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Pregnancy in Patients of Advanced Maternal Age
Anesthesiology Clin 24 (2006) 637–646
Pregnancy in Patients of Advanced Maternal Age Ferne R. Braveman, MD Department of Anesthesiology, Section of Obstetric Anesthesiology, Yale University School of Medicine, 333 Cedar Street, PO Box 208051, New Haven, CT 06520-8051, USA
Pregnancy is not a ‘‘medical problem’’ but rather a normal physiologic state. The pregnant woman becomes a patient who has medical problems only when her preexisting status, be it advanced age, preexisting medical conditions, or other problems, prevents her from tolerating the normal physiologic changes associated with pregnancy. In 2002, almost 14% of all births in the United States were to women 35 years or older [1]. In Canada, in 2002, live births to women 30 to 34 years old were 30.6% of all births; to women aged 35 to 39 years, 14.1%; and to women 40 years or older, 2.6% [2]. Some studies have reported higher maternal morbidity and perinatal morbidity and mortality in older gravidas [3,4], thus suggesting that pregnancy in older women may be a ‘‘medical problem.’’ This article summarizes the normal physiology of pregnancy, reviews the present thinking with respect to advanced maternal age (AMA), and reviews the management of medical problems associated with pregnancy in older women.
Normal physiologic changes of pregnancy The demands of the growing fetus result in physiologic adaptations in the mother. Weight gain (12 kg) in pregnancy results primarily from an increase in the uterus and its contents, increases in blood and interstitial volume, and fat deposition. Increased metabolic needs of the fetus result in increased maternal oxygen consumption of 30% to 60%. Carbon dioxide production also increases. Minute ventilation increases by almost 50% in response to increased carbon dioxide production and elevated maternal progesterone levels. Blood gas changes include an increase in PaO2 and a
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decrease in PaCO2, which results in a respiratory alkalosis with metabolic compensation (Table 1). During labor, there can be a further increase of up to 200% in minute ventilation and an increase of up to 75% in oxygen consumption. As early as 5 weeks’ gestation, there is an increase in cardiac output. Cardiac output increases by 40% of nonpregnant values by the end of the first trimester and by 50% by the end of the second trimester. During labor, cardiac output increases by an additional 40% in the second stage. An additional 20% increase in cardiac output is seen during uterine contractions. Immediately postpartum, cardiac output can be as high as 75% above prelabor values, which can be significant for the patient who has preexisting cardiovascular disease. The change in cardiac output is attributed initially to an increase in heart rate (20%–25% above the prepregnant rate). Stroke volume increases by about 30% by the end of the second trimester and remains level until delivery. Stroke volume in labor increases due to autotransfusion as blood is displaced from the uterus. Systolic blood pressure is essentially unchanged in pregnancy. Diastolic blood pressure falls by 20%, consistent with a decrease in systemic vascular resistance. Renal blood flow is increased by 80% at the end of the second trimester, falling slightly near term. Uterine blood flow at term is increased to five times that of the nonpregnant woman. Blood volume increases due to an increase in plasma volume, which reaches a maximum increase of approximately 40% by the end of the second trimester. Red blood cell mass increases to approximately 30% above prepregnant values, which results in an increase in total blood volume of 45% at term. Blood volume increases are greater in multiple pregnancies and in pregnancies with large singleton fetuses. Pregnancy is a state of increased platelet turnover and clotting. Platelet counts can be decreased; however, bleeding time is normal. Clotting factors increase in pregnancy, resulting in shortened prothrombin time and partial thromboplastin times and changes in the thromboelastogram, which suggest a hypercoagulable state. Lower esophageal sphincter tone is decreased from two effects: displacement of the stomach upward and muscle relaxation due to the effects of Table 1 Blood gases in term pregnancy
Paco2 (mm Hg) Pao2 (mm Hg) pH Bicarbonate (mEq/L)
Term
NonPregnancy
30 103 7.44 20
40 100 7.40 24
(Y) ([) ([) (Y)
Abbreviations: Paco2, arterial partial pressure of carbon dioxide; Pao2, arterial partial pressure of oxygen.
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PREGNANCY IN OLDER WOMEN
progestins. Thus, heartburn occurs frequently. Gastric emptying is not altered in pregnancy, although it is slowed during labor. As mentioned earlier, renal blood flow is increased in pregnancy. Glomerular filtrate rate increases by 50%, resulting in a decrease in blood urea nitrogen (BUN) and creatinine. Normal BUN and creatinine values at term are abnormal and indicate renal dysfunction. Pregnancy is characterized by insulin resistance, caused by placental lactogen secretion. This resistance resolves rapidly after delivery. Fasting glucose levels are lower in pregnancy than in a nonpregnant patient due to the high glucose use of the fetus. In summary, pregnancy affects all organ systems (Table 2). AMA and associated morbidities may confound these normal physiologic changes.
Problems associated with advanced maternal age Patients and health care professionals hold the view that AMA results in poorer outcomes. Medically, this view is rationalized by the higher incidence of chronic medical conditions in older patients. In one study, 47% of pregnant women older than 45 years had preexisting medical problems [4]. Cleary-Goldman and colleagues [5] identified 38% of 36,000 patients older than 35 years as taking medication for preexisting conditions. In addition, many older pregnant patients have been infertile, subfertile, or have had a previous poor obstetric outcome. Seven percent had a prior preterm delivery and 26% had a previous miscarriage. As a result of these factors, patients of AMA are treated differently, even if they are healthy and regardless of any scientific basis for this treatment. AMA is independently associated with maternal morbidities including gestational diabetes, preeclampsia, placental abruption, and cesarean delivery. In addition, older gravidas are more likely to have a weight of greater than 70 kg, hypertension, diabetes mellitus, and a bad obstetric history. These medical problems complicate the pregnancy and its management. Table 2 Physiologic changes of pregnancy at terms Variable
Change
Amount of change
Total blood volume Plasma volume Cardiac output Minute ventilation Oxygen consumption Functional residual capacity Fibrinogen
[ [ [ [ [ Y Y
25%–40% 40%–50% 50% 50% 20% 20% 50%
Adapted from Santos AC, Braveman FB, Finster M. Obstetric anesthesia. In: Barash PB, Cullen BF, Stoelting RK, editors. Clinical anesthesia. 5th edition. Philadelphia: Lippincott Williams and Wilkins; 2006. p. 1152; with premission.
