Surgery in the Pregnant Patient

The pregnant patient presents a unique clinical challenge for the general surgeon. About 7% of pregnancies are complicated by nonobstetric surgical problems, and an estimated 1 in 500 pregnancies will need an operation for nonpregnancy-related issues. Table 72.1 is adapted from a 10-year review of the hospital episode statistic of all admissions to English NHS hospitals. Of 6.5 million pregnancies, 47,600 nonobstetric surgeries occurred, and 12,500 were abdominal of any kind. In a review of 44 papers and 12,452 patients, the effects of nonobstetric surgical procedures on maternal and fetal outcomes were studied; a maternal death rate of 0.006% and a miscarriage rate of 5.8% were reported. Most indications for surgical intervention are common for the patient’s age group and unrelated to pregnancy, such as acute appendicitis, symptomatic cholelithiasis, perianal, soft tissue, breast masses, or trauma.

Table 72.1

Operations performed out of 6.5 million pregnancies in the United Kingdom from 2002–2012.

Adapted from Balinskaite V, Bottle A, Sodhi V, et al. The risk of adverse pregnancy outcomes following nonobstetric surgery during pregnancy: Estimates from a retrospective cohort study of 6.5 million pregnancies. Ann Surg . 2017;266:260–266. ENT , Ear, nose, and throat.

	Number Of Operations (%)
Abdominal, any kind	12493 (26.2)
Appendectomy	3062 (6.4)
Cholecystectomy	1306 (2.7)
Dental	5365 (11.3)
Skin, nail	4762 (10.0)
Orthopedic	4563 (9.6)
ENT	3060 (6.4)
Perianal	2977 (6.2)
Breast	1884 (4.0)
Cancer	710 (1.5)

Changes in maternal anatomy and physiology and safety of the fetus are among the issues of which the surgeon must be cognizant. The presentation of surgical diseases in the pregnant patient may be atypical or may mimic signs and symptoms of a normal pregnancy. A standard evaluation may be unreliable because of pregnancy-associated changes in diagnostic tests or laboratory test results. Finally, many physicians may be more hesitant to employ diagnostic evaluation and treatment. Any of these factors may result in a delay in diagnosis and treatment, adversely affecting maternal and fetal outcome. The fundamental principle of managing a pregnant woman with a nonobstetric surgical problem is to not penalize the patient, and her care, for being pregnant. There are two patients to be sure, but the baby’s health is dependent on the mother’s. Although consultation with an obstetrician is ideal when caring for a pregnant patient, the surgeon needs to be aware of this fundamental principle when this resource is unavailable. This chapter discusses key points when caring for the pregnant patient who presents with nonobstetric surgical disorders.

Physiologic Changes of Pregnancy

Progesterone and estrogen, two of the principal hormones of pregnancy, mediate many of the maternal physiologic changes in pregnancy. Normal laboratory values differ in the gravid compared with the nonpregnant patient. The diaphragm can be elevated in pregnancy up to 4 cm, and the lower chest wall can widen up to 7 cm. These changes may also mimic similar pathophysiology that occurs in nonpregnant women who have cardiac or liver disease. Elevated progesterone levels, as well as decreased serum motilin, result in smooth muscle relaxation, producing multiple effects on several organ systems. In the stomach, this decreased smooth muscle tone results in diminished gastric tone and motility. The lower esophageal sphincter tone is also decreased and, when combined with increased intraabdominal pressure, results in an increase in the incidence of gastroesophageal reflux. Small bowel motility is reduced, increasing small bowel transit time. Absorption of nutrients, however, remains unchanged, with the exception of iron absorption, which is increased because of increased iron requirements. In the colon, pregnancy-related changes usually manifest as constipation. This is caused by a combination of increased colonic sodium and water absorption, decreased motility, and mechanical obstruction by the gravid uterus. An increase in portal venous pressure, and therefore an increase in the pressure in the collateral venous circulation, results in dilation of the veins at the gastroesophageal junction. This is of importance only if the patient had esophageal varices before becoming pregnant. The most common result of the increased portal venous pressure is dilation of the hemorrhoidal veins, leading to the well-known complaint of hemorrhoids.

