Prenatal screening for Zika encephalopathy with ultrasound: what is the optimal time window?
2017; Elsevier BV; Volume: 1; Issue: 1 Linguagem: Inglês
10.1016/s2352-4642(17)30002-0
ISSN2352-4650
Autores Tópico(s)Viral Infections and Vectors
ResumoZika virus-induced encephalopathy resulting in microcephaly was shown with fetal neuroimaging at 21–30 weeks of gestation in French Polynesia1Jouannic JM Friszer S Leparc-Goffart I Garel C Eyrolle-Guignot D Zika virus infection in French Polynesia.Lancet. 2016; 387: 1051-1052Summary Full Text Full Text PDF PubMed Scopus (87) Google Scholar and in Brazil,2Oliveira Melo AS, G Malinger, R Ximenes, PO Szejnfeld, Alves Sampaio S, Bispo de Filippis AM Zika virus intrauterine infection causes fetal brain abnormality and microcephaly: tip of the iceberg? Ultrasound Obstet Gynecol 47: 6–7.Google Scholar and microcephaly was regarded as the tip of the iceberg for extensive encephalopathic changes. Microcephaly appears to be a late effect of the encephalopathy, and birth defects (including microcephaly) might manifest later even when head size is described as normal at birth.3van der Linden V Pessoa A Dobyns W et al.Description of 13 infants born during October 2015-January 2016 with congenital Zika virus infection without microcephaly at birth—Brazil.MMWR Morb Mortal Wkly Rep. 2016; 65: 1343-1348Crossref PubMed Scopus (293) Google Scholar In women who were infected during the first trimester while travelling though endemic areas, the encephalopathy was diagnosed in second trimester fetal ultrasound studies, with pathological correlation.4Driggers RW Ho CY Korhonen EM et al.Zika virus infection with prolonged maternal viremia and fetal brain abnormalities.N Engl J Med. 2016; 374: 2142-2151Crossref PubMed Scopus (645) Google Scholar, 5Mlakar J Korva M Tul N et al.Zika virus associated with microcephaly.N Engl J Med. 2016; 374: 951-958Crossref PubMed Scopus (1844) Google Scholar Zika-associated birth injuries have been found in 6% of pregnant women in the USA with laboratory evidence of recent Zika infection, and this number rose to 11% of women whose infection occurred during the first trimester.6Honein MA Dawson AL Petersen EE et al.US Zika Pregnancy Registry CollaborationBirth defects among fetuses and infants of US women with evidence of possible Zika virus infection during pregnancy.JAMA. 2017; 317: 59-68Crossref PubMed Scopus (348) Google Scholar Honein and colleagues6Honein MA Dawson AL Petersen EE et al.US Zika Pregnancy Registry CollaborationBirth defects among fetuses and infants of US women with evidence of possible Zika virus infection during pregnancy.JAMA. 2017; 317: 59-68Crossref PubMed Scopus (348) Google Scholar reported no birth defects with infection later in the pregnancy. However, a Brazilian study7Brasil P Pereira Jr, JP Moreira ME et al.Zika virus infection in pregnant women in Rio de Janeiro.N Engl J Med. 2016; 375: 2321-2334Crossref PubMed Scopus (1281) Google Scholar reported birth defects in up to 55% of pregnancies infected in the first trimester, 52% in the second trimester, and 29% in the third trimester. The Article by Bruno Schaub and colleagues8Schaub B Gueneret M Jolivet E et al.Ultrasound imaging for identification of cerebral damage in congenital Zika virus syndrome: a case series.Lancet Child Adolesc Health. 2017; (published online June 13)http://dx.doi.org/10.1016/S2352-4642(17)30001-9Summary Full Text Full Text PDF Scopus (25) Google Scholar reviewed the findings of 31 prenatal ultrasound examinations done on 14 fetuses that were diagnosed with infection with Zika virus, during a Zika outbreak on the French Caribbean island of Martinique in 2016. The infections were established by confirmation of Zika virus presence in all affected fetuses. The Zika virus serology of the mothers was also described in detail, and all infections were estimated to have occurred during the first trimester or early second trimester. At 16–20 weeks of gestation, four (33%) of 12 ultrasounds were abnormal, nine (90%) of ten ultrasounds were abnormal at 20–24 weeks, all five (100%) were abnormal at 24–28 weeks of gestation, and all four (100%) were abnormal after 28 weeks of gestation. Abnormalities that became more frequent at increasing weeks of gestation were ventriculomegaly, brain tissue loss, abnormalities of the corpus callosum, parenchymal calcifications, abnormal gyration, and posterior fossa abnormalities. Microcephaly was common but not universal (nine [64%] of 14 fetuses), probably because of the timing of the scans. With their observations, Schaub and colleagues contribute to an interesting theory on how Zika virus attacks the fetal brain, which requires further correlation with neuropathological studies. Apparently, the brain is formed normally in the early embryological period, but brain tissues are subsequently broken down (tissue loss) or fail to develop properly (hypoplasia or dysgenesis) as a result of the devastating effects of the virus on neural stem cells. The corpus callosum appears to be present in the cases described by Schaub and colleagues (by virtue of the presence of a normal pericallosal artery, a finding not encountered in true absence of this structure), but remained thin because of poor development of crossing white matter fibres. The same pathogenesis probably applies to the observed underdevelopment of posterior fossa structures. The fact that this study focused on ultrasonography is appropriate in the low-resource settings in which most of these infections occur, settings where fetal MRI is often not readily available. The description by Soares de Oliveira-Szejnfeld and colleagues9Soares de Oliveira-Szejnfeld P Levine D Melo AS et al.Congenital brain abnormalities and Zika virus: what the radiologist can expect to see prenatally and postnatally.Radiology. 