Plasmodium falciparuminfection during pregnancy impairs fetal head growth: prospective and populational-based retrospective studies
Authors: Dombrowski Jamille Gregório , de Souza Rodrigo Medeiros , Lima Flávia Afonso , Bandeira Carla Letícia , Murillo Oscar , de Sousa Costa Douglas , Machado Peixoto Erika Paula , dos Passos Cunha Marielton , de Andrade Zanotto Paolo Marinho , Bevilacqua Estela , Grigolin Grisotto Marcos Augusto , de Lima Antonio Carlos Pedroso , da Motta Singer Julio , Campino Susana , Clark Taane Gregory , Epiphanio Sabrina , Gonçalves Lígia Antunes , Farias Marinho Cláudio Romero 
Published: October 2017

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 withPlasmodium falciparumduring pregnancy. Multivariate logistic regression analyses revealed thatP. falciparuminfection 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 wereP. 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 Registry