Issues in Pregnancy Outcome

Educational Objectives

The goal of this program is to improve the recognition and management of peripartum cardiomyopathy (PPCM) and improve management of patients’concerns during the perinatal period. After hearing and assimilating this program, the clinician will be better able to:

1.   Recognize the risk factors for PPCM.

2.   Describe the clinical presentation and list diagnostic criteria for PPCM.

3.   Participate with cardiologists in the management of patients with PPCM.

4.   Discuss the risk of recurrence and the overall prognosis for patients with PPCM.

5.   Address concerns commonly experienced during the perinatal period.

Faculty Disclosure

In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning committee to disclose relevant financial relationships within the past 12 months that might create any per­sonal conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, the faculty and plan­ning committee reported nothing to disclose.

Acknowledgments

Dr. Martin was recorded at Obstetric Intensive Care: A Simplified Approach, sponsored by Scottsdale Healthcare, and held November 13-15, 2008, in Phoenix, AZ. Ms. Bishop was recorded at Antepartum & Intrapartum Management, sponsored by the University of California, San Francisco, School of Medicine, and held on June 11-13, 2009 in San Francisco, CA.

Peripartum Cardiomyopathy

Stephanie R. Martin, DO, Assistant Director and Section Chair, Pikes Peak Maternal Fetal Medicine, Memo­rial Health System, Colorado Springs, CO

Risk factors: multiparity; advanced maternal age; multifetal gestation; preeclampsia; hypertension; preexisting car­diac disease (however, true peripartum cardiomyopathy occurs independent of preexisting cardiac disease); associ­ation with use of tocolytics questionable; more common in other parts of world, which suggests racial and environmental factors

Mortality: cardiomyopathy (CM) accounts for »8% of pregnancy deaths (increased from 6%); 90% occur in first 2 mo postpartum; most likely in first 6 wk postpartum; 50% during first year after delivery, after which risk for death decreases; 3-fold higher risk for death among black women

Diagnostic criteria: systolic heart failure (HF) within last month of pregnancy or 5 mo postpartum; absence of iden­tifiable cause for HF; echocardiography (ECHO) criteria  —left ventricular (LV) systolic dysfunction; ejection frac­tion (EF) <45%; shortening fraction (SF) measurement of how efficient muscle working to eject blood from heart; enlarged end diastolic volume (EDV) in LV; LV weakens, stops contracting well, and enlarges; low percentage of blood ejected from LV with each heartbeat; early vs peripartum cardiomyopathy (PPCM)  —  data show prognosis worse for women with CM early in pregnancy compared to women with PPCM

Clinical presentation: signs and symptoms  —  similar to those of pregnancy (eg, dyspnea, peripheral edema, orthop­nea, fatigue); high index of suspicion warranted; misdiagnosis (eg, asthma) common, and risk unrecognized; labo­ratory findings  —  complete blood count (CBC) typically normal; liver function tests may be elevated if right HF involved; markers of myocardial infarction (MI) normal unless patient had MI; creatinine may be elevated; electro­cardiography (ECG) nonspecific; atrial fibrillation with significant dilation of left atrium; chest x-rays  —  cardiomegaly and pulmonary edema; plural effusion uncommon; diagnosis made by ECHO; B-type natriuretic peptide (BNP)  —  released by ventricles in response to overdistention and increasing pressure; elevated in propor­tion to degree of overdistention; negative value helpful (if within normal range [<20 pg/mL], safe to conclude HF unlikely); obtain if CM suspected, but ECHO not available; preeclampsia, renal failure, or sepsis may cause false positive; threshold for abnormal value not firmly established

Etiologic theories: not idiopathic CM presenting at pregnancy; 80% of CM in women develops around time of preg­nancy; viral myocarditis  —  coxsackie virus identified in approximately one-third of nonpregnant patients with CM; high levels of autoantibodies and cytokines (indicating inflammation of heart muscle) also found; recruitment of T cells (cytotoxic) results in further cardiac damage; endomyocardial biopsies have high false-negative rate; of non­pregnant patients with autopsy-proven myocarditis, only two-thirds had biopsy-positive myocarditis before death; similar in PPCM (positive biopsies in 62%-76%); pregnant mice more susceptible to enteroviral infections; one Af­rican study related presence of anti-Chlamydia pneumoniae antibiodies with PPCM

