Geburtshilfe Frauenheilkd 2013; 73(12): 1218-1227
DOI: 10.1055/s-0033-1360195
DGGG Review
GebFra Science
Georg Thieme Verlag KG Stuttgart · New York

Antibiotic Therapy for Premature Rupture of Membranes and Preterm Labor and Effect on Fetal Outcome

Antiinfektiöse Therapie bei vorzeitigem Blasensprung und Wehentätigkeit und Fetal Outcome
B. Seelbach-Goebel
Krankenhaus der Barmherzigen Brüder – Klinik St. Hedwig, Lehrstuhl für Frauenheilkunde und Geburtshilfe der Universität Regensburg, Regensburg
› Author Affiliations
Further Information

Publication History

received 08 November 2013
revised 19 November 2013

accepted 19 November 2013

Publication Date:
20 December 2013 (online)

   Permissions and Reprints

Abstract

In Germany almost 10 % of children are born before the end of 37th week of gestation. In at least one quarter of these cases, ascending infection of the vagina plays a causative role, particularly during the early weeks of gestation. If, in addition to the decidua, the amniotic membrane, amniotic fluid and the umbilical cord are also affected, infection not only triggers uterine contractions and premature rupture of membranes but also initiates a systemic inflammatory reaction on the part of the fetus, which can increase neonatal morbidity. Numerous studies and meta-analyses have found that antibiotic therapy prolongs pregnancy and reduces neonatal morbidity. No general benefit of antibiotic treatment was found for premature uterine contractions. But it is conceivable that a subgroup of pregnant women would benefit from antibiotic treatment. It is important to identify this subgroup of women and offer them targeted treatment. This overview summarizes the current body of evidence on antibiotic treatment for impending preterm birth and the effect on neonatal outcomes.

Zusammenfassung

In Deutschland kommen fast 10 % aller Kinder vor Vollendung der 37. Schwangerschaftswoche zur Welt. In mindestens einem Viertel davon spielt eine aszendierende Infektion aus der Vagina eine kausale Rolle, insbesondere in einem niedrigen Gestationsalter. Sind neben der Dezidua die Eihäute, das Fruchtwasser und die Nabelschnur davon betroffen, werden durch entzündliche Prozesse nicht nur Wehen oder ein vorzeitiger Blasensprung ausgelöst, sondern auch eine systemische inflammatorische Reaktion des Fetus selbst in Gang gesetzt, welche die neonatale Morbidität negativ beeinflussen kann. Als Therapiemaßnahme bei vorzeitigem Blasensprung hat sich in zahlreichen Studien und Metaanalysen eine antibiotische Behandlung bewährt, indem die Schwangerschaft prolongiert und die neonatale Morbidität reduziert werden konnte. Bei vorzeitiger Wehentätigkeit hat sich dagegen ein Benefit generell nicht nachweisen lassen. Es ist aber anzunehmen, dass es eine Subgruppe von Schwangeren gibt, die dennoch davon profitieren könnte. Es gilt diese zu identifizieren und gezielt zu behandeln. Die vorliegende Übersicht umreißt die derzeitige Evidenzlage zur antibiotischen Behandlung bei drohender Frühgeburt und zum neonatalen Outcome.

Key words

premature rupture of membranes - impending preterm birth - premature uterine contractions - antibiosis for impending preterm birth

Schlüsselwörter

vorzeitiger Blasensprung - drohende Frühgeburt - vorzeitige Wehen - Antibiose bei drohender Frühgeburt

Supporting Information

 

