Maternal azithromycin therapy for Ureaplasma parvum intraamniotic infection improves fetal hemodynamics in a nonhuman primate model.
Administration, Intravenous
Amnion
Amniotic Fluid
/ immunology
Animals
Anti-Bacterial Agents
/ therapeutic use
Aorta
/ diagnostic imaging
Azithromycin
/ therapeutic use
Blood Flow Velocity
Cardiac Output
/ physiology
Chorioamnionitis
/ drug therapy
Disease Models, Animal
Ductus Arteriosus
/ diagnostic imaging
Echocardiography, Doppler
Female
Fetal Heart
/ physiopathology
Hemodynamics
/ physiology
Injections
Interleukin-6
/ immunology
Macaca mulatta
Middle Cerebral Artery
/ diagnostic imaging
Pregnancy
Pregnancy Complications, Infectious
/ drug therapy
Pulmonary Artery
/ diagnostic imaging
Pulsatile Flow
Ultrasonography, Doppler
Ultrasonography, Prenatal
Umbilical Arteries
/ diagnostic imaging
Ureaplasma
Ureaplasma Infections
/ drug therapy
Doppler ultrasound
azithromycin
chorioamnionitis
preterm birth
Journal
American journal of obstetrics and gynecology
ISSN: 1097-6868
Titre abrégé: Am J Obstet Gynecol
Pays: United States
ID NLM: 0370476
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
06
11
2019
revised:
09
04
2020
accepted:
18
04
2020
pubmed:
29
4
2020
medline:
24
11
2020
entrez:
29
4
2020
Statut:
ppublish
Résumé
Ureaplasma parvum infection is a prevalent cause of intrauterine infection associated with preterm birth, preterm premature rupture of membranes, fetal inflammatory response syndrome, and adverse postnatal sequelae. Elucidation of diagnostic and treatment strategies for infection-associated preterm labor may improve perinatal and long-term outcomes for these cases. This study assessed the effect of intraamniotic Ureaplasma infection on fetal hemodynamic and cardiac function and the effect of maternal antibiotic treatment on these outcomes. Chronically catheterized pregnant rhesus monkeys were assigned to control (n=6), intraamniotic inoculation with Ureaplasma parvum (10 Umbilical and fetal pulmonary artery vascular impedances were significantly increased in animals from the intraamniotic inoculation with Ureaplasma parvum group (P<.05). Azithromycin treatment restored values to control levels. Amniotic fluid prostaglandin F2 alpha levels were significantly higher in animals with abnormal umbilical artery pulsatility index (>1.1) than in those with normal blood flow (P<.05; Spearman ρ=0.6, P<.05). In the intraamniotic inoculation with Ureaplasma parvum group, left ventricular cardiac output was significantly decreased (P<.001), and more animals had abnormal right-to-left ventricular cardiac output ratios (defined as >1.6, P<.05). Amniotic fluid interleukin-6 concentrations were elevated in cases of abnormal right-to-left ventricular cardiac output ratios compared with those in normal cases (P<.05). Fetal hemodynamic alterations were associated with intraamniotic Ureaplasma infection and ameliorated after maternal antibiotic treatment. Doppler ultrasonographic measurements merit continuing investigation as a diagnostic method to identify fetal cardiovascular and hemodynamic compromise associated with intrauterine infection or inflammation and in the evaluation of therapeutic interventions or clinical management of preterm labor.
Sections du résumé
BACKGROUND
Ureaplasma parvum infection is a prevalent cause of intrauterine infection associated with preterm birth, preterm premature rupture of membranes, fetal inflammatory response syndrome, and adverse postnatal sequelae. Elucidation of diagnostic and treatment strategies for infection-associated preterm labor may improve perinatal and long-term outcomes for these cases.
OBJECTIVE
This study assessed the effect of intraamniotic Ureaplasma infection on fetal hemodynamic and cardiac function and the effect of maternal antibiotic treatment on these outcomes.
