Cardiovascular Considerations

To accommodate growing requirements for oxygen and nutrition delivery, cardiac output increases by an estimated 30–50%. The vasodilating effects of prostacyclin and progesterone in addition to the low vascular resistance of the placenta cause a reduction in systemic vascular resistance, contributing to increased cardiac output. This is augmented further by increases in both heart rate and stroke volume as pregnancy progresses.

Of particular clinical importance, this new elevated baseline cardiac output can be threatened through otherwise innocuous surgical positioning. By the second trimester, the gravid uterus emerges more prominently from the pelvis and can cause clinically significant compression of the inferior vena cava in the supine and lithotomy positions, with resultant acute drop in venous return and cardiac output. Hence, standard supine and lithotomy positions should be avoided in favor of right-sided elevation of 15–20 degrees to accomplish a left lateral tilt, thereby reducing uterine compression of the vena cava and optimally preserving cardiac output.

Respiratory Considerations

Several competing alterations will affect respiratory and airway considerations in the pregnant patient. The enlarging gravid uterus ascends from the pelvis and – in concert with pregnancy-related weight gain – can exert mechanical restriction on respiration. These combined effects may result in a subsequent decline in functional residual capacity. Offsetting these mechanical concerns, early in the first trimester both respiratory rate and tidal volume increase. These changes lead to increased minute ventilation and address increasing maternal and fetal oxygen requirements. A clinically pertinent effect of the increased minute ventilation is observation of a mild respiratory alkalosis, attenuated by increased renal bicarbonate secretion.

Airway management is complicated by anatomic changes of pregnancy. The aforementioned weight gain of pregnancy increases the difficulty of intubation. Furthermore, edema of the oropharynx, larynx, and trachea may limit endotracheal tube placement and increase risk of bleeding and trauma related to establishment of an airway. Finally, concerns regarding decreased reliability of the gastroesophageal sphincter lead to increased risk of regurgitation and aspiration.

Hematologic Considerations

Blood volume increases throughout pregnancy, ultimately increasing up to 40–50% by term. Because the expansion of plasma outpaces the increase in red blood cell volume, there is a resultant dilutional anemia associated with pregnancy. Additionally, a leukocytosis up to 15,000 WBC per microliter may be encountered during normal pregnancy, thereby potentially raising a false concern for systemic infection. Finally, pregnancy is considered a hypercoagulable state due to increased fibrinogen, factor VII, VIII, X, and XII and decreased fibrinolysis, increasing the risk of thromboembolic events.

Renal Considerations

There is a physiologic 30–50% increase in glomerular filtration rate during pregnancy. At the tubular level, there is a subsequent increase in urinary excretion of calcium and uric acid, which are both potential promoters of stone formation. Additionally, urine pH is typically elevated, potentially related to increased urinary bicarbonate excretion to compensate for the aforementioned respiratory alkalosis. Increased excretion of citrate and thiosulfate, putative inhibitors of stone formation, is thought to offset the effects of the hypercalciuria.

At the macroscopic level, mechanical compression by the gravid uterus at the level of the pelvic brim leads to dilation of the ureter and renal pelvis. This is most pronounced on the right side, with right greater than left dilation seen in 86% of imaging in one retrospective study. The differential lateralization is likely related to both typical dextrorotation of the uterus as well as protective cushioning of the left ureter provided by the sigmoid colon. Besides mechanical events, hormonal effects also contribute with a suspected progesterone-mediated decrease in ureteral peristalsis.

Epidemiology

Renal colic secondary to urolithiasis is considered the most common cause of nonobstetric hospitalization in the pregnant patient. Widely varying estimates suggest that up to 1 : 200 women may suffer renal colic during pregnancy. Gravid stone formers are most likely to be Caucasian. Of those suffering stones during pregnancy, the majority will present in the latter half of gestation.

The majority presenting with stones during pregnancy were not previously identified stone formers, but rather first-time stone formers. Among those who are affected by urolithiasis during pregnancy, their subsequent risk of recurrent stone formation remains to be defined.

Etiology of Stone Disease During Pregnancy

A myriad of potential etiologic factors in stone formation during pregnancy have been proposed. Physiologic changes of urine chemistry increase the lithogenicity of urine during pregnancy. In particular, maternal hypercalciuria, hyperuricosuria, and elevated urine pH are all well-recognized pro-lithogenic changes during gestation. The alkaline urine dramatically reduces solubility of calcium phosphate, which is reflected in the fact that approximately 75% of stones in pregnancy are calcium phosphate. Despite substantial predisposition to stone formation, it is reassuring to remember that most women do not have stones during pregnancy, a fact attributed to the physiologic protection in the form of increased urinary inhibitors of stone formation including citrate.