  • References

  • 1 Goldenberg RL, Culhane JF, Iams JD et al. Epidemiology and causes of preterm birth. Lancet 2008; 371: 75-84
    CrossrefPubMedGoogle Scholar
  • 2 AQUA-Institut für angewandte Qualitätsförderung und Forschung im Gesundheitswesen GmbH. 2011 (a), Gesetzliche Grundlagen § 137a SGB V zur „Umsetzung der Qualitätssicherung und Darstellung der Qualität“ im deutschen Gesundheitswesen. Online: http://www.sqg.de/hintergrund/gesetzliche-grundlagen/index.html
    Google Scholar
  • 3 Muglia LJ, Katz M. The enigma of spontaneous preterm birth. N Engl J Med 2010; 362: 529-535
    Google Scholar
  • 4 Mercer B. Antibiotics in the management of PROM and preterm labor. Obstet Gynecol Clin North Am 2012; 39: 65-76
    CrossrefGoogle Scholar
  • 5 Onderdonk AB, Hecht L, Thomas F et al. Colonization of second trimester placenta parenchyma. Am J Obstet Gynecol 2008; 199: 52.e1-52.e10
    Google Scholar
  • 6 Tita AT, Anrews WW. Diagnosis and management of clinical chorioamnionitis. Clin Perinatol 2010; 37: 339-354
    CrossrefGoogle Scholar
  • 7 De Felice C, Toti P, Laurini RN et al. Early neonatal brain injury in histologic chorioamnionitis. J Pediatr 2001; 138: 101-104
    Google Scholar
  • 8 De Felice C, Toti P, Parrini S et al. Histologic chorioamnionitis and severitiy of illess in very low birth weight newborns. Pedriatr Crit Care Med 2005; 6: 293-302
    Google Scholar
  • 9 Mehta R, Nanjundaswamy S, Shen-Schwarz S et al. Neonatal morbidity and placental pathology. Indian J Pediatr 2006; 73: 25-28
    CrossrefGoogle Scholar
  • 10 Watterberg KL, Demers LM, Scott SM et al. Chorioamnionitis and early lung inflammation in infants in whom bronchopulmonary dysplasia develops. Pediatrics 1996; 97: 210-215
    CrossrefPubMedGoogle Scholar
  • 11 Graham EM, Holcroft CJ, Rai KK et al. Neonatal cerebral white matter injury in preterm infants is associated with culture positive infections and only rarely with metabolic acidosis. Am J Obstet Gynecol 2004; 191: 1305-1310
    CrossrefPubMedGoogle Scholar
  • 12 Dammann O, Leviton A, Bartels DB et al. Lung and brain damage in preterm newborns. Are they related? How? Why?. Biol Neonate 2004; 85: 305-313
    CrossrefGoogle Scholar
  • 13 Salafia CM, Minior VK, Rosenkrantz TS et al. Maternal, placental and neonatal associations with early germinal matrix/intraventricular hemorrhage in infants born before 32 weeksʼ gestation. Am J Perinatol 1995; 12: 429-436
    Article in Thieme ConnectGoogle Scholar
  • 14 Been JV, Rours IG, Kornelisse RF et al. Histologic chorioamnionitis, fetal involvement, and antenatal steroids: effects on neonatal outcome in preterm infants. Am J Obstet Gynecol 2009; 201: 587.e1-587.e8
    Google Scholar
  • 15 Andrews WW, Goldenberg RL, Faye-Peterson O et al. The Alabama preterm birth study: polymorphonuclear and mononuclear cell placental infiltrations, other markers of inflammation and outcomes in 23–32 week preterm newborn infants. Am J Obstet Gynecol 2006; 195: 803-808
    CrossrefPubMedGoogle Scholar
  • 16 Dempsey E, Vhen MF, Kokottis T et al. Outcome of neonates less than 30 weeksʼ gestation with histologic chorioamnionitis. Am J Perinatol 2005; 22: 155-159
    Article in Thieme ConnectGoogle Scholar
  • 17 Baud O, Emilie D, Pelletier E et al. Amniotic fluid concentrations of interleukin-1beta, interleukin-6 and TNF-alpha in chorioamnionitis before 32 weeks of gestation: histological associations and neonatal outcome. Br J Obstet Gynaecol 1999; 106: 72-77
    Google Scholar
