Objective: To examine the influence of vaginal probiotic administration as an adjunct to standard antibiotic treatment on perinatal outcome in women with preterm premature rupture of membranes (PPROM). Materials and Methods: This was a prospective randomized trial of cases with PPROM (24-34 weeks) that were admitted to our department between 2011 and 2015. Forty-nine cases received vaginal probiotics for 10 days in combination with antibiotic prophylaxis and were compared to 57 others that received only antibiotics for the same time period. Results: The mean gestational age at birth (35.49 vs. 32.53 weeks), the mean duration of the latency period (5.60 vs. 2.48 weeks), and the mean birth weight (2,439.08 vs. 2,004.81 g) were significantly higher in the study group in comparison to the controls. Moreover, the neonates of the study group had a lower chance to enter the neonatal intensive care unit or the neonatal special care unit, shorter total hospitalization time, and lower need for oxygen administration and mechanical ventilation, as well as lower length of oxygen administration. Conclusions: Vaginal probiotics as an adjunct to antibiotic prophylaxis in women with PPROM prolonged the latency period and improved the perinatal outcome.

1.
Maxwell GL: Preterm premature rupture of membranes. Obstet Gynecol Surv 1993;48:576-583.
2.
Merenstein GB, Weisman LE: Premature rupture of the membranes: neonatal consequences. Semin Perinatol 1996;20:375-380.
3.
Nourse CB, Steer PA: Perinatal outcome following conservative management of midtrimester pre-labour rupture of the membranes. J Paediatr Child Health 1997;33:125-130.
4.
Merenstein GB, Weisman LE: Premature rupture of the membranes: neonatal consequences. Semin Perinatol 1996;20:375-380.
5.
Wu YW, Colford JM Jr: Chorioamnionitis as a risk factor for cerebral palsy: a meta-analysis. JAMA 2000;284:1417-1424.
6.
Killbride HW, Thibealt DW: Neonatal complications of preterm premature rupture of membranes, pathophysiology and management. Clin Perinatol 2001;28:761-785.
7.
Broekhuizen FF, Gilman M, Hamilton PR: Amniocentesis for gram stain and culture in preterm premature rupture of the membranes. Obstet Gynecol 1985;66:316-321.
8.
Naeff RW, Allbert JR, Ross EL, Weber BM, Martin RW, Morrison JC: Premature rupture of membranes at 34 to 37 weeks' gestation: aggressive versus conservative management. Am J Obstet Gynecol 1998;178:126-130.
9.
Mercer BM: Preterm premature rupture of the membranes. Obstet Gynecol 2003;101:178-193.
10.
ACOG Committee on Practice Bulletins-Obstetrics: ACOG Practice Bulletin No 80: premature rupture of membranes. Clinical management guidelines for obstetrician-gynecologists. Obstet Gynecol 2007;109:1007-1019.
11.
Kenyon SL, Taylor DJ, Tarnow-Mordi W; ORACLE Collaborative Group: Broad-spectrum antibiotics for preterm, prelabour rupture of fetal membranes: the ORACLE I randomised trial. ORACLE Collaborative Group. Lancet 2001;357:979-988.
12.
Kenyon S, Boulvain M, Neilson JP: Antibiotics for preterm rupture of membranes. Cochrane Database Syst Rev 2013;12:CD001058.
13.
Blackwell SC, Berry SM: Role of amniocentesis for the diagnosis of subclinical intra-amniotic infection in preterm premature rupture of the membranes. Curr Opin Obstet Gynecol 1999;11:541-547.
14.
Salminen S, Bouley C, Boutron-Ruault MC, Cummings JH, Franck A, Gibson GR, Isolauri E, Moreau MC, Roberfroid M, Rowland I: Functional food science and gastrointestinal physiology and function. Br J Nutr 1998;80:S147-S171.
15.
FAO/WHO: Guidelines for the evaluation of probiotics in food. London, Ontario: Food and Agriculture Organization of United Nations and World Health Organization Working Group report; 2002. Available from: http://www.who.int.
16.
Guarner F, Malagelada JR: Gut flora in health and disease. Lancet 2003;361:512-519.
17.
Ley RE: Obesity and the human microbiome. Curr Opin Gastroenterol 2010;26:5-11.
18.
Vitali B, Cruciani F, Baldassarre ME, Capursi T, Spisni E, Valerii MC, Candela M, Turroni S, Brigidi P: Dietary supplementation with probiotics during late pregnancy: outcome on vaginal microbiota and cytokine secretion. BMC Microbiol 2012;12:236.
19.
Othman M, Alfirevic Z, Neilson JP: Probiotics for preventing preterm labour. Cochrane Database Syst Rev 2007;1:CD005941.
20.
Lindsay KL, Walsh CA, Brennan L, McAuliffe FM: Probiotics in pregnancy and maternal outcomes: a systematic review. J Matern Fetal Neonatal Med 2013;26:772-778.
21.
Van de Vusse L, Hanson L, Safdar N: Perinatal outcomes of prenatal probiotic and prebiotic administration: an integrative review. J Perinat Neonatal Nurs 2013;27:288-301.
22.
Myhre R, Brantsæter AL, Myking S, et al: Intake of probiotic food and risk of spontaneous preterm delivery. Am J Clin Nutr 2011;93:151-157.
23.
Yang S, Reid G, Challis JRG, Kim SO, Gregory B, Gloor GB, Bocking AD: Is there a role for probiotics in the prevention of preterm birth? Front Immunol 2015;6:62.