In addition to alterations in smooth muscle tone and motility, other notable changes occur in the gastrointestinal tract. The function of the gallbladder is altered, as is the chemical composition of bile. During the second and third trimesters, the volume of the gallbladder may be twice that found in the nonpregnant state, and gallbladder emptying is markedly slower. Up to 4% of pregnant patients have gallstones on routine obstetric ultrasound. Still, only 1 of every 1000 pregnant patients develops symptoms. It is unknown whether the increased biliary stasis, changes in bile composition, or combination of these two factors results in an increased risk for gallstone formation, but the risk for developing gallstones increases with multiparity. However, the incidence of symptomatic cholelithiasis during pregnancy is similar to the incidence in age-related nonpregnant women.

Some of the changes of pregnancy closely resemble those of liver disease. These include spider angiomas and palmar erythema from elevated serum estrogen levels. Hypoalbuminemia is also seen along with elevated serum cholesterol, alkaline phosphatase, and fibrinogen levels. Serum bilirubin and hepatic transaminase levels remain unchanged during pregnancy.

In the cardiovascular system, peripheral vascular resistance is decreased as a consequence of diminished vascular smooth muscle tone. Cardiac output increases by as much as 50% during the first trimester of pregnancy. Initially, this is caused by an increased stroke volume resulting from an increase in plasma volume and red blood cell mass, but a gradual increase in maternal heart rate also is a contributing factor. Cardiac output falls back to almost normal late in pregnancy, usually during 36 to 40 weeks, gestation. During the third trimester, cardiac output is dramatically decreased when the mother is lying supine. This is caused by compromised venous return from the lower extremity caused by compression of the inferior vena cava by the gravid uterus. In the supine position, the inferior vena cava may be completely occluded; venous drainage of the lower extremities is through collateral channels. With this drop in preload, an increase in sympathetic tone usually maintains peripheral vascular resistance and blood pressure. However, up to 10% of patients may experience supine hypotensive syndrome in which the sympathetic response is not adequate to maintain blood pressure. During anesthesia induction in the operating room, anesthetic agents may inhibit the compensatory sympathetic response, causing a more precipitous fall in blood pressure. This finding is of particular importance in evaluating the pregnant trauma patient, who must be rolled onto the left side down lateral decubitus position to accurately assess blood pressure. The pregnant patient should always be placed in the left lateral decubitus position during any procedures performed during the third trimester, relieving caval compression by the enlarged uterus.

Inguinal swelling secondary to varicosities of the round ligament is also a phenomenon that occurs during pregnancy. The increase in swelling is a result of hormonal and mechanical changes. It is often mistaken for an inguinal or femoral hernia. Appropriate treatment includes careful physical examination and ultrasound if needed. The varicosities generally resolve postpartum.

Oxygen consumption increases during pregnancy. Minute ventilation increases by 50% because of an increase in tidal volume, which appears to be a result of an elevated serum progesterone level. Progesterone not only increases the sensitivity of the respiratory centers to carbon dioxide (CO ₂ ), but it also acts as a direct stimulant to the respiratory centers. As a consequence of the increased minute ventilation, the maternal partial arterial oxygen tension (PaO ₂ ) level during late pregnancy ranges from 104 to 108 mm Hg and the maternal partial arterial CO ₂ (PaCO ₂ ) level ranges from 27 to 32 mm Hg. Renal compensation maintains a normal maternal pH. The decreased PaCO ₂ level increases the CO ₂ gradient from the fetus to the mother, facilitating CO ₂ transfer from the fetus to the mother. These findings are critical in managing the ventilator dependent pregnant patient during and after surgery. The oxygen-hemoglobin dissociation curve of maternal blood is shifted to the right; this, coupled with the increased affinity of fetal hemoglobin for oxygen, results in increased oxygen transfer to the fetus. Elevation of the diaphragm by as much as 4 cm results in a decrease in total lung volume by 5%. Diminished expiratory reserve volume and residual volume result in a functional residual capacity that is 20% lower than that in the nonpregnant woman. Vital capacity and inspiratory reserve volume remain stable.

