NAC-STBBI Recommendations on Pregnancy Screening for Chlamydia trachomatis and Neisseria gonorrhea

Abstract

Background: Chlamydia trachomatis and Neisseria gonorrhoea are the most common bacterial sexually transmitted infections globally and the most common of the reported sexually transmitted infections in Canada. Undetected and untreated infections in pregnant women/pregnant individuals could lead to adverse pregnancy outcomes and risk of ophthalmia neonatorum and neonatal pneumonia in neonates.

Objective: In 2023, the National Advisory Committee on Sexually Transmitted and Blood-Borne Infections (NAC-STBBI) updated the Public Health Agency of Canada's (PHAC) recommendations on prenatal screening for C. trachomatis and N. gonorrhoea to optimize the prevention of adverse pregnancy outcomes, as well as ophthalmia neonatorum and neonatal pneumonia.

Methods: A health technology assessment and a systematic review were undertaken. A decision-analytic model was used due to lack of comparative studies on the effects of screening strategies on adverse pregnancy outcomes, ophthalmia neonatorum and neonatal pneumonia that met the inclusion criteria. The Working Group used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to develop the recommendations. The recommendations were peer-reviewed, voted by the NAC-STBBI and shared with stakeholder groups and Canadian provinces and territories.

Results: Screening all pregnant women/pregnant individuals at first and third trimesters and screening high-risk individuals at first trimester and all at third trimester strategies are cost-effective regardless of the different assumptions in non-high-risk and high-risk settings. Overall, testing in pregnancy is acceptable to pregnant women/pregnant individuals, but there may be some feelings of stigma when the offered testing is perceived to be targeted.

Conclusion: The relevant PHAC STBBI guides were updated in 2023 with the NAC-STBBI recommendations. This work could be adopted or adapted by guideline development groups in Canadian provinces and territories, as well as in other countries, as appropriate, considering factors that are specific to the settings.

Introduction

The Public Health Agency of Canada (PHAC) provides national leadership for the prevention and control of sexually transmitted and blood-borne infections (STBBI) through the development of evidence-based public health guidelines ^{Footnote 1}. Starting in 2019, the recommendations in these guidelines (formerly the Canadian Guidelines on Sexually Transmitted Infections) are being developed by the National Advisory Committee on STBBI (NAC-STBBI), an external advisory body of subject matter experts from across Canada using a rigorous, systematic and transparent process (unpublished document, Shanmugasegaram S/Public Health Agency of Canada, Methods Manual for the Public Health Agency of Canada Sexually Transmitted and Blood-Borne Infections Recommendations, 2019) ^{Footnote 1Footnote 2}.

Chlamydia trachomatis (CT) and Neisseria gonorrhoea (NG) are the most common bacterial sexually transmitted infections (STIs) globally ^{Footnote 3} and the most frequent of the reported STI in Canada ^{Footnote 4}. Between 2010 and 2019, rates of reported cases of CT infection increased by 33.1% (94,716–139,386 cases; 278.5–370.8 per 100,000 population) and those of NG infection increased by 181.7% (11,381–35,443 cases; 33.5–94.3 per 100,000 population) in Canada ^{Footnote 4Footnote 5}. Chlamydia trachomatis and NG infections are often asymptomatic in females ^{Footnote 6}. Undetected and untreated infections in pregnant women/pregnant individuals (PWPI) could lead to pregnancy-related complications, sexual transmission, and transmission to neonates in the perinatal period ^{Footnote 7Footnote 8}. Untreated CT infection in the birthing parent carries a 30%–50% risk of ophthalmia neonatorum and a 10%–20% risk of CT pneumonia ^{Footnote 9} and NG infection in the birthing parent carries a 30% risk of the neonate developing ophthalmia neonatorum ^{Footnote 10Footnote 11}.

In 2016, the Canadian Paediatric Society posted a position statement (reaffirmed in January 2021) advocating for the enhancement of programs for routine screening and treatment of pregnant women ^{Footnote 12}. Canadian studies show that prenatal screening rates for CT and NG infections are suboptimal with approximately 15%–22% of pregnant persons not being screened at least once for these infections ^{Footnote 13Footnote 14Footnote 15}. Given the increasing rates of reported cases of CT and NG in the general population and suboptimal rates of prenatal screening for CT and NG in Canada, in 2023 the NAC-STBBI reviewed and updated PHAC's previous recommendations ^{Footnote 16Footnote 17} on prenatal screening for CT and NG infections to optimize the prevention of adverse pregnancy outcomes, as well as ophthalmia neonatorum and neonatal pneumonia. A summary of the guideline ^{Footnote 18} is provided herein. This work could be adopted or adapted by guideline development groups in Canadian provinces and territories, as well as in other countries, as appropriate, considering factors that are specific to the settings.

