Tag Archives: #pregnancyultrasound

Reproductive Medicine – First Trimester Aneuploidy Screening – Part 1

© 2018, GENASSIST, Inc.     

By Keith S. Wexler, MBA, CFO, Business Development Director, GENASSIST, Inc.

Paul Wexler, M.D., F.A.C.O.G., Medical Director, GENASSIST, Inc.

Clinical Professor, Department of OB/GYN, University of Colorado Health Sciences Center

Clinical Professor, Division of Genetics/Dept. of Pediatrics, Univ. of Colorado/The Children’s Hospital

OVERVIEW: We have known for years that children with chromosomal abnormalities and some structural abnormalities may demonstrate subtle differences on clinical examination. Likewise, the mother’s age at conception, and the mode of conception [i.e. Invitro Fertilization (IVF) and the use of frozen eggs] can affect the calculated risk for a child with a chromosomal abnormality.

Just as the ethnic background can affect the likelihood of specific disorders (i.e. Cystic Fibrosis, Sickle Cell Anemia, Tay Sachs, Thalassemia etc) these differences can affect the ultrasound findings (e.g. biochemical blood results and fetal nasal bone).

Even with Maternal Fetal DNA testing, “ultrasound markers” will continue to be useful for early fetuses at “risk” in addition to screening for aneuploidy:

  • Crown Rump Length (CRL): Small differences in the CRL can affect risk and should be measured with a fetus in a neutral position.
  • Ductus Venosus: This measurement is also difficult to get at 11-14 weeks gestation. The ductus venosus connects the fetal umbilical cord to the inferior vena cava at the level of the diaphragm. The “a” wave is reversed in 3% of chromosomally normal fetuses and approximately 65% of fetuses with Trisomy 21. It is also associated with cardiac defects.
  • Fetal Heart Rate (FHR): Fetal heart rate is slightly increased in fetuses with Trisomy 21 (Down Syndrome). It may be much higher in fetuses with Trisomy 13 (75% of fetuses with Trisomy 13 have a FHR >175 beats per minutes). Not all labs use FHR in their calculations. Labs that use FHR in their calculations will increase the risk for Trisomy 13 even if the FHR increase is only due to increased fetal movement.
  • Fronto Maxillary Facial Angle: 50% of fetuses with Trisomy 21 have an increased angle which is measured from a line drawn from the upper surface of the palate and interior aspect of the maxilla to the external surface of the frontal bones of the forehead in a midsagital view of the face.
  • Nasal Bone: The fetal nasal bone is visualized at 11-13 weeks in 98% of chromosomally normal fetuses and 35% of Trisomy 21 fetuses. Rescan in one week will usually identify a nasal bone in a chromosomally normal fetus. Visualization of a nasal bone in a fetus in a “face down” position may difficult or impossible.
  • Nuchal Translucency (NT): The NT is increased in 95% of Trisomy 21 fetuses, 70% of Trisomy 18 fetuses, 85% of Trisomy 13 fetuses and 5% of chromosomally normal fetuses. Chromosomally normal fetuses with an increased NT (>3.5 mm) have a higher risk for cardiac defects, musculo-skeletal abnormalities, infections, rare genetic syndromes and fetal death. If an increased NT resolves by 20 weeks gestation, the prognosis is good.

A fetal echocardiogram at 22-24 weeks gestation should be considered in chromosomally normal fetuses with increased NT and all fetuses with chromosomal abnormalities.

Tricuspid Regurgitation: Tricuspid regurgitation may be difficult to measure and is seen in approximately 1% of chromosomally normal fetuses and 55% of fetuses with Trisomy 21. It is also seen in fetuses with cardiac defects. As with fetuses with increased NT, a fetal echocardiogram at 22-24 weeks gestation should be considered.

ANALYSIS:

1st Trimester Aneuploidy Screening & “Ultrasound Markers” are still an important Non Invasive Prenatal Testing [NIPT] tool for the healthcare provider. 1st Trimester screening should continue to be used to help evaluate the “low risk” patient who is not a candidate for Maternal Fetal DNA testing and the “high risk” patient who declines having invasive testing, i.e. CVS or amniocentesis, even when indicated.  

Maternal Fetal DNA testing usually will not identify structural problems unrelated to a chromosomal abnormality. 

Reproductive Medicine – Paternal Age & Maternal Age

© 2018, GENASSIST, Inc.     

By Keith S. Wexler, MBA, CFO, Business Development Director

Paul Wexler, M.D., F.A.C.O.G., Medical Director, GENASSIST, Inc.

Clinical Professor, Department of OB/GYN, University of Colorado Health Sciences Center

Clinical Professor, Division of Genetics/Dept. of Pediatrics, Univ. of Colorado/The Children’s Hospital 

PATERNAL AGE:

If Paternal Age is Greater than 40 years: Several studies in the 1980’s and the early 1990’s suggested a slight increased risk for children with a new disease for the family due to a change in a gene inherited from an older father. Also, the possibility of a slightly higher incidence of Down syndrome was raised. When the age of the mother is taken into account, there appears to be little, if any, increased risk (less than 1%) for Down syndrome due to paternal age.

