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Microcephaly and Zika Virus – an Update
Matthew Loichinger, D.O.Minnesota Perinatal PhysiciansApril 15, 2016
Case Presentation
31 year old Caucasian G2P1001 Dated by first trimester ultrasound In Costa Rica at 19 weeks: 2/2/16-2/9/16Several bug bites but otherwise asymptomatic Level II with outside OBGYN at 21 weeks normalEFW 26th percentile BUT…HC 5th percentile
Case Presentation
Perinatal consult requested 23 weeks: MPP Level II ultrasound also normal
Things to consider Does this patient have microcephaly? Do I test this patient for Zika Virus? What ARE the current Zika Virus recommendations? How do I follow this patient?
Case Presentation
Microcephaly
Smaller-than-normal head circumference (HC)HC preferred over biparietal diameter (BPD) BPD inaccurate if breech, oligohydramnios, multiple gestation
HC 2SD below mean vs. 3SD below meanWith 2SD below the mean, 2.5% of population is microcephalic Using 3SD below the mean is more clinically meaningful Associated with mental retardation, developmental delay
Microcephaly Microencephaly (small brain)
Microcephaly
Sonographic FindingsHC 3SD below the mean for GA Frontal-lobe measurements and Thalamic-
frontal-lobe distance Small studies: below 2SD in most cases Not widely used
Microcephaly
Diagnosis cannot be excluded with 2nd trimester ultrasoundHead growth may not slow appreciably until 3rd
trimesterDoppler ultrasound may identify abnormal
intracranial vascular anatomy Reduced blood supply to cerebral hemispheres microcephaly Not widely used
Microcephaly
Differential diagnosis Injury: ischemic or hemorrhagic strokeVertically transmitted infection CMV, Toxo, Rubella, Zika
Drugs: fetal hydantoin syndrome, FASSyndromes: T13, T18, Cri-du-chat, DiGeorge,
etcOther: placental insufficiency, radiation
exposure, malnutrition, PKU
Microcephaly
ManagementObtain H&P (febrile illness, prenatal exposures,
etc)Detailed US: intracranial AND extracranial
abnormalitiesKaryotyping via amniocentesisCounselingDifficult due to lack of long term data (Zika)
Microcephaly
Delivery: if isolated, community hospital OKPostnatal referral to medical genetics and
pediatric neurology Timing/mode of delivery independent of
microcephalyAssociated abnormalities: deliver at tertiary care
center
Microcephaly
Long-term outcome Isolated microcephaly: MR (IQ <70) in 25%Microcephaly + other malformations/congenital infection: POOR
PROGNOSIS
HC persistently 3SD below mean in infancy: 51% have IQ below 70 at 7 years of age Includes non-isolated microcephaly
HC – 2-3 SD: 11% have IQ <70Recurrence risk of idiopathic severe
microcephaly is 6-20% (avg 12%)
Microcephaly
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Zika Virus
Zika Virus
First human case in 1952
SE Asia, Africa, Pacific Islands
14 documented cases prior to 2007
Spread through the bite of an Aedes species mosquito Also dengue and chikungunya Symptoms: fever, rash, joint pain, conjunctivitis within
2 weeks of travel Typically mild, lasting several days to a week Infection confers immunity Feb 1, 2016: WHO declares public health emergency
of international concern (PHEIC)
Zika Virus
Brazilian outbreak of Zika since May 2015 Increased incidence of microcephalyAssociation versus causationZika virus isolated in brains of microcephalic babies
Incidence 1.6 in 1000 (0.16%) live births in US Incidence in Brazil (2012-2015) as high as 8%Previously 2.8%
4-fold increase in cases
Zika Virus
Pesticide NOT responsiblePyriproxyfen approved by WHOUsed for decades in Brazil and elsewhere with
no increase in cases of microcephaly
Zika Virus
As of 4/6/16: 346 travel-associated disease cases in US (12 in MN) 0 locally acquired vector-borne cases in US 12 cases in US Virgin Islands, 325 in Puerto Rico
Prevention is keyBites occur primarily during the dayCover up: Long-sleeve clothing, screens,
mosquito netting on beds, Air conditioningUse EPA-registered repellent (see CDC.gov) If symptomatic, avoid additional mosquito bites
for 1 week
Zika Virus
Zika Virus
Increasing evidence supports the link between Zika infection during pregnancy and adverse pregnancy outcomes Pregnancy loss, microcephaly, and other brain and eye
abnormalities. Transmission of Zika to the fetus has been documented
in all trimesters Zika RNA has been detected in fetal tissue from early
missed abortions, amniotic fluid, term neonates, and the placenta.
