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CDC Guidance on Zika and Pregnancy


On July 24, 2017, the CDC released interim guidance on management of pregnant women with possible Zika exposure.  The CDC based this update on (1) declining prevalence of Zika virus disease in the WHO’s Region of the Americas (Americas) and (2) evidence of prolonged detection of Zika virus IgM antibodies beyond 12 weeks after infection, thus limiting an IgM test’s ability to distinguish whether an infection has occurred before or during the pregnancy.


The definition of ‘possible Zika virus exposure’ is unchanged and still includes

  • travel to, or residence in, an area with risk for mosquito-borne Zika virus transmission; or
  • sex with a partner who has traveled to or resides in an area with risk for mosquito-borne Zika virus transmission

Ask all pregnant women in the US and US territories about possible Zika virus exposure before pregnancy and again at every prenatal visit

  • Pregnant women should be advised not travel to any area with risk for Zika virus transmission
  • Pregnant women with a sex partner who has traveled to or lives in an area with risk for Zika virus transmission should be advised on the use condoms or abstain from sex for the duration of the pregnancy

Testing pregnant women with recent possible Zika virus exposure and symptoms

  • Symptoms include acute onset of fever, maculopapular rash, arthralgia, or conjunctivitis
  • Recent exposure is defined as a possible exposure or infection during the current pregnancy or 8 weeks before conception or 6 weeks before the last menstrual period
  • Updated recommendations include concurrent Zika virus NAT and serologic testing as soon as possible through 12 weeks after symptom onset

Testing pregnant women who are asymptomatic with ongoing possible Zika virus exposure

  • Ongoing possible Zika virus exposure includes those who reside in or travel frequently (e.g., daily or weekly) to an area with risk for Zika virus transmission
  •  Offer Zika virus NAT testing three times during pregnancy
    • NAT testing should be offered at the initiation of prenatal care, and if Zika virus RNA is not detected on clinical specimens, two additional tests should be offered during the course of the pregnancy coinciding with prenatal visits
  • IgM testing is no longer routinely recommended because IgM can persist for months after infection
  • The optimal timing and frequency of testing of asymptomatic pregnant women with NAT alone is unknown

Additional Zika testing is not recommended following laboratory–confirmed Zika virus infection diagnosis that has been made before or during the current pregnancy

  • Diagnosis is laboratory-confirmed by one of the following:
    • NAT, or
    • Serology: positive/equivocal Zika virus or dengue virus IgM and Zika virus plaque reduction neutralization test (PRNT) ≥10 and dengue virus PRNT <10 results

Testing pregnant women who are asymptomatic who have recent possible Zika exposure (travel or sexual exposure) but without ongoing possible Zika virus exposure

  • Routine Zika virus testing is not recommended
  • Testing should be considered using a shared patient-provider decision-making model based on patient preferences and values, clinical judgment, a balanced assessment of risks and expected outcomes, and the jurisdiction’s recommendations
  • With the decline in the prevalence of Zika virus disease, the updated recommendations for the evaluation and testing of pregnant women with recent possible Zika virus exposure but without ongoing possible exposure are now the same for all areas with any risk for Zika virus transmission

Testing pregnant women who have recent possible Zika virus exposure and who have a fetus with prenatal ultrasound findings consistent with congenital Zika virus syndrome 

  • Test for Zika virus to determine the etiology of the birth defects
  • Testing of the mother should include both NAT and IgM tests
  • Possible Zika virus–associated birth defects that meet the CDC surveillance case definition include the following:
    • Brain abnormalities and/or microcephaly
    • Intracranial calcifications
    • Ventriculomegaly
    • Neural tube defects and other early brain malformations
    • Eye abnormalities
    • Other consequences of central nervous system dysfunction including arthrogryposis (joint contractures), congenital hip dysplasia, and congenital deafness
  • Individualize the use of amniocentesis
    • Limited data on usefulness
    • NAT testing should be performed on amniocentesis specimens
    • Zika virus RNA in the amniotic fluid might indicate fetal infection but a negative result does not exclude congenital Zika virus infection
    • Optimal time to perform amniocentesis to diagnose congenital Zika virus infection is unknown

