Consequences of Obstetric Complications

Educational Objectives

The goal of this program is to improve prevention and management of obstetric complications and their possible long-term consequences. After hearing and assimilating this program, the clinician will be better able to:

1.   Manage specific cardiac, hepatic, and airway complications that affect women with preeclampsia.

2.   Describe strategies for treating hematomas and ruptures of the liver in preeclamptic patients.

3.   Identify appropriate screening methods for cerebrovascular complications in preeclamptic patients.

4.   Explain long-term health risks associated with gestational diabetes.

5.   List recommendations for screening and management of blood pressure and dyslipidemia.

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. In their lectures, Drs. Belfort and Ramin present information that is related to the off-label or investiga­tional use of therapies, products, or devices.

Acknowledgments

Dr. Belfort was recorded at Obstetric Intensive Care: A Simplified Approach, presented November 13-15, 2008, in Phoenix, AZ, by Scottsdale Healthcare. Dr. Ramin was recorded at the 20th Annual Focus on the Female Patient, presented July 26-30, 2009, in Kiawah Island, SC, by the Southern Medical Association. The Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.

Preeclamptic Catastrophes

Michael A. Belfort, MD, PhD, Professor, Department of Obstetrics and Gynecology, University of Utah School of Medicine, and Director, Perinatal Research, Maternal-Fetal Services of Utah, Salt Lake City

Overview: preeclampsia associated with cerebrovascular, cardiac, hepatic, and airway complications; cerebrovascular  —eclampsia and stroke most common; data support importance of systolic blood pressure (BP); intracranial hemorrhage (ICH); cerebral edema

Causes of maternal mortality: Hospital Corporation of America data  —  pulmonary embolism most preventable cause of death in women who undergo cesarean section; complications of preeclampsia most common cause of death (16% of patients), followed by amniotic fluid embolism, obstetric hemorrhage, cardiac disease, and pulmo­nary thromboembolism

Cerebrovascular Complications

Stroke and BP: threshold BP for stroke unclear; cerebral injury may result from rate of BP change rather than abso­lute BP (rapid change may overwhelm cerebral autoregulation)

Relationship between eclampsia and stroke: unclear whether 2 different conditions or linked together through, eg, prothrombotic mutations, migraine headaches, vascular instability, collagen vascular disease; unclear whether hy­pertension alone or endothelial damage alone or combination of these with linking catalyst

Cerebral edema

Types: vasogenic  —  reversible breakdown in blood-brain barrier; cytotoxic  —  99.5% indicative of developing in­farct

Imaging: vasogenic and cytotoxic identical on traditional computed tomography (CT) and magnetic resonance im­aging (MRI); diffusion-weighted MRI  —  differentiates between types of edema and shows microinfarcts

Study of healthy pregnant vs preeclamptic pregnant women without headache: healthy women  —  middle cerebral artery resistance index decreases as pressure increases within normal range; preeclamptic women without headache  —  when mean arterial pressure increases, physiologic vasoconstriction occurs via autoregulation

Study of preeclamptic women with headache: concluded that headache indicates loss of autoregulation

Study of mild vs severe preeclampsia: mild cases have normal cerebral perfusion pressure (ie, can autoregulate); much greater proportion of severe preeclamptics unable to autoregulate

Treatment: labetalol (eg, Normodyne, Trandate)  —  reduces cerebral perfusion pressure; magnesium sulfate  —  now believed to act in manner similar to labetalol

Intracerebral hemorrhage: sudden neurogenic hypertension  —can be sign rather than cause; 38% of ICHs show dy­namic growth in volume over first 24 hr; better chance for intact survival if hemorrhage drained by neurosurgeon

Diagnosis of cerebrovascular catastrophes: clinical evaluation; CT sensitive for infarction and hemorrhage; MRI better for cerebellar and brainstem abnormalities, arteriovenous malformations, aneurysms, and angiomas; can use angiography and lumbar puncture

Use of CT or MRI: atypical or prolonged seizure; acute psychosis; seizures despite therapeutic magnesium sulfate level; focal deficits or prolonged coma; late postpartum eclampsia; uncertain diagnosis

Sagittal sinus venous thrombosis (SSVT): diagnosis requires MR venography; SSVT possible in cases of normal CT with minor edema; treatment  —  anticoagulation