It has been hypothesized that stagnant urine in a hydronephrotic system may contribute to stone formation. Thus the aforementioned “physiologic” hydronephrosis of pregnancy may be causative or coincidental to stone formation during pregnancy. As previously noted, direct external impingement upon the ureter by the enlarged uterus at the level of the iliac vessels is oft considered a primary means for mid- and proximal ureteral dilation. Ureteral dilation may additionally be a result of progesterone-induced relaxation of ureteral smooth muscle. It is important to note that this dilation may obfuscate both diagnosis of ureterolithiasis and the differentiation of obstructing stone from unrelated loin pain during pregnancy.

Diagnosis of Stones During Pregnancy

The diagnosis of urolithiasis remains an imperfect art. The abdominal and loin pain of renal colic – as well as their associated nausea and emesis – are not unique to nephrolithiasis. Indeed, a large retrospective review confirmed clinical signs and symptoms alone are often inadequate to predict obstructing stones during pregnancy. Even among women hospitalized for suspected acute renal colic during pregnancy, stone was confirmed in only 29%. This clinical experience underscores the challenge of accurate diagnosis despite the availability of powerful diagnostic tools and enhanced imaging techniques. Attempting to predict the 29% of pregnant women with a confirmed stone diagnosis, this study found left-sided hydronephrosis >10 mm as the only significant predictor on multivariable analysis. This emphasizes the confusion caused by frequent right-sided hydronephrosis and underscores the fact that the ubiquity of right-sided renal pelvic dilation in later gestation reduces the utility of ultrasound.

Nevertheless, with widespread prenatal use confirming its safety profile, ultrasound (US) remains the cornerstone of diagnostic imaging during pregnancy ( Fig. 17.1 ). No adverse effects to mother or child have been identified. With neither ionizing radiation nor intravenous contrast administration, US is widely accepted as appropriate for use during pregnancy.

Ultrasound shows an obstructing right proximal ureteral stone in a pregnant patient.

In the setting of a markedly dilated ureter, the sonographer may be able to follow the ureteral course and identify an obstructing ureteral stone, although this is the exception as opposed to the rule. Transvaginal ultrasound may allow visualization of distal ureteral stones between the transducer and the bladder when located near the ureterovesical junction. Finally, functional information may be inferred from Doppler US measurements of systolic and diastolic renal arcuate arterial blood flow. An increased renal resistive index has been utilized to successfully differentiate nonobstructive hydronephrosis of pregnancy from hydronephrosis due to ureteral obstruction.

Although computerized tomography (CT) has clearly emerged as preferred imaging for urolithiasis in the general population, concerns regarding fetal radiation exposure continue to limit its use in pregnancy ( Fig. 17.2 ). Advocates for CT, however, point out that its accuracy outperforms both US and magnetic resonance imaging (MRI), and radiation doses can be reduced to levels considered below the threshold for inducing fetal anomalies ( Fig. 17.3 ).

Low-dose CT scan demonstrates a small left ureteral stone (arrow) in a pregnant patient.

MRI of a pregnant patient with right renal colic. A, T2-weighted MRI without contrast reveals right hydronephrosis (arrow). B, Filling defect noted on HASTE MRI without contrast in the right proximal ureter later confirmed to be a 5-mm ureteral stone.

Management of Stone Disease in Pregnancy

An accurate diagnosis is of great importance, as symptomatic urolithiasis has been linked to maternal and fetal morbidity. Definitive diagnosis of a ureteral stone may clarify management options but is often elusive in the parturient. In the absence of endoscopic inspection or CT demonstration, it is often impossible to confirm a ureteral stone. Therefore conservative options remain attractive in order to reduce occurrence of unnecessary surgical interventions ( Fig. 17.4 ). As in the general population, in the absence of absolute indications to intervene one may pursue a course of active surveillance to assess for stone passage.

Management considerations for the pregnant patient with symptomatic urolithiasis.

