Pregnancy: Physiologic Changes and Laboratory Values

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By Christine Cartwright, RN, MSN

LEARNING OBJECTIVES

Upon completion of this course, you will be able to:

• Identify abnormal laboratory results for a variety of pathologic problems during pregnancy.
• Describe normal and abnormal physiologic changes of pregnancy.

CARDIOVASCULAR AND HEMATOLOGIC CHANGES

Normal and Expected Changes

Maternal circulation changes during pregnancy to accommodate an increase in blood volume of up to 50%. Because of the increase in workload, upon auscultation of the heart you may hear a split first sound, a systolic murmur, or even a third heart sound. The increased blood volume peaks in the third trimester and returns to pre-pregnant state somewhere around 2 to 3 weeks postpartum (Blackburn, 2008).

The increased blood supply includes a 45% to 50% increase in plasma volume and 20% to 30% increase in red blood cells. Since these percentages are not equal, the subsequent hemoglobin (HGB)/hematocrit (HCT) will reflect a normal physiologic anemia of pregnancy. The HCT will appear to fall as the volume increases more than the packed cell count.

During pregnancy, the systemic vascular resistance (SVR) of the blood vessels lowers due to increased levels of hormones. This decreasing SVR is an expected result of the increasing progesterone and prostaglandin levels, which relax smooth muscle, producing vasodilatation.

As a result of the increased volume and decreased resistance, cardiac output rises. Therefore, you normally will see a lowering of the blood pressure, especially in the second trimester. This sometimes causes dizziness or feeling faint in women as they rise to standing during the second trimester. Their pressure should stabilize and approach pre-pregnancy numbers by the third trimester. An abnormal rise in blood pressure could be an indication of preeclampsia, which involves multiple systems of the patient. (Keep this expected decrease in SVR in mind when you read the preeclampsia section later in this course.)

White blood cell (WBC) counts, especially neutrophils, increase naturally during pregnancy. During active labor there may be another normal increase, even in the absence of infection. In nonpregnant patients a normal WBC count is somewhere between 5 and 10 (5,000–10,000 cells/mm³), but for pregnancy those normal values can be between 6 and 16 in the third trimester and may reach 20 to 30 in labor and early postpartum. When evaluating for infection, therefore, you need to look for other clinical indicators—such as increased temperature, bacteriuria, WBC in urine, uterine tenderness, and fetal tachycardia—and document them.

NORMAL HEMATOLOGIC VALUES

	Nonpregnant	Pregnant
Hemoglobin (HGB)	12–16 g/dl	11.5–15 g/dl
Hematocrit (HCT)	36–48	32–36.5
Red blood cells (RBC)	4–5.36	no change
White blood cells (WBC)	4–10.6	6–20

Pregnancy is typically considered a hypercoagulable state—meaning that most pregnant women clot more readily than normal and are predisposed to deep-vein thrombosis or other clot-related conditions. During pregnancy there is an increase in certain factors in the clotting cascade due to normal adaptation (see table). Platelets are usually unchanged in pregnancy, and increased levels of platelets are rare. Normal levels should be 140,000 to 300,000 per mm³.

NORMAL LEVELS FOR CLOTTING FACTORS

	Nonpregnant	Pregnant
Factor V	50–150	Increased
Protein S	61–161	30–70
Antithrombin	80–130	Should remain stable (a decrease indicates increased thrombosis risk)

Abnormal Changes

The following changes represent abnormal findings:

• Diastolic murmur or very loud systolic murmur
• Rising blood pressure before the 20th week (see “Preeclampsia” below)
• WBC levels above 20–30,000 cells/mm³, or shifts in the differential, especially a larger percentage of bands/stabs appearing, or a sharp increase in WBC level
• A true anemia: HGB <11.5 g/dl and HCT <30%

ANEMIA

To evaluate the genesis of anemia, the following laboratory values are taken into consideration.