Management of cerebrovascular catastrophes: unaltered by pregnancy; immediate evacuation of life-threatening hematoma required in viable patient; indications for surgery  —clinical deterioration in patient with moderate or large lobar hemorrhage or any cerebellar hemorrhage >3 cm; brainstem compression or hydrocephalus from ventricu­lar obstruction; vascular malformation; indications for medical management  —small hemorrhages; minimal neuro­logic deficits; Glasgow Coma Score <4

Cardiopulmonary Issues

Overview: include pulmonary edema, hypertensive cardiomyopathy, myocardial infarction (MI), and ventricular tachycardia

Cardiomyopathy: hypertensive  —  seen in severely eclamptic women; most patients with pulmonary edema and se­vere hypertension have some degree of diastolic dysfunction; peripartum  —  associated with systolic dysfunction, and can result in pulmonary edema and cardiac failure; usually characterized by low BP

Diastolic dysfunction: causes of fulminant pulmonary edema, cardiac failure, and sudden death; more common in chronic hypertension; abnormal distensibility of heart during diastole; seen with increased, normal, or decreased ejection fraction; main features  —  development of effort intolerance, dyspnea, venous congestion, or pulmonary edema; seen in 30% of congestive cardiac failure patients; recommend electrocardiography during pregnancy for patients with severe chronic hypertension; systolic dysfunction  —  systolic curve moves downward and to right, which creates narrowing and drop of pressure-volume curve; diastolic dysfunction not associated with systolic dysfunction  —  shift in pressure-volume curve upward and leftward; sudden onset of coughing and “asthma attack” should be considered sign of pulmonary edema until proven otherwise; document normal pulse oximetry and BP

Ventricular tachycardia and sudden death: South African study  —  21 women with hypertensive crisis, preeclamp­sia, and prolonged periods of severe hypertension; before BP controlled, 61% of patients had significant ventricular tachycardia; in same study, authors reported on 24-hr Holter monitoring in 40 eclamptic women given hydralazine (eg, Apresoline) vs labetalol for postpartum hypertension management; 81% in hydralazine group had serious ven­tricular arrhythmias vs 17% in labetalol group

Acute coronary syndrome: of 1.5 million deliveries, 9 of 95 deaths had cardiac causes; included 5 MIs in women with no known coronary disease; troponin study  —  2 preeclamptic women with acute myocardial syndrome; signif­icantly elevated troponin levels (troponin elevated in preeclampsia alone); ST or T wave abnormalities in both women (resolved with delivery); take-home message  —preeclampsia may increase risk for MI; measure troponin in patients with chest pain

Hepatic Complications

Hepatic hemorrhage: liver has mottled appearance; Glisson’s capsule lifted off underlying tissue by bleeding within liver (distinct from external trauma, where capsule ruptures first); surgical management  —  cannot use tamponade in pregnant women (use drain instead); open abdomen, cut small segment of falciform ligament to drop liver for­ward, and pack between diaphragm and liver to stop bleeding; give patient blood and blood products to manage coagulopathy; resuscitate; incidence  —  1 in 45,000 to 225,000

Hemolytic anemia, elevated liver enzymes, and low platelet count (HELLP) syndrome: found in 2.2% of patients with hepatic hemorrhage; right lobe most common; high (30%) but decreasing maternal mortality; with severe upper abdominal pain and characteristic laboratory values, assume HELLP syndrome in preeclamptic patient (do not assume dyspepsia); management  —  laparotomy for confirmed rupture; with stable hematoma, monitor and be prepared for surgery; forego imaging if clinical picture indicative of HELLP; surgery as described above; concur­rent delivery advisable; anticipate acute respiratory distress syndrome and renal failure; observe patient for Shee­han’s syndrome

Pancreatitis: caused by ischemia; may be precipitated by use of loop diuretics; differential diagnosis  —  aortic dissec­tion

Airway Complications

Acute laryngeal edema: can lead to seizure and airway obstruction

Questions and Answers

Steroids and HELLP syndrome: randomized controlled trials suggest no benefit from high-dose antenatal steroids for management; not standard of care; delivery recommended as conservative management

Role of benzodiazepines in eclampsia: if used, shorter-acting drugs preferable; speaker uses standard care; in cases of bradycardia associated with eclampsia, infant improves with resuscitation of mother

