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