Intrapartum azithromycin to prevent maternal and neonatal sepsis and deaths: A systematic review with meta-analysis

doi:10.1111/1471-0528.17655

Meta-Analysis

. 2024 Feb;131(3):246-255.

doi: 10.1111/1471-0528.17655. Epub 2023 Sep 10.

Intrapartum azithromycin to prevent maternal and neonatal sepsis and deaths: A systematic review with meta-analysis

Ilari Kuitunen^{1

2}, Maiju Kekki^{3

4}, Marjo Renko^{1

2}

Affiliations

¹ Department of Paediatrics, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.
² Department of Paediatrics, Kuopio University Hospital, Kuopio, Finland.
³ Department of Obstetrics, Tampere University Hospital, Tampere, Finland.
⁴ Tampere Centre for Child and Maternal Health Research, Tampere University, Tampere, Finland.

PMID: 37691261
DOI: 10.1111/1471-0528.17655

Meta-Analysis

Intrapartum azithromycin to prevent maternal and neonatal sepsis and deaths: A systematic review with meta-analysis

Ilari Kuitunen et al. BJOG. 2024 Feb.

. 2024 Feb;131(3):246-255.

doi: 10.1111/1471-0528.17655. Epub 2023 Sep 10.

Authors

Ilari Kuitunen^{1

2}, Maiju Kekki^{3

4}, Marjo Renko^{1

2}

Affiliations

¹ Department of Paediatrics, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.
² Department of Paediatrics, Kuopio University Hospital, Kuopio, Finland.
³ Department of Obstetrics, Tampere University Hospital, Tampere, Finland.
⁴ Tampere Centre for Child and Maternal Health Research, Tampere University, Tampere, Finland.

PMID: 37691261
DOI: 10.1111/1471-0528.17655

Abstract

Objectives: A systematic review with met-analysis was performed to summarise the evidence on the effect of intrapartum azithromycin on maternal and neonatal infections and deaths.

Search strategy: PubMed, Scopus and Web of Science databases were searched in March 2023.

Selection criteria: Randomised controlled trials comparing intrapartum single-dose of azithromycin with placebo.

Data collection and analysis: Maternal infections, maternal mortality, neonatal sepsis, neonatal mortality. We used the random-effects Mantel-Haenszel method to calculate risk ratios (RR) with 95% confidence intervals (95% CI). We assessed risk of bias of the included studies and estimated the evidence certainty using the GRADE approach.

Main results: After screening 410 abstracts, five studies with 44 190 women and 44 565 neonates were included. The risk of bias was low in four and had some concerns in one of the studies. The risk of endometritis was 1.5% in the azithromycin group and 2.3% in the placebo group (RR 0.64, 95% CI 0.55-0.75), and the evidence certainty was high. The respective risk for chorioamnionitis was 0.05% and 0.1% (RR 0.50, 95% CI 0.22-1.18; evidence certainty moderate). The wound infection rate was lower in the azithromycin group (1.6%) than in the placebo group (2.5%), RR 0.52 (95% CI 0.30-0.89; moderate certainty evidence). The maternal sepsis rate was 1.1% in the azithromycin group and 1.7% in the placebo group (RR 0.66, 95% CI 0.56-0.77; evidence certainty high). Mortality rates did not show evidence of a difference (0.09% versus 0.08%; RR 1.26, 95% CI 0.65-2.42; moderate certainty evidence). The neonatal mortality rate was 0.7% in the azithromycin group and 0.8% in the placebo group (RR 0.94, 95% CI 0.76-1.16; moderate certainty evidence). The neonatal sepsis rate was 7.6% in the azithromycin group and 7.4% in the placebo group (RR 1.02, 95% CI 0.96-1.09; moderate certainty evidence).

Conclusions: Intrapartum administration of azithromycin to the mother reduces maternal postpartum infections, including sepsis. Impact on maternal mortality remains undecided. Azithromycin does not reduce neonatal sepsis or mortality rates.

Keywords: azithromycin; meta-analysis; mortality; perinatal outcomes; sepsis.

