Fragile X syndrome is an X-linked disorder that causes mental retardation. It is caused by a repeat in the
6. Fetal effects: Decreased intermittent placental perfu- perfu-sion secondary to vasospasm is thought to be
responsi-ble for the increased incidence of intrauterine growth restriction (<10% estimated fetal weight for gesta-tional age), oligohydramnios, and increased perinatal mortality of infants born to mothers with preeclamp-sia. An increased incidence of placental abruption is also seen. With the stress of uterine contractions dur-ing labor, the placenta may be unable to adequately oxygenate the fetus. This may result in signs of intra-partum uteroplacental insufficiency. Specifically, a non-reassuring fetal-heart-rate pattern may necessitate cesarean delivery.
Presumably because of vasospastic changes, placental size and func-tion are decreased. The results are progressive fetal hypoxia and malnutrition, as well as an increase in the incidence of intrauterine growth restriction and oligohydramnios.
Genetic predisposition
Inadequate trophoblastic invasion of maternal spiral arteries Immune response genes Histocompatibility antigens Race
Placental ischemia
Hypertension Proteinuria
Edema
Preeclampsia
Eclampsia
Generalized endothelial cell injury Parity
Vasospasm Vascular
permeability
Maternal vascular disease
edothelin NO PGI2
Placental endothelial toxin?
Convulsions
DIC Hypertension Diabetes Sympathetic vasoconstrictor activity
FIGURE 16.1. Proposed pathways and markers implicated in the development of preeclampsia and eclampsia. DIC = dis-seminated intravascular coagulation; NO䡠 = nitric acid; PGI2= prostacyclin.
EVALUATION
The history and physical examination are directed toward detection of pregnancy-associated hypertensive disease and its signs and symptoms. A review of current obstetric records, if available, is especially helpful to ascertain changes or progression in findings. Visual disturbances, es-pecially scotomata, or unusually severe or persistent headaches are indicative of vasospasm. Right-upper-quadrant pain may indicate liver involvement, presumably involving disten-tion of the liver capsule. Any history of loss of conscious-ness or seizures, even in the patient with a known seizure disorder, may be significant.
The position of the patient influences blood pressure. It is lowest with the patient lying in the lateral position, high-est when the patient is standing, and at an intermediate level when she is sitting. The choice of the correct-size blood pressure cuff also influences blood pressure readings, with falsely high measurements noted when normal-sized cuffs are used on large patients. Also, during the course of pregnancy, blood pressure typically declines slightly in the second trimester, increasing to prepregnant levels as gestation nears term (Fig. 16.2). If a patient has not been seen previously, there is no baseline blood pressure against which to compare new blood pressure determinations, thereby making the diagnosis of pregnancy-related hyper-tension more difficult.
The patient’s weight is compared with her pregravid weight and with previous weights during this pregnancy, with special attention to excessive or too-rapid weight gain.
Peripheral edema is common in pregnancy, especially in the lower extremities.
Indeed, the puffy-faced, edematous, hypertensive preg-nant woman is the classic picture of preeclampsia. Careful blood pressure determination in the sitting and supine positions is necessary. Funduscopic examination may de-tect vasoconstriction of retinal blood vessels indicative of similar vasoconstriction of other small vessels. Tenderness over the liver, attributed partly to hepatic capsule disten-sion, may be associated with complaints of right-upper-quadrant pain. The patellar and Achilles’ deep tendon reflexes should be carefully elicited, and hyperreflexia noted. The demonstration of clonus at the ankle is espe-cially worrisome.
The maternal and fetal laboratory evaluations for pregnancy complicated by hypertension are presented in Table 16.1 and demonstrate, by the wide range of tests, the multisystem effects of hypertension in pregnancy.
Maternal liver dysfunction, renal insufficiency, and coagulopathy are significant concerns and require serial evaluation. Evaluation of fetal well-being with ultrasonography, and a nonstress test and/or biophysical profile are important.
MANAGEMENT
The goal of management of hypertension in pregnancy is to bal-ance the management of both fetus and mother and to optimize the outcome for each. Maternal blood pressure should be mon-itored and the mother should be observed for the sequelae of the hypertensive disease. Intervention for maternal indi-cations should occur when the risk of permanent disability or death for the mother without intervention outweighs the risks to the fetus caused by intervention. For the fetus, there should be regular evaluation of fetal well-being and fetal growth, with intervention becoming necessary if the intra-uterine environment provides more risks to the fetus than delivery with subsequent care in the newborn nursery.
