怀孕期间感染兹卡病毒与胎儿死亡、CNS损伤等严重结果有关


  【24drs.com】根据在线发表于3月4日新英格兰医学期刊,巴西里约热内卢监测病例初步报告,怀孕期间感染兹卡病毒(Zika virus,ZIKV)和胎儿死亡、中枢神经系统(CNS)损伤、生长受限、胎盘功能不全等严重后果有关。
  
  里约热内卢Oswaldo Cruz基金会Patricia Brasil医师等人写道,我们的研究结果为孕妇感染兹卡病毒和胎儿与胎盘异常之关联提供更多证据,和造成先天性感染的其它病毒不同,此症会引起子宫内发育迟缓与胎盘功能不全。
  
  之前已认为孕妇感染兹卡病毒与新生儿畸形有关联。从2015年9月到2016年2月,研究者纳入88名有皮疹的孕妇,其中72人(82%)的血液和/或尿液反转录酶聚合酶链反应检测发现为兹卡病毒阳性,研究者采取临床检查和一系列的超音波持续追踪这些妇女。
  
  虽然孕妇本身的症状相对轻微,婴儿却发生严重后果,包括2例在妊娠36、38周时死亡、子宫内生长受限合并或未合并小头畸形、心室钙化或其它CNS病灶、羊水量异常、脑或脐动脉血流异常。
  
  作者们写道,应密切监测疑似或确认感染兹卡病毒的妇女,监于胎儿死亡和子宫内生长受限的风险,应使用一系列的超音波检查,以评估胎盘功能不全的迹象。在兹卡病毒和先天性异常结果之间建立一个具有科学可信度的关联,是极其重要的,以便在巴西与全球有效且成功地因应这波流行病。
  
  妇女在妊娠5-38周出现疑似急性兹卡病毒感染,典型症状是下行(descending)斑疹或斑丘疹,94%患者出现瘙痒;关节痛;结膜充血;头痛。发烧情况并不明显,仅不到三分之一患者(28%)发生,且大部份是短期间且轻微。
  
  相较于兹卡病毒阴性的妇女,阳性者比较可能有斑丘疹(44% vs 12%;P = .02)、结膜相关症状(58% vs 13%;P = .002)与淋巴结肿大(41% vs 6%;P = .02)。65%的兹卡阳性妇女和41%的兹卡阴性妇女发生关节痛,未达统计上的显著差异(P = .16)。
  
  研究作者们写道,相较于急性兹卡病毒感染检测阴性的妇女,病毒检测阳性的妇女,其独特临床表征包括结膜充血、淋巴结肿大、没有呼吸道症状。除了斑疹或斑丘疹,对于疑似兹卡病毒感染者应特别注意这些临床表征。仅28%妇女有轻微发烧,因此,如果根据出现发烧来定义病例,会错失超过70%的案例。
  
  所有的兹卡阴性妇女与42名兹卡阳性妇女(58%)接受了胎儿超音波检查,都卜勒超音波显示,42名兹卡阳性妇女有12人(29%)出现胎儿异常,而16名兹卡阴性妇女都没有;2名兹卡阳性妇女在第一孕期时流产,胎儿死亡率为4.8%。
  
  作者认为这些是令人担忧的结果,因为这些患者都是没有会造成不良怀孕结果之其它风险因素的健康妇女,超音波发现的不良结果如下所列:
  * 子宫内生长受限,合并或未合并小头畸形(n = 5),
  * 脑或脐动脉血流异常(n = 4)
  * 颅内钙化(n = 4)
  * 其它CNS变化(n = 2)
  * 羊水过少和无羊水(n = 2)
  * 其它畸形(n = 1):蚓部发育不全、Blake氏囊肿、胎儿潜在的内翻足合并颅内钙化、子宫内生长受限、小头畸形、以及负面的遗传结果。
  
  42名兹卡病毒阳性妇女中,有8人进行胎儿超音波并生下她们的婴儿(6名活产与2名死产),都确认有超音波检查时发现的异常。
  
  在妊娠期间的任一时间点受到感染,妇女的胎儿都有发现异常,虽然在第一孕期受到感染的胎儿于胚胎发育过程中已经发现病理变化迹象,受感染胎儿的CNS异常也会迟至27周时才会发生。
  
  研究者指出,兹卡病毒感染的许多方面类似于麻疹,尤其是孕妇皮疹、关节痛、皮肤搔痒、淋巴结肿大无高烧、以及子宫内生长受限。在1959-1965年美国大流行的婴儿先天性麻疹中,约有85%也曾出现这些症状。
  
  研究作者们结论表示,对于2015-2016年巴西兹卡病毒感染和1959-1965年美国麻疹感染之关注有一大差异,也就是人们的免疫能力。2015-2016年的巴西兹卡病毒感染,没有人有兹卡病毒的抗体。相对的,美国的麻疹大流行时,有20,000例先天性麻疹症候群,但是,在1959年,只有17.5%的孕龄妇女没有麻疹抗体。
  
  资料来源:http://www.24drs.com/
  
  Native link:Zika Virus Infection in Pregnancy Linked to Severe Outcomes Including Fetal Death, CNS Injury

Zika Virus Infection in Pregnancy Linked to Severe Outcomes Including Fetal Death, CNS Injury

By Laurie Barclay, MD
Medscape Medical News

Zika virus (ZIKV) infection in pregnancy is linked to severe fetal outcomes including death, central nervous system (CNS) injury, growth restriction, and placental insufficiency, according to a preliminary report of a surveillance case series from Rio de Janeiro, Brazil, published online March 4 in the New England Journal of Medicine.

