Physiologic Adaptation to Pregnancy Case File
Eugene C. Toy, MD, Konrad P. Harms, MD, Keith O. Reeves, MD, Cristo Papasakelariou, MD, FACOG
Case 1
A 22-year-old primigravida is seen in your office at 28 weeks’ gestation for a routine prenatal visit. Her pregnancy has been uneventful to date. She expresses her concern about several moles on her back, which have been enlarging over the past several weeks and for increasing difficulty with constipation. She also relates less energy to complete her job-related responsibilities at work and feels it may be related to the 18-lb weight gain she has experienced since becoming pregnant. She also has noted some gradual shortness of breath over the past 4 to 6 weeks especially when she climbs the three flights of stairs to her office at work. She wears contact lenses and relates that her visual acuity is not as good as before she became pregnant.
Physical examination reveals her height to be 5 ft 8 in, her weight to be 158 lb, and her blood pressure to be 90/60 mm Hg. She has several pigmented nevi over her shoulders and back. She has a darkened line on her skin from her xiphoid process to her symphysis. Examination of her heart reveals a 2/6 systolic ejection murmur heard best over the second left intercostal space. Her lungs are clear to auscultation and percussion. Abdominal examination reveals a 28 cm fundal height with normal bowel sounds, and she has trace pretibial pitting edema.
Laboratory values reveal a hemoglobin level of 12.0 g/dL and a platelet count of 125,000/mm3. Urinalysis reveals no nitrites or leukocyte esterase, 2+ glucose, and no albuminuria. Fasting metabolic package reveals a sodium of 138 mEq/L (normal 135-145), potassium of 4.6 mEq/L (normal 3.5-5.0), calcium level of 9.2 mg/dL (normal 9.3-10.1), and albumin level of 3.1 g/dL (normal 3.3-4.0). Fasting glucose level was 65 mg%.
➤ Does this patient have any metabolic or physiologic changes not associated with a normal pregnancy?
➤ What is your next step in her evaluation?
ANSWERS TO CASE 1:
Physiologic Adaptation to Pregnancy
Summary: This is a 22-year-old primigravida who is 28 weeks’ pregnant. She has the following complaints: enlarging skin moles, lack of energy, weight gain, mild dyspnea on exertion, and blurred vision. Your significant clinical findings are BP 90/60 mm Hg, several pigmented nevi, a grade 2/6 systolic ejection murmur, a fundal height 28 cm, and trace pretibial pitting edema. The significant lab results are platelet count of 125,000/mm3, 2+ glucosuria and negative albuminuria on urinalysis, and a fasting serum glucose of 65 mg/dL.
➤ Metabolic or physiologic changes not associated with a normal pregnancy: No, all the symptoms, signs, and laboratory values are consistent with the physiologic adaptations of pregnancy.
➤ Next step in evaluation: The following are indicated in this patient: (1) Careful dermatological evaluation of her pigmented nevi to rule out the presence of malignant melanoma. (2) Thyroid function studies should be drawn to evaluate her “lack of energy,” and (3) This patient should be advised to report any worsening of her shortness of breath.
ANALYSIS
Objectives
- Be familiar with the physiologic adaptations associated with a normal pregnancy.
- Be able to differentiate between certain signs and symptoms that can be common to both disease processes and to physiologic adaptations of pregnancy.
- Learn to counsel patients of signs and symptoms to expect during a normal pregnancy.
US Preventive Services Task Force Study Quality
Level I. Evidence obtained from at least one properly designed randomized controlled trial.
Level II-1. Evidence obtained from well-designed controlled trials without randomization.
Level II-2. Evidence obtained from well-designed cohort or case-control analytic studies, preferably from more than one center or research group.
Level II-3. Evidence obtained from multiple time series with or without the intervention. Dramatic results in uncontrolled experiments could also be regarded as this type of evidence.
Level III. Opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees.
Considerations
This 22-year-old primigravida has presented to your office at 28 weeks’ gestation with signs and symptoms that commonly occur in pregnancy but that may be the evidence of disease. Initial evaluation includes differentiating normal from pathologic processes, reassuring the gravida about those which are normal, and educating her to discern the difference. Thus, an awareness of the physiologic changes of pregnancy such as the increase in cardiac output, intravascular volume, glomerular filtration rate are essential in the interpretation of the history, physical, and lab findings in pregnancy.
