an optimum for examinations performed in the first trimester when crown–rump length is within 5 days

of the date of conception in 95% of the cases.3–5 The embryonic period refers to the earliest stages of

development and extends to the end of the eighth week, by which time organogenesis has occurred. The

fetal period lasts from the ninth week to birth. During this period, growth and development of tissues

formed during embryogenesis occur in preparation for birth. By the beginning of the third trimester, the

fetus may survive if born prematurely.6 Survival outside the womb depends on the adaptation of fetal

organ systems for independent function at the time of birth. The functional status of the respiratory

system is crucial in determining fetal viability. Periviable birth is defined as birth from 200/7 weeks

through 256/7 weeks. Infants born before 20 weeks are considered abortions. Infants born at 20 weeks

and 21 weeks do not survive. The survival data for births at 22, 23, 24, and 25 weeks of gestation,

excluding infants with birth weights lower than 401 g, greater than 1,000 g, and infants with major

anomalies, are 6%, 26%, 55%, and 72%, respectively.7 Surfactant, a complex mixture of phospholipids

consisting mostly of phosphatidylcholine, is necessary for reduction of surface tension at the alveolar–

air interface and proper oxygen exchange. Surfactant production begins by the 20th week of gestation

but is present in only small amounts before 24 weeks.6 One of the most significant advances in the

reduction of morbidity of prematurity has been the use of antenatal corticosteroids. Binding of

corticosteroids in the fetal lung not only increases secretion of phosphatidylcholine but also induces

morphologic development of pulmonary epithelial cells and increases neonatal lung compliance.

Corticosteroids stimulate development of other organ systems as well, decreasing the incidence of

necrotizing enterocolitis, intraventricular hemorrhage, periventricular leukomalacia, and death. The

maximum developmental effects can be seen as early as 24 hours after maternal administration of

dexamethasone or betamethasone, and administration at the first sign of premature onset of labor can

improve survival, particularly before birth between 22 and 25 weeks.8–10

UTERINE ANATOMY AND PHYSIOLOGY OF LABOR

2 The uterus is a muscular organ responsible for reception, implantation, development, and expulsion of

the fetus. In the nonpregnant woman, the uterus lies in the pelvis, weighs approximately 70 g, and has a

cavity volume of 10 mL. To accommodate the fetus, placenta, and amniotic fluid, the uterus increases in

size and weight and its walls become thinner. By the end of the first trimester, the uterus moves out of

the pelvis and by 20 weeks reaches the level of the umbilicus. By term, its capacity is 500 to 1,000

times greater than that in the nonpregnant state. With progressive increase in size, the uterus contacts

the anterior abdominal wall, displaces the bowel laterally and superiorly, and almost reaches the liver

(Fig. 106-1).11 Coupled with its ascent from the pelvis, the uterus usually rotates to the right due to the

presence of the rectosigmoid on the left side of the pelvis. When the pregnant woman lies supine, the

uterus rests on the vertebral column and compresses the abdominal great vessels, particularly the

inferior vena cava. Right before the last weeks of pregnancy, the uterus undergoes sporadic,

nonrhythmic and painless contractions that are known as Braxton Hicks contractions. The intensity of

these contractions varies between 5 and 25 mm Hg. At term, these contractions become wellcoordinated, reaching pressures up to 80 mm Hg. The factors responsible for the onset and maintenance

of normal labor at term are not completely understood. Multiple mechanisms are responsible for the

spontaneous contraction–relaxation cycles in human myometrium, including changes in intracellular

calcium concentrations, alteration in membrane potential, phosphorylation and dephosphorylation of

myosin light-chain kinase, activation of phosphatases, and recruitment of a number of intracellular

signal pathways. During pregnancy, uterine contractility is maintained in a state of quiescence through

the action of various inhibitors that include but are not limited to progesterone, prostacyclin, relaxin,

parathyroid hormone–related peptide, nitric oxide, calcitonin gene-related peptide, adrenomedullin, and