Chronic Hypertension
The management of patients with chronic hypertension in preg-nancy involves closely monitoring maternal blood pressure and watching for the superimposition of preeclampsia or eclampsia, and following the fetus for appropriate growth and fetal well-being. Medical treatment of essential hypertension has been disappointing, in that no significant improvement in preg-nancy outcome has been demonstrated with treatment.
Antihypertensive medication in women with chronic hyper-tension is generally not given unless the systolic blood pressure is 150 to 160 mm Hg or the diastolic blood pressure 100 to
125
120
115
110
70 75
65
mmHg
0
16 20 24 28 32 36 40
Weeks of gestation Systolic
Diastolic
FIGURE 16.2. Range of blood pressures in normotensive pregnancy. Note the decrease in blood pressure in the sec-ond trimester.
However, persistent edema unresponsive to resting in the supine position is not normal, especially when it also involves the upper extremities, sacral region, and face.
110 mm Hg. The purpose of such medications is to reduce the likelihood of maternal stroke. Methyldopa is a com-monly used antihypertensive medication for this purpose, although a combined alpha-and-beta-blocker (such as la-betalol) and calcium-channel blockers (such as nifedipine) are also commonly used. It was formerly taught that uretics were contraindicated during pregnancy, but di-uretic therapy is no longer discontinued, and indeed is usually continued, in the patient who already has been on such therapy before becoming pregnant.
Preeclampsia
The severity of the preeclampsia and the maturity of the fetus are the primary considerations in the management of preeclampsia. Care must be individualized, but there are well-accepted general guidelines.
The mainstay of management for patients with mild preeclampsia is rest and frequent monitoring of mother and fetus.
Testing for suspected fetal growth restriction or oligohydramnios and twice-weekly nonstress tests, biophysical profiles, or both, are commonly employed and should be repeated as indicated, accord-ing to maternal condition. Testaccord-ing is recommended twice weekly for suspected fetal growth restriction or oligo-hydramnios. Ultrasound examination for fetal growth and amniotic fluid assessment is recommended every 3 weeks.
Daily fetal movement assessment also may prove useful.
Hospitalization is often initially recommended for women with new-onset preeclampsia. After maternal and fetal conditions are serially assessed, subsequent manage-ment may be continued in the hospital, at a day-care unit, or at home on the basis of the initial assessment.
For the patient with worsening preeclampsia or the patient who has severe preeclampsia, management is often best accom-plished in a tertiary-care setting. Daily laboratory tests and fetal surveillance may be indicated. Stabilization with mag-nesium sulfate, antihypertensive therapy (as indicated), monitoring for maternal and fetal well-being, and deliv-ery by either induction or cesarean delivdeliv-ery are required.
For almost a century, magnesium sulfate has been used to prevent and to treat eclamptic convulsions. Other anticonvulsants, such as diazepam and phenytoin, are rarely used because they are not as efficacious as magne-sium and because they have potential adverse effects on the fetus. Magnesium sulfate is administered by intramuscular or intravenous routes, although the latter is far more common.
In 98% of cases, convulsions will be prevented. Therapeutic levels are 4 to 6 mg/dL with toxic concentrations having pre-dictable consequences (Table 16.2). Frequent evaluations of the patient’s patellar reflex and respirations are necessary to monitor for manifestations of rising serum magnesium concentrations. In addition, because magnesium sulfate is excreted solely from the kidney, maintenance of urine output of at least 25 mL/hour will help avoid accumulation 16.1 Laboratory Assessment of Pregnant Hypertensive Patients
Test or Procedure Rationale
Maternal studies
Complete blood count Increasing hematocrit may signify worsening vaso-constriction and decreased intravascular volume Decreasing hematocrit may signify hemolysis Platelet count Thrombocytopenia is associated with worsening
disease
Coagulation profile (PT, PTT) Coagulopathy is associated with worsening disease Liver function studies Hepatocellular dysfunction is associated with
worsening disease
Serum creatinine Decreased renal function is associated with
Uric acid worsening disease
24-hour urine Creatinine clearance Total urinary protein
Fetal studies (To assess for pregnancy-associated hypertension effects on the fetus) Ultrasound examination
Fetal weight and growth IUGR
Amniotic fluid volume Oligohydramnios
NST and/or biophysical profile Placental status (indirect assessment)
IUGR = intrauterine growth restriction; NST = nonstress test; PT = prothrombin time; PTT = partial thromboplastin time.
T A B L E
dangerous to the fetus. Labetalol is another agent used to manage severe hypertension (Table 16.3).
