国家儿童专家引领新病毒研究：先天齐卡病毒感染与胎儿脑部异常显著，尽管正常的超声检查
华盛顿，DC -传染齐卡病毒分离从21周大的胎儿大脑脑组织造成广泛破坏后& ndash；尽管超声检查发现没有小头畸形在周13，16，标志17，根据2016年3月30日在线发表的一份报告中新英国医学杂志（NEJM）。
“虽然这是一个案例，它带来了令人不安的问题，可以告知未来的研究，”研究的共同资深作者，热爱杜立石，医学学士，在胎儿医学研究所主任和儿童国家卫生系统的胎儿与转化医学部主任。“越来越多的证据表明，齐卡病毒可以坚持孕妇血液周初次感染后，争论如何监测这些怀孕的变化，”博士杜立石说。
六署名作者隶属于儿童的国家，那里的孕妇寻求更深入的评估自己的齐卡病毒检测呈阳性后，国际旅行后。
AccoRDing to THe Centers for Disease Control and Prevention （CDC), Zika viral transmission is occurring extensively THroughout Central and SouTH America; THe agency now asks pregnant women to consider delaying travel to THose regions. The mosquito-borne infection can be passed by pregnant women to developing fetuses and has been implicated in a growing number of cases of Brazilian infants born wiTH microcephaly, a condition characterized by undersized heads and severe brain damage. The World HealTH Organization has declared THe Zika epidemic a Public HealTH Emergency of International Concern.
33岁的芬兰妇女的情况进行了总结NEJM was 11 weeks pregnant when she and her husband traveled on vacation to Mexico, Guatemala, and Belize from November 22 THrough 29, 2015. The pair told researchers THat THey had been bitten by mosquitoes during THeir trip, particularly in Guatemala. One day after returning to THeir home in Washington, DC, THe woman got sick, experiencing eye pain, muscle pain, and a mild fever （37.5 C) THat lasted for five days. On THe second day of her fever, she developed a rash. Her husband suffered similar symptoms at THe same time.
A series of fetal ultrasounds THat began one week after her symptoms subsided （13, 16, and 17 weeks of gestation) showed no evidence of microcephaly or brain calcifications THat can signal Zika infection in THe womb. The womans blood, however, tested positive for viral fragments （RNA) THat furTHer testing confirmed to be a strain of THe Zika virus circulating in THe current epidemic. More sophisticated testing, also conducted by THe CDC, corroborated THat THe virus was closely related to Guatemalan strains.
由19TH week, an ultrasound revealed significant abnormalities in THe fetus brain. This timeframe is a critical period in THe development of THe fetal brain, as THe brain normally grows larger and more complex as it builds THe neural foundation THat will be relied upon for life. In THis fetus, however, THe cerebral cortex appeared THin and THere was extra space between THe cerebral cortex and THe cranium, an indication THat while THe skull continued to grow, THe brain was not keeping pace.
By THe 20TH week, fetal magnetic resonance imaging （MRI) showed severe atrophy THroughout THe brain, especially in THe frontal lobe, involved in decision-making, and THe parietal lobe, where all incoming sensory information is processed and stored to facilitate learning, vision, hearing, touch, and taste. The MRI imaging technology peers into THe womb, providing a clear view of soft tissue, and showed THat THe corpus callosum, which should be fully grown by THe 20TH week, was significantly shorter THan normal. The anterior to posterior lengTH was 14 mm, compared wiTH THe normal lengTH of 18 to 22 mm for THat age.
“The Zika virus infection, which resulted in extensive cell deaTH, occurred at a time when THe brain was most vulnerable,” said study co-auTHor Roberta DeBiasi, MD, Chief of THe Division of Infectious Disease at Childrens National. Given THe grave prognosis, THe couple elected to terminate THe pregnancy at 21 weeks gestational age.
On THe day THe woman terminated THe pregnancy, her blood surprisingly still tested positive for Zika RNA, some 10 weeks after her initial exposure. Eleven days after terminating THe pregnancy, no evidence of Zika was found in THe womans blood, saliva, or urine.
Imaging THat was done from 1920 weeks of gestational age showed significant structural abnormalities in THe brain. Indeed, from THe 16TH20TH week, THe fetal head circumference decreased from THe 47TH24TH percentile. Yet, THis fetus did not meet THe THreshold – a head circumference below THe 3RD percentile – to be diagnosed wiTH microcephaly.
The aborted fetus brain, however, weighed 30 grams, less THan THe normal size of 49 grams. And high concentrations of Zika virus were found in THe fetal brain using two different detection meTHods. Direct viral infection of neurons in THe neocortex – THe THin layer on THe surface of THe brain THat plays a role in sight, hearing, and language – resulted in “significant” cell deaTH, accoRDing to THe study auTHors. “The neurons THat were partly mature were THe most affected; THe less developed and THe more developed brain cells were spared,” said Cheng-Ying Ho, MD, PhD, a Childrens National neuropaTHologist and co-lead study auTHor.
While THe concentration of virus at 21 weeks was highest in THe fetal brain, umbilical coRD, and placenta, lower concentrations of Zika virus also made its way to THe developing fetus muscle, liver, lung, and spleen tissues as well as THe amniotic fluid, THe research team writes. Zika virus isolated from THe fetus brain remained infectious when tested, growing easily in a human neuroblastoma cell line.
“The high amount of virus in THe fetal brain and THe placenta are concerning and suggest THat THe virus may be able to hide from THe immune system THere,” Dr. DeBiasi said. “Equally concerning is Zikas apparent preference for fetal brain cells, where it replicates efficiently and can do damage silently,” Dr. du Plessis added.
Indeed, THe research team hypoTHesizes THat THe womans persistent Zika infection was a “consequence of viral replication in THe fetus or placenta, which had high viral loads.” Thus, early ultrasounds THat appear to be “normal,” and a single blood test performed after THe pregnant womans symptoms subside boTH have THe potential to provide a false sense of security about THe healTH of THe moTHer and her offspring.
“What our paper suggests is THat physicians should use caution in reassuring patients who have normal fetal ultrasound examinations early in THeir pregnancies, as THese single snapshots in time may not capture infection-associated fetal brain abnormalities THat may worsen as THe pregnancy progresses,” Dr. du Plessis said.
“A number of viruses have THe capability to pass from an infected pregnant woman to her fetus and to damage THe brain. However, Zika is unique compared wiTH oTHer mosquito-borne viruses, such as dengue and chikungunya, in its capacity to infect and seriously harm THe developing fetal brain,” said Dr. DeBiasi. “More research is needed to determine if serial measurements and blood tests could more accurately detect and, ultimately, predict fetal abnormalities following Zika infection. Learning more about THe specific brain cells THat Zika infects and THe stage of pregnancy when THis is most damaging may help us to identify THerapeutic targets and provide clearer guidance for pregnant women.”
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About Children’s National HealTH System
Children's National HealTH System, based in Washington, DC, has been serving THe nation's children since 1870. Children's National is a Leapfrog Group Top Hospital, Magnet® designated, and was ranked among THe top 10 pediatric hospitals by 美国新闻与世界报道2015-16年. Home to THe Children's Research Institute and THe Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National is one of THe nation's top NIH-funded pediatric institutions. WiTH a community-based pediatric network, seven regional outpatient centers, an ambulatory surgery center, two emergency rooms, an acute care hospital, and collaborations THroughout THe region, Children's National is recognized for its expertise and innovation in pediatric care and as an advocate for all children. For more information, visit ChildrensNational.org, or follow us on Facebook and Twitter.
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