vasoactive intestinal peptide. Parturition begins as a consequence of release from the inhibitory effects

of pregnancy on the myometrium as well as recruitment of uterine stimulants such as estrogen,

oxytocin, and stimulatory prostaglandins (e.g., PGE2, PGF2α, IL-1, and IL-6). The final common

pathway toward parturition appears to be maturation and activation of the fetal hypothalamic–

pituitary–adrenal (HPA) axis. The result is a dramatic increase in production of the C19 steroid

dehydroepiandrosterone sulfate. The cellular and molecular factors that are responsible for maturation

of the fetal HPA axis seem to be associated with the gestational age-dependent upregulation of a

number of critical genes within each component of the HPA axis: corticotropin-releasing hormone

(CRH) from the fetal hypothalamus, proopiomelanocortin from the fetal pituitary, and

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Adrenocorticotropic hormone (ACTH) receptor and steroidogenic enzymes in the fetal adrenal gland.

Animal models have shown that undernutrition of the mother around the time of conception leads to

precocious activation of the fetal HPA and preterm birth. This suggests that, although maturation of the

fetal HPA axis is developmentally regulated and the timing of parturition may be determined by a

“placental clock” set shortly after implantation, stress may accelerate this clock. Levels of CRH in the

maternal circulation increase from between 10 and 100 pg/mL in nonpregnant women to between 500

and 300 pg/mL in the third trimester of pregnancy and then decrease precipitously after delivery. The

source of the excess CRH is the placenta. The production of CRH by the placenta is upregulated by

corticosteroids produced primarily by the fetal adrenal glands at the end of pregnancy. Under the

influence of estrogen, hepatic-derived CRH-binding protein concentrations also increase in pregnancy.

Circulating CRH levels increase and CRH-binding protein levels decrease before the onset of both term

and preterm labor, resulting in a marked increase in free, biologically active CRH. At a molecular level,

CRH acts by binding to specific nuclear receptors and affecting transcription of target genes. A number

of CRH receptor isoforms dominate, and CRH promotes myometrial quiescence by inhibiting the

production and increasing the degradation of prostaglandins, increasing intracellular cyclic adenosine

monophosphate, and stimulating nitric oxide synthetase activity. At term, CRH acts primarily through

its low-affinity receptor isoforms, which promotes myometrial contractility by stimulating prostaglandin

production from the decidua and fetal membranes and potentiating the contractile effects of oxytocin

and prostaglandins on the myometrium.12

Figure 106-1. Enlarging uterus during gestation. At 12 weeks, the uterus rises out of the pelvis into the abdomen. At 20 weeks, the

fundus is at the height of the umbilicus, and at 36 weeks, the uterus reaches to the upper abdomen.

PREMATURE ONSET OF LABOR

3 Preterm birth is defined as birth between 200/7 weeks and 366/7 weeks of gestation. The diagnosis is

made clinically on the basis of the presence of regular uterine contractions accompanied by a change in

cervical dilatation, effacement, or both, or initial presentation with regular contractions and cervical

dilatation of at least 2 cm. Although only 12% of all live births in the United States fit this criterion,

prematurity is responsible for approximately 70% of neonatal deaths, 36% of infant deaths, 25% to 50%

of cases of long-term neurologic impairment in children, and a high cost to the health care system.13–17

Preterm labor with intact membranes is not the only cause of preterm birth; numerous preterm births

are preceded by either rupture of membranes or medical/surgical problems necessitating delivery.18,19

The etiology of preterm labor is often multifactorial, but the onset of labor from fetal and uterine stress

during surgical manipulation or intra-abdominal inflammatory processes is of most concern to the

surgeon. Bacterial infection of the amniotic tissues or peritoneum leads to a local increase in eicosanoids

and the onset of labor.20 Endotoxin acts on inflammatory cells to increase production of IL-1 and IL-6,

which also amplify local prostaglandin production. All of these factors can act in concert to initiate and

propagate preterm labor. Uterine activation and increased expression of gap junctions as well as

oxytocin receptors can be induced by uterine stretch.21 Uterine trauma due to surgical manipulation can

affect these same mechanisms, leading to premature uterine contractions. The interrelations at various

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levels between the inflammatory response, uterine and maternal trauma, and the initiation of labor can

represent the body’s attempt to expel the fetus from a hostile uterine environment.

