Dynamics of Submicroscopic Plasmodium falciparum Infections Throughout Pregnancy: A Preconception Cohort Study in Benin

Abstract

Background: In the context of global malaria elimination efforts, special attention is being paid to submicroscopic Plasmodium falciparum infections. In pregnant, sub-Saharan African women, such infections are more prevalent than microscopic infections, and are thought to have adverse effects on both mothers' and newborns' health. However, no study has studied the dynamics and determinants of these infections throughout pregnancy. Retard de Croissance Intra-uterin et Paludisme (RECIPAL), a preconception cohort study carried out in Benin between 2014 and 2017, represented a unique opportunity to assess this issue.

Methods: We used data from 273 pregnant Beninese women who were followed-up from preconception to delivery. We studied the dynamics of and factors influencing submicroscopic (and microscopic) P. falciparum infections during the 3 trimesters of pregnancy, using an ordinal logistic mixed model.

Results: The incidence rate of submicroscopic P. falciparum infections during pregnancy was 12.7 per 100 person-months (95% confidence interval [CI] 10.8-14.9), compared to 6.7 per 100 person-months (95% CI 5.5-8.1) for microscopic infections. The prevalences were highest in the first trimester for both submicroscopic and microscopic infections. After adjustment for potential confounding factors, we found that those of young age and those with a submicroscopic P. falciparum infection prior to pregnancy were at significantly higher risks of submicroscopic and microscopic infections throughout pregnancy, with a more pronounced effect in the first trimester of pregnancy.

Conclusions: The first trimester of pregnancy is a particularly high-risk period for P. falciparum infection during pregnancy, especially for the youngest women. Malaria prevention tools covering the preconception period and early pregnancy are urgently needed to better protect pregnant women and their newborns.

Keywords: dynamic; preconception cohort; pregnancy; sub-Saharan Africa; submicroscopic P. falciparum infections.

Figure 1.

Construction of the Plasmodium falciparum infection status per trimester variable, in a hypothetical pregnant woman who would have attended 2 visits in the first trimester, 3 visits in the second trimester, and 3 visits in the third trimester. If at the 2 visits in the first trimester the woman was diagnosed as negative, in the second trimester she was diagnosed as negative/submicroscopic/negative, and at least at 1 of the 3 visits in the third trimester she was diagnosed as microscopic, she was therefore classified, respectively, as having a negative infection status, submicroscopic infection status, and microscopic infection status for the first, second and third trimesters. Abbreviations: Micro, microscopic P. falciparum infection at the visit; Neg, no P. falciparum infection (negative) at the visit; Sub, submicroscopic P. falciparum infection at the visit.

Figure 2.

Flow chart of Retard de Croissance Intra-uterin et Paludisme (RECIPAL) study, June 2014–August 2017, Benin. Abbreviation: WRA, women of reproductive age.

Figure 3.

Dynamics of Plasmodium falciparum infections before and during pregnancy, Retard de Croissance Intra-uterin et Paludisme (RECIPAL) 2014–2017, Benin.

Figure 4.

Proportion of women with submicroscopic and microscopic infection status in each trimester of pregnancy, Retard de Croissance Intra-uterin et Paludisme (RECIPAL) 2014–2017, Benin. P values are from Chi-square tests.

Figure 5.

Predicted probabilities from the ordinal logistic mixed model of the occurrences of submicroscopic Plasmodium falciparum infections per trimester, according to maternal age and presence of submicroscopic P. falciparum infection before conception (Retard de Croissance Intra-uterin et Paludisme [RECIPAL] 2014–2017, Benin). P values correspond to the t-test comparisons. *Indicates a t-test comparison between the predicted probabilities of having a submicroscopic P. falciparum infection at the first trimester of pregnancy for the youngest women (P value = .1059). **Indicates a t-test comparison between the predicted probabilities of having a submicroscopic P. falciparum infection at the second trimester of pregnancy for the youngest women (P value = .5212). ***Indicates a t-test comparison between the predicted probabilities of having a submicroscopic P. falciparum infection at the third trimester of pregnancy for the youngest women (P value = .3554).

Figure 6.

Predicted probabilities from the ordinal logistic mixed model of the occurrence of microscopic Plasmodium falciparum infections per trimester, according to maternal age and presence of submicroscopic P. falciparum infection before conception (Retard de Croissance Intra-uterin et Paludisme [RECIPAL] 2014–2017, Benin). P values correspond to the t-test comparisons. *Indicates a t-test comparison between the predicted probabilities of having a microscopic P. falciparum infection at the first trimester of pregnancy for the youngest women (P value < .0001). **Indicates a t-test comparison between the predicted probabilities of having a microscopic P. falciparum infection at the second trimester of pregnancy for the youngest women (P value = .0810). ***Indicates a t-test comparison between the predicted probabilities of having a microscopic P. falciparum infection at the third trimester of pregnancy for the youngest women (P value = .5404).