Obstetric Complications Leading to
Chronic Diseases in Adults

Kirk D. Ramin, MD, Associate Professor, Department of Obstetrics, Gynecology and Women’s Health, Univer­sity of Minnesota, Minneapolis

Preeclampsia and Long-Term Outcomes

Chesley’s Hypertensive Disorders in Pregnancy (Lindheimer, 1999): looked at differences in outcomes between primigravida, nulligravida, and multigravida patients with preeclampsia; found prolonged preeclampsia does not lead to chronic hypertension; no increased risk for hypertension in eclamptic primipara; in eclamptic multiparas, mortality risk increases 3-fold (80% of deaths due to hypertensive disease); preexisting chronic hypertension likely

van Pampus (2005): laser Doppler imaging performed in vivo 15 to 25 yr after 10 preeclamptic and 10 normotensive pregnancies; impaired microvascular function seen only in women with preeclampsia

Aagaard-Tillery (2006): »2600 of 52,000 non-preeclamptic patients with cancer vs »760 of 17,000 preeclamptic pa­tients with cancer; suggests preeclampsia protective against development of cancer later in life; led to hypothesis that mechanism of abnormal placental development (which may cause preeclampsia) also causes inability to pro­vide sufficient blood supply to sustain cancer

Paltiel (2009): certain cancers (eg, stomach, breast, ovary, kidney, lung, larynx) increased in women with preeclamp­sia as primigravidas; may be explained by environmental or genetic factors common to preeclampsia and cancer, not by preeclampsia itself

Krabbendam (2009): after 4-wk cycling program, improvement seen in venous vascular function in formerly pre­eclamptic women; suggests reduced sympathetic activity; may improve maternal vascular adaptation to early preg­nancy and reduce risk for recurrent gestational hypertension; no change in basal BP or cardiac output; resting heart rate decreased by 7%, venous compliance increased by 18%, and plasma volume increased by 8%

Gestational Diabetes

Overview: complicates 2% to 5% of all pregnancies; rate equal to that of undiagnosed glucose intolerance in non­pregnant women of same age; Metzger recommendation (2007)  —  test high-risk pregnant women (eg, those with obesity, family history, type 2 diabetes) during first prenatal visit; O’Sullivan (1973)  —  women with gestational di­abetes have increased risk for hypertension, hyperlipidemia, electrocardiographic abnormalities, and overall risk for death; take-home message  —  diagnosis during pregnancy indicative of need for care in future

Long-term outcomes: Vohr and Boney (2008)  —  women with obesity and previous history of gestational diabetes at increased risk of developing metabolic syndrome, compared to those without history; risk of children developing metabolic syndrome with increasing age associated with maternal obesity, gestational diabetes, hyperglycemia in third trimester, macrosomia, and childhood obesity; Boyd study  —  gestational diabetes associated with high lifelong risk for progression to type 2 disease (³50% over lifetime); lifestyle modifications or taking drugs for type 2 diabe­tes reduces risk for long-term consequences; offspring at high risk of developing obesity and abnormal glucose me­tabolism; animal study shows that increased risks in offspring due to maternal diet high in fat (resulting epigenetic alterations in fetal chromatin structure through covalent modification of histones), rather than postnatal environ­ment

BP and Dyslipidemia Recommendations

Blood pressure (Canadian Heart Education Program, 2009): dietary sodium  —  for normotensive patients, <2300 mg/day; for hypertensive patients, 1500 to 2300 mg/day; aerobic exercise  —  30 to 60 min (4-5 days/wk); waist size  —  for men, <102 cm (40 in); for women, <88 cm (35 in); important for providers to counsel patients; body mass index  —  18.5 to 24.9; alcohol  —  for men, <14 units/wk; for women, <9 units/wk; diet  —  low in saturated fats and cholesterol; plenty of fruits, vegetables, fiber, and proteins; stress management  —  discuss lifestyle changes to reduce or cope with stress; BP thresholds  —  <140/90 mm Hg; patients with diabetes and chronic kid­ney disease, <130/80 mm Hg; 130/80 mm Hg possibly more appropriate for younger patients, especially those with risk for atherosclerosis, target organ damage, and comorbid conditions; initial therapy  —  thiazide diuretics for most patients; angiotensin-converting enzyme (ACE) inhibitors (except in blacks); long-acting calcium chan­nel blockers; angiotensin receptor blockers (ARBs)