In the kidney, there is an increase in the glomerular filtration rate by 50% that accompanies a 75% increase in renal plasma flow. Urinary glucose excretion increases as a direct consequence of the increased glomerular filtration rate. The blood urea nitrogen level decreases by 25% during the first trimester and is maintained at that level for the remainder of the pregnancy. The serum creatinine level also decreases by the end of the first trimester from a nonpregnant value of 0.8 to 0.7 mg/dL and may be as low as 0.5 mg/dL by term. A five- to tenfold increase in the serum renin level occurs with a subsequent four- to fivefold increase in the angiotensin level. Although the pregnant patient is apparently less sensitive to the hypertensive effects of the increased angiotensin, elevated aldosterone levels result in an increase in sodium reabsorption, overcoming the natriuresis produced by elevated progesterone levels. Serum sodium levels are decreased, however, because the increase in sodium reabsorption is less than the increase in plasma volume. Serum osmolality is decreased to 270 to 280 mOsm/kg.

The increase in plasma volume and red blood cell mass is accompanied by a progressive rise in the leukocyte count during pregnancy, an important consideration when evaluating for systemic signs of infection. During the first trimester, the white blood cell count ranges from 3000 to 15,000 cells/mm ³ , increasing to a range of 6000 to 16,000 cells/mm ³ during the second and third trimesters. The platelet count progressively declines throughout pregnancy, whereas the mean platelet volume tends to increase after 28 weeks’ gestation.

Increasing platelet counts together with high levels of circulating estrogen, increasing procoagulants, and progressive venous stasis generates a hypercoagulable state during normal pregnancy. Plasma fibrinogen, vonWillebrand factor, and factors II, V, VII, VIII, IX, X, XII increase, while protein S and the response to activated protein C decrease. Serum plasminogen activator inhibitor 1 (PAI1) and placental PAI2 increase, decreasing the bodies’ response to intrinsic tissue plasminogen activator (tPA), resulting in a decrease in fibrinolysis. ^, Increasing pressure from the gravid uterus on the inferior vena cava together with decreased venous tone contribute to venous stasis that progresses with increasing pregnancy. The end result is a fivefold increase in the risk of venous thromboembolism during pregnancy, that increases to more than twentyfold during the puerperium. In women with inherited hypercoagulable mutations, the risk of thrombosis increases further still. Despite these alterations in the coagulation cascade and platelet count, bleeding and clotting times are unchanged.

Safety Concerns in Pregnancy

Radiologic Concerns

Radiographic studies remain useful diagnostic tools for the pregnant patient. The greatest concern with radiation exposure is the risk to the fetus from the exposure. The accepted maximum dose of ionizing radiation during the entire pregnancy is 5 cGy. The fetus is at the highest risk from radiation exposure from the preimplantation period to approximately 15 weeks’ gestation. Primary organogenesis occurs during this time and the teratogenic effects of radiation, particularly to the developing central nervous system, are at their highest. Perinatal radiation exposure has also been associated with childhood leukemia and certain childhood malignancies. The radiation dose that has been associated with congenital malformation is higher than 10 cGy. As shown in Table 72.2 , radiation exposure to the fetus with the doses from the more common radiology procedures is well below that threshold. Nonetheless, prudence on the part of the clinician is required to avoid unnecessary fetal exposure to ionizing radiation, especially during the first and early second trimesters, when the risk from exposure is greatest.

Table 72.2

Fetal radiation exposure with radiographic imaging.