  • 18 Dexter SC, Pinar H, Malee MP et al. Outcome of very low birth weight infants with histopathologic chorioamnionitis. Obstet Gynecol 2000; 96: 172-177
    CrossrefGoogle Scholar
  • 19 Tauscher MK, Berg D, Brockmann M et al. Association of histologic chorioamnionitis, increased levels of cord blood cytokines, and intracerebral hemorrhage in preterm neonates. Biol Neonate 2003; 83: 166-170
    CrossrefGoogle Scholar
  • 20 Kaukola T, Herva R, Perhomaa M et al. Population cohort associating chorioamnionitis, cord inflammatory cytokines and neurologic outcome in very preterm, extremely low birth weight infants. Pediatr Res 2006; 59: 478-483
    CrossrefGoogle Scholar
  • 21 Yoon BH, Jun JK, Romero R et al. Amniotic fluid inflammatory cytokines (interleukin-6, interleukin-1beta, and tumor necrosis factor-alpha), neonatal white matter lesions, and cerebral palsy. Am J Obstet Gynecol 1997; 177: 19-26
    CrossrefPubMedGoogle Scholar
  • 22 Lee J, Oh KJ, Yang HJ et al. The importance of intraamniotic inflammation in the subsequent development of atypal chronic lung disease. J Matern Fetal Neonatal Med 2009; 22: 917-923
    CrossrefGoogle Scholar
  • 23 Shatrov JG, Birch SC, Lam LT et al. Chorioamnionitis and cerebral palsy. Obstet Gynecol 2010; 116: 387-392
    CrossrefPubMedGoogle Scholar
  • 24 Wu YW. Systematic review of choriamnionitis and cerebral palsy. Ment Retard Dev Disabil ResRev 2002; 8: 25-29
    Google Scholar
  • 25 Leviton A, Allred EN, Kuban KC et al. Microbiologic and histologic characteristics of the extremely preterm infantʼs placenta predict white matter damage and later cerebral palsy: The ELGAN study. Pediatric Research 2010; 67: 95-101
    CrossrefGoogle Scholar
  • 26 Nasef N, Shabaan A, Schurr P et al. Effect of clinical and histological chorioamnionitis on the outcome of preterm infants. Am J Perinatology 2013; 30: 59-68
    Google Scholar
  • 27 Romero R, Espinoza J, Goncalves LF et al. The role of inflammation and infection in preterm birth. Semin Reprod Med 2007; 25: 21-39
    Article in Thieme ConnectPubMedGoogle Scholar
  • 28 Gomez R, Romero R, Ghezzi F et al. The fetal inflammatory response syndrome. Am J Obstet Gynecol 1998; 179: 194-202
    CrossrefPubMedGoogle Scholar
  • 29 Been JV, Zimmermann LJ. Histologic chorioamnionitis and respiratory outcome in preterm infants. Arch Dis Child Fetal Neonatal Ed 2009; 94: F218-F225
    CrossrefPubMedGoogle Scholar
  • 30 Yoon BH, Romero R, Park JS et al. Fetal exposure to an intraamniotic inflammation and the development of cerebral palsy at the age of three years. Am J Obstet Gynecol 2000; 182: 675-681
    CrossrefPubMedGoogle Scholar
  • 31 Minagawa K, Tsuji Y, Ueda H et al. Possible correlation between high levels of IL-18 in the cord blood of preterm infants and neonatal development of periventricular leukomalacia and cerebral palsy. Cytokine 2002; 17: 164-170
    CrossrefGoogle Scholar
  • 32 Hansen-Pupp I, Halli AL, Hellstrom-Westas I et al. Inflammation at birth is associated with subnormal development in very preterm infants. Pediatr Res 2009; 64: 183-188
    Google Scholar
  • 33 Goldenberg RL, Hauth JC, Andrews WW. Intrauterine infection and preterm delivery. N Engl J Med 2000; 342: 1500-1507
    CrossrefPubMedGoogle Scholar
  • 34 Onderdonk AB, Delaney ML, DuBois AM et al. Detection of bacteria in placental tissues obtained from extremely low gestational age neonates. Am J Obstet Gynecol 2008; 198: 110.e1-110.e7
    Google Scholar
  • 35 Romero R, Sirtori M, Oyarzun E et al. Infection and labor. V: Prevalence, microbiology, and clinical significance of intraamnonic infection in women with preterm labor and intact membranes. Am J Obstet Gynecol 1989; 161: 817-824
