Middle Cerebral Artery Dopplers and Abnormal Neonatal Outcomes among Pregnant Women with Zika Virus Infection.

OBJECTIVE: The aim of this study was to investigate the role of middle cerebral artery (MCA) Doppler measurements for the prediction of abnormal neonatal outcomes in pregnancies affected by Zika virus (ZIKV). METHODS: Secondary analysis of a prospective cohort of pregnant women diagnosed with ZIKV infection from September 2015 to December 2016 at a single regional referral center. Ultrasonography with measurements of MCA peak systolic velocity (PSV), PSV multiples of the median (MoM) for gestational age, and pulsatility index (PI) were collected. The primary outcome was a composite abnormal neonatal outcome. MCA Doppler values of normal and abnormal neonatal outcomes were compared with Wilcoxon rank sum test. The predictive value of MCA Dopplers for development of abnormal neonatal outcome was calculated by logistic regression. RESULTS: One-hundred twenty-seven ZIKV-positive pregnancies with MCA Doppler measurements and known neonatal outcomes were included. Of the 132 neonates, 66 (50%) had an abnormal neonatal outcome. Lower MCA PSV (p = 0.027) and PSV MoM (p = 0.008) were associated with abnormal neonatal outcomes. There was no significant difference in MCA PI. Abnormal neonatal outcomes had lower MCA PSV by 5.36 cm/s (95% confidence interval [CI]: 0.95-9.77, p = 0.018) and lower MCA PSV MoM by 0.13 (95% CI: 0.05-0.22, p = 0.002). MCA PSV of 30 cm/s had a 65% predicted probability of an abnormal neonatal outcome (95% CI: 51-79%). CONCLUSION: In ZIKV-infected pregnancies, lower MCA PSV and PSV MoM measurements were seen with abnormal neonatal outcomes. This may represent a physiologic response to fetal ZIKV infection. Evaluation of MCA Dopplers may be of clinical utility in the surveillance of ZIKV-affected pregnancies. KEY POINTS: · Significantly lower MCA PSV is associated with abnormal neonatal outcomes in ZIKV pregnancies.. · Lower MCA PSV may reflect the underlying neuropathology of ZIKV exposure on the fetus.. · There is potential utility for MCA Doppler evaluation in antepartum surveillance of ZIKV pregnancies..

Avaliação do padrão de restrição do crescimento fetal em gestantes infectadas pelo vírus Zika / Evaluation of the pattern of fetal growth restriction in pregnant women infected with Zika virus

O foco principal desta Dissertação é a caracterização da restrição de crescimento em fetos expostos à infecção pelo vírus Zika (ZIKV) durante a gestação. A população de estudo é formada por mulheres com gestações únicas e testes moleculares positivos para a infecção pelo ZIKV detectados durante a gestação e que foram acompanhadas no IFF entre janeiro de 2016 e março de 2017. Optamos por dividir em dois grupos: fetos de crescimento normal e fetos com crescimento restrito e em faixas de idade gestacional para facilitar a interpretação; o critério diagnóstico para a restrição de crescimento foi a medida da circunferência abdominal abaixo do percentil 10 para a idade gestacional. As variáveis biométricas fetais foram reclassificadas em Z-scores conforme a idade gestacional e, juntamente com as variáveis Dopplervelocimétricas, foram analisadas comparando-se os dois grupos, utilizando o teste t-Student. Observamos que em todas as faixas analisadas, houve diferença significativa entre os parâmetros biométricos, principalmente as circunferências cefálica e abdominal, o fêmur apresentou menor discrepância entre grupos. Na avaliação Dopplervelocimétrica, destacou-se a diferença no índice de pulsatilidade da artéria umbilical. Por fim, descrevemos as malformações congênitas mais frequentes no grupo de fetos restritos, como microcefalia, ventriculomegalia, calcificações intracranianas e artrogripose. Os achados deste estudo sugerem que o vírus Zika interfere no crescimento fetal de uma forma mais seletiva, prejudicando apenas parcialmente o crescimento de ossos longos, e que também promove algum grau de insuficiência placentária, o que explicaria o aumento na resistência ao fluxo sanguíneo umbilical neste grupo de fetos acometidos.

