ABSTRACT
Congenital Zika syndrome (CZS) is a cluster of malformations induced by Zika virus (ZIKV) infection and the underline mechanisms involved in its occurrence are yet not fully understood. Along with epidemiological and environmental factors, the genetic host factors are suggested as important to the CZS occurrence and development, however, few studies have evaluated this. This study enrolled a total of 245 individuals in a case-control association study compound a cohort of high specific interest constituted by 75 mothers who had delivered CZS infants, their 76 infants, and 47 mothers that had delivered healthy infants, and their 47 infants. Sixteen single-nucleotide polymorphisms on TREM1, CXCL10, IL4, CXCL8, TLR3, TLR7, IFNR1, CXCR1, IL10, CCR2 and CCR5 genes were genotyped to investigate their association as risk factors to CZS. The results show an association between C allele at TREM1 rs2234246 and C allele at IL4 rs224325 in mothers infected with ZIKV during pregnancy, with the increased susceptibility to CZS occurrence in their infants and the SNP CXCL8 rs4073 and the G allele at CXCL10 rs4508917 with presence of CZS microcephaly in the infants. Furthermore, the T allele at CXCL8 rs4073 and TRL7 rs179008 SNPs were associated with the severity of microcephaly in children with CZS. These results suggest that these polymorphisms in genes of innate immune responses addressed here are associated to increased risk of occurrence and severity of CZS in pregnant mothers infected with ZIKV and their CZS infants.
Subject(s)
Microcephaly , Zika Virus Infection , Female , Humans , Infant , Pregnancy , Chemokine CXCL10/genetics , Interleukin-4/genetics , Microcephaly/genetics , Microcephaly/virology , Polymorphism, Single Nucleotide , Toll-Like Receptor 7/genetics , Triggering Receptor Expressed on Myeloid Cells-1/genetics , Zika Virus , Zika Virus Infection/congenital , Zika Virus Infection/geneticsABSTRACT
OBJETIVO: Identificar a prevalência de malformações congênitas do sistema nervoso central (SNC) e malformações associadas diagnosticadas pela ultrassonografia obstétrica. MATERIAIS E MÉTODOS: Estudo observacional, transversal, descritivo, em instituição de referência para gestações de alto risco. RESULTADOS: Malformações congênitas do SNC estiveram presentes sem outras malformações associadas em 65,78%, com a distribuição: hidrocefalia (37,5%), mielomeningocele (15%), encefalocele (12,5%), agenesia de corpo caloso (12,5%), anencefalia (12,5%), holoprosencefalia (7,5%), Dandy-Walker (7,5%), Arnold-Chiari (5,0%), hidranencefalia (5,0%), meningocele (5,0%), cisto aracnoideo (2,5%). Malformações congênitas de outros sistemas estiveram associadas às do SNC: craniofacial (73,9%), ortopédica (65,2%), cardiovascular (34,8%), geniturinária (30,4%), gastrintestinal (30,4%), respiratória (8,7%), sindrômica (8,7), oftalmológica (4,3%). A sensibilidade ultrassonográfica no estudo de malformações fetais do SNC foi 79,4%. A taxa de falso-negativos foi 20,5%. Dentre as limitações quantificáveis destaca-se o oligodrâmnio, presente em 25% dos falso-negativos. CONCLUSÃO: A ultrassonografia obstétrica possui boa sensibilidade no rastreio de malformações fetais do SNC, em especial com o aperfeiçoamento constante e domínio na utilização de métodos especializados, como o Doppler e a ultrassonografia volumétrica (3D/4D), contribuindo para firmar-se como modalidade de escolha nesta rotina. Complementar ao método, a ressonância magnética pode vir a fornecer subsídios para uma ainda melhor assistência perinatal.
OBJECTIVE: To identify and evaluate the prevalence of congenital central nervous system (CNS) malformations and associated defects diagnosed by obstetric ultrasonography. MATERIALS AND METHODS: Observational, descriptive, cross-sectional study developed in an institution of reference for high-risk pregnancies. RESULTS: Congenital CNS malformations without other associated defects were present in 65.78% of cases, as follows: hydrocephalus (37.5%), myelomeningocele (15%), encephalocele (12.5%), corpus callosum agenesis (12.5%), anencephaly (12.5%), holoprosencephaly (7.5%), Dandy-Walker (7.5%), Arnold-Chiari (5.0%), hydranencephaly (5.0%), meningocele (5.0%), arachnoid cyst (2.5%). Congenital malformations of other systems were associated with such malformations, as follows: craniofacial (73.9%), orthopedic (65.2%), cardiovascular (34.8%), genitourinary (30.4%), gastrointestinal (30.4%), respiratory (8.7%), syndromic (8.7%), ophthalmologic (4.3%). The sonographic sensitivity in the study of CNS malformations was 79.4%. The rate of false-negative results was 20.5%. Oligohydramnios, present in 25% of false-negative studies, stands out among the quantifiable limitations. CONCLUSION: Obstetric ultrasonography presents good sensitivity in the screening for fetal CNS malformations, specially with the constant improvement and control of specialized methods such as Doppler and volumetric ultrasonography (3D/4D), contributing to consolidate its role as a modality of choice in this routine. Magnetic resonance imaging may play a supplementary role, providing information for an even better perinatal care.