"[O]ur findings provide further support for a link between maternal ZIKV infection and fetal and placental abnormalities that is not unlike that of other viruses that are known to cause congenital infections characterized by intrauterine growth restriction and placental insufficiency," write Patricia Brasil, MD, from Fundacao Oswaldo Cruz, Rio de Janeiro, and colleagues.

Maternal ZIKV infection has previously been associated with neonatal microcephaly. From September 2015 through February 2016, the investigators enrolled 88 pregnant women with rash, of whom 72 (82%) tested positive for ZIKV in blood and/or urine by reverse-transcriptase polymerase chain reaction assays. The researchers followed the women prospectively with clinical examinations and serial ultrasound.

Despite relatively mild symptoms in the mothers, the infants experienced grave outcomes. These included two deaths at 36 and 38 weeks of gestation, in utero growth restriction with or without microcephaly, ventricular calcifications or other CNS lesions, and abnormal amniotic fluid volume or cerebral or umbilical artery flow.

"Women with suspected or confirmed ZIKV infection should be monitored closely, with serial ultrasonography to evaluate for signs of placental insufficiency, given the risks of fetal death and intrauterine growth restriction," the study authors write. "The establishment of a scientifically credible link between ZIKV and abnormal congenital findings is of utmost importance for the effective and successful management of this epidemic in Brazil and worldwide."

Maternal Symptoms Relatively Mild, but Fetal Outcomes Severe

Women presented with suspected acute ZIKV infection at 5 to 38 gestational weeks. Characteristic symptoms were descending macular or maculopapular rash, which was pruritic in 94%; joint pain; conjunctival injection; and headache. Fever was not a prominent finding, occurring in less than one third of the patients (28%), and was mostly short-term and low-grade when present.

Compared with women who were negative for ZIKV, those who were positive were more likely to have maculopapular rash (44% vs 12%; P = .02), conjunctival involvement (58% vs 13%; P = .002), and lymphadenopathy (41% vs 6%; P = .02). Joint pain occurred in 65% of ZIKV-positive women and in 41% of ZIKV-negative women, which was not a statistically significant difference (P = .16).

"As compared with women who tested negative for acute ZIKV infection, women who tested positive for the virus had distinctive clinical features of ZIKV infection that included conjunctival injection, lymphadenopathy, and absence of respiratory symptoms," the study authors write. "These clinical features, in addition to a macular or maculopapular rash with pruritus, should raise the suspicion for ZIKV infection. Low-grade fever was found in only 28% of the women; therefore a case definition that is based on the presence of fever would miss more than 70% of cases."

All ZIKV-negative women had fetal ultrasound, as did 42 ZIKV-positive women (58%). Doppler ultrasound showed fetal abnormalities in 12 (29%) of the 42 ZIKV-positive women compared with none of the 16 ZIKV-negative women. Two ZIKV-positive women miscarried during the first trimester, yielding a fetal death rate of 4.8%.

The authors describe these findings as "worrisome," because the patients were all healthy women with no other risk factors for adverse pregnancy outcomes. Adverse ultrasound findings included the following:

  • in utero growth restriction with or without microcephaly (n = 5),

  • abnormal cerebral or umbilical artery flow (n = 4),

  • cerebral calcifications (n = 4),

  • other CNS alterations (n = 2),

  • oligohydramnios and anhydramnios (n = 2), and

  • additional malformations (n = 1): agenesis of the vermis, Blake's pouch cyst, and potentially a club foot in a fetus with cerebral calcifications, intrauterine growth restriction, microcephaly, and negative genetic findings.

Eight of the 42 ZIKV-positive women undergoing fetal ultrasonography delivered their babies (six live births and two stillbirths), with confirmation of abnormalities detected on ultrasound.

Abnormalities were noted in the fetuses of women who were infected at any week of gestation. Although fetuses infected in the first trimester had findings suggestive of pathologic change during embryogenesis, CNS abnormalities also occurred in fetuses infected as late as 27 weeks.

Similarities to Rubella, but Without Population Immunity

The investigators note that many aspects of ZIKV infection resemble those of rubella, notably maternal rash, joint pain, pruritus, and lymphadenopathy without high fever, as well as intrauterine growth restriction, seen in approximately 85% of babies with congenital rubella in the 1959 to 1965 US pandemic.

"A major difference of concern between ZIKV infections in Brazil in 2015–2016 and rubella virus infections in the U.S. pandemic of 1959–1965 is the level of population immunity," the study authors conclude. "In Brazil in 2015–2016, none of the population has antibodies to ZIKV. In contrast, in the United States during the rubella epidemic, there were 20,000 cases of the congenital rubella syndrome, but in 1959 only 17.5% of women of childbearing age lacked rubella antibodies."

This study was not supported by any research funds. The authors have disclosed no relevant financial relationships.

N Engl J Med. Published online March 4, 2016.

    



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