Prenatal diagnosis or prenatal screening (note that prenatal diagnosis and prenatal screening refer to two different types of tests) is testing for diseases or conditions in a fetus or embryo before it is born. The aim is to detect birth defects such as neural tube defects, Down syndrome, chromosome abnormalities, genetic disorders and other conditions, such as spina bifida, cleft palate, Tay Sachs disease, sickle cell anemia, thalassemia, cystic fibrosis, Muscular dystrophy, and fragile X syndrome. Screening can also be used for prenatal sex discernment. Common testing procedures include amniocentesis, ultrasonography including nuchal translucency ultrasound, serum marker testing, or genetic screening. In some cases, the tests are administered to determine if the fetus will be aborted, though physicians and patients also find it useful to diagnose high-risk pregnancies early so that delivery can be scheduled in a tertiary care hospital where the baby can receive appropriate care.

Qualifying risk factors

Because of the miscarriage and fetal damage risks associated with amniocentesis and CVS procedures, many women prefer to first undergo screening so they can find out if the fetus’ risk of birth defects is high enough to justify the risks of invasive testing. Since screening tests yield a risk score which represents the chance that the baby has the birth defect, the most common threshold for high-risk is 1:270. A risk score of 1:300 would therefore be considered low-risk by many physicians. However, the trade-off between risk of birth defect and risk of complications from invasive testing is relative and subjective; some parents may decide that even a 1:1000 risk of birth defects warrants an invasive test while others wouldn’t opt for an invasive test even if they had a 1:10 risk score.

ACOG guidelines currently recommend that all pregnant women, regardless of age, be offered invasive testing to obtain a definitive diagnosis of certain birth defects. Therefore, most physicians offer diagnostic testing to all their patients, with or without prior screening and let the patient decide.

The following are some reasons why a patient might consider her risk of birth defects already to be high enough to warrant skipping screening and going straight for invasive testing.

• Women over the age of 35
• Women who have previously had premature babies or babies with a birth defect, especially heart or genetic problems
• Women who have high blood pressure, lupus, diabetes, asthma, or epilepsy
• Women who have family histories or ethnic backgrounds prone to genetic disorders, or whose partners have these
• Women who are pregnant with multiples (twins or more)
• Women who have previously had miscarriages

Maternal serum screening

First trimester maternal serum screening can check levels of free β-hCG, PAPP-A, intact or beta hCG, or h-hCG in the woman’s serum, and combine these with the measurement of nuchal translucency (NT). Some institutions also look for the presence of a fetal nasalbone on the ultrasound.

Second trimester maternal serum screening (AFP screening, triple screen, quad screen, or penta screen) can check levels of alpha fetoprotein, β-hCG, inhibin-A, estriol, and h-hCG (hyperglycosolated hCG) in the woman’s serum.

The triple test measures serum levels of AFP, estriol, and beta-hCG, with a 70% sensitivity and 5% false-positive rate. It is complemented in some regions of the United States, as the Quad test (adding inhibin A to the panel, resulting in an 81% sensitivity and 5% false-positive rate for detecting Down syndrome when taken at 15–۱۸ weeks of gestational age).^[14]

The biomarkers PAPP-A and β-hCG seem to be altered for pregnancies resulting from ICSI, causing a higher false-positive rate. Correction factors have been developed and should be used when screening for Down’s syndrome in singleton pregnancies after ICSI,^[15] but in twin pregnancies such correction factors have not been fully elucidated.^[15] In vanishing twin pregnancies with a second gestational sac with a dead fetus, first trimester screening should be based solely on the maternal age and the nuchal translucency scan as biomarkers are altered in these cases.