APPROACH TO
Physiologic Adaptation to Pregnancy
Skin Changes
Pregnancy produces many changes in the skin that are commonly noted by patients. Increased pigmentation in the skin occurs in over 90% of pregnant women. Areas noted to be commonly involved include the face, the areola of the breast, the linea alba, the axilla, and the genital skin. Melasma gravidarum (the mask of pregnancy) involves the forehead, the cheeks, and the bridge of the nose. Pigmented nevi are also commonly affected.
Melanocyte-stimulating hormone (MSH) is increased in pregnancy. This and other sex steroids may be responsible for the generalized hyperpigmentation seen in pregnancy. This hyperpigmentation seems to be more pronounced in dark-skinned women than in those with fair complexions.
Other changes occur in the skin as a result of vascular engorgement and vessel proliferation. Spider angiomata are particularly common in Caucasian women. These are most commonly seen in the sun-exposed areas of the body. Blushing of the palms and the soles of the feet can be seen. This is transient and resolves postpartum.
Changes are also seen in hair growth. In the immediate postpartum period the percentage of hair follicles in the telogen phase (resting phase) reaches 30% to 40%. This results in hair loss. This loss is transient and resolves spontaneously in around 6 to 12 months.
Striae gravidarum (stretch marks of pregnancy) occur in 50% of all pregnancies. Involving the abdomen, the breast, the buttocks, and the thighs, these are thought to represent linear tears in dermal skin under the influence of estrogen. Striae appear red in the present pregnancy, pale slowly after delivery, and there is no known method of prevention.
Weight Gain
Weight gain in pregnancy has been the subject of great debate for many years. Current recommendations for weight gain in pregnancy should be based on the Institute of Medicine guidelines. These guidelines suggest for the normal woman a weight gain of 25 to 35 lb. For overweight women a weight gain of 15 to 25 lb is more appropriate and for the obese woman a weight gain of 15 lb is suggested. Normal weight is defined by the World Health Organization and the National Institutes of Health as a body mass index (BMI) of 18.9 to 24.9, overweight as a BMI of 25 to 29.9, and obesity as a BMI of 30 or greater.
Cardiovascular Changes
Significant cardiovascular changes occur in the pregnant woman beginning as early as the fifth week of gestation. While most are easily recognizable, many can be mistaken for cardiac disease.
During pregnancy, the heart is displaced upward and to the left from changes in the shape of the rib cage and from superior displacement of the diaphragm. It also rotates on its long axis. This moving of the apex of the heart in a lateral fashion can be misperceived on chest x-ray as representing cardiomegaly. Other changes in the structure of the heart resemble those found as a result of physical training. Physiologic myocardial hypertrophy is a result of expanded blood volume, peaks at 30 to 34 weeks’ gestation, and reverses itself after the pregnancy is over.
Cardiac output (CO) is the product of stroke volume (SV) and heart rate (HR). During pregnancy CO is increased tremendously. By 5 weeks gestation it rises to 10 % over prepregnancy levels and by 34 weeks peaks at some 50% above those levels seen prior to pregnancy. Heart rate begins to rise in the first trimester and continues to rise until it peaks at 15 to 20 beats above normal at 34 weeks. Cardiac output varies greatly with maternal position. It is highest in the knee-chest and lateral recumbent positions and lowest in the supine position (some 30% lower). Late in pregnancy because of the development of a dilated paravertebral collateral circulation, venous return from the lower extremities is maintained in the supine position even when the vena cava is completely occluded by the pregnant uterus. In spite of this, 5% to 10% of pregnant women show signs of “supine hypotension,” and experience dizziness, nausea, and even syncope when supine. This may represent a failure of those women to develop an adequate paravertebral collateral system.
Systemic vascular resistance (SVR) diminishes in early pregnancy. Reaching its nadir at mid-pregnancy, it gradually rises until term but even then remains approximately 20% lower than prior to pregnancy. This phenomenon is thought to be a direct effect of progesterone on the smooth muscle in the capillary beds, and increased levels of circulating nitric oxide and cyclic adenosine monophosphate also play a role. Since the pregnant woman’s blood pressure is a product of her cardiac output and SVR, we see a similar change in blood pressure throughout pregnancy.
