In utero exposure to malaria is associated with metabolic traits in adolescence: The Agogo 2000 birth cohort study

Abstract

Summary Objectives: Malaria in pregnancy (MiP) contributes to fetal undernutrition and adverse birth outcomes, and may constitute a developmental origin of metabolic diseases in the offspring. In a Ghanaian birth cohort, we examined the relationships between MiP-exposure and metabolic traits in adolescence.Methods: MiP at delivery was assessed in 155 mother-child pairs. Among the now teenaged children (mean age, 14.8 years; 53% male), we measured fasting plasma glucose (FPG), body mass index (BMI), and systolic and diastolic blood pressure (BP). Associations of MiP with the adolescents' FPG, BMI, and BP were examined by linear regression.Results: At delivery, 45% were MiP-exposed, which increased FPG in adolescence, adjusted for mother's age at delivery, parity and familial socio-economic status (infected vs. uninfected: mean ΔFPG = 0.20 mmol/L; 95% confidence interval (CI): 0.01, 0.39; p = 0.049). As a trend, this was discernible for BP, particularly for microscopic infections (mean Δsystolic BP = 5.43 mmHg; 95% CI: 0.00, 10.88; p = 0.050; mean Δdiastolic BP = 3.67 mmHg; 95% CI: −0.81, 8.14; p = 0.107). These associations were largely independent of birth weight, gestational age and teenage BMI. Adolescent BMI was not related to MiP. Conclusions:In rural Ghana, exposure to malaria during fetal development contributes to metabolic conditions in young adulthood.

Intrauterine programming of obesity and type 2 diabetes

“…Metabolic and immune pathways are extensively integrated in health and disease. Specific metabolites in the cholesterol and tricarboxylic acid (TCA) cycle have an effect on inflammation [14, 15], and, conversely, infectious diseases in pregnancy may contribute to developmental origins of metabolic conditions [16]. Viral infections in pregnancy, specifically by enteroviruses [17], have been associated with type 1 diabetes in the offspring, though the mechanisms are complex and evidence circumstantial [18, 19].…”

Epidemiological links between malaria parasitaemia and hypertension

“…This result is consistent with a causal effect of malaria parasitaemia on hypertension, if the currently observed malaria parasitaemia circumstances reflect a more general and long-term propensity to efficiently fight a Plasmodium infection, which is more prevalent than among those not currently having malaria parasitaemia. In this case, the lower level of BP among the participants with more latent malaria may reflect that they possibly had fewer severe infections and pro-inflammatory episodes over the life course [7,9,12–14].…”

“…In this case, the participants may have experienced more severe infections and pro-inflammatory episodes in the past, mediating the effect on high BP. In-utero exposure to microscopic malaria was associated with BP in adolescents [12]. Fever, characteristic of symptomatic malaria results from inflammation and may lead to haemodynamic changes, which raise BP to improve perfusion and restore homeostasis [45,46].…”

“…Proposed direct effects of malaria parasitaemia include the promotion, in the long-term, of an atherosclerosis-promoting pro-inflammatory state because of repeated infections [7,9–11]. In-utero and early life effects of malaria parasitaemia on low birth weight, malnutrition and stunting, are established risk factors for CVD later in life [7,12–16]. In pregnant women, malaria parasitaemia effect on preeclampsia puts them at risk for hypertension [7].…”

SNP rs6564851 in the BCO1 Gene Is Associated with Varying Provitamin a Plasma Concentrations but Not with Retinol Concentrations among Adolescents from Rural Ghana

“…Between June and August 2015, 200 adolescent boys and girls from the Agogo 2000 birth cohort were reassessed and underwent a health check-up as part of the follow-up on the impact of gestational malaria on health outcomes [ 26 ]. The inclusion criteria for this cross-sectional study were turning 15 in the year that the study was conducted, informed written consent, absence of pregnancy and no previous diagnosis of type 1 diabetes [ 13 ].…”