Medical expulsive therapy (MET) with alpha-blockers is an increasingly embraced adjunctive therapy aimed at increasing stone passage rate. To date, there has been only one study specifically reporting upon MET with tamsulosin during pregnancy. This retrospective study of 27 pregnant patients receiving tamsulosin to expedite passage of presumed ureteral stones specifically assessed perinatal outcomes. In this cohort study, subjects were matched not for predictors of stone passage (e.g., stone size or stone location) but rather for risk factors for adverse neonatal outcomes (tobacco use, prematurity, or small for gestational age). Thus, stone passage was not a primary outcome and the trial was not designed to assess for this. Nevertheless, they observed a 24% increased stone passage rate in the MET group and reported that there was no statistically significant difference in perinatal outcomes. There were two cases of sudden infant death syndrome in the MET group and none in the control group, although the authors noted that there was no obvious mechanistic explanation for this, and the difference was not significant (p = 0.11).

If conservative management is not indicated (e.g., uncontrollable pain or nausea, bilateral obstruction or unilateral obstruction of a solitary functioning kidney with subsequent worsening renal function) or if attempts at conservative management have failed, surgical intervention may be considered. These maneuvers include temporizing options including ureteral stent or nephrostomy tube placement, as well as definitive ureteroscopic stone removal. Shock wave lithotripsy (SWL) is contraindicated during pregnancy due to concerns of catastrophic fetal injury from shock wave injury.

Epidemiology and Risk Factors of Urinary Tract Infections During Pregnancy

UTIs represent a significant public health burden; over 10 million ambulatory visits and nearly 1 million emergency department visits in the United States are attributed to UTIs annually. Women bear the majority of these infections, and pregnancy itself is an independent risk factor for UTIs. Other risk factors for UTIs include diabetes, sexual intercourse, urologic instrumentation, history of UTIs in childhood, functional/anatomic abnormalities of the urinary tract, etc.

UTIs are the most common bacterial infection occurring during pregnancy. Several normal physiologic changes occur during pregnancy that may contribute to an increased risk of UTI. These include dilation of the urinary tract, compression of the bladder by the growing uterus, urinary stasis and increased reflux, and changes to the urine itself, which may favor bacteriuria

UTIs may be categorized anatomically into broad categories of cystitis if confined to the lower tract (including asymptomatic bacteriuria) and pyelonephritis if the UTI involves the upper urinary tract. Of particular importance, pregnancy increases the risk of cystitis progressing to pyelonephritis by 40%.

Implications of Urinary Tract Infections and Asymptomatic Bacteriuria During Pregnancy

UTIs during pregnancy are associated with both maternal morbidity and adverse outcomes for the fetus including preterm birth and low birth weight. In fact, several professional organizations recommend both screening for and treating even asymptomatic bacteriuria during pregnancy, including the U.S. Preventative Task Force (USPTF), the American College of Obstetricians and Gynecologists (ACOG), and the American Academy of Family Physicians. Due to these recommendations screening is implemented in the vast majority of obstetric care.

Asymptomatic bacteriuria (ASB) is defined as ≥10 ⁵ colony forming units of a single bacterium per milliliter of urine in two urine samples. ASB is diagnosed in approximately 5% of pregnant women. Considered a benign condition for nonpregnant patients, ASB during pregnancy increases the risk of maternal pyelonephritis, preterm delivery, and low fetal birth weight. A recent Cochrane review confirmed that antibiotic treatment of ASB reduced incidence of low birth weight but not preterm deliveries. The USPTF recommends first trimester screening with a urine culture, although a positive urinalysis without culture should still receive proper treatment. Following treatment for ASB, a follow-up culture should confirm effective treatment, with consideration for prophylactic treatment for the remainder of the pregnancy.

Pyelonephritis due to ASB in pregnancy has decreased significantly in the setting of routine screening; however, it remains a significant health burden being diagnosed in 1–2% of pregnant women. Pyelonephritis is a clinical diagnosis, and urine culture is the diagnostic test of choice. Blood cultures are inconsistently positive in pregnancy and official recommendations are not in place for routine blood cultures per a recent Cochrane review. The majority of patients are admitted to the hospital and treated with IV fluids and empiric antibiotics until urine cultures are finalized. There is no established standard duration of treatment; however, a 7–14 day course is the most often recommended. Follow-up cultures should confirm effective eradication of the infection. The bacteria most often responsible for UTIs in pregnancy are outlined in Table 17.1 .

Management of Urinary Tract Infections During Pregnancy

It is important to consider both the mother and the fetus when selecting antibiotic therapy. As this remains a dynamic topic, consider consultation with a pharmacist and an obstetrician to assist with antibiotic selection and dosage. Local antibiograms and susceptibility should also be examined. Treatment duration generally increases based on the severity of the infection. Classic recommendations suggest 3–7 days of therapy for ASB or cystitis and up to 14 days for pyelonephritis. A recent Cochrane review evaluated the duration of treatment for ASB and concluded that more data are needed and the recommendation is a standard course until these data are available.