Updated Interim Guidance for Prenatal Management of Pregnant Women with Laboratory Evidence of Possible Zika Virus Infection

  • Serial fetal ultrasounds every 3 to 4 weeks with focus on neuroanatomy and growth
  • Recent data suggests a period of at least 15 weeks between infection and microcephaly detection on prenatal ultrasound and MRI
  • Based on 17 cases with confirmed prenatal maternal Zika virus
    • Median time between Zika virus symptoms and microcephaly was 18 weeks (range 15–24 weeks)
    • Earliest sign of congenital Zika syndrome was clubfoot
    • MRI findings: microcephaly, ventriculomegaly, polymicrogyria, and calcifications

The comprehensive approach to testing placental and fetal tissues has been updated

  • Testing placental and fetal tissue specimens can be performed for diagnostic purposes in certain scenarios
  • Example of a possible scenario: A fetus or infant with possible Zika virus-associated birth defects but maternal definitive diagnosis is not available
  • In all cases, infants or fetuses with possible Zika virus–associated birth defects should also be evaluated for other etiologies of congenital anomalies
  • Testing of placental tissues for Zika virus infection is not routinely recommended for asymptomatic pregnant women who have recent possible Zika virus exposure but without ongoing possible exposure and who have a live born infant without evidence of possible Zika virus–associated birth defects

Zika virus IgM testing as part of preconception counseling to establish baseline IgM results for nonpregnant women with ongoing possible Zika virus exposure is not warranted

  • Zika virus IgM testing is no longer routinely recommended for asymptomatic pregnant women with ongoing possible Zika virus exposure

Learn More – Primary Sources:

Update: Interim Guidance for Health Care Providers Caring for Pregnant Women with Possible Zika Virus Exposure — United States (Including U.S. Territories), July 2017 

CDC: Zika Virus For Healthcare Providers

CDC: Areas with Risk of  Zika

Serial Head and Brain Imaging of 17 Fetuses With Confirmed Zika Virus Infection in Colombia, South America

US Zika Pregnancy Registry Collaboration: Birth Defects Among Fetuses and Infants of US Women With Evidence of Possible Zika Virus Infection During Pregnancy

ACOG Zika Tool Kit 

ACOG Committee Opinion 784: Management of Patients in the Context of Zika Virus

Marfan Syndrome: a Reportable ACMG Secondary Finding


  • Marfan syndrome is a genetic, multi-systemic disorder that affects connective tissue. It occurs in 1 out of every 5,000-10,000 individuals and is caused by pathogenic variants in the Fibrillin 1 (FBN1) gene. Penetrance is high, and most individuals with a mutation will have some finding related to the disorder.
  • Marfan syndrome is considered a classic example of variable expressivity, as some individuals may have mild symptoms and signs, such as skeletal changes, while others may have life-threatening effects if left unchecked, such as risk for aortic rupture.
  • There are rigorous clinical criteria required for diagnosis of Marfan syndrome. In addition, there is clinical and genetic overlap with other related disorders.
    • Referral to a medical genetic service is required to determine if an individual is suspected of having Marfan syndrome, Loews-Dietz syndrome or Familial Thoracic Aortic Aneurysms and Dissections
    • Multiple speciality services may be involved in management; however, referral to cardiology is critical 

NOTE: Because medical interventions can prevent severe morbidity and mortality, Marfan syndrome and related disorders are on the ACMG list of secondary findings. In summary, the ACMG document on reporting such findings makes the following recommendations:

  • In the course of genetic testing for research or clinical care, the laboratory may identify variants in genes unrelated to the initial indication for testing, but nevertheless may have important health implications
  • Results of such secondary findings should be communicated to the individuals who may benefit from this knowledge
  • An individual can ‘opt out’ of receiving secondary findings


  • Findings may appear in childhood or adulthood
  • While height is the clinical characteristic most noted in Marfan syndrome, it is important to take in to account familial background – is the individual taller than expected for his/her family?
  • Phenotype-Genotype correlation is poor
  • Genetic consultation and multi-disciplinary team management is essential to maximize outcomes and prevent untoward events such that life expectancy can equal that of unaffected populations
    • Treatment and prevention of serious manifestations such as dissecting aortic aneurysm may include medication, such as beta-blockers and/or surgeries
    • Patients may be cautioned to avoid: contact sports, cardiovascular stimulants, LASIK correction and activities that cause joint injury or pain
    • Pneumothorax prevention may include avoiding breathing against resistance (such as horn instruments)
    • Consider Marfan syndrome or any related disorders a high risk pregnancy due to risk of aortic dissection – arrange for high risk referral preconception if possible


It is important to keep in mind, given the variable expressivity of Marfan syndrome, this list includes most possible findings, but any single affected individual will likely manifest only some of the following:

  • Eye:
    • Myopia
    • Ectopia lentis (lens displacement)
    • Risk for retinal detachment, glaucoma and cataracts
  • Skeletal:
    • Excessive growth with dolichostenomelia of long bones
    • Overgrowth of ribs causing pectus excavatum or pectus carinatum
    • Joint laxity and arachnodactyly (long, slender digits) which leads to classic finding of the positive ‘wrist sign’ and ‘thumb sign’
  • Facial and dental features:
    • Long narrow face, with deep set eyes, flat cheekbones and receding chin
    • High arched palate with overcrowding of teeth
  • Cardiovascular: connective tissue in the aorta can be affected leading to risk of aortic dilatation/dissection/rupture, aortic valve regurgitation, left heart failure
    • Children with severe Marfan syndrome may be affected with mitral valve prolapse and heart failure and managed surgically
  • Other systems:
    • Dural ectasia can result in back and leg pain, causing weakness and numbness
    • Pneumothorax from lung bullae


  • Loeys-Dietz syndrome: This syndrome is also characterized by skeletal characteristics commonly associated with Marfan syndrome, such as pectus excavatum or pectus carinatum, scoliosis, joint laxity, arachnodactyly and club foot (talipes equinovarus). Facial features can be prominent in severe cases, including craniosynostosis and wide spaced eyes, as well as cleft palate. However, the major distinguishing findings are related to vascular abnormalities leading to aneurysms and possible dissection beyond the aortic root – such as the cerebral, thoracic and abdominal arteries, and in some cases arterial tortuosity
    • Findings may appear in childhood or adulthood
    • Mutations that can lead to severe disease are found in TGFBR1, TGFBR2, and SMAD3 genes
    • Due to emphasis on cardiovascular manifestations, individuals are cautioned against contact sports or drugs that stimulate cardiovascular output
  • Familial Thoracic Aortic Aneurysms and Dissections (TAAD): Similar to Marfan syndrome and Loews-Dietz syndrome, there is increased risk of aortic aneurysm, dissection and rupture. In the case of TAAD, it is the thoracic aorta (usually ascending) that is most prominently affected. However, the abdominal aorta and brain vasculature may demonstrate abnormal dilatation. Skeletal anomalies can overlap with Marfan syndrome, including tall stature, joint laxity, and pectus excavatum and pectus carinatum. Other findings may include livedo reticularis (purplish skin discoloration due to constriction of dermal capillaries particularly in mutations in ACTA2). There is also increased risk of coronary artery disease and stroke.
    • Findings may appear in childhood or adulthood
    • Mutations that can lead to severe disease are found in ACTA2, TGFBR1, TGFBR2, MYH11, FBN1 and SMAD3


What gene/protein is affected and what does it do?

