Characterizing the inclusion of pregnant and breastfeeding people in infectious diseases randomized controlled trials: a targeted literature review

Sarah C J Jorgensen; Simona Miljanic; Najla Tabbara; Deborah Somanader; Christopher L Y Tse; Charmaine De Castro; Isabelle Malhamé; Stephen E LapinskY; Lisa Burry

doi:10.1016/j.cmi.2021.10.024

Characterizing the inclusion of pregnant and breastfeeding people in infectious diseases randomized controlled trials: a targeted literature review

Clin Microbiol Infect. 2022 Jun;28(6):801-811. doi: 10.1016/j.cmi.2021.10.024. Epub 2021 Nov 10.

Authors

Sarah C J Jorgensen¹, Simona Miljanic², Najla Tabbara², Deborah Somanader³, Christopher L Y Tse⁴, Charmaine De Castro⁵, Isabelle Malhamé⁶, Stephen E LapinskY⁷, Lisa Burry⁸

Affiliations

¹ Institute of Medical Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Department of Pharmacy, Mount Sinai Hospital, Toronto, ON, Canada; Antimicrobial Stewardship Program, University Health Network, Sinai Health System, Toronto, ON, Canada. Electronic address: [email protected].
² Department of Pharmacy, Mount Sinai Hospital, Toronto, ON, Canada.
³ Antimicrobial Stewardship Program, University Health Network, Sinai Health System, Toronto, ON, Canada.
⁴ Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.
⁵ Library Services, Mount Sinai Hospital, Toronto, ON, Canada.
⁶ Department of Medicine, Division of General Internal Medicine, McGill University Health Centre, Montreal, QC, Canada; Center for Outcomes Research and Evaluation, Research Institute of McGill University Health Centre, Montreal, QC, Canada.
⁷ Division of Respirology, Mount Sinai Hospital, Toronto, ON, Canada; Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada.
⁸ Institute of Medical Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Department of Pharmacy, Mount Sinai Hospital, Toronto, ON, Canada; Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada; Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada.

PMID: 34768020
DOI: 10.1016/j.cmi.2021.10.024

Abstract

Objectives: Severe complications of infectious diseases can occur during pregnancy. Evidence-based prevention and treatment strategies are critical to improve maternal and neonatal health outcomes. Despite this medical need, pregnant and breastfeeding people have been systematically excluded from biomedical research. The objective of this study was to characterize representation of pregnant and breastfeeding people in randomized controlled trials (RCTs) evaluating a broad range of interventions for infectious diseases.

Methods: Pregnancy and breastfeeding inclusion criteria were examined in infectious diseases RCTs published between 1 January 2017, and 31 December 2019, in the top five highest impact general medicine and the top three highest impact infectious diseases and HIV journals.

Results: Of 376 RCTs, 5.3% and 1.9% included pregnant and breastfeeding people, respectively. Justification for exclusion was documented in 36/271 (13.3%) studies that explicitly excluded pregnant people. Most studies excluding pregnant people (177/271, 65.3%) required at least one form of contraception, abstinence and/or negative pregnancy test(s) as part of participation. Only 11/271 (4.1%) studies excluding pregnant people allowed participants to continue the intervention if unintended pregnancy occurred during the study. When both pregnant and non-pregnant people were eligible, pregnant people made up <3% of participants. Only 2/48 (4.2%) vaccine studies included pregnant people; 13/234 (5.5%) drug studies included pregnant people. All studies of procedures, devices, behaviour/education and supplements/vitamins explicitly excluded or did not address pregnancy eligibility criteria. Only 2/20 (10.0%) RCTs including pregnant people collected pharmacokinetic data.

Discussion: This study demonstrates widespread exclusion of pregnant and breastfeeding people from infectious disease RCTs.

Keywords: Antimicrobials; Equity; Infectious diseases; Pregnancy; Research; Vaccines.

Publication types

Review

MeSH terms

Breast Feeding*
Communicable Diseases* / drug therapy
Female
Humans
Infant, Newborn
Pregnancy
Randomized Controlled Trials as Topic