640
BRAVEMAN
Gestational diabetes, for which AMA is an independent risk factor, is discussed in the following section. It can lead to increased maternal and infant morbidity. Placental abruption, which is independently associated with AMA and a complication of preeclampsia and chronic hypertension, is also reviewed later and is a leading cause of maternal hemorrhage. Pregestational hypertension occurs more frequently in patients older than 30 years [6]. Patients who have chronic hypertension are more likely than normotensive patients to develop superimposed preeclampsia (78%), to deliver by cesarean section (71%), and to deliver between 34 and 37 weeks’ gestation. Even if they do not develop preeclampsia, hypertensive parturients are still at greater risk for placental abruption, congestive heart failure, pulmonary edema, and hypertensive encephalopathy. Cesarean delivery is performed more frequently in women of AMA. In some patients, cesarean delivery is related to confounding problems such as hypertension, preeclampsia, placental abruption, or fetal macrosomia. AMA is also independently associated with an increased likelihood for cesarean delivery. Lin and Xirasager [7] reported that over a 5-year period, ‘‘request cesarean delivery’’ rates rose steadily in all patients but rose disproportionately in patients of AMA. Women older than 34 years were twice as likely to request cesarean delivery than parturients 25 years or younger. The cesarean delivery rate was 37% for mothers 30 to 34 years old and 47.5% for mothers older than 34 years [8]. The complex sociodemographic explanation for the increased requests for cesarean delivery is yet to be fully ascertained, and the long-term medical cost has yet to be defined. Cesarean delivery is associated with increased maternal risk. Short-term risks of cesarean delivery include hemorrhage, infection, ileus, and aspiration pneumonitis. Hysterectomy following cesarean delivery occurs 10 times more frequently than following vaginal delivery. The risk of maternal death is 16 times greater with cesarean delivery. Long-term morbidity includes adhesions, bowel obstruction, bladder injury, and increased risk for placenta previa or ectopic pregnancy in subsequent pregnancies [9]. Older women believe that their age makes their infant more vulnerable and, as such, believe that a controlled cesarean delivery is safer than vaginal delivery. Other explanations for increased requests for cesarean delivery include concerns about physical stamina, protection of the pelvic floor from damage, refusal to undergo labor pain, and social convenience. Patient beliefs run counter to the many studies that show that cesarean delivery in the absence of clinical indications increases maternal mortality and perinatal morbidity [9,10]. Perinatal complications are also significant in patients of AMA. Multiple gestations [11] (iatrogenic and naturally occurring) are more common in older gravidas. Miscarriage, congenital anomalies, preterm delivery, low birth weight, and intrauterine and neonatal death may also increase with age [2–4].
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PREGNANCY IN OLDER WOMEN
Obstetric and anesthetic management of maternal conditions associated with advanced maternal age Diabetes mellitus Diabetes is one of the most common medical conditions in pregnancy, occurring in approximately 2% to 3% of all parturients, with the incidence increasing primarily due to the increasing incidence of obesity. This number is higher in AMA, with 8% of these pregnancies complicated by diabetes. Approximately 10% of all parturients who have diabetes have preexisting diabetes, with the remainder presenting during pregnancy (gestational diabetes). A classification system (Table 3) describes diabetes associated with pregnancy and may be predictive of neonatal outcome. The progressive insulin resistance that develops during pregnancy results from normal increases in cortisol, progesterone, and placental lactogen. When a woman is unable to sufficiently increase insulin production to compensate for these normal hormonal changes, gestational diabetes results. Women who have gestational diabetes are at increased risk for developing type 2 diabetes mellitus later in life. In patients who have preexisting diabetes, progressive increases in insulin requirements occur due to pregnancy-associated insulin resistance. Several complications occur more frequently in diabetic parturients. Preeclampsia is more common, as is the risk for cesarean delivery. Women who have pregestational diabetes have a 3 to 10 times greater risk for cesarean delivery than nondiabetics; those who have gestational diabetes have a 1.5 times greater risk. Uteroplacental perfusion is decreased by 35% to 45% in patients who have diabetes compared with those who do not. This decrease occurs even in patients who have well-controlled diabetes. Preterm labor is twice more likely to occur in women who have pregestational diabetes than in parturients who do not. The incidence of major fetal malformations in fetuses of mothers who have diabetes is 10%dtwo to six times greater than it is in fetuses of mothers who do not have diabetes. Strict glucose control may decrease this incidence. Intrauterine fetal demise (IUFD) occurs more frequently in Table 3 Classification of diabetes in pregnancy Class
Onset
Cormorbidities
Therapy
A
Gestational
None
B C D F R H
Pregestational Pregestational (juvenile onset) Pregestational Pregestational Pregestational Pregestational
None None Benign retinopathy Nephropathy Proliferative retinopathy Cardiac
A1 – diet A2 – insulin Insulin Insulin Insulin Insulin Insulin Insulin
Data from American College of Obstetricians and Gynecologists. Management of diabetes mellitus in pregnancy. Technical bulletin no. 92. Washington, D.C.: ACOG, 1986:1.
