Testing an infection model to explain excess risk of preterm birth with long-term iron supplementation in a malaria endemic area
| العنوان: | Testing an infection model to explain excess risk of preterm birth with long-term iron supplementation in a malaria endemic area |
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| المؤلفون: | Stephen A Roberts, Halidou Tinto, Bernard J. Brabin |
| المصدر: | Malaria Journal, Vol 18, Iss 1, Pp 1-13 (2019) Malaria Journal |
| بيانات النشر: | BMC, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Gastrointestinal Diseases, Hepcidin, Physiology, qv_183, law.invention, 0302 clinical medicine, Randomized controlled trial, law, 2. Zero hunger, 0303 health sciences, biology, Incidence (epidemiology), Absolute risk reduction, Gestational age, 3. Good health, ws_420, Infectious Diseases, Malaria Pathway, Premature Birth, Female, medicine.symptom, Risk, lcsh:Arctic medicine. Tropical medicine, Adolescent, Dual infection model, lcsh:RC955-962, Iron, 030231 tropical medicine, Inflammation, wa_395, lcsh:Infectious and parasitic diseases, Young Adult, 03 medical and health sciences, Burkina Faso, medicine, Humans, lcsh:RC109-216, 030304 developmental biology, business.industry, Research, Preterm birth, Models, Theoretical, medicine.disease, wa_320, wc_750, Malaria, Dietary Supplements, biology.protein, Parasitology, business |
| الوصف: | Background In view of recent evidence from a randomized trial in Burkina Faso that periconceptional iron supplementation substantially increases risk of spontaneous preterm birth ( Methods The analysis developed a model based on a dual hit inflammatory mechanism arising from simultaneous malaria and gut infections, supported in part by published trial results. This model is developed to understand mechanisms linking iron supplementation, malaria and gestational age. Background literature substantiates synergistic inflammatory effects of these infections where trial data is unavailable. A path modelling exercise assessed direct and indirect paths influencing preterm birth and gestation length. Results A dual hit hypothesis incorporates two main pathways for pro-inflammatory mechanisms, which in this model, interact to increase hepcidin expression. Trial data showed preterm birth was positively associated with C-reactive protein (P = 0.0038) an inflammatory biomarker. The malaria pathway upregulates C-reactive protein and serum hepcidin, thereby reducing iron absorption. The enteric pathway results from unabsorbed gut iron, which induces microbiome changes and pathogenic gut infections, initiating pro-inflammatory events with lipopolysaccharide expression. Data from the trial suggest that raised hepcidin concentration is a mediating catalyst, being inversely associated with shorter gestational age at delivery (P = 0.002) and positively with preterm incidence (P = 0.007). A segmented regression model identified a change-point consisting of two segments before and after a sharp rise in hepcidin concentration. This showed a post change hepcidin elevation in women with increasing C-reactive protein values in late gestation (post-change slope 0.55. 95% CI 0.39–0.92, P Conclusions Following long-term iron supplementation, dual inflammatory pathways that mediate hepcidin expression and culminate in progesterone withdrawal may account for the reduction in gestational age observed in first pregnancies in this area of high malaria exposure. If correct, this model strongly suggests that in such areas, effective infection control is required prior to iron supplementation to avoid increasing preterm births. Trial registration NCT01210040. Registered with Clinicaltrials.gov on 27th September 2010 |
| وصف الملف: | application/vnd.openxmlformats-officedocument.wordprocessingml.document |
| اللغة: | English |
| تدمد: | 1475-2875 |
| DOI: | 10.1186/s12936-019-3013-6 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9408bd9509d3b2052590b6a9177a341c http://link.springer.com/article/10.1186/s12936-019-3013-6 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....9408bd9509d3b2052590b6a9177a341c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14752875 |
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| DOI: | 10.1186/s12936-019-3013-6 |