Antibiotic prophylaxis before amniocentesis: a proven and effective method to preserve fetal life
PRENATAL DIAGNOSIS Prenat Diagn 2009; 29: 1095–1096. Published online in Wiley InterScience (www.interscience.wiley.com) CORRESPONDENCE Antibiotic prophylaxis before amniocentesis: a proven and effective method to preserve fetal life
APGA trial (Giorlandino et al., 2009) is today the
Alfirevic and Pilu point out the attention on a cru-
biggest randomized controlled trial (RCT) ever per-
cial point: is the antibiotic prophylaxis effective in any
formed in prenatal diagnosis, designed accurately to
gestational age? In our series the stratification by gesta-
eliminate all possible confounders and to concentrate the
tional age adjusted with the Mantel-Haenszel test (table
results exclusively on a unique variable: the antibiotic.
not shown) showed that antibiotics reduced the rate of
In this phase, it was imperative to eliminate any bias
foetal death between 16 and 18 weeks of gestational
and to administer the study in only one centre by only
age. Before 16 weeks of gestation, antibiotics reduced
one operator. The strength of the study and its general
the rates of preterm premature rupture of membranes
validity is based on the fact that all possible confounders
but not foetal death. After 18 weeks of gestation no
were eliminated, leaving only the antibiotic prophylaxisto ‘make a difference’ between the two groups tested.
treatment effect was recorded either for foetal death
In this trial we demonstrated an eightfold decrease
or preterm premature rupture. However, both before
in the abortion rate from 1/348 in the control group to
16 weeks and after 18 weeks the sample size is too small
1/3031 in the treatment group. Also well suggested by
(only 4176 cases) to detect a statistically significant dif-
Alfirevic and Pilu and reported in the paper as well, a
multicentric trial among centres of similar experience is
We chose a follow-up period of 4 weeks because other
needed to investigate about the external validity of the
authors reported the same follow-up period (Tabor et al.,
trial. However, considering the particular study design
1986; Johnson et al., 1999; Perni et al., 2004; Eddleman
and its results, it seems improbable that such a big
et al., 2006). We strongly believed that a follow-up
difference (about 80%) between the two groups in terms
till birth was not suggested because it would introduce
of abortions would not be confirmed (even if in different
a huge bias related to other prognostic factors which
differed from the short-term effect of amniocentesis.
Alfirevic and Pilu reported that Tabor et al. (1986) and
Finally Alfirevic and Pilu reported some concerns
Eddleman et al. (2006) described a miscarriage rate of
about the reassurance for a worldwide use of antibi-
two- to threefold increase in twin pregnancies over sin-
otic in pregnancy related to the results of the ORACLE.
gletons. Concerning Tabor’s study, we believe that after23 years the improvement of the skill of the operator
First of all ORACLE (Kenyon et al., 2001) has a lot of
and the routine use of continuous-ultrasound guidance
bias. The association of neurological damage and perina-
during the procedure dramatically reduced the abortion
tal infection is well described (Jacobsson and Hagberg,
rate even in the multiple procedures. The authors did a
2004); probably is the prolonged exposure to the infec-
minor mistake citing the Eddleman’s FASTER database
tions of these foetuses, in women whose membrane was
(Eddleman et al., 2006) giving that in this study were
already broken, that cause the damaging environment.
enrolled only singleton viable pregnancies.