It is not possible to test for all conditions due to a mutation in a gene due to advanced paternal age. Couples who are concerned are encouraged to have a Level II ultrasound between 15 and 22 weeks gestation. Amniocentesis for advanced paternal age is not medically recommended but may be justifiable in some families.

*A recent study, that is ongoing, has suggested a possible relationship between increasing maternal age and/or paternal age (greater than 40 years) and autism in a child. Reference: Israel & Mt. Sinai, NY. *Some recent studies have suggested risk may be as high as 1:50 to 1:80.

MATERNAL AGE:

Since approximately 1972 when amniocentesis first became available for prenatal diagnosis for genetic testing, the basis for recommending the procedure was based upon the theory that since a woman is born with all the eggs she will have in her lifetime she will have a greater chance of having a child with a chromosome abnormality as she ages.

Most women are choosing Non Invasive Prenatal Screening (1st Trimester Screening) and/or Maternal Fetal DNA screening before deciding upon amniocentesis.

(Table 1) illustrates the percentage of babies born with a chromosome abnormality for every 100 pregnancies in that group. The 35 year old has an asterisk (*) because this was selected by the American College of OB/GYN as the age at which patients need to be offered prenatal diagnosis by Chorionic Villus Sampling (CVS) or amniocentesis because the patient has a greater risk of having an abnormality than miscarrying from the procedure (1 in 270 procedures).

In 2007, the American College of OB/GYN allowed all women of all ages to have the option of amniocentesis regardless of age since the miscarriage risk in four published studies was found to be as low as 6 per 10,000 procedures (0.06%) which is less than a maternal age related risk alone.

*In the article “Procedure-related risk of miscarriage following amniocentesis and chorionic villus sampling: a systematic review and meta-analysis” in Ultrasound Obstet Gynecol. 2015 Jan;45(1):16-26 by Akolekar R et al, the procedure related risk following amniocentesis was 0.04% to 0.26% and following CVS was 0.22%.

(TABLE 1)

Maternal Age Less Than 20 Years Old                             0.05% to 0.08% risk

Maternal Age 20 to 24 Years Old                                      0.08% to 0.10% risk

Maternal Age 25 to 29 Years Old                                      0.08% to 0.15% risk

Maternal Age 30 to 34 Years Old                                      0.12% to 0.20% risk

*Maternal Age 35 to 39 Years Old                                    0.30% to 0.80% risk

Maternal Age 40 to 42 Years Old                                      0.90% to 1.50% risk

Maternal Age 43 to 45 Years Old                                      1.50% to 3.00% risk

Maternal Age 46 to 49 Years Old                                      2.00% to 10.00% risk

Maternal Age Greater Than 50 Years Old                       Greater than 10.00% risk

Ultrasound Markers – Choroid Plexus Cyst(s)

© 2017, GENASSIST, Inc.     

By Keith S. Wexler, MBA, Maternal Fetal Medicine, Prenatal Diagnosis and Biotech/Life Sciences Consultant, GENASSIST, Inc.

Paul Wexler, M.D., F.A.C.O.G., Medical Director, GENASSIST, Inc.

Clinical Professor, Department of OB/GYN, University of Colorado Health Sciences Center

Clinical Professor, Division of Genetics/Dept. of Pediatrics, Univ. of Colorado/The Children’s Hospital

Choroid Plexus Cyst(s): A cyst or cysts found in the middle of the fetal brain which are small fluid filled spaces in the ventricles within the spongy layer of cells and vessels.

One or more of these cysts may be found on ultrasound in 1% to 2% of normal fetuses and 30% to 50% of fetuses with three #18 chromosomes (Trisomy 18 or Edward Syndrome).

Choroid Plexus Cyst(s) which can solitary or one of multiple ultrasound markers and can vary in size from 1 few millimeters to 25 millimeters or greater, is felt to be a strong ultrasound marker for Trisomy 18 and a possible indication for Maternal Fetal DNA, Chorionic Villus Sampling (CVS) or amniocentesis.

Choroid Plexus Cyst(s), like many isolated ultrasound findings should encourage the healthcare provider to perform a careful ultrasound evaluation to attempt to find other ultrasound markers suggestive of aneuploidy (an abnormal number of chromosomes).

Rarely, fetuses with Trisomy 21 (Down Syndrome) will also demonstrate a Choroid Plexus Cyst(s) but the relationship between Trisomy 21 and Choroid Plexus Cyst(s) is weak.