If anemia is from low iron, you will see the following on the smear results:

• Microcytic/hypochromic cells
• Serum ferritin <11 ng/ml (mg/L)
• Transferrin saturation level <16%
• Serum iron <30 mcg/dl
• Mean corpuscular hemoglobin concentration (MCHC) <30 g/dl
• Iron-binding capacity increased (>400 mcg/dl)

If anemia is from folic acid deficiency, you will see:

• Enlarged red blood cells, meaning the MCHC will be increased (higher); this is directly opposite of iron-deficiency anemia

INCREASED CLOTTING

Although all women experience some expected changes in clotting, there are defective clotting conditions that greatly affect the outcomes of some pregnancies.

Patients with histories of multiple, unexplained miscarriages or a history of deep-vein thrombosis are often worked up for clotting conditions, which include antiphospholipid antibodies, antithrombin deficiencies, factor V Leiden mutations, and factors C and S deficiencies. Abnormal increased clotting arises either from abnormal functioning of factors that assist in clotting or abnormal functioning of factors that control or slow clotting.

Abnormal Clotting Conditions

Antithrombins (AT) are important regulators of the coagulation cascade because they inhibit thrombin (clot) formation. Antithrombin deficiencies can be inherited or pregnancy-induced. Antithrombins work mainly to inhibit factor Xa and factor IXa, so a deficiency means increased risk of clotting. Of note: Heparin enhances the effect of antithrombin III—leading to more effective anti-clotting action. Since heparin enhances AT III, if this factor is not present, heparin may not be an effective anticoagulant for therapy.

Factor V Leiden mutation is the name of a specific mutation that results in thrombophilia, or an increased tendency to form abnormal blood clots in blood vessels. People who have the factor V Leiden mutation are at somewhat higher-than-average risk for a clot to form in veins such as the deep veins of the legs (deep-vein thrombosis) or for a clot that travels through the bloodstream and lodges in the lungs (pulmonary embolism). In a woman where this mutation is present, clots may form within the placenta, cutting off nutrition and oxygen to the developing fetus.

Protein S and protein C are important inhibitors of the coagulation cascade, and a deficiency increases the risk of clots. These protein deficiencies are usually genetic. Protein C helps to degrade the prothrombotic factor VIII (von Willebrand factor). Protein S is a co-factor to protein C.

Antiphospholipid Syndrome (APS). According to ACOG (2007): “The lupus anticoagulant and anticardiolipin antibodies, the most widely accepted antibodies of clinical use, have been associated with a variety of medical problems, including arterial and venous thromboses, autoimmune thrombocytopenia, and fetal loss (2–7). In addition to fetal loss, several obstetric complications have been associated with antiphospholipid antibodies, including preeclampsia, intrauterine growth restriction, placental insufficiency, and preterm delivery (8, 9).”

Black (2006) writes the following: “In APS, antiphospholipid antibodies consist of lupus anticoagulant, anticardiolipin antibodies, and antibodies that recognize specific target molecules such as beta2 glycoprotein I, prothrombin, protein C, protein S, and annexin V (Leiden). The exact mechanism in which these antibodies cause or promote thrombosis is not known.”

Laboratory Tests

A physician may order the following diagnostic and assessment laboratory tests in evaluating a patient with frequent miscarriages or history of clotting:

• Antiphospholipid syndrome: medium-to-high positive IgG or IgM anticardiolipin antibodies or detection of lupus anticoagulant; APTT, KCT, dRVVT, and ELISAs for detection of cardiolipin antibodies.
• Thrombosis: laboratories and panels checking for mutations and various clotting factors such as ANT, protein C, protein S, dRVVT, LAPTT, CLABORATORY, HOMO, F5LDNA, F2MUT, HINTRP, and LINTRP.