Examination Type	Estimated Fetal Radiation Exposure (cGy)
Two-view chest radiography	0.00007
Cervical spine radiography	0.002
Pelvis radiography	0.04
Head CT	<0.050
Abdomen CT	2.60
Upper GI series	0.056
Barium enema	3.986
HIDA scanning	0.150

CT, Computed tomography; GI, gastrointestinal; HIDA, hepatobiliary iminodiacetic acid.

Magnetic resonance imaging (MRI) avoids exposure to ionizing radiation but poses an unknown risk to the fetus. Animal studies have shown no teratogenic effect or increased incidence of fetal death or congenital malformations from the electromagnetic radiation, static magnetic field, radiofrequency magnetic fields, or intravenous (IV) contrast agents used during MRI. Theoretically, the gradient magnetic fields may produce electric currents in the patient and the high-frequency currents induced by radiofrequency fields may cause local generation of heat. The long-term effect of exposure is not known. The National Radiological Protection Board has advised against the use of MRI during the first trimester of pregnancy. MRI has become the diagnostic modality of choice however, in the work up of complex fetal anomalies in the second and third trimester.

Contrast media may be administered with various techniques of body imaging. If computed tomography (CT) has been performed during pregnancy with iodide contrast, neonatal thyroid function should be checked during the first week after delivery. No effect on the fetus has been observed after the use of gadolinium contrast medium with MRI.

Ultrasonography is routinely used by obstetricians during pregnancy. Although tissue heating and cavitation are theoretical effects of ultrasound exposure, such effects have never been reported. Ultrasound may be a helpful alternative diagnostic tool when trying to avoid exposure to ionizing radiation but does have some limitations. Deeper structures are difficult to visualize and may be obscured by superficial structures that are more echo dense. Ultrasound imaging has a limited field of view and is highly operator-dependent. Despite these limitations, certain disease processes, such as a palpable breast mass or suspected appendicitis, may be evaluated effectively and safely.

Medication Concerns

The surgeon will, on occasion, need to prescribe medications to treat the pregnant patient with surgical disease. In this section, we provide an overview of medications the surgeon may commonly prescribe. The list is by no means comprehensive and, prior to using any medication, consultation with the patient’s obstetrician is necessary. It is noteworthy that over 50% of pregnant woman take at least one medication with an average of 2.6 medications, and the use of four or more medications in the first trimester has tripled (9.9%–27.6%) over the past three decades.

In 1979, the U.S. Food and Drug Administration (FDA) established five letter risk categories (i.e., A, B, C, D, X) to indicate the potential fetal risk if used during pregnancy. In 2015 the FDA developed a new labeling system known as the Pregnancy and Lactation Labeling Rule (PLLR) in an effort to provide more relevant information for better provider decision-making and patient-specific counseling. This new classification system removes the pregnancy risk category lettering system and provides information in a narrative form in order to more accurately describe the risks involved with using medications in pregnancy. ^, The lettering system is to be removed entirely by June 2020. One limitation of PLLR is medications (both prescription and over-the-counter) approved prior to June 1, 2001 do not have to provide a narrative summary, potentially making it more difficult for providers to locate information on pregnancy risk.

Despite this new classification system, the five pregnancy risk categories are most commonly referenced and utilized.

Category A: These drugs have been tested and found to be safe during pregnancy. Category A includes drugs such as folic acid, vitamin B6, and some thyroid medicines in prescribed doses.
Category B: These drugs are frequently used during pregnancy and do not appear to cause major birth defects or other problems. Category B includes some antibiotics, prednisone, insulin, acetaminophen (Tylenol), aspartame (Equal, NutraSweet), famotidine (Pepcid), and ibuprofen (Advil, Motrin) before the third trimester. Pregnant women should not take ibuprofen during the last 3 months of pregnancy.

