Prenatal Diagnosis and Tests of Fetal Well-Being

OVERVIEW OF PRENATAL DIAGNOSIS

Fetal well-being depends on maternal health (see Chapter 6, page 336 for gestational diabetes screening). Many routine prenatal tests assess maternal health and well-being. Prenatal testing usually includes a complete blood count or hemoglobin and hematocrit, Rh type and ABO blood group, red cell antibody screening, rubella immunity status, glucose challenge testing (see Chapter 6), urinalysis, maternal serum alpha₁-fetoprotein (MS-AFP) or maternal quadruple marker test or quad screen, hepatitis B testing, culture for sexually transmitted diseases, the syphilis immunoglobulin G (IgG) test, and surveillance for group B streptococci. Screening for HIV infection is recommended for all pregnant women to improve the care of HIV-positive women and to identify infants at risk; perinatal transmission is the primary route of HIV infection in children.

Tests in this chapter monitor the status of the maternal-fetal unit, identify the fetus at risk for intrauterine asphyxia, aid in the early diagnosis of infection, and identify genetic and biochemical disorders and major anomalies. (See Chapter 11 for more on genetic disorders.) Tests are also performed to predict normal fetal outcome or to identify the fetus at risk for asphyxia during labor (Table 15.1).

Noninvasive prenatal testing for fetal aneuploidy is available for women at increased risk of aneuploidy. Extraction of fetal cells from the maternal circulation (fetal cell sorting) is performed for screening of trisomy 21, 18, and 13, although it does not replace the need for diagnosis by chorionic villus sampling (CVS) or amniocentesis.

FIRST AND SECOND TRIMESTER SCREENING

First trimester screening provides early testing for aneuploidy between 11 and 13 weeks. Screening includes biochemical markers for pregnancy-associated plasma protein A (PAPP-A), free β human chorionic gonadotropin (hCG), and ultrasound measurement of fetal nuchal translucency (FNT). The detection rate for first trimester screening is 80%, with false-positive rate of 5%. First trimester combined screening can also screen for trisomy 18, and NT alone may detect trisomy 18, trisomy 13, and other chromosomal abnormalities. The maternal triple or quadruple screen tests are offered to pregnant women during their second trimester to identify risks for chromosome disorders such as Down syndrome (trisomy 21); major birth defects, including open neural tube defects such as spina bifida; placental insufficiency; and oligohydramnios. The evaluation consists of three or four separate blood protein tests done on maternal serum between 15 and 21 weeks of gestation: MS-AFP is decreased in Down syndrome and neural tube defects, unconjugated estriol (E₃) is decreased in Down syndrome, and β-hCG is increased in Down syndrome. Results are reported as multiples of the median (MoM). The triple screen detection rate for Down syndrome is approximately 69% (false-positive rate of 5%), 80% for neural tube defects, and 60% for trisomy 18 (false-positive rate of 0.2%). The detection rate for Down syndrome with quadruple screen is 81%. Combining first and second trimester screening improves the detection rate to 94% to 96%, with a 5% false-positive rate. Quad screen includes AFP, hCG, E₃, and inhibin A.

The maternal triple and quadruple tests are screening tests; therefore, an abnormal (positive) result is not diagnostic, and further testing with ultrasound, amniocentesis, and genetic counseling is indicated. The markers can be positive in normal variations such as multiple births or miscalculated gestational age.

Ultrasound testing is a method of assessing fetal well-being that has become a diagnostic tool for assessment of fetal age, health, growth, and identification of anomalies. Level I ultrasound assesses gestational age, number of fetuses, fetal death, and the condition of the placenta. Level II ultrasound assesses specific congenital anomalies or abnormalities. In some diagnostic centers, fetal echocardiography is also available. An additional ultrasound marker for Down syndrome is the absence or hypoplasia of nasal bones in fetuses at 11 to 14 weeks’ gestation. When combining this marker

with PAPP-A, β-hCG, and FNT, the detection rate for Down syndrome is significantly increased. Color-enhanced Doppler ultrasound is used to measure the velocity and direction of blood flow in fetal and uterine anatomy, to provide information about placental function, and as an especially good predictor of outcome for fetuses that are small for gestational age (see Chapter 13). American Congress of Obstetricians and Gynecologists (ACOG) guidelines support the use of umbilical artery Doppler surveillance in the management of intrauterine growth restriction. Middle cerebral artery Doppler assessment is used to predict fetal anemia in at-risk pregnancies. Ultrasound also includes three-dimensional (3D) and four-dimensional (4D) technologies. In fetal medicine, the use of these technologies may provide assessment of fetal anomalies of the limbs, thorax, spine, central nervous system, and face. Some centers use 4D ultrasound for guided needle procedures such as amniocentesis and cordocentesis to improve accuracy of the procedure. Three- and four-dimensional ultrasound is also used to evaluate fetal heart function and structure.