    CrossrefGoogle Scholar
  • 36 Romero R, Gonzales R, Sepulveda W et al. Infection and labor. VIII. Microbial invasion of the amniotic cavity in patients with suspected cervical incompetence: prevalence and clinical significance. Am J Obstet Gynecol 1992; 167: 1086-1091
    CrossrefGoogle Scholar
  • 37 Romero R, Yoon BH, Mazor M et al. A comparative study of the diagnostic performance of amniotic fluid glucose, white blood cell count, interleukin-6, and gram stain in the detection of microbial invasion in patients with preterm premature rupture of membranes. Am J Obstet Gynecol 1993; 169: 839-851
    CrossrefPubMedGoogle Scholar
  • 38 Yoon BH, Romero R, Park JS et al. Microbial invasion of the amniotic cavity with Ureaplasma urealyticum is associated with a robust host response in fetal, amniotic, and maternal compartments. Am J Obstet Gynecol 1998; 179: 1254-1260
    CrossrefGoogle Scholar
  • 39 Yoon BH, Chang JW, Romero R. Isolation of Ureaplasma urealyticum from the amniotic cavity and adverse outcome in preterm labor. Obstet Gynecol 1998; 92: 77-82
    CrossrefGoogle Scholar
  • 40 Lee SE, Romero R, Park CW et al. The frequency and significance of intraamniotic inflammation in patients with cervical insufficiency. Am J Obstet Gynecol 2008; 198: 633.e1-633.e8
    Google Scholar
  • 41 Egawa T, Morioka I, Morisawa T et al. Ureaplasma urealyticum and Mycoplasma hominis presence in umbilical cord is associated with pathogenesis of funisitis. Kobe J Med Sci 2007; 53: 241-249
    Google Scholar
  • 42 Oh KJ, Lee KA, Sohn YK et al. Intraamniotic infection with genital mycoplasmas exhibits a more intense inflammatory response than intraamniotic infection with other microorganisms in patients with preterm premature rupture of membranes. Am J Obstet Gynecol 2010; 203: 211.e1-211.e8
    Google Scholar
  • 43 Goldenberg RL, Andrews WW, Goepfert AR et al. The Alabama Preterm Birth Study: umbilical cord blood Ureaplasma urealyticum and Mycoplasma hominis cultures in very preterm newborn infants. Am J Obstet Gynecol 2008; 198: 43.e1-43.e5
    CrossrefGoogle Scholar
  • 44 Choi SJ, Park SD, Jang IH et al. The prevalence of vaginal microorganisms in pregnant women with preterm labor and preterm birth. Ann Lab Med 2012; 32: 194-200
    CrossrefGoogle Scholar
  • 45 Capoccia R, Greub G, Baud D. Ureaplasma urealyticum, Mycoplasma hominis and adverse pregnancy outcomes. Curr Opin Infect Dis 2013; 26: 231-240
    CrossrefGoogle Scholar
  • 46 Eschenbach DA, Nugent RP, Rao AV et al. A randomized placebo-controlled trial of erythromycin for the treatment of Ureaplasma urealyticum to prevent premature delivery. The Vaginal Infections and Prematurity Study Group. Am J Obstet Gynecol 1991; 164: 734-742
    CrossrefGoogle Scholar
  • 47 Raynes Greenow CH, Roberts CL, Bell JC et al. Antibiotics for ureaplasma in the vagina in pregnancy. Cochrane Database Syt Rev 2011; (9) CD003767
    Google Scholar
  • 48 Steel JH, Malatos S, Kennea N et al. Bacteria and inflammatory cells in fetal membranes do not always cause preterm labor. Pediatr Res 2005; 57: 404-411
    CrossrefGoogle Scholar
  • 49 Kenyon S, Boulvain M, Neilson JP. Antibiotics for preterm rupture of membranes. Cochrane Database Syst Rev 2010; (8) CD001058
    Google Scholar
  • 50 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. Lancet 2001; 357: 979-988
    CrossrefGoogle Scholar