  • FBN1: mutations in FBN1 gene cause Marfan syndrome
  • Fibrillin: protein is a key component of extracellular microfibrils and can be found in both elastic and non-elastic tissues in multiple organ systems


  • Marfan syndrome is an autosomal dominant disorder
  • 75% of individuals will inherit a mutation from one of his/her parents; in the other 25%, there is a de novo mutation

Risks to family members and future offspring:

  • If a parent of an affected individual carries the pathogenic variant, the brothers and sisters of that individual have a 50% chance of having the variant
  • In the case of a de novo mutation, there is still a low risk to brothers and sisters because of the possibility that a parent may have germline mosaicism
  • Offspring have a 50% chance of inheriting the variant and therefore having Marfan syndrome
    • Preimplantation genetics and prenatal testing is available

Learn More – Primary Sources:

ACMG Recommendations for Reporting Incidental Findings in Clinical Exome and Genome Sequencing

Marfan Syndrome: Gene Reviews

Loeys-Dietz Syndrome: Gene Reviews

Thoracic Aortic Aneurysms and Aortic Dissections

Marfan Foundation: For Healthcare Providers

Marfan Scoring System Calulator







Locate a genetic counselor or genetics services:

Genetic Services Locator-ACMG

Genetic Services Locator-NSGC

Genetic Services Locator-CAGC

Trisomy 18 – Key Findings, Prenatal Screening and Prognosis


  • Trisomy 18 (47,XX,+18 or 47,XY,+18) is also referred to as Edwards syndrome
  • Second most common trisomy after Down syndrome
    • Present in approximately 1/5000 live births
    • Prevalence during pregnancy is considerably higher: 1/2500-1/2600 due to the high frequency of fetal loss and pregnancy termination after prenatal diagnosis
    • Approximately 72% of trisomy 18 pregnancies result in loss between 12 weeks to term
    • 50% survive longer than one week
    • 5% to 10% of infants will survive past the first year
    • There are individuals who have survived into adulthood but require significant care
      • Intellectual disability is profound and overall, the developmental age in older children is 6-8 months
  • May affect almost every organ system but the following findings are particularly common and may be identified on prenatal ultrasound. Most affected fetuses have multiple findings:
    • Prenatal/postnatal growth deficiency
    • Cleft lip and palate
    • Congenital heart defects (80-100%), most commonly one of the following:
      • Ventricular septal defect (VSD)
      • Atrial septal defect (ASD)
      • Patent ductus arteriosis (PDA)
      • Polyvalvular disease
    • Major limb malformations (5-10%): radial ray anomalies and other preaxial limb defects
    • Abnormal limb posture: clenched fists, clubbing, rocker bottom feet
    • Horseshoe kidney
    • CNS structural defects:
      • Cerebellar hypoplasia
      • Agenesis of the corpus callosum
      • Hydrocephalus with or without an open neural tube defect
  • Other findings may not be apparent until postnatal life, such as feeding difficulties


Trisomy 18 (Edwards syndrome) is a condition caused by an extra chromosome 18 that is present at the time of conception.  Most cases (90%) are the result of nondisjunction during meiosis, which is typically a sporadic occurrence.  In some affected individuals a chromosomal imbalance is the cause, inherited from a parent who has a balanced karyotype (i.e. Robertsonian translocation). There is also a small portion of affected individuals that have partial Trisomy 18 which may be the result of a parental translocation. A small proportion of affected individuals are diagnosed with mosaic Trisomy 18.


  • Risk increases with maternal age
  • ACOG requires all women be offered prenatal screening (biochemical/ cfDNA) or invasive testing (amniocentesis / CVS)
    • Screening tests used to detect fetal Down syndrome also include risk assessment for Trisomy 18
    • Offer confirmatory testing following a positive screening test for Trisomy 18 due to the potential for false positive results
      • Strongly consider a false positive screening test if the prenatal ultrasound is normal as most affected fetuses will have multiple anomalies
  • If there is a family history or previous Trisomy 18 pregnancy, refer for genetic counseling

Note: ACMG provides healthcare professionals with open access ‘ACT Sheets’ to guide next steps following a positive NIPS report for trisomy 18 (see ‘Learn More – Primary Sources’ below)