TABLE 15.1 Maternal Fetal Testing During Pregnancy

Tests and Procedures	Indications	Follow-Up and Interventions for Positive Test Results
First Trimester (1-14 wk)
Human chorionic gonadotropin (hCG) levels	Confirm normal progress of pregnancy or if suspected for ectopic pregnancy, threatened or missed abortion, or to monitor success of insemination or in vitro fertilization	Levels increase 66% or double every 36-48 hr; if levels off or decline, may be ectopic or miscarriage. Usually, two tests are done 48 hr apart and often follow-up with ultrasound. Dramatic increase may indicate multiple fetuses.
Prenatal Profile
Complete blood count (CBC) or hemoglobin/hematocrit (Hb/Hct)	Detection of anemia defined by the Centers for Disease Control and Prevention as below 11/33 in first trimester. CBC with red blood cell (RBC) indices for detection of carrier state of hemoglobinopathies	Anemia is treated with iron supplementation. Follow-up test is repeated at 28 wk and as indicated. Hb electrophoresis, Sickledex, or high-powered liquid chromatography and isoelectric focusing for those at risk for hemoglobinopathies: African Americans (sickle cell disease); Italian, Greek, or Corsican (β-thalassemia); and Southeast Asian (α-thalassemia)
ABO, Rh	Blood typing to identify Rh-negative women and ABO group for incompatibility	Intervention for Rh-negative women is to receive Rh immunoglobulin (RhoGAM) prophylaxis. Identification of type O women for consideration of ABO incompatibility in neonatal jaundice
Rubella immunity status	Identify nonimmune women to avoid possible exposure to rubella and report any possible exposure; considered immune if there is a documented dose of rubella vaccine or an immune serologic test result	Instruction to nonimmune women to report exposure to rubella for immunoglobulin prophylaxis; immunization is recommended postpartum.
HIV	All should be counseled for screening to reduce perinatal transmission to infant.	Positive results indicate need to recommend antiretroviral treatment and discussion about possible cesarean delivery to reduce perinatal transmission as well as avoidance of breast-feeding if indicated. Follow-up testing may be needed for high-risk individuals.
Syphilis antibody immunoglobulin G (IgG)	Identify syphilis infection in pregnant women to reduce fetal infection	Positive result indicates need for treatment with penicillin or other antibiotic if allergy exists.
Venereal Disease Research Laboratory		Follow-up testing may be needed for high-risk individuals.
Hepatitis B surface antigen	All pregnant women should be screened to identify chronic disease carriers.	Follow-up includes immunization of those with negative test but considered high risk for acquiring hepatitis B during pregnancy, and positive results indicate need to immunize infant with hepatitis B immune globulin and hepatitis B vaccine as soon as possible after birth.
Antibody screen	All pregnant women should be screened to identify isoimmunized women.	If positive result, test is repeated to identify specific maternal antibody (e.g., anti-D, C, c, E, e, Kell, Duffy, Kidd).
Varicella status	All pregnant women unless reliable history of varicella as a measure of immunity	If nonimmune and with history of exposure, needs varicella titer within 24-48 hr; if needed, varicellazoster immune globulin given within 96-144 hr of exposure. Varicella vaccine can be given postpartum.
Papanicolaou test	All pregnant women without a documented normal Pap test within the past 6 mo	Positive results may need follow-up with a colposcopy or repeat Pap test. Most often, treatment is delayed until postpartum.
Urinalysis, urine culture	All pregnant women are screened for asymptomatic bacteriuria.	Positive results of > 100,000 colonies of single organism should be treated and high-risk patients screened each trimester.
For At-Risk Patients
Wet prep	All pregnant women at risk for preterm birth	Positive clue cells, trichomonads, or Candida indicates need for treatment.
Gonorrhea	Pregnant women with risk factors	Positive results should be treated with appropriate antibiotic therapy, and test of cure should be obtained.
Chlamydia	Pregnant women with risk factors	Positive results should be treated with appropriate antibiotic therapy, and test of cure should be obtained.
Genital herpes culture if active lesion	All pregnant women with active lesion	Positive test may be treated with antiviral medication, and patient may be counseled regarding risks and benefits of cesarean delivery.
Tuberculosis test	High-risk pregnant women or symptomatic	Follow-up may include chest x-ray with shielding preferred after 12 wk and treatment with medications during pregnancy.
Chorionic villus sampling (CVS)	Pregnant women at risk for fetal genetic or biochemical disorders or those with abnormal ultrasound	Positive test requires follow-up genetic counseling or discussion of treatment options.
Fetal nuchal translucency (FNT; may be combined with pregnancy-associated plasma protein A [PAPP-A], β-hCG to increase detection rate)	Any pregnant woman presenting by 11-13 wk can be screened, particularly desired screening for Down syndrome, trisomy 13, trisomy 18, Turner’s syndrome.	Positive test follow-up with counseling regarding CVS or amniocentesis for definitive diagnosis. Positive test can be associated with other fetal conditions if no chromosomal abnormality.
Fetal cell-free nucleic acids—screening test to detect trisomy 13, 18, or 21	At-risk women include age 35 yr or older, ultrasound findings show increased risk for aneuploidy, history of a child with trisomy, or positive first or second trimester screening. Can be offered after 10 wk of gestation	Positive test indicates need for genetic counseling and further testing for confirmation of test results.
Carrier testing for cystic fibrosis (CF). American Congress of Obstetricians and Gynecologists (ACOG) recommends standard screening test should include 25 disease-causing mutations for CF	ACOG recommends that all pregnant women of northern European and Ashkenazi Jewish origin be offered carrier testing for CF as standard of care. Also, individuals with family history of CF, reproductive partners of individuals with CF, couples with one or both Caucasian partners who are pregnant or planning a pregnancy	Genetic counseling for positive test Those with a negative screening should be aware that they may be a carrier for mutation not included in the test.
