懷孕期間感染茲卡病毒與胎兒死亡、CNS損傷等嚴重結果有關


  【24drs.com】根據線上發表於3月4日新英格蘭醫學期刊,巴西里約熱內盧監測病例初步報告,懷孕期間感染茲卡病毒(Zika virus,ZIKV)和胎兒死亡、中樞神經系統(CNS)損傷、生長受限、胎盤功能不全等嚴重後果有關。
  
  里約熱內盧Oswaldo Cruz基金會Patricia Brasil醫師等人寫道,我們的研究結果為孕婦感染茲卡病毒和胎兒與胎盤異常之關聯提供更多證據,和造成先天性感染的其他病毒不同,此症會引起子宮內發育遲緩與胎盤功能不全。
  
  之前已認為孕婦感染茲卡病毒與新生兒畸形有關聯。從2015年9月到2016年2月,研究者納入88名有皮疹的孕婦,其中72人(82%)的血液和/或尿液反轉錄酶聚合酶鏈反應檢測發現為茲卡病毒陽性,研究者採取臨床檢查和一系列的超音波持續追蹤這些婦女。
  
  雖然孕婦本身的症狀相對輕微,嬰兒卻發生嚴重後果,包括2例在妊娠36、38週時死亡、子宮內生長受限合併或未合併小頭畸形、心室鈣化或其他CNS病灶、羊水量異常、腦或臍動脈血流異常。
  
  作者們寫道,應密切監測疑似或確認感染茲卡病毒的婦女,鑑於胎兒死亡和子宮內生長受限的風險,應使用一系列的超音波檢查,以評估胎盤功能不全的跡象。在茲卡病毒和先天性異常結果之間建立一個具有科學可信度的關聯,是極其重要的,以便在巴西與全球有效且成功地因應這波流行病。
  
  婦女在妊娠5-38週出現疑似急性茲卡病毒感染,典型症狀是下行(descending)斑疹或斑丘疹,94%患者出現瘙癢;關節痛;結膜充血;頭痛。發燒情況並不明顯,僅不到三分之一患者(28%)發生,且大部份是短期間且輕微。
  
  相較於茲卡病毒陰性的婦女,陽性者比較可能有斑丘疹(44% vs 12%;P = .02)、結膜相關症狀(58% vs 13%;P = .002)與淋巴結腫大(41% vs 6%;P = .02)。65%的茲卡陽性婦女和41%的茲卡陰性婦女發生關節痛,未達統計上的顯著差異(P = .16)。
  
  研究作者們寫道,相較於急性茲卡病毒感染檢測陰性的婦女,病毒檢測陽性的婦女,其獨特臨床表徵包括結膜充血、淋巴結腫大、沒有呼吸道症狀。除了斑疹或斑丘疹,對於疑似茲卡病毒感染者應特別注意這些臨床表徵。僅28%婦女有輕微發燒,因此,如果根據出現發燒來定義病例,會錯失超過70%的案例。
  
  所有的茲卡陰性婦女與42名茲卡陽性婦女(58%)接受了胎兒超音波檢查,都卜勒超音波顯示,42名茲卡陽性婦女有12人(29%)出現胎兒異常,而16名茲卡陰性婦女都沒有;2名茲卡陽性婦女在第一孕期時流產,胎兒死亡率為4.8%。
  
  作者認為這些是令人擔憂的結果,因為這些患者都是沒有會造成不良懷孕結果之其他風險因素的健康婦女,超音波發現的不良結果如下所列:
  * 子宮內生長受限,合併或未合併小頭畸形(n = 5),
  * 腦或臍動脈血流異常(n = 4)
  * 顱內鈣化(n = 4)
  * 其他CNS變化(n = 2)
  * 羊水過少和無羊水(n = 2)
  * 其他畸形(n = 1):蚓部發育不全、Blake氏囊腫、胎兒潛在的內翻足合併顱內鈣化、子宮內生長受限、小頭畸形、以及負面的遺傳結果。
  
  42名茲卡病毒陽性婦女中,有8人進行胎兒超音波並生下她們的嬰兒(6名活產與2名死產),都確認有超音波檢查時發現的異常。
  
  在妊娠期間的任一時間點受到感染,婦女的胎兒都有發現異常,雖然在第一孕期受到感染的胎兒於胚胎發育過程中已經發現病理變化跡象,受感染胎兒的CNS異常也會遲至27週時才會發生。
  
  研究者指出,茲卡病毒感染的許多方面類似於麻疹,尤其是孕婦皮疹、關節痛、皮膚搔癢、淋巴結腫大無高燒、以及子宮內生長受限。在1959-1965年美國大流行的嬰兒先天性麻疹中,約有85%也曾出現這些症狀。
  
  研究作者們結論表示,對於2015-2016年巴西茲卡病毒感染和1959-1965年美國麻疹感染之關注有一大差異,也就是人們的免疫能力。2015-2016年的巴西茲卡病毒感染,沒有人有茲卡病毒的抗體。相對的,美國的麻疹大流行時,有20,000例先天性麻疹症候群,但是,在1959年,只有17.5%的孕齡婦女沒有麻疹抗體。
  
  資料來源: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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