Learn More – Primary Sources:

ACOG Practice Bulletin No. 226: Screening for Fetal Chromosomal Abnormalities

ACMG: Noninvasive Prenatal Screening via Cell-Free DNA [Trisomy 18: Positive Cell Free DNA Screen]

GHR: Trisomy 18

The Trisomy 18 Syndrome

NIH-GARD: Trisomy 18 

Locate a genetic counselor or genetics services:

Genetic Services Locator-ACMG

Genetic Services Locator-NSGC

Genetic Services Locator-CAGC

Locate a Maternal Fetal Medicine Specialist

Maternal Fetal Medicine Specialist Locator-SMFM

Practical obstetrics info for your women's healthcare practice

Prenatal Detection of Clubfoot – Key Points

Clubfoot, congenital talipes equinovarus, is one of the most common orthopedic conditions diagnosed on prenatal ultrasound with an incidence of 1-3 per 1000 at birth.


  • In a fetus with clubfoot, the long axis of the foot (the sole) and the tibia can be seen in the same plane on ultrasound
    • False positive rate of clubfoot diagnosed by ultrasound may be as high as 10-19%
  • 90% of clubfoot diagnoses are made in the first and second trimester
    • Detectable on ultrasound as early as 9 weeks gestation
  • Male predominance (M:F, 2:1)

Club Foot

Anatomy & Physiology, Connexions Web Site, Jun 19, 2013


Underlying Causes


  • Mendelian: Part of a genetic syndrome, especially a neuromuscular condition, such as arthrogryposis or congenital myotonic dystrophy
    • May be inherited as an autosomal dominant condition
    • Can occur in isolation
  • Chromosomal abnormality such as trisomy 18
  • Multifactorial birth defects such as neural tube defects that negatively impact fetal movement

Factors External to the Fetus

  • Environmental factors that restrict fetal movement such as
    • oligohydramnios
    • twinning
    • amniotic band syndrome

Bilateral vs. Unilateral

  • Bilateral vs. unilateral  diagnosed prenatally in an approximately 1:1 ratio
  • Bilateral more likely to be confirmed at birth compared to unilateral (87.9% vs. 65.9%)
  • Bilateral is not more likely than unilateral to be associated with additional anomalies at birth
    • Overall in singletons, 11% with isolated club foot on prenatal ultrasound had additional findings at birth

Risk of Aneuploidy:

  • Risk of aneuploidy is increased in complex club foot (additional anomalies present)
    • Complex:  approximately 30%
    • Isolated:  Between 1.7% – 3.6% (literature suggests may be associated with sex chromosome aneuploidy)
  • ACOG guidance recommends offering
    • prenatal aneuploidy screening or diagnostic testing (amniocentesis or CVS) for all pregnant women regardless of age
    • Invasive testing using microarray in the setting of fetal structural anomalies seen on prenatal ultrasound
  • If suspected or diagnosed, refer for genetic counseling, MFM and pediatric orthopedic consultation for further discussion to determine possible etiologies, clubfoot correction, surgical and nonsurgical options

Learn More – Primary Sources:

Diagnostic accuracy, work-up and outcomes of pregnancies with clubfoot detected by prenatal sonography

Outcome of prenatally diagnosed isolated clubfoot

ACOG Practice Bulletin No. 162: Prenatal Diagnostic Testing for Genetic Disorders

ACOG Practice Bulletin 226: Screening for Fetal Chromosomal Abnormalities

ACOG Committee Opinion No. 682: Microarrays and Next-Generation Sequencing Technology: The Use of Advanced Genetic Diagnostic Tools in Obstetrics and Gynecology

Locate a Genetic Counselor or Genetics services:

Genetic Services Locator-ACMG

Genetic Services Locator-NSGC

Genetic Services Locator-CAGC

Locate a Maternal Fetal Medicine Specialist

Maternal Fetal Medicine Specialist Locator-SMFM