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BRAVEMAN
infants of mothers who have diabetes, which is likely related to decreased uteroplacental perfusion. Fetal macrosomia (with increased risk for cesarean delivery) and vaginal birth–related trauma are other complications of diabetes in pregnancy. The focus of obstetric management of the mother who has diabetes is strict glycemic control. A blood glucose concentration of 60 to 120 mg/dL is ideal. Therapy may be with an insulin pump for continuous infusion of insulin or with frequent insulin injections. Because most pregnant women who have diabetes are gestational diabetics, glucose tolerance tests are routinely administered to patients at high risk for diabetes, including those of AMA. Diligent fetal surveillance may decrease the risk for IUFD. Twiceweekly assessment, beginning at 30 to 32 weeks with a non–stress test and, if indicated, a biophysical profile, is recommended. Some obstetricians advocate elective induction at 38 or more weeks of gestation to avoid late stillbirth and to decrease the delivery risks associated with macrosomia. Anesthetic assessment should address the likelihood of comorbidities such as cardiovascular or renal disease. Autonomic neuropathy may increase the occurrence of hypotension with anesthesia and the risk for aspiration secondary to gastroparesis. Epidural labor analgesia not only provides excellent analgesia but the associated attenuation of pain-related elevation of plasma catecholamine concentrations may also improve uteroplacental perfusion. When the anesthesiologist suspects autonomic dysfunction, extra precaution against hypotension is advised; vigorous hydration and slow dosing of the epidural catheter should attenuate the hypotensive response to neuraxial analgesia. If hypotension does occur, then aggressive treatment is recommended to avoid compromise of uteroplacental perfusion. Compromise of uteroplacental blood flow associated with diabetes may place these patients at increased risk for cesarean delivery due to nonreassuring fetal heart rate assessment. Thus, epidural labor analgesia is more prudent than combined spinal epidural techniques. Anesthesia for cesarean delivery can be with spinal or epidural analgesia; there is no specific recommendation for one or the other in the patient who has diabetes. Aggressive glycemic control and treatment of hypotension are necessary. When general anesthesia is administered, metaclopramide should be administered to minimize aspiration risk associated with gastroparesis. Again, measures to minimize hypotension should be taken pre- and intraoperatively. These measures include the use of left uterine displacement, hydration, and treatment with vasopressors as needed. Hypertensive disorders Preeclampsia Preeclampsia is defined as the development of hypertension with proteinurea after 20 weeks of gestation. AMA is one of many risk factors for
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PREGNANCY IN OLDER WOMEN
preeclampsia; other risk factors include chronic hypertension, multiple gestation, and obesitydconditions more common in patients of AMA. Definitive management of preeclampsia is delivery. When the risk to the fetus from prematurity is great, the risk to the mother must be weighed against the risk to the fetus. Bed rest and close fetal monitoring is recommended until 37 weeks’ gestation or until maternal or fetal deterioration occur. At the least, 48 hours of expectant management to administer corticosteroids for fetal lung maturity should be attempted. Magnesium sulfate is administered to preeclamptic patients for seizure prophylaxis. Its anticonvulsant effects occur centrally, at the N-methyl-Daspartate receptors. A bolus of 4 g administered intravenously followed by 1 to 2 g/h should achieve therapeutic levels of 4 to 6 mEq/L. Magnesium sulfate may also cause a decrease in systemic vascular resistance and an increase in cardiac index, which can improve uteroplacental perfusion in these patients. Severe hypertension requires antihypertensive therapy. Blood pressures greater than 160 to 170 mm Hg systolic or 105 to 110 mm Hg diastolic should be reduced to 140 to 155 mm Hg systolic and 9 to 105 mm Hg diastolic. Greater reductions in blood pressure might compromise fetal wellbeing by decreasing uteroplacental perfusion. Hydralazine, labatolol, and nifedipine are effective in treating pregnancy-induced hypertension. If hypertension is refractory to these therapies, then an arterial catheter should be placed and a continuous infusion of an antihypertensive started. Nitroglycerin or, if needed, sodium nitroprusside can be administered as infusions (Table 4). Anesthetic management of the preeclamptic parturient requires a preanesthetic assessment that first focuses on the airway examination because airway edema may jeopardize tracheal intubation if a general anesthetic is necessary. Preeclamptic patients are often intravascularly depleted and thus prone to hypotension with regional anesthesia. Invasive monitoring, with a central venous pressure or pulmonary artery catheter may be necessary if the patient has pulmonary edema or oliguria unresponsive to a fluid challenge. Table 4 Antihypertensive therapy Drug
Dose
Side effects
Methyldopa Hydralazine
250–500 mg po/IV tid 20–40 mg po qid for long-term therapy 5–10 mg IV for acute blood pressure control (may repeat as needed 15–30 min) 10–30 mg po q 8 h
Sedation Reflex tachycardia
Nifedipine Labetalol Nitroglycerine Nitroprusside
5–10 mg IV, may repeat as needed 5–10 min 5–20 mg/min IV, titrate to effect 0.5–10 mg/kg/min IV, titrate to effect, limit to 6 hours of use
Abbreviation: IV, intravenously.
Headache, reflex tachycardia Headache Fetal cyanide toxicity, maternal tachyphylaxis
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BRAVEMAN
Laboratory assessment should include hematocrit to determine the degree of hemoconcentration, platelet count because 15% of preeclamptic patients may be thrombocytopenic, and BUN and creatinine to determine whether renal dysfunction is present. Epidural analgesia prevents the exaggerated response to catecholamines associated with labor pain and facilitates blood pressure control. Vasospasm associated with preeclampsia may compromise uterine blood flow. Epidural analgesia may improve perfusion. The presence of a functioning epidural also decreases the risk for general anesthesia should a cesarean delivery be needed. Before administering epidural analgesia, adequate hydration is required. Rapid treatment of hypotension is important (hypotension is defined as a 20% drop from the patient’s baseline). Ephedrine is the vasopressor of choice. Epinephrine should be avoided in the test dose because it may cause a significant increase in blood pressure. When cesarean delivery is required, spinal or epidural anesthesia may be instituted. Hypotension must be aggressively treated [6]. When general anesthesia cannot be avoided, awake intubation should be considered. All patients should receive sodium bicitrate, metoclopramide, and an H2 receptor antagonist. Hypertension occurring with intubation or at emergence from general anesthesia can lead to intracerebral hemorrhage. Prevention and rapid control of hypertension is thus important. Also important is that magnesium sulfate enhances sensitivity to all neuromuscular blocking agents and, thus, if general anesthesia is administered, then a peripheral nerve stimulator should be used for monitoring and extubation should be delayed until the patient meets all extubation criteria. Chronic hypertension Chronic hypertension (blood pressure O140/90 mm Hg) is present in approximately 5% of pregnant patients and may be present in the absence of preeclampsia. It occurs almost twice as frequently in patients of AMA. Up to 90% of chronic hypertensive pregnant patients develop superimposed preeclampsia. Independent of the development of preeclampsia, chronic hypertension with a diastolic blood pressure of 100 mm Hg in early pregnancy is associated with a higher risk for placental abruption and intrauterine growth retardation. Hypertension of 4 or more years’ duration may also be associated with ischemic heart disease or renal insufficiency. Treatment of chronic hypertension should be instituted to maintain blood pressure below 140/90 mm Hg. Methyldopa and labetolol are frequently used for therapy. Nifedipine or a thiazide diuretic can be added if needed. Angiotensin-converting enzyme inhibitors are contraindicated in pregnancy due to an associated increase in fetal deaths. Anesthetic management is similar to that of the preeclamptic patient. Patients who have long-standing disease should have a 12-lead EKG. Without coexisting preeclampsia, a platelet count is unnecessary.
