Azithromycin to Prevent Sepsis or Death in Women Planning a Vaginal Birth.
Female
Humans
Infant, Newborn
Pregnancy
Azithromycin
/ administration & dosage
Perinatal Death
/ etiology
Pregnancy Complications, Infectious
/ epidemiology
Sepsis
/ epidemiology
Stillbirth
/ epidemiology
Anti-Bacterial Agents
/ administration & dosage
Delivery, Obstetric
/ methods
Neonatal Sepsis
/ epidemiology
Administration, Oral
Pregnancy Outcome
/ epidemiology
United States
/ epidemiology
Journal
The New England journal of medicine
ISSN: 1533-4406
Titre abrégé: N Engl J Med
Pays: United States
ID NLM: 0255562
Informations de publication
Date de publication:
30 Mar 2023
30 Mar 2023
Historique:
medline:
31
3
2023
pubmed:
10
2
2023
entrez:
9
2
2023
Statut:
ppublish
Résumé
The use of azithromycin reduces maternal infection in women during unplanned cesarean delivery, but its effect on those with planned vaginal delivery is unknown. Data are needed on whether an intrapartum oral dose of azithromycin would reduce maternal and offspring sepsis or death. In this multicountry, placebo-controlled, randomized trial, we assigned women who were in labor at 28 weeks' gestation or more and who were planning a vaginal delivery to receive a single 2-g oral dose of azithromycin or placebo. The two primary outcomes were a composite of maternal sepsis or death and a composite of stillbirth or neonatal death or sepsis. During an interim analysis, the data and safety monitoring committee recommended stopping the trial for maternal benefit. A total of 29,278 women underwent randomization. The incidence of maternal sepsis or death was lower in the azithromycin group than in the placebo group (1.6% vs. 2.4%), with a relative risk of 0.67 (95% confidence interval [CI], 0.56 to 0.79; P<0.001), but the incidence of stillbirth or neonatal death or sepsis was similar (10.5% vs. 10.3%), with a relative risk of 1.02 (95% CI, 0.95 to 1.09; P = 0.56). The difference in the maternal primary outcome appeared to be driven mainly by the incidence of sepsis (1.5% in the azithromycin group and 2.3% in the placebo group), with a relative risk of 0.65 (95% CI, 0.55 to 0.77); the incidence of death from any cause was 0.1% in the two groups (relative risk, 1.23; 95% CI, 0.51 to 2.97). Neonatal sepsis occurred in 9.8% and 9.6% of the infants, respectively (relative risk, 1.03; 95% CI, 0.96 to 1.10). The incidence of stillbirth was 0.4% in the two groups (relative risk, 1.06; 95% CI, 0.74 to 1.53); neonatal death within 4 weeks after birth occurred in 1.5% in both groups (relative risk, 1.03; 95% CI, 0.86 to 1.24). Azithromycin was not associated with a higher incidence in adverse events. Among women planning a vaginal delivery, a single oral dose of azithromycin resulted in a significantly lower risk of maternal sepsis or death than placebo but had little effect on newborn sepsis or death. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; A-PLUS ClinicalTrials.gov number, NCT03871491.).
Sections du résumé
BACKGROUND
BACKGROUND
The use of azithromycin reduces maternal infection in women during unplanned cesarean delivery, but its effect on those with planned vaginal delivery is unknown. Data are needed on whether an intrapartum oral dose of azithromycin would reduce maternal and offspring sepsis or death.
METHODS
METHODS
In this multicountry, placebo-controlled, randomized trial, we assigned women who were in labor at 28 weeks' gestation or more and who were planning a vaginal delivery to receive a single 2-g oral dose of azithromycin or placebo. The two primary outcomes were a composite of maternal sepsis or death and a composite of stillbirth or neonatal death or sepsis. During an interim analysis, the data and safety monitoring committee recommended stopping the trial for maternal benefit.