2016; 281: 203-218Crossref PubMed Scopus (194) Google Scholar of postnatal neuroimaging findings using CT and MRI for Zika-induced encephalopathy9Soares de Oliveira-Szejnfeld P Levine D Melo AS et al.Congenital brain abnormalities and Zika virus: what the radiologist can expect to see prenatally and postnatally.Radiology. 2016; 281: 203-218Crossref PubMed Scopus (194) Google Scholar has less clinical relevance than the studies using ultrasound to elucidate its pathogenesis and improve diagnosis. Schaub and colleagues9Soares de Oliveira-Szejnfeld P Levine D Melo AS et al.Congenital brain abnormalities and Zika virus: what the radiologist can expect to see prenatally and postnatally.Radiology. 2016; 281: 203-218Crossref PubMed Scopus (194) Google Scholar recommend that screening for fetal Zika virus encephalopathy be done at 22–26 weeks of gestation, to allow for detection of all cases and timely prognostication for the purpose of termination of pregnancy. Notably, 12 of the 13 pregnant women who had a live fetus opted for termination of pregnancy when confronted with the abnormal ultrasound findings, an option that is not available to most affected women in Brazil. The results of this study have major implications for optimising screening for fetal Zika virus encephalopathy in the most affected developing nations, and also in high-income nations,10Petersen EE Polen KN Meaney-Delman D et al.Update: interim guidance for health care providers caring for women of reproductive age with possible Zika virus exposure—United States, 2016.MMWR Morb Mortal Wkly Rep. 2016; 65: 315-322Crossref PubMed Scopus (100) Google Scholar where the issues hinge on the permissibility of legal abortion of a viable fetus. Screening too early might miss significant abnormalities, whereas screening too late might place the expectant mother in a difficult position because legal termination of pregnancy might be no longer available in her state or country.11Aiken AR Scott JG Gomperts R Trussell J Worrell M Aiken CE Requests for abortion in Latin America related to concern about Zika virus exposure.N Engl J Med. 2016; 375: 396-398Crossref PubMed Scopus (1) Google Scholar One has to realise that to poor women in the most affected countries, even access to basic prenatal care such as fetal ultrasound screening might be out of reach.11Aiken AR Scott JG Gomperts R Trussell J Worrell M Aiken CE Requests for abortion in Latin America related to concern about Zika virus exposure.N Engl J Med. 2016; 375: 396-398Crossref PubMed Scopus (1) Google Scholar Termination of pregnancy is illegal in many Latin American countries where Zika virus infections are most prevalent, and can be very difficult to obtain in many southern states of the USA and in Puerto Rico, where most of the imported cases (ie, from women travelling to South America and becoming infected, or imported through mosquito populations) are to be expected. This situation has inflated the politically charged discussion on the limits of legal termination of pregnancy in the USA, and even the provision of contraception to prevent this devastating sexually transmitted disease has been challenged by the proposed defunding of Planned Parenthood and the United Nations Population Fund by the current federal government administration of the USA. It seems that the Zika virus crisis revolves around restrictions to free choice in reproductive health for the most underprivileged women in developing and developed countries alike.11Aiken AR Scott JG Gomperts R Trussell J Worrell M Aiken CE Requests for abortion in Latin America related to concern about Zika virus exposure.N Engl J Med. 2016; 375: 396-398Crossref PubMed Scopus (1) Google Scholar Unless this politically motivated interference with reproductive choice is addressed, the birth of many children with profound psychomotor retardation will continue because of missed opportunities for the only remedy: prevention. I declare no competing interests. Ultrasound imaging for identification of cerebral damage in congenital Zika virus syndrome: a case seriesUltrasound monitoring appears to be a good screening strategy to monitor Zika virus-exposed pregnancies. Public health efforts should focus on scanning at 22–26 weeks of gestation. Identification of ventriculomegaly, cortical atrophy, calcifications, and anomalies of the corpus callosum should prompt laboratory screening for Zika virus. Full-Text PDF
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