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Prenatal Care

Diagnosing Microcephaly

Microcephaly is defined as a head circumference measurement that is smaller than a certain value for fetuses or infants of the same age and sex. This measurement value for microcephaly is usually less than 2 standard deviations (SDs) below the average. The measurement value also may be designated as less than the 3rd percentile.

Microcephaly may be diagnosed during pregnancy with ultrasound. Microcephaly is most easily diagnosed by ultrasound late in the second trimester or early in the third trimester of pregnancy. Although microcephaly and intracranial calcifications are typically detected during ultrasounds in the late second and early third trimester of pregnancy, these findings might be detected as early as 18-20 weeks gestation. However, detection by prenatal ultrasound can be challenging at this gestational age due to fetal position and fetal motion artifact. The optimal time to perform ultrasound screening for fetal microcephaly is not known. In the absence of microcephaly, the presence of intracranial calcifications before 22 weeks gestation might suggest a risk for the future development of microcephaly. In addition, fetal abnormalities, including microcephaly, may not be apparent on the fetal ultrasound, but may be apparent at delivery or develop postnatally.

Clinical Management of Pregnant Women with Possible Zika Virus Infection

Interpretation of laboratory results* Prenatal management
  • Recent Zika virus infection
  • Recent flavivirus infection; specific virus cannot be identified
Consider serial ultrasounds every 3–4 weeks to assess fetal anatomy and growth. Decisions regarding amniocentesis should be individualized for each clinical circumstance.§
  • Presumptive recent Zika virus infection**
  • Presumptive recent flavivirus infection**
Consider serial ultrasounds every 3–4 weeks to assess fetal anatomy and growth. Amniocentesis might be considered; decisions should be individualized for each clinical circumstance.
  • Recent dengue virus infection
Clinical management in accordance with existing guidelines.††
  • No evidence of Zika virus or dengue virus infection
Prenatal ultrasound to evaluate for fetal abnormalities consistent with congenital Zika virus syndrome.

Fetal abnormalities present: repeat Zika virus RNA NAT and IgM test; base clinical management on corresponding laboratory results.

Fetal abnormalities absent: base obstetric care on the ongoing risk for Zika virus exposure risk to the pregnant woman.

Abbreviations: CSF = cerebrospinal fluid; IgM = immunoglobulin M; IHC = immunohistochemical; PRNT = plaque reduction neutralization test; RNA NAT = RNA nucleic acid testing

Footnotes

* Refer to the previously published guidance for testing interpretation.

Fetal abnormalities consistent with congenital Zika virus syndrome include microcephaly, intracranial calcifications, and brain and eye abnormalities.

§ Healthcare providers should discuss risks and benefits of amniocentesis with their patients. It is not known how sensitive or specific rRT-PCR testing of amniotic fluid is for congenital Zika virus infection, whether a positive result is predictive of a subsequent fetal abnormality, and if it is predictive, what proportion of infants born after infection will have abnormalities.

** rRT-PCR or PRNT should be performed for positive or equivocal IgM results as indicated. PRNT results that indicate recent flavivirus infection should be interpreted in the context of the currently circulating flaviviruses. Refer to the laboratory guidance for updated testing recommendations. Because of the overlap of symptoms and areas where other viral illnesses are endemic, evaluate for possible dengue or chikungunya virus infection.

†† http://apps.who.int/iris/bitstream/10665/44188/1/9789241547871_eng.pdf [PDF - 1.5 MB].

Fetal Ultrasound

Fetal ultrasound is generally performed in pregnancies between 18-20 weeks of gestation to assess fetal anatomy as part of routine obstetrical care. Although microcephaly and intracranial calcifications are typically detected during ultrasounds in the late second and early third trimester of pregnancy, these birth defects might be detected as early as 18-20 weeks gestation. Zika can cause microcephaly and other severe brain defects, and Zika virus infection during pregnancy has been linked to other adverse pregnancy and birth outcomes, including fetal loss and eye abnormalities. Hence, additional ultrasounds might provide an opportunity to identify birth defects consistent with congenital Zika virus infection and assist in determining clinical management.

Safety

Ultrasound is performed during pregnancy when medical information is needed. It has been used during pregnancy for many years and has not been associated with adverse maternal, fetal, or neonatal outcomes. Ultrasound operators are trained to use the lowest power for the minimum duration of time to obtain the needed information. There is consensus among various national and international medical organizations (American College of Radiology, American College of Obstetricians and Gynecologists, and the Society of Maternal and Fetal Medicine) that ultrasound is safe for the fetus when used appropriately.

Accuracy

The accuracy of ultrasound to detect microcephaly in the setting of maternal Zika virus is not known and will depend on many factors such as the timing of maternal infection relative to the timing of screening, severity of microcephaly, patient factors (e.g., obesity), gestational age, equipment used, and the expertise of the person performing the ultrasound. Because the absence of congenital microcephaly and intracranial calcifications on ultrasound at one point in pregnancy does not exclude future microcephaly, additional ultrasounds may be considered at the discretion of the healthcare provider. CDC will update guidance for women and their healthcare providers as more information related to Zika virus infection and microcephaly becomes available.

Sensitivity

The sensitivity of prenatal ultrasound for detection of microcephaly depends on a range of factors (e.g., timing of screening, severity of microcephaly, patient factors). In a study of congenital microcephaly not caused by Zika virus infection, prenatally diagnosed microcephaly correlated with neonatal microcephaly approximately 57% of the time.

Fetal MRI

Fetal MRI is not a screening tool and should be used only to answer specific questions raised by ultrasound or used in occasional specific high-risk situations. Interpretation of fetal MRI requires specialized expertise and has limited availability in the United States.

Amniocentesis

Amniocentesis is a medical procedure in which a small amount of amniotic fluid is removed from the sac surrounding the fetus for testing. Consideration of amniocentesis should be individualized based on the patient’s clinical circumstance. Amniocentesis has been used in the evaluation of other congenital infections and may be considered in the evaluation of potential Zika virus infection. Healthcare providers should discuss the risks and benefits of amniocentesis with their patients.

Amniocentesis is not recommended until after 15 weeks of gestation. Amniocentesis performed at ≥15 weeks of gestation is associated with lower rates of complications than when performed at earlier gestational ages (≤14 weeks of gestation). However, the optimal time to perform amniocentesis to diagnose congenital Zika virus infection is not known and should be individualized according to the patient’s clinical circumstances. Referral to a maternal-fetal medicine specialist may be warranted. Healthcare providers should discuss the risks and benefits of amniocentesis with their patients.

A positive Zika virus RNA NAT result from amniotic fluid might indicate fetal infection. This information would be useful for pregnant women and their healthcare providers to assist in determining clinical management (e.g., antepartum testing, scheduling serial ultrasounds, delivery planning). Although a negative Zika virus RNA NAT result from amniotic fluid does not exclude congenital Zika virus infection, it may prompt a work-up for other causes of microcephaly (e.g., other infections, genetic disorders).

We do not know:

  • The optimal time to perform amniocentesis to diagnose congenital Zika virus infection.
  • How sensitive or specific tests of amniotic fluid are for congenital Zika virus infection.
  • If a positive result is predictive of a subsequent fetal abnormality.
  • If a positive result is predictive, what proportion of infants born after infection will have abnormalities.
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