  • 51 Mercer B, Miodovnik M, Thurnau G et al. The NICHD-MFMU Network. Antibiotic therapy for reduction of infant morbidity after preterm premature rupture of the membranes: a randomized controlled trial. JAMA 1997; 278: 989-995
    CrossrefGoogle Scholar
  • 52 Lockwood CJ, Costigan K, Ghidini A et al. Double-blind placebo-controlled trial of piperacillin prophylaxis in preterm membrane rupture. Am J Obstet Gynecol 1993; 169: 970-976
    CrossrefGoogle Scholar
  • 53 Amon E, Lewis SV, Sibai BM et al. Ampicillin prophylaxis in preterm premature rupture of the membranes: a prospective randomized study. Am J Obstet Gynecol 1988; 159: 539-543
    Google Scholar
  • 54 Christmas JT, Cox SM, Andrews W et al. Expectant management of preterm ruptured membranes: effects of antimicrobial therapy. Obstet Gynecol 1992; 80: 759-762
    Google Scholar
  • 55 Fuhr N, Becker C, van Baalen A et al. Antibiotic therapy for preterm premature rupture of membranes: results of a multicenter study. J Perinat Med 2009; 34: 203-206
    Google Scholar
  • 56 Johnson MM, Sanchez-Ramos L, Vaughn AJ et al. Antibiotic therapy in preterm premature rupture of the membranes: a randomized prospective double-blind study. Am J Obstet Gynecol 1990; 163: 743-747
    CrossrefGoogle Scholar
  • 57 Owen J, Groome LJ, Hauth JC. Randomized trial of prophylactic antibiotic therapy after preterm amnion rupture. Am J Obstet Gynecol 1993; 169: 976-981
    CrossrefGoogle Scholar
  • 58 Segel SY, Miles AM, Clothier B et al. Duration of antibiotic therapy after preterm premature rupture of fetal membranes. Am J Obstet Gynecol 2003; 189: 799-802
    CrossrefGoogle Scholar
  • 59 Lewis DF, Adair CD, Robichaux AG et al. Antibiotic therapy in preterm premature rupture of fetal membranes. Am J Obstet Gynecol 2003; 189: 799-802
    CrossrefGoogle Scholar
  • 60 Yudin MH, van Schalkwyk J, Van Eyck N et al. Antibiotic therapy in preterm premature rupture of membranes. J Obstet Gynaecol Can 2009; 31: 863-867
    Google Scholar
  • 61 AWMF Leitlinie Nr. 015/029 Empfehlungen zum Vorgehen beim vorzeitigen Blasensprung.
    Google Scholar
  • 62 McGregor IA, French JL, Reller LB et al. Adjunctive erythromycin treatment for idiopathic preterm labour: Results of a randomized, double blinded, placebo-controlled trial. Am J Obst Gynecol 1986; 154: 98-103
    Google Scholar
  • 63 McGregor IA, French I, Seo K. Adjunctive clindamycin therapy for preterm labor: results of a double-blinded placebo-controlled trial. Am J Obstet Gynecol 1991; 165: 867-875
    CrossrefGoogle Scholar
  • 64 Morales WJ, Angel JL, OʼBrien WF et al. A randomized study of antibiotic therapy in idiopathic preterm labor. Obstet Gynecol 1988; 72: 829-833
    Google Scholar
  • 65 Norman K, Pattinson RC, de Souza J et al. Ampicillin and metronidazole treatment in preterm labour: a multicentre, randomised controlled trial. Br J Obstet Gynecol 1994; 101: 404-408
    Google Scholar
  • 66 Nadisaukiene R, Bergström S, Kilda A. Ampicillin in the treatment of preterm labor: a randomised, placebo-controlled study. Gynecol Obstet Invest 1996; 41: 89-92
    CrossrefGoogle Scholar
  • 67 Svare J, Langhoff-Roos J, Andersen LF et al. Ampicillin-metronidazole treatment in idiopathic preterm labour: a randomised controlled multicentre trial. Br J Obstet Gynaecol 1997; 104: 892-897
    Google Scholar
  • 68 Oyarzún E, Gómez R, Rioseco A et al. Antibiotic treatment in preterm labor and intact membranes; a randomized, double-blinded, placebo-controlled trial. J Matern Fetal Med 1998; 7: 105-110
    CrossrefGoogle Scholar
