A 35-year-old gravida 2, para 1, female came to clinic with her spouse and 2 year old daughter for a prenatal appointment. She was only 15 weeks into her pregnancy but had recently moved and wanted to establish care. She was scheduled for an amniocentesis next week and was very anxious because a first cousin’s son was recently diagnosed with a “genetic problem,” where he is expected to have mental retardation.
The mother has no other information about this infant, but that her cousin has been devastated by the news.
The family history revealed heart disease and stroke in relatives in their 70’s on the mother’s side. The father’s side of the family had lung cancer and diabetes. The two year old sibling was well and her medical records were being transferred.
The family had no other specific concerns and the rest of the interview revealed no specific concerns about the physical, mental or psycho-social health of the family.
The family was counseled to try to find out more information about the affected infant cousin – most importantly the name of the problem and how it was diagnosed. The family was also told that depending on the particular problem that other information may also be helpful such as obtaining medical records. Once this information was known, the family was told to discuss it with their obstetrician who could then make
appropriate arrangements to have them counseled prior to the amniocentesis and arrange for specific testing of the “genetic problem” if it is available. The pediatrician also offered to help review the medical information with the family and assist in the decision-making process if they wished.
Early prenatal care has been shown to improve the obstetrical and pediatric outcomes for families. As part of routine prenatal care, the mother has numerous tests performed to determine risk factors for screening of potentially harmful health problems.
Indications for referrals for prenatal diagnosis include:
Child or Family members with
- Multiple malformations in a child or a family history of such a problem
- Mental retardation or developmental delays or family history of such a problem
- Known or suspected metabolic disorder such as neonatal deaths, failure to thrive, organomegaly or loss of developmental milestones
- Birth defects such as cleft lip/palate, clubfoot, congenital heart disease, or neural tube defects
- Unusual looking child especially if he/she also has failure to thrive, developmental delays or mental retardation
- Known chromosomal abnormality
- Known hereditary disorders and/or where the family has questions about recurrence risks
- Family history of hearing loss, blindness, neurodegenerative disorders, short stature, premature heart disease, immune deficiency, abnormalities of the hair, skin, bones, or cancer
- Primary amenorrhea, aspermia, infertility or abnormal sexual development in the parents
- Recurrent pregnancy loss or stillbirth (usually two or more)
- Advanced parental age – mother > 35 years, father >55 years
- Related closely by blood
- Member of a specific ethnic group with an increased risk of a specific genetic disease
- Questions about prenatal diagnosis for any disorder
- Exposure to potential teratogens
- A hereditary disorder who is considering a pregnancy
- Abnormal prenatal testing such as multiple marker screening or fetal ultrasound
Testing can include chromosomal analysis (which tests the total numbers or large parts of chromosomes, examples include Down Syndrome and Trisomy 18), molecular genetic studies (which tests single gene changes or small parts of chromosomes, examples include Duchenne muscular dystrophy or Fragile X) or biochemical studies (tests for an over- or under-production of a specific biochemical, examples include Smith-Lemli-Opitz or Tay-Sachs Disease).
Prenatal diagnostic techniques include:
- Amniocentesis is usually performed at 15-18 weeks gestation by removing a small amount of amniotic fluid. Risks include fetal loss (0.5% overall), chorioamnionitis, fetal injury and maternal Rh sensitization.
- Chorionic villus sampling is usually performed at 10-12 weeks gestation by removing a small amount of the placenta transcervically. The risks include a higher rate of fetal loss than amniocentesis and limb reduction abnormalities.
- Fetal blood sampling is performed by inserting a spinal needle into the umbilical artery or vein. The risks include fetal loss of 1-2%.
- Preimplantation genetic diagnosis is performed on invitro fertilized eggs at an early stage of development. This is only performed in a limited number of centers.
- Ultrasound can be performed at any gestational age, but usually around 18-22 weeks of gestation for a wide variety of indications. The risks include over- or under-diagnosis of physical abnormalities.
- Magnetic resonance imaging can be performed in the second and third trimesters to follow-up abnormalities seen on ultrasound. This can be useful for central nervous system problems but is limited because of fetal movement.
- Fetal echocardiography is performed generally after 20 weeks gestation.
The pediatrician’s role in prenatal diagnosis may include:
- Counseling the family about risks and benefits
- Being familiar with local and regional resources for diagnosis
- Care coordination with other healthcare providers obstetricians, maternal-fetal medicine specialists, clinical geneticists or genetic counselers, and neonatologists
- Reviewing the information provided by other health care providers
- Assisting in, and supporting the family in the decision-making process
The risk for chromosomal abnormalities and Down Syndrome specifically increases with increased maternal age. According to the American College of Obstetricians and Gynecologists, women with a singleton pregnancies who will be 35 years of age or more at birth should be offered prenatal diagnosis for chromosomal abnormalities.
The risks for chromosomal abnormalities from a 1983 article in JAMA are:
Maternal Age at Delivery Risk for All Chromosomal Risk for Down Abnormalities Syndrome 33 1/345 1/602 34 1/270 1/485 35 1/213 1/376 36 1/169 1/289 37 1/132 1/224 38 1/103 1/174 39 1/81 1/136 40 1/64 1/106 41 1/50 1/82 42 1/39 1/63 43 1/31 1/49 44 1/24 1/38 45 1/19 1/30 46 1/15 1/23 47 1/12 1/18 48 1/9 1/14 49 1/7 1/11
Questions for Further Discussion
1. What are the current recommendations for prenatal screening for cystic fibrosis?
2. What are the current recomendations for prenatal screening for parents of Eastern European Jewish heritage?
3. What changes are being considered for post-natal universal screening of infants for metabolic diseases?
To Learn More
To view pediatric review articles on this topic from the past year check PubMed.
Information prescriptions for patients can be found at Pediatric Common Questions, Quick Answers for this topic: Birth Defects.
To view current news articles on this topic check Google News.
Hook EB, Cross PK, Schreinemachers, DM. Chromosomal abnormality rates at amniocentesis and in live-born infants. JAMA. 1983:249(15);2034-38.
ACOG Practice Bulletin. Clinical Management Guidelines for Obstetrician-Gynecologists. Prenatal diagnosis of fetal chromosomal abnormalities. Obstet Gynecol. 2001 May;97:suppl 1-12. Available from the Internet at: http://www.guideline.gov/summary/summary.aspx?doc_id=3976&nbr=3115&string=Prenatal+AND+diagnosis+AND+fetal+AND+chromosomal+AND+abnormalities (cited 6/2/05).
American Academy of Pediatrics Clinical Report. Prenatal Screening and Diagnosis for Pediatricians. Pediatrics. 2004:114:889-894. Available from the Internet at: http://www.guideline.gov/summary/summary.aspx?view_id=1&doc_id=5741 (rev. 9/2004, cited 5/23/05).
University of Washington. GeneTests. Available from the Internet at: http://www.geneclinics.org/servlet/access?id=8888891&key=KSDx8qL4ONueK&fcn=y&fw=vVyI&filename=/concepts/primer/primerwhoshould.html (rev. 2005, cited 5/23/05).
Mountain States Genetic Network. Indications for Genetic Counseling Referrals. Available from the Internet at: http://www.mostgene.org/dir/indicate.htm (cited 5/23/05).
Donna M. D’Alessandro, MD
Associate Professor of Pediatrics, Children’s Hospital of Iowa
July 18, 2005