Medical Conditions in Early Pregnancy
Medical conditions can occur in early pregnancy and, although rare, can cause significant maternal and fetal morbidity. Often, women with these diseases can initially present to an obstetric triage or emergency room setting and may even necessitate referral to a tertiary care center. Prompt recognition and treatment of medical conditions during pregnancy can help to optimize maternal and fetal outcomes. The focus of this chapter will be on a few of the most common medical conditions that can present in early pregnancy: pyelonephritis, nephrolithiasis, and pancreatitis. Pregnancy is a risk factor for pyelonephritis, which may occur due to lack of treatment or incomplete treatment of bacteriuria. Nephrolithiasis and pancreatitis often present with nonspecific symptoms such as abdominal pain, nausea, and vomiting that can mimic other conditions seen in early pregnancy and are part of the differential when evaluating pregnant women in an obstetric triage or emergency room setting.
Pyelonephritis complicates approximately 1% to 2% of all pregnancies and can lead to significant maternal and fetal morbidity (Hill, Sheffield, McIntire, & Wendel, 2005). This can include sepsis, acute respiratory distress syndrome (ARDS), preterm birth, anemia, low birth weight, and renal insufficiency (Wing, Fassett, & Getahun, 2014). Pregnant women are thought to be more susceptible to pyelonephritis due to compression of the ureters by the gravid uterus, progesterone-mediated smooth muscle relaxation, increased glomerular filtration rate, and increased risk of bacteriuria during pregnancy. Approximately 21% of pyelonephritis during pregnancy occurs in the first trimester (Hill et al., 2005).
116Pregnant women with pyelonephritis often have a history of a urinary tract infection or asymptomatic bacteriuria. Women with asymptomatic bacteriuria have an approximately 20- to 30-fold increased risk of developing pyelonephritis compared to women without bacteriuria (Jolley & Wing, 2010). Other risk factors for pyelonephritis include a previous history of pyelonephritis, sickle cell disease/trait, and diabetes. Approximately 13% of women with pyelonephritis in pregnancy may have at least one maternal risk factor (Hill et al., 2005).
Pregnant women with pyelonephritis may present with any of the following symptoms: fever, flank pain, dysuria, urinary frequency, costovertebral angle tenderness (CVAT), chills, nausea, or vomiting. In severe cases, they may present with signs and symptoms of septic shock including hypotension, tachycardia, shortness of breath, or multisystem organ failure. In contrast, women with a simple urinary tract infection may be asymptomatic or complain of localized symptoms only such as frequency, urgency, or dysuria.
The diagnosis of acute pyelonephritis can be made on the clinical findings of fever (>38°C), flank pain, and CVAT with the laboratory finding of bacteriuria (Jolley & Wing, 2010). However, women with a simple urinary tract infection usually do not have any significant physical examination findings.
LABORATORY AND IMAGING STUDIES
A urinalysis can confirm that bacteriuria is present (>8 to 12 white blood cells/high power field) in a clean catch specimen (<2 to 4 epithelial cells). A urine culture obtained from a midstream clean catch specimen can isolate the microorganism and confirm the diagnosis by looking for greater than 100,000 colony forming units (Jolley & Wing, 2010). The most common pathogens associated with pyelonephritis are listed in Exhibit 11.1.
Other laboratory evaluation includes a complete blood count and serum chemistry evaluation. Elevation of the white blood cell count may be seen. In addition, there may be electrolyte abnormalities and transient renal insufficiency (Hill et al., 2005). The utility of obtaining blood cultures in the setting of pyelonephritis has been debated in the literature. Wing, Park, DeBuque, and Millar (2000) demonstrated that a change in management due to bacteremia alone occurred in only 1% of cases. There are no randomized controlled trials to comparing outcomes of pyelonephritis in pregnancy with or without blood cultures (Gomi, Goto, Laopaiboon, Usui, & Mori, 2015). However, blood cultures may be considered if the woman shows signs or symptoms of sepsis or has medical comorbidities.
Occurrence of Pathogens Associated With Pyelonephritis in Pregnancy
• Escherichia coli (83%)
• Streptococcus species (21.4%)
• Klebsiella pneumoniae (7.6%)
• Staphylococcus species (6.5%)
• Proteus mirabilis (4.9%)
• Enterococcus species (5.7%)
Source: Adapted from Wing et al. (2014).
The differential diagnosis for pyelonephritis in pregnancy includes other disorders of genitourinary, gastrointestinal, and pulmonary systems. Other conditions that can present in a similar fashion include acute cystitis, nephrolithiasis, viral syndrome, renal failure, pneumonia, pancreatitis, appendicitis, and gastroenteritis.
CLINICAL MANAGEMENT AND FOLLOW-UP
Unlike a simple urinary tract infection or asymptomatic bacteriuria, which can be managed as an outpatient with oral antibiotics, the standard management of pyelonephritis in pregnancy is admission to the hospital for inpatient management. Archabald, Friedman, Raker, and Anderson (2009) found that maternal morbidity and obstetric outcomes did not differ between first-trimester pyelonephritis compared with second-/third-trimester pyelonephritis. Given this data, it is recommended that all pregnant women with pyelonephritis, regardless of trimester, be admitted for parenteral antibiotics, antipyretics, and intravenous hydration.
Cephalosporins are recommended as first-line therapy for pyelonephritis during pregnancy (Jolley & Wing, 2010) due to the increasing resistance of Escherichia coli to ampicillin. An appropriate initial regimen is ceftriaxone 2g intravenously every 24 hours. Aminoglycosides (i.e., gentamicin) can be considered in cases of cephalosporin allergy, but it has been associated with ototoxicity following prolonged fetal exposure (Le, Briggs, McKeown, & Bustillo, 2004). Fluoroquinolones are avoided in pregnancy.
Parenteral antibiotics can be continued until the pregnant woman has shown clinical improvement and has been afebrile for 24 to 48 hours. Because of the risk of capillary endothelial damage from bacteria-mediated endotoxins and subsequent risk of respiratory insufficiency and acute respiratory distress syndrome (ARDS), aggressive hydration during this time should be used with caution and urine output monitored closely. Treatment with oral antibiotics tailored to the sensitivity of the microorganism can be continued for 14 days following intravenous treatment. It is recommended that a post treatment urine culture as a test of cure be sent (Glaser & Schaeffer, 2015).
If there is no clinical improvement seen in 48 to 72 hours, further evaluation for bacterial resistance, urolithiasis, renal abscess, and urinary tract abnormalities can be considered. In addition, broadening antibiotic coverage and imaging the urinary tract system with ultrasound or magnetic resonance imaging (MRI) may be warranted.
Recurrent pyelonephritis can occur in 6% to 8% of women with pyelonephritis in pregnancy (Lenke, VanDorsten, & Schifrin, 1983). Suppressive therapy is recommended for the duration of the pregnancy and up to 6 weeks postpartum with either nitrofurantoin 100 mg orally or cephalexin 250 to 500 mg orally at bedtime. Suppressive therapy may be considered in subsequent pregnancies.
Symptomatic nephrolithiasis affects approximately 1 in 244 to 1 in 2,000 pregnancies (Rosenberg et al., 2011; Srirangam, Hickerton, & Van Cleynenbreugel, 2008). As noted previously, changes in the urinary tract during pregnancy include 118an increased glomerular filtration rate, compression of the ureters due to the gravid uterus, and progesterone-mediated smooth muscle relaxation. Despite the normal physiologic changes in pregnancy, the prevalence of nephrolithiasis is thought to be similar to the nonpregnant population (Rosenberg et al., 2011). This may be due to increased production of citrate and magnesium during pregnancy, since both are thought to be urinary stone inhibitors (Meria, Hadjadj, Jungers, & Daudon, 2010). Symptomatic nephrolithiasis presents in the second or third trimesters in approximately 80% to 90% of cases (Butler, Cox, Eberts, & Cunningham, 2000).
Pregnant women with symptomatic nephrolithiasis may present with back or flank pain, lower abdominal pain, dysuria, or hematuria. Nausea and/or vomiting may also be present. Flank or abdominal pain is the most common symptom, occurring in approximately 85% to 100% of patients (Srirangam et al., 2008). Pain is often described as intermittent and colicky in nature. Frank hematuria is reported to occur in 15% to 30% of cases (Srirangam et al., 2008). Microscopic hematuria may not be present in up to 25% of women with diagnosed calculi (Travassos et al., 2009). Women may report a history of nephrolithiasis in the past.
On physical examination, pregnant women might appear uncomfortable and in visible pain. Palpation of the flanks is used to evaluate for CVAT. Tachycardia may be present as part of the pain response.
A urinalysis and urine culture can assess for hematuria and pyuria, suggestive of an underlying infection. A complete blood count may indicate evidence of systemic infection. A baseline creatinine is helpful to confirm normal renal function. Straining the urine of pregnant women with suspected nephrolithiasis may demonstrate the spontaneous passage of stones.
Imaging of the renal system may be helpful in confirming the diagnosis of renal calculi. Renal ultrasonography is often used as the first-line imaging modality. However, the sensitivity of ultrasound in confirming urolithiasis ranges from 34% to 86% (Srirangam et al., 2008). In addition, ultrasound may be unable to distinguish an obstruction due to calculi or physiologic hydronephrosis. Ultrasound may be used to see ureteral jets that would indicate the passage of urine at the uretero-vesical junction. The absences of ureteral jets is sensitive and specific for obstruction in the nonpregnant population but up to 15% of asymptomatic pregnant women may also have this finding (Masselli et al., 2013). In the setting of symptoms that are not improving or worsening, other imaging modalities that can be considered include an abdominal flat plate x-ray, MRI, or single-shot intravenous pyelography. Magnetic resonance imaging can differentiate physiologic hydronephrosis from obstruction but is expensive and may not be readily available (Masselli, Weston, & Spencer, 2015). It is, however, safe to use in pregnancy as it does not employ ionizing radiation.
The differential diagnosis of nephrolithiasis includes other genitourinary and gastrointestinal disorders as well as conditions related to pregnancy itself. The differential diagnoses for nephrolithiasis are listed in Exhibit 11.2.
If there is a clinical suspicion for nephrolithiasis in pregnancy, the first steps are aggressive hydration and pain control. Pregnant women may need to be admitted to the hospital for pain management. Opiates, either intravenously or orally, can be used for analgesia in pregnancy. Nonsteroidal anti-inflammatory drugs (NSAIDs) are to be avoided, especially in the third trimester, due to risks of oligohydramnios and premature closure of the ductus arteriosus. If a superimposed infection is suspected, antibiotic therapy can be initiated while awaiting final urine culture results. Antiemetics can also be administered if the woman’s symptoms include nausea or vomiting. Approximately 64% to 84% 119of renal calculi pass spontaneously (Srirangam et al., 2008). Urine is strained to assess for passage of calculi.