STUDY DESIGN
Chronically catheterized pregnant rhesus monkeys were assigned to control (n=6), intraamniotic inoculation with Ureaplasma parvum (10
RESULTS
Umbilical and fetal pulmonary artery vascular impedances were significantly increased in animals from the intraamniotic inoculation with Ureaplasma parvum group (P<.05). Azithromycin treatment restored values to control levels. Amniotic fluid prostaglandin F2 alpha levels were significantly higher in animals with abnormal umbilical artery pulsatility index (>1.1) than in those with normal blood flow (P<.05; Spearman ρ=0.6, P<.05). In the intraamniotic inoculation with Ureaplasma parvum group, left ventricular cardiac output was significantly decreased (P<.001), and more animals had abnormal right-to-left ventricular cardiac output ratios (defined as >1.6, P<.05). Amniotic fluid interleukin-6 concentrations were elevated in cases of abnormal right-to-left ventricular cardiac output ratios compared with those in normal cases (P<.05).
CONCLUSION
Fetal hemodynamic alterations were associated with intraamniotic Ureaplasma infection and ameliorated after maternal antibiotic treatment. Doppler ultrasonographic measurements merit continuing investigation as a diagnostic method to identify fetal cardiovascular and hemodynamic compromise associated with intrauterine infection or inflammation and in the evaluation of therapeutic interventions or clinical management of preterm labor.
Identifiants
pubmed: 32343954
pii: S0002-9378(20)30463-4
doi: 10.1016/j.ajog.2020.04.015
pmc: PMC7591241
mid: NIHMS1634206
pii:
doi:
Substances chimiques
Anti-Bacterial Agents
0
Interleukin-6
0
Azithromycin
83905-01-5
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
578.e1-578.e11Subventions
Organisme : NICHD NIH HHS
ID : K99 HD090229
Pays : United States
Organisme : NIH HHS
ID : P51 OD011092
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Références
Pharmacol Ther. 2014 Aug;143(2):225-45
pubmed: 24631273
Pediatr Res. 2011 May;69(5 Pt 1):442-7
pubmed: 21258263
J Matern Fetal Neonatal Med. 2004 Sep;16(3):146-57
pubmed: 15590440
Am J Obstet Gynecol. 2003 Nov;189(5):1445-51
pubmed: 14634584
Lancet. 2001 Mar 31;357(9261):989-94
pubmed: 11293641
Cardiovasc Res. 2003 Oct 15;60(1):156-64
pubmed: 14522418
Lancet. 2008 Oct 11;372(9646):1319-27
pubmed: 18804276
Nat Commun. 2018 Jan 17;9(1):263
pubmed: 29343712
Pediatr Res. 2009 May;65(5 Pt 2):84R-90R
pubmed: 19190528
J Perinat Med. 2005;33(1):17-21
pubmed: 15841608
Pediatr Res. 2006 Feb;59(2):180-4
pubmed: 16439575
Am J Obstet Gynecol. 1998 Nov;179(5):1254-60
pubmed: 9822511
Fetal Diagn Ther. 2012;32(1-2):17-21
pubmed: 22777135
Clin Exp Obstet Gynecol. 2001;28(1):17-9
pubmed: 11332581
J Obstet Gynaecol. 2013 Nov;33(8):768-75
pubmed: 24219711
Am J Obstet Gynecol. 2019 Aug;221(2):142.e1-142.e22
pubmed: 30928566
Echocardiography. 2004 Oct;21(7):669-72
pubmed: 15488100
Dev Med Child Neurol. 2012 Jul;54(7):640-6
