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Twenty percent of very preterm neonates (23-32 weeks of gestation) are born with bacteremia caused by genital Mycoplasmas

Refers to article:

The Alabama Preterm Birth Study: Umbilical cord blood Ureaplasma urealyticum and Mycoplasma hominis cultures in very preterm newborn infants
Robert L. Goldenberg, William W. Andrews, Alice R. Goepfert, Ona Faye-Petersen, Suzanne P. Cliver, Waldemar A. Carlo, John C. Hauth
American Journal of Obstetrics & Gynecology
January 2008 (Vol. 198, Issue 1, Pages 43.e1-43.e5)
Abstract | Full Text | Full-Text PDF (123 KB) | Summary PDF (95 KB)

Article Outline

• References

• Copyright

Robert Goldenberg and the team at the University of Alabama report in this issue of the Journal that 23% of neonates who are born between 23 to 32 weeks of gestation have positive umbilical blood cultures for genital mycoplasmas (Ureaplasma urealyticum and Mycoplasma hominis).1 Newborns with positive blood cultures had a higher frequency of a neonatal systemic inflammatory response syndrome, higher serum concentrations of interleukin-6 and more frequent histologic evidence of placental inflammation (chorioamnionitis and funisitis) than those with negative cultures.1

See related article, page 43

These observations are important because they underscore that (1) 1 of every 4 preterm neonates (23-32 weeks of gestation) is born with fetal bacteremia, (2) genital mycoplasmas are a frequent cause of congenital fetal infection, and (3) U. urealyticum was the most frequent isolate. Simultaneous colonization with M. hominis and U. urealyticum was present in 22% of newborns with a positive umbilical blood culture.

The article provides compelling evidence that congenital fetal infection is more frequent than was previously realized. The detection of genital mycoplasmas is not part of routine clinical practice in obstetrics and neonatology. Similarly, standard treatment for suspected neonatal sepsis does not include antibiotics that are effective against these microorganisms. Therefore, this report has important implications.

The data used in the article were derived from the Alabama Preterm Birth Study, which was sponsored by the National Institute of Child Health and Human Development/National Institutes of Health. The study included 457 consecutive singleton pregnancies that delivered preterm between 23 and 32 weeks of gestation; 351 women/neonate pairs had umbilical cord blood cultures for genital mycoplasmas. Patients with spontaneous preterm delivery had a significantly higher rate of positive umbilical cord blood culture for U. urealyticum and/or M. hominis than those with indicated preterm delivery (34.7% vs 3.2%; P < .0001). The earlier the gestational age at delivery, the higher the rate of a positive umbilical cord blood culture. Neonates with a positive culture for U. urealyticum and/or M. hominis were more likely to have biochemical evidence of systemic inflammation, as determined by an elevated umbilical cord blood concentration of interleukin-6 (57.6% vs 19.7%; P < .0001), systemic inflammatory response syndrome (41.3% vs 25.7%; P = .007), and bronchopulmonary dysplasia (26.8% vs 10.1%; P = .0001). However, the association with bronchopulmonary dysplasia did not remain significant after adjusting for maternal race, gestational age at delivery, and neonatal gender.

The initial uncertainties about whether genital mycoplasmas can cause fetal/neonatal disease are disappearing in light of the accumulating evidence that these microorganisms have been implicated in neonatal sepsis,2, 3, 4, 5, 6 pneumonia,3, 5, 6, 7, 8, 9, 10 meningitis,4, 11, 12 and brain damage.13, 14, 15, 16 Moreover, colonization of the neonatal respiratory tract with these organisms is a risk factor for chronic lung disease.3, 17, 18, 19, 20, 21 A recent comprehensive review of the role of genital mycoplasmas by Waites et al22 updates the classic review of the subject by Cassell et al.23

It is interesting to note that genital mycoplasmas are found frequently in the lower genital tract of sexually active women and normal pregnant women.23, 24, 25, 26, 27, 28, 29, 30 Their presence alone constitutes neither evidence of disease nor a risk factor for preterm birth.31, 32, 33 Yet, they are the microorganisms most frequently isolated from the amniotic fluid in women with preterm labor,34, 35, 36, 37, 38 preterm premature rupture of membranes,38, 39 cervical insufficiency,40 a short cervix,41 mid-trimester genetic amniocentesis,8, 21, 42, 43, 44, 45, 46 spontaneous labor at term,47 term premature rupture of membranes,48 and clinical chorioamnionitis.49, 50 Therefore, a critical issue is why and how such microorganisms gain access to the amniotic cavity in some women but not in most. Whatever the explanation, it is now clear that these microorganisms can induce an inflammatory response in the amniotic cavity, fetus, and mother.51, 52, 53, 54, 55, 56, 57, 58

The findings of Goldenberg et al1 raise important questions: (1) Should neonatal microbiologic work-up include the detection of genital mycoplasmas?; (2) If so, should this be undertaken with cultivation or molecular methods?; (3) Can screening for neonatal bacteremia be accomplished in the clinical setting, rather than the research setting, with the use of umbilical cord blood?; (4) Should the antimicrobial treatment of suspected neonatal sepsis include antibiotics that are effective against U. urealyticum and/or M. hominis?; and (5) Can treatment of these organisms prevent the short- and long-term consequences of disease? Investigators have begun to address these questions.59, 60, 61, 62, 63, 64, 65, 66, 67, 68

The seminal observations reported by Goldenberg et al stress the importance of the host-microbial interaction in the lower and upper genital tracts of pregnant women as well as in the fetus and neonate.

References

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a Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, MD, and Detroit, MI

b Department of Obstetrics and Gynecology and Center for Molecular Medicine and Genetics, Wayne State University/Hutzel Hospital, Detroit, MI

c Department of Obstetrics and Gynecology, University of California, Irvine, CA.

Address correspondence to Roberto Romero, MD, Chief, Perinatology Research Branch, Program Director for Obstetrics and Perinatology, Division of Intramural Research, NICHD/NIH/DHHS, Wayne State University/Hutzel Women’s Hospital, 3990 John R–Box #4, Detroit, MI 48201.

This work was supported by the Intramural Research Program of the National Institute of Child Health and Human Development, NIH, DHHS.

Reprints not available from the authors.

PII: S0002-9378(07)02185-0

doi:10.1016/j.ajog.2007.11.031

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