24.
Kavak SB, Kavak E, Ilhan R, Atilgan R, Arat O, Deveci U, Sapmaz E: The efficacy of ampicillin and Lactobacillus casei rhamnosus in the active management of preterm premature rupture of membranes remote from term. Drug Des Devel Ther 2014;8:1169-1173.
25.
Dugoua JJ, Machado M, Zhu X, Chen X, Koren G, Einarson TR: Probiotic safety in pregnancy: a systematic review and meta-analysis of randomized controlled trials of Lactobacillus, Bifidobacterium, and Saccharomyces spp. J Obstet Gynaecol Can 2009;31:542-552.
26.
Jick H, Holmes LB, Hunter JR, Madsen S, Stergachis A: First-trimester drug use and congenital disorders. JAMA 1981;246:343-346.
27.
Kukkonen K, Savilahti E, Haahtela T, Juntunen-Backman K, Korpela R, Poussa T, Tuure T, Kuitunen M: Long-term safety and impact on infection rates of postnatal probiotic and prebiotic (synbiotic) treatment: randomized, double-blind, placebo-controlled trial. Pediatrics 2008;122:8-12.
28.
Allen SJ, Jordan S, Storey M, Thornton CA, Gravenor M, Garaiova I, Plummer SF, Wang D, Morgan G: Dietary supplementation with lactobacilli and bifidobacteria is well tolerated and not associated with adverse events during late pregnancy and early infancy. J Nutr 2010;140:483-488.
29.
Pelucchi C, Chatenoud L, Turati F, Galeone C, Moja L, Bach JF, La Vecchia C: Probiotics supplementation during pregnancy or infancy for the prevention of atopic dermatitis: a meta-analysis. Epidemiology 2012;23:402-414.
30.
Barrett HL, Callaway LK, Nitert MD: Probiotics: a potential role in the prevention of gestational diabetes? Acta Diabetol 2012;49(suppl 1):S1-S13.
31.
DiGiulio DB, Callahan BJ, McMurdie PJ, Costello EK, Lyell DJ, Robaczewska A, Sun CL, Goltsman DS, Wong RJ, Shaw G, Stevenson DK, Holmes SP, Relman DA: Temporal and spatial variation of the human microbiota during pregnancy. Proc Natl Acad Sci USA 2015;112:11060-11065.
32.
Donati L, Di Vico A, Nucci M, Quagliozzi L, Spagnuolo T, Labianca A, Bracaglia M, Ianniello F, Caruso A, Paradisi G: Vaginal microbial flora and outcome of pregnancy. Arch Gynecol Obstet 2010;281:589-600.
33.
O'Hanlon DE, Moench TR, Cone RA: Vaginal pH andmicrobicidal lactic acid when lactobacilli dominate the microbiota. PLoS One 2013;8:e80074.
34.
Aroutcheva AA, Simoes JA, Faro S: Antimicrobial protein produced by vaginal Lactobacillus acidophilus that inhibits Gardnerella vaginalis. Infect Dis Obstet Gynecol 2001;9:33-39.
35.
Hawes SE, Hillier SL, Benedetti J, Stevens CE, Koutsky LA, Wolner-Hanssen P, Holmes KK: Hydrogen peroxide-producing lactobacilli and acquisition of vaginal infections. J Infect Dis 1996;174:1058-1063.
36.
Yeganegi M, Watson CS, Martins A, Kim SO, Reid G, Challis JR, Bocking AD: Effect of Lactobacillus rhamnosus GR-1 supernatant and fetal sex on lipopolysaccharide-induced cytokine and prostaglandin regulating enzymes in human placental trophoblast cells: implications for treatment of bacterial vaginosis and prevention of preterm labor. Am J Obstet Gynecol 2009;200:532-538.
37.
Cadieux P, Burton J, Gardiner G, Braunstein I, Bruce AW, Kang CY, Reid G: Lactobacillus strains and vaginal ecology. JAMA 2002;287:1940-1941.
38.
Reid G, Millsap K, Bruce AW: Implantation of Lactobacillus casei var rhamnosus into vagina. Lancet 1994;344:1229.
39.
Mastromarino P, Vitali B, Mosca L: Bacterial vaginosis: a review on clinical trials with probiotics. New Microbiol 2013;36:229-238.
40.
Larsson PG, Brandsborg E, Forsum U, Pendharkar S, Andersen KK, Nasic S, Hammarström L, Marcotte H: Extended antimicrobial treatment of bacterial vaginosis combined with human lactobacilli to find the best treatment and minimize the risk of relapses. BMC Infect Dis 2011;11:223.
41.
Pendharkar S, Brandsborg E, Hammarström L, Marcotte H, Larsson PG: Vaginal colonisation by probiotic lactobacilli and clinical outcome in women conventionally treated for bacterial vaginosis and yeast infection. BMC Infect Dis 2015;15:255.
42.
Keski-Nisula L, Kyynäräinen HR, Kärkkäinen U, Karhukorpi J, Heinonen S, Pekkanen J: Maternal intrapartum antibiotics and decreased vertical transmission of Lactobacillus to neonates during birth. Acta Paediatr 2013;102:480-485.
43.
Barrons R, Tassone D: Use of Lactobacillus probiotics for bacterial genitourinary infections in women: a review. Clin Ther 2008;30:453-468.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.