Once anticonvulsant and antihypertensive therapies are established in patients with severe preeclampsia or eclampsia, attention is directed toward delivery. Induction of labor is often attempted, although cesarean delivery may be needed either if induction is unsuccessful or not possible, or if the maternal or fetal status is worsening. At delivery, blood loss must be closely monitored, because patients with pre-eclampsia or pre-eclampsia have significantly reduced blood volumes. After delivery, patients remain in the labor and delivery area for 24 hours (longer if the clinical situation warrants) for close observation of their clinical progress and further administration of magnesium sulfate to pre-vent postpartum eclamptic seizures. Approximately 25%
of eclamptic seizures occur before labor, 50% occur during labor, and 25% occur in the first 24 hours after delivery.
Usually, the vasospastic process begins to reverse itself in the first 24 to 48 hours after delivery, as manifested by a brisk diuresis.
Eclampsia
The eclamptic seizure is life-threatening for mother and fetus. Maternal risks include musculoskeletal injury (including biting the tongue), hypoxia, and aspiration. Maternal therapy consists of inserting a padded tongue blade, restraining gently as needed, providing oxygen, assuring maintenance of an adequate airway, and gaining intravenous access.
Eclamptic seizures are usually self-limited, so medical apy should be directed to the initiation of magnesium ther-apy (4 to 6 g slowly, intravenously) to prevent further seizures. If a patient receiving magnesium sulfate experi-Magnesium Toxicity
Serum Concentration
(mg/dL) Manifestation
1.5–3 Normal concentration
4–6 Therapeutic levels
5–10 Electrocardiogram changes
8–12 Loss of patellar reflex
9–12 Feeling of warmth, flushing
10–12 Somnolence; slurred speech
15–17 Muscle paralysis; respiratory
difficulty
30 Cardiac arrest
Antihypertensive Medications Used in Pregnancy
Medication Mechanism of Action Effects
Thiazide
Methyldopa
Hydralazine
Propranolol
Labetalol
Nifedipine
CNS = central nervous system; CO = cardiac output; RBF = renal blood flow.
Decreased plasma volume and CO
False neurotransmission, CNS effect
Direct peripheral vasodilation
β-adrenergic blocker α- and β-adrenergic blocker Calcium-channel blocker
CO decreased; RBF decreased; maternal depletion; neonatal thrombo-cytopenia
CO unchanged; RBF unchanged; fever, maternal lethargy, hepatitis, and hemolytic anemia
CO increased; RBF unchanged or increased; maternal flushing, headache, tachycardia, lupus-like syndrome
CO decreased; RBF decreased; maternal increased uterine tone with possible decrease in placental perfusion; neonatal depressed respirations
CO unchanged; RBF unchanged; maternal tremulousness, flushing, headache; neonatal depressed respirations; contraindicated in women with asthma and heart failure
CO unchanged; RBF unchanged; maternal orthostatic hypotension and headache (also a tocolytic); no neonatal effects known
16.2
T A B L E
16.3
T A B L E
of the drug. Reversal of the effects of excessive magne-sium concentrations is accomplished by the slow intra-venous administration of 10% calcium gluconate, along with oxygen supplementation and cardiorespiratory sup-port, if needed.
Antihypertensive therapy is initiated if, on repeated measurements, the systolic blood pressure is >160 mm Hg or if diastolic blood pressure exceeds 105 to 110 mm Hg.
Hydralazine is often the initial antihypertensive medica-tion of choice, given in 5- to 10-mg increments intra-venously until an acceptable blood pressure response is obtained. A 10- to 15-minute response time is usual. The goal of such therapy is to reduce the diastolic pressure to the 90-to 100-mm Hg range. Further reduction of the blood pressure may impair uterine blood flow to rates that are
ences a seizure, additional magnesium sulfate (usually 2 g slowly) can be given, and a blood level obtained. Other anticonvulsant therapy with diazepam or similar drugs is generally not warranted.
Transient uterine hyperactivity for up to 15 minutes is associated with fetal heart rate changes, including brady-cardia or compensatory tachybrady-cardia, decreased variability, and late decelerations. These are self-limited and are not dangerous to the fetus unless they continue for 20 minutes or more. Delivery during this time imposes unnecessary risk for mother and fetus and should be avoided. Arterial blood gases are often obtained, any metabolic disturbance should be corrected, and a Foley catheter should be placed to mon-itor urinary output. If the maternal blood pressure is high, if maternal urinary output is low, or if there is evidence of cardiac disturbance, consideration of a central venous catheter and, perhaps, continuous electrocardiogram mon-itoring is appropriate.