Methods

After prioritizing the topic for recommendation development, a Working Group composed of experts from NAC-STBBI was formed to develop the recommendations. The Working Group developed the questions and an external evidence review team prepared the protocol. Working Group members and a patient group rated the relative importance of outcomes (both beneficial and harmful) for decision-making, based on the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach ^{Footnote 19}. The external evidence review team conducted a health technology assessment consisting of a clinical review, an economic analysis and a review of patients' perspectives and experiences ^{Footnote 20Footnote 21}. The outcomes of importance considered for the development of the recommendations are as follows:

• Number and percent of NG and/or CT infections detected at screening (including new or repeat infections)
  • Surrogate outcome: number of females treated for infection
  • Surrogate outcomes: true positives and false negatives and false positives and true negatives
• Adverse obstetric outcomes (preterm and still births)
• Number of females declining screening
• Anxiety/fears
• Number and percent of ophthalmia neonatorum cases
• Number and percent of neonatal pneumonia cases

The eligibility criteria for the evidence reviews performed to develop the recommendations included studies conducted in countries comparable to Canada's healthcare context. In the absence of published literature evidence, the Working Group considered other types of evidence, including surveillance and epidemiology information and a decision-analytic model to support the development of the recommendations. The external evidence review team constructed a decision-analytic model of prenatal screening for NG and/or CT infections to predict the outcomes for PWPI and their newborns in Canada ^{Footnote 20}. The model evaluated the impact of strategies for screening all or only high-risk PWPI at first, second and/or third trimesters and at labour, over approximately one year.

Published literature and clinical experts in obstetrics and gynecology, as well as in adult and paediatric infectious diseases informed the structure and inputs. Given uncertainties of some model parameters and assumptions in the base-case analysis, sensitivity analyses were performed, assuming a lifetime horizon, higher prevalence of infections in PWPI, higher rates of transmission to newborns, lower costs of tests, and greater risk of poor outcomes in PWPI with NG or CT. Outcomes included neonatal CT or NG infections, adverse outcomes to PWPI, preterm births, quality-adjusted life years (QALY) and costs. Further details on the decision-analytic model considerations are available (see Appendix, Supplemental material, List S1) ^{Footnote 22Footnote 23}. A systematic review on acceptability, feasibility, equity and resource use of prenatal screening for NG and CT was also conducted to support the development of the recommendations ^{Footnote 24}.

The GRADE Evidence to Decision framework was drafted to help the Working Group use evidence in a structured and transparent way to develop the recommendations ^{Footnote 19}. The Working Group assessed the balance between benefits and harms, patient values and preferences, resource use, equity, acceptability and feasibility using the GRADE approach ^{Footnote 19}. The Working Group also drafted the recommendations using the GRADE wording for direction and strength ^{Footnote 19Footnote 25}. The NAC-STBBI Statement, including details such as the evidence considered and the recommendations, was prepared. The recommendations were reviewed by external peer-reviewers (outside of NAC-STBBI) with expertise in obstetrics and gynaecology and adult and paediatric infectious diseases, voted by the NAC-STBBI members and shared with Canadian provinces and territories and relevant stakeholder groups. The NAC-STBBI Statement was published on PHAC's website in May 2023 ^{Footnote 18}. The relevant PHAC STBBI guides were updated in 2023 with the NAC-STBBI recommendations.

Results

Systematic reviews of the benefits, harms, feasibility, acceptability, resource use and the impact on equity of different screening strategies for NG and CT screening in PWPI were conducted ^{Footnote 20Footnote 21Footnote 24}. Given the lack of published literature directly comparing different screening strategies, a decision-analytic model specific to the Canadian setting was used to inform the recommendations. Table 1 shows a summary of the evidence on the effect of select screening strategies on important outcomes to PWPI and their newborns. Other strategies were also considered during the recommendation development process (see Appendix, Supplemental material, Table S1).

