Prenatal testing is a tool that can be used to detect some birth defects at various stages prior to birth. Prenatal testing consists of prenatal screening and prenatal diagnosis, which are aspects of prenatal care that focus on detecting problems with the pregnancy as early as possible. These may be anatomic and physiologic problems with the health of the zygote, embryo, or fetus, either before gestation even starts (as in preimplantation genetic diagnosis) or as early in gestation as practicable. Screening can detect problems such as neural tube defects, chromosome abnormalities, and gene mutations that would lead to genetic disorders and birth defects such as spina bifida, cleft palate, Down syndrome, trisomy 18, Tay–Sachs disease, sickle cell anemia, thalassemia, cystic fibrosis, muscular dystrophy, and fragile X syndrome. Some tests are designed to discover problems which primarily affect the health of the mother, such as PAPP-A to detect pre-eclampsia or glucose tolerance tests to diagnose gestational diabetes. Screening can also detect anatomical defects such as hydrocephalus, anencephaly, heart defects, and amniotic band syndrome.
Prenatal screening focuses on finding problems among a large population with affordable and noninvasive methods. Prenatal diagnosis focuses on pursuing additional detailed information once a particular problem has been found, and can sometimes be more invasive. The most common screening procedures are routine ultrasounds, blood tests, and blood pressure measurement. Common diagnosis procedures include amniocentesis and chorionic villus sampling. 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.
Prenatal testing in recent years has been moving towards non-invasive methods to determine the fetal risk for genetic disorders. The rapid advancement of modern high-performance molecular technologies along with the discovery of cell-free fetal DNA (cffDNA) in maternal plasma has led to new methods for the determination of fetal chromosomal aneuploidies. This type of testing is referred to as non-invasive prenatal testing (NIPT) or as non-invasive prenatal screening. Invasive procedures remain important, though, especially for their diagnostic value in confirming positive non-invasive findings and detecting genetic disorders. Birth defects have an occurrence between 1 and 6%.
Purpose There are three purposes of prenatal diagnosis: (1) to enable timely medical or surgical treatment of a condition before or after birth, (2) to give the parents the chance to abort a fetus with the diagnosed condition, and (3) to give parents the chance to prepare psychologically, socially, financially, and medically for a baby with a health problem or disability, or for the likelihood of a stillbirth. Prior information about problems in pregnancy means that healthcare staff as well as parents can better prepare themselves for the delivery of a child with a health problem. For example, Down syndrome is associated with cardiac defects that may need intervention immediately upon birth.
Name of test (category)'WhenInvasivityHowTurnaround timeTests/Screens forAssociated risksRoutine prenatal testsMaternal weightEvery checkup appointmentNon-invasiveScaleImmediatelyBaselines, pre-pregnancy weight estimates, tracking weight gain/loss, pattern observationNAMaternal blood pressure/Preeclampsia screenEvery checkup appointmentNon-InvasiveBlood pressure cuffImmediatelyPre-eclampsia/hypertensionNAMaternal urinalysis/urine test screenPeriodicallyNon-invasiveUrine collection~a few minutes – ~1 weekhCG, diabetes, dehydration, preeclampsia, kidney and bladder infection/diseaseNAUltrasoundPeriodicallyNon-invasive/InvasiveAbdominal or Transvaginal~1 day – ~1 weekFetal development, neural tube defects, birth defects, and various other physical abnormalities (see below for specific ultrasound tests)NAFetal heart-rate monitoringWeek 12 – onwardNon-invasiveHandheld abdominal doppler or fetoscopeImmediatelyHeart rate irregularitiesNA Genetic prenatal testsCarrier screening (Screen)Anytime (before or during pregnancy)Less invasiveCheek swab or blood draw~2–4 weeksDetermining if a parent carries specific genes associated with certain (primarily autosomal recessive) conditionsVery low risk, however there is the potential for bruising, pain, nerve damage, fainting, haematoma, bacterial infection, and bloodborne pathogen exposure.Chorionic villus sampling/Biopsy, CVS (diagnostic)Week 8 – 14InvasiveTransabdominal or transcervical insertion of a needle, forceps or syringe to obtain a fetal placenta tissue sample~1–2 weeksChromosomal abnormalities, birth defectsMiscarriage, preterm labor/delivery, infection, cramping, bleeding, premature rupture of amniotic membrane, baby limb defectsCell-free fetal DNA (cfDNA) Test/Noninvasive prenatal test (NIPT) (screen)Week 10 – onwardLess invasiveBlood draw~1–2 weeksGender, chromosomal abnormalitiesVery low risk, however there is the potential for bruising, pain, nerve damage, fainting, haematoma, bacterial infection, and bloodborne pathogen exposure.First trimester screeningWeek 10 – 13InvasiveNuchal translucency ultrasound & blood prick/draw~1 weekChromosomal abnormalities, birth defects, heart