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28 January 2025: Articles  China

Severe Neonatal Asphyxia Associated with Infection: A Case Report

Unusual clinical course, Diagnostic / therapeutic accidents, Educational Purpose (only if useful for a systematic review or synthesis)

Dandan Wang1ABDEG, Weiwei Fan2CF, Tingting Yan2BCD, Tianming Yuan1AD, Xuchen Zhou2ACEG

DOI: 10.12659/AJCR.946249

Am J Case Rep 2025; 26:e946249

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Abstract

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BACKGROUND: Ureaplasma urealyticum (UU) is a common microorganism that has been associated with a variety of obstetric and neonatal complications, such as infertility, stillbirth, histologic chorioamnionitis, neonatal sepsis, respiratory infections, and central nervous system infections. However, it is rare for it to cause severe neonatal asphyxia. This rarity is the focus of our case report, which aims to highlight the potential severity of UU infections in newborns.

CASE REPORT: A male neonate was delivered vaginally at 40+5 weeks of gestation, with a history of premature rupture of membranes at 7 hours and low amniotic fluid volume. After birth, he had no spontaneous breathing at birth, with cyanosis around the mouth and extremities and flaccid limbs. The Apgar score was a low 3, indicating severe asphyxia. Immediate medical interventions were undertaken, including cardiopulmonary resuscitation, tracheal intubation, and airway clearing. Despite these efforts, the newborn required transfer to our hospital with the assistance of an invasive ventilator. Upon admission, UU DNA was detected in the sputum at 3.25×10⁴ copies/mL. He received erythromycin for infection, mechanical ventilation, milrinone combined with sildenafil to reduce pulmonary arterial hypertension, and glycerol fructose to reduce intracranial pressure. Although these treatments successfully controlled the infection, the infant suffered significant neurological damage. Tragically, the family decided to cease treatment, and the neonate died at 12 days of age.

CONCLUSIONS: Ureaplasma urealyticum infection can cause severe neonatal asphyxia. We report the present case to raise awareness about the importance of early detection and intervention for UU in pregnant women to improve maternal and neonatal outcomes.

Keywords: Ureaplasma urealyticum, Asphyxia, Infant, Treatment Outcome

Introduction

Ureaplasma urealyticum (UU) is a common microorganism in the human urogenital tract and is prevalent in the environment. It is currently classified into 2 biovars, comprising 14 serotypes. Biovar1, known as Ureaplasma parvum (UPA), includes serotypes 1, 3, 6, and 14, while biovar 2, known as Ureaplasma urealyticum (UUR), includes the remaining 10 serotypes [1]. UU is detected in 40–80% of sexually active women on the vaginal or cervical mucosa and in 7.73% of hospitalized neonates [2,3]. UU has reached a high prevalence rate [4], but it is often considered a low-virulence commensal in the female reproductive tract and thus has not received adequate attention. Nevertheless, it is associated with various obstetric complications and neonatal diseases, including infertility, stillbirth, histologic chorioamnionitis, neonatal sepsis, respiratory infections, and central nervous system infections [5–7]. However, reports of neonatal asphyxia caused by this pathogen are rare. Here, to enhance awareness among healthcare providers, we report a case of severe asphyxia due to UU infection.

Case Report

The patient was a male neonate, 6 hours old, the second child born to his mother. He was delivered vaginally at 40 weeks 5 days of gestation with a birth weight of 3990 grams. The membranes had ruptured before term for 7 hours, with clear amniotic fluid estimated at approximately 50 ml. No abnormalities were noted in the umbilical cord or placenta. The mother was in good health, with no evidence of vaginitis or cervicitis, and she denied any history of sexually transmitted infections or surgeries. Due to a lack of awareness about prenatal care and limited financial resources, no routine prenatal checkups were conducted. The duration of the first stage of labor was 6 hours 30 minutes. The neonate exhibited no spontaneous respiration at birth, with cyanosis around the mouth and extremities and flaccid limbs. His Apgar scores were 3 at 1 minute (heart rate 2, color 1, respiration 0, muscle tone 0, reflex irritability 0) and 4 at 5 minutes (heart rate 1, reflex irritability 1, color 2, respiration 0, muscle tone 0) following initial resuscitation, which included airway clearance, stimulation, and assisted ventilation. At 10 minutes, his Apgar score remained 4 (heart rate 2, color 2, respiration 0, reflex irritability 0, muscle tone 0) despite continued resuscitative efforts, including cardiopulmonary resuscitation, endotracheal intubation, and airway clearance. On March 2, 2024, the neonate was immediately admitted to the neonatal unit of a local hospital and placed on invasive mechanical ventilation. Initial complete blood count (CBC) revealed: white blood cell (WBC) count 23.88×109/L, red blood cell (RBC) count 4.29×1012/L, hemoglobin concentration 158 g/L, platelet count 378×109/L, lymphocyte percentage 32.5%, neutrophil percentage 53.5%, and C-reactive protein (CRP) 10 mg/L. Blood gas analysis showed a pH of 7.16, partial pressure of oxygen (PaO2) of 80 mmHg, partial pressure of carbon dioxide (PaCO2) of 45 mmHg, bicarbonate concentration of 12.7 mmol/L, lactate concentration of 14.6 mmol/L, and a base excess of −18.1 mmol/L. He received intravenous penicillin sodium to control the infection. After 5 hours of unsuccessful treatment, he was transferred to our hospital. On examination at our facility, the infant’s temperature was not increased, pulse was 128 beats per minute, respiration 6 breaths per minute, blood pressure 84/54 mmHg, and weight 4100 grams. He was comatose with pale skin and a tense anterior fontanelle measuring 1.5×1.5 cm. His pupils were round and equal, absent pupillary light reflexes, approximately 3 mm in diameter. His neck was soft. He exhibited sighing respirations with a positive retraction sign of 3 fossae and coarse breath sounds with minimal wet rales. A cardiac examination revealed a strong heart sound and a grade 2/6 murmur in the precordial area. His abdomen was soft, with the liver palpable 4 cm below the right costal margin, and the spleen was not palpable. Bowel sounds were noted once per minute. The neonate displayed generalized edema with a capillary refill time exceeding 3 seconds. Muscle strength and tone were absent, scoring 0 on both assessments. Primitive reflexes, including the Moro, suck, rooting, and grasp reflexes, were not elicited.

Upon admission, a series of laboratory and imaging investigations were conducted. The CBC revealed a WBC count of 26×109/L, an RBC count of 4.09×1012/L, a hemoglobin concentration of 146 g/L, and a platelet count of 380×109/L. The lymphocyte percentage was 36%, and the neutrophil percentage was 60.9%. The CRP level was elevated at 15 mg/L. Blood gas analysis indicated severe acidosis with a pH of 6.99, a PaO2 of 83 mmHg, a PaCO2 of 44.3 mmHg, a bicarbonate concentration of 9.6 mmol/L, a lactate concentration of 15.9 mmol/L, and a base excess of −18.9 mmol/L. Cardiac enzyme levels were markedly elevated, with serum creatine kinase at 1981 U/L (normal range 50–310 U/L) and serum creatine kinase-MB isoenzyme activity at 193 U/L (normal range 0.0–24.0 U/L). A chest X-ray demonstrated findings consistent with type II respiratory distress syndrome (Figure 1). Cranial ultrasonography revealed mild bilateral dilation of the frontal horns of the lateral ventricles. Cardiac ultrasonography showed slightly reduced left ventricular systolic function (ejection fraction: 49%), significant tricuspid regurgitation, moderate mitral regurgitation, mild aortic regurgitation, a patent ductus arteriosus (3 mm), a left-to-right shunt at the great artery level, and a patent foramen ovale (3 mm). Severe pulmonary hypertension was noted, with an estimated pressure of 162 mmHg. Abdominal ultrasonography indicated hepatomegaly with the liver extending 38 mm below the costal margin. Blood cultures, cerebrospinal fluid analysis, liver and renal function tests, blood ammonia levels, and coagulation profiles were within normal limits.

Following admission, the neonate was placed on high-frequency oscillatory ventilation (HFO mode: mean airway pressure: 14 cmH2O, amplitude: 23 cmH2O, frequency: 9 Hz, F102: 100%). Cefotaxime combined with penicillin was administered for antimicrobial therapy. Dopamine and dobutamine were used to improve circulation, while milrinone combined with sildenafil was employed to reduce pulmonary hypertension. Mannitol and fructose were administered to alleviate cerebral edema, and supportive care was provided to correct metabolic acidosis. On the third day of treatment, a repeat CBC showed a WBC count of 41.35×109/L, an RBC count of 3.19×1012/L, a hemoglobin concentration of 123 g/L, and a platelet count of 215×109/L. The lymphocyte percentage was 6.7%, and the neutrophil percentage was 90.4%. CRP was elevated at 17.48 mg/L. Concurrently, nucleic acid testing of the maternal cervical secretions for UU, and a DNA test of the neonate’s sputum for UU showed 3.25 E+04 copies/ml. Consequently, penicillin was discontinued, and erythromycin injection was initiated for antimicrobial therapy. By the tenth day of treatment, CBC and cardiac enzyme levels had normalized. However, the neonate remained comatose, with absent pupillary light reflexes and limb muscle strength graded as I. Brain MRI revealed cytotoxic edema in the bilateral frontal and parietal lobes and corpus callosum (genu and splenium), ischemic-hypoxic encephalopathy, subarachnoid hemorrhage, and subcutaneous soft tissue swelling in the left temporal and bilateral parietal regions (Figure 2). Electroencephalography (EEG) demonstrated severe low voltage. Due to the poor prognosis, the family requested the withdrawal of treatment, and the infant died at 12 days of age.

Discussion

The positive result for UU in the neonatal sputum sample was consistent with the findings in the maternal cervical secretions, and the infant exhibited signs of respiratory distress immediately after birth. WBC and CRP levels were elevated, indicating intrauterine UU infection, likely transmitted vertically from mother to infant. Research indicates that UU can be vertically transmitted from mother to fetus via 3 main pathways [8]. The first pathway is ascending infection, where UU enters the amniotic cavity, proliferates, and migrates to the fetal lungs, primarily occurring early in pregnancy. The second one is hematogenous spread, where UU can be detected in placental and umbilical cord blood samples, potentially leading to fetal organ involvement, chorioamnionitis and congenital pneumonia. The last one is through an infected maternal birth canal, potentially causing skin and mucosal infections and even respiratory tract colonization [9]. In this case, the neonate’s sputum tested positive for UU DNA, consistent with the positive maternal cervical secretion culture, identifying UU as the sole pathogen.

UU infection has been associated with a range of neonatal complications, including pneumonia [1], bronchopulmonary dysplasia [10], necrotizing enterocolitis [11], and neurological abnormalities [12–14]. However, severe asphyxia in term neonates due to UU infection is extremely rare and has not been previously reported. In this case, the severe neonatal asphyxia was likely attributable to multiple factors, including UU infection, premature rupture of membranes, and oligohydramnios. Premature rupture of membranes and reduced amniotic fluid may have been secondary to UU infection. Thus, we postulate that UU infection could be the initiating factor leading to neonatal asphyxia. The exact mechanisms remain unclear, and we hypothesize the following potential causes. One mechanism involves the interaction of UU membrane-associated lipoproteins with Toll-like receptors on the surface of the amnion and chorion, inducing a significant increase in pro-inflammatory cytokines and chemokines within the amniotic fluid, including IL-1, IL-6, IL-8, tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein, and granulocyte colony-stimulating factor [15].

These cytokines and chemokines promote neutrophil infiltration and the release of matrix metalloproteinases (MMPs) [16]. MMPs can degrade the chorion and amnion, leading to its rupture and the remodeling of cervical collagen, which softens and matures the cervix. This process reduces its capacity to withstand intrauterine pressure, making it prone to rupture [17]. In the present case, the neonate experienced premature rupture of membranes (PROM), resulting in significantly reduced amniotic fluid volume (approximately 50 ml). The absence of the cushioning effect of amniotic fluid allowed direct pressure of the uterine wall on the fetus, increasing umbilical cord pressure, reducing blood flow, and precipitating fetal hypoxia and subsequent asphyxia.

Additionally, intrauterine UU infection can hydrolyze urea to produce ammonia, which reacts with water in tissues to form ammonium hydroxide. This compound can damage respiratory epithelial cells at high concentrations [18], leading to respiratory distress in the fetus. Furthermore, UU can induce apoptosis in alveolar epithelial type II cells and macrophages, compromising the integrity of the alveolar-capillary barrier. This results in the lungs being directly exposed to pro-inflammatory cytokines, triggering an immune response characterized by neutrophil and macrophage accumulation and subsequent pulmonary tissue damage [19–22], thereby increasing the risk of neonatal asphyxia. In this case, the neonate exhibited progressively elevated WBC and CRP levels after delivery, indicative of an immune response, and chest radiographs suggested respiratory distress syndrome. These changes correlate with the inflammatory and pathological responses induced by UU infection in the respiratory tract.

Effective management of UU infection necessitates prompt and aggressive therapeutic intervention [23]. Macrolide antibiotics, including erythromycin, azithromycin, and clarithromycin, are commonly used to treat neonatal infections [24]. Despite initial broad-spectrum antibiotic therapy with penicillin and third-generation cephalosporins to cover common pathogens like Group B Streptococcus and Enterobacteriaceae, the treatment outcome was poor. Following the positive UU DNA test on day 3, the antibiotic regimen was switched to erythromycin. This change led to a normalization of WBC and CRP levels, indicating controlled inflammation. However, the irreversible brain damage caused by asphyxia could not be mitigated, and the neonate ultimately died. This case underscores the critical need for heightened vigilance regarding UU infection in the female reproductive tract, particularly in pregnant women. Early screening for UU and proactive intervention are essential to improve neonatal outcomes and prevent adverse events such as asphyxia and neurological damage.

Conclusions

Here, we report a case of neonatal suffocation in a newborn with respiratory distress symptoms immediately after birth. The positive result of UU in the newborn sputum sample was consistent with the result in the maternal cervical secretions. The elevated white blood cell and CRP levels indicate intrauterine UU infection, which may be vertically transmitted from the mother to the infant. In conclusion, UU infection can be vertically transmitted from mother to fetus, leading to severe neonatal asphyxia and potentially fatal outcomes. Healthcare providers must remain vigilant and proactive in identifying and treating UU infections to safeguard the well-being of both mother and child and prevent tragic outcomes such as the one described in our case report.

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American Journal of Case Reports eISSN: 1941-5923
American Journal of Case Reports eISSN: 1941-5923