MQ versus IPTp-SP was 136.30 US$ (2012 US$) (95%CI 131.41; 141.18) per disability-adjusted life-year (DALY) averted, or 237.78 US$ (95%CI 230.99; 244.57), depending on whether estimates from Gabon were included or not. For HIV-positive women, the ICER per DALY averted for IPTp-MQ added to CTXp, versus CTXp alone was 6.96 US$ (95%CI 4.22; 9.70). In HIV-negative women, moderate shifts of variables such as malaria incidence, drug cost, and IPTp efficacy increased the ICERs above the cost-effectiveness threshold. In HIV-positive women the intervention remained cost-effective for a substantial (up to 21 times) increase in cost per tablet.ConclusionsAddition of IPTp with an effective antimalarial to CTXp was very cost-effective in HIV-positive women. IPTp with an efficacious antimalarial was more cost-effective than IPTp-SP in HIV-negative women. However, the poor tolerability of MQ does not favour its use as IPTp. Regardless of HIV status, prevention of malaria in pregnancy with a highly efficacious, well tolerated antimalarial would be cost-effective despite its high price.Trials registrationClinicalTrials.gov NCT 00811421; Pan African Trials Registry PACTR2010020001429343 and PACTR2010020001813440.

Project description:Malaria in pregnancy poses a great risk to both mother and fetus. In Ghana, malaria accounts for 3.4% of deaths and 16.8% of all hospital admissions in pregnant women. In 2014, Ghana updated her policy on intermittent preventive treatment of malaria in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP) to reflect the updated policy of the WHO. This study determined the level of uptake of sulfadoxine pyrimethamine (SP) to serve as baseline for monitoring progress and also reviewed stock levels of SP, a key factor in the programme implementation.A cross-sectional hospital-based study was carried out among nursing mothers who had delivered within 12 weeks and were seeking postnatal care at Osu Government Maternity Home in Accra. Antenatal record books of the mothers were reviewed and data collected on number of visits and receipt of IPTp-SP. Mothers were interviewed and data collected on their background characteristics and obstetric history. Data on SP stock levels for the past 6 months were also reviewed. Logistic regression analysis was carried out to determine antenatal indicators on uptake of IPTp-SP using Stata version 12.The proportion of uptake of three-five doses of SP were: IPT3 (87.5%), IPT4 (55.7%) and IPT5 (14.5%). The proportion of women who received the first dose of SP at 16 weeks of gestation was 21.3%. Women who made ≥4 visits were more likely to receive ≥3 doses of SP than those who made <4 visits (AOR = 4.57, 95% CI 1.15-18.16, p < 0.05). Women receiving the first dose of SP in the third trimester were less likely to receive ≥3 doses of SP than those who received the drug in the second trimester (AOR = 0.04, 95% CI 0.01-0.16, p < 0.05). Stock levels of SP were adequate to meet the demands by the pregnant women at the Maternity Home for the period under review.The uptake of ≥3 doses of SP was high in the study area. Frequent visits to the antenatal clinic and early uptake of the first dose of SP by pregnant women are necessary to achieve the new target of five or more doses of SP.

Project description:BACKGROUND:Growing concerns about the waning efficacy of IPTp-SP warrants continuous monitoring and evaluation. This study determined coverage of IPTp-SP and compared the effectiveness of the 3-dose to 2-dose regimen on placental malaria (PM) infection and low birth weight (LBW) in the Mount Cameroon area. METHODS:Consenting pregnant women were enrolled consecutively through a cross-sectional survey at delivery at four antenatal clinics, two each from semi-rural and semi-urban settings from November 2016 to December 2017. Reported IPTp-SP use, demographic and antenatal clinic (ANC) data of the mothers and neonate birth weights were documented. Maternal haemoglobin concentration was measured using a haemoglobinometer and PM infection diagnosed by placental blood microscopy. Logistic regression analysis was used to model study outcomes. RESULTS:Among the 465 parturient women enrolled, 47.0% (203), 34.7% (150), 18.3% (79) and 7.1% (33) reported uptake of ≥ 3, 2.1 dose(s) and no SP, respectively. Uptake of ≥ 3 doses varied significantly (p < 0.001) according to type of medical facility, timing of ANC initiation and number of ANC visits. The prevalence of PM was 18.5% where uptake of ≥ 3 SP doses (AOR = 2.36: 95% CI 1.41-4.87), primiparity (AOR = 2.13: 95% CI 1.19-3.81), semi-rural setting (AOR = 1.85: 95% CI 1.12-3.04) increased odds of infection. Also, three or more dosing was associated (p < 0.001) with increased PM density notably among women from semi-urban areas. Compared with third trimester, ANC initiation in the second trimester (AOR: 0.39: 95% CI 0.20-0.74) lower odds of infection. The prevalence of LBW infants was 7.3% and were generally those of anaemic (AOR: 4.6: 95% CI 1.03-20.57) and semi-rural (AOR: 5.29: 95% CI 1.73-16.15) women. Although ≥ 3 (AOR: 0.31: 95% CI 0.11-0.87) and 2 (AOR: 0.32: 95% CI 0.11-0.93) doses of SP was associated with lower odds of LBW, ≥ 3 doses were not associated with additional increase in birth weight nor maternal haemoglobin levels when compared with 2 doses. CONCLUSION:In the Mount Cameroon area, reported uptake of IPTp with ≥ 3 SP doses did not provide observable prophylactic benefits. SP resistance efficacy studies are necessary.