Pulmonary Injury as a Complication of Urinary Tract Infection in Pregnancy

Prevalence and types of UTIs in pregnancy

UTIs are prevalent among pregnant women and can present significant risks to the health of both the mother and the fetus. Expectant mothers often experience asymptomatic bacteriuria, a type of UTI that lacks noticeable symptoms^[15,16] For instance, in one study, approximately 26.0% of pregnant women attending two private tertiary medical college hospitals in Dhaka were found to have asymptomatic bacteriuria,^[17] whereas another study reported a prevalence rate of 35% among pregnant women.^[18]

UTIs during pregnancy are characterized by the substantial presence of bacteria anywhere in the urinary tract, with pyelonephritis representing the most severe bacterial infection that can lead to perinatal and maternal complications.^[8-12,19] Pregnancy-induced physiological changes create favorable conditions for bacterial colonization in both the lower and upper urinary tract.^[13,18] Consequently, it is advisable for all pregnant women to undergo urine culture screening for bacteriuria, and asymptomatic bacteriuria should be promptly addressed to prevent potential complications.^[20] Treatment should be guided by the results of urine culture and sensitivity tests, and antibiotics should be administered for seven days.^[21]

Risk factors of UTIs in pregnancy

Various factors elevate the risk of UTIs during pregnancy, including lower socioeconomic status,^[14,22,23] history of UTIs, sexual activity during pregnancy, anemia, multiparity,^[24] and factors such as illiteracy and the first trimester of pregnancy. Screening for UTIs in pregnant women, especially those with these risk factors, is crucial to prevent complications, such as severe preeclampsia.

Clinical presentation, diagnosis, and screening of UTIs in pregnancy

UTIs in pregnant women can manifest with different symptoms, depending on several factors. Some women may experience increased incontinence, while others may report heightened nocturia.^[25] Women with recurrent UTIs may exhibit less dysuria but more severe symptoms, significantly affecting their daily lives.^[26] Premenopausal women suspected of having UTIs may present with higher symptom severity and discomfort scores, including symptoms such as feeling unwell, painful urination, and dysuria.^[26]

The most effective method for diagnosing UTIs in pregnant women involves urine culture and antimicrobial susceptibility testing.^[27] This entails collecting a clean voided midstream urine sample from pregnant women and sending it to the laboratory for analysis. Urine samples were examined and cultured to detect the presence of bacteria and other infection-causing pathogens. The isolated pathogens were then tested for susceptibility to various antibiotics to determine the most appropriate treatment.^[28,29] Regular screening for significant bacteriuria in all pregnant women is crucial to mitigate adverse effects on both maternal and fetal health.^[28] In addition, it is essential to consider the gestational age of the pregnant woman, as UTI occurrence tends to increase as the pregnancy progresses.

Types of pulmonary complications

Pulmonary complications can arise in pregnant women with UTIs due to various factors. These complications may include respiratory issues, pulmonary edema, and exacerbation of preexisting conditions, such as asthma. It is important to note that UTIs themselves may not directly cause pulmonary complications, but physiological changes associated with pregnancy can increase this risk.^[3,30] In addition, respiratory conditions such as pneumonia and tuberculosis can also pose risks during pregnancy, potentially leading to maternal and fetal morbidity.^[30] Early diagnosis and prompt treatment are crucial for managing these complications and ensuring positive outcomes in pregnant women with UTIs.

Frequency of pulmonary complications due to UTIs

In the available literature, a few cases of ARDS resulting from UTI pyelonephritis during pregnancy have been reported.^[31-34] Approximately 1–2% of women develop acute pyelonephritis as a consequence of persistent UTIs, which has been associated with an increased risk of pulmonary edema under certain circumstances. In contrast, ARDS is infrequently associated with acute pyelonephritis in nonpregnant women. Therefore, a theoretical connection between UTIs and pulmonary injuries in pregnant women has been proposed. Pregnant women with UTI symptoms and signs of hypoxia during their third trimester should be monitored for ARDS.^[31] Notably, no data in the literature explicitly addresses the co-occurrence of UTIs and pulmonary injuries, underscoring the need for systematic reviews to provide precise statistics on their frequency and prevalence.

Connection between the urinary and respiratory systems

A close and intricate connection exists between kidney and lung function in both healthy and ill states. Renal and pulmonary functions play essential roles in maintaining acid-base balance, regulating the levels of carbon dioxide and bicarbonate, controlling blood pressure, and managing fluid balance. These interactions commence during fetal development and frequently contribute to the onset and progression of various diseases. In pregnancy, urine plays a critical role as a component of the amniotic fluid and influences pulmonary development and growth.^[36] In addition, during the first trimester of pregnancy, the kidney serves as the primary source of proline, which plays a crucial role in the maturation of the lung parenchyma and collagen synthesis.^[37]

How UTIs can lead to pulmonary injury?

