Association of Prenatal Ultrasonographic Findings With Adverse Neonatal Outcomes Among Pregnant Women With Zika Virus Infection in Brazil

Pereira, José Paulo; Nielsen‐Saines, Karin; Sperling, Jeffrey D.; Maykin, Melanie; Damasceno, Luana; Cardozo, Renan Fonseca; Valle, Helena Abreu; Dutra, Beatriz Ribeiro Torres; Gama, Helder Dotta; Adachi, Kristina; Zin, Andréa; Tsui, Irena; Vasconcelos, Zilton; Brasil, Patrícia; Moreira, Maria Elizabeth Lopes; Gaw, Stephanie L.

doi:10.1001/jamanetworkopen.2018.6529

Cited by 19 publications

(31 citation statements)

References 32 publications

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“…Limited data suggest that when present, abnormal findings detected on prenatal ultrasound are associated with abnormal findings on physical examination and in postnatal neuroimaging; however, the absence of abnormal prenatal findings is not a predictor of a normal neonatal outcome. 31 True cases of microcephaly and/or CNS defects detected prenatally alone might not have been ascertained. Finally, differentiating birth defects associated with ZIKV infection from those associated with other congenital infections is complicated due to continued evolving data on the congenital ZIKV phenotype, resulting in classification bias.…”

Section: Original Articlesmentioning

confidence: 99%

Etiology of Microcephaly and Central Nervous System Defects during the Zika Epidemic in Colombia

Galang¹,

Avila²,

Valencia³

et al. 2020

The Journal of Pediatrics

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Objective To estimate the prevalence of microcephaly and central nervous system (CNS) defects during the Zika virus (ZIKV) epidemic in Colombia and proportion attributable to congenital ZIKV infection. Study design Clinical and laboratory data for cases of microcephaly and/or CNS defects reported to national surveillance between 2015 and 2017 were reviewed and classified by a panel of clinical subject matter experts. Maternal and fetal/infant biologic specimens were tested for congenital infection and chromosomal abnormalities. Infants/fetuses with microcephaly and/or CNS defects (cases) were classified into broad etiologic categories (teratogenic, genetic, multifactorial, and unknown). Cases classified as potentially attributable to congenital ZIKV infection were stratified by strength of evidence for ZIKV etiology (strong, moderate, or limited) using a novel strategy considering birth defects unique or specific to ZIKV or other infections and laboratory evidence. Results Among 858 reported cases with sufficient information supporting a diagnosis of microcephaly or CNS defects, 503 were classified as potentially attributable to congenital ZIKV infection. Of these, the strength of evidence was considered strong in 124 (24.7%) cases; moderate in 232 (46.1%) cases; and limited in 147 (29.2%). Of the remaining, 355 (41.4%) were attributed to etiologies other than ZIKV infection (syphilis, toxoplasmosis, rubella, cytomegalovirus, herpes 1 and herpes 2 viruses only, n = 32 [3.7%]; genetic, n = 16 [1.9%]; multifactorial, n = 42 [4.9%]; unknown, n = 265 [30.9%]). Conclusions Fifty-eight percent of cases of microcephaly and/or CNS defects were potentially attributable to congenital ZIKV infection; however, the strength of evidence varied considerably. This surveillance protocol might serve as a model approach for investigation and etiologic classification of complex congenital conditions. (J Pediatr 2020;222:112-9). See editorial, p 15 I n 2015, the Colombian National Institute of Health (INS) began Zika virus (ZIKV) surveillance, including protocols for testing and management of pregnant women and infants with suspected ZIKV infection. 1,2 In 2016, the World Health Organization declared a Public Health Emergency of International Concern prioritizing global efforts to prevent ZIKV transmission and to perform surveillance for ZIKV transmission and for adverse outcomes related to congenital ZIKV infection, including microcephaly and birth defects of the central nervous system (CNS). 3-6 Building on its existing birth defects surveillance infrastructure, the INS established an enhanced surveillance protocol focused on microcephaly and CNS defects to monitor potential increases in birth prevalence; identify possible causes, including congenital ZIKV infection; determine proportion of reported cases potentially attributable to ZIKV; and direct appropriate public health intervention. The first confirmed case of ZIKV-related congenital microcephaly in Colombia was reported in April 2016. 7 A preliminary report of surveillance

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Section: Original Articlesmentioning

confidence: 99%

Etiology of Microcephaly and Central Nervous System Defects during the Zika Epidemic in Colombia

Galang¹,

Avila²,

Valencia³

et al. 2020

The Journal of Pediatrics

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“…oligohydramnios). The same study also found that fetal Doppler measurements of the middle cerebral artery were associated with abnormal neonatal outcomes (adjusted odds ratio of 20�2, 95% CI 3�2-132�6) [16]; these measurements can be technically difficult to obtain by sonographers with limited training in low-and middle-income countries. In contrast, obtaining the HC: FL ratio only requires that the sonographer measure the HC and FL, which represents skills typically learned early in ultrasound training.…”