Venous blood pressure rises in the lower extremities gradually during pregnancy. Femoral venous pressure rises from 10 cm H2O to 25 cm H2O at term. Consequently edema, hemorrhoids, varicose veins, and an increased risk of deep vein thrombosis are common.
It is often difficult to distinguish between signs and symptoms caused by physiologic adaptations to pregnancy and those of true cardiac disease. S1 becomes louder by the end of the first trimester, and 90% of pregnant women will develop an S3. Systolic ejection murmurs along the left sternal border develop in more than 90% of pregnant women, thought to be caused by increased blood flow across the pulmonic and aortic valves.
Dyspnea can be seen in both pregnancy and with cardiac disease. The dyspnea associated with pregnancy usually arises gradually prior to 20 weeks gestation and by the third trimester is present in 75% of pregnancies. While fatigue, orthopnea, syncope, and chest discomfort can be experienced in normal pregnancy, the presence of hemoptysis, angina, increasing orthopnea, or nocturnal dyspnea should be evaluated promptly.
Respiratory System
Because of increased hyperemia and increased estrogen levels the nasopharyngeal mucosa becomes edematous and irritated. Nasal stuffiness, epistaxis, and nasal polyps occur frequently during pregnancy, and resolve spontaneously postpartum.
Due primarily to change in the size and shape of the chest cavity, the following alterations in lung capacities are seen:
- Respiratory rate—Unchanged
- Vital capacity—Unchanged
- Inspiratory capacity—Increased 5% to 10%
- Tidal volume—Increased 30% to 50%
- Inspiratory reserve volume—Unchanged
- Functional residual capacity—Decreased 20%
During pregnancy, increased levels of progesterone cause a state of relative hyperventilation resulting in a chronic respiratory alkalosis. This relatively low pCO2 in the pregnant mother is beneficial in clearing CO2 from the fetal circulation.
Hematologic Changes
Maternal blood volume is comprised of the plasma volume plus the red blood cell mass. This total blood volume begins increasing as early as 6 weeks gestation and plateaus at 30 to 34 weeks of pregnancy, increasing by some 40% to 50% in most gravidas. Plasma volume begins to increase at 10 weeks gestation and plateaus at 30 weeks’ gestation while the red blood cell mass begins increasing at 10 weeks and continues its rise until term. The reasons for these expansions remain unknown. The use of iron supplementation has been shown to enhance the increase in RBC mass from 18% to 30% by term. Since at mid-pregnancy the plasma volume increases more than that of red blood cell mass, there appears a transient physiologic anemia of pregnancy.
A gradual decline in platelets has been observed throughout pregnancy, but 98% of pregnant women will have platelet counts of greater than 116,000/mm3. Values below this should be evaluated for causes of thrombocytopenia.
Renal Changes
Renal plasma flow begins to rise early in pregnancy becoming 75% higher than prior to pregnancy by 16 weeks gestation. Glomerular filtration rate rises as early as 5 to 7 weeks and reaches a level 50% greater than in the nonpregnant female.
The altered mechanism of handling glucose in the proximal tubules during pregnancy remains to be completely understood. Glucose excretion into the urine occurs in most pregnant women. While the nonpregnant female excretes less than 100 mg/d, in pregnancy this can reach 1 to 10 g of glucose per day.
The Eye
Pregnancy affects the eye in two ways. Corneal thickening develops as early as the first trimester and lasts until several weeks postpartum. Pregnant women can perceive this as loss of visual acuity especially those who wear glasses or contact lenses. Intraocular pressure drops by as much as 10% during pregnancy. There appears to be little to no change in visual fields in pregnancy.
Comprehension Questions
1.1 A 25-year-old G3P2A0 patient presents complaining of chest discomfort with usual daily activities. This patient is at 26 weeks’ gestation and as part of your workup a chest x-ray is read as consistent with cardiomegaly. Which of the following is the best diagnostic test to rule out congestive heart failure?
A. ECG with rhythm strip
B. MRI of the chest cavity
C. Echocardiography evaluation
D. Arterial blood gases
1.2 A 36-year-old woman at 34 weeks’ gestation presents for her routine prenatal visit. Her urine dip for glucose is noted to be 4+. Of note an O’Sullivan test (1-h GTT) done at 28 weeks was returned as 110 mg/dL. Which of the following is the most appropriate course of action?
