RT Journal Article SR Electronic T1 Plasmodium falciparum infection during pregnancy impairs fetal head growth: prospective and populational-based retrospective studies JF bioRxiv FD Cold Spring Harbor Laboratory SP 203059 DO 10.1101/203059 A1 Jamille Gregório Dombrowski A1 Rodrigo Medeiros de Souza A1 Flávia Afonso Lima A1 Carla Letícia Bandeira A1 Oscar Murillo A1 Douglas de Sousa Costa A1 Erika Paula Machado Peixoto A1 Marielton dos Passos Cunha A1 Paolo Marinho de Andrade Zanotto A1 Estela Bevilacqua A1 Marcos Augusto Grigolin Grisotto A1 Antonio Carlos Pedroso de Lima A1 Julio da Motta Singer A1 Susana Campino A1 Taane Gregory Clark A1 Sabrina Epiphanio A1 Lígia Antunes Gonçalves A1 Cláudio Romero Farias Marinho YR 2017 UL http://biorxiv.org/content/early/2017/10/13/203059.abstract AB Background Malaria in pregnancy is associated with adverse effects on the fetus and newborns. However, the outcome on a newborn’s head circumference (HC) is still unclear. Here, we show the relation of malaria during pregnancy with fetal head growth.Methods Clinical and anthropometric data were collected from babies in two cohort studies of malaria-infected and non-infected pregnant women, in the Brazilian Amazon. One enrolled prospectively (PCS, Jan. 2013 to April 2015) through volunteer sampling, and followed until delivery, 600 malaria-infected and non-infected pregnant women. The other assembled retrospectively (RCS, Jan. 2012 to Dec. 2013) clinical and malaria data from 4697 pregnant women selected through population-based sampling. The effects of malaria during pregnancy in the newborns were assessed using a multivariate logistic regression. According with World Health Organization guidelines babies were classified in small head (HC < 1 SD below the median) and microcephaly (HC < 2 SD below the median) using international HC standards.Results Analysis of 251 (PCS) and 232 (RCS) malaria-infected, and 158 (PCS) and 3650 (RCS) non-infected women with clinical data and anthropometric measures of their babies was performed. Among the newborns, 70 (17.1%) in the PCS and 934 (24.1%) in the RCS presented with a small head (SH). Of these, 15 (3.7%) and 161 (4.2%), respectively, showed microcephaly (MC). The prevalence of newborns with a SH (30.7% in PCS and 36.6% in RCS) and MC (8.1% in PCS and 7.3% in RCS) was higher among babies born from women infected with Plasmodium falciparum during pregnancy. Multivariate logistic regression analyses revealed that P. falciparum infection during pregnancy represents a significant increased odds for the occurrence of a SH in newborns (PCS: OR 3.15, 95% CI 1.52-6.53, p=0.002; RCS: OR 1.91, 95% CI 1.21-3.04, p=0.006). Similarly, there is an increased odds of MC in babies born from mothers that were P. falciparum-infected (PCS: OR 5.09, 95% CI 1.12-23.17, p=0.035). Moreover, characterization of placental pathology corroborates the association analysis, particularly through the occurrence of more syncytial nuclear aggregates and inflammatory infiltrates in placentas from babies with the reduced head circumference.Conclusions This work indicates that falciparum-malaria during pregnancy presents an increased likelihood of occurring reduction of head circumference in newborns, which is associated with placental malaria.Trial Registration registered as RBR-3yrqfq in the Brazilian Clinical Trials RegistryANCAntenatal careANG-1 and ANG-2Angiopoietins 1 and 2CIConfidence intervalscmcentimetersgGramsHChead circumferenceH&EHematoxylin-EosinHMCJHospital da Mulher e da Criança do JuruáIUGRIntrauterine growth retardationIQRInterquartile rangesLBWLow birth weightLMPLast menstrual periodMCMicrocephalyMoHMinistry of HealthNHCNormal head circumferenceNINon-infectedODOptical densityOROdds ratioPCSProspective cohort studyPfPlasmodium falciparumPvPlasmodium vivaxRCSRetrospective cohort studySDstandard deviationsSHSmall headSIVEPEpidemiological Surveillance Information SystemSNASyncytial nuclear aggregatesTIE-2TEK receptor tyrosine kinaseTMATissue microarrayTORCHabbreviation for Toxoplasma, rubella, cytomegalovirus, and Herpes simplexVEGFAVascular endothelial growth factor AWHOWorld Health OrganizationWHO-CGSWHO child growth standards.