RESULTS
RESULTS
A total of 29,278 women underwent randomization. The incidence of maternal sepsis or death was lower in the azithromycin group than in the placebo group (1.6% vs. 2.4%), with a relative risk of 0.67 (95% confidence interval [CI], 0.56 to 0.79; P<0.001), but the incidence of stillbirth or neonatal death or sepsis was similar (10.5% vs. 10.3%), with a relative risk of 1.02 (95% CI, 0.95 to 1.09; P = 0.56). The difference in the maternal primary outcome appeared to be driven mainly by the incidence of sepsis (1.5% in the azithromycin group and 2.3% in the placebo group), with a relative risk of 0.65 (95% CI, 0.55 to 0.77); the incidence of death from any cause was 0.1% in the two groups (relative risk, 1.23; 95% CI, 0.51 to 2.97). Neonatal sepsis occurred in 9.8% and 9.6% of the infants, respectively (relative risk, 1.03; 95% CI, 0.96 to 1.10). The incidence of stillbirth was 0.4% in the two groups (relative risk, 1.06; 95% CI, 0.74 to 1.53); neonatal death within 4 weeks after birth occurred in 1.5% in both groups (relative risk, 1.03; 95% CI, 0.86 to 1.24). Azithromycin was not associated with a higher incidence in adverse events.
CONCLUSIONS
CONCLUSIONS
Among women planning a vaginal delivery, a single oral dose of azithromycin resulted in a significantly lower risk of maternal sepsis or death than placebo but had little effect on newborn sepsis or death. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; A-PLUS ClinicalTrials.gov number, NCT03871491.).
Identifiants
pubmed: 36757318
doi: 10.1056/NEJMoa2212111
pmc: PMC10627427
mid: NIHMS1889154
doi:
Substances chimiques
Azithromycin
83905-01-5
Anti-Bacterial Agents
0
Banques de données
ClinicalTrials.gov
['NCT03871491']
Types de publication
Journal Article
Multicenter Study
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
1161-1170Subventions
Organisme : NICHD NIH HHS
ID : U24 HD092094
Pays : United States
Organisme : NICHD NIH HHS
ID : UG1 HD076465
Pays : United States
Organisme : NICHD NIH HHS
ID : UG1 HD076474
Pays : United States
Organisme : NICHD NIH HHS
ID : UG1 HD078439
Pays : United States
Investigateurs
Trecious Mweemba
(T)
Ernest Banda
(E)
Mwansa Chimfwembe
(M)
Ruth Nakazwe
(R)
Monica Collins
(M)
Sixto Leal
(S)
Akila Subramaniam
(A)
Charitharth Vivek Lal
(CV)
Suchita Parepalli
(S)
Anna Aceituno
(A)
Jean Kim
(J)
Kay Jackson
(K)
Alexis Williams
(A)
Marissa Trotta
(M)
Menachem Miodovnik
(M)
Jackie Wallace
(J)
Gustave Lomendje
(G)
Michel Kalonji
(M)
Miyalu Junior
(M)
Jackie Patterson
(J)
Paulin Takoy
(P)
Justin Gado
(J)
Joel Bosenya
(J)
Emmanuel Kalombo
(E)
Charles Kombi
(C)
Maynor Manrique
(M)
Jamie Westcott
(J)
Md Shahjahan Siraj
(MS)
Qazi Sadeq-Ur-Rahman
(Q)
Lolit Singh
(L)
Amita Farzana
(A)
Farhana Jahan
(F)
Zarin Tasnim Maliha