The main focus of this Dissertation is the characterization of growth restriction in fetuses exposed to Zika virus infection during pregnancy. The study population consists of women with singleton pregnancies and positive molecular tests for ZIKV infection detected during pregnancy and who were followed at Instituto Fernandes Figueira between January, 2016 and March, 2017. Then, they were divided into two groups: fetuses with adequate growth and fetuses with restricted growth and we stratified them in gestational age strata to facilitate interpretation; the diagnostic criterion for the growth restriction was the abdominal circumference below the 10th percentile for gestational age. Fetal biometric variables were reclassified into Z-scores according to gestational age and, along with Dopplervelocimetric variables, they were analyzed by comparing the two groups using Student's t-test. We observed that in all analyzed strata, there was significant difference between biometric parameters, especially head and abdominal circumferences, femur length displayed lower discrepancy between groups. On Dopplervelocimetric evaluation, we highlight the difference in the umbilical artery pulsatility index. Finally, we describe the most frequent congenital malformations in the group of restricted fetuses, such as microcephaly, ventriculomegaly, intracranial calcifications and arthrogryposis. The findings of this study suggest that the Zika virus interferes in fetal growth in a more selective form, partially harming femoral growth, and that it also promotes some degree of placental insufficiency, which could explain the increase in umbilical blood flow resistance in the group of affected fetuses.

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

Importance: Congenital Zika virus infection causes a spectrum of adverse birth outcomes, including severe birth defects of the central nervous system. The association of prenatal ultrasonographic findings with adverse neonatal outcomes, beyond structural anomalies such as microcephaly, has not been described to date. Objective: To determine whether prenatal ultrasonographic examination results are associated with abnormal neonatal outcomes in Zika virus-affected pregnancies. Design, Setting, and Participants: A prospective cohort study conducted at a single regional referral center in Rio de Janeiro, Brazil, from September 1, 2015, to May 31, 2016, among 92 pregnant women diagnosed during pregnancy with Zika virus infection by reverse-transcription polymerase chain reaction, who underwent subsequent prenatal ultrasonographic and neonatal evaluation. Exposures: Prenatal ultrasonography. Main Outcomes and Measures: The primary outcome measure was composite adverse neonatal outcome (perinatal death, abnormal finding on neonatal examination, or abnormal finding on postnatal neuroimaging). Secondary outcomes include association of specific findings with neonatal outcomes. Results: Of 92 mother-neonate dyads (mean [SD] maternal age, 29.4 [6.3] years), 55 (60%) had normal results and 37 (40%) had abnormal results on prenatal ultrasonographic examinations. The median gestational age at delivery was 38.6 weeks (interquartile range, 37.9-39.3). Of the 45 neonates with composite adverse outcome, 23 (51%) had normal results on prenatal ultrasonography. Eleven pregnant women (12%) had a Zika virus-associated finding that was associated with an abnormal result on neonatal examination (adjusted odds ratio [aOR], 11.6; 95% CI, 1.8-72.8), abnormal result on postnatal neuroimaging (aOR, 6.7; 95% CI, 1.1-38.9), and composite adverse neonatal outcome (aOR, 27.2; 95% CI, 2.5-296.6). Abnormal results on middle cerebral artery Doppler ultrasonography were associated with neonatal examination abnormalities (aOR, 12.8; 95% CI, 2.6-63.2), postnatal neuroimaging abnormalities (aOR, 8.8; 95% CI, 1.7-45.9), and composite adverse neonatal outcome (aOR, 20.5; 95% CI, 3.2-132.6). There were 2 perinatal deaths. Abnormal findings on prenatal ultrasonography had a sensitivity of 48.9% (95% CI, 33.7%-64.2%) and a specificity of 68.1% (95% CI, 52.9%-80.1%) for association with composite adverse neonatal outcomes. For a Zika virus-associated abnormal result on prenatal ultrasonography, the sensitivity was lower (22.2%; 95% CI, 11.2%-37.1%) but the specificity was higher (97.9%; 95% CI, 88.7%-99.9%). Conclusions and Relevance: Abnormal results on prenatal ultrasonography were associated with adverse outcomes in congenital Zika infection. The absence of abnormal findings on prenatal ultrasonography was not associated with a normal neonatal outcome. Comprehensive evaluation is recommended for all neonates with prenatal Zika virus exposure.