Before starting therapy for clots or deep-vein thrombosis, several panels may be drawn to assess the patient’s status or to support a diagnosis of thrombosis. Ongoing laboratory tests will monitor for therapeutic goals. Therapy-monitoring laboratory tests include:

• PTT (partial thromboblastin time; looks at the intrinsicpathway) and PT/INR (prothrombin time/international normalized ratio; the extrinsicpathway): both monitor the effects of anti-coagulation therapy.
  • Normal PTT is 23–37 seconds. The PTT used to be the standard monitoring laboratory test for heparin therapy. Heparin therapy is now monitored by measuring the unfractionated heparin assay laboratory result (anti-Xa activity), not the PTT.
  • Normal PT is 11–13 seconds, and normal INR is 0.8–1.2 IU (international units). The goal is to increase INR to 2–3.5 IU. Coumadin is used on the extrinsic pathway. (Note: Those using Coumadin should avoid foods with vitamin K due to their effect on the extrinsic pathway. Pregnant women are not given Coumadin until after delivery.)
• Anti-Xa test is the most accurate assay for monitoring unfractionated heparin therapy and is the only assay available for monitoring low-molecular-weight heparin (Lovenox).

MONITORING HEPARIN THERAPY

Type	Therapeutic	Prophylactic
Note: All values are given in anti-Xa units/mL plasma.
Unfractionated	0.3–0.7	0.1–0.4
Low molecular-weight	0.5–1.0	0.2–0.4

INCREASED BLEEDING

Patients at increased risk for bleeding are those lacking clotting factors or platelets, or whose clotting factors do not function properly.

Low platelets may result from: HELLP (hemolysis, elevated liver enzymes, and low platelets); ITP (idiopathic thrombocytopenia purpura); TTP (thrombotic thrombocytopenia); or HUS (hemolytic uremic syndrome). Platelets may also be lowered due to multiple microclots or for unknown reasons. Platelet levels below 100,000 per mm³ need to be monitored carefully. Continued declining levels are suspicious for micro-clotting conditions and disseminated intravascular coagulation (DIC).

As clots form and break down, clotting factors and fibrinolytic factors are used up. The presence of fibrin split products and an elevated D-dimer indicate that clots are being broken down in the body. Disseminated intravascular coagulation (DIC) occurs if the process is taking place too rapidly for the body to replace the factors used. Laboratory values will show that clotting has taken place, but in DIC there are signs that the process has gotten out of hand, such as bleeding from intravenous (IV) or injection sites, hemorrhage, and cardiovascular collapse.

VALUES FOR DISSEMINATED INTRAVASCULAR COAGULATION

	Normal	DIC
*Also called fibrin degradation products (FSP or FDP) when clots are broken down. **D-dimer is made when clots are broken down.
Fibrinogen (Factor I)	170–470 mg/dl	Decreased or falling
Platelets	140,000–300,000 per mm3	<100,000 per mm3
Fibrin split products*	<10 mcg/ml	Increased >10mcg/ml
D-dimer**	0–0.5 mcg/ml	>0.5 mcg/ml

RENAL CHANGES

Normal and Expected Changes

The renal system undergoes many changes in pregnancy to accommodate increased metabolic and circulatory requirements. The system now clears the body of both maternal and fetal waste and is affected by the increased blood volume and lowered systemic vascular resistance. As previously mentioned, progesterone has a relaxing effect on vascular tissue, thus enhancing the renal blood flow and function. The increased plasma flow into the renal system causes the glomerular filtration rate (GFR) to rise dramatically.

Renal clearance of many substances is generally elevated in pregnancy, causing lower-than-usual serum levels of the renal markers blood-urea-nitrogen (BUN) and creatinine. Increased filtration does not mean enhanced reabsorption, however. The increase in glucose load during pregnancy is often spilled into the urine and not reabsorbed. Therefore, spillage of some glucose in pregnancy is not always indicative of pathology This may lead to the pregnant woman developing urinary tract infections (UTIs).

The anatomy of the pregnant uterus causes changes in the location and pressure of other internal organs. The bladder becomes slightly concave and is displaced forward and upward. The uterus causes the ureters to become dilated and more tortuous, especially the right ureter. Detectable hydronephrosis or hydroureter during pregnancy is considered normal and may take 3 to 4 months post delivery to fully resolve.