The FDA offers the following classifications for prescription drugs that should not be taken during pregnancy:

Category C: These are drugs that are more likely to cause problems for the mother or fetus, and drugs for which safety studies have not been finished. Most of these drugs do not have safety studies in progress. These drugs often come with a warning that they should be used only if the benefits of taking them outweigh the risks. This is something the surgeon would need to discuss with the patient’s obstetrician. These drugs include prochlorperazine (Compazine), pseudoephedrine (Sudafed), fluconazole (Diflucan), and ciprofloxacin (Cipro). Some antidepressants are also included in this group.
Category D: These include drugs that have clear health risks for the fetus and include alcohol, lithium, phenytoin (Dilantin), and except for select circumstances, most forms of chemotherapy.
Category X: These drugs have been shown to cause birth defects and should never be taken during pregnancy. These include drugs to treat skin conditions such as cystic acne (isotretinoin [Accutane]) and psoriasis (etretinate [Tegison], acitretin [Soriatane]), thalidomide (sedative), and diethylstilbestrol (DES; prevents miscarriage) that was used up until 1971 in the United States and until 1983 in Europe.

Analgesics

Over-the-Counter Medications

Acetaminophen, the active ingredient in Tylenol, is considered safe during pregnancy. Well researched by scientists, acetaminophen is used primarily for headaches, fever, aches, pains, and sore throat. It can be used during all three trimesters of pregnancy.

Nonsteroidal antiinflammatory drugs (NSAIDs) include aspirin, ibuprofen (Advil, Motrin), and naproxen (Aleve). Aspirin, which contains salicylic acid as its active ingredient, should generally be avoided by expectant mothers because it can pose risks for the mother and fetus. Generally, aspirin is not recommended during pregnancy; the exception being low-dose aspirin (60–100 mg daily) is sometimes recommended for pregnant women with recurrent pregnancy loss, clotting disorders, and preeclampsia.

The use of higher doses of aspirin poses various risks depending on the stage of pregnancy. During the first trimester, use of higher doses of aspirin poses a concern for pregnancy loss and congenital defects. Taking higher doses of aspirin during the third trimester increases the risk of the premature closure of a vessel in the fetus’s heart. Use of high-dose aspirin for long periods in pregnancy also increases the risk of bleeding in the brain of premature infants.

Ibuprofen and naproxen are safer options, but both should be used with caution during pregnancy. They are considered safe in the first two trimesters but are ill advised in the final three months because they can also increase bleeding during delivery and increased risk for birth defects.

Prescription Medications

Prescription analgesics are available in several different forms and brand names, including codeine, tramadol, hydrocodone and acetaminophen (Vicodin, Norco, Lortab), oxycodone (OxyContin), oxycodone and acetaminophen (Percocet), morphine (MS Contin), meperidine (Demerol), and fentanyl (Duragesic, Sublimaze). These drugs may be used occasionally in pregnant patients when the benefits of the drug outweigh the potential risks. Opioids such as methadone (Dolophine) and buprenorphine (Butrans) are often used in pregnant patients with opioid use disorder to prevent withdrawal or the nonmedical use of opioids. ^,

However, there is no known safe level of narcotic use during pregnancy. Risks to the fetus include poor fetal growth, stillbirth, preterm delivery, and a very low risk of birth defects. Chronic use of opioids during pregnancy can lead to neonatal abstinence syndrome. Used late in pregnancy and close to delivery, a neonate is at increased risk of withdrawal symptoms and respiratory depression.

Antibiotics

Antibiotics may be necessary to treat various surgery-related infections in pregnancy. The common antibiotics used are listed by class.

Aminoglycosides

In general, aminoglycosides including gentamicin, tobramycin, and amikacinare determined to be low risk to the fetus and are used commonly in pregnancy and surrounding labor and delivery. The only well-known risk seen with other aminoglycosides (i.e., kanamycin and streptomycin) when used during pregnancy is fetal auditory nerve damage to the eighth cranial nerve causing deafness. No epidemiological studies have demonstrated congenital anomalies in infants whose mothers were treated with aminoglycosides during pregnancy. Only one case report exists of gentamicin use in pregnancy where congenital defects were exhibited. Nephrotoxicity has been observed in many patients receiving aminoglycosides, which raises the concern of whether fetal kidney damage may occur with maternal treatment. Although fetal renal damage after maternal gentamicin treatment has not been documented, there have been cases of severe neonatal nephropathy after therapy with this drug.

