Adverse pregnancy outcomes are associated with Plasmodium vivax malaria in a prospective cohort of women from the Brazilian Amazon

Abstract

Background Malaria in Brazil represents one of the highest percentages of Latin America cases, where approximately 84% of infections are attributed to Plasmodium (P.) vivax. Despite the high incidence, many aspects of gestational malaria resulting from P. vivax infections remain poorly studied. As such, we aimed to evaluate the consequences of P. vivax infections during gestation on the health of mothers and their neonates in an endemic area of the Amazon. Methods and findings We have conducted an observational cohort study in Brazilian Amazon between January 2013 and April 2015. 600 pregnant women were enrolled and followed until delivery. After applying exclusion criteria, 329 mother-child pairs were included in the analysis. Clinical data regarding maternal infection, newborn’s anthropometric measures, placental histopathological characteristics, and angiogenic and inflammatory factors were evaluated. The presence of plasma IgG against the P. vivax (Pv) MSP119 protein was used as marker of exposure and possible associations with pregnancy outcomes were analyzed. Multivariate logistic regression analysis revealed that P. vivax infections during the first trimester of pregnancy are associated with adverse gestational outcomes such as premature birth (adjusted odds ratio [aOR] 8.12, 95% confidence interval [95%CI] 2.69–24.54, p < 0.0001) and reduced head circumference (aOR 3.58, 95%CI 1.29–9.97, p = 0.01). Histopathology analysis showed marked differences between placentas from P. vivax-infected and non-infected pregnant women, especially regarding placental monocytes infiltrate. Placental levels of vasomodulatory factors such as angiopoietin-2 (ANG-2) and complement proteins such as C5a were also altered at delivery. Plasma levels of anti-PvMSP119 IgG in infected pregnant women were shown to be a reliable exposure marker; yet, with no association with improved pregnancy outcomes. Conclusions This study indicates that P. vivax malaria during the first trimester of pregnancy represents a higher likelihood of subsequent poor pregnancy outcomes associated with marked placental histologic modification and angiogenic/inflammatory imbalance. Additionally, our findings support the idea that antibodies against PvMSP119 are not protective against poor pregnancy outcomes induced by P. vivax infections.

Pregnancy and malaria: the perfect storm

“…Although P. vivax- infected erythrocytes do not sequester in the placenta, vivax malaria has been associated with maternal anemia and low birth weight. In Brazil, P. vivax in the first trimester of pregnancy was associated with premature birth (aOR 8.12, 95% CI 2.69, 24.54) and reduced head circumference (aOR 3.58, 95% CI 1.29, 9.97) [41 ▪ ]. P. vivax was also associated with placental monocyte infiltrates and dysregulation of angiopoietin-2 and complement C5a production, processes previously reported in P. falciparum malaria.…”

Total Hemoglobin Trajectories from Pregnancy to Postpartum in Rural Northeast Brazil: Differences between Adolescent and Adult Women

“…Generally, hemoglobin levels drop from the first to third trimester of pregnancy [ 3 ] and return to pre-pregnancy levels postpartum [ 4 ]. However, when iron stores drop drastically during pregnancy, complications like gestational anemia [ 5 ], insufficient fetal weight gain [ 6 ], and maternal and fetal mortality [ 7 ] can arise.…”

“…During adolescence, there is a greater physiological need for hemoglobin due to increased erythrocytic mass for rapid somatic growth [ 11 ] and menstruation onset [ 2 ]. Pregnancy imposes additional hemoglobin requirements [ 2 , 6 ], rendering pregnant adolescents vulnerable to anemia and adverse maternal and child health consequences, like intrauterine growth retardation [ 11 ] and low birth weight [ 6 ].…”

Predictors of knowledge and use of long-lasting insecticidal nets for the prevention of malaria among the pregnant women in Pakistan

“…Low birth weight, abortion, and miscarriage are serious health problems due to gestational anaemia resulting from malaria [ 7 , 8 ]. These and other adverse outcomes during pregnancy can be worse in areas where P. falciparum or Plasmodium vivax are endemic [ 9 , 10 ]. Pregnant women are, therefore, three times more at risk of dying due to malaria compared to non-pregnant women [ 11 ].…”