defectsVery low risk, however there is the potential for bruising, pain, nerve damage, fainting, haematoma, bacterial infection, and bloodborne pathogen exposure.Alpha-fetoprotein (AFP)/modified sequential/multiple marker/quad/triple/maternal serum test (screen)Weeks 14 – 22Less invasiveBlood draw~1–2 weeksMaternal hormone levels, risk of gestational hypertension and preeclampsia, chromosome abnormalities, neural tube defectsVery low risk, however there is the potential for bruising, pain, nerve damage, fainting, haematoma, bacterial infection, and bloodborne pathogen exposure.Second trimester screening (screen)Week 15 – 22InvasiveUltrasound and multiple markers or quad screen blood draw~1–2 weeksChromosomal abnormalities, neural tube defects, abdominal wall defects, heart defects, other major physical defectsVery low risk, however there is the potential for bruising, pain, nerve damage, fainting, haematoma, bacterial infection, and bloodborne pathogen exposure.Amniocentesis (diagnostic)Week 15 – 20InvasiveTransabdominal needle insertion to obtain an amniotic fluid sample~2 weeksChromosomal abnormalities, autosomal genetic conditions, neural tube defects, abdominal wall defects, birth defectsMiscarriage (1%), preterm labor/delivery, infection, cramping, bleeding, premature rupture of amniotic membraneCordocentesis/Percutaneous umbilical cord blood sampling (PUBS) (diagnostic)Week 17 – onwardInvasiveFetal blood sample from umbilical cord~3 daysChromosomal abnormalities, blood disorders (fetal hemolytic disease)Miscarriage (1–2%), preterm labor/delivery, infection, bleeding, decreased fetal heart rate, premature rupture of amniotic membrane, deathPreimplantation genetic diagnosis (PGD) (screen)During IVF, prior to implantationNon-invasiveIVF embryo examination~1–2 weeksChromosomal abnormalities, autosomal recessive conditionsNA Additional prenatal testsGlucose challenge test (screen)Week 26 – 28Less invasiveMaternal blood draw after ingestion of glucose drink~1–2 daysTo indicate the possibility of gestational diabetesVery low risk, however there is the potential for bruising, pain, nerve damage, fainting, haematoma, bacterial infection, and bloodborne pathogen exposure.Oral glucose tolerance test (OGTT) (screen)Week 26 – 28Less invasiveMaternal blood draws before and after ingestion of glucose drink, requires fasting~2–3 daysTo properly diagnose gestational diabetes following an abnormal result from the glucose challenge screenVery low risk, however there is the potential for bruising, pain, nerve damage, fainting, haematoma, bacterial infection, and bloodborne pathogen exposure.Non-stress testWeek 28 – onwardNon-invasiveAbdominal contraction/Fetal heart rate beltImmediatelyFetal heart rate vs movement, oxygen levels (indicating problems stemming from the placenta or umbilical cord), fetal distressNAGroup B Strep TestWeek 36 – 38InvasiveVaginal swab~1–2 daysBacteria indicating Group B StrepNACervix dilation checkWeek 37 – onwardInvasiveThe doctor takes a manual measurement inside the cervixImmediatelySigns or progress of dilation, prodromal laborInfection, premature rupture of amniotic membraneExternal fetal monitoringDuring Labor, after rupture of amnioatic sacInvasiveSpiral wire electrode attached to body part (typically the scalp) of fetus via cervical insertionImmediatelyHeart rate irregularities, monitoring fetal heart rateFetal bruising/infection at attachment siteKleihauer-Betke/Fetal cells in maternal blood (FCMB) test (screen)SituationalLess invasiveBlood draw<1 dayFetal red blood cells in the mother's blood, fetomaternal hemorrhageVery low risk, however there is the potential for bruising, pain, nerve damage, fainting, haematoma, bacterial infection, and bloodborne pathogen exposure.
Prenatal screening
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 15–18 weeks of gestational age).
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 syndrome in singleton pregnancies after ICSI, but in twin pregnancies such correction factors have not been fully elucidated. 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.
Advances in prenatal screening Measurement of fetal proteins in maternal serum is a part of standard prenatal screening for fetal aneuploidy and neural tube defects. Computational predictive model shows that extensive and diverse feto-maternal protein trafficking occurs during pregnancy and can be readily detected non-invasively in maternal whole blood. This computational approach circumvented a major limitation, the abundance of maternal proteins interfering with the detection of fetal proteins, to fetal proteomic analysis of maternal blood. Entering fetal gene transcripts previously identified in maternal whole blood into a computational predictive model helped develop a comprehensive proteomic network of the term neonate. It also shows that the fetal proteins detected in pregnant woman's blood originate from a diverse group of tissues and organs from the developing fetus. Development proteomic networks dominate the functional characterization of the predicted proteins, illustrating the potential clinical application of this technology as a way to monitor normal and abnormal fetal development.