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

Christie L Walker,Brittney Mason,Marie-Térèse E Little,Kristina M Adams Waldorf,Aris T Papageorghiou,Noah Ehinger,Eric O Ohuma,Christine Curry,Unzila Nayeri,Elizabeth Oler,Irina Burd

doi:10.1371/journal.pone.0233023

Christie L Walker, Brittney Mason + Show 9 more

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https://doi.org/10.1371/journal.pone.0233023

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Abstract

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 femur-sparing 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 femur-sparing profile of growth restriction determined using INTERGROWTH-21st 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 ZIKV-associated congenital injuries in the neonatal period. A more stringent threshold with a Z-score ≤ -2 was associated with a 90% specificity (95% CI 81–95%), 81% NPV (95% CI 77–85%). Excluding cases of fetal microcephaly, HC: FL (Z-score ≤ -2) demonstrated a similar specificity (89%, 95% CI 81–95%) with superior NPV (87%, 95% CI 84–90%). The sonographic recognition of a normally proportioned fetus may be useful prenatally to exclude a wider spectrum of ZIKV-associated congenital injuries detected postnatally.

Highlights

IntroductionIntrauterine growth restriction (IUGR) is a known sequela of Zika virus (ZIKV) and other teratogenic viral infections [19], but whether aberrant fetal growth might predict congenital injuries in pregnancies exposed to ZIKV is unknown
We first observed an unusual femur-sparing pattern of Intrauterine growth restriction (IUGR) in a nonhuman primate model of congenital Zika virus (ZIKV) infection; in these experiments, there was an arrest of fetal head growth, while the long bones continued to grow normally. [20, 21] This striking profile of fetal growth was seen in a majority of pregnant women from New York City acquiring ZIKV through travel; a lack of postnatal data precluded correlation with congenital ZIKV injury in this study
The principal study finding is that an head circumference (HC): femur length (FL) ratio greater than the 3rd centile in a normocephalic fetus is associated with an 87% NPV for the postnatal detection of congenital ZIKVassociated injuries

Summary

Introduction

Intrauterine growth restriction (IUGR) is a known sequela of ZIKV and other teratogenic viral infections [19], but whether aberrant fetal growth might predict congenital injuries in pregnancies exposed to ZIKV is unknown. [20, 21] This striking profile of fetal growth was seen in a majority of pregnant women from New York City acquiring ZIKV through travel; a lack of postnatal data precluded correlation with congenital ZIKV injury in this study. Prenatal ultrasound biometric measurements of the fetus from pregnancies with a ZIKV infection were correlated with postnatal testing to determine the diagnostic accuracy of a femur-sparing profile of IUGR to predict ZIKV-associated congenital injury. The prenatal diagnosis of aberrant fetal growth may aid in identification of neonates at high risk for impaired development who warrant early interventions

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