Most antimicrobials can cross the placenta; thus, care must be taken to avoid teratogens. Of note, as of June 2015 the FDA no longer uses the classic letter categorization for labeling these drugs. Instead, drugs are now classified for their phase of care including pregnancy and lactation, as well as for concerns regarding reproductive potential. Commonly used antibiotics are displayed in Table 17.2 . Specific considerations are detailed in the following section.

Nitrofurantoin, often used to treat urinary infections in nonpregnant women, has been a source of controversy during pregnancy. A meta-analysis incorporating over 90,000 pregnant women receiving nitrofurantoin during the first trimester reported conflicting results. Analysis limited to cohort studies demonstrated no association of the antibiotic with major malformations in the offspring. However, analysis of the case-control studies showed a 22% increased odds for major malformations. This has been refuted in other large population-based studies, and the ACOG currently does not recommend against nitrofurantoin in the first trimester in the setting if other antimicrobials are unavailable.

Similar concerns exist for trimethoprim-sulfamethoxazole (TMP-SMX), and as such, many avoid this antibiotic in both the first trimester and final week of pregnancy. In addition, as a folic acid antagonist, any gravid woman taking TMP-SMX should also receive a folic acid supplement.

Fosfomycin is emerging as a potentially safe and effective option during pregnancy; however, data are limited. A review of three randomized control trials of fosfomycin trometamol for both asymptomatic bacteriuria and lower UTIs showed that a single dose of fosfomycin had similar efficacy compared to cefuroxime and amoxicillin/clavulanic acid for the treatment of both conditions in pregnant women.

UTIs and their treatment during pregnancy remain a dynamic topic. Poor maternal and fetal outcomes are associated with UTIs, and screening for asymptomatic bacteriuria is now the standard of care. Recommendations for specific antimicrobial agent and duration of treatment should come from a multidisciplinary team including a urologist, obstetrician, and pharmacist. Follow-up test of cure is important and women who fail to clear their infection should remain on prophylactic antibiotics for the remainder of their pregnancy.

Epidemiology

Of an estimated 810,170 annual cancer diagnoses in women, approximately 5% arise from the urinary tract. The largest cohort study to examine the incidence of malignancy among pregnant women took place in the early 1980s and identified a rate of approximately 2.35/10,000 women. Of note, other than cancer, pregnancy is the only condition in which the natural immune system is altered to allow tolerance. Several studies have examined whether or not pregnancy itself is a risk factor for malignancies and have generally concluded that pregnancy does not increase the risk of malignancy.

Renal Tumors

Renal cell carcinoma (RCC) is the most common renal tumor diagnosed in the pregnant patient. Additionally angiomyolipoma, oncocytoma, and Wilm’s tumor have been reported.

Identification of a renal mass is more challenging in a gravid female patient. Hematuria may be mistaken for vaginal bleeding, hypertension may be attributed to preeclampsia, the gravid body habitus limits the physical exam, and cross-sectional imaging is less frequently employed during pregnancy.

However, once a renal mass is identified, the decision between intervention and observation is dependent on the size and stage of the mass, the suspected histopathologic subtype, and the pregnancy trimester. Treatment early in pregnancy subjects the developing fetus to risk for miscarriage or teratogenicity, whereas delaying treatment in favor of extending the pregnancy may subject the mother to risk of tumor growth or metastasis.

Successful radical nephrectomies have been reported during early pregnancy with the pregnancy continued to completion with delivery of a healthy infant. However, it has been suggested that based on the slow growth rate of small early-staged RCCs, surgical intervention may be delayed until fetal lungs have matured at the end of the second trimester, early third trimester, or even until the postpartum period. If delayed until the third trimester, one may consider concomitant nephrectomy and cesarean delivery, although in most cases the nephrectomy can be performed without having to induce labor. A single case report described a patient who elected conservative management, although over the gestation her mass tripled in size, ultimately metastasizing and leading to death 1 year after delivery of a healthy infant. Although clearly unusual, this case report underscores the need to consider the potential aggressiveness of malignancy rather than automatically deferring treatment until postpartum.