UTIs can indeed have implications for pulmonary health. Uremia, which is a consequence of UTIs, can lead to alterations in various aspects of respiratory function, including respiratory drive, mechanics, muscle function, and gas exchange.^[38] Furthermore, UTIs can result in a range of systemic effects including volume overload, anemia, immune suppression, extraosseous calcification, malnutrition, electrolyte imbalances, and acid-base disturbances. These systemic effects can indirectly affect the pulmonary system.^[39]

In patients undergoing chronic peritoneal dialysis, adaptations may occur that help mitigate the typical reductions in lung volumes, oxygen levels, and respiratory muscle strength observed during acute peritoneal dialysis.[10]

The role of infection, inflammation, and immune response on pulmonary injury

The UTIs can lead to bacterial colonization of urine, potentially resulting in fulminant sepsis and subsequent respiratory failure.^[40] Inflammation triggers lung injury by activating neutrophils and promoting their recruitment to the lungs, leading to impaired lung function and tissue damage.^[41] The release of microbicidal substances by activated neutrophils into the extracellular space can paradoxically harm host tissues.^[42] Early pulmonary inflammation in acute lung injury (ALI) involves the accumulation of activated neutrophils in the lungs.^[43] Platelets have also been found to stimulate the development of neutrophil extracellular traps (NETs) in transfusion-related acute lung injury (TRALI), further exacerbating lung endothelial injury.^[44] Proinflammatory cytokines, which play critical roles in ALI pathogenesis, are associated with inflammation-induced lung injury. Inflammation is a key factor in the initiation and progression of various diseases.

Symptoms and signs of pulmonary injury in pregnant women with UTIs

Severe pyelonephritis during pregnancy can lead to pulmonary injury due to a systemic inflammatory response, affecting approximately 2% of women.^[45] Pyelonephritis is associated with significant maternal and fetal morbidities, including conditions such as ARDS, sepsis, pulmonary embolism, and maternal or fetal death.^[46] Symptoms of pulmonary injury include shortness of breath, coughing (potentially with bloody sputum), dizziness, chest pain, and leg swelling. Other signs indicative of pulmonary injury may include acute onset of dyspnea, tachypnea, tachycardia, pleuritic chest pain, and severe dyspnea.^[47,48]

Challenges in diagnosis and differentiation from other conditions

Diagnosing pulmonary injury in pregnant women can be challenging, primarily because the physiological changes that occur during pregnancy can mimic the symptoms of other conditions.^[49] In addition, UTIs may mask the inflammatory symptoms of pulmonary injuries. For example, instead of an immediately suspected respiratory system pathology, symptoms such as fever, dyspnea, cough, leukocytosis, and tachycardia might be considered signs of septicemia or Systemic Inflammatory Response Syndrome (SIRS) resulting from an underlying UTI.

As a result, diagnosing pulmonary complications in pregnant women with UTIs can be clinically challenging. Nevertheless, specific tests and imaging techniques can aid in diagnosing particular conditions. Pulmonary embolism in pregnant women can be diagnosed using ventilation-perfusion (V/Q) scanning or CT pulmonary angiography, while the diagnosis of ARDS relies on the identification of bilateral pulmonary infiltrates on chest X-ray or CT scan, along with the PaO2/FiO2 ratio.^[50]

Treatment

Managing pulmonary complications during pregnancy can be challenging because of the anatomical and physiological changes. Treatment strategies often focus on symptom management and ensuring adequate oxygenation. The following are specific treatment approaches for pulmonary complications during pregnancy:^[49]

1. Bacterial Pneumonia: The primary treatment for bacterial pneumonia during pregnancy involves supportive care with oxygen, proper antibiotics, bronchodilators, and, if necessary, ventilator support.^[51]

2. Pulmonary Hypertension and Pulmonary Edema: These complications can arise in benign hydatidiform pregnancies due to trophoblastic pulmonary embolism (PE). Management may include supportive care such as oxygen and diuretics to reduce fluid overload.

3. Aspiration Pneumonia: Treatment for aspiration pneumonia is primarily supportive and includes oxygen, bronchodilators, antibiotics, and ventilatory support if needed.

4. Asthma: A multidisciplinary care team can help pregnant women manage their asthma symptoms and prevent exacerbations that may lead to hospitalization.

5. Thromboembolic Disease: Pregnancy increases the risk of thromboembolic events. Treatment may involve anticoagulation therapy, such as low-molecular-weight heparin, to prevent and manage these complications.^[52]

6. Amniotic Fluid Embolism: This rare but life-threatening condition during pregnancy requires supportive treatment that focuses on maintaining adequate oxygenation and managing hemodynamic stability.

Prevention

Preventive measures are essential to maintain respiratory health during pregnancy. The following are some recommendations:^[53]

• Asthma Management: Pregnant women with asthma should continue their medication as usual, as pregnancy does not significantly affect the peak expiratory flow rate (PEFR) and forced expiratory volume in one second (FEV1). Safe treatments include inhaled and nebulized b2-agonists, inhaled and oral steroids, oral and intravenous theophyllines, and intravenous magnesium sulfate.

• Respiratory Infections: Aggressive treatment of respiratory infections before delivery is crucial to prevent complications.

• Preventing Blood Clots: All pregnant women can take steps to prevent blood clots. These measures include wearing compression stockings, maintaining physical activity, and staying well-hydrated.

Ideally, women with chronic pulmonary conditions should be evaluated before pregnancy to establish baseline pulmonary function, assess disease chronicity, evaluate inflammatory activity, determine disease staging, and assess treatment responses. These steps can contribute to improved management and outcomes during pregnancy.