PREGNANCY IN OLDER WOMEN
645
Placental abruption Obstetric hemorrhage is a leading cause of maternal and neonatal mortality. Abruption is one of the causes of serious hemorrhage. It is the premature separation of the placenta from the deciduas resulting in hemorrhage that jeopardizes the fetus and mother. Abruption occurs in approximately 1% of pregnancies, with hypertension and AMA being two of the risk factors. Fetal demise is high with abruption: 119 per 1000 births versus 8 per 1000 of all other causes for IUFD. Maternal complications include hemorrhage, disseminated intravascular coagulation, and acute renal failure. Anesthetic management of the patient who has an abruption is fluid resuscitation. Blood products must be readily available and are often administered. Further management depends on the obstetric management. In the case of severe abruption, general anesthesia is preferred for cesarean delivery because the patient is usually hypovolemic. When the patient has been in labor with an epidural in place, it is acceptable to use epidural anesthesia for cesarean delivery if the patient is hemodynamically stable. Obesity Parturients of AMA are more likely than other parturients to weigh over 70 kg. The presence of obesity has significant implications for the mother and fetus. The obese parturient is at increased risk for chronic hypertension, preeclampsia, gestational diabetes, and thromboembolic disease. Obesity affects the progress of labor and is associated with increased risk for cesarean delivery. Anesthesia-related morbidity and mortality is increased, primarily related to airway difficulties. Fetal macrosomia associated with obesity leads to a greater risk for shoulder dystocia and birth trauma. Infants are at greater risk for congenital anomalies, stillbirth, and early neonatal death. Anesthetic management of the obese patient presents significant challenges. The patient should be encouraged to receive epidural analgesia early in labor to decrease the likelihood of requiring general anesthesia for an emergency delivery. Obesity presents technical challenges to epidural placement: anatomic landmarks may be obscured and the depth to the epidural space may be greater, which can result in displacement of the catheter in the subcutaneous tissue. Continuous spinal analgesia may be considered; however, combined spinal epidural, with the concern of undetected misplacement of the epidural catheter, it is not recommended. For cesarean delivery, regional anesthesia is preferred. If general anesthesia is used, awake or fiberoptic-assisted intubation may be needed. Obese patients are also technically challenging for the obstetrician. The choice of anesthetic administered and the duration of the anesthetic block should acknowledge the likelihood of a longer duration of surgery.
646
BRAVEMAN
Summary The care of the pregnant patient of AMA is often the care of a high-risk pregnancy. Comorbidities (preexisting or pregnancy-related), combined with high maternal expectation, place these patients at greater need for intervention during pregnancy and parturition. Thirty-eight percent of these patients are treated for preexisting medical conditions and almost half have preexisting medical conditions. Gravidas of AMA are also more likely to develop pregnancy-related illness. Cesarean delivery is more common in older parturients than in women younger than 35 years. Gravidas who have preexisting conditions or who develop illness should be cared for, whenever possible, in a facility capable of managing high-risk pregnancies.
References [1] Hamilton BE, Martin JA, Sutton PD. Births: preliminary data for 2002. National Vital Statistics Reports. Hyattsville (MD): National Center for Health Statistics; 2003. [2] Joseph KS, Allen AC, Dodds L, et al. The perinatal effects of delayed childbearing. Obstet Gynecol 2005;105:1410–8. [3] Jacobson B, Ladford L, Milsom I. Advanced maternal age and adverse perinatal outcome. Obstet Gynecol 2004;104:727–33. [4] Callaway LK, Lust K, McIntyre HD. Pregnancy outcomes in women of very advanced maternal age. Aust N Z J Obstet Gynaecol 2005;45:12–6. [5] Cleary-Goldman J, Malone FD, Vidaver J, et al. Impact of maternal age on obstetric outcome. Obstet Gynecol 2005;105:983–90. [6] Vigil-DeGracia P, Montufar-Rueda C, Smith A. Pregnancy and severe chronic hypertension maternal outcome. Hypertens Pregnancy 2004;23(3):285–93. [7] Lin H-C, Xirasager S. Maternal age and the likelihood of a maternal request for cesarean delivery: a 5-year population-based study. Am J Obstet Gynecol 2005;192:848–55. [8] Lin H-C, Sheen T-C, Tang C-H, et al. Association between maternal age and the likelihood of a cesarean section: a population-based multivariate logistic regression analysis. Acta Obstet Gynecol Scand 2004;83:1178–83. [9] Rajendran AO, Bolaji S II. Should doctors perform an elective caesarean section on request? Maternal choice alone should not determine method of delivery. BMJ 1998;317(1756):463–5. [10] Bell JS, Campbell DM, Graham WJ, et al. Do obstetric complications explain high caesarean section rates among women over 30? A retrospective analysis. BMJ 2001;322:894–5. [11] Oleszcuk JJ, Keith LG, Oleszczuk AK. The paradox of old maternal age in multiple pregnancies. Obstet Gynecol Clin North Am 2005;32:69–80.