Tocolysis

4 To date, there is no evidence that tocolytic therapy has associated direct benefit on improving

neonatal outcome, except for short-term prolongation of pregnancy (up to 48 hours) to allow for the

administration of antenatal steroids, transport of the patient to a tertiary care facility, and fetal

neuroprotection.22–24 In general, tocolysis is indicated between viability (24 weeks of gestation) and 34

weeks of gestation in women with preterm contractions with cervical change. However, it is accepted to

administer tocolytics before viability after events known to cause preterm labor, such as intraabdominal surgery and in utero fetal surgery although evidence of efficacy for such intervention is

lacking.25,26 Prostaglandin synthesis inhibitors, magnesium sulfate, beta2

-adrenergic agonists, and

calcium channel blockers represent the four most common pharmacologic agents used as tocolytics.

Because of the importance of prostaglandins in the initiation of uterine contraction, prostaglandin

synthetase inhibitors are used to stop premature labor. Indomethacin is the nonsteroidal drug used most

frequently for tocolysis because of its quick onset of action and ease of dosing. Studies report a 95%

tocolytic success rate at 48 hours and a potential delay in delivery of 1 week in 80% of patients.27

Magnesium sulfate has long been used in the treatment of preeclampsia and has gained acceptance as a

tocolytic and more recently as a neuroprotective agent to reduce the risk and severity of cerebral palsy

when birth is anticipated before 32 weeks of gestation. Most data support the theory that magnesium

exerts its effects by calcium antagonism. High intracellular magnesium concentrations inhibit Ca2+

entry into myometrial cells, interfering with actin–myosin coupling. High magnesium concentrations

also increase the sensitivity of K+ channels, favoring hyperpolarization and uterine relaxation. Maternal

serum levels necessary to inhibit myometrial contractility range between 4 and 9 mg/dL, two to six

times normal levels.28 Beta2

-adrenergic agonists used in the treatment of preterm labor include ritodrine

and terbutaline. Stimulation of uterine beta2

receptors leads to activation of adenylate cyclase and an

increase in intracellular cyclic adenosine monophosphate (cAMP) concentration. Activation of -

dependent protein kinase A inhibits myosin light-chain phosphorylation and actin–myosin coupling.

Protein kinase A activity is also associated with increased Ca2+ efflux, decreased Ca2+ influx, and

increased K+ conductance. All these actions lead to myometrial relaxation. Because of reports of serious

maternal side effects and possible adverse behavioral effects in offspring after in utero exposure to

terbutaline, the U.S. Food and Drug Administration (FDA) issued a warning regarding the

aforementioned agent and suggested that its use be limited to short-term inpatient acute tocolysis

particularly in the setting of tachysystole.29,30 Calcium channel blockers inhibit entry of calcium through

voltage-dependent Ca2+ channels. The use of oral nifedipine can abolish uterine activity and prevent

delivery with minimal maternal side effects and no reported fetal or neonatal adverse effects.31

However, maternal and fetal side effects can be serious with other tocolytic agents. Premature

constriction of the fetal ductus arteriosus and necrotizing enterocolitis with the use of indomethacin has

been reported and can result in neonatal pulmonary hypertension and even death.32,33 Maternal

cardiovascular side effects, including pulmonary edema, can occur in 5% of beta2 agonist users and 10%

of those treated with magnesium. Although this complication is rare, it can result in maternal death.