Ultrasound	Pregnancy confirmation Viability, rule out (R/O) ectopic pregnancy, gestational age, fetal assessment	Follow-up ultrasound level I or II
PAPP-A	Screening for chromosomal abnormalities (can be used in combined testing with FNT and β-hCG based on maternal age)	Lower in pregnancies if fetus has Down syndrome
Preimplantation genetic diagnosis	Genetic testing of an early embryo at 6- to 8-cell stage (3 d after fertilization) examined for aneuploidy, structural chromosomal abnormalities, single-gene disorders, X-linked disorders	Embryos are implanted after genetic testing rules out abnormalities.
Gestational glucose screening—1 hr	Screening for gestational diabetes risk	Positive tests require a 3-hr oral (100 g) glucose tolerance test for diagnosis of gestational diabetes.
Second Trimester (15-28 wk)
Triple screen (hCG, unconjugated estriol [uE₃], maternal serum alpha-fetoprotein [AFP]) Quadruple screen adds inhibin A	Screening for Down syndrome, trisomy 18, and possibly Turner’s syndrome, triploidy, Smith-Lemli-Opitz syndrome. Low inhibin A increases the detection of Down syndrome and trisomy 18.	Genetic counseling, evaluation by perinatologist, possibly level II ultrasound and amniocentesis
Amniocentesis	Amniotic fluid studies of fetal genetics to identify abnormalities, karyotyping to identify chromosomal disorders	Genetic counseling
Ultrasound 18-20 wk, level I or II	Facilitate amniocentesis, determine or confirm estimated date of delivery and fetal viability, R/O abnormal pregnancy, intrauterine growth retardation (IUGR), congenital anomalies, oligo- or polyhydramnios. Identify placental location, cervical length, multiple gestation, amniotic fluid index (AFI) Level II: assess specific anomalies in fetal anatomy such as congenital heart defects, omphalocele, anencephaly; identify ultrasound markers that increase risk for genetic abnormalities	Positive results may require repeat or serial ultrasound evaluations, MRI, 3D or 4D ultrasound, or genetic counseling.
Umbilical artery Doppler tests	Identify abnormal placental function in at-risk pregnancies such as pregnancy-induced hypertension, IUGR. Identify fetal acidosis, hypoxia.	Positive results may indicate need for further monitoring or need to deliver infant.
Fetoscopy	Identify fetal developmental defects, blood disorders such as hemophilia A and B, sickle cell anemia; perform therapeutic interventions, sample fetal tissue	Positive results may require interventions or need for care conference for plan of delivery of abnormal infant.
Percutaneous umbilical blood sampling	Need for fetal blood sampling with less risk than fetoscopy. Identify such disorders as hemophilia, hemoglobinopathies, infections, drug levels, chromosomal abnormalities, cord blood pH.	Positive results may indicate need for treatment, immediate delivery, or genetic counseling.
Serum-Integrated Screening
PAPP-A from first trimester screening Alpha fetoprotein monoclonal antibody (AFP3), inhibin A in second trimester	Prenatal screening for Down syndrome	Genetic counseling, evaluation by perinatologist, possibly level II ultrasound and amniocentesis
Fully Integrated Screening
FNT and PAPP-A in first trimester AFP3, inhibin A in second trimester	Prenatal screening for Down syndrome	Genetic counseling, evaluation by perinatologist, possibly level II ultrasound and amniocentesis
Third Trimester (29-40 wk)
Fetal fibronectin	With symptoms of preterm labor, if intact membranes and <3 cm dilation, may help to predict preterm delivery	Positive results predict probable delivery in next 7-14 d.
Nonstress test, contraction stress test, oxytocin challenge test, breast stimulation test, fetal activity acceleration determination	Assess fetal heart rate (FHR) in response to fetal movement or contractions to assess fetal well-being, fetal hypoxia, tolerance to labor	Positive result may indicate need for further testing, induction of labor, or immediate delivery.
Biophysical profile	Used in high-risk pregnancy to assess fetal well-being or diagnose fetal hypoxia or distress	Positive result may indicate need for further testing, induction of labor, or immediate delivery.
Amniocentesis	Determine fetal lung maturity, fetal infections or fetal hematologic disorders, previous history of erythroblastosis	Lecithin/sphingomyelin ratio of >2 indicates lung maturity and, if delivered, lessens chance of respiratory distress syndrome
Group B streptococcus screening	All pregnant women should be screened for anogenital group B streptococcus colonization between 35 and 37 wk.	Positive results indicate colonization and indication for antibiotic prophylaxis intrapartum.
Fetal oxygen saturation (FSpO₂) monitoring	Indicated if FHR monitoring is not reassuring or difficult to interpret; can be used if membranes are ruptured, vertex presentation, >36 wk	FSpO₂ <30% for >10 min is probably hypoxemia, indicating need for intervention or delivery.
Ultrasound	Indicated to determine fetal position, placenta previa, abruption or maturity, FHR if unable to Doppler fetal heart tones, assess fetal growth, AFI, estimate fetal weight, R/O multiple gestation, anomalies	To determine fetal well-being, need for immediate delivery or induction of labor, or need for follow-up ultrasounds
Amniotic fluid fern test AmniSure detects human protein in amniotic fluid (PAMG-1)	Determine rupture of membranes	Positive results may indicate need to deliver within 24 hr or induction of labor if no spontaneous labor.
Human placental lactogen	High-risk pregnancies to evaluate placental function	Decreased or falling levels may indicate need for further testing of fetal well-being.
Electronic fetal monitoring	Indicated antepartum to evaluate fetal well-being for high-risk pregnancies, during or after procedures, for symptoms of preterm labor, decreased fetal movement, maternal drug administration. Indicated intrapartum intermittently for low-risk pregnancies or continuously for high-risk pregnancies, during oxytocin administration, epidural anesthesia, or other interventions	Signs of fetal distress warrant interventions to improve fetal oxygenation or immediate delivery.

