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Zika virus infection: Evaluation of pregnant women and fetuses Laleh Eslamian MD, Perinatologist Professor of Obstetrics & Gynecology TUMS There is no evidence to suggest: O Pregnant women are more susceptible to Zika virus infection. O Transmission of Zika virus infection through breastfeeding. O Pregnant women experience more severe disease than nonpregnant women, however, viremia may persist longer in pregnant women. Congenital infection Zika virus infection in all trimesters has been associated with fetal abnormalities. O Microcephaly O Fetal loss and stillbirth O Ocular abnormalities: include focal pigment mottling, chorioretinal atrophy, and optic nerve abnormalities O Other CNS abnormalities (eg, ventriculomegaly, global hypogyria, hydranencephaly) O Hydrops fetalis O Fetal growth restriction O In areas with no known mosquito-borne Zika virus transmission, healthcare providers should determine whether the pregnant woman is at risk because of her travel or sexual history. O Women who is @ risk or who live in an area with known Zika virus transmission should be asked about symptoms consistent with Zika virus infection. Women with no exposure to Zika virus O For pregnant women with no relevant epidemiologic exposure, laboratory testing or fetal screening for Zika virus infection is not indicated. Women with symptoms consistent with possible Zika virus infection O Should have both lab testing and ultrasound exam within 2 weeks of epidemiologic exposure. O For patients presenting <7 days after onset of symptoms, check serum Zika virus RNA (RTPCR). A positive test is diagnostic of infection. O If the RT-PCR is negative and the patient is ≥4 days after the onset of symptoms, check Zika virus IgM and neutralizing antibody titers. A positive test is presumptive of infection. Asymptomatic women with possible but not ongoing exposure to Zika virus O Should have both laboratory testing and ultrasound examination. O Should have Zika virus IgM and neutralizing antibody titers checked 2 to 12 weeks following exposure. O A negative IgM result 2 to 12 weeks following exposure suggests absence of a recent infection. Asymptomatic women with ongoing risk for Zika virus infection O Should have both laboratory testing and ultrasound examination. O Zika virus IgM and neutralizing antibody titers are warranted at the initiation of prenatal care. A positive test is diagnostic of infection. O If the initial test is negative and performed in the 1st or early 2nd trimester, repeat testing at 18 to 20 weeks. O A negative IgM result 2 to 12 weeks following exposure suggests absence of a recent infection. EVALUATION OF FETAL LOSS AND STILLBIRTH O Fetal tissue testing is warranted for fetal losses in women with history of Zika exposure, together with either symptoms consistent with Zika virus infection during or within two weeks of exposure or findings of fetal microcephaly. O Zika virus RT-PCR and histopathologic examination with immunohistochemical staining should be performed on fetal tissues, including the umbilical cord and placenta. SCREENING FOR FETAL INFECTION O Ultrasound is the major modality used to screen for fetal Zika virus infection, but MRI is more sensitive. O Ultrasound findings associated with fetal Zika virus infection may be detected as early as 18 to 20 weeks gestation in some cases. O The two major ultrasound findings suggestive of congenital Zika virus infection are: 1) microcephaly 2) intracranial calcification O The International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) interim guidance on ultrasound for Zika virus infection in pregnancy recommends a baseline ultrasound examination for: 1) women with Zika virus exposure and symptoms 2) positive serology or proven Zika virus infection 3) or exposure and/or symptoms without positive serology results. O If the baseline examination is normal, the ISUOG recommends serial ultrasound examinations every 4-6 weeks, if possible. O If the baseline examination is abnormal, referral to a specialist for neurosonography of the fetal brain is recommended. O In the absence of microcephaly, if the head circumference is small or not enlarging appropriately, MRI may detect abnormalities not visible on ultrasound and may be useful. Amniocentesis O Zika virus reverse-transcription polymerase chain reaction (RT-PCR) positivity in amniotic fluid is diagnostic of fetal viral exposure but not predictive of outcome. O The indications for diagnostic amniocentesis, the appropriate gestational age for testing, and the interpretation of the test are uncertain. O Decisions regarding amniocentesis should be tailored to individual clinical circumstances. Amniocentesis is offered to women with either of the following: O Fetal microcephaly (3SD below the mean for gestational age), intracranial calcifications, and/or ventriculomegaly, regardless of maternal laboratory test results for Zika virus infection. O Positive or inconclusive maternal laboratory test results for Zika virus infection. Timing of amniocentesis O For women with characteristic sonographic findings of fetal Zika virus infection, amniocentesis upon diagnosis and as early as 15 to 16 weeks is reasonable. But not <15 weeks because of an increased risk of pregnancy loss. O For women with positive or inconclusive Zika virus test results and a normal-appearing fetus, the optimal timing for performance of amniocentesis is uncertain. 6-8 weeks after maternal infection is suggested. O If amniocentesis is performed 6-8 weeks after maternal infection and false-negative results are suspected, a repeat amniocentesis later in gestation may be considered. Interpretation of amniocentesis result O The sensitivity and specificity of Zika virus RT-PCR testing of amniotic fluid for diagnosis of congenital infection are not known and likely depend on timing of amniocentesis after onset of maternal infection. O A positive RT-PCR result on amniotic fluid should be considered suggestive of intrauterine infection. O If the test was performed because of maternal laboratory findings or viral exposure and the fetus appears normal, it is unknown whether a positive amniotic fluid RT-PCR result is predictive of a subsequent fetal abnormality and, if so, what proportion of infants will have abnormalities. O If the RT-PCR is negative and the fetus is abnormal, evaluation for other causes of the fetal abnormalities should be considered. Antepartum fetal monitoring O Infected fetuses are at risk for stillbirth. O If antenatal testing is performed (eg, nonstress test, biophysical profile) and results are abnormal, early delivery may be appropriate, depending on the clinical scenario. NEWBORN EVALUATION O All newborns should undergo thorough evaluation within 24 hours of birth. O The occipitofrontal circumference should be measured. O Diagnostic criteria for congenital infection —the presence of Zika virus RNA in any of the samples collected, including amniotic fluid, placenta, umbilical cord, newborn serum, or newborn CSF. In addition, congenital infection may be established by the presence of Zika virus IgM antibodies in newborn serum or CSF, with confirmatory neutralizing antibody titers that are ≥4-fold higher than dengue virus neutralizing antibody titers. EVALUATION OF WOMEN AND NEWBORNS WITH PERIPARTUM ZIKA VIRUS EXPOSURE O Maternal-fetal transmission of Zika virus can occur during labor and delivery. O There are no reports of Zika virus infection acquired by an infant at the time of delivery leading to microcephaly. O Maternal and newborn laboratory testing is indicated during the first two weeks of life if the mother had relevant epidemiologic exposure within two weeks of delivery and had ≥2 of the following manifestations of Zika virus infection: rash, conjunctivitis, arthralgia, or fever Planning pregnancy O There is no evidence that women who have had a prior Zika virus infection are at risk of birth defects in future pregnancies. O CDC recommends that: 1) women who have had a Zika virus infection should wait at least eight weeks after symptom onset before attempting conception. 2) men with symptomatic Zika virus infection (confirmed or suspected) wait at least six months before having unprotected sex. 3) asymptomatic men with Zika virus exposure (via travel to mosquito transmission areas or sexual contact) wait at least eight weeks before unprotected sex. Thank You