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The Malaria in Pregnancy (MiP) Library is a regularly updated, comprehensive bibliographic database of published and unpublished literature relating to malaria in pregnancy, including a trial registry of planned and ongoing trials. The MiP library is a product of the Malaria in Pregnancy Consortium and is available free of charge.

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Article highlights from the update in January 2020

Article highlights from the update in January 2022:

 

In January 2021, 165 new entries were added to the MiP library. New entries include peer reviewed journal articles, PhD and MSc theses, reports, and conference abstracts. Here we highlight new articles that may be of particular interest.


Reviews and meta-analyses

Intermittent screening and treatment (IST) of detected malaria infection has been explored as an alternative to intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP), the current WHO guideline. Gutman et al. (2021) compared results from randomized trials evaluating these strategies using individual patient data from 4 of the 5 studies identified. There was no difference in adverse pregnancy outcomes, but subpatent infections were more common in ISTp recipients. Compared to the absence of malaria infections, subpatent malaria was associated with higher low birthweight, lower mean birthweight and higher preterm delivery.

Epidemiology

Leuba et al. (2021) examined risk factors for malaria infection by PCR among primigravidae in the first trimester, the part of pregnancy which cannot be protected by IPTp-SP, using data from a multicountry trial. The prevalence varied widely (6% in Zambia, 38% in Kenya and 63% in the Democratic Republic of Congo). In Kenya, first trimester malaria was associated with shorter height and younger age. In all sites, malaria infection was associated with lower education.

There is a complex relationship between malaria and iron metabolism; in this update three articles aim to clarify this relationship. Serum ferritin reflects the size of total body iron stores and can be used to detect iron deficiency anaemia, which in pregnant women is defined as a ferritin <15 μg/L. However, ferritin levels are affected by inflammation and infection, including malaria, and other assays such as hepcidin levels can be used alternatively to assess iron status see e.g. Dignass et al. (2018) for an overview. A secondary analysis of a cohort of 315 pregnant and 1949 non-pregnant adolescents in Burkina Faso reviewed body iron stores before and during pregnancy Roberts et al. (2021) . At recruitment 11% had low body iron stores. Higher hepcidin concentration in the wet season corresponded with rising malaria prevalence and use of prescriptions, but with no change in body iron stores. A cross-sectional study among 145 pregnant women in Ghana demonstrated that iron-supplemented women with asymptomatic parasitemia had increased free heme, a cytotoxic product from erythrocyte destruction, compared with non-malaria iron-supplemented women Nti et al. (2021). A secondary analysis of a malaria prevention trial in Papua New Guinea evaluated the association between ferritin levels and iron-deficiency at enrolment and birth outcome at delivery Unger et al. (2021) and noted a striking difference by randomized treatment arm (all participants received iron supplementation); among participants who received an SP dose and a treatment course of chloroquine only at enrolment, higher ferritin levels were associated with lower birthweights (-26 grams, 95% CI -50, -1) and increased odds of low birth weight (aOR 1.15, 95% CI 1.00-1.32). Among participants treated with intermittent SP and azithromycin, no effect of ferritin level was seen on birthweight (9 grams, 95% CI -13, 31) and higher ferritin levels were associated with reduced adjusted odds of low birth weight (aOR 0.80, 95% CI 0.67, 0.94). As a possible explanation, the authors noted the broad antimicrobial properties of SPAZ.

Three articles relate to malaria in pregnancy and neurological development of the child. Vera (2022) reported negative effects of in utero exposure to malaria on educational attainment, which were stronger with first trimester exposure, when investigating long-term relationships of malaria outbreaks in Brazil. Videman et al. (2021) examined long term effects of three malaria in pregnancy interventions on infant outcomes; the trial examined IPTp-SP 2 doses, vs. monthly SP doses, vs. monthly SP and two times azithromycin in Malawi. Children of women in the SPAZ arm had reduced stunting by 13 years of age, but there was no impact on cognitive performance. Weckman et al. (2021) evaluated children two years after a trial in Malawi where mothers were randomized to IPTp-SP or IST. They found that children with intra-uterine exposure to malaria between 33 and 37 weeks of gestation had delayed language development across the 2-year follow-up.

Malaria prevention

LLINs have the advantage that they can protect a pregnant woman from malaria early in pregnancy, before she visits the antenatal clinic. Roh et al. (2022) evaluated the effect of a long-lasting insecticidal nets (LLIN) campaign on pregnancy outcomes; they estimated that the LLIN-campaign was associated with a 26% (95% CI 7–41) reduction in stillbirth incidence and a 15% (95% CI 7-33) reduction in LBW incidence over a 9-month period. The effect on incidence of stillbirth was greatest for women delivering 7–9 months after the campaign for whom the LLINs would have covered most of their pregnancy. No difference was detected between different types of nets that were used (piperonyl butoxide treated nets that may restore pyrethroid sensitivity and conventional LLINs) but the sample size may have been too small. Ameyaw et al. (2021) examined factors associated with optimal IPTp uptake using DHS data from 20 sub-Saharan countries (2012-2018) and concluded that low uptake was associated with low maternal knowledge, and low national economic status based on gross national income per capita; 53.9% and 25.9% of the variation in optimum IPTp-SP uptake were attributable to community-level and country-level factors, respectively. Apanga et al. (2021) used 17 multiple indicator cluster surveys from sub-Saharan countries (2013-2019) to evaluate the association between early antenatal visits and uptake of three or more doses of SP; IPTp-3+ was 30% higher among mothers who had earlier 1st ANC visits, defined as ANC contact within the first trimester of pregnancy. Darteh et al. (2021) used Malaria Indicator Survey data from 12 sub-Saharan countries (2015-2019); IPTp-SP 3+ was associated with higher maternal education level, older age group, and no exposure to malaria message on the radio or television. The average coverage of IPTp-SP 3+ was 31%. De-Gaulle et al. (2021) used ANC observations in Ghana to assess appropriate delivery of IPTp and ITNs among antenatal clinic attendees; about 24% and 41% of clients did not receive IPTp or an ITN respectively, despite being eligible. Doumbia et al. (2021) developed and implemented a checklist for health care workers to improve IPTp uptake and noted an increase in uptake of IPTp-SP by directly observed treatment before (0%) and after the implementation (59%, n=100).

Comorbidity

Dambrun et al. (2021) conducted a retrospective study on toxoplasmosis from a cohort in Benin in 2008-2010; seroprevalence rate was 52.6%. Toxoplasmosis seropositive pregnant women tended to present lower malaria infection during pregnancy and at delivery. A cross-sectional study in Burkina Faso among 402 pregnant women reported 12.9% of women had a malaria infection in combination with at least one sexually transmittable or reproductive tract infection Lingani et al. (2021). Bacterial vaginosis was very common (67.7%) and only 10% of the coinfections were symptomatic. Using routine data for two years in two rural districts in Burkina Faso, Zango et al. (2021) examined the effect of coinfections: both miscarriage and stillbirth were associated with malaria (aOR 1.31, 1.07 – 1.59), curable STI (aOR 1.65, 1.06 – 2.59), and coinfection (aOR 2.00, 1.13 – 3.52). Lastly, Burt et al. (2021) documented the impact of 3 months of lock down during COVID in a Ugandan district when IPTp-SP and other antenatal services decreased. During lockdown and immediately post-lockdown there was an increase in the number of women treated for high blood pressure, eclampsia and pre-eclampsia (218 more/month), adverse pregnancy outcomes (stillbirths, low birthweight and premature births), the rate of neonatal unit admissions, neonatal deaths and abortions. Maternal mortality remained stable.