A. Reassure patient that this is a normal occurrence in pregnancy and no further evaluation is necessary.
B. Random finger stick blood sugar to assure euglycemic state.
C. Repeat O’Sullivan.
D. Proceed to a 3-hour GTT.
1.3 A 36-year-old G4P3A0 patient presents at 30 weeks’ gestation for her routine prenatal visit. Her prenatal course has been unremarkable up to the present. Her BP is 110/65 mm Hg, and her urine is negative for both protein and glucose. She mentions that she has noticed blurred vision for the past few weeks. She has worn contact lenses for several years and has an appointment to have her eyes checked. On gross evaluation of her visual fields they appear intact and symmetrical. Which of the following is the most appropriate advice for this patient?
A. Proceed with ophthalmologic evaluation and have her prescriptions updated on her contact lenses.
B. Proceed with ophthalmologic evaluation to assure that visual fields are intact but delay changes in her lenses until after the puerperium.
C. Ignore all changes in visual acuity or visual field changes as these are normal for pregnancy.
D. In the absence of headaches visual change can be ignored.
ANSWERS
1.1 C. In pregnancy the heart is displaced up and to the left. It also rotates on its long axis to the left. On x-ray this can be confused with cardiomegaly. This should be evaluated with an echocardiogram, especially if the patient is complaining of dyspnea or orthopnea.
1.2 B. Although the alteration in glucose handling in the proximal tubules remains to be accurately understood, glucosuria is common in the gravid female. The nonpregnant female excretes less than 100 mg/d. In pregnancy 90% of women with normal blood sugars will excrete up to 10 g per day.
1.3 B. Because of thickening of the cornea in pregnancy decreased visual acuity can occur. Eye testing is best done in the nonpregnant state. The presence of decreased visual fields, however, deserves evaluation.
Clinical Pearls
See US Preventative Services Task Force Study Quality levels of evidence
➤ Cardiac output increases by almost 50% during pregnancy. It is position dependent and actually falls in the supine and standing positions (Level II-3).
➤ Pregnancy causes a chronic respiratory alkalosis.The resulting decrease in maternal pCO2 promotes the clearing of CO2 from the fetal circulation (Level II-3).
➤ Though not completely understood, glucosuria is common in pregnant women even with normal blood sugars (Level II-3).
➤ Two common effects of pregnancy on the eye are corneal thickening and decreased intraocular pressure (Level II-3).
REFERENCES
1. Bernstein I, Zeigler W, Badger G. Plasma volume expansion in early pregnancy. Obstet gynecol. 2001;97:669.
2. Bhagwat A, Engel P. Heart disease and pregnancy. Cardiol Clin. 1995;13:163.
3. Davison J, Hytten F. The effect of pregnancy on the renal handling of glucose. Br J Obstet Gynaecol. 1975;82:374.
4. Davison J, Noble F. Glomerular filtration during and after pregnancy. J Obstet Gynaecol Br Commonw. 1974;81:588.
5. Dinn R, Harris A, Marcus P. Ocular changes in pregnancy. Graefes Arch Clin Exp Ophthalmol. 2003;58:137.
6. Duvekot J, Peeters L. Maternal cardiovascular hemodynamic adaptation to pregnancy. Obstet Gynecol surv. 1994;49:S1.
7. MacGillivray I, Rose G, Rowe B. Blood pressure survey in pregnancy. Clin Sci. 1969;37:395.
8. O’Brien JR. Platelet count in normal pregnancy. J Clin Patho. 1976;29:174.
9. O’Rourke R, Ewy G, Marcus F, et al. Cardiac auscultation in pregnancy. Med Ann D C. 1970;39:92.
10. Parmley T, O’Brien T. Skin changes during pregnancy. Clin Obstet Gynecol. 1990;33:713.
11. Schatz M, Zeiger R. Diagnosis and management of rhinitis during pregnancy. Allergy Proc. 1988;9:545. A clinical approach to the cold symptoms of pregnancy
12. Theunissen I, Parer J. Fluid and electrolytes in pregnancy. Clin Obstet Gynecol. 1994;37:3. This is a good review of how pregnancy alters fluid and electrolyte handling.
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