Although magnetic resonance imaging (MRI) is used at some prenatal centers, it is still under investigation for diagnostic evaluation in pregnancy, especially in the final trimester (see Chapter 16). MRI is most often used to define central nervous system defects. Some of the advantages of MRI during pregnancy are that it is a noninvasive technique, it permits easy differentiation between fat and soft tissue, it does not require a full bladder, and it can show the entire fetus in one scan. Currently, MRI confirms fetal abnormalities found by ultrasound and can be used for pelvimetry, placental localization, and determination of size. Fetal MRI is used at medical centers that specialize in fetal diagnosis and treatment (particularly those that perform fetal surgery). Ultrafast MRI is used for evaluation of congenital anomalies that are potentially correctable, such as congenital diaphragmatic hernia, neck masses that result in airway obstruction, myelomeningocele, and cleft lip and cleft palate. MRI is especially useful for definition of maternal anatomy in cases of suspected intra-abdominal or retroperitoneal disease.

• Maternal Serum Alpha-Fetoprotein (MS-AFP)

The measurement of MS-AFP is offered between 15 and 21 weeks’ gestation when AFP concentration rises dramatically, and the test is used to screen for fetal abnormalities and neural tube defects. Approximately 90% of infants with neural tube defects are born to parents who have no recognized risk factors for the disorder. Maternal quadruple screen (MoM: AFP, hCG, and E₃ and inhibin A) aids in identifying Down syndrome risk. The test also detects complications of pregnancy, and AFP serves as a tumor marker in nonpregnant women. This test is also used to detect pregnancy complications such as intrauterine growth retardation, fetal distress, and fetal demise. It can also be used to diagnose and monitor hepatocellular, testicular, ovarian, and malignant liver diseases.

Reference Values

Normal

At 15 to 21 weeks’ gestation: 10 to 150 ng/mL or 10 to 150 µg/L

Normal adult level: <10 ng/mL or <10 µg/L

MoM: 0.5 to 2.5 (calculated by dividing the patient’s AFP by median AFP for a normal pregnancy at the same gestational age). An AFP MoM <2.5 is reported as screen negative. A screen negative result indicates that the calculated AFP MoM falls below the cutoff of 2.5 MoM. A negative screen does not guarantee absence of a neural tube defect.

Procedure

Obtain a 10-mL venous blood sample (red-topped tube). Observe standard precautions. Label specimen with the patient’s name, date, and test(s) ordered and place specimen in a biohazard bag. Provide information for the laboratory about the duration of pregnancy, patient’s weight, ethnicity, and presence of diabetes.
Plan the first screening at 15 to 18 weeks. If the result is normal, no further screening is necessary. If MS-AFP is low, consider ultrasound studies to determine exact fetal age. A second screening may be done after an initial elevated MS-AFP. If the result is normal, no further screening is necessary.

Clinical Implications

Abnormal levels should be followed by ultrasound and amniocentesis.

Elevated MS-AFP can indicate:
- Neural tube defects of spina bifida (a vertebral gap) or anencephaly (>2.5 MoM)
- Underestimation of gestational age
- Multiple gestation (>4.5 MoM)
- Threatened abortion
- Other congenital abnormalities
Elevated MS-AFP early in pregnancy is associated with:
- Congenital nephrosis
- Duodenal atresia
- Umbilical hernia or protrusion
- Sacrococcygeal teratoma
Elevated MS-AFP in the third trimester is associated with:
- Esophageal atresia
- Fetal teratoma
- Hydrencephaly
- Rh isoimmunization
- Gastrointestinal tract obstruction
Low MS-AFP is associated with:
- Long-standing fetal death
- Down syndrome (trisomy 21)
- Other chromosome abnormalities (trisomy 13, trisomy 18)
- Hydatidiform mole
- Pseudopregnancy

Interfering Factors

Obesity causes low MS-AFP.
Race is a factor: MS-AFP levels are 10% to 15% higher in African Americans and are lower in Asians than in Caucasians.
Insulin-dependent diabetes results in low MS-AFP levels.

Interventions

Pretest Patient Care

Explain the reason for testing the patient’s blood.
Determine the gestational age from the last menstrual period. If the last menstrual period is not known, determine gestational age with ultrasound.
Follow guidelines in Chapter 1 for safe, effective, informed pretest care.

Posttest Patient Care

Collaborate with the healthcare provider to interpret the outcome and counsel the patient about the results.
Explain the possible need for further testing.
Elevated maternal AFP levels should be followed by a second screening or ultrasound studies for fetal age.
Low maternal AFP levels should be followed by ultrasound studies and then by amniocentesis.
Follow guidelines in Chapter 1 for safe, effective, informed posttest care.

• Circulating Cell-Free DNA

Fetal “cell-free” nucleic acids (DNA and RNA) are found in the maternal circulation, are unique to the current pregnancy, and are thought to be from the placenta. Circulating cell-free DNA is taken from the plasma of maternal whole blood. Testing is available to detect fetal aneuploidies for chromosome 21, 18, and 13. The test can also determine X and Y chromosomes. This noninvasive test can be performed as early as 10 weeks’ gestation with results available in 1 week. ACOG recommends that women, regardless of age, be offered prenatal screening for aneuploidy by screening or invasive testing. Cell-free DNA testing is one method of noninvasive screening for women at risk for aneuploidy. It is not recommended as a screening test for low-risk women at this time due to lack of testing in the low-risk population.

Indications for cell-free DNA testing for aneuploidy:

Maternal age of 35 years or older at delivery
Ultrasound findings of fetus indicating increased risk for aneuploidy
Prior history of pregnancy with trisomy
Positive first or second trimester sequential or integrated screen or quad screen
Parental balanced Robertsonian translocation with increased risk of fetal trisomy 13 or trisomy 21
Cell-free DNA testing can identify 99% of Down syndrome, 99.9% of trisomy 18, and 91.7% of trisomy 13.

Reference Values

Normal

Negative test indicates no evidence of aneuploidies for 21, 18, or 13.

Positive

Trisomy 21, trisomy 18, or trisomy 13 detected

Interventions

Pretest Patient Care

Discuss family history with the patient to determine whether patient should be offered other forms of prenatal screening or invasive testing depending on the genetic syndrome. Pretest counseling should include the discussion that cell-free DNA is not a diagnostic test but has a high sensitivity and specificity.
Follow guidelines in Chapter 1 for safe, effective, informed pretest care.

Posttest Patient Care

Refer to a genetics counselor and maternal fetal medicine provider for diagnostic testing and consultation if test is positive.
Follow guidelines in Chapter 1 for safe, effective, informed posttest care.

• Hormone Testing

Normally, the amounts of all steroid hormones increase as pregnancy progresses. The maternal unit responds to altered hormone levels even before the growing uterus is apparent. Serial testing may be done to monitor rising levels of a particular hormone over a period of time. Decreasing levels indicate that the maternal-placental-fetal unit is not functioning normally. Biochemical analyses of several hormones can be used to monitor changes in the status of the maternal-fetal unit (see Chapters 3 and 6).

In early pregnancy, hCG in maternal blood provides evidence of a viable pregnancy. The hCG in maternal serum is measured as a sensitive pregnancy test (the hCG level increases 66% to 100% every 48 hours during pregnancy). Also, it is used to monitor the success of in vitro fertilization or insemination, to diagnose trophoblastic tumor, to diagnose ectopic pregnancy (indicated by a
decrease in hCG over a 48-hour period), and to screen for Down syndrome in pregnancy. For further discussion of pregnancy tests, see Chapter 6.
Together with prolactin and luteinizing hormone (LH), hCG prolongs the life of the corpus luteum once the ovum is fertilized. It stimulates the ovary for the first 6 to 8 weeks of pregnancy, before placental synthesis of progesterone begins. Its function later in pregnancy (in maternal blood) is unknown.
PAPP-A, a circulating placental protein, has been shown to increase the stimulatory effects of placental insulin-like growth factors. Decreased serum levels in the maternal circulation in the first 10 weeks after conception are associated with uncomplicated full-term low birth weights. PAPP-A levels are detectable within 30 days after conception and slowly increase throughout the first 30 weeks of gestation. Maternal serum levels are 0.43 µg/L (12 pmol/L). Increased PAPP-A occurs in Down pregnancy.
Late in pregnancy, the levels of E₃ and human placental lactogen (hPL) in maternal blood reflect fetal homeostasis. hPL is a protein hormone produced by the placenta. Testing of hPL evaluates only placental functioning. Blood testing of the patient usually begins after the 30th week and may be done weekly thereafter. A concentration of 1 µg/mL (46 nmol/L) hPL may be detected at 6 to 8 weeks of gestation. The level slowly increases throughout pregnancy and reaches 7 µg/mL (324 nmol/L) at term before abruptly dropping to zero after delivery. hPL functions primarily as a fail-safe mechanism to ensure nutrient supply to the fetus, for example, at times of maternal starvation. However, it does not appear to be required for a successful pregnancy outcome (see Chapter 6).

• Estriol (E₃)

E₃ is the predominant estrogen in the blood and urine of pregnant women and is of fetal origin. Normal production serves as a measure of the integrity of the maternal-fetal unit and of fetal well-being.

This test is used during pregnancy to evaluate fetal disorders and is part of the maternal triple screen. Declining serial values indicate fetal distress, although in some high-risk pregnancies, E₃ is not reduced. A single determination cannot be interpreted in a meaningful fashion. E₃ is decreased in Down syndrome and in trisomy 18. An elevated serum or unconjugated E₃ above 3 multiples of the gestational age mean, or with an absolute value of >2.1 ng/mL, can indicate pending labor or fetal congenital adrenal hyperplasia.

Reference Values

Normal

Weeks of Gestation	E₃ (ng/mL)	SI Units (nmol/L)
28-30	38-140	132-485
32	35-330	121-1144
34	45-260	156-901
36	46-350	159-1277
38	59-570	214-1976
40	90-460	306-1595
Levels peak in the middle or late afternoon. The day-to-day variation is 12% to 15%.

Interfering Factors

Administration of radioactive isotopes within the previous 48 hours interferes with this test.

Estrogen or progesterone therapy can interfere with test results.

Drugs that can cause decreased levels include vitamins and some phenothiazines.

Tetracycline can increase levels.

Interventions

Pretest Patient Care

Explain test purpose and procedures. Serial testing may be required. See Hormone Testing.
No fasting is necessary.
Follow guidelines in Chapter 1 for safe, effective, informed pretest care.

Posttest Patient Care

Review test results; report and record findings. Modify the nursing care plan as needed. Continuously low E₃ values are sometimes seen in normal pregnancy. A decreasing trend is indicative of fetal distress. Provide counseling and support.
Follow guidelines in Chapter 1 for safe, effective, informed posttest care.

• Human Placental Lactogen (hPL) (Chorionic Somatomammotropin)

hPL is a growth-promoting hormone of placental origin and is similar to hCG (see Hormone Testing).