Pregnancy in Patients of Advanced Maternal Age Ferne R. Braveman, MD Department of Anesthesiology, Section of Obstetric Anesthesiology, Yale University School of Medicine, 333 Cedar Street, PO Box 208051, New Haven, CT 06520-8051, USA
Pregnancy is not a ‘‘medical problem’’ but rather a normal physiologic state. The pregnant woman becomes a patient who has medical problems only when her preexisting status, be it advanced age, preexisting medical conditions, or other problems, prevents her from tolerating the normal physiologic changes associated with pregnancy. In 2002, almost 14% of all births in the United States were to women 35 years or older [1]. In Canada, in 2002, live births to women 30 to 34 years old were 30.6% of all births; to women aged 35 to 39 years, 14.1%; and to women 40 years or older, 2.6% [2]. Some studies have reported higher maternal morbidity and perinatal morbidity and mortality in older gravidas [3,4], thus suggesting that pregnancy in older women may be a ‘‘medical problem.’’ This article summarizes the normal physiology of pregnancy, reviews the present thinking with respect to advanced maternal age (AMA), and reviews the management of medical problems associated with pregnancy in older women.
Normal physiologic changes of pregnancy The demands of the growing fetus result in physiologic adaptations in the mother. Weight gain (12 kg) in pregnancy results primarily from an increase in the uterus and its contents, increases in blood and interstitial volume, and fat deposition. Increased metabolic needs of the fetus result in increased maternal oxygen consumption of 30% to 60%. Carbon dioxide production also increases. Minute ventilation increases by almost 50% in response to increased carbon dioxide production and elevated maternal progesterone levels. Blood gas changes include an increase in PaO2 and a
E-mail address: [email protected] 0889-8537/06/$ - see front matter Ó 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.atc.2006.05.002 anesthesiology.theclinics.com
638
BRAVEMAN
decrease in PaCO2, which results in a respiratory alkalosis with metabolic compensation (Table 1). During labor, there can be a further increase of up to 200% in minute ventilation and an increase of up to 75% in oxygen consumption. As early as 5 weeks’ gestation, there is an increase in cardiac output. Cardiac output increases by 40% of nonpregnant values by the end of the first trimester and by 50% by the end of the second trimester. During labor, cardiac output increases by an additional 40% in the second stage. An additional 20% increase in cardiac output is seen during uterine contractions. Immediately postpartum, cardiac output can be as high as 75% above prelabor values, which can be significant for the patient who has preexisting cardiovascular disease. The change in cardiac output is attributed initially to an increase in heart rate (20%–25% above the prepregnant rate). Stroke volume increases by about 30% by the end of the second trimester and remains level until delivery. Stroke volume in labor increases due to autotransfusion as blood is displaced from the uterus. Systolic blood pressure is essentially unchanged in pregnancy. Diastolic blood pressure falls by 20%, consistent with a decrease in systemic vascular resistance. Renal blood flow is increased by 80% at the end of the second trimester, falling slightly near term. Uterine blood flow at term is increased to five times that of the nonpregnant woman. Blood volume increases due to an increase in plasma volume, which reaches a maximum increase of approximately 40% by the end of the second trimester. Red blood cell mass increases to approximately 30% above prepregnant values, which results in an increase in total blood volume of 45% at term. Blood volume increases are greater in multiple pregnancies and in pregnancies with large singleton fetuses. Pregnancy is a state of increased platelet turnover and clotting. Platelet counts can be decreased; however, bleeding time is normal. Clotting factors increase in pregnancy, resulting in shortened prothrombin time and partial thromboplastin times and changes in the thromboelastogram, which suggest a hypercoagulable state. Lower esophageal sphincter tone is decreased from two effects: displacement of the stomach upward and muscle relaxation due to the effects of Table 1 Blood gases in term pregnancy
Paco2 (mm Hg) Pao2 (mm Hg) pH Bicarbonate (mEq/L)
Term
NonPregnancy
30 103 7.44 20
40 100 7.40 24
(Y) ([) ([) (Y)
Abbreviations: Paco2, arterial partial pressure of carbon dioxide; Pao2, arterial partial pressure of oxygen.
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PREGNANCY IN OLDER WOMEN
progestins. Thus, heartburn occurs frequently. Gastric emptying is not altered in pregnancy, although it is slowed during labor. As mentioned earlier, renal blood flow is increased in pregnancy. Glomerular filtrate rate increases by 50%, resulting in a decrease in blood urea nitrogen (BUN) and creatinine. Normal BUN and creatinine values at term are abnormal and indicate renal dysfunction. Pregnancy is characterized by insulin resistance, caused by placental lactogen secretion. This resistance resolves rapidly after delivery. Fasting glucose levels are lower in pregnancy than in a nonpregnant patient due to the high glucose use of the fetus. In summary, pregnancy affects all organ systems (Table 2). AMA and associated morbidities may confound these normal physiologic changes.
Problems associated with advanced maternal age Patients and health care professionals hold the view that AMA results in poorer outcomes. Medically, this view is rationalized by the higher incidence of chronic medical conditions in older patients. In one study, 47% of pregnant women older than 45 years had preexisting medical problems [4]. Cleary-Goldman and colleagues [5] identified 38% of 36,000 patients older than 35 years as taking medication for preexisting conditions. In addition, many older pregnant patients have been infertile, subfertile, or have had a previous poor obstetric outcome. Seven percent had a prior preterm delivery and 26% had a previous miscarriage. As a result of these factors, patients of AMA are treated differently, even if they are healthy and regardless of any scientific basis for this treatment. AMA is independently associated with maternal morbidities including gestational diabetes, preeclampsia, placental abruption, and cesarean delivery. In addition, older gravidas are more likely to have a weight of greater than 70 kg, hypertension, diabetes mellitus, and a bad obstetric history. These medical problems complicate the pregnancy and its management. Table 2 Physiologic changes of pregnancy at terms Variable
Change
Amount of change
Total blood volume Plasma volume Cardiac output Minute ventilation Oxygen consumption Functional residual capacity Fibrinogen
[ [ [ [ [ Y Y
25%–40% 40%–50% 50% 50% 20% 20% 50%
Adapted from Santos AC, Braveman FB, Finster M. Obstetric anesthesia. In: Barash PB, Cullen BF, Stoelting RK, editors. Clinical anesthesia. 5th edition. Philadelphia: Lippincott Williams and Wilkins; 2006. p. 1152; with premission.