Immunologic theories: elevated markers of inflammation related primarily to hyperactive immune response; autoan­tibodies against cardiac tissue proteins demonstrated in PPCM patients (antibodies formed to smooth muscle of uterus may crossreact with smooth muscle of heart); second hypothesis  —“recovered immunity” postpartum leads to pathologic immune reaction to fetal cells sequestered in cardiac tissue

Malnutrition: studies show poor nutrition associated with CM; Nigerian women ingest Kanwa (dried lake salt) 40 days postpartum; low selenium levels suggested (not supported by data)

Other theories: no evidence terbutaline causes CM, but can unmask subclinical cardiac disease; familial etiology ap­parently exception rather than rule

Cardiovascular changes in pregnancy: slight increase in heart rate; significant increase in stroke volume (singleton data; multifetal gestation changes unknown); systemic vascular resistance decreases to accommodate increase in flow and cardiac output; no change in mean arterial pressure; significant increase in oxygen consumption; risk fac­tors predicting adverse cardiac events during pregnancy  —  history of HF (including CM), transient ischemic at­tack, stroke, or arrhythmia; prepregnancy New York Heart Association class III or IV; left heart obstruction; low EF; risk for adverse event with no risk factors, 5%; 25% risk with one risk factor and 75% risk for adverse event with ³2; risk for maternal mortality with PPCM with persistent LV dysfunction same as with pulmonary hyperten­sion or Marfan syndrome

Principles of management: reduce cardiac preload and afterload; improve contractility; b-blockers reduce myocar­dial oxygen requirement (attempt preload and afterload reduction first); LV preload  —  amount of blood being re­turned to left side of heart; measured by wedge pressure (requires central line); as preload increases, amount of blood returned to left side of heart increases; with continued increase, heart unable to pump out blood (goes to lungs); LV afterload  —  measured by systemic vascular resistance; measurement requires central line, but can use diastolic blood pressure (DBP) as indirect indicator (the higher the number, the higher the resistance); ability of heart to pump blood goes down as resistance goes up; contractility  —reflection of how efficiently heart pumping (strength of heart muscle); ventricular EDV  —  amount of blood left in LV after contraction; EF should never be 100% (normal range 50%-70%); if heart muscle not pumping efficiently, EF eventually decreases, EDV increases, and heart enlarges; management of BP critical to management; systolic BP (SBP) reflective of cardiac output; pulse pressure  —  SBP minus DBP; cardiac output  —stroke volume times heart rate; cardiac output affected by control­ling fluid volume or heart rate

Management: afterload reduction (vascular resistance)  —vasodilators (eg, hydralazine); goal for SBP <110 mm Hg; angiotensin-converting enzyme (ACE) inhibitor (eg, enalapril) [eg, Vasotec]) postpartum; preload reduction  —  diuretic to reduce fluid volume; use caution in undelivered patients; improve contractility  —  digoxin; dosage gen­erally higher for pregnant women; follow serum levels (therapeutic range 1-2 ng/mL); b-blocker therapy  —  can be given to control heart rate and reduce myocardial work; anticoagulation  —  no clear data; the greater the dilation, the greater the risk for blood clot; use low threshold for prophylactic anticoagulation; miscellaneous  —  low salt diet; fluid restriction; close monitoring with multiple ECHOs; cardiac rehabilitation program once symptoms con­trolled; pentoxifylline (Trental)  —anti-inflammatory agent; improves heart function clinically and serologically in patients with idiopathic dilated CM; well tolerated; bromocriptine  —  possible new therapy; cathepsin D cleaves prolactin; in mouse model, cleavage of byproduct can lead to PPCM; addition of bromocriptine (prolactin inhibitor) prevented PPCM; improved survival in 5 women in Africa with pregnancy after PPCM; one case report of bro­mocriptine-associated CM; further study warranted

Delivery issues: CM alone not indication for cesarean delivery; patient can labor and still maintain excellent cardiac function; regional anesthesia controls pain and improves afterload; consider assisted vaginal delivery; data show delivering patient improves LV function

Prognosis: »50% of patients recover LV function; recovery more likely if initial EF >30%; poor recovery associated with dilated LV and poor contractility at time of diagnosis; 85% mortality by 5 yr if cardiac function does not nor­malize within 6 mo; dobutamine stress ECHO good predictor of recovery; study looked at maternal outcomes of subsequent pregnancies in women with PPCM; even in women with apparent recovery (EF >50%), 9% had persis­tent postpartum deterioration and »20% had worsening cardiac function; another study suggested women with CM considering pregnancy should undergo dobutamine stress ECHO to determine cardiac reserve

Conclusion: subsequent pregnancies should be discouraged in women with history of PCCM; termination not neces­sarily warranted

Prenatal Questions: “Is it Safe To”…

Judith T. Bishop, CNM, MPH, MSN, Professor of Obstetrics, Gynecology and Reproductive Sciences, Univer­sity of California, San Francisco, School of Medicine

“Can I paint the nursery?”

Background: paint contains lead, zinc, and aluminum; thinners and solvents in paint emit volatile organic com­pounds (VOCs); VOCs emitted as gases from household cleaners, printers, copiers, permanent markers, and paint strippers; lead paint discontinued in 1970s because of serious hazard to fetuses and children; oil-based paint contains solvents; requires turpentine or mineral spirits for clean-up; most house paints acrylic; no solvents, clean up with soap and water, but still emit VOCs; exposure to VOCs results in eye and throat irritation, respira­tory problems, nausea, and dizziness; long-term exposure linked to kidney and liver disease and cancer

Reproductive outcomes: studies of paint exposure based on abusive recreational sniffing or occupational exposure; characteristics similar to fetal alcohol syndrome, intrauterine growth restriction, and dysmorphic features seen among offspring of women engaged in sniffing toluene; animal and human studies looking at association be­tween occupational paint exposure of mother or father showed infertility, stillbirth, birth defects, developmental disorders, and childhood cancers; current data of insufficient quantity and quality to make definitive statements about risk (even at level of occupational exposure)

Recommendations: VOC levels  —  250 g/L allowed in latex paint  (low-odor or low-VOC paint); Green Seal stan­dards <50 g/L VOC; zero- or no-VOC paints <10 g/L; use low-VOC paint; ventilate area being painted; dispose of leftover paints; level of exposure in painting room not likely issue

Should I take omega-3’s?

Background: essential polyunsaturated fatty acids; omega-3’s include alpha linolenic acid (ALA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA); linolenic acid (LA) omega-6; ALA and LA obtained only from diet; limited synthesis of DHA and EPA from LA (dietary intake important as well); fetus obtains omega fatty ac­ids by placental transfer and newborn from breast milk; omega-6  —  found in corn, sunflower, cottonseed, and soy oil; American diet estimated to supply 10 to 20 times daily requirement; omega-3  —  fish and fish oil main sources; flaxseed oil best vegetable source; deficiency result of low consumption of fish in American diet; levels of omega-3 in meat and eggs affected by changes in feeding of livestock; high levels of omega-6 in American diet inhibit incorporation of omega-3

Omega-3s and pregnancy: rapid growth of new tissues and organ systems in perinatal period increases metabolic demand for long chain fatty acids (particularly DHA; concentrated in retinal and neural cell membranes); impor­tant for brain development, visual acuity, and cognition (particularly during last trimester and first 18 mo of life); pregnant women and their babies have measurably more DHA in blood when mother increases DHA consump­tion (food or supplements); grade B evidence supports importance for healthy pregnancy; data show fish oil sup­plementation from 22nd wk of pregnancy until delivery increases fatty acids in fetus and mother; early evidence suggests improved problem-solving skills and improved visual acuity in infants of mothers with increased DHA intake during pregnancy; no consensus among professional organizations on omega-3 supplementation during pregnancy; drawbacks of supplements  —gastrointestinal upset; may lower BP, raise blood sugar, cause bleeding problems, and cause vitamin E deficiency (unless supplemented with vitamin E); vitamin A or D toxicity if tak­ing fish liver oil; nasopharyngitis; products unregulated; supplements do not replace nutrition of whole foods

Recommendations: emphasize balanced healthy diet; advise decrease in omega-6 intake to boost omega-3s (elimi­nation of, eg, fast foods, fried foods, bottled salad dressings); aim for equivalent of 200 to 300 mg DHA daily in context of other omega-3s; omega-3-enriched foods available; consider supplements for vegans, vegetarians, and individual cases

Can I fly when I’m pregnant? most security devices do not emit radiation; cosmic radiation exposure much higher in plane than on ground level; radiation safety standards in United States and Europe recommend maximum an­nual exposure limit of 1 mSv; 1-mSv limit recommended for 40 wk of pregnancy; commercial jets at high alti­tude pressurized for 5000 to 8000 ft (considered safe for healthy woman); risk for venous thromboembolism (VTE) doubles (to 1 in 6000) with flight ³4 hr; primary cause probably immobilization; hemoconcentration from low humidity in cabin and fluid restriction; no association with hypobaric hypoxia found; risk of VTE begins in first trimester

Prophylaxis and recommendations: ambulation; isometric exercises; pharmacologic prophylaxis (one dose of low-molecular weight heparin); currently no recommendation for general pharmacologic prophylaxis; significant re­duction in asymptomatic DVT when compression socks worn for flights >4 hr; airlines have no official policy about flying when pregnant; American College of Obstetricians and Gynecologists (ACOG) states air travel safe for healthy women with normal pregnancy £36 wk gestation; speaker provides note based on patient’s prefer­ence, if medically appropriate; consider distance and destination; compression socks, ambulation, and hydration advised, regardless of gestation; patient should take contact number and copy of obstetric record

Can I sleep on my back? compression of inferior vena cava causes decrease in venous return and cardiac output; no recommendations about sleep, but ACOG states women should avoid supine exercise as much as possible; data found uterine blood flow during supine exercise twice that during supine rest (ie, prohibition unfounded for asymp­tomatic physically active women); speaker found no reports of ill effects, damage, or death of fetus associated with sleeping on back (finding sleep position that allows adequate rest during pregnancy more important)

Editor’s Note

Organization of Teratology Information Specialists (OTIS): www.OTISpregnancy.org 866-626-6847

California Teratogen Information Service:www.CTISpregnancy.org800-523-3749

Suggested Reading

American College of Obstetricians and Gynecologists, Committee on Obstetric Practice: ACOG committee opinion. Air Travel during pregnancy. Int J Gynaecol Obstet 76:338, 2002; Demakis JG et al: Natural course of peripartum cardio­myopathy. Circulation 44:1053, 1971; Dorbala S: Risk stratification of women with peripartum cardiomyopathy at initial presentation: a dobutamine stress echocardiography study. J Am Soc Echocardiogr 18:45, 2005; Elkayam U et al: Maternal and fetal outcomes of subsequent pregnancies in women with peripartum cardiomyopathy. N Engl J Med 344:1567, 2001; Elkayam U et al: Pregnancy-associated cardiomyopathy: clinical characteristics and a comparison between early and late presentation. Circulation 111:2050, 2005; Greenberg JA et al: Omega-3 fatty acid supplementation during pregnancy. Rev Obstet Gynecol 1:162, 2008; Koren G: Is air travel in pregnancy safe? Can Fam Physician 54:1241, 2008; Lampert MB et al: Contractile reserve in patients with peripartum cardiomyopathy and recovered left ventricular function. Am J Obstet Gy­necol 176:189, 1997; Hueston WJ et al: Common questions patients ask during pregnancy. Am Fam Physician 51:1465, 1995; Pearson GD et al: Peripartum cardiomyopathy: National Heart, Lung, and Blood Institute and Office of Rare Dis­eases (National Institutes of Health) workshop recommendations and review. JAMA 289:1183, 2000; Siu SC et al: Prospec­tive multicenter study of pregnancy outcomes in women with heart disease. Circulation 104:515, 2001; Sliwa K et al: The addition of pentoxifylline to conventional therapy improves outcome in patients with peripartum cardiomyopathy. Eur J Heart Fail 4:305, 2002; Wigle DT et al: Environmental hazards: evidence for effects on child health. J Toxicol Environ Health B Crit Rev 10:3, 2007; Yashodhara BM et al: Omega-3 fatty acids: a comprehensive review of their role in health and disease. Postgrad Med J 85:84, 2009.