Evidence suggests that, as screening is added to each trimester (whether screening all individuals or high-risk groups, i.e., younger than 25 years), there are fewer number of newborns with infection; however, providing screening at the third trimester (in particular for all) may reduce the numbers the most compared to adding screening at the first or second trimester(s). Although the sensitivity and specificity of the assays for the detection of NG and CT are high, there is still a risk of false negative (resulting in a missed infection at that trimester) and false positive (resulting in treatment of individuals who do not have an infection) results; however, the evidence from the model suggests that there are little to no differences in those numbers between the different strategies.

While the absolute cost differences are small, there are differences in QALY (i.e., the cost per additional benefit of a strategy compared to another strategy) with high-risk screening. When reviewing most strategies across the analyses, the evidence suggests that adding screening at more trimesters and screening all at a trimester was more costly and provided fewer benefits. Strategy 2 (screening all at first and third trimester) and Strategy 3 (screening high-risk individuals at first trimester and all at third trimester) may be cost-effective (more health benefit at a lower cost) regardless of the different assumptions in non-high-risk and high-risk settings. Although the costs per additional benefit were lower when screening all only in the third trimester (Strategy 4), there were more infections than with Strategy 2 or Strategy 3. Data for Strategy 1, where all PWPI are screened at first and third trimesters and high-risk individuals are screened at second trimester, may still be cost-effective but the cost per additional benefit was remarkably higher than the other strategies. Adding screening to the second trimester (e.g., Strategy 6 versus Strategy 5), did not reduce newborn infections and was still costly.

There is some evidence available about the feasibility and acceptability of screening for NG and CT infections in PWPI ^{Footnote 24}. Overall, testing in pregnancy may be acceptable to PWPI ^{Footnote 26}, but there may be some feelings of stigma when they are offered testing and it is perceived to be targeted ^{Footnote 27}. This could be reduced by offering universal testing ^{Footnote 26}.

Recommendations

For the purpose of these recommendations ^{Footnote 26}, screening is defined as testing asymptomatic individuals. The following recommendations apply to screening of asymptomatic PWPI. These recommendations do not replace recommendations to test and treat PWPI who have symptoms compatible with NG or CT infection or after sexual contact with a person known to have a NG or CT.

The NAC-STBBI suggests screening all PWPI for NG and CT during the first trimester or at the first antenatal visit, and again in the third trimester (conditional recommendation; low certainty evidence).

The NAC-STBBI suggests screening PWPI at the time of labour for NG and CT in any of the following situations (conditional recommendation; low certainty evidence):

• No prenatal screening has occurred (no valid results available at the time of labour)
• Third trimester screening has not occurred
• A positive test result was obtained for NG or CT during pregnancy without appropriate follow-up, including treatment and a test-of-cure

Discussion

Screening all PWPI at first and third trimesters and screening high-risk individuals at first trimester and all at third trimester strategies are cost-effective regardless of the different assumptions in non-high-risk and high-risk settings. Overall, testing in pregnancy is acceptable to PWPI, but there may be some feelings of stigma when the offered testing is perceived to be targeted.

The updated (in 2023) recommendations ^{Footnote 18} are particularly important in settings where neonatal ocular prophylaxis for the prevention of ophthalmia neonatorum is not part of the current practice. These recommendations do not replace recommendations to test and treat PWPI who have symptoms compatible with NG or CT infection or after a sexual contact with a person infected by NG or CT.

Evidence suggests that screening all individuals could remove the fear of stigmatization and discrimination and normalize the testing practice ^{Footnote 26}. In addition, the Working Group agreed that screening all PWPI may be more practical than clinicians' efforts to gather risk factors from PWPI and partners. Further, co-infection rates for NG and CT are high ^{Footnote 28Footnote 29} and combined testing for these STIs could contribute to the acceptability and feasibility of screening.

In settings where there are limited laboratory capacities, priority could be given to screening PWPI with higher risk of those infections during the first trimester (or at the first antenatal visit) and screening all PWPI in the latter part of the third trimester. When identifying PWPI at high-risk for NG and CT infection, risks similar to individuals younger than 25 years old could be used. For positive test results, healthcare providers could continue explaining to PWPI the risk of false positive tests.