640
BRAVEMAN
Gestational diabetes, for which AMA is an independent risk factor, is discussed in the following section. It can lead to increased maternal and infant morbidity. Placental abruption, which is independently associated with AMA and a complication of preeclampsia and chronic hypertension, is also reviewed later and is a leading cause of maternal hemorrhage. Pregestational hypertension occurs more frequently in patients older than 30 years [6]. Patients who have chronic hypertension are more likely than normotensive patients to develop superimposed preeclampsia (78%), to deliver by cesarean section (71%), and to deliver between 34 and 37 weeks’ gestation. Even if they do not develop preeclampsia, hypertensive parturients are still at greater risk for placental abruption, congestive heart failure, pulmonary edema, and hypertensive encephalopathy. Cesarean delivery is performed more frequently in women of AMA. In some patients, cesarean delivery is related to confounding problems such as hypertension, preeclampsia, placental abruption, or fetal macrosomia. AMA is also independently associated with an increased likelihood for cesarean delivery. Lin and Xirasager [7] reported that over a 5-year period, ‘‘request cesarean delivery’’ rates rose steadily in all patients but rose disproportionately in patients of AMA. Women older than 34 years were twice as likely to request cesarean delivery than parturients 25 years or younger. The cesarean delivery rate was 37% for mothers 30 to 34 years old and 47.5% for mothers older than 34 years [8]. The complex sociodemographic explanation for the increased requests for cesarean delivery is yet to be fully ascertained, and the long-term medical cost has yet to be defined. Cesarean delivery is associated with increased maternal risk. Short-term risks of cesarean delivery include hemorrhage, infection, ileus, and aspiration pneumonitis. Hysterectomy following cesarean delivery occurs 10 times more frequently than following vaginal delivery. The risk of maternal death is 16 times greater with cesarean delivery. Long-term morbidity includes adhesions, bowel obstruction, bladder injury, and increased risk for placenta previa or ectopic pregnancy in subsequent pregnancies [9]. Older women believe that their age makes their infant more vulnerable and, as such, believe that a controlled cesarean delivery is safer than vaginal delivery. Other explanations for increased requests for cesarean delivery include concerns about physical stamina, protection of the pelvic floor from damage, refusal to undergo labor pain, and social convenience. Patient beliefs run counter to the many studies that show that cesarean delivery in the absence of clinical indications increases maternal mortality and perinatal morbidity [9,10]. Perinatal complications are also significant in patients of AMA. Multiple gestations [11] (iatrogenic and naturally occurring) are more common in older gravidas. Miscarriage, congenital anomalies, preterm delivery, low birth weight, and intrauterine and neonatal death may also increase with age [2–4].
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Obstetric and anesthetic management of maternal conditions associated with advanced maternal age Diabetes mellitus Diabetes is one of the most common medical conditions in pregnancy, occurring in approximately 2% to 3% of all parturients, with the incidence increasing primarily due to the increasing incidence of obesity. This number is higher in AMA, with 8% of these pregnancies complicated by diabetes. Approximately 10% of all parturients who have diabetes have preexisting diabetes, with the remainder presenting during pregnancy (gestational diabetes). A classification system (Table 3) describes diabetes associated with pregnancy and may be predictive of neonatal outcome. The progressive insulin resistance that develops during pregnancy results from normal increases in cortisol, progesterone, and placental lactogen. When a woman is unable to sufficiently increase insulin production to compensate for these normal hormonal changes, gestational diabetes results. Women who have gestational diabetes are at increased risk for developing type 2 diabetes mellitus later in life. In patients who have preexisting diabetes, progressive increases in insulin requirements occur due to pregnancy-associated insulin resistance. Several complications occur more frequently in diabetic parturients. Preeclampsia is more common, as is the risk for cesarean delivery. Women who have pregestational diabetes have a 3 to 10 times greater risk for cesarean delivery than nondiabetics; those who have gestational diabetes have a 1.5 times greater risk. Uteroplacental perfusion is decreased by 35% to 45% in patients who have diabetes compared with those who do not. This decrease occurs even in patients who have well-controlled diabetes. Preterm labor is twice more likely to occur in women who have pregestational diabetes than in parturients who do not. The incidence of major fetal malformations in fetuses of mothers who have diabetes is 10%dtwo to six times greater than it is in fetuses of mothers who do not have diabetes. Strict glucose control may decrease this incidence. Intrauterine fetal demise (IUFD) occurs more frequently in Table 3 Classification of diabetes in pregnancy Class
Onset
Cormorbidities
Therapy
A
Gestational
None
B C D F R H
Pregestational Pregestational (juvenile onset) Pregestational Pregestational Pregestational Pregestational
None None Benign retinopathy Nephropathy Proliferative retinopathy Cardiac
A1 – diet A2 – insulin Insulin Insulin Insulin Insulin Insulin Insulin
Data from American College of Obstetricians and Gynecologists. Management of diabetes mellitus in pregnancy. Technical bulletin no. 92. Washington, D.C.: ACOG, 1986:1.