HELLP Syndrome
Patients with HELLP syndrome are often multiparous and have blood pressure recordings lower than those of many preeclamptic patients. The liver dysfunction may be
man-ifest as right-upper-quadrant pain, and is all too commonly misdiagnosed as gallbladder disease or indigestion. Major morbidity and mortality with unrecognized HELLP make accurate diagnosis imperative. The first symptoms are often vague, including nausea and emesis and a nonspecific viral-like syndrome. Treatment of these gravely ill patients is best done in a high-risk obstetric center and consists of cardiovascu-lar stabilization, correction of coagulation abnormalities, and delivery. Platelet transfusion before or after delivery is indicated if the platelet count is <20,000/mm3, and it may be advisable to transfuse patients with a platelet count
<50,000/mm3before proceeding with a cesarean birth.
Management of cases of HELLP syndrome should be individualized based on gestational age at presentation, maternal symptoms, physical examination, laboratory find-ings, and fetal status.
SUGGESTED READINGS
American College of Obstetricians and Gynecologists. Chronic hypertension in pregnancy. ACOG Practice Bulletin No. 29.
Obstet Gynecol. 2001;98(1):177–185.
American College of Obstetricians and Gynecologists. Diagnosis and management of preeclampsia and eclampsia. ACOG Practice Bulletin No. 33. Obstet Gynecol. 2002;99(1):159–167.
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17 Multifetal Gestation
This chapter deals primarily with APGO Educational Topic:
Multifetal Gestation
Students should understand that multifetal gestations require modifications in antepartum, intrapartum, and postpartum care.
Topic 20:
183
• Diamnionic/Monochorionic: If division occurs be-tween the 4th and 8th day following fertilization, the chorion has already begun to develop, whereas the amnion has not. Therefore, each fetus will later be sur-rounded by an amnion, but a single chorion will surround both twins.
• Monoamnionic/Monochorionic: In 1% of monozy-gotic gestations, division occurs between days 9 and 12, after development of both the amnion and the chorion, and the twins will share a common sac. Division there-after is incomplete, resulting in the development of con-joined twins. The fetuses may be fused in a number of ways, with the most common involving the chest and/or abdomen. This rare condition is seen in approximately 1 in 70,000 deliveries. This condition is associated with a mortality rate of up to 50%.
RISKS OF MULTIFETAL GESTATION
Multifetal pregnancies are associated with increased peri-natal morbidity, 3 to 4 times that of a comparable singleton pregnancy.
he overall incidence of multiple gestations in the United States is almost 3%, but these pregnancies account for a disproportionate share of perinatal morbidity and mortality. The natural rate of twinning is approximately 1 in 90, and is slightly higher in blacks than in whites. The rate is rising as a result of an increase in mater-nal age and the more frequent use of assisted reproductive tech-nologies (ART) and ovulation-induction agents. Since 1980, there has been a 65% increase in the frequency of twins, and a 500% increase in triplet and high-order births. It is estimated that 43% of triplet and high-order gestations result from ART procedures and 38% from ovulation induction; spontaneous conception accounts for the re-mainder. Although the exact mechanism is not known, monozygotic twinning is also higher in pregnancies con-ceived using ART.
Twin gestations can be characterized as dizygotic (fra-ternal) or monozygotic (identical). Dizygotic twins occur when two separate ova are fertilized by two separate sperm.
Monozygotic twins result from the division of the fertil-ized ovum after conception. There is a marked difference in the incidence of twinning in various populations, almost exclusively the result of the incidence of dizygotic twinning.
The incidence of monozygotic twinning is fairly constant around the world, at approximately 1 in 250 pregnancies.
Increasing maternal age and increasing parity are independent risk factors for dizygotic twinning, and rates are higher among mothers of families with twins.
NATURAL HISTORY
The following describes the various developmental se-quences possible when the monozygotic conceptus sepa-rates into twins (also called chorionicity) [Fig. 17.1]:
• Diamnionic/Dichorionic: If division of the conceptus occurs within 3 days of fertilization, each fetus will be surrounded by an amnion and chorion.
T
The most significant cause of morbidity is preterm labor and delivery.
Compared with singleton pregnancies, which are delivered at an average gestational age of 40 weeks, twins are deliv-ered at an average of 37 weeks, triplets at 33 weeks, and quadruplets at an average of 29 weeks. Thus, with each additional fetus, the length of gestation is decreased by approximately 4 weeks. Other associated morbidities include intrauterine growth restriction, hydramnios (in approximately 10% of multiple gestations, predominantly monochorionic gesta-tions), preeclampsia (3 times more frequent in twin gestagesta-tions), congenital anomalies, postpartum hemorrhage, placental
