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Journal of Perinatology (2010) 30, 359–362

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PERINATAL/NEONATAL CASE PRESENTATION


Congenital pneumonia with sepsis caused by intrauterine
infection of Ureaplasma parvum in a term newborn: a first case
report
I Morioka1, H Fujibayashi1, E Enoki2, N Yokoyama1, H Yokozaki2 and M Matsuo1
1
Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan and 2Department of Pathology, Kobe University
Graduate School of Medicine, Kobe, Japan

C-reactive protein value of 10.6 mg per 100 ml. Culture of her


We present an autopsy case of intrauterine pneumonia in a term newborn vaginal mucus found Candida albicans. Owing to maternal
in whom Ureaplasma parvum was confirmed by PCR examinations, infectious signs and non-reassuring fetal status, a vacuum-assisted
including a novel diagnostic tool for detecting pathogens that caused vaginal delivery was performed. Membranes finally ruptured 101 h
neonatal infections using multiplex PCR. This is the first report of before delivery. In histopathological examinations, the placenta
U. parvum being implicated in the pathogenesis of congenital pneumonia and umbilical cord were markedly infiltrated with inflammatory
with sepsis in a term newborn. cells, resulting in a diagnosis of chorioamnionitis and funisitis,
Journal of Perinatology (2010) 30, 359–362; doi:10.1038/jp.2009.145 respectively.
Keywords: Ureaplasma parvum; intrauterine infection; pneumonia; The infant did not have surface anomalies and was vigorous at
sepsis; multiplex polymerase chain reaction; term newborn birth with Apgar scores of 8 at 1 min and 9 at 5 min. Within 3.5 h
after birth, the infant developed respiratory and circulation failure
requiring endotracheal intubation and cardiopulmonary
Introduction resuscitation, and was transferred to the neonatal intensive care
Ureaplasma parvum is a bacterium inhabitant of the unit in Kobe University Hospital.
genitourinary tract in women, which was recently subclassified On admission, the infant had peripheral cyanosis, poor muscle
from Ureaplasma urealyticum and is known to infect humans.1 tonus and respiratory distress despite artificial ventilation. The
Intrauterine infections of U. parvum are associated with the white blood cell count was 45 600 per ml, platelet count was
development of chorioamnionitis, funisitis, preterm delivery and 31.8  104 per ml, serum C-reactive protein value was 0.92 mg per
chronic lung diseases of preterm newborns.1 However, little is 100 ml, blood sugar value was 320 mg per 100 ml, IgG value was
known about the pathogenicity of U. parvum in a human term 799 mg per 100 ml and IgM value was 14 mg per 100 ml. b-D
fetus and newborn, and there are no reports of intrauterine glucan in blood was negative. Venous blood gas analysis showed
infection by U. parvum causing congenital pneumonia in a that pH was 6.780, pCO2 was 85.0 mm Hg, HCO3 was
human term newborn. Here, we report a term newborn with 11.9 mmol l 1 and base excess was 20.3 mmol l 1 under
intrauterine pneumonia in whom U. parvum was detected by our intermittent mechanical ventilation with peak pressures of
novel multiplex PCR method2 and a direct sequencing analysis. 18 mm Hg. A chest radiograph found slight opacifications and air
leaks from both lungs. Echocardiography revealed no congenital
heart malformations and no intracranial hemorrhage. No evidence
Case of persistent pulmonary hypertension was found because of the
A 3330 g male infant was born after 40 weeks of gestation. There foramen ovale or ductus arteriosus with a left-to-right blood
was no family history of immunodeficiency. Pregnancy was stream. Congenital metabolic disorder was not found by tandem
uncomplicated. Before labor, his mother had signs of fever and mass spectrometry-based newborn blood screening. Despite
premature rupture of the membranes. Laboratory investigations intravenous administrations of amikacin sulfate, fosfluconazole
showed a white blood cell count of 25 300 per ml and a serum and g-globulin, and intensive cardiorespiratory support, severe
hypoxemia and acidosis continued. Finally, the infant died within
Correspondence: Dr I Morioka, Department of Pediatrics, Kobe University Graduate School of 9 h after birth due to respiratory failure.
Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
E-mail: ichim@med.kobe-u.ac.jp Autopsy revealed congestive lungs (Figure 1a). Microscopy
Received 5 July 2009; accepted 18 August 2009 showed extensive pneumonitis involving the respiratory bronchioles
Congenital pneumonia caused by Ureaplasma parvum
I Morioka et al
360