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infants of mothers who have diabetes, which is likely related to decreased uteroplacental perfusion. Fetal macrosomia (with increased risk for cesarean delivery) and vaginal birth–related trauma are other complications of diabetes in pregnancy. The focus of obstetric management of the mother who has diabetes is strict glycemic control. A blood glucose concentration of 60 to 120 mg/dL is ideal. Therapy may be with an insulin pump for continuous infusion of insulin or with frequent insulin injections. Because most pregnant women who have diabetes are gestational diabetics, glucose tolerance tests are routinely administered to patients at high risk for diabetes, including those of AMA. Diligent fetal surveillance may decrease the risk for IUFD. Twiceweekly assessment, beginning at 30 to 32 weeks with a non–stress test and, if indicated, a biophysical profile, is recommended. Some obstetricians advocate elective induction at 38 or more weeks of gestation to avoid late stillbirth and to decrease the delivery risks associated with macrosomia. Anesthetic assessment should address the likelihood of comorbidities such as cardiovascular or renal disease. Autonomic neuropathy may increase the occurrence of hypotension with anesthesia and the risk for aspiration secondary to gastroparesis. Epidural labor analgesia not only provides excellent analgesia but the associated attenuation of pain-related elevation of plasma catecholamine concentrations may also improve uteroplacental perfusion. When the anesthesiologist suspects autonomic dysfunction, extra precaution against hypotension is advised; vigorous hydration and slow dosing of the epidural catheter should attenuate the hypotensive response to neuraxial analgesia. If hypotension does occur, then aggressive treatment is recommended to avoid compromise of uteroplacental perfusion. Compromise of uteroplacental blood flow associated with diabetes may place these patients at increased risk for cesarean delivery due to nonreassuring fetal heart rate assessment. Thus, epidural labor analgesia is more prudent than combined spinal epidural techniques. Anesthesia for cesarean delivery can be with spinal or epidural analgesia; there is no specific recommendation for one or the other in the patient who has diabetes. Aggressive glycemic control and treatment of hypotension are necessary. When general anesthesia is administered, metaclopramide should be administered to minimize aspiration risk associated with gastroparesis. Again, measures to minimize hypotension should be taken pre- and intraoperatively. These measures include the use of left uterine displacement, hydration, and treatment with vasopressors as needed. Hypertensive disorders Preeclampsia Preeclampsia is defined as the development of hypertension with proteinurea after 20 weeks of gestation. AMA is one of many risk factors for
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preeclampsia; other risk factors include chronic hypertension, multiple gestation, and obesitydconditions more common in patients of AMA. Definitive management of preeclampsia is delivery. When the risk to the fetus from prematurity is great, the risk to the mother must be weighed against the risk to the fetus. Bed rest and close fetal monitoring is recommended until 37 weeks’ gestation or until maternal or fetal deterioration occur. At the least, 48 hours of expectant management to administer corticosteroids for fetal lung maturity should be attempted. Magnesium sulfate is administered to preeclamptic patients for seizure prophylaxis. Its anticonvulsant effects occur centrally, at the N-methyl-Daspartate receptors. A bolus of 4 g administered intravenously followed by 1 to 2 g/h should achieve therapeutic levels of 4 to 6 mEq/L. Magnesium sulfate may also cause a decrease in systemic vascular resistance and an increase in cardiac index, which can improve uteroplacental perfusion in these patients. Severe hypertension requires antihypertensive therapy. Blood pressures greater than 160 to 170 mm Hg systolic or 105 to 110 mm Hg diastolic should be reduced to 140 to 155 mm Hg systolic and 9 to 105 mm Hg diastolic. Greater reductions in blood pressure might compromise fetal wellbeing by decreasing uteroplacental perfusion. Hydralazine, labatolol, and nifedipine are effective in treating pregnancy-induced hypertension. If hypertension is refractory to these therapies, then an arterial catheter should be placed and a continuous infusion of an antihypertensive started. Nitroglycerin or, if needed, sodium nitroprusside can be administered as infusions (Table 4). Anesthetic management of the preeclamptic parturient requires a preanesthetic assessment that first focuses on the airway examination because airway edema may jeopardize tracheal intubation if a general anesthetic is necessary. Preeclamptic patients are often intravascularly depleted and thus prone to hypotension with regional anesthesia. Invasive monitoring, with a central venous pressure or pulmonary artery catheter may be necessary if the patient has pulmonary edema or oliguria unresponsive to a fluid challenge. Table 4 Antihypertensive therapy Drug
Dose
Side effects
Methyldopa Hydralazine
250–500 mg po/IV tid 20–40 mg po qid for long-term therapy 5–10 mg IV for acute blood pressure control (may repeat as needed 15–30 min) 10–30 mg po q 8 h
Sedation Reflex tachycardia
Nifedipine Labetalol Nitroglycerine Nitroprusside
5–10 mg IV, may repeat as needed 5–10 min 5–20 mg/min IV, titrate to effect 0.5–10 mg/kg/min IV, titrate to effect, limit to 6 hours of use
Abbreviation: IV, intravenously.
Headache, reflex tachycardia Headache Fetal cyanide toxicity, maternal tachyphylaxis
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Laboratory assessment should include hematocrit to determine the degree of hemoconcentration, platelet count because 15% of preeclamptic patients may be thrombocytopenic, and BUN and creatinine to determine whether renal dysfunction is present. Epidural analgesia prevents the exaggerated response to catecholamines associated with labor pain and facilitates blood pressure control. Vasospasm associated with preeclampsia may compromise uterine blood flow. Epidural analgesia may improve perfusion. The presence of a functioning epidural also decreases the risk for general anesthesia should a cesarean delivery be needed. Before administering epidural analgesia, adequate hydration is required. Rapid treatment of hypotension is important (hypotension is defined as a 20% drop from the patient’s baseline). Ephedrine is the vasopressor of choice. Epinephrine should be avoided in the test dose because it may cause a significant increase in blood pressure. When cesarean delivery is required, spinal or epidural anesthesia may be instituted. Hypotension must be aggressively treated [6]. When general anesthesia cannot be avoided, awake intubation should be considered. All patients should receive sodium bicitrate, metoclopramide, and an H2 receptor antagonist. Hypertension occurring with intubation or at emergence from general anesthesia can lead to intracerebral hemorrhage. Prevention and rapid control of hypertension is thus important. Also important is that magnesium sulfate enhances sensitivity to all neuromuscular blocking agents and, thus, if general anesthesia is administered, then a peripheral nerve stimulator should be used for monitoring and extubation should be delayed until the patient meets all extubation criteria. Chronic hypertension Chronic hypertension (blood pressure O140/90 mm Hg) is present in approximately 5% of pregnant patients and may be present in the absence of preeclampsia. It occurs almost twice as frequently in patients of AMA. Up to 90% of chronic hypertensive pregnant patients develop superimposed preeclampsia. Independent of the development of preeclampsia, chronic hypertension with a diastolic blood pressure of 100 mm Hg in early pregnancy is associated with a higher risk for placental abruption and intrauterine growth retardation. Hypertension of 4 or more years’ duration may also be associated with ischemic heart disease or renal insufficiency. Treatment of chronic hypertension should be instituted to maintain blood pressure below 140/90 mm Hg. Methyldopa and labetolol are frequently used for therapy. Nifedipine or a thiazide diuretic can be added if needed. Angiotensin-converting enzyme inhibitors are contraindicated in pregnancy due to an associated increase in fetal deaths. Anesthetic management is similar to that of the preeclamptic patient. Patients who have long-standing disease should have a 12-lead EKG. Without coexisting preeclampsia, a platelet count is unnecessary.
