Correspondence
tinct order in which organisms of different species increase
in number according to the grade of flora on Gram staining.
Gardnerella vaginalis and Mycoplasma hominis, for example,
have maximal numbers in the grade-III category (i.e. BV)
compared with the intermediate grade II. The latter is a distinct entity, and its amalgamation with grade III diminishes
the sensitivity and positive predictive value of Gram-stain
scoring, and women with this diagnosis fail to respond to
clindamycin, unlike women with grade III.3
Finally, the authors feel that the finding of an association between M. hominis and PTB was remarkable. They
seem to regard the existence of M. hominis as a separate
entity, whereas, in large numbers, it is a feature of BV. A
large number of organisms is the key, yet Donders et al.,
despite referring to a quantitative method of detection, do
not mention the numbers of organisms present. Some
22 years ago it was demonstrated that M. hominis organisms in large numbers [‡ 105 ccu (colour change unit – a
unit to measure the quantity of M. hominis present)]
were isolated from 18% of women admitted in spontaneous preterm labour between 26 and 34 completed weeks
of gestation, compared with 0% from women not in
labour, but delivered electively at the same gestational age
for fetomaternal indications (P < 0.05).4
Our perception of the role of various microbes and how
they influence the changes that occur in BV has been widened
by the recent identification of hitherto unknown vaginal bacteria that are associated with BV.5 The relation between the
‘new’ bacteria and the criteria espoused by Donders et al.,
based on vaginal wet preparations, remains to be seen. j
References
1 Donders GG, Van Calsteren K, Bellen G, Reybrouck R, Vanden Bosch
T, Riphagen I, et al. Predictive value for preterm birth of abnormal
vaginal flora, bacterial vaginosis and aerobic vaginitis during the first
trimester of pregnancy. BJOG 2009;116:1315–24.
2 Hay PE, Lamont RF, Taylor-Robinson D, Morgan DJ, Ison C, Pearson J.
Abnormal bacterial colonisation of the genital tract and subsequent
preterm delivery and late miscarriage. Br Med J 1994;308:295–8.
3 Taylor-Robinson D, Morgan DJ, Sheehan M, Rosenstein IJ, Lamont RF.
Relation between Gram-stain and clinical criteria for diagnosing bacterial vaginosis with special reference to Gram grade II evaluation. Int
J STD AIDS 2003;14:6–10.
4 Lamont RF, Taylor-Robinson D, Wigglesworth JS, Furr PM, Evans RT,
Elder MG. The role of mycoplasmas, ureaplasmas and chlamydiae in
the genital tract of women presenting in spontaneous early preterm
labour. J Med Microbiol 1987;24:253–7.
5 Haggerty CL, Totten PA, Ferris M, Martin DH, Hoferka S, Astete SG,
et al. Clinical characteristics of bacterial vaginosis among women testing positive for fastidious bacteria. Sex Transm Dis 2009;85:242–8.
RF Lamonta & D Taylor-Robinsonb
a
Northwick Park Institute of Medical Research, Harrow, UK
Emeritus Professor of Genitourinary Microbiology and Medicine,
Imperial College, London, UK
b
120
Accepted 2 September 2009.
DOI: 10.1111/j.1471-0528.2009.02403.x
The role of bacterial vaginosis, aerobic vaginitis,
abnormal vaginal flora and the risk of preterm birth
Author’s Reply
Sir,
I very much appreciate the response to our manuscript arguing that abnormal vaginal flora (AVF), aerobic vaginitis (AV)
and a newly defined entity, ‘partial BV’, may be as important
predictors of preterm birth (PTB) as full bacterial vaginosis
(BV). In common to all of these conditions are increased
vaginal pro-inflammatory cytokines and leukocytes, known
risk factors for PTB, but which are typically absent in women
with BV.1 Therefore, at present, it is a matter of discussion if
antibiotics given early in pregnancy is the most appropriate
action, or whether we should try to modulate the immune
response to a certain microbial environment.2
In this population (mean age 29 ± 4.4 years) Chlamydia
is present in 1%, 70% of which are excluded by the tests
used. Furthermore, elimination of Chlamydia by antibiotics
is unsuccessful in reducing PTB.3
The fact that some studies applying strict criteria for BV
were not successful in predicting adverse pregnancy outcome
cannot be contradicted by Phil Hay’s study. When presenting
his data for the first time in Genoa in 1990, his and our
group simultaneously showed that lactobacillary gradings
(LBGs) were predicitive for PTB, but in the corresponding
paper of Hay et al., not LBGs, but BV by Nugent scoring had
suddenly replaced AVF. Furthermore, these authors needed
to include intermediate flora (Nugent 4–6) in order to have
significant data on most of their outcomes. It is still our conviction that treatment with metronidazole of women with
Nugent 7–10, without taking into account the women with
immune responses to aerobic flora and/or sexually transmitted infections (STIs), has rather a devastating effect on pregnancy, and that this results from the fact that the wrong
condition has been targeted for treatment, and aerobic flora
has not been taken into consideration.
I’m particularly happy that you seem to agree that the
term ‘intermediate flora’ according to Nugent is a complete
misnomer, as this flora is a garbage bin for any type of
flora that cannot be defined as either ‘normal’ or ‘full BV’,
rather than just a transitional zone between the two.
Accordingly, as you recognised, this ‘garbage bin flora’ has
another composition, another pathogenicity and is not
responsive to metronidazole, and less so to clindamycin.