  • 69 Newton ER, Dinsmoor MJ, Gibbs RS. A randomized, blinded, placebo-controlled trial of antibiotics in idiopathic preterm labor. Obstet Gynecol 1989; 74: 562-566
    Google Scholar
  • 70 Romero R, Sibai B, Caritis S et al. Antibiotic treatment of preterm labour with intact membranes: a multicenter, randomized double blind, placebo-controlled trial. Am J Obstet Gynecol 1993; 169: 764-774
    CrossrefGoogle Scholar
  • 71 Watts DH, Krohn MA, Hillier SL et al. Randomized trial of antibiotics in addition to tocolytic therapy to treat preterm labor. Infect Dis Obstet Gynecol 1994; 1: 220-227
    CrossrefGoogle Scholar
  • 72 Gordon M, Samuels P, Shubert P et al. A randomized, prospective study of adjunctive ceftizoxime in preterm labour. Am J Obstet Gynecol 1995; 172: 1546-1552
    CrossrefGoogle Scholar
  • 73 Cox SM, Bohman Van R, Sherman ML et al. Randomized investigation of antimicrobials for the prevention of preterm birth. Am J Obstet Gynecol 1996; 174: 206-210
    CrossrefGoogle Scholar
  • 74 Kenyon SL, Taylor DJ, Tarnow-Mordi W et al. Broad-spectrum antibiotics for spontaneous preterm labour: the ORACLE II randomized trial. Lancet 2001; 357: 989-994
    CrossrefGoogle Scholar
  • 75 King J, Flenady V. Prophylactic antibiotics for inhibiting preterm labour with intact membranes. Cochrane Database Syst Rev 2002; (4) CD000246
    Google Scholar
  • 76 Ovalle A, Romero R, Gómez R et al. Antibiotic administration to patients with preterm labor and intact membranes: is there a beneficial effect in patients with endocervical inflammation?. J Matern Fetal Neonatal Med 2006; 19: 453-464
    CrossrefGoogle Scholar
  • 77 Peaceman AM, Andrews WW, Thorp JM et al. Fetal fibronectin as a predictor of preterm birth in patients with symptoms. Am J Obstet Gynecol 1997; 177: 13-16
    CrossrefGoogle Scholar
  • 78 Sukchaya K, Phupong V. A comparative study of positive rate of placental alpha-microglobulin 1 test in pre-term pregnant women with and without uterine contraction. J Obstet Gynaecol 2013; 33: 566-568
    CrossrefGoogle Scholar
  • 79 Andrews WW, Sibai BM, Thom EA et al. Randomized clinical trial of metronidazole plus erythromycin to prevent spontaneous preterm delivery in fetal fibronectin-positive women. Obstet Gynecol 2003; 101: 847-855
    CrossrefGoogle Scholar
  • 80 Shennan A, Crawshaw S, Briley A et al. A randomized controlled trial of metronidazole for the prevention of preterm birth in women positive for cervicovaginal fetal fibronectin: the PREMET Study. BJOG 2006; 113: 65-74
    Google Scholar
  • 81 Hendler J, Andrews WW, Carey CJ et al. The relationship between resolution of asymptomatic bacterial vaginosis and spontaneous preterm birth in fetal fibronectin-positive women. Am J Obstet Gynecol 2007; 197: 488.e1-488.e5
    Google Scholar
  • 82 Kenyon S, Pike K, Jones DR et al. Childhood outcomes after prescription of antibiotics to pregnant women with preterm rupture of the membranes; 7-year follow-up of the ORACLE trial. Lancet 2008; 372: 1310-1318
    CrossrefGoogle Scholar
  • 83 Kenyon S, Pike K, Jones DR et al. Childhood outcomes after prescription of antibiotics to pregnant women with spontaneous preterm labour: 7-year follow-up of the ORACLE II trial. Lancet 2008; 372: 1319-1327
    CrossrefGoogle Scholar
  • 84 Marlow N, Pike K, Bower E et al. Characteristics of children with cerebral palsy in the ORACLE children study. Dev Med Child Neurol 2012; 54: 640-646
    CrossrefGoogle Scholar
  • 85 Kenyon S, Taylor DJ. The effect of the publication of a major clinical trial in a high impact journal on clinical practise: the ORACLE Trial experience. BJOG 2002; 109: 1341-1343