Section: Plos Onementioning

confidence: 89%

“…Notably, the sensitivity and PPV of the HC: FL ratio was poor, which is in accordance with other studies of the limited sensitivity of ultrasound to detect the broader spectrum of congenital ZIKV-associated injuries. [7,14,16] Unfortunately, the addition of fetal MRI to prenatal ultrasound does not appear to increase sensitivity for detection of congenital ZIKV-associated injuries. [9] A study to determine the diagnostic accuracy of a diverse set of sonographic abnormalities (e.g.…”

Section: Plos Onementioning

confidence: 99%

“…placentomegaly, oligohydramnios) in combination with known ZIKVassociated anomalies found an adjusted odds ratio of 27.2 (95% CI 2�5-296�6) for abnormal neonatal outcomes. [16] The real-world application of various sonographic findings for the prediction of ZIKV-associated postnatal outcomes becomes challenging, particularly when there is a single abnormal finding that might be atypical of ZIKV-associated anomalies (e.g. oligohydramnios).…”

Section: Plos Onementioning

confidence: 99%

“…[7,14] Although ultrasound remains the most available method for prenatal diagnosis of ZIKV-associated birth defects, studies suggest it is insufficient to predict the widening array of congenital ZIKV injury. [15][16][17][18] The lack of a prenatal diagnostic test to either predict or rule out ZIKV-associated anomalies represents a major clinical challenge in ZIKVendemic areas.…”

Section: Introductionmentioning

confidence: 99%

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Ultrasound prediction of Zika virus-associated congenital injury using the profile of fetal growth

et al. 2020

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Zika virus (ZIKV) is a mosquito-transmitted flavivirus, recently linked to microcephaly and central nervous system anomalies following infection in pregnancy. Striking findings of disproportionate growth with a smaller than expected head relative to body length have been observed more commonly among fetuses with exposure to ZIKV in utero compared to pregnancies without ZIKV infection regardless of other signs of congenital infection including microcephaly. This study's objective was to determine the diagnostic accuracy of femursparing profile of intrauterine growth restriction for the identification of ZIKV-associated congenital injuries on postnatal testing. A retrospective cohort study of pregnant women with possible or confirmed ZIKV infection between January 1, 2016 and December 31, 2017 were included. Subjects were excluded if no prenatal ultrasound was available. A femursparing profile of growth restriction determined using INTERGROWTH-21 st sonographic standard for head circumference to femur length (HC: FL). Congenital injuries were determined postnatally by imaging, comprehensive eye exam and standard newborn hearing screen. A total of 111 pregnant women diagnosed with ZIKV infection underwent fetal ultrasound and 95 neonates had complete postnatal evaluation. Prenatal microcephaly was detected in 5% of fetuses (6/111). Postnatal testing detected ZIKV-associated congenital injuries in 25% of neonates (24/95). A HC: FL Z-score �-1.3 had a 52% specificity (95% CI 41-63%), 82% negative predictive value (NPV, 95% CI 73-88%) for the detection of ZIKVassociated congenital injuries in the neonatal period. A more stringent threshold with a Zscore �-2 was associated with a 90% specificity (95% CI 81-95%), 81% NPV (95% CI 77-PLOS ONE

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Can Ultrasound Be Used to Reassure Pregnant Women Infected by Zika Virus?

Levine

2018

JAMA Netw Open

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The aim of the study by Pereira et al 1 was to assess the association between prenatal ultrasonographic findings and neonatal outcomes among pregnant women with confirmed Zika virus infection. This is a follow-up study from that reported by Brasil et al 2 in which, from September 2015 through May 2016, 345 pregnant women with acute illness and rash within the preceding 5 days were initially eligible. Ultimately, 182 pregnant women had a positive result confirmed by reversetranscription polymerase chain reaction for Zika virus and were offered ultrasonographic examination, of whom 92 (51%) opted for at least 1 second-or third-trimester ultrasonographic examination and had known neonatal outcomes. A key finding of the study is that a negative ultrasonographic result cannot be used to reassure parents that the outcome of the pregnancy will be normal.

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Association of Prenatal Ultrasonographic Findings With Adverse Neonatal Outcomes Among Pregnant Women With Zika Virus Infection in Brazil

Cited by 19 publications

References 32 publications

Etiology of Microcephaly and Central Nervous System Defects during the Zika Epidemic in Colombia

Etiology of Microcephaly and Central Nervous System Defects during the Zika Epidemic in Colombia

Ultrasound prediction of Zika virus-associated congenital injury using the profile of fetal growth

Can Ultrasound Be Used to Reassure Pregnant Women Infected by Zika Virus?

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