PubMed Disclaimer

Cited by

Effectiveness of intrapartum azithromycin to prevent infections in planned vaginal births in low-income and middle-income countries: a post-hoc analysis of data from a multicentre, randomised, double-blind, placebo-controlled trial.
Carlo WA, Tita ATN, Moore JL, Mwenechanya M, Chomba E, Hemingway-Foday JJ, Kavi A, Metgud MC, Goudar SS, Derman RJ, Lokangaka A, Tshefu A, Bauserman M, Patterson JK, Shivkumar P, Waikar M, Patel A, Hibberd PL, Nyongesa P, Esamai F, Ekhaguere OA, Bucher S, Jessani S, Tikmani SS, Saleem S, Goldenberg RL, Billah SM, Lennox R, Haque R, Petri W, Mazariegos M, Krebs NF, Babineau DC, McClure EM, Koso-Thomas M; A-PLUS Trial Group. Carlo WA, et al. Lancet Glob Health. 2025 Apr;13(4):e689-e697. doi: 10.1016/S2214-109X(24)00562-X. Lancet Glob Health. 2025. PMID: 40155106 Free PMC article. Clinical Trial.
Effect of intrapartum azithromycin on gut microbiota development in early childhood: A post hoc analysis of a double-blind randomized trial.
Sanyang B, de Silva TI, Camara B, Beloum N, Kanteh A, Manneh J, de Steenhuijsen Piters WAA, Bogaert D, Sesay AK, Roca A. Sanyang B, et al. iScience. 2024 Aug 3;27(9):110626. doi: 10.1016/j.isci.2024.110626. eCollection 2024 Sep 20. iScience. 2024. PMID: 39262807 Free PMC article.
Effect of intrapartum azithromycin on early childhood gut mycobiota development: post hoc analysis of a double-blind randomized trial.
Sanyang B, Dabrowska MB, Amenyogbe N, Camara B, Beloum N, Jammeh M, Bojang D, Goodall J, Mohammed N, Sesay AK, Roca A, de Silva TI. Sanyang B, et al. Nat Commun. 2025 Aug 9;16(1):7356. doi: 10.1038/s41467-025-62142-w. Nat Commun. 2025. PMID: 40783383 Free PMC article. Clinical Trial.
Intrapartum and postpartum antibiotic use in seven low- and middle-income countries: Findings from the A-PLUS trial.
Saleem S, Yasmin H, Moore JL, Rahim A, Shakeel I, Lokangaka A, Tshefu A, Bauserman M, Mwenechanya M, Chomba E, Goudar SS, Kavi A, Derman RJ, Krebs NF, Figueroa L, Mazariegos M, Nyongesa P, Bucher S, Esamai F, Patel A, Waikar M, Shivkumar P, Hibberd PL, Petri WA, Billah SM, Haque R, Carlo WA, Tita A, Koso-Thomas M, Hemingway-Foday J, McClure EM, Goldenberg RL. Saleem S, et al. BJOG. 2025 Jan;132(1):72-80. doi: 10.1111/1471-0528.17930. Epub 2024 Aug 14. BJOG. 2025. PMID: 39140197 Clinical Trial.
Can the use of azithromycin during labour reduce the incidence of infection among puerperae and newborns? A systematic review and meta-analysis of randomized controlled trials.
Ye H, Hu J, Li B, Yu X, Zheng X. Ye H, et al. BMC Pregnancy Childbirth. 2024 Mar 14;24(1):200. doi: 10.1186/s12884-024-06390-6. BMC Pregnancy Childbirth. 2024. PMID: 38486177 Free PMC article.

References

REFERENCES

1. Seale AC, Mwaniki M, Newton CR, Berkley JA. Maternal and early onset neonatal bacterial sepsis: burden and strategies for prevention in sub-Saharan Africa. Lancet Infect Dis. 2009;9(7):428-438. https://doi.org/10.1016/S1473-3099(09)70172-0
1. GBD 2019 Under-5 Mortality Collaborators. Global, regional, and national progress towards sustainable development goal 3.2 for neonatal and child health: all-cause and cause-specific mortality findings from the Global Burden of Disease Study 2019. Lancet. 2021;398(10303):870-905. https://doi.org/10.1016/S0140-6736(21)01207-1
1. Smaill FM, Grivell RM. Antibiotic prophylaxis versus no prophylaxis for preventing infection after cesarean section. Cochrane Database Syst Rev. 2014;2014(10):CD007482. https://doi.org/10.1002/14651858.CD007482.pub3
1. WHO recommendation on prophylactic antibiotics for women undergoing caesarean section [cited 2023 Apr 5]. Available from: https://apps.who.int/iris/handle/10665/341865
1. Subramaniam A, Ye Y, Mbah R, Mbunwe DM, Pekwarake S, Bunwi EY, et al. Single dose of oral azithromycin with or without amoxicillin to prevent peripartum infection in laboring, high-risk women in Cameroon: a randomized controlled trial. Obstet Gynecol. 2021;138(5):703-713. https://doi.org/10.1097/AOG.0000000000004565