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Placental abruption Obstetric hemorrhage is a leading cause of maternal and neonatal mortality. Abruption is one of the causes of serious hemorrhage. It is the premature separation of the placenta from the deciduas resulting in hemorrhage that jeopardizes the fetus and mother. Abruption occurs in approximately 1% of pregnancies, with hypertension and AMA being two of the risk factors. Fetal demise is high with abruption: 119 per 1000 births versus 8 per 1000 of all other causes for IUFD. Maternal complications include hemorrhage, disseminated intravascular coagulation, and acute renal failure. Anesthetic management of the patient who has an abruption is fluid resuscitation. Blood products must be readily available and are often administered. Further management depends on the obstetric management. In the case of severe abruption, general anesthesia is preferred for cesarean delivery because the patient is usually hypovolemic. When the patient has been in labor with an epidural in place, it is acceptable to use epidural anesthesia for cesarean delivery if the patient is hemodynamically stable. Obesity Parturients of AMA are more likely than other parturients to weigh over 70 kg. The presence of obesity has significant implications for the mother and fetus. The obese parturient is at increased risk for chronic hypertension, preeclampsia, gestational diabetes, and thromboembolic disease. Obesity affects the progress of labor and is associated with increased risk for cesarean delivery. Anesthesia-related morbidity and mortality is increased, primarily related to airway difficulties. Fetal macrosomia associated with obesity leads to a greater risk for shoulder dystocia and birth trauma. Infants are at greater risk for congenital anomalies, stillbirth, and early neonatal death. Anesthetic management of the obese patient presents significant challenges. The patient should be encouraged to receive epidural analgesia early in labor to decrease the likelihood of requiring general anesthesia for an emergency delivery. Obesity presents technical challenges to epidural placement: anatomic landmarks may be obscured and the depth to the epidural space may be greater, which can result in displacement of the catheter in the subcutaneous tissue. Continuous spinal analgesia may be considered; however, combined spinal epidural, with the concern of undetected misplacement of the epidural catheter, it is not recommended. For cesarean delivery, regional anesthesia is preferred. If general anesthesia is used, awake or fiberoptic-assisted intubation may be needed. Obese patients are also technically challenging for the obstetrician. The choice of anesthetic administered and the duration of the anesthetic block should acknowledge the likelihood of a longer duration of surgery.
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Summary The care of the pregnant patient of AMA is often the care of a high-risk pregnancy. Comorbidities (preexisting or pregnancy-related), combined with high maternal expectation, place these patients at greater need for intervention during pregnancy and parturition. Thirty-eight percent of these patients are treated for preexisting medical conditions and almost half have preexisting medical conditions. Gravidas of AMA are also more likely to develop pregnancy-related illness. Cesarean delivery is more common in older parturients than in women younger than 35 years. Gravidas who have preexisting conditions or who develop illness should be cared for, whenever possible, in a facility capable of managing high-risk pregnancies.
References [1] Hamilton BE, Martin JA, Sutton PD. Births: preliminary data for 2002. National Vital Statistics Reports. Hyattsville (MD): National Center for Health Statistics; 2003. [2] Joseph KS, Allen AC, Dodds L, et al. The perinatal effects of delayed childbearing. Obstet Gynecol 2005;105:1410–8. [3] Jacobson B, Ladford L, Milsom I. Advanced maternal age and adverse perinatal outcome. Obstet Gynecol 2004;104:727–33. [4] Callaway LK, Lust K, McIntyre HD. Pregnancy outcomes in women of very advanced maternal age. Aust N Z J Obstet Gynaecol 2005;45:12–6. [5] Cleary-Goldman J, Malone FD, Vidaver J, et al. Impact of maternal age on obstetric outcome. Obstet Gynecol 2005;105:983–90. [6] Vigil-DeGracia P, Montufar-Rueda C, Smith A. Pregnancy and severe chronic hypertension maternal outcome. Hypertens Pregnancy 2004;23(3):285–93. [7] Lin H-C, Xirasager S. Maternal age and the likelihood of a maternal request for cesarean delivery: a 5-year population-based study. Am J Obstet Gynecol 2005;192:848–55. [8] Lin H-C, Sheen T-C, Tang C-H, et al. Association between maternal age and the likelihood of a cesarean section: a population-based multivariate logistic regression analysis. Acta Obstet Gynecol Scand 2004;83:1178–83. [9] Rajendran AO, Bolaji S II. Should doctors perform an elective caesarean section on request? Maternal choice alone should not determine method of delivery. BMJ 1998;317(1756):463–5. [10] Bell JS, Campbell DM, Graham WJ, et al. Do obstetric complications explain high caesarean section rates among women over 30? A retrospective analysis. BMJ 2001;322:894–5. [11] Oleszcuk JJ, Keith LG, Oleszczuk AK. The paradox of old maternal age in multiple pregnancies. Obstet Gynecol Clin North Am 2005;32:69–80.