Moreover, the administration of macrolides in ORACLE
The APGA trial demonstrated the important role of the
is completely different from APGA in quantity (10 g
infections in the outcome of the amniocentesis. In fact
in ORACLE vs 1.5 g in APGA) and duration. On the
we speculated that preterm premature rupture of mem-
other hand, the pharmacodynamics of azithromycin is
branes could be caused by reactivation of an infection
well described and during pregnancy is safe, does not
that is latent in the membrane. Therefore, considering
have teratogenic effects, and is effective against a wide
that the presence of ureplasma and mycoplasma in the
range of microbes (Sarkar et al., 2006).
uterus is the first cause responsible for the rupture of
We are aware that, giving the highest clinical evidence
the membranes (Papantoniou et al., 2001; Perni et al.,2004), it is improbable that they could come into the
of the APGA trial (Ib–Recommendation A), there will
membranes from the skin both to the accurate disin-
be inevitable worldwide consequences in the clinical
fection of the skin and the use of all sterile disposable
guidelines, ethical and medico-legal practice. However,
material for each procedure. Finally these pathogens are
this is the price to pay to reduce abortion and pPROM
rarely present on the cutis. The ultrasound probe used
to carry out the amniocentesis is 8-cm tall, therefore theneedle needs to be longer because it must go through-
Claudio Giorlandino and Pietro Cignini∗
out the needle-probe. As yet reported in the paper no
Department of Prenatal Diagnosis, Artemisia Fetal-Maternal
bedrest was suggested, patient may resume all normal
activities, deferring heavy work, strenuous exercise and
∗ E-mail: email@example.comDOI: 10.1002/pd.2334
Copyright 2009 John Wiley & Sons, Ltd.
Kenyon S, Boulvain M, Neilson J. Antibiotics for preterm premature
rupture of membranes. Cochrane Database Syst Rev 2001(4):. CD001058.
Eddleman KA, Malone FD, Sullivan L, et al. 2006. Pregnancy loss
rates after midtrimester amniocentesis. Obstet Gynecol 108:
factors predisposing to fetal loss following a second trimester
amniocentesis. BJOG 108: 1053–1056.
Giorlandino C, Cignini P, Cini M, et al. 2009. Antibiotic Prophylaxis
Perni SC, Vardhana S, Korneeva I, et al. 2004. Mycoplasma hominis
before second-trimester Genetic Amniocentesis (APGA): a single-
and Ureaplasma urealyticum in midtrimester amniotic fluid:
centre open randomised controlled trial. Prenat Diagn 29(6):
association with amniotic fluid cytokine levels and pregnancy
outcome. Am J Obstet Gynecol 191: 1382–1386.
Jacobsson B, Hagberg G. 2004. Antenatal risk factors for cerebral
Sarkar M, Woodland C, Koren G, Einarson A. Pregnancy outcome
palsy [Review]. Best Pract Res Clin Obstet Gynaecol 18(3):
following gestational exposure to azithromycin. BMC PregnancyChildbirth 2006. 6: 8.
Johnson JM, Wilson RD, Singer J, et al. 1999. Technical factors
Tabor A, Philip J, Madsen M, Bang J, Obel EB, Norgaard-Pedersen
in early amniocentesis predict adverse outcome. Results of the
B. 1986. Randomised controlled trial of genetic amniocentesis in
Canadian Early (EA) versus Mid-trimester (MA) Amniocentesis
4606 low-risk women. Lancet 1: 1287–1293.
trial. Prenat Diagn 19: 732–738.
Copyright 2009 John Wiley & Sons, Ltd. Prenat Diagn 2009; 29: 1095–1096.
1. - DATOS BASICOS 1.1.- Aspectos generales Dominica, cuya denominación proviene del latín y otorgada por el navegante Cristóbal Colon ante su descubrimiento, el día domingo 3 de noviembre de 1493, es parte de las Islas de Barlovento, ubicada al norte del grupo sur de las Antillas Menores. Fue la última en ser colonizada por los europeos. Francia cedió esta isla a Gran Bretaña en 1763 como
UNION NATIONALE DE LA PETITE ET MOYENNE INDUSTRIE PREVENIR LES PME DE LA CONTREFACON ! Rapport réalisé par l’UNPMI Sous la direction de Monsieur Pierre WAINTRAUB Président de la Fédération Française de la Maroquinerie Avec la collaboration de Monsieur Dominique BROGGIO Juriste au sein de la Direction des Affaires Économiques de la CGPME Document élab