Prenatal Diagnosis and Genetic Counseling

Abstract

Birth defects are increasingly being identified prenatally, allowing the pediatric surgeon to become involved before presentation in the neonatal intensive care unit. Congenital malformations are the most frequent cause of mortality during the first year of life, accounting for approximately 20% of all infant deaths in the United States. The overall risk of birth defects for any couple undertaking a pregnancy is estimated at 3–5%, with 2–3% of those infants having major structural abnormalities identified prenatally and requiring evaluation and treatment as a newborn (Table 2.1). More functional birth defects and developmental changes, not recognizable as structural anomalies, can make up the additional 2–3% by the end of the first year of life. Minor birth defects are estimated at 8–10% but generally are not associated with significant morbidity.

Appendices

Summary Points

Birth defects are common − major malformations are detected at a frequency of 2–3% in utero and 1–2% postnatally.

Terms to describe birth defects include malformation, deformation, disruption, and dysplasia.

Types of genetic inheritance and mechanisms of genetic expression include autosomal recessive, autosomal dominant, X-linked, sporadic, multifactorial, imprinting, uniparental disomy, and mosaicism.

Genetic invasive testing is done prenatally dependent on gestational age: chorionic villus sampling (CVS) 10–35 weeks, amniocentesis 15–38 weeks, and cordocentesis 18–37 weeks.

Multiple anomaly terminology is described as syndrome (due to single etiology), sequence (primary defect but often heterogeneous etiology), and association (non-random ­collection of anomalies not known to represent a syndrome or sequence).

Parental counseling is required to clarify and educate regarding the fetal or neonatal births regarding their possible etiology, diagnostic testing to evaluate, and surveillance or treatment (with morbidity and mortality risks) protocol to be considered.

Editor’s Comment

Prenatal testing continues to evolve as newer and less invasive technologies are developed. Many women in the US undergo a quadruple screen (or “quad” screen, which has replaced the triple screen) in the second trimester, a test that measures serum levels of AFP, unconjugated estriol, hCG, and inhibin. It is more than 80% sensitive for neural tube defects and certain chromosomal abnormalities (trisomies 18 and 21), but has a 5% incidence of false positive results. A positive screen is usually followed by more detailed ­imaging or, in some cases, amniocentesis or CVS. Imaging modalities, including “3-D” ultrasound and fetal MRI, have also continued to improve significantly, allowing the prenatal characterization of complex structural anomalies such as heart defects and gastrointestinal abnormalities.

There are now a number of fetal diagnostic and therapeutic specialty centers where the care of the high-risk pregnant woman and fetuses with congenital anomalies can be coordinated and planned, sometimes allowing in utero intervention. What defines a pregnancy as high risk for birth defects is somewhat variable, but usually includes: women who are over 35 years of age; women who have a history of miscarriages or premature births or have given birth to a child with cardiac defects or genetic abnormalities; parents with an ethnic background associated with a high risk of certain genetic syndromes; multiple fetuses; and women with certain medical conditions (diabetes, systemic lupus erythematosus, seizure disorder). Regardless of the calculated risk of a birth defect, national groups like the American College of Obstetrics and Gynecology often recommend that all pregnant women be made aware of the prenatal screening tests that are available to them.