Tetracyclines

With the use of tetracyclines, including doxycycline, tetracycline, and minocycline, accumulation of the drugs occurs in developing teeth and long tubular bones. Ingestion during the second or third trimester of pregnancy can cause irreversible dental staining in childhood. Depression of bone growth (especially of the fibula in preterm pregnancies) can occur following in utero exposure to tetracyclines. Acute fatty metamorphosis of the liver in pregnancy following tetracycline therapy has been described and is often fatal. Epidemiological studies have not demonstrated a clear link between exposure to tetracyclines and congenital abnormalities. Therefore, a small risk cannot be excluded, but there is no indication of increased risk of malformations in children of women treated with this agent during pregnancy. Although data on the specific safety of doxycycline use during pregnancy is limited, it is assumed the risks of the dental staining and depression of bone growth by tetracyclines in general also pertain to doxycycline use during the second and third trimesters.

Metronidazole

Rare reports and studies have shown no consistent pattern of congenital malformations in infants exposed to metronidazole in utero, making its use in pregnancy controversial. Given the limited information available, and no conclusive human studies, the risk of birth defects caused by exposure to metronidazole during pregnancy appears to be low and is recommended by the Centers for Disease Control and Prevention (CDC) for the treatment of certain infections during pregnancy. It should be noted, however, the use of metronidazole in the first trimester for the treatment of vaginal trichomoniasis or bacterial vaginosis is contraindicated by the manufacturer.

Penicillins

Penicillins are a widely used group of antibiotics that include ampicillin, amoxicillin, nafcillin, penicillin G, penicillin V, and piperacillin. Although penicillins accumulate in amniotic fluid in large amounts during maternal ingestion, no adverse fetal effects have been associated with this group of medications. It must be noted that all penicillins may produce anaphylaxis during pregnancy or immediately after delivery. If anaphylaxis is severe and uncontrolled, it could result in compromising placental circulation and cause fetal damage or death. However, in general, the penicillins have not been shown to be teratogenic and there have been no recognized adverse effects caused by exposure to this antibiotic class. One point to note, drug elimination may be enhanced for some of the penicillins during pregnancy, thus, a higher dose may be needed to achieve optimal concentrations.

Cephalosporins

Cephalosporins are the most widely used class of antibiotics that include cefazolin, cephalexin, cefotetan, cefuroxime, cefoxitin, cefdinir, cefotaxime, cefpodoxime, ceftriaxone, cefepime, and ceftaroline. Based on their spectrum of activity against gram-positive and gram-negative bacteria, they are classified into five generations. Many of the first- and second-generation cephalosporins have been studied extensively in pregnant patients. It is thought most of them are not associated with any known or suspected teratogenic effects and are assumed safe for use during pregnancy. The third-, fourth-, and fifth- generation cephalosporins, however, have not been used extensively during pregnancy, and therefore there is little information known about their effects, but they are assumed + safe to use in pregnancy.

Lincosamide (Clindamycin)

The teratogenic risk of the use of Lincosamide antibiotics during pregnancy is undetermined and there is limited data. Clindaymycin, the most widely used antibiotic in this category, is considered in the same pregnancy risk class (FDA Pregnancy Category B) as amoxicillin, penicillin and vancomycin. The drug has been safely used in the second trimester as an effective treatment of bacterial vaginosis and abnormal vaginal flora.

Macrolides (Azithromycin)

Many reports describing the use of azithromycin in pregnancy have been published. Overall, no increase in the frequency of congenital anomalies was observed among infants of women treated with azithromycin at any time during pregnancy, and it is considered safe to use in pregnancy.