This test is used to evaluate placental function as an index of fetal well-being in at-risk pregnancies. Low hPL levels are associated with intrauterine growth retardation. Falling levels indicate a poor prognosis. The level of hPL correlates best with placental weight, but the clinical significance of this hormone is controversial.

Reference Values

Normal

Normal maternal serum: <0.5 µg/mL (<0.5 mg/L or <25 nmol/L)

1st Trimester: 0.2-2.1 µg/mL

2nd Trimester: 0.5-6.7 µg/mL

3rd Trimester: 4.5-12.8 µg/mL

Men and nonpregnant women: 0-0.1 µg/mL

Clinical Implications

Normal values are associated with normal intrauterine growth but do not ensure lack of complications.
Decreased or falling values are associated with:
- Growth retardation
- Placental disease
- Fetal death
- Hypertensive state
- Toxemia
- Aborting hydatidiform mole
- Choriocarcinoma
- Placental insufficiency
Low levels are also associated with some normal pregnancies.
Increased values are found in:
- Multiple pregnancies (twins or more)
- Placental site trophoblastic tumor
- Intact molar pregnancy
- Diabetes
- Rh incompatibility

Interfering Factors

Administration of radiopharmaceuticals 24 hours before venipuncture interferes with this test.

• Fetal Fibronectin (fFN)

Fetal fibronectin (fFN) is abundant in amniotic fluid and may be useful in the diagnosis of ruptured membranes. The detection of fFN in vaginal secretions before membrane rupture may be a marker for impending preterm labor within the next 7 to 14 days.

This test helps to predict a preterm delivery when the presenting symptoms are questionable so that early intervention (e.g., tocolytics, corticosteroids, transport to a tertiary center) can be initiated when indicated. This test is for women with intact membranes and cervical dilation <3 cm. fFN is secreted in early pregnancy to help attach the fertilized egg to the implantation site in the uterus, but it is not secreted after 22 weeks until near term. This test detects preterm labor from 24 until 34 weeks’ gestation.

Reference Values

Normal

Negative: <0.05 µg/mL or <0.05 mg/L (delivery is unlikely to occur within 14 days)

Positive: >0.05 µg/mL or >0.05 mg/L (delivery within 7 to 14 days)

Procedure

Using a sterile speculum, obtain secretions from the cervix and vagina by rotating a sterile Dacron swab near the outside of the cervix and the posterior fornix of the vagina. Observe standard precautions.
Label the specimen with the patient’s name, date and time of collection, and test(s) ordered. Place specimen in a biohazard bag and send the specimen to laboratory. Results may take 24 to 48 hours.

Interfering Factors

Vaginal bleeding
Ruptured membranes
Sexual intercourse within 24 hours of collection

Interventions

Pretest Patient Care

Explain test purpose and procedure to the patient.
Follow guidelines in Chapter 1 for safe, effective, informed pretest care.

Posttest Patient Care

Counsel the patient regarding test results and need for follow-up medication, tocolysis (inhibition of contractions), or preparation for probable delivery.
Be sure the patient knows the warning signs of preterm labor.
- Uterine contractions—a hard feeling over the entire surface of the uterus that lasts 20 seconds or longer. The contractions can be painless. If more than four are felt per hour, notify healthcare provider.
- Menstrual-like cramps felt low in abdomen; may be constant or come and go
- Pelvic pressure or fullness in the pelvic area or back of the thighs
- Backache—a dull pain in the lower back, either constant or rhythmic, that is not relieved by changing positions
- Persistent diarrhea
- Intestinal cramps with or without diarrhea
- Vaginal discharge that is greater than normal or changes in consistency or color (especially if it is pink, bloody, or greenish)
- A general feeling or sense that something is wrong
Explain the possible causes and increased risks associated with preterm labor and birth:
- Past preterm birth
- Spontaneous abortion in second trimester
- Uterine anomaly
- Diethylstilbestrol exposure
- Incompetent cervix
- Hydramnios
- Bleeding in second and third trimester
- Preterm labor
- Premature rupture of membrane
- Multiple gestation
- Preterm cervical dilation >2 cm (multipara) or >1 cm (primipara)
- Pregnancy weight <115 pounds
- Patient <15 years of age
Follow guidelines in Chapter 1 for safe, effective, informed posttest care.

TESTS TO PREDICT FETAL OUTCOME AND RISK FOR INTRAUTERINE ASPHYXIA

• Contraction Stress Test (CST)

This test is done in a hospital or clinic setting to assess fetal heart rate (FHR) in response to uterine contractions through electronic fetal monitoring.

Reference Values

Normal

The test result is negative if there are no late decelerations associated with at least three contractions within a 10-minute period.