pubmed: 22458348
Ultrasound Obstet Gynecol. 2010 Jul;36(1):26-31
pubmed: 20131338
Am J Obstet Gynecol. 2016 Jul;215(1):9-20
pubmed: 26821337
PLoS One. 2013;8(3):e58494
pubmed: 23516490
J Cardiol. 1995 Dec;26(6):357-66
pubmed: 8558414
Placenta. 2003 Aug;24(7):786-9
pubmed: 12852870
Clin Infect Dis. 2004 Oct 15;39(8):1113-22
pubmed: 15486833
Obstet Gynecol Sci. 2017 Jul;60(4):336-342
pubmed: 28791264
Curr Opin Obstet Gynecol. 2018 Dec;30(6):344-354
pubmed: 30299319
Pediatr Res. 2010 Dec;68(6):513-8
pubmed: 20736882
Curr Opin Pediatr. 2000 Apr;12(2):99-104
pubmed: 10763757
Ultrasound Med Biol. 2015 Apr;41(4):1020-8
pubmed: 25701524
J Appl Physiol (1985). 2010 Jun;108(6):1757-65
pubmed: 20339013
Lab Anim Sci. 1988 Jun;38(3):343-4
pubmed: 3411932
Australas J Ultrasound Med. 2013 Nov;16(4):158-167
pubmed: 28191192
PLoS One. 2019 Apr 3;14(4):e0214951
pubmed: 30943260
Reprod Sci. 2013 Jan;20(1):33-8
pubmed: 22991382
Am J Reprod Immunol. 2016 Apr;75(4):440-50
pubmed: 26777387
Ultrasound Obstet Gynecol. 2003 Jan;21(1):33-6
pubmed: 12528158
Exp Physiol. 2019 Feb;104(2):189-198
pubmed: 30578690
Am J Obstet Gynecol. 1993 Oct;169(4):764-74
pubmed: 8238130
Ment Retard Dev Disabil Res Rev. 2002;8(1):3-13
pubmed: 11921380
Am J Obstet Gynecol. 2018 Apr;218(4):438.e1-438.e16
pubmed: 29475580
Clin Perinatol. 2015 Dec;42(4):719-38
pubmed: 26593075
J Soc Gynecol Investig. 2002 May-Jun;9(3):152-7
pubmed: 12009389
J Ultrasound Med. 1991 Jun;10(6):327-30
pubmed: 1895375
Cochrane Database Syst Rev. 2013 Dec 02;(12):CD001058
pubmed: 24297389
Am J Obstet Gynecol. 2000 Nov;183(5):1124-9
pubmed: 11084553
J Physiol. 2013 Oct 15;591(20):5061-70
pubmed: 23878364
Pediatr Res. 2017 Aug;82(2):244-252
pubmed: 28422948
Pediatr Res. 2002 Mar;51(3):310-6
pubmed: 11861935
N Engl J Med. 2000 May 18;342(20):1500-7
pubmed: 10816189
Biol Neonate. 1999 Jun;76 Suppl 1:2-9
pubmed: 10393386
Reprod Sci. 2009 Jan;16(1):56-70
pubmed: 19122105
Clin Sci (Lond). 2014 Nov;127(9):559-69
pubmed: 24815024
Ann N Y Acad Sci. 1994 Sep 30;734:414-29
pubmed: 7978942
Am J Pathol. 2005 Jun;166(6):1585-92
pubmed: 15920144
Prostaglandins Leukot Essent Fatty Acids. 2002 May-Jun;66(5-6):525-7
pubmed: 12144874
Am J Obstet Gynecol. 2005 Mar;192(3):937-44
pubmed: 15746695
Am J Obstet Gynecol. 1998 Jul;179(1):194-202
pubmed: 9704787
J Matern Fetal Neonatal Med. 2017 Sep;30(18):2212-2218
pubmed: 27687157
Ultrasound Obstet Gynecol. 2020 Jun;55(6):806-814
pubmed: 31332850
Pharmacotherapy. 2015 Nov;35(11):1052-62
pubmed: 26598097
Am J Obstet Gynecol. 2019 Aug;221(2):140.e1-140.e18
pubmed: 30928565
J Infect Dis. 2014 Mar;209(6):898-904
pubmed: 24179112
Am J Obstet Gynecol. 2019 Aug;221(2):83-85
pubmed: 31358235
J Soc Gynecol Investig. 2003 Jul;10(5):283-90
pubmed: 12853089
Am J Obstet Gynecol. 2012 Dec;207(6):475.e1-475.e14
pubmed: 23111115
Magn Reson Med. 2016 Nov;76(5):1551-1562
pubmed: 26599502
Semin Fetal Neonatal Med. 2009 Aug;14(4):190-9
pubmed: 19109084