x200

Figure 1 (a) Macroscopic findings of both lungs show congestion. (b) Microscopy shows pneumonitis involving the respiratory bronchioles with infiltration of
inflammatory cells consisting of polymorphonuclear leucocytes and macrophages, and hyaline membrane formation. (c) Ureaplasma sp. was detected from blood by our
diagnostic tool using multiplex PCR. (d) U. parvum was also detected in the placenta and umbilical cord by PCR using a specific primer pair for detecting Ureaplasma
spp. (e) U. parvum was not detected in lung tissue by PCR. Extracted total DNA concentrations in blood, placenta, umbilical cord and lung tissue were 332.8, 12.7,
9.8 and 466.0 ng ml 1, respectively. HSV, herpes simplex virus; CMV, cytomegalovirus; GBS, group B Streptococcus; MRSA, methicillin-resistant Staphylococcus aureus;
PCL, positive control ladder; NC, negative control; PC, positive control.

Table 1 Clinical case reports of congenital pneumonia caused by intrauterine infection of Ureaplasma in term newborns

Author Quinn PA et al.6 Waites KB et al.7 Brus F et al.8 Our case


Published year 1985 1989 1991 2009
Gestational age 38 weeks 37 weeks 38 weeks 40 weeks
Birth weight 2750 g 2180 g 3600 g 3330 g
Onset of symptoms 22 h after birth 1 h after birth 12 h after birth 3.5 h after birth
Species U. urealyticum serovar 8 U. urealyticuma U. urealyticuma U. parvum
Sepsis + +
PPHN + +
Outcome Death Death Death Death
Abbreviations: U. urealyticum, Ureaplasma urealyticum; U. parvum, Ureaplasma parvum; PPHN, persistent pulmonary hypertension of the newborn; h, hours.
a
No information for serovar.

Journal of Perinatology
Congenital pneumonia caused by Ureaplasma parvum
I Morioka et al
361

with diffuse infiltration of inflammatory cells consisting of The genomic DNA of U. parvum was not detected from this
polymorphonuclear leucocytes and macrophages, and hyaline patient’s lung tissue. Recently, in a sheep or mouse pregnant
membrane formation (Figure 1b). The cause of death was model of intrauterine infection of U. parvum, it was found that
determined as intrauterine pneumonia, because the bilateral lungs U. parvum could not be recovered from lung tissues 2–3 days
already had severe infiltration of inflammatory cells soon after after birth in term pups.9,10 Therefore, in human term newborns,
birth. Bacterial and fungal cultures were negative in all specimens U. parvum may not be able to be recovered from lung tissues.
including blood, pharyngeal mucus, bronchoalveolar lavage and This observation is consistent with previous studies in the sheep
gastric fluid. However, an amplicon of the genomic DNA of model showing clearance of Ureaplasma from the nasal cavities
Ureaplasma sp. was detected from blood by a novel diagnostic tool soon after birth11 and an inability of Ureaplasma to colonize the
using multiplex PCR, which we recently established,2 and sepsis respiratory tract of older lambs.12 Further observations in more
was diagnosed (Figure 1c). U. parvum was also detected from the clinical cases of congenital pneumonia caused by intrauterine
placenta and umbilical cord, but not from the lung tissue, by PCR infection of U. parvum will be needed to show that U. parvum
examination using a specific primer pair for detecting Ureaplasma cannot be detected from lung tissues after birth in human term
spp.3,4 (Figures 1d and e). Direct sequencing analysis identified its newborns.
PCR products as U. parvum. In conclusion, this is the first case report that U. parvum is
implicated in the pathogenesis of congenital pneumonia with
sepsis in a human term newborn.
Discussion
Ureaplasma spp. are eubacteria, which belong to the class
Mollicutes. U. urealyticum was the only species known to infect
Conflict of interest
humans. This species was recently subdivided into two separate
species, U. urealyticum (serovars 2, 4, 5, 7–13) and U. parvum The authors declare no conflict of interest.
(serovars 1, 3, 6 and 14).1,5
To our knowledge, only three cases of congenital pneumonia
caused by intrauterine infection of Ureaplasma in term newborns Acknowledgments
have been previously reported (Table 1).6–8 The onset of symptoms
This work was supported by grants for scientific research from the Morinaga
was within 1 day after birth in all of the three cases. All cases died
Hoshi-kai Foundation and the Ministry of Education, Culture, Sports, Science and
despite intensive care, and postmortem microscopic examinations
Technology in Japan.
showed severe pneumonia as the cause of death. Some cases were
complicated with sepsis and/or persistent pulmonary hypertension
of the newborn. The species of Ureaplasma in all cases were
U. urealyticum. Therefore, our present case is the first report of References
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Journal of Perinatology

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