A normal (negative) contraction stress test (CST) implies that placental support is adequate, that the fetus is probably able to tolerate the stress of labor should it begin within 1 week, and that there is a low risk for intrauterine death due to hypoxia.

Interventions

Pretest Patient Care

Explain the reason for testing.
Follow guidelines in Chapter 1 for safe, effective, informed pretest care.

Posttest Patient Care

Review test results; report and record findings. Modify the nursing care plan as needed. Explain possible need for follow-up testing.
Follow guidelines in Chapter 1 for safe, effective, informed posttest care.

• Oxytocin Challenge Test (OCT); Nipple Stimulation Test; Breast Stimulation Test (BST)

These tests are performed after 28 weeks of gestation, when a nonstress test (NST) is nonreactive or a CST is either positive or unsatisfactory. Continuous external fetal monitoring is used. Because uterine contractions are associated with a reduction in uteroplacental blood flow, spontaneous, oxytocin-induced, or nipple stimulation-induced contractions with a frequency of three in 10 minutes may be used clinically as a standard test of fetoplacental respiratory function. Stress of this magnitude has been proved clinically useful in separating fetuses with suboptimal oxygen reserve from those with adequate reserve (the vast majority), and it does not significantly compromise the normal fetus.

Reference Values

Normal

The test result is negative if there are no late decelerations associated with at least three contractions within a 10-minute period.

A normal (negative) result is reassuring; it implies that placental reserve is sufficient should labor begin within 1 week. There is a false-normal rate of 1 to 2 per 1000 pregnancies. The procedure is usually repeated weekly.

Procedure

Be aware that contractions may occur spontaneously, after breast stimulation test (BST), or after administration of intravenous oxytocin to produce three good-quality contractions of at least 40 seconds’ duration each within a 10-minute period.
Monitor the FHR for reaction to this stress.

Clinical Implications

The presence of consistent and persistent late decelerations with most uterine contractions, regardless of their frequency, constitutes a positive (abnormal) OCT result. This is often associated with decreased baseline FHR variability, a lack of FHR acceleration with fetal movement, and a fetus at risk for intrauterine asphyxia.
The results of OCT can be categorized as follows:
- Negative: no late decelerations
- Positive: late decelerations following 50% or more of contractions, even if the frequency of the contractions is fewer than three in 10 minutes
- Equivocal: intermittent, late, or variable decelerations
- Unsatisfactory: fewer than three contractions within 10 minutes or a poor-quality tracing

Interventions

Pretest Patient Care

Explain test purpose and procedure.
Follow guidelines in Chapter 1 for safe, effective, informed pretest care.

Posttest Patient Care

Review test results; report and record findings. Modify the nursing care plan as needed. Counsel the patient accordingly about the meaning of fetal heart activity and movement.
Follow guidelines in Chapter 1 for safe, effective, informed posttest care.

• Nonstress Test (NST)

The NST can be performed in a hospital, a clinic, or possibly a home care setting. The NST is a screening test and can be safely done once a week. Test results reflect the functions of the fetal brainstem, autonomic nervous system, and heart.

Reference Values

Normal

Negative result: reactive NST

ACOG criteria for a reactive NST (with or without stimulation): two or more accelerations of FHR, peaking at least 15 beats/minute above the baseline FHR and lasting at least 15 seconds from baseline to baseline, within a 20-minute period

Procedure

Assess maternal vital signs, last oral intake (including medicines or street drugs), smoking history, and fetal movement history.
Apply external fetal monitor with the woman positioned off her back in lateral tilt position.
After 26 weeks of gestation, this assessment of the FHR pattern without contractions evaluates fetal oxygenation. Fetal movement may or may not be identified by the woman during the test. If gestation is <26 to 30 weeks, the fetus may not meet the criteria for a reactive NST yet may be a healthy fetus.
It is no longer recommended to feed the woman before this test because of the possibility of emergency delivery. Glucose does not alter the FHR pattern.
If unable to elicit FHR accelerations during NST, acoustic stimulation of a fetus that is not acidotic may evoke FHR accelerations that seem to predict fetal well-being. An artificial larynx (vibroacoustic stimulator) that is designed for fetal monitoring is placed on the patient’s abdomen, and the stimulus is activated for 1 to 2 seconds. The stimulus may be repeated up to three times for gradually increased durations up to 3 seconds to bring about FHR accelerations. Use of acoustic stimulation can shorten the time needed for reactive NST and reduce false-positive test results.

Tags: Fischbach's A Manual of Laboratory and Diagnostic Tests

Sep 25, 2018 | Posted by drzezo in PATHOLOGY & LABORATORY MEDICINE | Comments Off

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