Angiomyolipomas (AMLs) are the second most common renal mass diagnosed in pregnancy. Most AMLs are asymptomatic but when symptoms develop they include hematuria, flank pain, a palpable mass, and rarely hemorrhage. Size matters for these lesions; tumors >4 cm are more likely to rupture. As such, the feared complication of these tumors due to their high vascularity is spontaneous bleeding and/or hemorrhage. Treatment options in a pregnant patient are similar to those offered to the general population and include observation, embolization, or nephrectomy. Case reports have documented successful treatment of AMLs in pregnancy by all three options.

Adrenal Tumors

Adrenal incidentalomas may be identified on ultrasound. If small in character and nonfunctioning these should be managed with observation. Surveillance of these lesions has been recommended as they may represent undiagnosed pheochromocytomas.

Pheochromocytoma in pregnancy has been well described. Incidence is estimated to be 1/54,000 pregnancies. This was previously a morbid diagnosis carrying a fetal mortality rate >50%. With advances in early diagnosis and appropriate treatment the mortality rates are nearly 0% for the mother and approximately 15% for the fetus. Confounding its diagnosis are ambiguous symptoms; hypertension alone is often the only warning sign. Other classic symptoms may include headaches, dizziness, nausea and vomiting, vision changes, and palpitations. The hypertension may initially be attributed to eclampsia in a pregnant patient; however, pheochromocytoma is distinguished by its episodic hypertension presenting earlier in pregnancy and a lack of proteinuria. Plasma or urine catecholamines should be obtained if clinical suspicion arises. As in the nonpregnant patient, MRI is the first-line imaging modality for evaluation and localization of suspected pheochromocytoma.

Pheochromocytoma is treated with surgical excision, with attention to perioperative control of hypertension with a combination of alpha and beta blockade. Similar to RCC, intervention may depend upon gestational age. Reports have noted first trimester fetal mortality rates as high as 40%. Later in the third trimester, one may consider resection of the tumor and simultaneous cesarean section. Laparoscopic excision of pheochromocytoma during pregnancy has been reported with excellent outcomes. Delivery without treatment of the tumor is potentially treacherous due to the increased autonomic activity for the patient. Indeed, delivery method itself is controversial for this specific neoplasm. Data show that maternal mortality is increased for vaginal delivery versus cesarean.

Adrenocortical carcinomas may also present in pregnancy. These aggressive malignancies carry a poor prognosis. A case report has documented successful excision via laparoscopic adrenalectomy. These adrenal tumors may be functioning or nonfunctioning; if they secrete glucocorticoids they may cause Cushing’s syndrome. Alternatively, if they secrete aldosterone, they may present as preeclampsia with hypokalemia. Four cases of maternal adrenal tumors resulting in fetal virilization have been reported. In all four of these cases the maternal malignancy was not discovered until after delivery of the child.

Bladder Tumors

Case reports of bladder cancer in pregnancy extend back to the 1920s. Often heralded by hematuria, diagnosis may be delayed due to misattribution to vaginal bleeding, reported in up to 22% of cases. If concern arises for intravesical abnormality, cystoscopy can be performed safely in the pregnant patient. In addition, transurethral resection can be safely performed in pregnancy acknowledging the mass effect of the uterus on the bladder. Depending on the size of the mass, a staging and/or metastatic evaluation may be necessary.

Several other rare bladder tumors have been identified. Leiomyoma is a benign tumor that may present in the bladder. Four cases have been documented in pregnant patients. Cystoscopy, ultrasound, MRI, and tissue biopsy are important in the work-up to differentiate from its malignant counterpart, leiomyosarcoma. In pregnant patients with histologically confirmed leiomyoma, due to the benign nature of the diagnosis, surgical resection may be delayed until the postpartum period.

Ureteral Tumors

Ureteral cancer has been documented in pregnancy in two case reports. More commonly, benign lesions of the ureter may present as ureteral filling defects during pregnancy, including urolithiasis and malakoplakia.

Urethral Tumors

Urethral carcinomas are another rare urologic cancer. A case report from the 1970s described a woman with a urethral adenocarcinoma that was treated with surgical excision and radiotherapy following normal vaginal delivery of her child. There are several benign urethral lesions; these may increase in size during pregnancy. No emergent treatment is necessary. Finally, leiomyomas of the urethra have been documented in three pregnant patients; all three were treated successfully with surgical excision.

Urachal Tumors

Two case reports of urachal carcinoma diagnosed in pregnancy have been published. One presented as abdominal pain; the other as hematuria. The first case resulted in a normal term delivery after surgical excision. The second case resulted in cystectomy along with hysterectomy in the first trimester of pregnancy due to lymph node involvement.