Serum concentrations of magnesium needed for tocolysis (4 to 9 mg/dL) are not far from levels causing

ablation of deep tendon reflexes (9 to 13 mg/dL) or respiratory depression (14 mg/dL). The decision to

use tocolytics must be made only after the diagnosis of premature onset of labor is confirmed, and the

benefits of prolonging gestation outweigh the risks of tocolysis. Initiation of tocolytic therapy for

potential but unconfirmed preterm labor is discouraged.34 Maintenance therapy with any of the

aforementioned tocolytic agents has not been demonstrated to prolong pregnancy or improve neonatal

outcomes after an initial treated episode of threatened preterm birth and, therefore, should not be used

for this purpose.35–37

FETAL MONITORING

Perioperative fetal monitoring as well as the monitoring of premature uterine contractions is based on

technology developed for intrapartum fetal monitoring in the late 1950s and early 1960s. Observational

studies performed at that time and in the mid-1970s convincingly established a relationship between the

degree of fetal acidemia and the presence and depth of decelerations and decreased or absent fetal heart

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rate variability.38,39 Established heart rate patterns and variable cardiac responses to fetal and maternal

stimuli reflect an intact, well oxygenated central nervous system (CNS). Identification of deviation from

those patterns indicative of metabolic acidosis was hoped to decrease the incidence of hypoxic–ischemic

encephalopathy and death. Meta-analysis of randomized controlled trials comparing electronic fetal

monitoring with intermittent auscultation has failed to show that electronic fetal monitoring decreased

neurologic morbidity and mortality.40 Recently, researches using the US 2004-linked birth and infant

death data found that the use of electronic fetal monitoring was associated with a substantial decrease

in early neonatal morbidity particularly in preterm fetuses.41 However, authorities in the field remain

skeptical of the findings and have cautioned that an epidemiologic association between fetal monitoring

and reduced neonatal death does not establish causation.42 This controversy is not expected to be solved

any time in the near future, but the fact is that of the approximately 4 million live births a year in the

United States, 85% are assessed with fetal heart rate monitoring, making it the most common procedure

in pregnancy.43 Fetal heart rate monitoring may be performed externally or internally. Most external

monitor devices use the Doppler principle with computerized logic to count and interpret the Doppler

signals originating from the fetal heart and maternal uterus. Internal fetal heart rate monitoring is

accomplished with a spiral device attached to the fetal scalp or other presenting part. A transcervical

intrauterine pressure catheter is sometimes used to monitor more accurately the strength and frequency

of uterine contractions (Fig. 106-2). Both tracings are printed on a continuous strip of paper, with the

fetal heart rate plotted at the top of the graph and uterine activity at the bottom.

Fetal Heart Rate

Normal fetal heart rate during pregnancy ranges between 110 and 160 beats/min. A prolonged baseline

above 160 beats/min is considered a tachycardia, whereas that below 110 beats/min is a bradycardia.

These terms refer to long-term patterns, and minute-to-minute variability in the heart rate away from

baseline is known as acceleration and deceleration. Normal fetal heart rate tracings express continuous

adjustment in the vagal tone through variability in the heart rate. Short-term or beat-to-beat variability

is superimposed on broader, long-term variability of the baseline by three to five beats/min. The fetal

heart rate response governed by a nonacidotic, well-functioning vagal conduction system manifests both

long-term and short-term variability, with fluctuations of peaks and troughs ranging from 6 to 25

beats/min (Fig. 106-3). Decreased heart rate variability, either long or short term, can signal diminished

CNS activity. Although this can be a physiologic response of the fetal sleep–wake cycle or maternal

medication and sedatives, persistently decreased reactivity can signal CNS acidosis. Fetal heart rate

accelerations are normal findings in the second half of pregnancy and occur as a result of increased

sympathetic stimulation and decreased parasympathetic stimulation with fetal movements. Fetal heart

rate decelerations are usually encountered during uterine contractions of the intrapartum period.