Limitations

For the Canada's Drug Agency (formerly Canadian Agency for Drugs and Technologies in Health) health technology assessment ^{Footnote 20Footnote 21}, there was lack of published evidence on the impact of prenatal screening strategies for NG or CT on preventing ophthalmia neonatorum and neonatal pneumonia. For the systematic review on acceptability, feasibility, equity and resource use ^{Footnote 24}, limitations included the search not capturing eligible literature on acceptability, feasibility and equity of timing of repeating universal screening (e.g., third trimester or at delivery). In addition, it did not identify eligible literature on acceptability of prenatal screening for NG among partners of PWPI.

Future directions

Addressing several research gaps could help inform whether to update or reaffirm these recommendations in the future. There is a need for studies assessing the impact of prenatal screening strategies for NG and CT infections on preventing ophthalmia neonatorum and neonatal pneumonia. In addition, comparative studies on the number and rates (or proportions) of PWPI for whom screening was undertaken, treated, followed-up with a test-of-cure and rescreened could help inform future recommendations. Further, more studies are needed to monitor the impact and consequences of false positive tests. Also, primary studies on the acceptability, feasibility and equity of timing of repeating universal screening are required. Incidence and prevalence information on NG and CT infections in PWPI, ophthalmia neonatorum and neonatal pneumonia at the national level in Canada and more studies on adverse pregnancy outcomes of NG and CT are also required.

Conclusion

The NAC-STBBI reviewed and updated PHAC's recommendations for healthcare professionals on prenatal screening for CT and NG to optimize the prevention of adverse pregnancy outcomes, as well as ophthalmia neonatorum and neonatal pneumonia. The relevant PHAC STBBI guides were updated with the NAC-STBBI recommendations. This work could be adopted or adapted by guideline development groups in Canadian provinces and territories, as well as in other countries, as appropriate, considering factors that are specific to the settings.

Authors' statement

SS — Conceptualization, writing–original draft, writing–review & editing
UA — Writing–original draft, writing–review & editing
NS — Writing–review & editing
JB — Writing–review & editing
GO — Writing–review & editing
MY — Writing–review & editing
ACL — Writing–review & editing

This work was presented at the Society of Obstetricians and Gynaecologists of Canada's 2024 Annual Clinical and Scientific Conference in Edmonton, Alberta and at the 2025 Health Canada Science Forum in Ottawa, Ontario.

Competing interests

None.

ORCID numbers

None.

Acknowledgements

The authors would like to thank current and former members of the National Advisory Committee on Sexually Transmitted and Blood-Borne Infections (NAC-STBBI), Canada's Drug Agency (formerly Canadian Agency for Drugs and Technologies in Health) and external peer-reviewers.

NAC-STBBI Prenatal Screening for Neisseria gonorrhoeae and Chlamydia trachomatis Working Group

Members: Annie-Claude Labbé (Chair), Jared Bullard, Gina Ogilvie and Mark H Yudin

NAC-STBBI

Other members (voting): Ian M Gemmill (Chair), Troy Grennan (Vice-Chair), William A Fisher, Jennifer Gratrix, Todd F Hatchette, Tim T Y Lau, Ed Lee, Petra Smyczek and Marc Steben

Former NAC-STBBI members (non-voting): Max Chernesky, Ron Read, Joan Robinson and Ameeta Singh

Ex-officio representatives (non-voting): Ibrahim Khan, Irene Martin and Tom Wong

Public Health Agency of Canada (Secretariat)

Shamila Shanmugasegaram, Ulrick Auguste, Jennifer Pennock, Annie Fleurant-Ceelen, Stacy Sabourin and Margaret Gale-Rowe

External contributors

Canada's Drug Agency

Nancy Santesso (McMaster University)

External peer-reviewers

Julie van Schalkwyk

Romain Mandel

Funding

The National Advisory Committee on Sexually Transmitted and Blood-Borne Infections is supported by the Public Health Agency of Canada.

Appendix

Supplemental material is available upon request to the author: shamila.shanmugasegaram@phac-aspc.gc.ca

List S1: Decision-analytic model considerations

Table S1: Estimated outcomes, cost and cost-effectiveness of all different strategies to screen for Neisseria gonorrhoeae and Chlamydia trachomatis in pregnant women/pregnant individuals in Canada

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