(ZT)
Rumpa Kairy
(R)
Christian Chisolm
(C)
Robert A Sinkin
(RA)
Manjunath S Somannavar
(MS)
Kadappa Beniwadi
(K)
Sheetal U Harkuni
(SU)
Madiwalayya S Ganachari
(MS)
Umesh R Hundekar
(UR)
Ashadevi Patil
(A)
Ashwini Bharamashetti
(A)
Netravathi Alur
(N)
Surekha Nyamagoud
(S)
Chandrashekhar Kajagar
(C)
Sangappa M Dhaded
(SM)
Ashalata A Mallapur
(AA)
Ramesh Pol
(R)
Geetanjali M Katageri
(GM)
Umesh Y Ramadurg
(UY)
Bhuvaneshwari C Yelamali
(BC)
Aarti Bhurle
(A)
Shailaja R Bidri
(SR)
Sangamesh S Mathapati
(SS)
Mallanagowda M Patil
(MM)
Preeti G Patil
(PG)
Hidayatullah R Bijapure
(HR)
Chandrika R Doddihal
(CR)
Muttu R Gudadinni
(MR)
Smita O Bagali
(SO)
Frances Jaeger
(F)
Farnaz Naqvi
(F)
Naija Karim Ghanchi
(NK)
Zaheer Habib
(Z)
Imran Ahmed
(I)
Sana Roujani
(S)
Seemab Naqvi
(S)
Sayyeda Reza
(S)
Haleema Yasmin
(H)
Mashal Khan
(M)
Mehmood Shaikh
(M)
Hayat Bozdar
(H)
Prabir Das
(P)
Kunal G Kurhe
(KG)
Vaishali Khedikar
(V)
Chaitali Gedam
(C)
Savita Bhargav
(S)
Samreen Sadaf
(S)
Deepti Shrivastava
(D)
Abhay Gaidhane
(A)
Mugdha Jungari
(M)
Manish Jain
(M)
Manisha Nasre
(M)
Sunanda Shrikhande
(S)
Vijayshri Deotale
(V)
Edward A Liechty
(EA)
Amos Sagwe
(A)
Kevin Otieno
(K)
Milsort Kemboi
(M)
Anderson Misati
(A)
Gabriel Kigen
(G)
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Type : CommentIn
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2023 Massachusetts Medical Society.
Références
Lancet Glob Health. 2020 May;8(5):e661-e671
pubmed: 32353314
Am J Perinatol. 2019 Aug;36(10):1002-1008
pubmed: 30500967
Obstet Gynecol. 2021 Nov 1;138(5):703-713
pubmed: 34619734
N Engl J Med. 2013 May 2;368(18):1704-12
pubmed: 23635050
Obstet Gynecol. 2017 Oct;130(4):747-755
pubmed: 28885400
Obstet Gynecol. 2018 Sep;132(3):e103-e119
pubmed: 30134425
Clin Microbiol Infect. 2016 Jun;22(6):565.e1-9
pubmed: 27026482
Aust N Z J Obstet Gynaecol. 2017 Oct;57(5):540-551
pubmed: 28670748
N Engl J Med. 2012 May 17;366(20):1881-90
pubmed: 22591294
Eur J Pediatr. 2019 Mar;178(3):301-314
pubmed: 30470884
N Engl J Med. 2017 Aug 3;377(5):414-417
pubmed: 28658587
Am J Obstet Gynecol. 2008 Sep;199(3):303.e1-3
pubmed: 18771992
Obstet Gynecol. 2003 Jun;101(6):1183-9
pubmed: 12798523
Obstet Gynecol. 2008 Jan;111(1):51-6
pubmed: 18165392
Am J Obstet Gynecol. 2013 Mar;208(3):221.e1-8
pubmed: 23254249
Lancet. 2015 Jan 31;385(9966):430-40
pubmed: 25280870
Obstet Gynecol. 2017 Aug;130(2):328-334
pubmed: 28697108
Obstet Gynecol. 2009 Mar;113(3):675-682
pubmed: 19300334
Obstet Gynecol. 2002 Jul;100(1):101-6
pubmed: 12100810
Pediatrics. 2017 Feb;139(2):
pubmed: 28130432
Clin Infect Dis. 2018 Sep 28;67(8):1191-1197
pubmed: 29608659
Clin Infect Dis. 2020 Dec 15;71(12):3222-3225
pubmed: 32445474
N Engl J Med. 2016 Sep 29;375(13):1231-41
pubmed: 27682034