Therefore, future BV treatment studies should use the BV
definition according to Nugent alone, without first recognising and taking into account possible other important
ª 2009 The Authors Journal compilation ª RCOG 2009 BJOG An International Journal of Obstetrics and Gynaecology
Correspondence
vaginal flora types, whether these are AV, partial BV,
Atopobium vaginae, Mycoplasma sp. or other flora.
We agree that specific tests may be necessary for some
pathogens that cannot be seen by microscopy, such as mycoplasmata. Indeed, quantification of these bacteria could add
additional value, probably more so for Ureaplasma urealyticum than for Mycoplasma hominis, the latter of which has
always been annotated as having pathogenic activity in both
our present and previous studies.4 Although often associated
with BV, the finding of M. hominis may be of equal importance if found in association with other flora types than BV.
We hope our study stimulates more research to determine
the precise risk factors for preterm birth. j
References
1 Donders GG, Bosmans E, Dekeersmaecker A, Vereecken A, Van Bulck
B, Spitz B. Pathogenesis of abnormal vaginal bacterial flora. Am J
Obstet Gynecol 2000;182:872–8.
2 Romero R, Chaiworapongsa T, Kuivaniemi H, Tromp G. Bacterial vaginosis, the inflammatory response and the risk of preterm birth: a role
for genetic epidemiology in the prevention of preterm birth. Am J
Obstet Gynecol 2004;190:1509–19.
3 Silveira MF, Ghanem KG, Erbelding EJ, Burke AE, Johnson HL, Singh RH,
et al. Chlamydia trachomatis infection during pregnancy and the risk of
preterm birth: a case–control study. Int J STD AIDS 2009;20:465–9.
4 Donders GG, Van Bulck B, Caudron J, Londers L, Vereecken A, Spitz
B. Relationship of bacterial vaginosis and mycoplasmas to the risk of
spontaneous abortion. Am J Obstet Gynecol 2000;183:431–7.
G Donders
Heilig Hart Regional Hospital, Tienen, Belgium
Accepted 9 September 2009.
DOI: 10.1111/j.1471-0528.2009.02405.x
Inter-observer agreement in clinical decision-making
for abnormal cardiotocogram during labour:
a comparison between CTG and CTG plus STAN
Sir,
There are two main problems with this study.1
1. The authors use as the denominators for the estimation of the 95% confidence intervals the number of
trials of agreement. But these trials of agreement are not
independent of one another. It is the number of the
subjects that should be the denominator. The correct
95% confidence interval for the overall agreement of cardiotocography (CTG) is 0.78 (0.64, 0.93); and for CTG
plus ST waveform analysis (STAN) is 0.83 (0.70, 0.97).
With the number of subjects as the denominator, none
of the comparisons carried out by the authors reach the
conventional level of statistical significance. We are not
justified in concluding that CTG plus STAN is inferior
to cardiotocography alone in the decision to deliver, or
is superior to cardiotocography alone in the decision not
to deliver.
2. The authors estimate the proportions of agreement for
justified intervention and for justified non-intervention,
but these estimates are confounded by the design of their
study. Ten cases were selected where the infants had a pH
at birth of <7.05, and there were 20 cases where the pH at
birth was >7.05. In these 20 cases there were eight cases
with a pH of 7.05–7.10, still a significant degree of acidosis,
and usually indicating delivery. Obviously these were cases
indicated by STAN as not indicating delivery. Was the cutoff value between normal and abnormal chosen arbitrarily?
Was it chosen post hoc? Why choose pH as the outcome at
all, when we know that metabolic acidosis alone is a poor
predictor of cerebral palsy?
The preferred method of performing this study would be
to select a group of infants with hypoxic-ischaemic encephalopathy, and a group of infants who do not have hypoxicischaemic encephalopathy. This is preferable to a random
sample of all infants delivered. In well-grown infants at
term, progressive fetal hypoxia and metabolic acidosis can
occur, until a critical boundary is crossed when cardiovascular collapse results, with consequent spastic quadriplegia.
If that critical boundary is not crossed, complete recovery
of the infant is the rule, despite severe metabolic acidosis.
It is an ‘all-or-nothing’ phenomenon. Therefore, this study
should be repeated in a group of infants who have seizures
with severe metabolic acidosis, and a group of infants who
do not have seizures with severe metabolic acidosis. j
Reference
1 Vayssiere C, Tsatsaris V, Pirrello O, Cristini C, Arnaud C, Goffinet F.
Inter-observer agreement in clinical decision-making for abnormal cardiotocogram (CTG) during labour: a comparison between CTG and
CTG plus STAN. BJOG 2009;116:1081–8.
JM Grant
Consultant Obstetrician and Gynaecologist, Wishaw General
Hospital, Lanarkshire, ML2 0DP, UK
Accepted 22 July 2009.
DOI: 10.1111/j.1471-0528.2009.02395.x
Inter-observer agreement in clinical decision-making
for abnormal cardiotocogram during labour:
a comparison between CTG and CTG plus STAN
Authors’ Reply
Sir,
We thank JM Grant for his interest in our paper.1
His comments raise the issue of the difficulty of choosing
judgment criteria for evaluating decisions made during
ª 2009 The Authors Journal compilation ª RCOG 2009 BJOG An International Journal of Obstetrics and Gynaecology
121