PONE-D-20-40657

Frequency, timing and risk factors for primary maternal cytomegalovirus infection during pregnancy in Quebec.

PLOS ONE

Dear Dr. Boucoiran,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

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PLOS ONE

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Reviewers' comments:

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: No

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

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Reviewer #1: In the here presented manuscript by Balegamire et al. the authors examine the seroprevalence of expecting mothers in Montréal and compare their serostatus in the first trimester to their serostatus at delivery to determine the prevalence of primary maternal CMV infection during pregnancy. This data can be used to infer the number of congenital CMV infections and by that the number of newborns with potentially lifelong sequelae in the studied target population. The presented study is well written and the authors present their data overall in a very nice and understandable manner. The conclusions of the manuscript are fully in-line with the presented results and the authors do discuss the limitations of their approach and studied group of individuals. Furthermore, this data clearly points out that there is a sizeable vulnerable population of women of childbearing age in Montréal and the detection of primary infections in CMV negative expecting mothers is a clear indication that some of these infection will results in affected children that will required follow up care, potentially for the rest of their lives. Nevertheless, it has to be stated that the presented results are not entirely novel as similar data resulting in similar conclusion have been generated previously by multiple groups around the globe. Yet, the presented study is scientifically sound and might be of interest to researchers and physicians in the field and should be deemed worth publishing. There are a few minor corrections the authors should make to the manuscript before publication to help the reader better understand the presented results.

1) For Table 1 it might be helpful if the authors could explain in the text or the materials and methods section what their abbreviations on top of each row mean and what the difference between their unadjusted and adjusted analysis is.

2) Similarly, for table 2 further explanations on what the rate and what the unadjusted rate is are needed. Also, there are * and ** after Rate and Unadjusted RR, but I can’t find what these asterisks refer to.

3) I can’t find figure legends. Figure 1 is probably fine, but figure 2 and 3 might benefit from some figure legends explaining what is shown.

4) There are some formatting issue with missing gaps or additional full stops in lines 135, 201, 214, 222, 224 and 232

Reviewer #2: To the authors of PONE-D-20-40657

SF Balegamire et al submitted a manuscript entiteled

Frequency, timing and risk factors for primary maternal cytomegalovirus infection

during pregnancy in Quebec.

To PLOS One.

The authors report on CMV seroprevalence in the first trimester (T1) in pregnancy and risk factors for the rate of CMV primary infection in a cohort of Caucasian ethnicity in the Quebec Region.

In a retrospective study using cryopreserved serum samples of the “Grossesse en Sante de Quebec” in total N=7855 pregnant women were included. About half of this cohort were excluded (?, N=3744). From the remaining 4111 participants data from T1 and T3 (third trimester) were available, to observe potential seroconversion of seronegative pregnant women from T1 to T3. Seroconversion was defined by conversion from CMV IgG negative to CMV IgG positive. In T1, 3146 individuals were CMV seronegative and in T3, 28 cases of maternal seroconversions could be documented. This correlates with 0,9% of maternal seroconversion. In contrast, in the T1 seropositive cohort of 965 pregnant women, 113 showed CMV IgG+ IgM+, which were attributed to “possible recent infection”.

In total, 104 pregnant women were infected latently and 4 primary infections of the CMV IgG+ IgM+ cohort were defined by low CMV IgG avidity. Multivariate analysis revealed parity, ethnicity and country of birth as risk factors.

The results are discussed in detail and the paper contributes seroepidemiological data of an additional cohort of high income from a developed country.

However, there are some open questions with regard to virological methods.

1.) The authors should please add original data from their seroepidemiological study, like IgM indices, IgG levels and IgG avidity assays. This could help to understand the different subcohorts of the seropositive pool of 965 mothers.

2.) Why in the seroconversion data in T3 of primary infections no CMV IgG avidity data are given? It would also be helpful to see the original data of CMV IgG levels, IgM indices, and CMV IgG avidity.

3.) These lacking data should-if available- also be evaluated statistically to characterise CMV primary infections versus non-primary infections or latent CMV infections. Do all primary infected women in T3 really express clear low IgG avidity?

4.) Fig 2: how the drop in CMV seroconversion from 2005 to 2006 can be explained? Is it a potential bias, since in 2005 only 185 pregnant women were included?

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Reviewer #1: No

Reviewer #2: Yes: Klaus Hamprecht

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Frequency, timing and risk factors for primary maternal cytomegalovirus infection during pregnancy in Quebec.

PONE-D-20-40657R1

Dear Dr. Boucoiran,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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Kind regards,

Juliet V Spencer, Ph.D.

Academic Editor

PLOS ONE

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