NORMAL VALUES FOR RENAL FUNCTION

	Nonpregnant	Pregnant
Serum creatinine	0.6–1.2 mg/dl	0.53–0.9 mg/dl i
Serum BUN	9–11 mg/dl	8–10 mg/dl i
Serum uric acid	4.5–5.8 mg/dl	2–5.8 mg/dl
Urine Cr clearance	90–130 mL/min	150–200 mL/min
Urine uric acid	250–750 mg/24 hr	Increases
Urine glucose	60–115 mg/dl	Increases

Abnormal Changes

Abnormal values include:

• 24-hour urinary protein >300 mg
• Serum creatinine rising (indicates renal damage, possibly from preeclampsia)
• WBC >5 from urine sample (high-powered microscopic field)
• Bacteria >20 in urine sample (centrifuged urinalysis) (indicates UTI)

GASTROINTESTINAL CHANGES

Normal and Expected Changes

Increased progesterone levels also affect the gastrointestinal (GI) system of the pregnant woman. General tone, lower esophageal spincter tone, and motility are decreased. This predisposes the woman to increased incidence of reflux (heartburn) and constipation. As the gravid uterus displaces the internal organs, this incidence increases.

The liver increases its production of lipids and cholesterol. This change, combined with delayed gallbladder contraction (due to progesterone-influenced relaxation), may lead to increased gallstone formation (expected) or gallbladder disease (abnormal). The liver also plays a role in the production of the clotting factors previously discussed.

In addition to increased production of lipids and certain clotting factors, some enzymes found within the liver are also increased without indicating pathology. It is important to distinguish a normal rise in these levels from a pathologic change caused by organ damage or destruction arising, for example, from preeclampsia or hepatitis. In preeclampsia, microclots in the liver and capsular edema are danger signs, and if clotting factors become affected, the patient is at a high risk for disseminated intravascular coagulation (DIC). Diagnoses are not based upon a single abnormal value.

NORMAL HEPATIC VALUES

Liver Enzymes	Nonpregnant	Pregnant
Alanine transaminase (ALT)	3–78 U/L	Unchanged
Aspartate aminotransferase (AST)	3–70 U/L	Unchanged
Alkaline phosphatase (ALP)	20–145 ImU/ml	> up to 2–4 times
Lactate dihydrogenase (LDH)	300–650 U/L	Upper end of normal to 700 U/L

Abnormal Changes: Preeclampsia

Preeclampsia is a condition in which high blood pressure and protein in the urine develop in the late second or third trimester of pregnancy. Preeclampsia potentially affects every organ of the pregnant patient. Microclots develop within the vascular tissue, and their effects are typically seen according to which organ develops the clots.

DIAGNOSING PREECLAMPSIA

According to American College of Obstetricians and Gynecologists (2008), preeclampsia is diagnosed by:

• Blood pressure of 140 mm Hg systolic or higher; or 90 mm Hg diastolic or higher that occurs after 20 weeks of gestation in a woman with previously normal blood pressure
• Proteinuria, defined as urinary excretion of 0.3 g protein or higher in a 24-hour urine specimen

Severe preeclampsia is diagnosed if one or more of the following are present:

• Blood pressure of 160 mm Hg systolic or higher; or 110 mm Hg diastolic or higher on two occasions at least 6 hours apart while the patient is on bed rest
• Proteinuria of 5 g or higher in a 24-hour urine specimen or 3 g or higher on two random urine samples collected at least 4 hours apart
• Oliguria of less than 500 mL in 24 hours
• Cerebral or visual disturbances
• Pulmonary edema or cyanosis
• Epigastric or right upper-quadrant pain
• Impaired liver function
• Thrombocytopenia
• Fetal growth restriction

ASSESSING FOR COMPLICATIONS AND TREATMENTS

The following tests, signs, and symptoms are used to assess for complications or treatments of preeclampsia:

• DIC panel: A patient in severe preeclampsia may develop HELLP and/or DIC. (See DIC in the “Increased Bleeding” section above and HELLP in the “Pregnancy-Specific Diagnoses” section below.)
• Magnesium level: Preeclamptic patients on IV magnesium sulfate may have laboratory values drawn to establish therapeutic goals.
  • A normal magnesium level in an unsupplemented patient is 1.5–2.5 mg/dl (mEq/L).
  • The goal is 4–7mg/dl (mEq/L) for patients receiving IV magnesium therapy.
  • Magnesium levels >9 mg/dL (mEq/L) are potentially life threatening.
• Liver function panel: Used to assess whether preeclampsia is causing liver organ damage and/or HELLP syndrome. Assessment of the patient will reveal abdominal pain and tenderness in the upper-right quadrant, which may be caused by microclots and lead to liver capsular edema.
• 24-hour urine protein: Assesses whether kidney function is being affected by vascular spasming and microclotting found with preeclampsia. A level of >300 mg is indicative of mild preeclampsia; a level of >5 gm is indicative of severe preeclampsia. A patient with falling urinary output is especially at risk for magnesium overdose if clots from preeclamptic processess are affecting the renal blood flow.
• Neurological signs: Edema from leaking vascular tissue puts pressure on the optic nerve, and patients may report a distortion in their vision. Edema in the brain can cause severe headache and potentially life-threatening seizures.

TRAUMA IN PREGNANCY

A pregnant woman being evaluated after a trauma-related event (e.g., car wreck, fall, domestic violence) requires immediate, simultaneous assessment of both maternal and fetal well-being. The woman should undergo the standard post-trauma focused history and physical exam to determine whether she has sustained any injuries.

To assess the fetus’s heath, the pregnant woman should be asked immediately about:

• Leakage of blood and/or fluid from her vagina
• Any traumatic force directed at her abdomen or new-onset abdominal pain
• Changes in or absence of previous fetal movements (if indicated by gestational age)

Further assessment of fetal well-being can be done by fetal monitoring, ultrasound evaluation, and maternal blood work.

After establishing immediate safety, continued assessment is aimed at evaluating safety and observing for placental abruption, which is a risk after traumatic abdominal events.

Bleeding

Maternal bleeding may be indicated by falling hemoglobin and hematocrit or abnormal CBC (complete blood count); signs and symptoms of placental abruption, which can be partial and/or hidden; and signs and symptoms of DIC from abruption or alterations in the normal clotting cascade.

Fetal bleeding may be indicated by electronic fetal monitoring changes such as tachycardia followed by bradycardia, absent variability, decelerations, and/or sinusoidal tracing. A Kleihauer-Betke (KB) screen may be ordered to look for fetal blood cells that have entered maternal circulation; normally there are none.

Domestic Violence

Pregnancy is is a time of increased domestic violence. Signs may include bruises and injuries inconsistent with their explanation, blows or “falls” visible on the abdomen, poor weight gain, and frequently missed prenatal appointments. Every woman should be screened prenatally for risk of domestic violence and counseled on safety issues. Names and numbers of local agencies should be made available to the woman should she need help escaping from violence. Screening should be done in private if at all possible, as the woman may not feel free to admit to danger in front of her family or the abuser. To establish privacy, it is sometimes possible to resort to bathroom facilities.

ULTRASOUND DIAGNOSTICS

Ultrasound is an imaging technique that uses high-frequency sound waves reflecting off internal organs to create images. It has become ubiquitous as a diagnostic tool during pregnancy. The provider uses a bedside scan or orders more detailed exams by an expert ultrasound technician. Ultrasound is commonly used to assess fetal growth, development, and well-being. Some of the more common tests are described below.

BPP (Biophysical Profile)

The BPP evaluates several parameters. The fetus is given a score of either 0 (not meeting criteria) or 2 (meeting criteria) in each area. A perfect score of 10 indicates that all criteria are met. If the fetal heart rate tracing (nonstress test, or NST) is not obtained as part of the test, then the perfect score is 8. Areas assessed are:

• Fetal tone: assesses for one or more episodes of extension of fetal extremities with return to flexion
• Breathing movements: one of more episodes of rhythmic fetal breathing movements of at least 30 seconds in duration
• Amniotic fluid: largest area of fluid is greater than 2 cm without containing loops of the umbilical cord, or a calculated amniotic fluid index (AFI) between 8 and 18
• Fetal movement: movements of the arms, legs, or body observed
• Reactive heart rate tracing: NST that is reactive

NST (Nonstress Test)