Special situations: angina, MI, cardiac failure  —  give b-blocker and ACE inhibitor; cerebrovascular disease  —  ACE inhibitor and diuretic; chronic nondiabetic proteinuric renal disease  —ACE inhibitor or ARB; diabetes  —  ACE inhibitor and/or ARB; if no proteinuria, use thiazide diuretic and calcium channel blocker; elevated BP  —  if systolic BP elevated by ³20 mm Hg and/or diastolic BP elevated ³10 mm Hg, consider 2 first-line agents; all patients  —  give low-dose (“baby”) aspirin; write out specific recommendations; compliance challenging; not all physicians agree on specific recommendations; intense management  —  eg, retinal scans examining vasculature, annual treadmill tests and lipid measurements, of unproven benefit and cost-effectiveness; multi-drug formulations  —  recommended to increase compliance and reduce costs

Dyslipidemia screening and management: full lipid panel (9-12-hr fast) recommended for  —  men >40 yr of age; women >50 yr of age or postmenopausal; children, if extensive family history of monogenic lipid disorders (eg, familial hypercholesterolemia, chylomicronemia) or diabetes; tobacco users; hypertensives; who to screen  —  consider waist size measurement; review family history of coronary artery disease

Special situations: patients with hyperlipidemic manifestations, exertional chest pain, dyspnea, erectile dysfunc­tion, and evidence of atherosclerosis; frequency of screening  — at physician’s discretion; every 2 to 3 yr (more frequently if indicated by patient lifestyle); with major coronary artery disease risk factors (class IIa, level C), screen at any age

Suggested Reading

Aagaard-Tillery KM et al: Developmental origins of disease and determinants of chromatin structure: maternal diet modifies the primate fetal epigenome. J Mol Endocrinol 41:91, 2008; Aagaard-Tillery KM et al: Preeclampsia and subsequent risk of cancer in Utah. Am J Obstet Gynecol 195:691, 2006; Belfort MA et al: Cerebral hemodynamics in preeclampsia: cerebral per­fusion and the rationale for an alternative to magnesium sulfate. Obstet Gynecol Surv 61:655, 2006; Campbell NR et al: Hy­pertension in diabetes: a call to action. Can J Cardiol 25:299, 2009; Clark SL et al: Maternal death in the 21st century: causes, prevention, and relationship to cesarean delivery. Am J Obstet Gynecol 199:36, 2008; Cnossen JS et al: Accuracy of mean ar­terial pressure and blood pressure measurements in predicting pre-eclampsia: systematic review and meta-analysis. BMJ 336:1117, 2008; Cox J et al: A maternal high-fat diet is accompanied by alterations in the fetal primate metabolome. Am J Ob­stet Gynecol 201:281, 2009; Frishman WH et al: Pathophysiology and medical management of systemic hypertension in pre­eclampsia. Curr Hypertens Rep 8:502, 2006; Harris MI: Gestational diabetes may represent discovery of preexisting glucose intolerance. Diabetes Care 11:402, 1988; Krabbendam I et al: Exercise-induced changes in venous vascular function in non­pregnant formerly preeclamptic women. Reprod Sci 16:414, 2009; McCoy S, Baldwin, K: Pharmacotherapeutic options for the treatment of preeclampsia. Am J Health Syst Pharm 66:337, 2009; Metzger BE et al: Summary and recommendations of the Fifth International Workshop-Conference on Gestational Diabetes Mellitus. Diabetes Care 30:S251, 2007; Nabatian S et al: Acute coronary syndrome and preeclampsia. Obstet Gynecol 106:1204, 2005; Paltiel O et al: Cancer after pre-eclampsia: follow up of the Jerusalem perinatal study cohort. BMJ 328: 919, 2004; Pavlis T et al: Diagnosis and surgical management of spontaneous hepatic rupture associated with HELLP syndrome. J Surg Educ 66:163, 2009; van Pampus MG, Aarnoudse JG: Long-term outcomes after preeclampsia. Clin Obstet Gynecol 48:489, 2005; Vohr BR, Boney CM: Gestational diabetes: the forerunner for the development of maternal and childhood obesity and metabolic syndrome? J Matern Fetal Neonatal Med 21:149, 2008.