Ultrasound detection of a fetus with an increased likelihood of a trisomy is best for:

  • Trisomy 13 (Patau Syndrome) – 90%
  • Trisomy 18 (Edward Syndrome) – 80-90%
  • Trisomy 21 (Down Syndrome) – 50% to 70%

Maternal Fetal DNA studies are best for detection of:

  • Trisomy 21 (Down Syndrome) – Greater than 99%
  • Trisomy 18 (Edward Syndrome) – 97% to 98%
  • Trisomy 13 (Patau Syndrome) – 91% to 93%

*Chorionic Villus Sampling (CVS) and amniocentesis remain the best method for confirmation of an ultrasound marker for

Trisomy 13, Trisomy 18 or Trisomy 21. Chorionic Villus Sampling (CVS) is more likely to diagnose placental mosaicism and has a slightly greater miscarriage risk than amniocentesis, since the amniocentesis procedure is performed later in pregnancy.

Fetuses with Trisomy 18 often have several ultrasound markers in addition to the Choroid Plexus Cyst(s). However, we have followed two fetuses with Trisomy 18, confirmed by amniocentesis, that did not demonstrated any obvious ultrasound markers until after 18 weeks gestation and 21 weeks gestation respectively.

Ultrasound evaluation may identify additional Trisomy 18 markers including abnormal position of fingers, choroid plexus cyst(s), abnormal shaped head, 2 vessel cord, heart defects, intrauterine growth restriction (IUGR), omphalocele, neural tube defects and cystic hygroma.

As with all technology, a choroid plexus cyst(s) identified by ultrasound is not a confirmation that the baby has Trisomy 18.

Recommendation: **The patient needs to be aware of the guidelines from the American College of OB/GYN published in the OB/GYN Journal, Jan. 2007 recommends that “ideally, all women should be offered aneuploidy screening before 20 weeks gestation” and “all women regardless of age should have the option of invasive testing”.

Ultrasound – Fetal Echocardiogram

Ultrasound - Fetal Echo

© 2016            

By Keith S. Wexler, MBA, Maternal Fetal Medicine, Prenatal Diagnosis and Biotech Consultant, GENASSIST, Inc.

Paul Wexler, M.D., F.A.C.O.G., Medical Director, GENASSIST, Inc.

Clinical Professor, Department of OB/GYN, University of Colorado Health Sciences Center

Clinical Professor, Division of Genetics/Dept. of Pediatrics, Univ. of Colorado/The Children’s Hospital

Fetal Echocardiogram using pulsed Doppler and M Mode (timing of atrial and ventricular activity) will identify most but not all fetuses with clinically significant Congenital Heart Disease.

The incidence of Congenital Heart Disease in different studies varies depending on the inclusion or exclusion of mild or trivial lesions (between 0.4% to 7.5%).

Approximately 1-3% of fetuses will demonstrate cardiac arrhythmias. These arrhythmias can be either:

  • Bradycardia – heart rate less than 100 beats per minute (bpm)
  • Tachycardia – heart rate greater than 180 beats per minute (bpm)
  • Simply Irregular heart rate or pattern

Variation in the rate and rhythm is common and will vary with fetal activity and fetal respiration.

Most fetal cardiac arrhythmias are benign. However, persistent, severe fetal cardiac rate abnormalities can be associated with pulmonary effusions (fluid around the lungs) or pericardial effusions (fluid around heart), ascites (fluid in abdomen) or fetal edema (generalized fetal swelling).

Isolated Ventricular Septal Defects (VSD’s) are the most common type of Congenital Heart Disease. Not all of these defects will result in a newborn with clinical heart problems and many of the smaller ones usually involving the muscular part of the ventricular septum will close spontaneously by one year of age.

Patent Ductus Arteriosis after birth will mimic a small left to right atrial shunt which can also be seen in an Atrial Septal Defect (ASD).

A 4 chamber view of the fetal heart will help detect 30-60% of fetal congenital heart defects. Addition of visualization of a normal left ventricular outflow tract (LVOT= the aorta exiting from a normal left ventricle) and a normal right ventricular outflow tract (RVOT – the pulmonary artery arising from a normal right ventricle identified by a moderator band at the apex of the right ventricle) will help identify 80-85% of significant fetal congenital heart defects.

fetal-heat-rate-ultrasound-22w4d

Our protocol for Fetal Echocardiogram includes:

  • Identification of a 4 chamber heart with a heart filling approximately 1/3 of the chest with the cardiac apex pointing in a normal axis to the left with roughly equal sizes of the atria and ventricles.
  • Visualization of a normal cardiac rate and rhythm, a normal LVOT and RVOT, mitral, tricuspid, aortic and pulmonary valves, intact atrial and ventricular septae, patent foramen ovale which opens in the left atrium, arch of the aorta, ductus arteriosus and superior and inferior vena cava emptying into the right atrium.

 

At the time of the Fetal Echocardiogram a limited Level II ultrasound is performed:

  • Confirming a single or multiple gestation(s)
  • Location and integrity of the placenta
  • Cervical length
  • Fetal measurements
  • Comparison of menstrual and ultrasound gestational dates
  • Fetal presenting part
  • Amniotic Fluid Volume

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