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: pietrocignini@fastwebnet.it DOI: 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 Pregnancy Childbirth 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.

Source: http://www.claudiogiorlandino.it/sites/default/files/fulltext_0.pdf