Evaluation of decelerations during labor and as part of intraoperative fetal monitoring can give clues to

the status of the placental blood supply. A prolonged deceleration is a visually apparent decrease in the

fetal heart rate baseline that is 15 minutes or more, lasting 2 minutes or more but less than 10 minutes

in duration. Early decelerations are characterized by a symmetrical and gradual decrease and return of

the fetal heart rate that mirror uterine contractions and reflect increased vagal tone from a transient

increase in intracranial pressure. This pattern is considered a benign physiologic manifestation of a

functioning autonomic nervous system and has no adverse outcome. Variable decelerations are

distinctively recognized by their abrupt decrease in fetal heart rate of 15 beats/min or greater from the

onset of the deceleration to the beginning of the fetal heart rate nadir of 30 seconds, lasting 15 seconds

or greater, and less than 2 minutes in duration. When variable decelerations are associated with uterine

contractions, their onset, depth, and duration vary with successive uterine contractions. Isolated

variable decelerations have little clinical significance, but if persistent with inadequate recovery

between contractions, fetal hypoxemia and acidosis can occur. Late decelerations present usually as a

symmetrical and gradual decrease and return of the fetal heart rate associated with a uterine

contraction. The deceleration is delayed in timing, with its nadir occurring after the peak of the

contraction. Late decelerations have an ominous connotation as they usually represent significant

uteroplacental compromise; causes can range from maternal hypotension due to inferior vena cava

compression to hypoxia or anemia.44 Intraoperative fetal compromise as indicated by an ominous heart

rate tracing must be treated by correcting maternal hypotension or increasing oxygen delivery with

increased FIO2

, positional changes, aggressive fluid resuscitation, or blood transfusion. The inability to

improve the intrauterine milieu can necessitate an emergent cesarean section to prevent fetal demise.45

The decision to use continuous fetal heart rate monitoring during nonobstetric surgery in pregnancy is

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controversial and should be based on gestational age, type, site, duration, and extent of the procedure.

For previable pregnancies (<23 weeks), documentation of fetal heart activity by Doppler before and

after the procedure suffices.46 For viable gestations, there is less consensus for fetal heart rate

monitoring, but at a minimum, simultaneous electronic fetal heart rate and contraction monitoring

should be performed before and after the procedure to assess fetal well-being and the absence of

contractions. If the decision is to perform intraoperative electronic fetal heart monitoring, then all the

necessary provisions should be made to provide optimal safety for the mother and the fetus. These

include availability of obstetric care providers, anesthesiologists, neonatologists, and nurses working as

a team and ready to intervene during the surgical procedure for fetal indications. Informed operative

consent should thus be obtained in anticipation for a possible emergency delivery.47

Figure 106-2. Intraoperative and postoperative fetal monitoring using noninvasive surface Doppler and pressure sensor to monitor

uterine contractions. (Reproduced from Miller DA, Paul R. Antepartum–intrapartum monitoring. In: Scott JR, DiSaia PJ, Hammond

CB, et al., eds. Danforth’s Obstetrics and Gynecology. 8th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 1999:243–255.)

IMAGING MODALITIES IN THE PREGNANT PATIENT

5 The most commonly used imaging modalities during pregnancy include radiography, ultrasonography,

magnetic resonance imaging (MRI), and computed tomography (CT). The first and the latter are forms

of ionizing radiation. The risks of ionizing radiation are an important source of anxiety for health care

providers and patients that at times can force the physician to avoid the definitive diagnostic study of

choice for fear that any radiation exposure would result in an anomalous fetus. This misconception

could place both the mother and the fetus in greater danger from misdiagnosis. Although experimental

data regarding the effects of ionizing radiation on the developing human fetus are impossible to obtain,

animal exposure and follow-up of those inadvertently exposed to diagnostic and therapeutic radiation

have provided some information. Retrospective studies of atomic bomb survivors in Hiroshima,

Nagasaki, and victims of the atomic power plant disaster in Chernobyl have also allowed for evaluation

of the effects of massive radiation exposure in utero.48,49

Figure 106-3. Fetal heart variability. A: Short-term and long-term variability both absent: abnormal. B: Short-term variability

present, long-term variability absent: abnormal. C: Long-term variability present, short-term variability absent: abnormal. D: Both

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short- and long-term variability present: normal. (Reproduced from Miller DA, Paul R. Antepartum–intrapartum monitoring. In:

Scott JR, DiSaia PJ, Hammond CB, et al., eds. Danforth’s Obstetrics and Gynecology. 8th ed. Philadelphia, PA: Lippincott Williams &

Wilkins; 1999:243–255.)

Ionizing Radiation

Fetal effects of ionizing radiation depend on the dose absorbed by the fetal tissue and the stage of fetal

development during exposure. Exposure is defined as the amount of ionic charge created by the

radiation on passing through a defined mass of air. Units traditionally used to measure the effects of

ionizing radiation include the radiation absorbed dose (rad) and the roentgen equivalents man (rem).

Modern units include the gray (Gy) and sievert (Sv). According to the International System of Units, Gy

is the unit that describes the potential radiation exposure from medical diagnostic equipment, but rad is

the predominant measure used. One gray (Gy) is strictly defined as the deposition of 1.0 joule of energy

per kilogram of tissue, and 1 rad is 1% of 1 Gy. As a gross estimate, exposure to 1 roentgen gives an

absorbed dose of 1 rad or 10 mGy.

Sv is generally used to measure the public exposure to radiation as it accounts for factors such as type

of radiation amount of time exposed, level of protection, and distance from the radiation source. One

sievert (Sv) = 1 Gy = 100 rads. It is a misconception to assume that the radiation dose that a pregnant

woman is exposed to or absorbs is the same as that absorbed by the fetus as the latter is partially

protected from radiation injury by a pregnant woman’s surrounding soft tissues and uterus, both of

which generally stop alpha and beta particles from penetration if they are not ingested, injected, or

inhaled.50,51 Radiographic evaluation of the abdomen and pelvis is most likely to expose the fetus to

direct ionizing radiation, whereas examination of the extremities and chest leads to exposure from

scatter radiation only (Table 106-1).51 The potential deleterious consequences of radiation-induced

ionization of vital cellular structures can be divided into four categories: (1) lethal effects, (2)

teratogenic effect, (3) growth retardation, and (4) oncogenic potential. The occurrence of each effect

depends upon the gestational age at the time of radiation exposure, the dose of radiation absorbed by

the fetus, and fetal cellular repair mechanisms. The first three categories of adverse pregnancy

outcomes have a deterministic effect whereby a threshold or No-Adverse-Effect Level exists. After

exceeding the No-Adverse-Effect Level, a deterministic effect generally shows a gradient relationship

with the absorbed dose – the larger the absorbed dose, the more severe the effect. On the contrary,

cancer appears to have a stochastic effect in which, the probability, but not the severity of the effect,

increases with the radiation dose. Stochastic effects are monoclonal, resulting in changes to the cell

genome and altered differentiation and function of the affected cells.

Lethal Effects of Ionizing Radiation

The developing human is most sensitive to the lethal effects of ionizing radiation during the first 14

days after conception (3 to 4 weeks of gestational age). During this period, the “all or none” principle

applies to the radiation-exposed embryo; it either survives undamaged or succumbs. At that gestational

age, a dose of 100 to 200 mGy (10 to 20 rad) can be lethal for an embryo. Shortly thereafter, the

threshold for fetal death increases to 250 to 500 mGy (25 to 50 rad). The estimated radiation dose to

kill all embryos or fetuses less than 18 weeks of gestational age is 5,000 mGy (500 rad). At term, the

fetal risk equals the pregnant woman’s risk at 20,000 mGy (2,000 rad).52,53

Table 106-1 Radiation Dosing to the Conceptus and Uterus from Selected

Radiographic Examinations

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