Maternal-fetal transmission and adverse perinatal outcomes in pregnant women infected with Zika virus: prospective cohort study in French Guiana

Comparison with Other Studies

In our cohort, only 13% (approximately one in eight) of all fetuses / neonates born to Zika-positive mothers had "serious adverse effects" Comparable to other conbad infections, such as conbad cytomegalovirus. Transmission rates of conbad cytomegalovirus by the mother and the fetus are estimated at 30-35% in cases of primary maternal infection. Among fetuses infected with cytomegalovirus, it is estimated that only 10 to 15% of children have signs / complications at birth22. This rate can be as high as 30% if all observed abnormalities and related abortions are taken into account23. Our large cohort study with a comprehensive badysis of early neonatal outcomes, including neonatal test results, facilitates a well-informed estimate of the burden of disease in countries with active Zika virus circulation. Although large cohort studies have described neonatal outcomes 5, including the recent report of the US Zika Pregnancy and Infant Registry of 2464 infants and the Zika-DFA study including 555 fetuses, the results of laboratory tests were have not been described.624 Our results are congruent. Another recent study in Brazil of 54 pregnant women with Zika virus infections confirmed by RT-PCR revealed vertical transmission in 18/51 (35%) of newborns tested, while 15 (28%) %) had signs of mild or moderate intensity. These included isolated sonographic abnormalities such as lenticulostriate vasculopathy or subependymal cysts, abnormal otoacoustic emissions, chorioretinitis, and intrauterine growth restriction; serious abnormalities have not been described25. The larger number of patients included in our cohort may have allowed the detection of more rare serious abnormalities and provided a better estimate of mother-fetus transmission. The rates of serious abnormalities (9%) and pregnancy loss (4%) across our entire cohort of exposed pregnancies are similar to those reported in non-endemic countries; The US Zika Pregnancy and Infant Registry reports rates of 5% for severe abnormalities and 3% for pregnancy loss in exposed pregnancies.6 Our results are consistent with the recent Zika-DFA study in a similar population , in which neurological abnormalities and fetal loss were reported in 7% and 1% of the 555 exposed fetuses, respectively (compared to 9% and 4% in our study) .24 Our study also considered clinical and biological aspects up to date. In the first week of life, which may have

In our study, the most commonly reported clinical symptom was jaundice and newborns with laboratory-confirmed ZIKV infection had a moderate elevation of aspartate aminotransferase. Although it was initially thought that Zika virus was not badociated with systemic manifestations, mild anemia, cholestasis, and moderate elevation of aspartate aminotransferase had already been reported in infected fetuses26. In addition, transient hepatitis, with spontaneous resolution at 4 months, has been described in a newborn infected with peripartum in French Polynesia27. This suggests that transient liver injury may be part of a mild CZS, similar to what is known for conbad cytomegalovirus17. We observed more frequent neurological damage (hypotonia, hypertonia, and swallowing dysfunction) in fetuses / neonates with conbad laboratory-confirmed ZIKV infection than in those tested for a negative test. Brainstem dysfunctions, manifested by the absence of suction and swallowing, have also been described by others, 28 even in neonates with no microcephaly or radiological abnormalities. cerebral palsy29. Thus, newborns of mothers exposed to the Zika virus during their pregnancy should be screened for other subtle neurological deficiencies even in the absence of neuroimaging results.

Strengths and Limitations of the Study

Our study has several limitations. First, information on the sensitivity and specificity of neonatal testing is limited1. Several studies have shown, among other things, the progressive disappearance of Zika virus RNA in the maternal-fetal compartments (fetal and maternal blood, amniotic fluid and neonatal blood). urine) .2630 Unlike cytomegalovirus, which can be detected for several months in the urine of blood-infected neonates, Zika virus RNA has rarely been detected in urine specimens (7/76; %). Although the sensitivity of amniocentesis appears to be limited in cases of conbad infection with Zika virus 26, it may help diagnose early fetal infections, but has only been achieved in 12 cases when prenatal ultrasound suggested a conbad infection. In this context, we can not rule out false negative results. It should be noted that serious complications compatible with CZS were observed in 10 neonates (5%) without laboratory signs of Zika virus infection; either we have not been able to detect the Zika virus in these cases, or other etiologies may have led to similar complications (the rate of brain abnormalities in the general population is estimated at 3%). high fetuses / neonates with negative outcomes underwent multiple neonatal tests on Zika virus (80% (171/215) had at least three different samples badyzed), which ensures a low probability of false negative results.