The nonstress test is completed by placing the patient on an electronic fetal monitor, which uses ultrasound waves to track the fetal heart rate and a tocodynamometer to trace uterine activity. A reactive (good) tracing looks for:

• Normal heart rate baseline: depending on gestational age, somewhere between 110 and 160
• Accelerations: increases in the fetal heart rate above the baseline. In a fetus of >32 weeks’ gestation, in a 20-minute period at least 2 accelarations of at least 15 beats above the baseline for at least 15 seconds each time. In a fetus of <32 weeks’ gestation, the accelerations may only be 10 beats for 10 seconds.
• Variability: of the fetal heart rate between 2 and 25 beats per minute. A flat fetal heart rate baseline or one that undulates (sinusoidal tracing) are signs of potential fetal compromise.
• Decelerations: no decelerations below the fetal heart rate baseline

Umbilical Artery Flow Velocity

Fetal and placental blood flow is measured by Doppler ultrasound studies. Abnormal fetal circulation is shown by absent or reversed end diastolic flow velocity in the fetal umbilical artery or aorta, which suggests intrauterine fetal compromise. Absent end diastolic flow velocity is thought to result from increased downstream vascular resistance. This has been associated with an increased risk of necrotizing enterocolitis, cerebral hemorrhage, and neonatal morbidity.

PREGNANCY-SPECIFIC DIAGNOSES

Other common tests for the obstetric population include the following:

Fetal Fibronectin (fFn) Test

Fetal fibronectin (fFn) is found in cervicovaginal fluid until about 22 weeks’ gestation. It then is absent until it reappears within 2 weeks of term or preterm delivery. Serial tests done on a woman experiencing preterm contractions or labor are used as a predictor of preterm delivery. A positive fFn >50 in a singleton pregnancy is a moderate predictor that delivery will occur within 1 to 2 weeks.

Fetal Maturity Test

The lecithin/sphingomyelin (L/S) ratio is a test of amniotic fluid obtained through amniocentesis to determine fetal lung maturity. A ratio of 2 or greater in the presence of phosphatidyl glycerol (PG) is indicative of sufficient lung surfactant for prevention of neonatal respiratory distress syndrome (RDS). A mature fetal lung test before 39 weeks of gestation, in the absence of appropriate clinical circumstances, is not an indication for delivery because it does not mean the baby will not experience breathing difficulties after birth (ACOG, 2009).

Fetal Anomalies or Fetal Compromise

A patient who has a suspicious fetal heart rate (FHR) tracing on early monitoring (e.g., sinusoidal tracing, bradycardia, tachycardia) or a patient who presents with signs of a viral illness, abnormal ultrasounds, or an unexpected delivery of an infant with anomalies may prompt the provider to order a TORCH panel. The panel, named for the mnemonic “TORCH” (see below), measures the immune system status of the mother’s exposure to pathogens known to cause fetal anomalies or compromise.

TORCH PANEL

Toxoplasmosis	Toxoplasmosis can cause eye deformity, eye infections, and mental retardation by invading brain tissue.
Other	This includes any additional physician-ordered tests to screen for other infectious diseases.
Rubella	Infants born with rubella may show signs of heart defects, retarded growth, ocular defects, or pneumonia at birth. They may also develop problems later in childhood, including autism, hearing loss, brain involvement, immune system disorders, or thyroid disease. (Postpartum mothers may be immunized if their prenatal results were rubella non-immune or equivocal in order to protect future pregnancies.)
Cytomegalovirus (CMV)	Mothers exposed to CMV may have infants who suffer from hearing loss (15%) or mental retardation (30%). Newborns who acquire CMV during the birth process or shortly after birth may develop pneumonia, hepatitis, or various blood disorders.
Herpes	Disseminated herpes infections attack the liver, adrenal glands, and other body organs of the infant. Without treatment, the mortality rate is as high as 80%.

CONCLUSION

In caring for pregnant women and their unborn infants, it is important for the healthcare provider to understand the normal physiologic changes that occur during pregnancy. The provider can utilize various laboratory tests and diagnostic tools to assess the magnitude of these changes and to identify abnormal changes.