    CrossrefGoogle Scholar
  • 86 Kenyon S, Pike K, Jones D et al. Has publication of the results of the ORACLE Children Study changed practice in the UK?. BJOG 2010; 117: 1344-1349
    CrossrefGoogle Scholar
  • 87 Bizarro MJ, Dembry LM, Baltimore RS et al. Changing patterns in neonatal Escherichia coli sepsis and ampicillin resistance in the era of intrapartum antibiotic prophylaxis. Pediatrics 2008; 121: 689-696
    CrossrefGoogle Scholar
  • 88 Wright AJ, Unger S, Coleman BL et al. Maternal antibiotic exposure and risk of antibiotic resistance in neonatal early-onset sepsis: a case-cohort study. Pediatr Infect Dis J 2012; 31: 1206-1208
    CrossrefGoogle Scholar
  • 89 Thomas W, Speer CP. Chorioamnionitis: important risk factor or innocent bystander for neonatal outcome?. Neonatology 2011; 99: 177-187
    CrossrefPubMedGoogle Scholar
  • 90 Lahra MM, Beeby PJ, Jeffery HE. Intrauterine inflammation, neonatal sepsis, and chronic lung disease: a 13-year hospital cohort study. Pediatrics 2009; 123: 1314-1319
    CrossrefPubMedGoogle Scholar
  • 91 Chau V, Poskitt KJ, McFadden DE et al. Effect of chorioamnionitis on brain development and injury in premature newborns. Ann Neurol 2009; 66: 155-164
    CrossrefGoogle Scholar
  • 92 Perrone G, Anceschi MM, Capri O et al. Maternal C-reactive protein at hospital admission is a simple predictor of funisitis in preterm premature rupture of membranes. Gynecol Obstet Invest 2012; 74: 95-99
    CrossrefGoogle Scholar
  • 93 Canzeroni BJ, Grotegut CA, Swamy GK et al. Maternal serum interleukin-6 levels predict impending funisitis in preterm premature rupture of membranes after completion of antibiotics. J Matern Fetal Neonat Med 2012; 25: 1329-1332
    CrossrefGoogle Scholar
  • 94 Mercer BM, Crouse DT, Goldenberg RL et al. The antibiotic treatment of PPROM study: systemic maternal and fetal markers and perinatal outcomes. Am J Obstet Gynecol 2012; 206: 145.e1-145.e9
    Google Scholar
  • 95 Gotsch F, Romero R, Kusanovic JP et al. The anti-inflammatory limb of the immune response in preterm labor, intra-amniotic infection/inflammation, and spontaneous parturition at term: A role for interleukin-10. J Matern Fetal Neonat Med 2008; 21: 529-547
    CrossrefGoogle Scholar
  • 96 Sadowsky DW, Novy MJ, Witkin SS et al. Dexamethasone or interleukin-10 blocks interleukin-1beta-induced uterine contractions in pregnant rhesus monkeys. Am J Obstet Gynecol 2003; 188: 252-263
    CrossrefGoogle Scholar
  • 97 Rodts-Palenik S, Wyatt-Ashmead J, Pang Y et al. Maternal infection-induced white matter injury is reduced by treatment with interleukin-10. Am J Obstet Gynecol 2004; 191: 1387-1392
    CrossrefGoogle Scholar
  • 98 Mesples B, Plaisant F, Gressens P. Effects of interleukin-10 on neonatal excitotoxic brain lesions in mice. Brain Res Dev Brain Res 2003; 141: 25-32
    CrossrefGoogle Scholar
  • 99 Miller SP, Mayer EE, Clyman RI et al. Prolonged indomethacin exposure is associated with decreased white matter injury detected with magnetic resonance imaging in premature newborns at 24–28 weeksʼ gestation at birth. Pediatrics 2006; 117: 1626-1631
    CrossrefGoogle Scholar
  • 100 Hoyme UB, Saling E. Efficient prematurity prevention is possible by pH-self measurement and immediate therapy of threatening ascending infection. Eur J Obstet Gynecol Reprod Biol 2004; 10: 148-153
    Google Scholar
  • 101 Brocklehurst P, Gordon A, Heatley E et al. Antibiotics for treating bacterial vaginosis in pregnancy. Cochrane Database Syst Rev 2013; (1) CD000262
    Google Scholar