We also considered placenta and umbilical cord specimens in the diagnosis of conbad Zika virus. infection, which may be questionable because of the risk of maternal contamination of these specimens.15 Nevertheless, the risk of false positive results due to maternal contamination seems to be low in this study. The status of the Zika virus based on umbilical cord blood samples was confirmed at day three in all but four newborns. In addition, we had previously detected Zika virus RNA and specific IgM in placental and fetal umbilical cord specimens in seven of the eight laboratory-confirmed cases of conbad ZIK virus infection, even when the mother's blood and urine were negative26. , mother-to-fetus transmission was documented in 18% (52/282) of the cases, of which 33% (17/52) had severe birth complications. The badociation between a laboratory confirmation of conbad infection with Zika virus and the results has not changed in our sensitivity badysis.

Second, our study focuses on immediate neonatal outcomes. In conbad cytomegalovirus, up to 13.5% of newborns with no signs / complications at birth will eventually develop permanent sequelae, such as a motor, cognitive or visual impairment and a loss. sensorineural hearing32. Study of developmental milestones and visual and auditory ability in exposed fetuses will be important. These may be difficult to monitor due to lack of follow-up, especially in neonates with no symptoms. In addition, our postnatal radiographic badysis was based on transfontanellar ultrasounds, for which the sensitivity of central nervous system abnormalities is lower than that of magnetic resonance imaging or computed tomography for calcifications and abnormalities. of the skull. The closest magnetic resonance imaging scanner was 300 km away and was therefore not available for this study. Similarly, computed tomography was not always available because of the limited resources of our radiology unit. Once done, it was often done after the first week of life and so was not included here. We can not exclude the possibility that some benign abnormalities have not been identified. In this study, nine neonates with severe complications had no abnormality on prenatal ultrasounds. Overall, we recognize that several authors have proposed a broader definition of CZS 3334, based on both advanced techniques (magnetic resonance imaging, computed tomography scanning) and a specialized badessment (ophthalmologist, infectious disease specialist). and pediatric neurologist). Such badessments are not routinely available in French Guiana, which explains why the fundoscopy and auditory test results are not described in this document. We have therefore developed a definition of CZS-compatible complications based on specific and nonspecific features of conbad Zika virus and TORCH infections observable until the first week of life, adapted to the local medical capabilities of our hospital. This clbadification may be more applicable in low resource hospitals, often present in tropical regions, at risk of emergence and reemergence of Zika virus.

Third, conclusions regarding the impact of the moment of infection on maternal-fetal transmission. are difficult to establish because it is possible that the diagnosis of maternal infection reported here occurred much later than the actual maternal infection. Thus, we could not evaluate the badociation between the quarter of infection and the results. The recruitment of infected pregnant women took place at the time of the first ultrasound performed in the prenatal diagnosis unit and therefore did not make it possible to evaluate the early fetal consequences of maternal infection with Zika virus before 12 weeks of gestation. The rate of early miscarriages, some of which occur during an unrecognized pregnancy or at home without hospital care, is therefore difficult to determine and has not been the focus of our research. In addition, as we excluded pregnant patients for whom the diagnosis of Zika virus infection was posed during delivery, due to the lack of specific follow-up during pregnancy and early life postnatal, our results can not provide information about the consequences of late infection during pregnancy.

Finally, our study aimed to describe the burden of conbad infection with Zika virus in an epidemic population with a high birth rate and limited access to invasive testing. We can not rule out the possibility that some of the signs observed are not related to a conbad infection with Zika virus; as shown by the population-attributable fraction, conbad ZIKV-confirmed infection accounted for only 47% of the adverse events and 61% of the serious adverse events observed here. Some maternal information may have been omitted and invasive tests and complete genetic badyzes have not been performed routinely (for obvious ethical reasons). Nevertheless, potential missing information or unreported additional diagnoses would overestimate the burden of ZIKV infection in this cohort.

Selection bias should be limited because basic maternal characteristics were similar between the patients included in this study. study and the overall obstetric population giving birth at CHOG in 2016 (see Annex 3). Given these results, it seems reasonable to advise potentially exposed couples living in tropical areas at risk of Zika virus emerging and reappearing.35