Much is not yet known about Zika in pregnancy. Uncertainties include: Incidence of Zika infection among pregnant women in
areas of Zika transmission Rate of vertical transmission Rate with which infected fetuses manifest
complications such as microcephaly or demise
Zika Virus
Study using modeling based on the Zika outbreak in French Polynesia suggested microcephaly would occur in 1% of babies born to mothers infected in the first trimester Another recent cohort study from Brazil found
abnormal outcomes including stillbirth, growth restriction, and microcephaly and other sonographic abnormalities in 29% of fetuses of Zika infected mothers in all trimesters
Zika Virus
Zika, the new STDSpread from infected man via semen Virus present for as-yet unknown duration
Virus present in semen longer than in blood Virus “doesn’t stay long” in blood stream: 5-7 days?
Condom use or abstinence during pregnancy If traveled to area with ongoing transmission of Zika Symptomatic OR asyptomatic males
Zika Virus
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Zika Virus & Pregnancy Management
Evaluation of pregnant women with a history of travel to an area with ongoing ZIKV transmission
SYMPTOMATIC WOMEN (one or more of the following signs or symptoms: acute onset of fever, rash, arthralgia, conjunctivitis) during or within 2 weeks of travel, testing recommended using Zika RT PCR and Zika IgM. Also co-testing for dengue and chikungunya.
ASYMPTOMATIC WOMEN during or within 2 weeks of travel: Offer testing to pregnant women 2–12 weeks after exposure (travel) with Zika IgM
Zika Virus & Pregnancy Management
Testing performed at CDC via Minnesota Department of Health (MDH)
Must contact MDH before submitting specimens for Zika testing Call 651-201-5414 OR 1-877-676-5414
Perinatology consult recommended
Zika Virus & Pregnancy Management
Fetal Surveillance Ultrasound examinations are recommended for those
who have traveled to areas with ongoing Zika transmission. Obtain the first ultrasound 3–4 weeks after symptoms
or exposure or at 18–20 weeks (Whichever is first) Serial ultrasounds are recommended in the setting of
maternal infection (positive or inconclusive IgM and/or PCR), every 4 weeks Natural history of Zika in utero infection is not known, and the
time from exposure and infection to clinical manifestations is uncertain
Zika Virus & Pregnancy Management
Zika Virus and Pregnancy
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Zika Virus and Other Populations
Women Avoiding Pregnancy If planning travel to area of ongoing transmission,
discuss reliable contraception options to reduce risk of unintended pregnancy
Safety, effectiveness, availability, and acceptability should be considered when selecting a contraceptive method.
Zika Virus and Other Populations
Women Who Desire Pregnancy Women who are diagnosed with Zika disease should
wait at least 8 weeks from symptom onset to attempt pregnancy
Men diagnosed with Zika disease should wait at least 6 months from symptom onset to attempt pregnancy.
These are estimates derived from the upper limit estimate for Zika incubation (14 days) and approximate tripling of the longest published duration of known viremia after symptom onset.
Zika Virus and Other Populations
Breastfeeding The presence of Zika virus in breast milk has been
reported it is in very small amounts and unlikely to be harmful for the neonate Infection through oral intake is not known and any
effects of neonatal infection, as with adults, are likely to be mild and of short-term consequence. The benefits of breastfeeding likely outweigh the
potential neonatal risks. Therefore, the recommendation is that women should continue to breastfeed
Zika Virus and Other Populations
Asymptomatic pregnant traveler within 2-12 wksUltrasound not consistent with microcephaly No other associated findings: calcifications, ventriculomegaly,
cerebellar hypoplasia
Zika IgM testing recommended Follow up ultrasound in 4-6 weeksRoutine prenatal careProper condom use
Case Presentation
• Contact Information: 612-863-4502• MOMS Subspecialty Clinic: 612-863-4502/651-241-
6270)• Midwest Fetal Care Center: 855-693-3825
• MEFetalCare@allina.com• Children’s Physician Access: 612-343-2121
Minnesota Perinatal Physicians Contact Us
Fetology, 2nd edition.Soares JS, Regis CT, et al. Microcephaly in
northeast Brazil: a review of 16,208 births between 2012 and 2015 [Submitted]. Bull World Health Organization E-pub: 4 Feb 2016. cdc.gov/zika cdc.gov/zika/pdfs/denvchikvzikv-testing-
algorithm.pdf cdc.gov/mmwr
References
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