Association of Malaria Infection During Pregnancy With Head Circumference of Newborns in the Brazilian Amazon

Author(s):Show less -

Dombrowski, Jamille Gregorio ^[1] ; de Souza, Rodrigo Medeiros ^{[2, 1]} ; Lima, Flavia Afonso ^[1] ; Bandeira, Carla Leticia ^[1] ; Murillo, Oscar ^[1] ; Costa, Douglas de Sousa ^[1] ; Machado Peixoto, Erika Paula ^[1] ; Cunha, Marielton dos Passos ^[3] ; de Andrade Zanotto, Paolo Marinho ^[3] ; Bevilacqua, Estela ^[4] ; Grigolin Grisotto, Marcos Augusto ^[5] ; Pedroso de Lima, Antonio Carlos ^[6] ; Singer, Julio da Motta ^[6] ; Campino, Susana ^[7] ; Clark, Taane Gregory ^{[8, 7]} ; Epiphanio, Sabrina ^[9] ; Goncalves, Ligia Antunes ^[1] ; Farias Marinho, Claudio Romero ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Parasitol, Ave Prof Lineu Prestes 1374, BR-05508900 Sao Paulo - Brazil

^[2] Univ Fed Acre, Multidisciplinary Ctr, Acre - Brazil

^[3] Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Inst Biomed Sci, Dept Cell & Dev Biol, Sao Paulo - Brazil

^[5] CEUMA Univ, Maranhao - Brazil

^[6] Univ Sao Paulo, Inst Math & Stat, Dept Stat, Sao Paulo - Brazil

^[7] London Sch Hyg & Trop Med, Fac Infect & Trop Dis, London - England

^[8] London Sch Hyg & Trop Med, Fac Epidemiol & Populat Hlth, London - England

^[9] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin & Toxicol Anal, Sao Paulo - Brazil

• Document type: Journal article
• Source: JAMA NETWORK OPEN; v. 2, n. 5 MAY 2019.
• Web of Science Citations: 0

Abstract

IMPORTANCE Malaria during pregnancy is associated with adverse events for the fetus and newborn, but the association of malaria during pregnancy with the head circumference of the newborn is unclear. OBJECTIVE To investigate the association of malaria during pregnancy with fetal head growth. DESIGN, SETTING, AND PARTICIPANTS Two cohort studies were conducted at the general maternity hospital of Cruzeiro do Sul (Acre, Brazil) in the Amazonian region. One cohort study prospectively enrolled noninfected and malaria-infected pregnant women who were followed up until delivery, between January 2013 and April 2015. The other cohort study was assembled retrospectively using clinical and malaria data from all deliveries that occurred between January 2012 and December 2013. Data analyses were conducted from January to August 2017 and revised in November 2018. Clinical data from pregnant women and anthropometric measures of their newborns were evaluated. A total of 600 pregnant women were enrolled through volunteer sampling (prospective cohort study), and 4697 pregnant women were selected by population-based sampling (retrospective cohort study). After application of exclusion criteria, data from 251 (prospective cohort study) and 232 (retrospective cohort study) malaria-infected and 158 (prospective cohort study) and 3650 (retrospective cohort study) noninfected women were evaluated. EXPOSURE Malaria during pregnancy. MAIN OUTCOMES AND MEASURES The primary end point was the incidence of altered head circumference in newborns delivered from malaria-infected mothers compared with that from noninfected mothers. Secondary end points included measures of placental pathology relative to newborn head circumference. RESULTS In total, 4291 maternal-child pairs were analyzed. Among 409 newborns in the prospective cohort study, the mothers of 251 newborns had malaria during pregnancy, infected with Plasmodium vivax, Plasmodium falciparum, or both. Among 3882 newborns in the retrospective cohort study, 232 were born from mothers that had malaria during pregnancy. The prevalence of newborns with a small head (19 {[}30.7%] in the prospective cohort study and 30 {[}36.6%] in the retrospective cohort study) and the prevalence of microcephaly among newborns (5 {[}8.1%] in the prospective cohort study and 6 {[}7.3%] in the retrospective cohort study) were higher among newborns from women infected with P falciparum during pregnancy. Multivariate logistic regression analyses revealed that P falciparum infection during pregnancy represented a significant risk factor for the occurrence of small head circumference in newborns (prospective cohort study: odds ratio, 3.15; 95% CI, 1.52-6.53; P = .002; retrospective cohort study: odds ratio, 1.91; 95% CI, 1.21-3.04; P = .006). Placental pathologic findings corroborated this association, with more syncytial nuclear aggregates and inflammatory infiltrates occurring in placentas of newborns born with decreased head circumference. CONCLUSIONS AND RELEVANCE This study indicates that falciparum malaria during pregnancy is associated with decreased head circumference in newborns, which is in turn associated with evidence of placental malaria. (AU)

• FAPESP's process: 09/53889-0 - Study of the immunopathological mechanisms involved in pregnancy-associated malaria
• Grantee: Cláudio Romero Farias Marinho
• Support type: Research Grants - Young Investigators Grants
• FAPESP's process: 14/09964-5 - The role of inflammasomes in the pathogenesis of malaria during pregnancy: effects and mechanisms
• Grantee: Cláudio Romero Farias Marinho
• Support type: Regular Research Grants
• FAPESP's process: 14/20451-0 - The role of endothelial cells in the immunopathogenesis of murine malaria-associated ALI/ARDS: effects and mechanisms
• Grantee: Sabrina Epiphanio
• Support type: Regular Research Grants
• FAPESP's process: 14/17766-9 - A systemic approach to study permissivity on the Anticarsia gemmatalis multiple nucleopolyhedrovirus (AgMNPV)
• Grantee: Paolo Marinho de Andrade Zanotto
• Support type: Regular Research Grants
• FAPESP's process: 13/21728-2 - The use of modern autopsy techniques to investigate human diseases (MODAU)
• Grantee: Paulo Hilário Nascimento Saldiva
• Support type: Research Projects - Thematic Grants
• FAPESP's process: 13/00981-1 - Characterization of the role of dendritic cells in the recrudescence of malaria in pregnancy
• Grantee: Oscar Javier Murillo Gómez
• Support type: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 13/16417-8 - Autophagy in placental malaria: effects and mechanisms
• Grantee: Flávia Afonso Lima
• Support type: Scholarships in Brazil - Post-Doctorate
• FAPESP's process: 12/04755-3 - Association of gestational malaria with intrauterine growth restriction and low birth weight in the far-western Brazilian Amazon
• Grantee: Jamille Gregório Dombrowski
• Support type: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 18/20468-0 - Recrudescence of the malaria during pregnancy: effects and mechanisms
• Grantee: Cláudio Romero Farias Marinho
• Support type: Regular Research Grants
• FAPESP's process: 16/08204-2 - Genetic and phylodynamics diversity of emerging and re-emerging arboviruses (DENV, ZIKV and CHIKV) in the Northeast and Southeast regions of Brazil, 2014-2016
• Grantee: Marielton dos Passos Cunha
• Support type: Scholarships in Brazil - Doctorate
• FAPESP's process: 15/06106-0 - The role of inflammasomes in the pathogenesis of malaria during pregnancy: effects and mechanisms
• Grantee: Cláudio Romero Farias Marinho
• Support type: Research Grants - Visiting Researcher Grant - International