Sulfonamide Derivatives

Trimethoprim/sulfamethoxazole have been associated with increased risk of congenital malformations, namely neural tube defects, cardiovascular malformations, urinary tract defects, oral clefts, and clubfoot. This is mainly due to the trimethoprim component of the antibiotic. Due to trimethoprim being a dihydrofolate reductase inhibitor, it is thought folic acid supplementation can reduce the risk of congenital defects if they are administered prior to conception or concurrently with the antibiotic. Additionally, there is some concern over kernicterus with sulfonamide use. This agent should be avoided in pregnancy.

Fluoroquinolones

The use of fluoroquinolones (i.e., ciprofloxacin, levofloxacin, moxifloxacin, gemifloxacin) during pregnancy has not demonstrated an increased risk of congenital malformations. Although many reports of birth defects displayed in infants when fluoroquinolones were ingested during pregnancy, no pattern in these malformations has been identified. Ciprofloxacin has been the most studied of the fluoroquinolones in pregnant patients. Based on this information, it is thought ciprofloxacin does not have any teratogenic effects and is assumed safe for use during pregnancy. Levofloxacin, moxifloxacin, and gemifloxacin, however, have not been studied or used extensively during pregnancy and therefore there is little information known about their effects. However, animal studies of the fluoroquinolones have suggested some malformation risk, including fetal cartilage damage, and thus, their risk cannot be excluded. In general, it is accepted fluoroquinolones should be avoided in the first trimester, if a safer alternative is available to use.

Other Gram Positive Agents

Vancomycin and clindamycin are commonly used for multidrug resistant gram-positive infections or for penicillin-allergic patients. No studies or reports have attributed congenital malformations or other adverse events to their use, thus they are considered safe to use in pregnancy.

Summary of Antibiotic Use

Although antibiotics are commonly prescribed to pregnant women, details relating to the effects of many of these drugs remain poorly understood. If an antibiotic must be prescribed, it is important to be aware of the effects these drugs can have on pregnancies and to prescribe the most suitable agent with the least risk to the pregnancy.

Antithrombotic Agents Thrombotic Agents

Anticoagulants

Heparin

The recommended therapeutic agent used in pregnancy for the prevention and treatment of venous thromboemboli is low–molecular-weight heparin (Category B) which has largely replaced standard, unfractionated heparin (Category C). Neither of these agents cross the placenta and are safe in pregnancy, however unfractionated heparin may be associated with increased maternal bone loss.

Danaparoid

Danaparoid is a low–molecular-weight heparinoid with both anti-Xa and antithrombin effects. Danaparoid neither crosses the placenta nor is secreted in breast milk and thus is theoretically safe in pregnancy. ^, A review of the literature from 1981 and 2004 by Lindhoff-Last and colleagues reported use of danaparoid in 51 pregnancies with heparin intolerance with no adverse pregnancy effects. As it is a heparinoid, there remains the (remote) possibility of heparin-induced thrombocytopenia. However, it remains the anticoagulant of choice for use in pregnancy when heparin-induced thrombocytopenia has occurred.

Coumadin

While vitamin K antagonists such as warfarin are well-established and highly effective anticoagulants, they are contraindicated in pregnancy. Vitamin K antagonists cross the placenta and anticoagulate the fetus (Category D). Warfarin use during pregnancy has been associated with miscarriage, prematurity, lower birth weight, neurodevelopmental problems and fetal bleeding, as well as a risk of major birth defects with first trimester exposure. ^, ^, ^, In select circumstances, warfarin has been used in pregnant patients with newer mechanical aortic valves, targeting a lower international normalized ratio (INR) of 1.5 to 2.0 without complications for the mother or fetus. However, this use of warfarin is still investigational. In the postnatal period, however, warfarin is a suitable alternative to parenteral anticoagulants such as heparin. This transition usually takes place when risk of obstetric hemorrhage is low, commonly about days 5 to 7 after the delivery of the baby. It is not contraindicated in breastfeeding.

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