Reduced Birth Weight Caused by Sextuple Drug-Resistant Plasmodium falciparum Infection in Early Second Trimester.

Mutations in the Plasmodium falciparum genes Pfdhfr and Pfdhps, particularly the sextuple mutant haplotype threatens the antimalarial effectiveness of sulfadoxine-pyrimethamine (SP) as intermittent preventive treatment during pregnancy (IPTp). To explore the impact of sextuple mutant haplotype infections on outcome measures after provision of IPTp with SP, we monitored birth outcomes in women followed up from before conception or from the first trimester until delivery. Women infected with sextuple haplotypes, in the early second trimester specifically, delivered newborns with a lower birth weight compared with women who did not have malaria during pregnancy (difference, -267 g; 95% confidence interval, -454 to -59; P = .01) and women infected with less SP-resistant haplotypes (-461 g; -877 to -44; P = .03). Thus, sextuple haplotype infections seem to affect the effectiveness of SP for IPTp and directly affect birth outcome by lowering birth weight. Close monitoring and targeted malaria control during early pregnancy is therefore crucial to improving birth outcomes.

Anemia in late pregnancy induces an adaptive response in fetoplacental vascularization.

INTRODUCTION: Anemia during pregnancy may compromise fetal and newborn's health, however, little is known about how and when the fetoplacental vascularization is most vulnerable to anemia. METHODS: Using systematic and isotropic uniform random sampling, placental samples were collected from 189 placentas in a cohort study of Tanzanian women whose hemoglobin concentration was measured throughout pregnancy. Fetoplacental vessels and villi were defined as exerting either a transport or diffusion function. The vascularization patterns for transport and diffusion vessels and villi were assessed by stereology. Blood vessel length, surface area and diffusion distance as well as placental villi volume were calculated. RESULTS: Anemia from a gestational age of 23 weeks was significantly associated with increased fetoplacental vascularization in vessels and villi compared to women who were non-anemic throughout pregnancy. Transport surface vessel area: 0.31 m2 [95% CI: 0.18-0.55], P = 0.01; Transport villi volume 19.8 cm3 [95% CI: 6.37-33.2], P = 0.004, Transport vessel diameter 7.23 µm [95% CI: 1.23-13.3], P = 0.02. Diffusion vessel surface: 3.23 m2 [95% CI: 1.55-4.91], P < 0.001 and diffusion villi volume: 29.8 cm3 [95% CI: 10.0-49.5], P = 0.003). Finally, all the measured transport vessel and villi significantly parameters and diffusion vessel surface, vessel diameter and diffusion distance were associated with birth weight. DISCUSSION: Increased fetoplacental vascularization related to anemia from a gestational age of 23 weeks in pregnancy together with the association between fetoplacental vascularity and birth weight suggest that the timing of anemia determines the effect on fetoplacental vascularization and underlines the clinical relevance for proper development of fetoplacental vasculature.

Malaria in Early Pregnancy and the Development of the Placental Vasculature.

BACKGROUND: Pregnancy malaria has a negative impact on fetal outcome. It is uncertain whether infections in early pregnancy have a clinical impact by impeding the development of the placental vasculature. METHODS: Tanzanian women (n = 138) were closely monitored during pregnancy. Placentas collected at birth were investigated using stereology to establish the characteristics of placental villi and vessels. Placental vasculature measures were compared between women infected with malaria and controls. RESULTS: Compared with controls, placentas from women infected with malaria before a gestational age (GA) of 15 weeks had a decreased volume of transport villi (mean decrease [standard deviation], 12.45 [5.39] cm3; P = .02), an increased diffusion distance in diffusion vessels (mean increase, 3.33 [1.27] µm; P = .01), and a compensatory increase in diffusion vessel surface area (mean increase, 1.81 [0.74 m2]; P = .02). In women who had malaria before a GA of 15 weeks diffusion vessel surface area and transport vessel length distance were positive predictors for birth weight (multilinear regression: P = .007 and P = .055 for diffusion surface area and transport length, respectively) and GA at delivery (P = .005 and P = .04). CONCLUSIONS: Malaria infection in early pregnancy impedes placental vascular development. The resulting phenotypic changes, which can be detected at delivery, are associated with birth weight and gestational length. CLINICAL TRIALS REGISTRATION: NCT02191683.