Publication types

Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions

LinkOut - more resources

Full Text Sources
- Ovid Technologies, Inc.
- Wiley
Medical
- MedlinePlus Health Information
Miscellaneous
- NCI CPTAC Assay Portal

[1] Seale AC, Mwaniki M, Newton CR, Berkley JA. Maternal and early onset neonatal bacterial sepsis: burden and strategies for prevention in sub-Saharan Africa. Lancet Infect Dis. 2009;9(7):428-438. https://doi.org/10.1016/S1473-3099(09)70172-0

[2] Seale AC, Mwaniki M, Newton CR, Berkley JA. Maternal and early onset neonatal bacterial sepsis: burden and strategies for prevention in sub-Saharan Africa. Lancet Infect Dis. 2009;9(7):428-438. https://doi.org/10.1016/S1473-3099(09)70172-0

[3] GBD 2019 Under-5 Mortality Collaborators. Global, regional, and national progress towards sustainable development goal 3.2 for neonatal and child health: all-cause and cause-specific mortality findings from the Global Burden of Disease Study 2019. Lancet. 2021;398(10303):870-905. https://doi.org/10.1016/S0140-6736(21)01207-1

[4] GBD 2019 Under-5 Mortality Collaborators. Global, regional, and national progress towards sustainable development goal 3.2 for neonatal and child health: all-cause and cause-specific mortality findings from the Global Burden of Disease Study 2019. Lancet. 2021;398(10303):870-905. https://doi.org/10.1016/S0140-6736(21)01207-1

[5] Smaill FM, Grivell RM. Antibiotic prophylaxis versus no prophylaxis for preventing infection after cesarean section. Cochrane Database Syst Rev. 2014;2014(10):CD007482. https://doi.org/10.1002/14651858.CD007482.pub3

[6] Smaill FM, Grivell RM. Antibiotic prophylaxis versus no prophylaxis for preventing infection after cesarean section. Cochrane Database Syst Rev. 2014;2014(10):CD007482. https://doi.org/10.1002/14651858.CD007482.pub3

[7] WHO recommendation on prophylactic antibiotics for women undergoing caesarean section [cited 2023 Apr 5]. Available from: https://apps.who.int/iris/handle/10665/341865

[8] WHO recommendation on prophylactic antibiotics for women undergoing caesarean section [cited 2023 Apr 5]. Available from: https://apps.who.int/iris/handle/10665/341865

[9] Subramaniam A, Ye Y, Mbah R, Mbunwe DM, Pekwarake S, Bunwi EY, et al. Single dose of oral azithromycin with or without amoxicillin to prevent peripartum infection in laboring, high-risk women in Cameroon: a randomized controlled trial. Obstet Gynecol. 2021;138(5):703-713. https://doi.org/10.1097/AOG.0000000000004565

[10] Subramaniam A, Ye Y, Mbah R, Mbunwe DM, Pekwarake S, Bunwi EY, et al. Single dose of oral azithromycin with or without amoxicillin to prevent peripartum infection in laboring, high-risk women in Cameroon: a randomized controlled trial. Obstet Gynecol. 2021;138(5):703-713. https://doi.org/10.1097/AOG.0000000000004565

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Intrapartum azithromycin to prevent maternal and neonatal sepsis and deaths: A systematic review with meta-analysis

Affiliations

Intrapartum azithromycin to prevent maternal and neonatal sepsis and deaths: A systematic review with meta-analysis

Authors

Affiliations

Abstract

Similar articles

Cited by

References

REFERENCES

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous

Abstract

Similar articles

Cited by

References

REFERENCES

Publication types

MeSH terms

Substances

Related information

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous